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This Sporting Life was directed by Lindsay Anderson.
[ { "docid": "This_Sporting_Life", "text": "This Sporting Life is a 1963 British feature film based on the 1960 novel of the same name by David Storey , which won the 1960 Macmillan Fiction Award . It recounts the story of a rugby league footballer , Frank Machin , in Wakefield , a mining area of Yorkshire , whose romantic life is not as successful as his sporting life . Storey , a former professional rugby league footballer , also wrote the screenplay . The film stars Richard Harris , Rachel Roberts , William Hartnell and Alan Badel . It was directed by Lindsay Anderson . The film was Richard Harris 's first starring role , and won him a Best Actor Award at the 1963 Cannes Film Festival . He was also nominated for an Oscar for Best Actor in a Leading Role . Rachel Roberts won her second BAFTA award for This Sporting Life and an Oscar nomination for best actress . Harris was nominated for the BAFTA that year as well . The film opened at the Odeon Leicester Square in London 's West End on 7 February 1963 .", "title": "" } ]
[ { "docid": "This_Sporting_Life_(novel)", "text": "This Sporting Life is a 1960 novel by the English writer David Storey . It is set in Northern England and follows a man who tries to make it as a Rugby league player . It was the debut novel of Storey , himself a former player for Leeds . The book was the basis for Lindsay Anderson 's 1963 film This Sporting Life .", "title": "" }, { "docid": "O_Lucky_Man!", "text": "O Lucky Man ! is a 1973 British comedy-drama fantasy film , intended as an allegory on life in a capitalist society . Directed by Lindsay Anderson , it stars Malcolm McDowell as Mick Travis , whom McDowell had first played as a disaffected public schoolboy in his first film performance in Anderson 's film if ... ( 1968 ) . The film was entered into the 1973 Cannes Film Festival .", "title": "" }, { "docid": "David_Sherwin", "text": "David Sherwin ( born 1942 ) is a British screenwriter best known for his collaborations with director Lindsay Anderson and actor Malcolm McDowell on the films if ... ( 1968 ) ( for which Sherwin was nominated for a BAFTA Award for Best Screenplay ) , O Lucky Man ! ( 1973 ) and Britannia Hospital ( 1982 ) . Sherwin attended Tonbridge School , which provided much of the inspiration for the content of if ... In 1996 , Sherwin published a memoir , Going Mad in Hollywood : And Life with Lindsay Anderson , ( Andre Deutsch ) ISBN 978-0-233-98966-2 .", "title": "" }, { "docid": "Celebrities_Anonymous", "text": "Celebrities Anonymous is a 2009 American independent comedy film directed by Dennis Hemphill Jr. , starring Lindsay Zir , Joey Kern , Dianna Agron and Jamie Anderson . The film was produced by Lindsay Zir .", "title": "" }, { "docid": "If....", "text": "if ... . is a 1968 British drama film produced and directed by Lindsay Anderson satirising English public school life . Famous for its depiction of a savage insurrection at a fictitious boys ' boarding school , the X certificate film was made at the time of the May 1968 protests in France by a director who was strongly associated with the 1960s counterculture . The film stars Malcolm McDowell in his first screen role and his first appearance as Anderson 's `` everyman '' character Mick Travis . Richard Warwick , Christine Noonan , David Wood , and Robert Swann also star . if ... . won the Palme d'Or at the 1969 Cannes Film Festival . In 1999 , the British Film Institute named it the 12th greatest British film of the 20th Century ; in 2004 , the magazine Total Film named it the 16th greatest British film of all time .", "title": "" }, { "docid": "In_Celebration", "text": "In Celebration is a 1975 film directed by Lindsay Anderson . It is based in the 1969 stage production of the same name by David Storey which was also directed by Anderson . The movie was produced and released as part of the American Film Theatre , which adapted theatrical works for a subscription-driven cinema series . It was meant to be shown theatrically with tickets sold in advance .", "title": "" }, { "docid": "The_Life's_Romance_of_Adam_Lindsay_Gordon", "text": "The Life 's Romance of Adam Lindsay Gordon is a 1916 Australian feature-length film directed by W. J. Lincoln , based on the life of poet Adam Lindsay Gordon . Unlike many Australian silent movies , part of the film survives today .", "title": "" }, { "docid": "John_Anderson_(sportscaster)", "text": "John Anderson ( born May 13 , 1965 ) is a sports journalist from Green Bay , Wisconsin , and a host of the ESPN TV program SportsCenter since June 1999 . Since Brian Kenny 's departure to the MLB Network , he mostly appears on the 6-8pm edition with Lindsay Czarniak . He also co-hosted the TV series Wipeout .", "title": "" }, { "docid": "Sequence_(journal)", "text": "Sequence was a short-lived but influential British film journal founded in 1947 by Lindsay Anderson , Gavin Lambert and Karel Reisz . Anderson had returned to Oxford after his time with the army Intelligence Corps in Delhi , Lambert was a schoolfriend of Anderson from Cheltenham College who had dropped out of English at Magdalen College on discovering that he would have to study Middle English under C. S. Lewis , while Reisz was a chemistry graduate from Emmanuel College , Cambridge who later said `` I met Lindsay Anderson on a Green Line bus . I was going to the British Film Institute to look at some film for my editing book and he was going to see Ford 's The Iron Horse . '' Founded as the Film Society Magazine , the organ of the Oxford Film Society , in 1947 , with Penelope Houston as its first editor , the journal quickly changed its name to Sequence , and produced fourteen issues between 1947 and 1952 , the last few being edited by Reisz and Anderson . The British Free Cinema movement , co-founded in 1956 by Lindsay Anderson , Karel Reisz , Tony Richardson and Lorenza Mazzetti , drew on the principles first expressed by the journal . Articles from Sequence by Anderson were published in Lindsay Anderson : The Collected Writings edited by Paul Ryan ( London : Plexus , 2004 ) .", "title": "" }, { "docid": "Julian_Wintle", "text": "Julian Wintle ( 1913 -- 1980 ) was a British film and TV producer who battled with haemophilia throughout his life . He is best remembered for his work on TV 's The Avengers , where he oversaw the transition of the series to film , the introduction of Emma Peel , and the subsequent international success , in what is considered by many to be the series `` classic '' years ( 1965 -- 67 ) . Wintle was a member of the Bryanston Consortium from 1959 to 1963 . For several years , in the early 1960s he was head of Beaconsfield Film Studios , and a director of Independent Artists Ltd. , which produced Lindsay Anderson 's This Sporting Life ( 1963 ) among other projects . His sons are the musician and publisher Christopher Wintle and the writer Justin Wintle . He was the subject of a biography by Anne Francis , Julian Wintle . A Memoir , London , Dukeswood , 1984 . This contains an extensive filmography with many films listed for which he was executive producer .", "title": "" }, { "docid": "Lindsay_Anderson", "text": "Lindsay Gordon Anderson ( 17 April 1923 -- 30 August 1994 ) was a British feature film , theatre and documentary director , film critic , and leading light of the Free Cinema movement and the British New Wave . He is most widely remembered for his 1968 film if ... , which won the Palme d'Or at Cannes Film Festival and was Malcolm McDowell 's cinematic debut . He is also notable , though not a professional actor , for playing a minor role in the Academy Award winning film Chariots of Fire . Malcolm McDowell produced a 2007 documentary about his experiences with Lindsay Anderson , Never Apologize .", "title": "" }, { "docid": "Glory!_Glory!", "text": "Glory ! Glory ! is a 1989 televangelism comedy film directed by Lindsay Anderson and starring Ellen Greene that originally aired on HBO in two parts .", "title": "" }, { "docid": "Lindsay_Anderson_(footballer)", "text": "Lindsay Anderson ( 2 September 1883 -- 12 November 1962 ) was a former Australian rules footballer who played with Melbourne in the Victorian Football League ( VFL ) .", "title": "" }, { "docid": "In_Celebration_(play)", "text": "In Celebration is a 1969 play by the English writer David Storey . It is set in a Nottinghamshire mining town and tells the story of three brothers who visit their parents for their 40th wedding anniversary . According to Storey , the three brothers are based on aspects of himself : `` One was a very passive nature , the second was a kind of conformist nature , and the third was a kind of bolshie nature that did n't want to have anything to do with the other two . '' The play took three days to write . It premiered in 1969 at the Royal Court Theatre , where it was directed by Lindsay Anderson and ran for twelve weeks . Anderson also directed a 1975 film adaptation with the same title .", "title": "" }, { "docid": "John_Howlett", "text": "John Howlett is an English author and screenwriter living in Rye , East Sussex . He started his writing career by co-writing the screenplay of the 1968 feature film if ... '' , directed by Lindsay Anderson .", "title": "" }, { "docid": "The_Long_and_the_Short_and_the_Tall_(play)", "text": "The Long and the Short and the Tall is a play written by British playwright Willis Hall . Set in the Second World War , the play premiered at the Royal Court Theatre in London in January 1959 ; it was directed by Lindsay Anderson and starred Peter O'Toole and Robert Shaw . It was Anderson 's first major production for the Royal Court , transferring to London 's West End in April 1959 . The play 's name comes from the lyrics of the 1917 song `` Bless 'Em All '' . A film adaptation was released in 1961 . Directed by Leslie Norman , it stars Laurence Harvey , Richard Harris , Richard Todd and David McCallum . A TV drama followed in 1979 which starred Michael Kitchen , Mark McManus and Richard Morant .", "title": "" }, { "docid": "The_Wreck_(1913_film)", "text": "The Wreck is an Australian film directed by W. J. Lincoln based on a poem by Adam Lindsay Gordon about the ride to help by a farmhand who has witnessed a shipwreck . It is considered a lost film . The movie was made in 1913 but not released until 1915 . W. J. Lincoln later made a film of Gordon 's life , The Life 's Romance of Adam Lindsay Gordon ( 1916 ) .", "title": "" }, { "docid": "Look_Back_in_Anger_(1980_film)", "text": "Look Back in Anger is a 1980 British film starring Malcolm McDowell , Lisa Banes and Fran Brill , and directed by Lindsay Anderson and David Hugh Jones . The film is based on John Osborne 's play Look Back in Anger .", "title": "" }, { "docid": "The_Pleasure_Garden_(1953_film)", "text": "The Pleasure Garden is a short film written and directed by James Broughton in 1953 . Among its crew was Peter Price as sound editor . Cast members included the subsequent director Lindsay Anderson and Broughton 's artistic collaborator Kermit Sheets .", "title": "" }, { "docid": "Repsol_Sport_Centre", "text": "Repsol Sport Centre , formerly known as the Talisman Centre and Lindsay Park Sports Centre , is a multi-sports complex in Calgary , Alberta , Canada . The name of the facility was changed in March 2002 , after the City of Calgary sold the naming rights for 10 million dollars to Talisman Energy for 20 years which was later bought out by Repsol and resulted in another name change . Repsol Sport Centre operates under a dual mandate as directed by The City of Calgary to support both Members and Sport Partner Athletes . ◾ To provide training and competition facilities and services for the development of Calgary 's high performance athletes in their respective dryland and aquatic sports . ◾ To provide facilities , programs and services for the wellness and recreational sporting needs of the citizens of Calgary . The complex attracts over 1.8 million visitors annually . The complex itself is run by the non-profit Lindsay Park Sports Society , a 13-member board and Civic Partner of the City of Calgary .", "title": "" }, { "docid": "Devil's_Due_(film)", "text": "Devil 's Due is a 2014 American found footage supernatural horror film directed by Matt Bettinelli-Olpin and Tyler Gillett , and written by Lindsay Devlin . The film stars Allison Miller , Zach Gilford , and Sam Anderson . The film was released on January 17 , 2014 .", "title": "" }, { "docid": "The_Changing_Room", "text": "The Changing Room is a 1971 play by David Storey , set in a men 's changing room before , during and after a rugby league football game . It premiered at the Royal Court Theatre on 9 November 1971 , directed by Lindsay Anderson . The 1973 Broadway production , directed by Michael Rudman , won several awards including the New York Drama Critics ' Circle award for Best Play and the Tony Award for Best Featured Actor for John Lithgow .", "title": "" }, { "docid": "David_Gladwell", "text": "David Gladwell ( born 1935 ) is a British film editor and director . His most notable films as editor include If ... ( 1968 ) and O Lucky Man ! ( 1973 ) both by director Lindsay Anderson . In 1981 , Gladwell directed the adaptation of the Doris Lessing novel Memoirs of a Survivor starring Julie Christie .", "title": "" }, { "docid": "Love_of_Life_Orchestra", "text": "Collaborators on their recording Extended Niceties have included Arto Lindsay and David Byrne Early members of the band included Laurie Anderson ( electric violin ) , Blue Gene Tyranny ( keyboards ) , Ken Deifik ( harmonica ) , Scott Johnson guitar , Rhys Chatham ( flute ) , Peter Zummo ( trombone ) , Arthur Russell ( cello ) , Kathy Acker ( vocals ) , and Jill Kroesen ( vocals ) .", "title": "" }, { "docid": "Wakefield_Express", "text": "The Wakefield Express is the newspaper serving the City of Wakefield district in West Yorkshire , England . It was established in 1852 and was the subject of a centenary film directed by Lindsay Anderson in 1952 . The newspaper is owned by Johnston Press and edited by Mark Bradley . After 155 years of publication as a broadsheet , it changed to a tabloid format in March 2007 .", "title": "" }, { "docid": "The_Long_and_the_Short_and_the_Tall", "text": "The Long and the Short and the Tall may refer to : The Long and the Short and the Tall ( play ) , a 1959 play , directed by Lindsay Anderson , starring Peter O ' Toole and Robert Shaw The Long and the Short and the Tall ( film ) , a 1961 film , directed by Leslie Norman , starring Laurence Harvey , David McCallum , Richard Harris and Richard Todd `` Bless 'Em All '' ( also known as `` The Long And The Short And The Tall '' ) , a 1917 song by Fred Godfrey , first recorded by George Formby in 1940", "title": "" }, { "docid": "WQME", "text": "WQME is a medium market Contemporary-Christian format radio station in Anderson , Indiana broadcasting on 98.7 FM . It is a Class A FM station with an Effective Radiated Power of 4,500 watts . It is owned by Anderson University . WQME offers several nationally syndicated programs , including New Life Live ! , Family Life Today , and CBH Viewpoint . The station also offers Hey Howard , Soul 2 Soul , Direct Connection , and Homecoming Radio . Other programs include After Midnight , a program for young adults ; Talk 'N Sports with Dave Edwards , featuring interviews with local athletes and coaches ; and Consider this with Big Joe Clark , a show focused on personal finance and the economy . WQME 's staff includes General Manager Donald Boggs and Program Director Matt Rust , who also hosts the Morning Show on weekday mornings . Other staff include Jerry Morton , engineer ; Norma Armogum , certified traffic director ; and Becky Melson , bookkeeper .", "title": "" }, { "docid": "Mick_Travis", "text": "Michael Arnold `` Mick '' Travis is a character played by Malcolm McDowell in three films directed by British film director Lindsay Anderson and written by David Sherwin . Travis features not so much as a single character with a character arc , but as an everyman character whose role changes according to the needs of the storyteller . In 1968 's if ... , his first appearance ( and McDowell 's film debut ) , Travis first appears as a disaffected public school boy whose anti-establishment attitude and experiences lead to armed insurrection at a private school . The film was made at Cheltenham College , Lindsay Anderson 's old school , and many of the scenes drew heavily on his experience in the Officers Training Corps at Cheltenham , which he had joined in May 1937 . It also draws heavily upon Tonbridge School , where the two screenwriters both went , and several characters , including the child-abusing chaplain , are based on real people who taught at Tonbridge . In O Lucky Man ! , cowritten by Sherwin and McDowell , Travis becomes a picaresque character , often compared to Voltaire 's ingénu character Candide , in a satirical drama that starts with Travis 's first job as a mobile coffee salesman and , after many adventures involving arms-sale scandals , experiments in human-animal genetics by the mad scientist Doctor Millar ( played with relish by Graham Crowden ) , and a sojourn with the musician Alan Price , ends in his rebirth as a film star , thanks to a slap by a film director played in a cameo by Anderson -- the scene was a depiction of McDowell 's first audition in which McDowell was slapped ( according to script , which he had not read ) by Christine Noonan , who played ` the girl ' in if ... . and briefly appeared ( in two roles ) in O Lucky Man ! In Britannia Hospital , written by Sherwin , Travis is a reporter attempting to make an investigative documentary about a hospital where Doctor Millar , the mad geneticist from O Lucky Man ! is continuing his unspeakable experiments . While spying on an experiment to create a new human being from assembled body parts , Travis is captured by the hospital staff . A power cut renders the experiment 's human head unusable , so Millar decapitates Travis and attaches his head to the creature . On being given life , the creature ( played by McDowell ) attacks Millar , forcing Millar to stab and dismember it .", "title": "" }, { "docid": "1969_Cannes_Film_Festival", "text": "The 22nd Cannes Film Festival was held from 8 to 23 May 1969 . At this festival a new non-competitive section called `` Directors ' Fortnight '' is added , in response to the cancellation of the 1968 festival . The Grand Prix du Festival International du Film went to the If ... . by Lindsay Anderson . The festival opened with Sweet Charity , directed by Bob Fosse .", "title": "" }, { "docid": "Craig_Anderson_(actor)", "text": "Craig Anderson is an Australian director and actor best known for his comedic turns in the Australian television series ' Double the Fist , Review with Myles Barlow , Laid , and award winning short films Life in a Datsun , Demon Datsun , Life in a Volkswagen . Anderson has also directed the horror feature Red Christmas starring Dee Wallace . Anderson has a First Class Honors in Performance and Theory from the University of Western Sydney and has almost completed a PhD on which looks at various Epistemologies of Comedy . In 2000 , Anderson began a successful career as an MC and judge at film festivals including the Newcastle Film Festival , the Shootout Film Festival held annually in Newcastle , and the Funny Bone 500 . In November 2008 Anderson featured in three episodes of the ABC TV show Review With Myles Barlow . Double the Fist co-star Bryan Moses also featured in three episodes of the series . In addition Anderson served as associate producer and first assistant director on the series During 2011 Anderson produced and directed several web series ( Bernie , Late Night Angel Weenie Baby ) that screened on various Sydney Morning Herald digital spaces , and ABC 's iView . Anderson is currently in development on a new comedy series for ABC entitled Love.Sick . He will be working with Stevo Petckovic and Melinda Clomovska of which he worked previously on for the short film A Family Affair ( which was a finalist at Tropfest 2011 ) . The six episode series about untold love stories is set to air in September 2012 . In 2013 Craig was the subject of a six-part Observational Documentary series Next Stop Hollywood , which followed him around Hollywood during pilot series . In 2014 Craig shared directing duties on Australia 's first Indigenous sketch Comedy series Black Comedy . In 2014 he ( and fellow director Bec Cole ) were nominated for an AACTA award for Best Direction in TV .", "title": "" } ]
163773
Wishful Drinking is based on a show developed by Carrie Fisher and Joshua Ravetch.
[ { "docid": "Wishful_Drinking", "text": "Wishful Drinking is an autobiographical humor book by American actress and author Carrie Fisher , published by Simon & Schuster in 2008 . Fisher 's book was based on her one-woman stage show , which she developed with writer/director Joshua Ravetch . The show debuted at The Geffen Playhouse with Ravetch directing . It enjoyed a successful Broadway run and then toured in other cities . In 2010 , HBO filmed a feature-length documentary of the stage play .", "title": "" } ]
[ { "docid": "Joshua_Ravetch", "text": "Joshua Ravetch is an American writer/director born in Los Angeles , California who co-created and directed Carrie Fisher 's one-woman show Wishful Drinking , which had a successful run on Broadway . He also co-wrote and directed Dick Van Dyke in his first-ever one man show , `` Step in Time ! A Musical Memoir , '' which premiered at The Geffen Playhouse . Ravetch , a graduate of the Stella Adler Conservatory in Manhattan , took over Ms. Adler 's signature script-interpretation classes before assuming the post as artistic director at the Stella Adler Conservatory West .", "title": "" }, { "docid": "Joshua_Mark_Thomas", "text": "Joshua Mark Thomas is an accomplished interior designer and photographer . He was born in Montana , possibly Proctor , on August 21 , 1973 to Mark & Dianne Thomas . After various moves throughout the country , including to New York , Los Angeles , and Las Vegas , he settled in Atlanta , Georgia , where he attended the Savannah College of Art & Design . Joshua 's early career including the design and manufacture of detailed , high-end dresses and costumes for ballroom dancers , and his clients included many of the countries top dancers who are still performing professionally today . He was an on-air cast member of HGTV 's Designed to Sell for all Atlanta seasons and is the current photographer for HGTV 's Curb Appeal . Joshua 's textile work has also been featured on The Today Show , HGTV 's Designed to Sell , and with various John Gidding Design Inc. projects , including at the upscale furniture store , Artefacto ( currently in their Atlanta , GA Style House ) . His work has also recently been in Loft Life magazine , which shows both his textiles as part of the Artefacto Style House and his photography , as credited in the article , in Jezebel magazine , where he 's shown as part of the Designed to Sell cast , and in Atlanta Woman 's Magazine , which shows his textile work as part of Designed to Sell , as well as crediting his photography work . In 2009 , his work ( both photography and textiles ) was featured in the remodel of Carrie Fisher 's dressing room at Studio 54 for her production of Wishful Drinking . He also owns a textile and design firm named J Thomas Design and a fine art photography business , J Thomas Fine Art . His textile work has appeared on almost every episode of seasons 25 - 28 of Designed to Sell .", "title": "" }, { "docid": "Carrie_Fisher", "text": "Carrie Frances Fisher ( October 21 , 1956 -- December 27 , 2016 ) was an American actress , writer and humorist who first became known for playing Princess Leia in the Star Wars film series . Her other film roles included Shampoo ( 1975 ) , The Blues Brothers ( 1980 ) , Hannah and Her Sisters ( 1986 ) , The ` Burbs ( 1989 ) , and When Harry Met Sally ... ( 1989 ) . Fisher wrote several semi-autobiographical novels , including Postcards from the Edge and the screenplay for the film of the book , as well as an autobiographical one-woman play , and its non-fiction book , Wishful Drinking , based on the play . She worked on other writers ' screenplays as a script doctor . In later years , she earned praise for speaking publicly about her experiences with bipolar disorder and drug addiction . The daughter of the singer Eddie Fisher and actress Debbie Reynolds , Fisher and her mother appear in Bright Lights : Starring Carrie Fisher and Debbie Reynolds , a 2016 documentary about their relationship . It premiered at the 2016 Cannes Film Festival . Fisher died of cardiac arrest on December 27 , 2016 , at age 60 , four days after experiencing a medical emergency during a transatlantic flight from London to Los Angeles . Her final film , Star Wars : The Last Jedi , is scheduled to be released on December 15 , 2017 .", "title": "" }, { "docid": "One_November_Yankee", "text": "One November Yankee is a play by American writer Joshua Ravetch . It was first performed at The Pasadena Playhouse before opening at The NoHo Arts Center in 2012 . The play starred two time Emmy winner , and TV 's Hot Lips Houlihan from M * A * S * H * , Loretta Swit , and LA Law 's Harry Hamlin . The set was designed by Dana Moran Williams . The film rights were picked up by Pam Williams Productions as a feature film for Ravetch to adapt and direct .", "title": "" }, { "docid": "Joshua_Fisher_(musician)", "text": "Joshua Fisher ( born 1989 ) is a singer-songwriter from Lewisham in South London , currently living in Norwich , England . His debut EP , `` Atlas '' was scheduled to be released on 25 October 2010 by independent London based label Polymorph Records . `` Atlas '' features four songs , which have been co-produced by Roger Pusey -- former Producer of iconic recordings on The Smiths albums Hatful of Hollow and `` Louder Than Bombs '' . Joshua cites Nick Drake , Bright Eyes and The Waterboys among his influences .", "title": "" }, { "docid": "The_Princess_Diarist", "text": "The Princess Diarist is a 2016 memoir written by Carrie Fisher , based on diaries she kept as a young woman around the time she starred in the 1977 film Star Wars . The book is the third memoir Fisher wrote , in addition to four novels and a one-woman Broadway show . It is Fisher 's final book , as she died five weeks after its release on December 27 , 2016 . The book describes Fisher 's affair with co-star Harrison Ford in `` cringe-worthy '' , albeit educational , detail . At the time of the relationship , Ford was married with two children and in his early 30s .", "title": "" }, { "docid": "Wish_You_Were_Here_(1952_song)", "text": "`` Wish You Were Here '' is a popular song with music and lyrics by Harold Rome , the title tune from his 1952 show , Wish You Were Here ( musical ) . It was introduced in the show and on the RCA Victor cast album by Jack Cassidy . The best-known version was recorded by Eddie Fisher becoming a # 1 hit in 1952 on RCA Victor 47-4830 ( 45 rpm ) and 20-4830 ( 78 rpm ) .", "title": "" }, { "docid": "Joshua_Francis_Fisher", "text": "Joshua Francis Fisher ( February 17 , 1807 Philadelphia - January 21 , 1873 ) was a United States author and philanthropist .", "title": "" }, { "docid": "Friends_of_Peter_G.", "text": "`` Friends of Peter G. '' is the tenth episode of the ninth season of the animated comedy series Family Guy . It aired on Fox in the United States on February 13 , 2011 . The episode follows Peter and Brian as they are forced to join Alcoholics Anonymous , due to their excessive drinking , much to their chagrin . Soon , however , Peter crashes his car while driving home drunk , and is approached by Death , who shows him what his life will be like if he continues to drink alcohol , as well if he had never drunk at all . The episode was written by Brian Scully and directed John Holmquist . It received mostly mixed reviews from critics for its storyline and many cultural references . According to Nielsen ratings , it was viewed in 5.99 million homes in its original airing . The episode featured guest performances by H. Jon Benjamin , Adam Carolla , Carrie Fisher , Phil LaMarr , Jessica Stroup and Laura Vandervoort , along with several recurring guest voice actors for the series . It was first announced at the 2010 San Diego Comic-Con International .", "title": "" }, { "docid": "Kitty_Fisher", "text": "Kitty Fisher ( 1741 -- 1767 ) was a prominent British courtesan . From her teen years onwards , Fisher carefully developed her public image , which was boosted by attention from Sir Joshua Reynolds and other artists . By emphasizing Fisher 's beauty , audacity , and charm , portraits and newspaper and magazine articles promoted her reputation and prompted spectators to view her with redoubled awe . She was one of the world 's first celebrities famous not for being an actress , musician or member of the royalty , but simply for being famous . Her life exemplifies the emergence of mass media publishing and fame in an era when capitalism , commercialism , global markets , and rising emphasis on public opinion were transforming England .", "title": "" }, { "docid": "Testament_of_Man", "text": "The Testament of Man ( 1943-1960 ) , a twelve-volume series of novels by the American author Vardis Fisher , traces the physical , psychological and spiritual evolution of Western civilization from Australopithecus to the present . The series explores a pantheon of subjects : myth , ritual , language , family , sex and especially sin , guilt and religion . Each work emphasizes a particular pathway that Fisher considered of paramount importance in the development of the modern world and our current views . `` Enlightened minds must wonder what the world would be like today if the torrent -LSB- that carries us along -RSB- had taken another channel at any one of a dozen moments in history . What if Greek values had triumphed in that war more than twenty − one centuries ago ? '' Fisher traced a specific pathway in which ape-like creatures segued to Middle Eastern tribes , followed by the development of Judaism and Christianity . The task consumed two decades after prodigious preparation . By his own account , Fisher read more than 2,000 books and essays on a wide range of subjects - religion , anthropology , archaeology , music , food , psychology , evolution and climate . In The Great Confession , `` Part III : The Orphans '' Fisher describes his research in detail . In order to get into the mind of the ape-man , he lived like one , dwelling in caves , walking , eating , hunting and sleeping as he imagined they had . He observed apes in zoos and conducted behavioral experiments with animals . For example , he concluded that contrary to popular belief , animals did not generally recognize people by scent . He was convinced that Western religion developed out of fear , particularly that of the father . Judaism was the only ancient religion without a mother figure . All volumes in the series are based on similar themes and characters , or personas . One theme is the role of gender in the rise of human civilization . He holds that female 's feelings run deeper ; she was more practical since her first duties were to home , food and children . The man , uninvolved with family , is egotistical , shallow and alone , yet this solitude gives rise to intellectual breakthroughs that radically changed ancient beliefs . One recurrent character is the misunderstood male genius , the neurotic thinker who suddenly grasps a unique thought that becomes increasingly influential to future generations . An intellectually strong woman often appears . She understands better than the male and assists in his quest into the unknown . Fisher 's interest in men 's long subjugation of women is a dominant theme throughout . The controversial subject matter met with frequent , scathing denunciation that centered on three elements - his treatment of religion , sexual content and anthropological conclusions . Many reviewers objected to Fisher 's penchant for interrupting the story with explanatory comments for the reader . Particularly reviled was his treatment of historical and Biblical characters , religion in general , and Christianity and Judaism specifically . The Valley of Vision ( 1951 ) , a novel of Solomon and his court , evoked a fierce review in TIME : The project was viewed as a financial risk and had trouble finding a publisher despite Fisher 's fame as a popular Western novelist . When he presented Jesus Came Again : A Parable ( 1956 ) , Caxton Press refused to publish it due to the heretical nature of the story . They thought the tale of a misunderstood , neurotic Jesus ( `` Joshua '' ) who was all too human , and not the man who satisfied the universal yearnings of the times for a Messiah , was too controversial . The project was picked up by Swallow Publishing , which printed the rest of the series . Fisher considered religion not as a cultural , collective phenomenon but as the consequences of individual insight due to sexual longings , loneliness and genius .", "title": "" }, { "docid": "Harriet_Frank_Jr.", "text": "Harriet Frank Jr. ( born March 2 , 1917 ) is an American film writer and producer . Working alongside her husband , Irving Ravetch , Frank received numerous awards during her lengthy career , including the New York Film Critics Circle Awards and the Writers Guild of America Award , and several nominations . Frank and Ravetch are considered one of the all-time great screenwriting couples , and many of their works are recognised classics of their genres . Frank began her writing career after World War II , under Metro-Goldwyn-Mayer 's young writer 's training program , where she first met her future husband . She married Ravetch in 1946 but worked independently for ten years , finally collaborating with him in 1957 , a relationship that continued for the remainder of her career . During 33 years of collaboration , they created the screenplays for a variety of films , mainly adaptations of the works of American authors . Frank and Ravetch maintained a close working relationship with director Martin Ritt throughout their career , collaborating with him on eight occasions ; after initially being suggested by Ravetch to direct The Long , Hot Summer ( 1958 ) , Ritt would eventually draw the couple out of inactivity on three occasions , hiring them to write the screenplays for Norma Rae ( 1979 ) , Murphy 's Romance ( 1985 ) and Stanley & Iris ( 1990 ) . The latter was both the last film directed by Ritt ( who died later that year ) and the last for which Frank and Ravetch wrote the screenplay .", "title": "" }, { "docid": "Wish_(Joshua_Redman_album)", "text": "Wish is a 1993 album by jazz saxophonist Joshua Redman .", "title": "" }, { "docid": "Wishing_well", "text": "A wishing well is a term from European folklore to describe wells where it was thought that any spoken wish would be granted . The idea that a wish would be granted came from the idea that water housed deities or had been placed there as a gift from the gods , since water was a source of life and often a scarce commodity . The Germanic and Celtic peoples considered springs and wells sacred places . Sometimes the places were marked with wooden statues possibly of the god associated with the pool . Germanic peoples were known to throw the armour and weapons of defeated enemies into bogs and other pools of water as offerings to their gods . Water was seen to have healing powers and therefore wells became popular with many people drinking , bathing or just simply wishing over it . Some people believe that the guardians or dwellers of the well would grant them their wish if they paid a price . After uttering the wish , one would generally drop coins in the well . That wish would then be granted by the guardian or dweller , based upon how the coin would land at the bottom of the well . If the coin landed heads up , the guardian of the well would grant the wish , but the wish of a tails up coin would be ignored . It was thus potentially lucky to throw coins in the well , but it depended on how they landed . The tradition of dropping pennies in ponds and fountains stems from this . Coins would be placed there as gifts for the deity to show appreciation . This may be a leftover from ancient mythology such as Mímir 's Well from Nordic myths , also known as the `` Well of Wisdom '' , a well that could grant you infinite wisdom provided you sacrificed something you held dear . Odin was asked to sacrifice his right eye which he threw into the well to receive not only the wisdom of seeing the future but the understanding of why things must be . Mímir is the Nordic god of wisdom , and his well sits at the roots of Yggdrasil , the World Tree which draws its water from the well . Another theory is people may have unknowingly discovered the biocidal properties of both copper and silver ; the two metals traditionally used in coins . Throwing coins made of either of these metals could help make the water safer to drink . Wells that were frequented by those that threw coins in may have been less affected by a range of bacterial infections making them seem more fortunate and may have even appeared to have cured people suffering from repeated infections . In November 2006 the `` Fountain Money Mountain '' reported that tourists throw just under 3 million pounds sterling per year into wishing wells .", "title": "" }, { "docid": "Eddie_Fisher_(singer)", "text": "Edwin John `` Eddie '' Fisher ( August 10 , 1928 -- September 22 , 2010 ) was an American singer and actor . He was the most successful pop singles artist during the first half of the 1950s , selling millions of records and hosting his own TV show . Fisher divorced his first wife , actress Debbie Reynolds , to marry Reynolds ' best friend , actress Elizabeth Taylor , after Taylor 's husband , film producer Mike Todd , was killed in a plane crash . The scandalous affair was widely reported , bringing unfavorable publicity to Fisher . He later married Connie Stevens . Fisher fathered Carrie Fisher and Todd Fisher with Reynolds , and Joely Fisher and Tricia Leigh Fisher with Stevens .", "title": "" }, { "docid": "Caffeinated_drink", "text": "A caffeinated drink , or caffeinated beverage , is a drink that contains caffeine , a stimulant that is legal and popular in most developed countries . The most common naturally caffeinated beverages are coffee and tea , which in one form or another ( usually served hot , but sometimes iced ) feature in most world cultures . Other drinks are artificially caffeinated as part of their production process . These include certain soft drinks ( primarily cola drinks ) , and also energy drinks designed as a stimulant , and to perpetuate activity at times when the user might ordinarily be asleep . The consumption of caffeinated drinks is often intended entirely or partly for the physical and mental effects of caffeine . Examples include the consumption of tea or coffee with breakfast in many westernized societies , in order to ` wake oneself up ' , or the deliberate consumption of energy drinks by students wishing to study through the night , or revellers seeking to maintain an alert attitude during social recreation . Caffeine can cause a physical dependence , if consumed in excessive amounts . The need for caffeine can be identified when individuals feel headaches , fatigue and muscle pain 24 hours after their last energy drink . Some commercially distributed drinks contain guarana , a South American berry with a caffeine content about twice that of coffee beans . Many caffeinated drinks also have decaffeinated counterparts , for those who enjoy the taste , but wish to limit their caffeine intake because of its physical effects , or due to religious or medical perceptions of the drug and its effects . In recent years , some alcoholic beverage companies have begun to manufacture caffeinated alcoholic beverages . The manufacturing of such beverages has been met with much controversy .", "title": "" }, { "docid": "Joshua_Fisher", "text": "Joshua Fisher ( 1707 -- February 1 , 1783 ) was a prominent Philadelphia merchant involved in transatlantic trade and mapmaking as applied to nautical charts . He made the first nautical chart of the Delaware River and Delaware Bay , and established the first merchant packet line between London and Philadelphia .", "title": "" }, { "docid": "The_Joshua_Light_Show", "text": "The Joshua Light Show , created by Joshua White , was a liquid light show . It was known for its psychedelic art and served as a lighting backdrop behind many live band performances during the late 1960s and early 1970s . Joshua White studied electrical engineering , theatrical lighting , and magic lantern techniques at Carnegie Tech and also film making at University of Southern California . Performances were held every weekend . The light shows used multiple image-making devices including film projectors , slide projectors , overhead projectors , color wheels , watercolors , oil colors , and glass crystals . These all would be arranged on two levels for their performances . The Joshua Light Show based their shows on four elements ; projection of pure color , concrete imagery , variety of color effects and shaping of the light .", "title": "" }, { "docid": "Kev_Seed", "text": "Kevin `` Kev '' Seed ( born 27 July 1968 ) is an English radio DJ . He has presented shows on Rock FM and Radio City , and most recently , the former Breakfast Presenter for Wish FM . In April 2016 , it was announced he would be joining the presenting line-up at Wirral Radio . Seed first joined Radio City in 1990 . Two years later , he moved to the Preston-based station Rock FM for five years . In 1997 , he re-joined Radio City and presented The Kev Seed Breakfast Show for 11 years before moving to the Drivetime show ( 4pm -- 7pm ) in August 2008 . He presented the early evening Drivetime show on the Liverpool radio station Radio City 96.7 until October 2008 , when he was suspended and then sacked after pleading guilty to a drink-driving charge . Although he appealed , it was reported on 11 November that the station management had upheld their decision . In October 2009 , Seed started his new job as the Breakfast Presenter for Wish FM , the Radio Station for Wigan & St Helens , a year after leaving Radio City . He is also to begin presenting a show on 107.6 Juice FM from 29 November . He now no longer presents on either stations . As of 2014 , he is voice of Sainsbury 's on various radio stations .", "title": "" }, { "docid": "NG_Knight_Ramune_&_40", "text": "For the final OVA , see Knights of Ramune . was a Japanese television series of 1990 . It was one of the Lamune group of television shows and OVAs , and the `` NG '' in the title stands for `` new generation '' . In all there were 3 OVA series ( NG Knight Lamune & 40 EX , NG Knight Lamune & 40 DX , VS Knight Lamune & 40 Fresh ) and a sequel anime television series ( VS Knight Lamune & 40 Fire ) . This show is not related to the anime series Lamune of 2005 . The original concept for the show was developed by Takehiko Ito , much of the story was written by Satoru Akahori , and the mecha design was done by Rei Nakahara . ( Collectively this team is known as `` B3 '' . ) All anime and OVA in the series were produced by Starchild Records , and the show was broadcast on TV Tokyo from April 6 , 1990 to January 4 , 1991 as well as on Nickelodeon India until June 3 , 2013 . The main storyline of the series involves a boy named Baba Lamune who is sucked into the video game `` King Sccasher . '' Lamune is a blood relative of the hero `` Lamuness , '' and in the program he is destined to save the world from the evil Don Harumage . `` Lamune '' is the name of a popular , lemon-flavored Japanese carbonated drink , and most character names in the series are based on drinks , such as the character Milk . The name `` Scassher '' is based on the name of a competitor to Lamune , namely `` Lemon Squash '' , a drink not franchised in America whose name is based on that of `` Orange Crush '' , which is .", "title": "" }, { "docid": "Jeffrey_V._Ravetch", "text": "Jeffrey Victor Ravetch ( born 1951 ) is a professor and head of the Laboratory of Molecular Genetics and Immunology at The Rockefeller University .", "title": "" }, { "docid": "Happily_Ever_After_(Magic_Kingdom)", "text": "Happily Ever After is a fireworks and projection mapping show which debuted at the Magic Kingdom on May 12 , 2017 . Unlike its predecessor , Wishes : A Magical Gathering of Disney Dreams , the show includes projection mapping across Cinderella Castle , lasers , and searchlights , in addition to pyrotechnics . The show includes characters and music from a wide array of Disney films . The music also includes a theme song from Angie Keilhauer and Jordan Fisher .", "title": "" }, { "docid": "Fisher's_Lane_Bridge", "text": "Fisher 's Lane Bridge is a historic stone arch bridge that carries Fisher 's Lane west of Ramona Avenue across Tacony Creek in Tacony Creek Park in Philadelphia , Pennsylvania . The closed-spandrel stone arch bridge has a single span of 54 ft and is 27.7 ft wide . It is currently open to traffic . Though claimed by some to have been re-built in 1796 , a still-legible cornerstone in the bridge masonry shows the year 1759 .", "title": "" }, { "docid": "Irving_Ravetch", "text": "Irving Dover Ravetch ( November 14 , 1920 -- September 19 , 2010 ) was an American screenwriter and film producer who frequently collaborated with his wife Harriet Frank , Jr. .", "title": "" }, { "docid": "Passenger_Fatty-Seven", "text": "`` Passenger Fatty-Seven '' is the tenth episode of the fifteenth season of the animated sitcom Family Guy , and the 279th episode overall . It aired on Fox in the United States on January 8 , 2017 , and is written by Alex Carter and directed by Greg Colton . The episode 's title is a play on the film Passenger 57 . This episode was dedicated in memory of cast member Carrie Fisher , who died on December 27 , 2016 after going into cardiac arrest while on a flight to Los Angeles on December 23 , 2016 . A slide showing her picture with the words `` In Loving Memory '' on top and `` Carrie Fisher 1956-2016 '' below was shown before the start of the episode .", "title": "" }, { "docid": "Superstar_USA", "text": "The WB 's Superstar USA is a television show which spoofed the popular show American Idol . Essentially that show 's polar opposite , Superstar USA told contestants they were looking for the best singer when they were actually looking for the worst . Hosted by Brian McFayden ( Ryan Seacrest 's double ) , people first audition before three judges ( the sarcastic Briggs , who also produces the show and could be considered the `` Simon '' of the show ; rapper Tone Lōc , the show 's answer to Randy Jackson ; and singer Vitamin C , put into Paula Abdul 's role ) in four cities across the United States . Finalists were chosen based on the lie that they were the most likely to be able to parlay their win into a successful recording contract based on talent . However , the audition process was the opposite of American Idol as good singers were mocked and told no , while bad singers were given gushing praise and passed to the next round . Said finalists were subjected to makeovers where they were encouraged to emulate pop stars . Contestants would then be falsely encouraged and praised by the judges as well as the stylists , choreographers and vocal coaches ; in particular , they would be encouraged to try and stretch their vocal range far beyond what they could actually reach . Contestants with charismatic personalities , such as the singer/songwriter pro-cheerleader Nina `` Diva '' , were heavily encouraged to follow all of the producer driven directives . Eventually the contest was `` won '' by a singer named Jamie Foss , a buxom young blonde girl ( who bore a resemblance to Jessica Simpson ) who could barely carry a tune . Throughout the competition she was constantly mocked by judges with thinly veiled references to the largeness of her breasts . She was awarded $ 50,000 in cash and a $ 50,000 budget to produce a record , which has not yet surfaced . The truth was revealed to her on stage in front of the audience she had just sung for , but Foss did not seem very upset with the truth . One producer , worried that the live audience members would not be able to respectfully compose themselves during the final performances , deceived the audience by falsely informing them that the singers were all terminally ill young people , who were having a wish fulfilled by a charitable organization . The Los Angeles Times reported the organization named by the producer was the Make a Wish Foundation , which later received an apology from the WB . In an interview with USA Today , executive producer Mike Fleiss straightened out the details : `` First of all , it was me . But I did not say ` Make-A-Wish . ' I said , ` Who 's heard of the One Wish Foundation ? ' and people raised their hands . There is no One Wish Foundation . It was a prank on top of a prank . It was the only way to get it to work . ''", "title": "" }, { "docid": "Celia_Fisher", "text": "Celia B. Fisher , is an American developmental psychologist , the Marie Ward Doty University Chair and Professor of Psychology , and founding director of the Fordham University Center for Ethics Education . In addition , she is currently the director of the Fordham HIV Prevention Research Ethics Training Institute , which provides training on research ethics issues and offers financial support for a mentored research project that will contribute to evidence - based research ethics practices . Fisher is past chair of the Environmental Protection Agency 's Human Studies Review Board , a past member of the DHHS Secretary 's Advisory Committee on Human Research Protections ( SACHRP ; and co-chair of the SACHRP Subcommittee on Children 's Research ) and a founding editor of the journal Applied Developmental Science . She chaired the American Psychological Association 's Ethics Code Task Force and the New York State Licensing Board for Psychology , and served on the National Institute of Mental Health Data Safety and Monitoring Board , and the Institute of Medicine 's Committee on Clinical Research Involving Children . She is author of Decoding the Ethics Code : A Practical Guide for Psychologists ; co-editor of eight books , including The Handbook of Ethical Research with Ethnocultural Populations and Communities and Research with High-Risk Populations : Balancing Science , Ethics , and Law ; and author of over 100 theoretical and empirical publications in the areas of ethics in medical and social science research and practice and life-span development . Fisher is the recipient of the Lifetime Achievement Award of Excellence in Human Research Protection from the Health Improvement Institute ( HII ) . Her federally funded research programs focus on ethical issues and well-being of vulnerable populations , including ethnic minority youth and families , active drug users , college students at risk for drinking problems , and adults with impaired consent capacity .", "title": "" }, { "docid": "Bright_Lights:_Starring_Carrie_Fisher_and_Debbie_Reynolds", "text": "Bright Lights : Starring Carrie Fisher and Debbie Reynolds ( on-screen title is simply Bright Lights ) is a 2016 documentary about the relationship between entertainer Debbie Reynolds ( in her final film appearance ) and her actress/daughter Carrie Fisher . It premiered at the 2016 Cannes Film Festival and on January 7 , 2017 on HBO . A few weeks before the film 's premiere broadcast , both Fisher and Reynolds died . On December 23 , Fisher went into cardiac arrest and succumbed four days later , while Reynolds had a severe stroke from which she died on the following day , December 28 .", "title": "" }, { "docid": "Joshua_Pearce", "text": "Joshua M. Pearce is an academic engineer at Michigan Tech known for his work on protocrystallinity , photovoltaic technology , open-source-appropriate technology , and open-source hardware including RepRap 3D printers . Dr. Pearce received his Ph.D. at The Pennsylvania State University , where his work on protocrystallinity helped develop low-cost amorphous silicon solar photovoltaic technology . His solar research continues . For example , his research group published a levelized cost of electricity study on solar energy showed solar electricity was economically competitive with fossil fuels over wide geographic regions . His research into BDRF modeling of reflectors showed potential solar systems output increases of 30 % . However , he is also a vocal advocate of an open-source approach to technical development . For his work related to open-source nanotechnology , Ars Technica compared him to American software freedom activist Richard Stallman . He applied open-source 3-D printing and electronics to scientific equipment design , where he has claimed both superior innovation and lower costs . Reviewing his book Open-Source Lab , 3-D Printing Industry wrote , `` This is a manual that every scientist should read and it holds a message so powerful and disruptive that the Anarchist Cookbook is a fairy tale in comparison . '' His research has shown that printing household items with a RepRap is less costly and better for the environment than purchasing conventionally manufactured goods . Similarly , his group developed the recyclebot , a waste plastic extruder , which drops the cost of 3D printing filament from $ 35/kg to ten cents per kg while making recycling even more environmentally beneficial . In 2013 his group released an open-source 3D printer capable of printing in steel , which cost less than US$ 1,200 . in order to encourage more rapid technological development according to Scientific American . This cost reduction was significant as the New York Times reported commercial metal printers at the time cost over US$ 500,000 . Following the same approach , Dr. Pearce developed the early work on open-source-appropriate technology , which is technology that is designed with special consideration to the environmental , ethical , cultural , social , political , and economical aspects of the community it is intended for that are designed in the same fashion as free and open-source software . For example , he further developed inexpensive methods such as SODIS to disinfect drinking water in the developing world , using sunlight , water bottles , and salt . Recently , the MIT Sloan Management Review reported that Dr. Pearce has combined many of his research areas developing solar powered 3-D printers to drive sustainable development .", "title": "" }, { "docid": "Polymorph_Records", "text": "Polymorph Records is a record label based in London , England . In 2010 they released the debut single by Jamie West , called `` Give Me Everything You Got '' . Their most recent release is by singer-songwriter Joshua Fisher who released his debut EP `` Atlas '' on 25 October 2010 . It was co-produced by Roger Pusey . Their latest signing is Jake Benson , a young singer from London .", "title": "" } ]
187
British male students are bullied more than British female students.
[ { "docid": "16855829", "text": "Bullying is still prevalent in schools and is clearly stressful for victims. 1 2 It may also have undesirable consequences for bullies, with antisocial behaviour persisting into adulthood. Victims are generally reported to be weaker than the bullies. 2 3 This would suggest that very short pupils are more likely to be victims and less likely to be the aggressors. The Wessex growth study allowed us to examine the prevalence of bullying, as experienced or perpetrated by pupils of different heights. Ninety two short normal adolescents who had been below the third centile for height at school entry4 and 117 controls matched for age and sex completed a bullying questionnaire, derived from work by Whitney and Smith.5 There were no refusals or any significant differences in sex or social class between the groups. Mean age (range) was 14.7 (13.4-15.7) years. Mean height SD scores were: short pupils −1.90 (−3.53 to −0.01), controls 0.31 (−1.41 …", "title": "Bullying in school: are short pupils at risk? Questionnaire study in a cohort." } ]
[ { "docid": "2867345", "text": "BACKGROUND A sexual dimorphism exists in the incidence and prevalence of coronary artery disease--men are more commonly affected than are age-matched women. We explored the role of the Y chromosome in coronary artery disease in the context of this sexual inequity. METHODS We genotyped 11 markers of the male-specific region of the Y chromosome in 3233 biologically unrelated British men from three cohorts: the British Heart Foundation Family Heart Study (BHF-FHS), West of Scotland Coronary Prevention Study (WOSCOPS), and Cardiogenics Study. On the basis of this information, each Y chromosome was tracked back into one of 13 ancient lineages defined as haplogroups. We then examined associations between common Y chromosome haplogroups and the risk of coronary artery disease in cross-sectional BHF-FHS and prospective WOSCOPS. Finally, we undertook functional analysis of Y chromosome effects on monocyte and macrophage transcriptome in British men from the Cardiogenics Study. FINDINGS Of nine haplogroups identified, two (R1b1b2 and I) accounted for roughly 90% of the Y chromosome variants among British men. Carriers of haplogroup I had about a 50% higher age-adjusted risk of coronary artery disease than did men with other Y chromosome lineages in BHF-FHS (odds ratio 1·75, 95% CI 1·20-2·54, p=0·004), WOSCOPS (1·45, 1·08-1·95, p=0·012), and joint analysis of both populations (1·56, 1·24-1·97, p=0·0002). The association between haplogroup I and increased risk of coronary artery disease was independent of traditional cardiovascular and socioeconomic risk factors. Analysis of macrophage transcriptome in the Cardiogenics Study revealed that 19 molecular pathways showing strong differential expression between men with haplogroup I and other lineages of the Y chromosome were interconnected by common genes related to inflammation and immunity, and that some of them have a strong relevance to atherosclerosis. INTERPRETATION The human Y chromosome is associated with risk of coronary artery disease in men of European ancestry, possibly through interactions of immunity and inflammation. FUNDING British Heart Foundation; UK National Institute for Health Research; LEW Carty Charitable Fund; National Health and Medical Research Council of Australia; European Union 6th Framework Programme; Wellcome Trust.", "title": "Inheritance of coronary artery disease in men: an analysis of the role of the Y chromosome" }, { "docid": "12789595", "text": "It is becoming “a truth universally acknowledged” that the education of undergraduate medical students will be enhanced through the use of computer assisted learning. Access to the wide range of online options illustrated in the figure must surely make learning more exciting, effective, and likely to be retained. This assumption is potentially but by no means inevitably correct. ### Box 1: Why fund computer assisted learning? Computer assisted learning is inevitable —Individual lecturers and departments are already beginning to introduce a wide range of computer based applications, sometimes in a haphazard way. Planned and coordinated development is better than indiscriminate expansion It is convenient and flexible —Courses supported by computer assisted learning applications may require fewer face to face lectures and seminars and place fewer geographical and temporal constraints on staff and students. Students at peripheral hospitals or primary care centres may benefit in particular Unique presentational benefits —Computer presentation is particularly suited to subjects that are visually intensive, detail oriented, and difficult to conceptualise, such as complex biochemical processes or microscopic images.1 Furthermore, “virtual” cases may reduce the need to use animal or human tissue in learning Personalised learning —Each learner can progress at his or her preferred pace. They can repeat, interrupt, and resume at will, which may have particular advantages for weaker students Economies of scale —Once an application has been set up, the incremental cost of offering it to additional students is relatively small Competitive advantage —Potential applicants may use the quality of information technology to discriminate between medical schools. A “leading edge” virtual campus is likely to attract good students Achieves the ultimate goal of higher education —The goal is to link people into learning communities. Computer applications, especially the internet and world wide web, are an extremely efficient way of doing this2 Expands pedagogical horizons —The most controversial argument for … RETURN TO TEXT", "title": "Computer assisted learning in undergraduate medical education." }, { "docid": "17374970", "text": "AIM To determine attrition and predictors of academic success among medical students at University of Split, Croatia. METHODS We analysed academic records of 2054 students enrolled during 1979-2008 period. RESULTS We found that 26% (533/2054) of enrolled students did not graduate. The most common reasons for attrition were 'personal' (36.4%), transfer to another medical school (35.6%), and dismissal due to unsatisfactory academic record (21.2%). Grade point average (GPA) and study duration of attrition students were significantly associated with parental education. There were 1126 graduates, 395 men and 731 women. Their average graduation GPA was 3.67±0.53 and study duration 7.6±2.44 years. During 5-year curriculum only 6.4% (42/654) of students graduated in time, and 55% (240/472) of students graduated in time after curriculum was extended to 6 years. Variables predicting whether a student will graduate or not were high school grades, entrance exam score and year of enrollment. Significant predictors of graduation grades were high school grades and entrance exam score. Entrance exam score predicted length of studying. CONCLUSION Preadmission academic qualifications and year of enrollment predict academic success in medical school. More attention should be devoted to high attrition.", "title": "Predictors of Attrition and Academic Success of Medical Students: A 30-Year Retrospective Study" }, { "docid": "24159217", "text": "CONTEXT No randomized controlled studies have been conducted to date on the effectiveness of psychological interventions for children with symptoms of posttraumatic stress disorder (PTSD) that has resulted from personally witnessing or being personally exposed to violence. OBJECTIVE To evaluate the effectiveness of a collaboratively designed school-based intervention for reducing children's symptoms of PTSD and depression that has resulted from exposure to violence. DESIGN A randomized controlled trial conducted during the 2001-2002 academic year. SETTING AND PARTICIPANTS Sixth-grade students at 2 large middle schools in Los Angeles who reported exposure to violence and had clinical levels of symptoms of PTSD. INTERVENTION Students were randomly assigned to a 10-session standardized cognitive-behavioral therapy (the Cognitive-Behavioral Intervention for Trauma in Schools) early intervention group (n = 61) or to a wait-list delayed intervention comparison group (n = 65) conducted by trained school mental health clinicians. MAIN OUTCOME MEASURES Students were assessed before the intervention and 3 months after the intervention on measures assessing child-reported symptoms of PTSD (Child PTSD Symptom Scale; range, 0-51 points) and depression (Child Depression Inventory; range, 0-52 points), parent-reported psychosocial dysfunction (Pediatric Symptom Checklist; range, 0-70 points), and teacher-reported classroom problems using the Teacher-Child Rating Scale (acting out, shyness/anxiousness, and learning problems; range of subscales, 6-30 points). RESULTS Compared with the wait-list delayed intervention group (no intervention), after 3 months of intervention students who were randomly assigned to the early intervention group had significantly lower scores on symptoms of PTSD (8.9 vs 15.5, adjusted mean difference, - 7.0; 95% confidence interval [CI], - 10.8 to - 3.2), depression (9.4 vs 12.7, adjusted mean difference, - 3.4; 95% CI, - 6.5 to - 0.4), and psychosocial dysfunction (12.5 vs 16.5, adjusted mean difference, - 6.4; 95% CI, -10.4 to -2.3). Adjusted mean differences between the 2 groups at 3 months did not show significant differences for teacher-reported classroom problems in acting out (-1.0; 95% CI, -2.5 to 0.5), shyness/anxiousness (0.1; 95% CI, -1.5 to 1.7), and learning (-1.1, 95% CI, -2.9 to 0.8). At 6 months, after both groups had received the intervention, the differences between the 2 groups were not significantly different for symptoms of PTSD and depression; showed similar ratings for psychosocial function; and teachers did not report significant differences in classroom behaviors. CONCLUSION A standardized 10-session cognitive-behavioral group intervention can significantly decrease symptoms of PTSD and depression in students who are exposed to violence and can be effectively delivered on school campuses by trained school-based mental health clinicians.", "title": "A mental health intervention for schoolchildren exposed to violence: a randomized controlled trial." }, { "docid": "24510595", "text": "PURPOSE Patients with daily or near-daily headaches are commonly seen in neurology practices and in headache subspecialty centers, but there is little information on the prevalence of this condition in the general population. We present the first US-based study describing the prevalence and characteristics of frequent headache in the general population. METHODS In Baltimore County, Maryland, 13 343 individuals 18 to 65 years of age were selected by random-digit dialing and interviewed by telephone about their headaches. Subjects reporting 180 or more headaches per year were classified as having frequent headache. Three mutually exclusive subtypes of frequent headache were identified: frequent headache with migrainous features, chronic tension-type headache, and unclassified frequent headache. RESULTS The overall prevalence of frequent headache was 4.1% (5.0% female, 2.8% male; 1.8:1 female to male ratio). Frequent headache was 33% more common in Caucasians (4.4%) than in African Americans (3.3%). In both males and females, prevalence was highest in the lowest educational category. Among frequent headache sufferers, more than half (52% female, 56% male) met criteria for chronic tension-type headache, almost one third (33% female, 25% male) met criteria for frequent headache with migrainous features, and the remainder (15% female, 19% male) were unclassified. Overall, 30% of female and 25% of male frequent headache sufferers met International Headache Society (IHS) criteria for migraine (with or without aura). CONCLUSIONS Frequent headache is common in the general population and is more prevalent in Caucasians and in those with less than a high school education. Chronic tension-type headache is more common than frequent headache with migrainous features, though the latter is more disabling. Although more common in females than males, the female preponderance of frequent headache is less marked than in migraine. The sex ratio varies by frequent headache subtype.", "title": "Prevalence of frequent headache in a population sample." }, { "docid": "36558211", "text": "OBJECTIVES To explore the different characteristics of high and low fat consumers, in particular their macronutrient intake and body mass index. DESIGN Reanalysis of data from the Dietary and Nutritional Survey of British Adults. Comparisons were made between groups defined as high and low fat consumers on the basis of 7-day weighed food records considered to be valid for energy intake. Individuals were classified in two ways according to the percentage energy from fat (FAT%) and the absolute amount of fat consumed (FATg). The criteria for classification of the high FAT% being > 45% (high fat) and < or = 35% (low fat). For the FATg group the threshold for the high fat group was > 138 g/day (men) and > 102 g/day (women), and for the low fat group < 85 g/day (men) and < 70 g/day (women). SETTING Dietary data was collected from private households in Great Britain between 1986 and 1987. SUBJECTS From the total population of 2197, individuals who were slimming, ill or had an EI: BMR of < 1.2 were excluded in order to use data which was most likely to represent habitual energy intakes. From the remaining 1240 subjects, 10.8% of this sample (6.1% of the total population) were classified as low fat consumers (76 men and 58 women) and 15.4% high fat (8.7% of the total population, 93 men and 98 women). MAIN OUTCOME MEASURES Macronutrient consumption and body mass index (BMI). RESULTS 30% of the subjects changed fat group classification when the criteria of defining high and low fat groups altered from FAT% to FATg. Nutrient intakes differed according to definition of the groups. The high fat FATg group ate significantly more of all nutrients than the low fat FATg group. However, this was not seen for the FAT% analysis, with the high fat group eating more fat and less carbohydrate. The average BMI tended to be higher in the high fat than the low fat groups, particularly in the FATg analysis. However, the high fat group contained a wide range of BMIs. Further exploration of BMI in the high fat groups, showed that age (an 11-year difference) was the only variable to distinguish individuals in the top and bottom quartiles of BMI. CONCLUSIONS High and low fat consumers differ according to a number of variables, and this is affected by how these groups are defined (FAT% or FATg). High fat consumers tend to have a higher BMI than low fat consumers, but not all high fat consumers are overweight or obese.", "title": "High and low fat consumers, their macronutrient intake and body mass index: further analysis of the National Diet and Nutrition Survey of British Adults." }, { "docid": "2295434", "text": "myfood24 Is an online 24-h dietary assessment tool developed for use among British adolescents and adults. Limited information is available regarding the validity of using new technology in assessing nutritional intake among adolescents. Thus, a relative validation of myfood24 against a face-to-face interviewer-administered 24-h multiple-pass recall (MPR) was conducted among seventy-five British adolescents aged 11-18 years. Participants were asked to complete myfood24 and an interviewer-administered MPR on the same day for 2 non-consecutive days at school. Total energy intake (EI) and nutrients recorded by the two methods were compared using intraclass correlation coefficients (ICC), Bland-Altman plots (using between and within-individual information) and weighted κ to assess the agreement. Energy, macronutrients and other reported nutrients from myfood24 demonstrated strong agreement with the interview MPR data, and ICC ranged from 0·46 for Na to 0·88 for EI. There was no significant bias between the two methods for EI, macronutrients and most reported nutrients. The mean difference between myfood24 and the interviewer-administered MPR for EI was -230 kJ (-55 kcal) (95 % CI -490, 30 kJ (-117, 7 kcal); P=0·4) with limits of agreement ranging between 39 % (3336 kJ (-797 kcal)) lower and 34 % (2874 kJ (687 kcal)) higher than the interviewer-administered MPR. There was good agreement in terms of classifying adolescents into tertiles of EI (κ w =0·64). The agreement between day 1 and day 2 was as good for myfood24 as for the interviewer-administered MPR, reflecting the reliability of myfood24. myfood24 Has the potential to collect dietary data of comparable quality with that of an interviewer-administered MPR.", "title": "Agreement between an online dietary assessment tool (myfood24) and an interviewer-administered 24-h dietary recall in British adolescents aged 11-18 years." }, { "docid": "6710713", "text": "OBJECTIVE To determine whether there are risk factors in a doctor's time at medical school that are associated with subsequent professional misconduct. DESIGN Matched case-control study. Setting Records from medical schools and the General Medical Council (GMC). PARTICIPANTS 59 doctors who had graduated from any one of eight medical schools in the United Kingdom in 1958-97 and had a proved finding of serious professional misconduct in GMC proceedings in 1999-2004 (cases); 236 controls (four for each case) were selected by systematic sampling from matching graduation cohorts. Case-control status was revealed by the GMC after completion of data entry. MAIN OUTCOME MEASURE Odds ratios for being a \"case,\" with multivariable conditional logistic regression of potential risk factors including pre-admission characteristics and progress during the course. These data were obtained from anonymised copies of the students' progress files held by their original medical schools. RESULTS Univariate conditional logistic regression analysis found that cases were more likely to be men, to be of lower estimated social class, and to have had academic difficulties during their medical course, especially in the early years. Multivariable analysis showed that male sex (odds ratio 9.80, 95% confidence interval 2.43 to 39.44, P=0.001), lower social class (4.28, 1.52 to 12.09, P=0.006), and failure of early or preclinical examinations (5.47, 2.17 to 13.79, P<0.001) were independently associated with being a case. CONCLUSIONS This small study suggests that male sex, a lower socioeconomic background, and early academic difficulties at medical school could be risk factors for subsequent professional misconduct. The findings are preliminary and should be interpreted with caution. Most doctors with risk factors will not come before the GMC's disciplinary panels.", "title": "Risk factors at medical school for subsequent professional misconduct: multicentre retrospective case-control study" }, { "docid": "84580585", "text": "This volume and its companion, Volume 350, are specifically designed to meet the needs of graduate students and postdoctoral students as well as researchers, by providing all the up-to-date methods necessary to study genes in yeast. Procedures are included that enable newcomers to set up a yeast laboratory and to master basic manipulations. Relevant background and reference information given for procedures can be used as a guide to developing protocols in a number of disciplines. Specific topics addressed in this book include cytology, biochemistry, cell fractionation, and cell biology.", "title": "Guide to yeast genetics and molecular biology" }, { "docid": "31543713", "text": "The recent development of microarray technology has led statisticians and bioinformaticians to develop new statistical methodologies for comparing different biological samples. The objective is to identify a small number of differentially expressed genes from among thousands. In quantitative proteomics, analysis of protein expression using two-dimensional gel electrophoresis shows some similarities with transcriptomic studies. Thus, the goal of this study was to evaluate different data analysis methodologies widely used in array analysis using different proteomic data sets of hundreds of proteins. Even with few replications, the significance analysis of microarrays method appeared to be more powerful than the Student's t test in truly declaring differentially expressed proteins. This procedure will avoid wasting time due to false positives and losing information with false negatives.", "title": "Data analysis methods for detection of differential protein expression in two-dimensional gel electrophoresis." }, { "docid": "34818263", "text": "As time passes, the AIDS pandemic continues to spike, affecting an estimated 38.6 million people worldwide. In response, a satellite health clinic is being d esigned by two Cal Poly students to serve the Maasai people living in the Kajiado district in Southern Kenya. The Maasai have traditionally lived as pastoralists, surviving off of their cattle with which they share their water, increasing the risk for contamination. However, as the population of Kenya increases, the land the Maasai have traditionally used for grazing is shrink­ ing. For this reason, some have turned to farming to maintain their liveli­ hood. These factors have contributed to the desertification and deforestation of their region. As the lifestyle of the Maasai evolves, they rely more on maize than meat and dairy products for their nutrients. All of these changes have contributed to the evolution of the Maasai culture. We will address these changes in order to better understand the Maasai, as well as highlight pos­ sible further aid needed to support their survival.", "title": "Current Health and Environmental Status of the Maasai People in Sub-Saharan Africa" }, { "docid": "3413083", "text": "BACKGROUND Following widespread rollout of chlamydia testing to non-specialist and community settings in the UK, many individuals receive a chlamydia test without being offered comprehensive STI and HIV testing. We assess sexual behaviour among testers in different settings with a view to understanding their need for other STI diagnostic services. METHODS A probability sample survey of the British population undertaken 2010-2012 (the third National Survey of Sexual Attitudes and Lifestyles). We analysed weighted data on chlamydia testing (past year), including location of most recent test, and diagnoses (past 5 years) from individuals aged 16-44 years reporting at least one sexual partner in the past year (4992 women, 3406 men). RESULTS Of the 26.8% (95% CI 25.4% to 28.2%) of women and 16.7% (15.5% to 18.1%) of men reporting a chlamydia test in the past year, 28.4% of women and 41.2% of men had tested in genitourinary medicine (GUM), 41.1% and 20.7% of women and men respectively tested in general practice (GP) and the remainder tested in other non-GUM settings. Women tested outside GUM were more likely to be older, in a relationship and to live in rural areas. Individuals tested outside GUM reported fewer risk behaviours; nevertheless, 11.0% (8.6% to 14.1%) of women and 6.8% (3.9% to 11.6%) of men tested in GP and 13.2% (10.2% to 16.8%) and 9.6% (6.5% to 13.8%) of women and men tested in other non-GUM settings reported 'unsafe sex', defined as two or more partners and no condom use with any partner in the past year. Individuals treated for chlamydia outside GUM in the past 5 years were less likely to report an HIV test in that time frame (women: 54.5% (42.7% to 65.7%) vs 74.1% (65.9% to 80.9%) in GUM; men: 23.9% (12.7% to 40.5%) vs 65.8% (56.2% to 74.3%)). CONCLUSIONS Most chlamydia testing occurred in non-GUM settings, among populations reporting fewer risk behaviours. However, there is a need to provide pathways to comprehensive STI care to the sizeable minority at higher risk.", "title": "Patterns of chlamydia testing in different settings and implications for wider STI diagnosis and care: a probability sample survey of the British population" }, { "docid": "36033696", "text": "OBJECTIVE The purpose of this project was to educate inpatients with psychotic disorders, many of whom were taking second-generation antipsychotics, about lifestyle changes they can make to combat weight gain. METHOD All inpatients on a Veterans Affairs acute inpatient schizophrenia treatment unit were invited to a 30-minute, didactic presentation given by a medical student and a psychology student under the supervision of the primary investigator. The topics covered included the health benefits of maintaining an ideal body weight by selecting foods according to the USDA Food Pyramid, determining adequate food portions, choosing healthy meals outside the home, and beginning and adhering to an exercise program. Subjects completed a 13-item quiz concerning their knowledge of food and nutrition before and after the presentation to determine its efficacy in teaching patients the material. RESULTS Fifty patients completed both the pre- and post-presentation tests. The mean percentage of correct answers on the pre-test was 85.6%, which rose to 89.3% on the post-test. This difference of 3.7% was statistically significant (t = 2.43, df = 49, p < 0.02), and the mean percent of improvement was 6.1%. CONCLUSIONS This study demonstrates that psychotic individuals are able to benefit from educational presentations about nutrition and a healthy lifestyle. A statistically significant improvement in test scores suggests that subjects gained an understanding of basic concepts related to food choices and fitness.", "title": "A wellness class for inpatients with psychotic disorders." }, { "docid": "45027320", "text": "BACKGROUND The aim of this study was to examine the clustering of four major lifestyle risk factors (smoking, heavy drinking, lack of fruit and vegetables consumption, and lack of physical activity), and to examine the variation across different socio-demographic groups in the English adult population. METHODS The study population was derived from the 2003 Health Survey for England (n=11,492). Clustering was examined by comparing the observed and expected prevalence of the different possible combinations. A multinomial multilevel regression model was conducted to examine the socio-demographic variation in the clustering of the four risk factors. RESULTS The study found that, when using British health recommendations, a majority of the English population have multiple lifestyle risk factors at the same time. Clustering was found at both ends of the lifestyle spectrum and was more pronounced for women than for men. Overall, multiple risk factors were more prevalent among men, lower social class households, singles, and people who are economically inactive, but less prevalent among home owners and older age groups. CONCLUSIONS The clustering of multiple risk factors provides support for multiple-behavior interventions as opposed to single-behavior interventions.", "title": "The prevalence and clustering of four major lifestyle risk factors in an English adult population." }, { "docid": "13445579", "text": "BACKGROUND AND PURPOSE IAs are found in 2.3% of adults; the mean age at detection is 52 years. Prevalence is <0.5% in young adults. Early studies suggest that 10%-50% of patients with aortic coarctation have IAs. Screening recommendations are variable. We sought to examine the prevalence of IAs through screening with MRA. MATERIALS AND METHODS Consecutive patients older than 16 years of age with coarctation undergoing brain MRA between May 1999 and October 2007 were included. MRA was performed by using a 1.5T scanner with a 3D time-of-flight protocol; simultaneous MR imaging was performed of the heart and aorta. Cerebral MRAs were double-reported by a neuroradiologist. Statistics are described as mean ± SD and median ± range. Continuous variables were compared by using Student t tests and Mann-Whitney U tests (categoric variables, by using the Fisher exact test). RESULTS One hundred seventeen MRAs were double-reported. The median age was 29 ± 11 years (range, 16-59 years). IAs were found in 12 patients (10.3%). The mean diameter of IAs was 3.9 mm (range, 2.0-8.0 mm). Patients with aneurysms were older (median, 37 years; range, 16-50 years) than those without (median, 23 years; range, 16-59 years; Z = -2.01, P = .04). Hypertension was more common in those with IAs (IA 83% versus no IA 43%, P = .01). There was no association between ascending aortopathy, bicuspid aortic valves, and IAs. CONCLUSIONS Patients with coarctation have a higher prevalence of IAs, occurring at an earlier age than in population studies. Whether routine screening is appropriate for this group of patients is unclear. Hypertension is likely to be an important pathophysiologic factor.", "title": "Results of screening for intracranial aneurysms in patients with coarctation of the aorta." }, { "docid": "13900610", "text": "BACKGROUND Self-harm and suicide are common in prisoners, yet robust information on the full extent and characteristics of people at risk of self-harm is scant. Furthermore, understanding how frequently self-harm is followed by suicide, and in which prisoners this progression is most likely to happen, is important. We did a case-control study of all prisoners in England and Wales to ascertain the prevalence of self-harm in this population, associated risk factors, clustering effects, and risk of subsequent suicide after self-harm. METHODS Records of self-harm incidents in all prisons in England and Wales were gathered routinely between January, 2004, and December, 2009. We did a case-control comparison of prisoners who self-harmed and those who did not between January, 2006, and December, 2009. We also used a Bayesian approach to look at clustering of people who self-harmed. Prisoners who self-harmed and subsequently died by suicide in prison were compared with other inmates who self-harmed. FINDINGS 139,195 self-harm incidents were recorded in 26,510 individual prisoners between 2004 and 2009; 5-6% of male prisoners and 20-24% of female inmates self-harmed every year. Self-harm rates were more than ten times higher in female prisoners than in male inmates. Repetition of self-harm was common, particularly in women and teenage girls, in whom a subgroup of 102 prisoners accounted for 17,307 episodes. In both sexes, self-harm was associated with younger age, white ethnic origin, prison type, and a life sentence or being unsentenced; in female inmates, committing a violent offence against an individual was also a factor. Substantial evidence was noted of clustering in time and location of prisoners who self-harmed (adjusted intra-class correlation 0·15, 95% CI 0·11-0·18). 109 subsequent suicides in prison were reported in individuals who self-harmed; the risk was higher in those who self-harmed than in the general prison population, and more than half the deaths occurred within a month of self-harm. Risk factors for suicide after self-harm in male prisoners were older age and a previous self-harm incident of high or moderate lethality; in female inmates, a history of more than five self-harm incidents within a year was associated with subsequent suicide. INTERPRETATION The burden of self-harm in prisoners is substantial, particularly in women. Self-harm in prison is associated with subsequent suicide in this setting. Prevention and treatment of self-harm in prisoners is an essential component of suicide prevention in prisons. FUNDING Wellcome Trust, National Institute for Health Research, National Offender Management Service, and Department of Health.", "title": "Self-harm in prisons in England and Wales: an epidemiological study of prevalence, risk factors, clustering, and subsequent suicide" }, { "docid": "21641088", "text": "Obesity is a multifactorial disease with a marked genetic component. The situation is further complicated by the heterogeneity of obesity demonstrated by the topographical distribution of body fat, e.g. upper body (central) and lower body (gluteal) obesity. Furthermore, the distribution of fat shows a stronger heritable tendency compared with total body fat. Central obesity is characterized by hyperinsulinaemia and insulin resistance, a feature in common with non-insulin dependent diabetes mellitus, hypertension and atherosclerosis. In order to study the molecular genetics of central obesity we have examined 56 severely obese (mean body mass index 40), unrelated British Caucasoid young non-diabetic women for associations of restriction fragment length polymorphism of candidate genes with anthropometric measurements and indices of insulin secretion and resistance. The candidate genes examined were insulin receptor, insulin sensitive glucose transporter and insulin. An association of the class 3 allele of the hypervariable region in the 5' flanking region of the insulin gene was found with upper segment obesity (P = 0.005). Furthermore, the class 3 allele was also associated with fasting hyperinsulinaemia (P = 0.01), stimulated insulin secretion (P = 0.01) and insulin resistance as calculated from the homeostatic model of assessment (HOMA; P = 0.008). No such associations were found with the other candidate genes studied. This data suggests that polymorphisms in the 5' flanking region of the insulin gene may affect expression of the gene and thereby modulate insulin production in severely obese female subjects.", "title": "Central obesity and hyperinsulinaemia in women are associated with polymorphism in the 5' flanking region of the human insulin gene." }, { "docid": "9211173", "text": "BACKGROUND Ovarian clear-cell and endometrioid carcinomas may arise from endometriosis, but the molecular events involved in this transformation have not been described. METHODS We sequenced the whole transcriptomes of 18 ovarian clear-cell carcinomas and 1 ovarian clear-cell carcinoma cell line and found somatic mutations in ARID1A (the AT-rich interactive domain 1A [SWI-like] gene) in 6 of the samples. ARID1A encodes BAF250a, a key component of the SWI–SNF chromatin remodeling complex. We sequenced ARID1A in an additional 210 ovarian carcinomas and a second ovarian clear-cell carcinoma cell line and measured BAF250a expression by means of immunohistochemical analysis in an additional 455 ovarian carcinomas. RESULTS ARID1A mutations were seen in 55 of 119 ovarian clear-cell carcinomas (46%), 10 of 33 endometrioid carcinomas (30%), and none of the 76 high-grade serous ovarian carcinomas. Seventeen carcinomas had two somatic mutations each. Loss of the BAF250a protein correlated strongly with the ovarian clear-cell carcinoma and endometrioid carcinoma subtypes and the presence of ARID1A mutations. In two patients, ARID1A mutations and loss of BAF250a expression were evident in the tumor and contiguous atypical endometriosis but not in distant endometriotic lesions. CONCLUSIONS These data implicate ARID1A as a tumor-suppressor gene frequently disrupted in ovarian clear-cell and endometrioid carcinomas. Since ARID1A mutation and loss of BAF250a can be seen in the preneoplastic lesions, we speculate that this is an early event in the transformation of endometriosis into cancer. (Funded by the British Columbia Cancer Foundation and the Vancouver General Hospital–University of British Columbia Hospital Foundation.).", "title": "ARID1A mutations in endometriosis-associated ovarian carcinomas." }, { "docid": "12561083", "text": "BACKGROUND Several studies have demonstrated that women with nonobstructive coronary disease have a high rate of subsequent investigations, rehospitalizations for recurrent chest pain, and repeat coronary angiography. The sex specificity of this finding is unclear. We therefore undertook an evaluation of sex differences in rehospitalization for acute coronary syndrome (ACS) or chest pain in patients with \"angiographically normal\" coronaries. METHODS A retrospective cohort study using prospectively collected angiographic and clinical data on all patients in British Columbia, Canada, presenting for their first cardiac catheterization with suspected ischemic heart disease but angiographically normal coronaries. RESULTS Among 32,856 patients, 7.1% of men versus 23.3% of women were angiographically normal (P < .001). Among angiographically normal patients, women were older and more likely to present with hypertension, prior stroke, chronic obstructive pulmonary disease, and peripheral vascular disease than men, but Canadian Cardiovascular Society class of angina did not vary by sex. Within 1 year, 1.0% died, (19 women, 18 men, P = .27) and 0.6% had a stroke (13 women, 9 men, P = .91). Readmission to hospital for ACS or chest pain requiring catheterization was significantly higher in women compared to men (adjusted OR 4.06; 95% CI 1.15-14.31). CONCLUSIONS In a contemporary, population-based cohort presenting for cardiac catheterization for suspected ischemia, women with angiographically normal coronaries were >4 times more likely to be readmitted to hospital for ACS/chest pain within 180 days compared to men. The observed sex difference has important social and economic implications and suggests that traditional diagnostic methods may not be optimal for women.", "title": "Angina with \"normal\" coronary arteries: sex differences in outcomes." }, { "docid": "18557974", "text": "High plasma total homocysteine (tHcy) concentration is reported to be a risk factor for vascular diseases. We investigated the extent to which serum folate and plasma tHcy respond to a high intake of natural folate from food. Thirty-seven healthy females volunteered t o participate in a crossover dietary intervention. The study included a baseline period and two 5-week diet periods (low- and high-folate diets) with a 3-week washout in between. The low-folate diet contained one serving of both vegetables and fruit/d, while during the high-folate diet the subjects ate at least seven servings of vegetables, berries, and citrus fruit/d. Serum and erythrocyte (RBC) folate, serum vitamin B (12), and plasma tHcy concentrations were measured at the base-line and at the end of each diet period. The mean concentrations of serum and RBC folate were 11.0 (SD 3.0) nmol/l and 412 (SD 120) nmol/l at the end of the low-folate diet and 78 (95 % CI 62, 94) % and 14 (95 % CI 8, 20) % higher in response to the high-folate diet (P< 0.001). The serum concentration of vitamin B12 remained unchanged during the intervention. The mean plasma tHcy concentration was 8.0 pmol/ at the end of the low-folate diet and decreased by 13 (95% CI 9, 18) % in response to the high-folate diet (P<0.001). In conclusion, a diet high in fresh berries, citrus fruit, and vegetables effectively increases serum and RBC folate and decreases plasma homocysteine.", "title": "British Journal of Nutrition (2003), 89, 295–301 q The Authors 2003 DOI: 10.1079/BJN2002776 Plasma homocysteine concentration is decreased by dietary intervention*" }, { "docid": "143381103", "text": "This article provides psychometric information on the second edition of the Beck Depression Inventory (BDI-II; A. T. Beck, R. A. Steer, & G. K. Brown, 1996), with respect to internal consistency, factorial validity, and gender differences. Both measures demonstrated high internal reliability in the full student sample. Significant differences between the mean BDI and BDI-II scores necessitated the development of new cutoffs for analogue research on the BDI-II. Results from exploratory and confirmatory factor analyses indicated that a 2-factor solution optimally summarized the data for both versions of the inventory and accounted for a cumulative 41% and 46% of the common variance in BDI and BDI-II responses, respectively. These factor solutions were reliably cross-validated, although the importance of each factor varied by gender. The authors conclude that the BDI-II is a stronger instrument than the BDI in terms of its factor structure.", "title": "A psychometric evaluation of the Beck Depression Inventory–II." }, { "docid": "23439808", "text": "We hypothesized that serum cystatin C can be a more predictable marker of arterial stiffness than serum creatinine and creatinine-based glomerular filtration rate (GFR). The aim of this study is to evaluate whether serum cystatin C is related to arterial stiffness independently of serum creatinine in subjects for whom serum creatinine is normal. A total of 2,018 individuals (1,120 males, 898 females) were enrolled. Mean brachial-ankle pulse wave velocity (baPWV) was used as a marker of arterial stiffness and sex-specific analysis was performed. A positive relationship between baPWV and serum cystatin C (Y=1109.0548+329.9102X, r2=0.056, p<0.001) was found in males. Stepwise multivariate regression analysis in males showed that age, waist circumference, heart rate, cystatin C level, triglyceride level, and fasting glucose were independent contributors to baPWV. In females, a positive relationship between baPWV and serum cystatin C (Y=1035.7828+402.2970X, r2=0.090, p<0.001) was found. Stepwise multivariate regression analysis showed that age, heart rate, cystatin C level, fasting glucose and insulin level were independent contributors to baPWV. Age, heart rate, fasting glucose and serum cystatin C were the significant variables in both genders that contributed to baPWV. In conclusion, this study confirmed that serum cystatin C was related to pulse wave velocity even in subjects with normal serum creatinine. This finding suggested that cystatin C could be a more predictable marker of arterial stiffness than serum creatinine and creatinine-based GFR.", "title": "Serum Cystatin C Is Related to Pulse Wave Velocity Even in Subjects with Normal Serum Creatinine" }, { "docid": "34228604", "text": "Females live longer than males in many species, including humans. We have traced a possible explanation for this phenomenon to the beneficial action of estrogens, which bind to estrogen receptors and increase the expression of longevity-associated genes, including those encoding the antioxidant enzymes superoxide dismutase and glutathione peroxidase. As a result, mitochondria from females produce fewer reactive oxygen species than those from males. Administering estrogens has serious drawbacks, however--they are feminizing (and thus cannot be administered to males) and may increase the incidence of serious diseases such as uterine cancer in postmenopausal women. Phytoestrogens, which are present in soy or wine, may have some of the favorable effects of estrogens without their undesirable effects. Study of gender differences in longevity may help us to understand the basic processes of aging and to devise practical strategies to increase the longevity of both females and males.", "title": "Why females live longer than males: control of longevity by sex hormones." }, { "docid": "6503534", "text": "A group of 27 Italian patients was screened for α-L-iduronidase mucopolysaccharidosis type I mutations. Mutations were found in 18 patients, with 28 alleles identified. The two most common mutations in northern Europeans (W402X and Q70X) accounted for 11% and 13% of the alleles, respectively. The R89Q mutation, uncommon in Europeans, was found only in one patient, accounting for 1 of 54 alleles (1.9%). The other mutations, P533R, A327P and G51D, accounted for 11%, 5.6% and 9.3% of the total alleles, respectively. Interestingly, the high frequency of the P533R mutation seems to be confined to Sicily and is higher than the 3% reported in a British/Australian study.", "title": "Mutations among Italian mucopolysaccharidosis type I patients" }, { "docid": "10209731", "text": "STUDY OBJECTIVE The aim of the study was to analyse differences in mortality from the main cardiovascular diseases (ischaemic heart disease, hypertensive disease, and cerebrovascular disease) among Chinese, Malays, and Indians in Singapore. DESIGN The study was a survey using national death registration data in Singapore for the five years 1980 to 1984. The underlying cause of death, coded according to the ninth revision of the International Classification of Diseases, was taken for the analyses. SETTING The study was confined to the independent island state of Singapore, population 2.53 million (Chinese 76.5%, Malays 14.8%, Indians 6.4%, Others 2.3%). Death registration is thought to be complete. SUBJECTS All registered deaths in the age range 30-69 years during the study period were analysed by ethnic group. MEASUREMENT AND MAIN RESULTS Indians had higher mortality from ischaemic heart disease than the other ethnic groups in both sexes, with age-standardised relative risks of Indian v Chinese (males 3.8, females 3.4), Indian v Malay (males 1.9, females 1.6), and Malay v Chinese (males 2.0, females 2.2). The excess mortality in Indians declined with age. For hypertensive disease Malays had the highest mortality, with age-standardised relative risks of Malay v Chinese (males 3.4, females 4.4), Malay v Indian (males 2.0, females 2.5), and Indian v Chinese (males 1.6, females 1.6). For cerebrovascular disease there was little ethnic difference except for lower rates in Chinese females, with age-standardised relative risks of Malay v Chinese (males 1.1, females 1.9), Malay v Indian (males 1.0, females 1.1), and Indian v Chinese (males 1.1, females 1.7). CONCLUSIONS There are significant differences in mortality from the three main cardiovascular diseases in the different ethnic groups in Singapore.", "title": "Cardiovascular diseases in Chinese, Malays, and Indians in Singapore. I. Differences in mortality." }, { "docid": "3552753", "text": "BACKGROUND In the assessment of severity in community acquired pneumonia (CAP), the modified British Thoracic Society (mBTS) rule identifies patients with severe pneumonia but not patients who might be suitable for home management. A multicentre study was conducted to derive and validate a practical severity assessment model for stratifying adults hospitalised with CAP into different management groups. METHODS Data from three prospective studies of CAP conducted in the UK, New Zealand, and the Netherlands were combined. A derivation cohort comprising 80% of the data was used to develop the model. Prognostic variables were identified using multiple logistic regression with 30 day mortality as the outcome measure. The final model was tested against the validation cohort. RESULTS 1068 patients were studied (mean age 64 years, 51.5% male, 30 day mortality 9%). Age >/=65 years (OR 3.5, 95% CI 1.6 to 8.0) and albumin <30 g/dl (OR 4.7, 95% CI 2.5 to 8.7) were independently associated with mortality over and above the mBTS rule (OR 5.2, 95% CI 2.7 to 10). A six point score, one point for each of Confusion, Urea >7 mmol/l, Respiratory rate >/=30/min, low systolic(<90 mm Hg) or diastolic (</=60 mm Hg) Blood pressure), age >/=65 years (CURB-65 score) based on information available at initial hospital assessment, enabled patients to be stratified according to increasing risk of mortality: score 0, 0.7%; score 1, 3.2%; score 2, 3%; score 3, 17%; score 4, 41.5% and score 5, 57%. The validation cohort confirmed a similar pattern. CONCLUSIONS A simple six point score based on confusion, urea, respiratory rate, blood pressure, and age can be used to stratify patients with CAP into different management groups.", "title": "Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study." }, { "docid": "9310407", "text": "INTRODUCTION Isotonic crystalloids play a central role in perioperative fluid management. Isooncotic preparations of colloids (for example, human albumin or hydroxyethyl starch) remain nearly completely intravascular when infused to compensate for acute blood losses. Recent data were interpreted to indicate a comparable intravascular volume effect for crystalloids, challenging the occasionally suggested advantage of using colloids to treat hypovolemia. General physiological knowledge and clinical experience, however, suggest otherwise. METHODS In a prospective study, double-tracer blood volume measurements were performed before and after intended normovolemic hemodilution in ten female adults, simultaneously substituting the three-fold amount of withdrawn blood with Ringer's lactate. Any originated deficits were substituted with half the volume of 20% human albumin, followed by a further assessment of blood volume. To assess significance between the measurements, repeated measures analysis of variance (ANOVA) according to Fisher were performed. If significant results were shown, paired t tests (according to Student) for the singular measurements were taken. P < 0.05 was considered to be significant. RESULTS A total of 1,097 ± 285 ml of whole blood were withdrawn (641 ± 155 ml/m(2) body surface area) and simultaneously replaced by 3,430 ± 806 ml of Ringer's lactate. All patients showed a significant decrease in blood volume after hemodilution (-459 ± 185 ml; P < 0.05) that did not involve relevant hemodynamical changes, and a significant increase in interstitial water content (+2,157 ± 606 ml; P < 0.05). The volume effect of Ringer's lactate was 17 ± 10%. The infusion of 245 ± 64 ml of 20% human albumin in this situation restored blood volume back to baseline values, the volume effect being 184 ± 63%. CONCLUSIONS Substitution of isolated intravascular deficits in cardiopulmonary healthy adults with the three-fold amount of Ringer's lactate impedes maintenance of intravascular normovolemia. The main side effect was an impressive interstitial fluid accumulation, which was partly restored by the intravenous infusion of 20% human albumin. We recommend to substitute the five-fold amount of crystalloids or to use an isooncotic preparation in the face of acute bleeding in patients where edema prevention might be advantageous.", "title": "The intravascular volume effect of Ringer's lactate is below 20%: a prospective study in humans" }, { "docid": "20610390", "text": "OBJECTIVES To investigate incidence, mortality and case survival trends for cancer of unknown primary site (CUP) and consider clinical implications. METHOD South Australian Cancer Registry data were used to calculate age-standardised incidence and mortality rates from 1977 to 2004. Disease-specific survivals, socio-demographic, histological and secular predictors of CUP, compared with cancers of known primary site, and of CUP histological types, using multivariable logistic regression were investigated. RESULTS Incidence and mortality rates increased approximately 60% between 1977--80 and 1981--84. Rates peaked in 1993--96. Male to female incidence and mortality rate ratios approximated 1.3:1. Incidence and mortality rates increased with age. The odds of unspecified histological type, compared with the more common adenocarcinomas, were higher for males than females, non-metropolitan residents, low socio-economic areas, and for 1977--88 than subsequent diagnostic periods. CUP represented a higher proportion of cancers in Indigenous patients. Case survival was 7% at 10 years from diagnosis. Factors predictive of lower case survival included older age, male sex, Indigenous status, lower socio-economic status, and unspecified histology type. CONCLUSION Results point to poor CUP outcomes, but with a modest improvement in survival. The study identifies socio-demographic groups at elevated risk of CUP and of worse treatment outcomes where increased research and clinical attention are required.", "title": "Exploring the epidemiological characteristics of cancers of unknown primary site in an Australian population: implications for research and clinical care." }, { "docid": "60515890", "text": "\" The Mouse Brain in Stereotaxic Coordinates\" is the most widely used and cited atlas of the mouse brain in print. It provides researchers and students with both accurate stereotaxic coordinates for laboratory use, and detailed delineations and indexing of structures for reference. The accompanying DVD provides drawings of brains structures that can be used as templates for making figures for publication. The 3rd edition is both a major revision and an expansion of previous editions. Delineations and photographs in the horizontal plane of section now complement the coronal and sagittal series, and all the tissue sections are now shown in high resolution digital color photography. The photographs of the sections and the intermediate sections are also provided on the accompanying DVD in high-resolution JP 2000 format. The delineations of structures have been revised, and naming conventions made consistent with Paxinos and Watson's \"Rat Brain in Stereotaxic Coordinates, 6th Edition\". The 3rd edition of this atlas is now in more practical 14\"x11\" format for convenient lab use. This edition is in full color throughout. It includes a CD of all plates and diagrams, as well as Adobe Illustrator files of the diagrams, and a variety of additional useful material. Coronal and sagittal diagrams are completely reworked and updated. Rhombomeric borders are included in sagittal figures, for the first time in mammals. Microscopic plates are scanned with a new method in much higher quality.", "title": "The Mouse Brain in Stereotaxic Coordinates" }, { "docid": "2052720", "text": "OBJECTIVE To investigate the association between gastric cancer and prior infection with Helicobacter pylori. DESIGN Case-control comparison of prevalence of IgG antibodies to H pylori in blood samples collected prospectively, before diagnosis of gastric cancer in the cases. Presence of H pylori antibody (greater than 10 micrograms IgG/ml) determined by enzyme linked immunosorbent assay (ELISA). SUBJECTS 29 men with a subsequent diagnosis of gastric cancer and 116 aged matched controls selected from over 22,000 middle aged men participating in two ongoing cohort studies (the British United Provident Association study and the Caerphilly collaborative heart disease study), who had provided blood samples during 1975-1982. RESULTS 20 of the 29 cases (69%) and 54 of the 116 controls (47%) were positive for H pylori specific antibody. The median specific IgG concentration was significantly higher in the cases than controls (90 micrograms/ml v 3.6 micrograms/ml, p less than 0.01). The estimated odds ratio for the risk of gastric cancer in those with a history of infection with H pylori was 2.77 (95% confidence interval 1.04 to 7.97, 2p = 0.039). CONCLUSIONS H pylori infection may be an important cause of gastric cancer; between 35% and 55% of all cases may be associated with such an infection.", "title": "Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation." } ]
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Decrease of p62 in prostate tumor stroma results in defective autophagy.
[ { "docid": "3701541", "text": "Hepatic stellate cells (HSCs) play critical roles in liver fibrosis and hepatocellular carcinoma (HCC). Vitamin D receptor (VDR) activation in HSCs inhibits liver inflammation and fibrosis. We found that p62/SQSTM1, a protein upregulated in liver parenchymal cells but downregulated in HCC-associated HSCs, negatively controls HSC activation. Total body or HSC-specific p62 ablation potentiates HSCs and enhances inflammation, fibrosis, and HCC progression. p62 directly interacts with VDR and RXR promoting their heterodimerization, which is critical for VDR:RXR target gene recruitment. Loss of p62 in HSCs impairs the repression of fibrosis and inflammation by VDR agonists. This demonstrates that p62 is a negative regulator of liver inflammation and fibrosis through its ability to promote VDR signaling in HSCs, whose activation supports HCC.", "title": "p62/SQSTM1 by Binding to Vitamin D Receptor Inhibits Hepatic Stellate Cell Activity, Fibrosis, and Liver Cancer." } ]
[ { "docid": "26735905", "text": "The tumor microenvironment plays a critical role in cancer progression, but the precise mechanisms by which stromal cells influence the epithelium are poorly understood. Here we show that p62 levels were reduced in the stroma of several tumors and that its loss in the tumor microenvironment or stromal fibroblasts resulted in increased tumorigenesis of epithelial prostate cancer cells. The mechanism involves the regulation of cellular redox through an mTORC1/c-Myc pathway of stromal glucose and amino acid metabolism, resulting in increased stromal IL-6 production, which is required for tumor promotion in the epithelial compartment. Thus, p62 is an anti-inflammatory tumor suppressor that acts through the modulation of metabolism in the tumor stroma.", "title": "Metabolic reprogramming of stromal fibroblasts through p62-mTORC1 signaling promotes inflammation and tumorigenesis." }, { "docid": "25576204", "text": "Malignant cells often display defects in autophagy, an evolutionarily conserved pathway for degrading long-lived proteins and cytoplasmic organelles. However, as yet, there is no genetic evidence for a role of autophagy genes in tumor suppression. The beclin 1 autophagy gene is monoallelically deleted in 40-75% of cases of human sporadic breast, ovarian, and prostate cancer. Therefore, we used a targeted mutant mouse model to test the hypothesis that monoallelic deletion of beclin 1 promotes tumorigenesis. Here we show that heterozygous disruption of beclin 1 increases the frequency of spontaneous malignancies and accelerates the development of hepatitis B virus-induced premalignant lesions. Molecular analyses of tumors in beclin 1 heterozygous mice show that the remaining wild-type allele is neither mutated nor silenced. Furthermore, beclin 1 heterozygous disruption results in increased cellular proliferation and reduced autophagy in vivo. These findings demonstrate that beclin 1 is a haplo-insufficient tumor-suppressor gene and provide genetic evidence that autophagy is a novel mechanism of cell-growth control and tumor suppression. Thus, mutation of beclin 1 or other autophagy genes may contribute to the pathogenesis of human cancers.", "title": "Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene." }, { "docid": "8702697", "text": "AIMS Tumor microenvironment is a strong determinant for the acquisition of metastatic potential of cancer cells. We have recently demonstrated that cancer-associated fibroblasts (CAFs) elicit a redox-dependent epithelial-mesenchymal transition (EMT) in prostate cancer (PCa) cells, driven by cycloxygenase-2/hypoxia-inducible factor-1 (HIF-1)/nuclear factor-κB pathway and enhancing tumor aggressiveness. Here, we investigated the involvement of microRNAs (miRNAs) in tumor-stroma interplay to identify possible tools to counteract oxidative stress and metastasis dissemination. RESULTS We found that miR-205 is the most downmodulated miRNA in PCa cells upon CAF stimulation, due to direct transcriptional repression by HIF-1, a known redox-sensitive transcription factor. Rescue experiments demonstrated that ectopic miR-205 overexpression in PCa cells counteracts CAF-induced EMT, thus impairing enhancement of cell invasion, acquisition of stem cell traits, tumorigenicity, and metastatic dissemination. In addition, miR-205 blocks tumor-driven activation of surrounding fibroblasts by reducing pro-inflammatory cytokine secretion. INNOVATION Overall, such findings suggest miR-205 as a brake against PCa metastasis by blocking both the afferent and efferent arms of the circuit between tumor cells and associated fibroblasts, thus interrupting the pro-oxidant and pro-inflammatory circuitries engaged by reactive stroma. CONCLUSION The evidence that miR-205 replacement in PCa cells is able not only to prevent but also to revert the oxidative/pro-inflammatory axis leading to EMT induced by CAFs sets the rationale for developing miRNA-based approaches to prevent and treat metastatic disease.", "title": "miR-205 hinders the malignant interplay between prostate cancer cells and associated fibroblasts." }, { "docid": "24349992", "text": "Loss of stromal fibroblast caveolin-1 (Cav-1) is a powerful single independent predictor of poor prognosis in human breast cancer patients, and is associated with early tumor recurrence, lymph node metastasis and tamoxifen-resistance. We developed a novel co-culture system to understand the mechanism(s) by which a loss of stromal fibroblast Cav-1 induces a \"lethal tumor micro-environment. \" Here, we propose a new paradigm to explain the powerful prognostic value of stromal Cav-1. In this model, cancer cells induce oxidative stress in cancer-associated fibroblasts, which then acts as a \"metabolic\" and \"mutagenic\" motor to drive tumor-stroma co-evolution, DNA damage and aneuploidy in cancer cells. More specifically, we show that an acute loss of Cav-1 expression leads to mitochondrial dysfunction, oxidative stress and aerobic glycolysis in cancer associated fibroblasts. Also, we propose that defective mitochondria are removed from cancer-associated fibroblasts by autophagy/mitophagy that is induced by oxidative stress. As a consequence, cancer associated fibroblasts provide nutrients (such as lactate) to stimulate mitochondrial biogenesis and oxidative metabolism in adjacent cancer cells (the \"Reverse Warburg Effect\"). We provide evidence that oxidative stress in cancer-associated fibroblasts is sufficient to induce genomic instability in adjacent cancer cells, via a bystander effect, potentially increasing their aggressive behavior. Finally, we directly demonstrate that nitric oxide (NO) over-production, secondary to Cav-1 loss, is the root cause for mitochondrial dysfunction in cancer associated fibroblasts. In support of this notion, treatment with anti-oxidants (such as N-acetyl-cysteine, metformin and quercetin) or NO inhibitors (L-NAME) was sufficient to reverse many of the cancer-associated fibroblast phenotypes that we describe. Thus, cancer cells use \"oxidative stress\" in adjacent fibroblasts (i) as an \"engine\" to fuel their own survival via the stromal production of nutrients and (ii) to drive their own mutagenic evolution towards a more aggressive phenotype, by promoting genomic instability. We also present evidence that the \"field effect\" in cancer biology could also be related to the stromal production of ROS and NO species. eNOS-expressing fibroblasts have the ability to downregulate Cav-1 and induce mitochondrial dysfunction in adjacent fibroblasts that do not express eNOS. As such, the effects of stromal oxidative stress can be laterally propagated, amplified and are effectively \"contagious\"--spread from cell-to-cell like a virus--creating an \"oncogenic/mutagenic\" field promoting widespread DNA damage.", "title": "Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution: A new paradigm for understanding tumor metabolism, the field effect and genomic instability in cancer cells." }, { "docid": "10463997", "text": "Objectives: Autophagy is a highly regulated process that has an important role in the control of a wide range of cellular functions, such as organelle recycling, nutrient availability and tissue differentiation. A recent study has shown an increased autophagic activity in the adipose tissue of obese subjects, and a role for autophagy in obesity-associated insulin resistance was proposed. Body mass reduction is the most efficient approach to tackle insulin resistance in over-weight subjects; however, the impact of weight loss in adipose tissue autophagy is unknown. Subjects:Adipose tissue autophagy was evaluated in mice and humans. Results:First, a mouse model of diet-induced obesity and diabetes was maintained on a 15-day, 40% caloric restriction. At baseline, markers of autophagy were increased in obese mice as compared with lean controls. Upon caloric restriction, autophagy increased in the lean mice, whereas it decreased in the obese mice. The reintroduction of ad libitum feeding was sufficient to rapidly reduce autophagy in the lean mice and increase autophagy in the obese mice. In the second part of the study, autophagy was evaluated in the subcutaneous adipose tissue of nine obese-non-diabetic and six obese-diabetic subjects undergoing bariatric surgery for body mass reduction. Specimens were collected during the surgery and approximately 1 year later. Markers of systemic inflammation, such as tumor necrosis factor-1α, interleukin (IL)-6 and IL-1β were evaluated. As in the mouse model, human obesity was associated with increased autophagy, and body mass reduction led to an attenuation of autophagy in the adipose tissue. Conclusion:Obesity and caloric overfeeding are associated with the defective regulation of autophagy in the adipose tissue. The studies in obese-diabetic subjects undergoing improved metabolic control following calorie restriction suggest that autophagy and inflammation are regulated independently.", "title": "Defective regulation of adipose tissue autophagy in obesity" }, { "docid": "31882215", "text": "We describe robust induction of autophagy during the reprogramming of mouse fibroblasts to induced pluripotent stem cells by four reprogramming factors (Sox2, Oct4, Klf4 and c-Myc), henceforth 4F. This process occurs independently of p53 activation, and is mediated by the synergistic downregulation of mechanistic target of rapamycin complex 1 (mTORC1) and the induction of autophagy-related genes. The 4F coordinately repress mTORC1, but bifurcate in their regulation of autophagy-related genes, with Klf4 and c-Myc inducing them but Sox2 and Oct4 inhibiting them. On one hand, inhibition of mTORC1 facilitates reprogramming by promoting cell reshaping (mitochondrial remodelling and cell size reduction). On the other hand, mTORC1 paradoxically impairs reprogramming by triggering autophagy. Autophagy does not participate in cell reshaping in reprogramming but instead degrades p62, whose accumulation in autophagy-deficient cells facilitates reprogramming. Our results thus reveal a complex signalling network involving mTORC1 inhibition and autophagy induction in the early phase of reprogramming, whose delicate balance ultimately determines reprogramming efficiency.", "title": "Autophagy and mTORC1 regulate the stochastic phase of somatic cell reprogramming" }, { "docid": "27647593", "text": "Cancer cells do not exist as pure homogeneous populations in vivo. Instead they are embedded in \"cancer cell nests\" that are surrounded by stromal cells, especially cancer associated fibroblasts. Thus, it is not unreasonable to suspect that stromal fibroblasts could influence the metabolism of adjacent cancer cells, and visa versa. In accordance with this idea, we have recently proposed that the Warburg effect in cancer cells may be due to culturing cancer cells by themselves, out of their normal stromal context or tumor microenvironment. In fact, when cancer cells are co-cultured with fibroblasts, then cancer cells increase their mitochondrial mass, while fibroblasts lose their mitochondria. An in depth analysis of this phenomenon reveals that aggressive cancer cells are \"parasites\" that use oxidative stress as a \"weapon\" to extract nutrients from surrounding stromal cells. Oxidative stress in fibroblasts induces the autophagic destruction of mitochondria, by mitophagy. Then, stromal cells are forced to undergo aerobic glycolysis, and produce energy-rich nutrients (such as lactate and ketones) to \"feed\" cancer cells. This mechanism would allow cancer cells to seed anywhere, without blood vessels as a food source, as they could simply induce oxidative stress wherever they go, explaining how cancer cells survive during metastasis. We suggest that stromal catabolism, via autophagy and mitophagy, fuels the anabolic growth of tumor cells, promoting tumor progression and metastasis. We have previously termed this new paradigm \"The Autophagic Tumor Stroma Model of Cancer Metabolism\", or the \"Reverse Warburg Effect\". We also discuss how glutamine addiction (glutaminolysis) in cancer cells fits well with this new model, by promoting oxidative mitochondrial metabolism in aggressive cancer cells.", "title": "Stromal-epithelial metabolic coupling in cancer: integrating autophagy and metabolism in the tumor microenvironment." }, { "docid": "10024681", "text": "Deregulation of microRNA (miRNA) expression can have a critical role in carcinogenesis. Here we show in prostate cancer that miRNA-205 (miR-205) transcription is commonly repressed and the MIR-205 locus is hypermethylated. LOC642587, the MIR-205 host gene of unknown function, is also concordantly inactivated. We show that miR-205 targets mediator 1 (MED1, also called TRAP220 and PPARBP) for transcriptional silencing in normal prostate cells, leading to reduction in MED1 mRNA levels, and in total and active phospho-MED1 protein. Overexpression of miR-205 in prostate cancer cells negatively affects cell viability, consistent with a tumor suppressor function. We found that hypermethylation of the MIR-205 locus was strongly related with a decrease in miR-205 expression and an increase in MED1 expression in primary tumor samples (n=14), when compared with matched normal prostate (n=7). An expanded patient cohort (tumor n=149, matched normal n=30) also showed significant MIR-205 DNA methylation in tumors compared with normal, and MIR-205 hypermethylation is significantly associated with biochemical recurrence (hazard ratio=2.005, 95% confidence interval (1.109, 3.625), P=0.02), in patients with low preoperative prostate specific antigen. In summary, these results suggest that miR-205 is an epigenetically regulated tumor suppressor that targets MED1 and may provide a potential biomarker in prostate cancer management.", "title": "Epigenetic-induced repression of microRNA-205 is associated with MED1 activation and a poorer prognosis in localized prostate cancer" }, { "docid": "8425533", "text": "A defining feature of mitochondria is their maternal mode of inheritance. However, little is understood about the cellular mechanism through which paternal mitochondria, delivered from sperm, are eliminated from early mammalian embryos. Autophagy has been implicated in nematodes, but whether this mechanism is conserved in mammals has been disputed. Here, we show that cultured mouse fibroblasts and pre-implantation embryos use a common pathway for elimination of mitochondria. Both situations utilize mitophagy, in which mitochondria are sequestered by autophagosomes and delivered to lysosomes for degradation. The E3 ubiquitin ligases PARKIN and MUL1 play redundant roles in elimination of paternal mitochondria. The process is associated with depolarization of paternal mitochondria and additionally requires the mitochondrial outer membrane protein FIS1, the autophagy adaptor P62, and PINK1 kinase. Our results indicate that strict maternal transmission of mitochondria relies on mitophagy and uncover a collaboration between MUL1 and PARKIN in this process.", "title": "Elimination of paternal mitochondria in mouse embryos occurs through autophagic degradation dependent on PARKIN and MUL1" }, { "docid": "23509593", "text": "BACKGROUND Prostate development and maintenance in the adult results from an interaction of stromal and glandular components. Androgens can drive this process by direct action on the stroma. We investigated whether there was a direct link between androgens and another key regulator of stromal cells, intracellular Ca2+ ([Ca2+ ]i ). METHODS Prostate stromal cells were freshly obtained and cultures derived from patients with benign prostatic hyperplasia. Gene expression in dihydrotestosterone treated and untreated cells was compared using Affymetrix gene expression arrays and Ca2+ regulated features were identified by Gene Ontology (GO). Changes in [Ca2+]i were determined in Fluo-4 loaded cells. Androgen regulation was confirmed by chromatin immunoprecipitaion. RESULTS Stromal cell cultures were sorted for expression of integrin α1 β1 , which enriched for cells expressing the androgen receptor (AR). We identified key functional categories, within the androgen-induced gene expression signature, focusing on genes involved in calcium signaling. From this analysis, stromal interaction molecule-1 (STIM1) was identified as a significantly differentially expressed gene with four relevant associated GO terms. DNA sequence analysis showed that the promoter region of STIM1 contained putative androgen response element sequences in which AR binding ability of STIM1 was confirmed. Androgens directly regulated STIM1 expression and STIM1 effects on store-operated calcium entry were inhibited by STIM1 knock-down. Reduced STIM1 expression in prostate stromal cells led to a reduction in basal Ca2+ levels, the amount of Ca2+ released by thapsigargin and a reduction in store filling following TG-induced store depletion. CONCLUSIONS These results indicate that androgens modulate [Ca2+]i through the direct regulation of the STIM1 gene by AR binding to the STIM1 promoter.", "title": "The calcium sensor STIM1 is regulated by androgens in prostate stromal cells." }, { "docid": "24632480", "text": "Aberrant protein misfolding may contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS) but the detailed mechanisms are largely unknown. Our previous study has shown that autophagy is altered in the mouse model of ALS. In the present study, we systematically investigated the correlation of the autophagic alteration with the motor neurons (MNs) degeneration in the ALS mice. We have demonstrated that the autophagic protein marker LC3-II is markedly and specifically increased in the spinal cord MNs of the ALS mice. Electron microscopy and immunochemistry studies have shown that autophagic vacuoles are significantly accumulated in the dystrophic axons of spinal cord MNs of the ALS mice. All these changes in the ALS mice appear at the age of 90 d when the ALS mice display modest clinical symptoms; and they become prominent at the age of 120 d. The clinical symptoms are correlated with the progression of MNs degeneration. Moreover, we have found that p62/SQSTM1 is accumulated progressively in the spinal cord, indicating that the possibility of impaired autophagic flux in the SOD1(G93A) mice. Furthermore, to our surprise, we have found that treatment with autophagy enhancer rapamycin accelerates the MNs degeneration, shortens the life span of the ALS mice, and has no obvious effects on the accumulation of SOD1 aggregates. In addition, we have demonstrated that rapamycin treatment in the ALS mice causes more severe mitochondrial impairment, higher Bax levels and greater caspase-3 activation. These findings suggest that selective degeneration of MNs is associated with the impairment of the autophagy pathway and that rapamycin treatment may exacerbate the pathological processing through apoptosis and other mechanisms in the ALS mice.", "title": "Rapamycin treatment augments motor neuron degeneration in SOD1(G93A) mouse model of amyotrophic lateral sclerosis." }, { "docid": "41710132", "text": "The tumor suppressor PML (promyelocytic leukemia protein) regulates cellular senescence and terminal differentiation, two processes that implicate a permanent exit from the cell cycle. Here, we show that the mechanism by which PML induces a permanent cell cycle exit and activates p53 and senescence involves a recruitment of E2F transcription factors bound to their promoters and the retinoblastoma (Rb) proteins to PML nuclear bodies enriched in heterochromatin proteins and protein phosphatase 1α. Blocking the functions of the Rb protein family or adding back E2Fs to PML-expressing cells can rescue their defects in E2F-dependent gene expression and cell proliferation, inhibiting the senescent phenotype. In benign prostatic hyperplasia, a neoplastic disease that displays features of senescence, PML was found to be up-regulated and forming nuclear bodies. In contrast, PML bodies were rarely visualized in prostate cancers. The newly defined PML/Rb/E2F pathway may help to distinguish benign tumors from cancers, and suggest E2F target genes as potential targets to induce senescence in human tumors.", "title": "Regulation of E2Fs and senescence by PML nuclear bodies." }, { "docid": "7548577", "text": "In the yeast Saccharomyces cerevisiae, glycogen is accumulated as a carbohydrate reserve when cells are deprived of nutrients. Yeast mutated in SNF1, a gene encoding a protein kinase required for glucose derepression, has diminished glycogen accumulation and concomitant inactivation of glycogen synthase. Restoration of synthesis in an snf1 strain results only in transient glycogen accumulation, implying the existence of other SNF1-dependent controls of glycogen storage. A genetic screen revealed that two genes involved in autophagy, APG1 and APG13, may be regulated by SNF1. Increased autophagic activity was observed in wild-type cells entering the stationary phase, but this induction was impaired in an snf1 strain. Mutants defective for autophagy were able to synthesize glycogen upon approaching the stationary phase, but were unable to maintain their glycogen stores, because subsequent synthesis was impaired and degradation by phosphorylase, Gph1p, was enhanced. Thus, deletion of GPH1 partially reversed the loss of glycogen accumulation in autophagy mutants. Loss of the vacuolar glucosidase, SGA1, also protected glycogen stores, but only very late in the stationary phase. Gph1p and Sga1p may therefore degrade physically distinct pools of glycogen. Pho85p is a cyclin-dependent protein kinase that antagonizes SNF1 control of glycogen synthesis. Induction of autophagy in pho85 mutants entering the stationary phase was exaggerated compared to the level in wild-type cells, but was blocked in apg1 pho85 mutants. We propose that Snf1p and Pho85p are, respectively, positive and negative regulators of autophagy, probably via Apg1 and/or Apg13. Defective glycogen storage in snf1 cells can be attributed to both defective synthesis upon entry into stationary phase and impaired maintenance of glycogen levels caused by the lack of autophagy.", "title": "Antagonistic Controls of Autophagy and Glycogen Accumulation by Snf1p, the Yeast Homolog of AMP-Activated Protein Kinase, and the Cyclin-Dependent" }, { "docid": "1084345", "text": "Chaperone-mediated autophagy (CMA), a selective mechanism for degradation of cytosolic proteins in lysosomes, contributes to the removal of altered proteins as part of the cellular quality-control systems. We have previously found that CMA activity declines in aged organisms and have proposed that this failure in cellular clearance could contribute to the accumulation of altered proteins, the abnormal cellular homeostasis and, eventually, the functional loss characteristic of aged organisms. To determine whether these negative features of aging can be prevented by maintaining efficient autophagic activity until late in life, in this work we have corrected the CMA defect in aged rodents. We have generated a double transgenic mouse model in which the amount of the lysosomal receptor for CMA, previously shown to decrease in abundance with age, can be modulated. We have analyzed in this model the consequences of preventing the age-dependent decrease in receptor abundance in aged rodents at the cellular and organ levels. We show here that CMA activity is maintained until advanced ages if the decrease in the receptor abundance is prevented and that preservation of autophagic activity is associated with lower intracellular accumulation of damaged proteins, better ability to handle protein damage and improved organ function.", "title": "Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function" }, { "docid": "24581365", "text": "CONTEXT The appropriate therapy for men with clinically localized prostate cancer is uncertain. A recent study suggested an increasing prostate cancer mortality rate for men who are alive more than 15 years following diagnosis. OBJECTIVE To estimate 20-year survival based on a competing risk analysis of men who were diagnosed with clinically localized prostate cancer and treated with observation or androgen withdrawal therapy alone, stratified by age at diagnosis and histological findings. DESIGN, SETTING, AND PATIENTS A retrospective population-based cohort study using Connecticut Tumor Registry data supplemented by hospital record and histology review of 767 men aged 55 to 74 years with clinically localized prostate cancer diagnosed between January 1, 1971, and December 31, 1984. Patients were treated with either observation or immediate or delayed androgen withdrawal therapy, with a median observation of 24 years. MAIN OUTCOME MEASURES Probability of mortality from prostate cancer or other competing medical conditions, given a patient's age at diagnosis and tumor grade. RESULTS The prostate cancer mortality rate was 33 per 1000 person-years during the first 15 years of follow-up (95% confidence interval [CI], 28-38) and 18 per 1000 person-years after 15 years of follow-up (95% CI, 10-29). The mortality rates for these 2 follow-up periods were not statistically different, after adjusting for differences in tumor histology (rate ratio, 1.1; 95% CI, 0.6-1.9). Men with low-grade prostate cancers have a minimal risk of dying from prostate cancer during 20 years of follow-up (Gleason score of 2-4, 6 deaths per 1000 person-years; 95% CI, 2-11). Men with high-grade prostate cancers have a high probability of dying from prostate cancer within 10 years of diagnosis (Gleason score of 8-10, 121 deaths per 1000 person-years; 95% CI, 90-156). Men with Gleason score of 5 or 6 tumors have an intermediate risk of prostate cancer death. CONCLUSION The annual mortality rate from prostate cancer appears to remain stable after 15 years from diagnosis, which does not support aggressive treatment for localized low-grade prostate cancer.", "title": "20-year outcomes following conservative management of clinically localized prostate cancer." }, { "docid": "25513319", "text": "Metabolic pathway reprogramming is a hallmark of cancer cell growth and survival and supports the anabolic and energetic demands of these rapidly dividing cells. The underlying regulators of the tumor metabolic program are not completely understood; however, these factors have potential as cancer therapy targets. Here, we determined that upregulation of the oncogenic transcriptional coregulator steroid receptor coactivator 2 (SRC-2), also known as NCOA2, drives glutamine-dependent de novo lipogenesis, which supports tumor cell survival and eventual metastasis. SRC-2 was highly elevated in a variety of tumors, especially in prostate cancer, in which SRC-2 was amplified and overexpressed in 37% of the metastatic tumors evaluated. In prostate cancer cells, SRC-2 stimulated reductive carboxylation of α-ketoglutarate to generate citrate via retrograde TCA cycling, promoting lipogenesis and reprogramming of glutamine metabolism. Glutamine-mediated nutrient signaling activated SRC-2 via mTORC1-dependent phosphorylation, which then triggered downstream transcriptional responses by coactivating SREBP-1, which subsequently enhanced lipogenic enzyme expression. Metabolic profiling of human prostate tumors identified a massive increase in the SRC-2-driven metabolic signature in metastatic tumors compared with that seen in localized tumors, further implicating SRC-2 as a prominent metabolic coordinator of cancer metastasis. Moreover, SRC-2 inhibition in murine models severely attenuated the survival, growth, and metastasis of prostate cancer. Together, these results suggest that the SRC-2 pathway has potential as a therapeutic target for prostate cancer.", "title": "Coactivator SRC-2-dependent metabolic reprogramming mediates prostate cancer survival and metastasis." }, { "docid": "982650", "text": "BACKGROUND & AIMS Tumor cells survive hypoxic conditions by inducing autophagy. We investigated the roles of microRNAs (miRNAs) in regulating autophagy of hepatocellular carcinoma (HCC) cells under hypoxic conditions. METHODS We used gain- and loss-of-function methods to evaluate the effect of miRNAs on autophagy in human HCC cell lines (Huh7 and Hep3B) under hypoxic conditions. Autophagy was quantified by immunoblot, immunofluoresence, and transmission electron microscopy analyses, and after incubation of cells with bafilomycin A1. We used a luciferase reporter assay to confirm associations between miRNAs and their targets. We analyzed growth of HCC xenograft tumors in nude mice. RESULTS miR-375 was down-regulated in HCC cells and tissues; it inhibited autophagy under hypoxic conditions by suppressing the conversion of LC3I to LC3II and thereby autophagic flux. The ability of miR-375 to inhibit autophagy was independent of its ability to regulate 3'-phosphoinositide-dependent protein kinase-1-AKT-mammalian target of rapamycin signaling, but instead involved suppression of ATG7, an autophagy-associated gene. miR-375 bound directly to a predicted site in the 3' untranslated region of ATG7. Up-regulating miR-375 or down-regulating ATG7 inhibited mitochondrial autophagy of HCC cells, reduced the elimination of damaged mitochondria under hypoxia, increased release of mitochondrial apoptotic proteins, and reduced viability of HCC cells. In mice, xenograft tumors that expressed miR-375 had fewer autophagic cells, larger areas of necrosis, and grew more slowly than tumors from HCC cells that expressed lower levels of miR-375. CONCLUSIONS miR-375 inhibits autophagy by reducing expression of ATG7 and impairs viability of HCC cells under hypoxic conditions in culture and in mice. miRNAs that inhibit autophagy of cancer cells might be developed as therapeutics.", "title": "miR-375 inhibits autophagy and reduces viability of hepatocellular carcinoma cells under hypoxic conditions." }, { "docid": "6790197", "text": "PURPOSE To accurately identify gene expression alterations that differentiate neoplastic from normal prostate epithelium using an approach that avoids contamination by unwanted cellular components and is not compromised by acute gene expression changes associated with tumor devascularization and resulting ischemia. EXPERIMENTAL DESIGN Approximately 3,000 neoplastic and benign prostate epithelial cells were isolated using laser capture microdissection from snap-frozen prostate biopsy specimens provided by 31 patients who subsequently participated in a clinical trial of preoperative chemotherapy. cDNA synthesized from amplified total RNA was hybridized to custom-made microarrays composed of 6,200 clones derived from the Prostate Expression Database. Expression differences for selected genes were verified using quantitative reverse transcription-PCR. RESULTS Comparative analyses identified 954 transcript alterations associated with cancer (q < 0.01%), including 149 differentially expressed genes with no known functional roles. Gene expression changes associated with ischemia and surgical removal of the prostate gland were absent. Genes up-regulated in prostate cancer were statistically enriched in categories related to cellular metabolism, energy use, signal transduction, and molecular transport. Genes down-regulated in prostate cancers were enriched in categories related to immune response, cellular responses to pathogens, and apoptosis. A heterogeneous pattern of androgen receptor expression changes was noted. In exploratory analyses, androgen receptor down-regulation was associated with a lower probability of cancer relapse after neoadjuvant chemotherapy followed by radical prostatectomy. CONCLUSIONS Assessments of tumor phenotypes based on gene expression for treatment stratification and drug targeting of oncogenic alterations may best be ascertained using biopsy-based analyses where the effects of ischemia do not complicate interpretation.", "title": "Prostate cancer-associated gene expression alterations determined from needle biopsies." }, { "docid": "27270151", "text": "In the past decade, insightful preclinical research has led to important breakthroughs in our understanding of pancreatic cancer. Even though the vast majority of pancreatic cancers are KRAS mutated, not all pancreatic cancer tumors are \"KRAS equal\"; there seems to be varying dependencies on the KRAS pathway. While KRAS-targeting therapies have been disappointing in the clinic, 'synthetic lethal' approaches hold promise in this setting. The pancreatic cancer stromal microenvironment appears to have contradictory roles. While there is evidence to suggest that stromal barrier prevents drug delivery, in other circumstances, stroma can play a protective role and its disruption enhances tumor dissemination. Clinical trials aimed at manipulating the various stromal components are in progress. BRCA mutation-related pancreatic tumors illustrate a unique subtype with enhanced susceptibility to DNA damaging agents and PARP-inhibition. DNA repair defects in cancer extend beyond germ line BRCA mutation and may extend the indications for DNA repair-targeting agents. Immune strategies are an area of active investigation in pancreatic cancer. Although the initial trials of single-agent checkpoint inhibitors have been negative, combinational approaches using immune-modifying agents and vaccines appear promising and goal is to identify an 'immune-therapy responsive' profile in pancreatic cancer.", "title": "Changing the course of pancreatic cancer--Focus on recent translational advances." }, { "docid": "38243984", "text": "PURPOSE The goal of this study was to evaluate prospectively the engraftment rate, factors influencing engraftment, and predictability of clinical outcome of low-passage xenografts from patients with resectable pancreatic ductal adenocarcinoma (PDA) and to establish a bank of PDA xenografts. EXPERIMENTAL DESIGN Patients with resectable PDA scheduled for resection at the Johns Hopkins Hospital were eligible. Representative pieces of tumor were implanted in nude mice. The status of the SMAD4 gene and content of tumor-generating cells were determined by immunohistochemistry. Gene expression was carried out by using a U133 Plus 2.0 array. Patients were followed for progression and survival. RESULTS A total of 94 patients with PDA were resected, 69 tumors implanted in nude mice, and 42 (61%) engrafted. Engrafted carcinomas were more often SMAD4 mutant, and had a metastatic gene expression signature and worse prognosis. Tumors from patients resistant to gemcitabine were enriched in stroma-related gene pathways. Tumors sensitive to gemcitabine were enriched in cell cycle and pyrimidine gene pathways. The time to progression for patients who received treatment with gemcitabine for metastatic disease (n = 7) was double in patients with xenografts sensitive to gemcitabine. CONCLUSION A successful xenograft was generated in 61% of patients attempted, generating a pool of 42 PDA xenografts with significant biological information and annotated clinical data. Patients with PDA and SMAD4 inactivation have a better engraftment rate. Engraftment is a poor prognosis factor, and engrafted tumors have a metastatic gene expression signature. Tumors from gemcitabine-resistant patients were enriched in stromal pathways.", "title": "Tumor engraftment in nude mice and enrichment in stroma- related gene pathways predict poor survival and resistance to gemcitabine in patients with pancreatic cancer." }, { "docid": "25738896", "text": "The thymic transcription factor autoimmune regulator (Aire) prevents autoimmunity in part by promoting expression of tissue-specific self-antigens, which include many cancer antigens. For example, AIRE-deficient patients are predisposed to vitiligo, an autoimmune disease of melanocytes that is often triggered by efficacious immunotherapies against melanoma. Therefore, we hypothesized that Aire deficiency in mice may elevate immune responses to cancer and provide insights into how such responses might be triggered. In this study, we show that Aire deficiency decreases thymic expression of TRP-1 (TYRP1), which is a self-antigen in melanocytes and a cancer antigen in melanomas. Aire deficiency resulted in defective negative selection of TRP-1-specific T cells without affecting thymic numbers of regulatory T cells. Aire-deficient mice displayed elevated T-cell immune responses that were associated with suppression of melanoma outgrowth. Furthermore, transplantation of Aire-deficient thymic stroma was sufficient to confer more effective immune rejection of melanoma in an otherwise Aire wild-type host. Together, our work showed how Aire deficiency can enhance immune responses against melanoma and how manipulating TRP-1-specific T-cell negative selection may offer a logical strategy to enhance immune rejection of melanoma.", "title": "Aire deficiency promotes TRP-1-specific immune rejection of melanoma." }, { "docid": "17671145", "text": "The androgen receptor (AR) is overexpressed and hyperactivated in human castration-resistant prostate cancer (CRPC). However, the determinants of AR overexpression in CRPC are poorly defined. Here we show that retinoic acid receptor-related orphan receptor γ (ROR-γ) is overexpressed and amplified in metastatic CRPC tumors, and that ROR-γ drives AR expression in the tumors. ROR-γ recruits nuclear receptor coactivator 1 and 3 (NCOA1 and NCOA3, also known as SRC-1 and SRC-3) to an AR-ROR response element (RORE) to stimulate AR gene transcription. ROR-γ antagonists suppress the expression of both AR and its variant AR-V7 in prostate cancer (PCa) cell lines and tumors. ROR-γ antagonists also markedly diminish genome-wide AR binding, H3K27ac abundance and expression of the AR target gene network. Finally, ROR-γ antagonists suppressed tumor growth in multiple AR-expressing, but not AR-negative, xenograft PCa models, and they effectively sensitized CRPC tumors to enzalutamide, without overt toxicity, in mice. Taken together, these results establish ROR-γ as a key player in CRPC by acting upstream of AR and as a potential therapeutic target for advanced PCa.", "title": "ROR-γ drives androgen receptor expression and represents a therapeutic target in castration-resistant prostate cancer" }, { "docid": "32766786", "text": "PURPOSE In the initial report of the Lupron Depot Neoadjuvant Prostate Cancer Study Group patients who received 3 months of androgen deprivation had a significant decrease in the positive margin rate. We monitored these patients for 5 years and to our knowledge present the longest followup of any neoadjuvant trial. MATERIALS AND METHODS A multi-institutional prospective randomized trial was performed between February 1992 and April 1994 involving patients with stage cT2b prostate cancer, including 138 who received 3 months of leuprolide plus flutamide before radical prostatectomy and 144 who underwent radical prostatectomy only. Patients were followed every 6 months with serum prostate specific antigen (PSA) testing for 5 years. Biochemical recurrence was defined as PSA greater than 0.4 ng./ml. RESULTS At 5 years there was no difference in the biochemical recurrence rate. PSA was less than 0.4 ng./ml. in 64.8% of the patients in the neoadjuvant androgen ablation plus prostatectomy and 67.6% in the prostatectomy only group (p = 0.663). CONCLUSIONS Although 3 months of androgen deprivation before radical prostatectomy resulted in an apparently significant decrease in positive surgical margins, a 5-year followup does not indicate any difference in the recurrence rate. Until studies document improvement in biochemical or clinical recurrence with longer periods of treatment, induction androgen deprivation before radical prostatectomy is not indicated.", "title": "Neoadjuvant androgen ablation before radical prostatectomy in cT2bNxMo prostate cancer: 5-year results." }, { "docid": "14131683", "text": "An increasingly recognized resistance mechanism to androgen receptor (AR)-directed therapy in prostate cancer involves epithelial plasticity, in which tumor cells demonstrate low to absent AR expression and often have neuroendocrine features. The etiology and molecular basis for this 'alternative' treatment-resistant cell state remain incompletely understood. Here, by analyzing whole-exome sequencing data of metastatic biopsies from patients, we observed substantial genomic overlap between castration-resistant tumors that were histologically characterized as prostate adenocarcinomas (CRPC-Adeno) and neuroendocrine prostate cancer (CRPC-NE); analysis of biopsy samples from the same individuals over time points to a model most consistent with divergent clonal evolution. Genome-wide DNA methylation analysis revealed marked epigenetic differences between CRPC-NE tumors and CRPC-Adeno, and also designated samples of CRPC-Adeno with clinical features of AR independence as CRPC-NE, suggesting that epigenetic modifiers may play a role in the induction and/or maintenance of this treatment-resistant state. This study supports the emergence of an alternative, 'AR-indifferent' cell state through divergent clonal evolution as a mechanism of treatment resistance in advanced prostate cancer.", "title": "Divergent clonal evolution of castration resistant neuroendocrine prostate cancer" }, { "docid": "33507866", "text": "A critical regulator of autophagy is the Class III PI3K Vps34 (also called PIK3C3). Although Vps34 is known to play an essential role in autophagy in yeast, its role in mammals remains elusive. To elucidate the physiological function of Vps34 and to determine its precise role in autophagy, we have generated Vps34(f/f) mice, in which expression of Cre recombinase results in a deletion of exon 4 of Vps34 and a frame shift causing a deletion of 755 of the 887 amino acids of Vps34. Acute ablation of Vps34 in MEFs upon adenoviral Cre infection results in a diminishment of localized generation of phosphatidylinositol 3-phosphate and blockade of both endocytic and autophagic degradation. Starvation-induced autophagosome formation is blocked in both Vps34-null MEFs and liver. Liver-specific Albumin-Cre;Vps34(f/f) mice developed hepatomegaly and hepatic steatosis, and impaired protein turnover. Ablation of Vps34 in the heart of muscle creatine kinase-Cre;Vps34(f/f) mice led to cardiomegaly and decreased contractility. In addition, while amino acid-stimulated mTOR activation was suppressed in the absence of Vps34, the steady-state level of mTOR signaling was not affected in Vps34-null MEFs, liver, or cardiomyocytes. Taken together, our results indicate that Vps34 plays an essential role in regulating functional autophagy and is indispensable for normal liver and heart function.", "title": "Class III PI3K Vps34 plays an essential role in autophagy and in heart and liver function." }, { "docid": "946756", "text": "A protein of molecular size 62,000 daltons (p62) was detected in HeLa cell nuclear extracts by UV cross-linking to mRNA precursors. p62 binds specifically to the polypyrimidine tract of the 3' splice site region of introns. p62 purified to homogeneity binds the polypyrimidine tract of pre-mRNAs. This binding does not require the AG dinucleotide at the 3' splice site. Alterations in the polypyrimidine tract that reduce the binding of p62 yield a corresponding reduction in the efficiency of formation of a U2 snRNP/pre-mRNA complex and splicing. The p62 protein is retained in the spliceosome, where it remains bound to the pre-mRNA. This polypyrimidine tract binding protein (pPTB) is proposed to be a critical component in recognition of the 3' splice site during splicing.", "title": "Identification and purification of a 62,000-dalton protein that binds specifically to the polypyrimidine tract of introns." }, { "docid": "52925737", "text": "BACKGROUND Exosomes are extracellular vesicles that mediate cellular communication in health and diseases. Neutrophils could be polarized to a pro-tumor phenotype by tumor. The function of tumor-derived exosomes in neutrophil regulation remains unclear. METHODS We investigated the effects of gastric cancer cell-derived exosomes (GC-Ex) on the pro-tumor activation of neutrophils and elucidated the underlying mechanisms. RESULTS GC-Ex prolonged neutrophil survival and induced expression of inflammatory factors in neutrophils. GC-Ex-activated neutrophils, in turn, promoted gastric cancer cell migration. GC-Ex transported high mobility group box-1 (HMGB1) that activated NF-κB pathway through interaction with TLR4, resulting in an increased autophagic response in neutrophils. Blocking HMGB1/TLR4 interaction, NF-κB pathway, and autophagy reversed GC-Ex-induced neutrophil activation. Silencing HMGB1 in gastric cancer cells confirmed HMGB1 as a key factor for GC-Ex-mediated neutrophil activation. Furthermore, HMGB1 expression was upregulated in gastric cancer tissues. Increased HMGB1 expression was associated with poor prognosis in patients with gastric cancer. Finally, gastric cancer tissue-derived exosomes acted similarly as exosomes derived from gastric cancer cell lines in neutrophil activation. CONCLUSION We demonstrate that gastric cancer cell-derived exosomes induce autophagy and pro-tumor activation of neutrophils via HMGB1/TLR4/NF-κB signaling, which provides new insights into mechanisms for neutrophil regulation in cancer and sheds lights on the multifaceted role of exosomes in reshaping tumor microenvironment.", "title": "Tumor-derived exosomes induce N2 polarization of neutrophils to promote gastric cancer cell migration" }, { "docid": "25915873", "text": "PURPOSE Therapies to target prostate cancer bone metastases have only limited effects. New treatments are focused on the interaction between cancer cells, bone marrow cells and the bone matrix. Osteoclasts play an important role in the development of bone tumors caused by prostate cancer. Since Src kinase has been shown to be necessary for osteoclast function, we hypothesized that dasatinib, a Src family kinase inhibitor, would reduce osteoclast activity and prostate cancer (PC-3) cell-induced osteoclast formation. RESULTS Dasatinib inhibited RANKL-induced osteoclast differentiation of bone marrow-derived monocytes with an EC(50) of 7.5 nM. PC-3 cells, a human prostate cancer cell line, were able to differentiate RAW 264.7 cells, a murine monocytic cell line, into osteoclasts, and dasatinib inhibited this differentiation. In addition, conditioned medium from PC-3 cell cultures was able to differentiate RAW 264.7 cells into osteoclasts and this too, was inhibited by dasatinib. Even the lowest concentration of dasatinib, 1.25 nmol, inhibited osteoclast differentiation by 29%. Moreover, dasatinib inhibited osteoclast activity by 58% as measured by collagen 1 release. EXPERIMENTAL DESIGN We performed in vitro experiments utilizing the Src family kinase inhibitor dasatinib to target osteoclast activation as a means of inhibiting prostate cancer bone metastases. CONCLUSION Dasatinib inhibits osteoclast differentiation of mouse primary bone marrow-derived monocytes and PC-3 cell-induced osteoclast differentiation. Dasatinib also inhibits osteoclast degradation activity. Inhibiting osteoclast differentiation and activity may be an effective targeted therapy in patients with prostate cancer bone metastases.", "title": "Dasatinib inhibits both osteoclast activation and prostate cancer PC-3-cell-induced osteoclast formation." }, { "docid": "22180793", "text": "The transition from androgen-dependent to castration-resistant prostate cancer (CRPC) is a lethal event of uncertain molecular etiology. Comparing gene expression in isogenic androgen-dependent and CRPC xenografts, we found a reproducible increase in N-cadherin expression, which was also elevated in primary and metastatic tumors of individuals with CRPC. Ectopic expression of N-cadherin in nonmetastatic, androgen-dependent prostate cancer models caused castration resistance, invasion and metastasis. Monoclonal antibodies against the ectodomain of N-cadherin reduced proliferation, adhesion and invasion of prostate cancer cells in vitro. In vivo, these antibodies slowed the growth of multiple established CRPC xenografts, blocked local invasion and metastasis and, at higher doses, led to complete regression. N-cadherin–specific antibodies markedly delayed the time to emergence of castration resistance, markedly affected tumor histology and angiogenesis, and reduced both AKT serine-threonine kinase activity and serum interleukin-8 (IL-8) secretion. These data indicate that N-cadherin is a major cause of both prostate cancer metastasis and castration resistance. Therapeutic targeting of this factor with monoclonal antibodies may have considerable clinical benefit.", "title": "Monoclonal antibody targeting of N-cadherin inhibits prostate cancer growth, metastasis and castration resistance" }, { "docid": "12009265", "text": "CONTEXT Many individuals take vitamins in the hopes of preventing chronic diseases such as cancer, and vitamins E and C are among the most common individual supplements. A large-scale randomized trial suggested that vitamin E may reduce risk of prostate cancer; however, few trials have been powered to address this relationship. No previous trial in men at usual risk has examined vitamin C alone in the prevention of cancer. OBJECTIVE To evaluate whether long-term vitamin E or C supplementation decreases risk of prostate and total cancer events among men. DESIGN, SETTING, AND PARTICIPANTS The Physicians' Health Study II is a randomized, double-blind, placebo-controlled factorial trial of vitamins E and C that began in 1997 and continued until its scheduled completion on August 31, 2007. A total of 14,641 male physicians in the United States initially aged 50 years or older, including 1307 men with a history of prior cancer at randomization, were enrolled. INTERVENTION Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily. MAIN OUTCOME MEASURES Prostate and total cancer. RESULTS During a mean follow-up of 8.0 years, there were 1008 confirmed incident cases of prostate cancer and 1943 total cancers. Compared with placebo, vitamin E had no effect on the incidence of prostate cancer (active and placebo vitamin E groups, 9.1 and 9.5 events per 1000 person-years; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.85-1.09; P = .58) or total cancer (active and placebo vitamin E groups, 17.8 and 17.3 cases per 1000 person-years; HR, 1.04; 95% CI, 0.95-1.13; P = .41). There was also no significant effect of vitamin C on total cancer (active and placebo vitamin C groups, 17.6 and 17.5 events per 1000 person-years; HR, 1.01; 95% CI, 0.92-1.10; P = .86) or prostate cancer (active and placebo vitamin C groups, 9.4 and 9.2 cases per 1000 person-years; HR, 1.02; 95% CI, 0.90-1.15; P = .80). Neither vitamin E nor vitamin C had a significant effect on colorectal, lung, or other site-specific cancers. Adjustment for adherence and exclusion of the first 4 or 6 years of follow-up did not alter the results. Stratification by various cancer risk factors demonstrated no significant modification of the effect of vitamin E on prostate cancer risk or either agent on total cancer risk. CONCLUSIONS In this large, long-term trial of male physicians, neither vitamin E nor C supplementation reduced the risk of prostate or total cancer. These data provide no support for the use of these supplements for the prevention of cancer in middle-aged and older men. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00270647.", "title": "Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial." } ]
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Matt Smith acted only on stage.
[ { "docid": "Matt_Smith_(actor)", "text": "Matthew Robert `` Matt '' Smith ( born 28 October 1982 ) is an English actor . He is best known for his role as the Eleventh Doctor in the BBC science fiction series Doctor Who , for which he received a BAFTA Award nomination in 2011 . Smith initially aspired to be a professional footballer , but spondylolysis forced him out of the sport . After joining the National Youth Theatre and studying Drama and Creative Writing at the University of East Anglia , he became an actor in 2003 , performing in plays like Murder in the Cathedral , Fresh Kills , The History Boys , and On the Shore of the Wide World in London theatres . Extending his repertoire into West End theatre , he has since performed in the stage adaptation of Swimming with Sharks with Christian Slater , followed a year later by a critically acclaimed performance as Henry in That Face . Smith 's first television role came in 2006 as Jim Taylor in the BBC adaptations of Philip Pullman 's The Ruby in the Smoke and The Shadow in the North , while his first major role in television came as Danny in the 2007 BBC series Party Animals . Smith , who was announced as the eleventh incarnation of the Doctor in January 2009 , is the youngest person to play the character in the British television series . He left the series at the end of the 2013 Christmas Day special , `` The Time of the Doctor '' . He portrayed both the physical embodiment and a holographic version of Skynet in Terminator Genisys ( 2015 ) . Since 2016 , he portrays Prince Philip , Duke of Edinburgh in Peter Morgan 's Netflix biographical drama series The Crown , opposite Claire Foy as Elizabeth II .", "title": "" } ]
[ { "docid": "The_Death_of_Bessie_Smith", "text": "The Death of Bessie Smith is a one-act play by American playwright Edward Albee , written in 1959 and premiered in West Berlin the following year . The play consists of a series of conversations between Bernie and his friend Jack , Jack and an off-stage Bessie , and black and white staff of a ` whites-only ' hospital in Memphis , Tennessee on the death date of the famous blues singer , Bessie Smith , who died in a car wreck .", "title": "" }, { "docid": "List_of_awards_and_nominations_received_by_Maggie_Smith", "text": "This is the list of awards and nominations received by Maggie Smith , whose acting career in motion pictures , television , and on stage spans over 60 years . Among her major competitive awards , Smith has won two Oscars , five BAFTAs ( including a record four for Best Actress ) , four Emmys and a Tony Award . Other significant awards include three Golden Globes , five Screen Actors Guild Awards , and a record five Best Actress Evening Standard Theatre Awards . Smith is one of only 14 actresses to have achieved the Triple Crown of Acting , which is competitive Academy Award , Emmy Award and Tony Award wins . Overall in her career to date she has won 58 competitive awards from 157 nominations . She has also received numerous honorary awards , including the BAFTA Special Award ( 1993 ) , the BAFTA Fellowship ( 1996 ) and the Special Olivier Award ( 2010 ) .", "title": "" }, { "docid": "Matt_Thompson_(film_director)", "text": "Matt Thompson ( born in Roseville , California on 19 May 1984 ) , is an American film director , producer , screenwriter and actor . He also directed some music videos and commercials and acted on stage productions . Born to Tim and Cindy Thompson , he grew up in Sacramento , California and graduated from Granite Bay High School , starting his acting debut at 18 and has appeared in many movies since . In 2009 he made his feature directorial debut with the feature film Listen to Your Heart ( 2010 film ) starring Cybill Shepherd , Kent Moran , Alexia Rasmussen and Ernie Sabella . He also played lead role of Stanley Kowalski in the stage presentation of A Streetcar Named Desire . He was named as one of 15 people to watch early in their careers by Sacramento Magazine in its March 2010 cover story .", "title": "" }, { "docid": "Bec_Gilbert", "text": "Rebecca Louise `` Bec '' Gilbert ( previously O'Connor ) is a fictional character from the Australian drama series Winners & Losers , played by Zoe Tuckwell-Smith . She made her debut screen appearance in the pilot episode `` Covert Aggression in Netball '' , which was broadcast on the Seven Network on 22 March 2011 . Tuckwell-Smith auditioned for the role of Bec . At the callback , she was introduced to Blair McDonough , who was cast as Bec 's partner , before she was given the role . Having previously appeared in guest parts , Winners & Losers marks Tuckwell-Smith 's major television acting debut . The series revolves around four `` losers '' who are reunited at their school reunion and then win the Oz Lotto . Bec was portrayed as being `` bright '' , `` rational '' and `` hard-working '' . Tuckwell-Smith thought Bec was a typical girl next door , but with a bit more complexity . She liked her character 's generosity and how she did not change after winning the Lotto . Reuniting with her friends -- Jenny ( Melissa Bergland ) , Frances ( Virginia Gay ) and Sophie ( Melanie Vallejo ) -- brought out Bec 's more playful side . Unlike the other girls , Bec was not given a cruel nickname at school and she knew that if she did not hang out with Jenny , she may have been popular . However , Bec stuck up for Jenny against the bullies from an early age and they remained best friends years after school . At the start of the first season , Bec had been with McDonough 's character , Matt O'Connor , for ten years , and engaged for four . Matt later called off their engagement and Bec had a brief relationship with Doug Graham ( Tom Wren ) . Bec and Matt reunited and married in the season finale episode , which also saw Bec learn that she was pregnant with Doug 's baby . Tuckwell-Smith liked that the writers had made Doug the father of Bec 's baby , calling it a great opportunity for drama . The actress also enjoyed playing out a pregnancy on-screen for the first time and liked the change it brought out in Bec 's personality . Bec spent the majority of the third season dealing with Matt 's death and learning that he had an affair . Bec and Tuckwell-Smith have received a mostly positive reception from television critics . Tuckwell-Smith departed the show on 12 August 2014 .", "title": "" }, { "docid": "Mike_Smith_(A&R_man)", "text": "Mike Smith started as an A&R man at MCA Publishing as a scout in 1988 , where he signed Blur , Levitation and scouted The Smashing Pumpkins . He then moved to EMI Publishing in 1992 , where he went on to sign acts , such as PJ Harvey , Elastica , Supergrass , Teenage Fan Club , Doves , Starsailor , The Beta Band , The Avalanches , Gorillaz , The White Stripes , The Libertines , The Scissor Sisters , The Arcade Fire , and Arctic Monkeys , as well as resigning Blur and progressing to the position of Head of A&R . He also worked with artists such as Robbie Williams , The Verve and Beth Orton . Smith moved to Columbia Records UK in 2006 to work as the Managing Director . In 2006 , he signed Mark Ronson and Calvin Harris . In 2007 , signings included The Ting Tings , MGMT , The Hugs , The Gossip and Glasvegas . The following year , he signed Miike Snow and Lissie to the label and in 2009 , Magnetic Man , Miles Kane and Paul Epworth . Band of Horses , Katy B , The Vaccines and Ryan Adams were all signed in 2010 and in the following year , he signed Madeon and The Civil Wars . Acts he also looked after included Kings of Leon , Bruce Springsteen , Bob Dylan , Foo Fighters , Matt Cardle , Ke $ ha , Sleigh Bells , and Kasabian . In April 2012 , Mike left Columbia to take up the role of President of Music at Mercury Records where he oversaw the signings of Iggy Azalea , The Vamps ( British band ) and Slaves ( UK band ) , as well as signing Duke Dumont and The Strypes . With the formation of Virgin / EMI Records in 2013 , from the merger of Virgin Records and Mercury Records , he signed The Chemical Brothers , The Libertines and Squeeze . Since 2010 , Mike has been a trustee of the charity , New Deal of The Mind , which works to encourage job creation within the creative industries . Mike has been sketching the musicians he has spent his lifetime watching and in 2009 , staged an exhibition of prints made from these drawings at Richard Goodall Gallery in Manchester . This was followed up in 2011 with a comprehensive show of his paintings , light boxes and prints at Somerset House . A further exhibition of the work was staged at Metropolis Group studios .", "title": "" }, { "docid": "Dad's_Garage_Theatre_Company", "text": "Dad 's Garage Theatre Company , located at 569 Ezzard St in the Old 4th Ward in Atlanta , Georgia , was founded in 1995 by Chris Blair , Marc Cram , Sean Daniels , John Gregorio , David Keeton , Joseph Limbaugh , Matt Stanton , and Matt Young . The small theater company has since achieved international recognition for original stage productions and Improvisational comedy . The current Artistic Director , Kevin Gillese , is a former director at Rapid Fire Theatre . Lara Smith is the current Managing Director .", "title": "" }, { "docid": "Tom_and_Matt_Smith", "text": "Tom Smith ( along with son Matt Smith ) are father and son jazz musicians best known for their work in the United States , Eastern Europe and China . Tom Smith ( father ) is a long time American university jazz professor , trombonist , researcher , wind symphony conductor , program creator and multiple Senior Fulbright Professor of Music at the Romanian National University of Music and Tibiscus University , with Senior Fulbright Professional Specialist appointments at University KwaZulu-Natal ( Durban , South Africa ) and the Serbian Academy of Music in Belgrade , as well as numerous American high school and community college positions , alongside an extended professorship at Pfeiffer University , and a three-year appointment as the first full-time American jazz studies professor at a Chinese university . In May 2013 , he became the 21st inductee into the DownBeat Jazz Education Hall of Fame . Tom was introduced to fine arts at an early age by his father , a noted trombonist , best known for his work with New Orleans traditional jazz artist Murphy Campo . Tom Smith was the longest continuous member of the North Carolina Artist-in-Residence Program ( 1984 -- 1992 ) , while based at three separate North Carolina community colleges . A widely acknowledged pioneer of the American community jazz movement ( having founded over fifty large community jazz ensembles ) his best known group was the Unifour Jazz Ensemble , an eighteen-piece big band and first entirely state funded big band in the United States , that placed seventh in the 1988 Down Beat Readers Poll . In that same poll , Smith placed fifth in the trombone category . As an improvising soloist , he has performed and toured with Louie Bellson , Clark Terry , McCoy Tyner , Joe Henderson , Chris Potter , the New York Voices , Nicholas Payton , Herb Ellis , Donald Byrd , Darius Brubeck and the Manhattan Transfer . Smith is also a noted music historian and researcher . In 2001 he and his research partner Gary Westbrook received recognition for identifying the musical fingerprint for identification of unknown personnel on early recordings . This and subsequent research has received widespread media exposure via National Public Radio 's Weekly Edition and Tech TV . In 2014 , Tom received the Brubeck Award for Jazz Research . Since 2002 , his works in global jazz education have drawn wide attention . Called by a former Fulbright Executive Director the premminent jazz Fulbright Scholar in the program 's history , Smith is the only foreigner to have been awarded The Romanian National Radio Prize . In 2005 , he founded and coordinated the Romanian Jazz Education Seminar , the first summer music camp staged in Romania , and cofounded the first western styled jazz music college in that country ( 2004 ) . In 2006 , his Fulbright work in South Africa included extensive assistance with township based initiatives , alongside devising a strategy to link university jazz education with local Zulu musicians . In 2008 , Smith was the recipient of the International Association for Jazz Education Jazz Ambassador Award , having already been awarded Outstanding Service to Jazz Education honors in 1998 , 2000 , 2001 , 2002 , 2003 , 2005 and 2006 . In 2009 , Tom received his eighth Fulbright Award ( a record for musician professors ) and accepted residency at the Serbia Academy of Music ( University of Arts ) drafting the curriculum for their jazz program . Later , he accepted guest jazz studies appointments in Budva , Montenegro . In 2010 , Tom and his wife Sarah relocated to Northeast China where he developed a jazz music strategy for teaching English to native Mandarin speakers . In 2011 he was appointed a professor of music at Ningbo University ( Zhejiang Province , China ) assigned to establish the first entirely functional jazz program on the Chinese mainland , that led to formation of numerous instrumental groups and a 40-member jazz choir . In 2013 , Tom was awarded the Camellia Award , for noteworthy artistic contributions towards social betterment for the Greater Ningbo Region . Website : tomsmithjazz.wix.com/music Matt Smith ( son ) ( born 1990 ) is an award winning jazz drum set musician , percussionist , hip hop mixologist , and radio/television personality who in 2006 , at age 16 , won the WFD World 's Fastest Drummer Extreme Sport Drumming competition in the Fastest Hands category . Matt is the son and grandson of two accomplished jazz musicians . He was introduced to the drums at age 9 , when Louie Bellson ( one of his father 's performing acquaintances ) gave him his first pair of drum sticks . Matt 's official début occurred at age 12 , when he performed for a jazz combo on Romanian National Television . At age 14 , he recorded a début album under his own name ( Coltrane Redeux ) featuring an all star European jazz lineup . In 2005 , Matt entered the Louie Bellson National Drumset Competition , and became the youngest finalist in that competition 's history.From 2005-2008 he held a number of speed drumming world records , and in 2007 , set the world speed endurance record when he performed 5,132 single strokes in five consecutive minutes . On June 26 , 2008 Matt set a traditional grip world speed record , when he recorded 1132 single strokes played in 1 minute - a record formerly held by Dream Theater drummer Mike Mangini . Since 2005 , Matt has performed and been interviewed on numerous American media outlets , including PBS , CBS Radio and CNN . In 2008 , a PBS news segment featuring Matt and drummer Johnny Rabb was nominated for an Arts and Entertainment News Documentary Emmy Award At age 18 , with speed drumming activities behind him , Matt began performing with a variety of diverse world class bands showcasing jazz , rock , hip hop , pop , funk and blues . In 2008 he was named a runner-up in the Rising Star category of the Drum Magazine Readers Poll . Matt is a 2009 graduate of the Atlanta Institute of Music , and from 2009-2011 resided in Europe , where he began production of nu jazz recordings , and performed with a diverse lineup of artists that included jazz pianist Darius Brubeck and Linkin Park singer Mike Shinoda.In 2011 , he signed on as house drummer with Euro blues headliner A. G. Weinberger on the weekly television show Acadeaua . In 2011 Matt relocated to Nashville , TN , where he works as a touring and session drummer .", "title": "" }, { "docid": "The_Clock_Maker", "text": "The Clock Maker is an American comic book published by Image Comics starting in January 2003 . The comic was written by Jim Krueger and pencilled by Matt Smith ( Act I ) and Jason Baroody ( Act II ) . The title was launched during a new superhero comics initiative at Image . The story is about a giant clockworks hidden within a hollow mountain in Switzerland . Hundreds of men that never age maintain the old behemoth 's operation . The clock is the cause and sustainer of the Earth 's revolutions -- and more , it is the gateway to Heaven itself . The first four issues were published as double-sized editions with a 1:1 reproduction ratio , meaning the original art was not resized when it was published . The books were folded in half to fit on standard news racks , and in the current sized protective polymer bags . The back cover of the fourth issue advertised a fifth , coming in June 2003 , however that issue was never published . Act II was never printed in the serial format , but only as a 48-page graphic novel ( ISBN 1-58240-377-5 ) in 2004 . Act three was intended to be published in the same manner , but , to this date , has never surfaced . Krueger maintains that the book will be out `` in the near future '' and that a collection will also be forthcoming .", "title": "" }, { "docid": "Doctrine_of_the_Trinity_Act_1813", "text": "The Doctrine of the Trinity Act 1813 ( 53 Geo . III c. 160 . sometimes called the Trinitarian Act 1812 ) was an Act of the Parliament of the United Kingdom . It amended the Blasphemy Act 1697 in respect of its Trinitarian provisions . The Blasphemy Act applied only to those educated in or having made profession of the Christian religion . The Act , passed July 21 , was also variously known as the Unitarian Relief Act ( Trinity Act ) , The Unitarian Toleration Bill , and Mr William Smith 's Bill , after Whig politician William Smith . The Act granted toleration for Unitarian worship , as previously the Toleration Act 1688 had only granted toleration to those Protestant dissenters who accepted the Trinity . The Blasphemy Act was repealed in 1967 , implicitly taking the Doctrine of the Trinity Act with it .", "title": "" }, { "docid": "Maggie_Smith", "text": "Dame Margaret Natalie Smith , ( born 28 December 1934 ) , known as Maggie Smith , is an English actress . She has had an extensive , varied career in stage , film and television spanning over sixty-five years . Smith has appeared in over 50 films and is one of Britain 's most recognisable actresses . A prominent figure in British culture for six decades , she was made a Dame by Queen Elizabeth II in 1990 for services to the performing arts , and received the Companion of Honour from the Queen in 2014 for services to drama . Smith began her career on stage at the Oxford Playhouse in 1952 and made her Broadway debut in New Faces of ' 56 . For her work on the London stage , she has won a record five Best Actress Evening Standard Awards ; for The Private Ear and The Public Eye ( 1962 ) , Hedda Gabler ( 1970 ) , Virginia ( 1981 ) , The Way of the World ( 1984 ) and Three Tall Women ( 1994 ) . She received Tony Award nominations for Private Lives ( 1975 ) and Night and Day ( 1979 ) , before winning the 1990 Tony Award for Best Actress in a Play for Lettice and Lovage . Other stage roles include Stratford Shakespeare Festival productions of Antony and Cleopatra ( 1976 ) and Macbeth ( 1978 ) , and West End productions of A Delicate Balance ( 1997 ) and The Breath of Life ( 2002 ) . On screen , Smith first drew praise for the crime film Nowhere to Go ( 1958 ) , for which she received her first BAFTA Award nomination . She has won two Academy Awards , winning Best Actress for The Prime of Miss Jean Brodie ( 1969 ) and Best Supporting Actress for California Suite ( 1978 ) . She is one of only six actresses to have won in both categories . She has won a record four BAFTA Awards for Best Actress , including for A Private Function ( 1984 ) and The Lonely Passion of Judith Hearne ( 1988 ) , a BAFTA for Best Supporting Actress for Tea With Mussolini ( 1999 ) , and three Golden Globe Awards . A six-time Oscar nominee , her other nominations were for Othello ( 1965 ) , Travels with My Aunt ( 1972 ) , A Room with a View ( 1986 ) , and Gosford Park ( 2001 ) . Smith played Professor Minerva McGonagall in the Harry Potter film series ( 2001 -- 11 ) . Other notable films include Love and Pain and the Whole Damn Thing ( 1973 ) , Death on the Nile ( 1978 ) , Clash of the Titans ( 1981 ) , Evil Under the Sun ( 1982 ) , Hook ( 1991 ) , Sister Act ( 1992 ) , The Best Exotic Marigold Hotel ( 2012 ) and The Lady in the Van ( 2015 ) . She won an Emmy Award in 2003 for My House in Umbria , to become one of the few actresses to have achieved the Triple Crown of Acting , and starred as Lady Violet Crawley , Dowager Countess of Grantham on Downton Abbey ( 2010 -- 15 ) , for which she won three Emmys , her first non-ensemble Screen Actors Guild Award and her third Golden Globe . Her honorary awards include the BAFTA Special Award ( 1993 ) , the BAFTA Fellowship ( 1996 ) , and the Special Olivier Award ( 2011 ) . She received the Stratford Shakespeare Festival 's Legacy Award in 2012 , and the Evening Standard Icon Award in 2013 .", "title": "" }, { "docid": "Matt_Smith", "text": "Matt or Matthew Smith may refer to :", "title": "" }, { "docid": "Matt_Smith_(TV_reporter)", "text": "Matt Smith is a British broadcaster .", "title": "" }, { "docid": "Matt_Harrington_(actor)", "text": "Matt Harrington is an American stage actor , best known for his work in the Broadway production of Matilda the Musical , in which he replaced Tony Award winner Gabriel Ebert in the role of Mr. Wormwood . Prior to performing in Matilda , Harrington was the only American actor to appear on stage in both productions of the critically acclaimed Broadway repertory of Twelfth Night and Richard III , starring Mark Rylance , at the Belasco Theatre . The productions originated at Shakespeare 's Globe in London and ultimately transferred to Broadway after a successful West End run .", "title": "" }, { "docid": "Matt_\"Money\"_Smith", "text": "Matt `` Money '' Smith ( born April 26 , 1973 ) is a United States sports radio personality . On January 8 , 2007 Smith began co-hosting The Petros and Money Show , with Petros Papadakis , which currently runs Monday-Friday from 2pm to 6pm .", "title": "" }, { "docid": "List_of_awards_and_nominations_received_by_Doctor_Who", "text": "Doctor Who is a British science fiction television programme produced and aired by the BBC . Originally shown from 1963 until 1989 , but was revived in 2005 . In 26 years , its original 1963 -- 1989 run won only two awards , a RTS Television Award and a Writer 's Guild of Great Britain Award . However , the revived series has received recognition from critics and the public , winning many awards . It has been nominated for a variety of different awards including 29 BAFTA TV Awards ( eight wins for the series ) , 27 Hugo Awards ( 6 wins ) , 16 Saturn Awards ( 3 wins ) , 24 National Television Awards ( 16 wins ) , 5 Writer 's Guild of Great Britain Awards ( two wins ) , and a total of 23 awards from BBC itself ( 14 wins ) . Amongst the wins for the series are a BAFTA TV Award for Best Drama Series , the most prestigious award for British television series ; it was the very first ( and to date only ) science fiction work to win . Matt Smith became the first Doctor Who actor to earn a BAFTA TV nomination in 2011 , receiving a Best Actor nomination for his role as the Eleventh Doctor , while Michelle Gomez became the first BAFTA TV-nominated Doctor Who actress in 2016 for her supporting role as Missy . It also won the only Saturn Award for Best International Series , and five Hugo Awards for Best Dramatic Presentation , Short Form . The series have received a record of 26 nominations in this last category in nine years only , making it the second television series in history after Star Trek to have more than two episodes nominated for a Hugo Award in a single year . Star Trek , the second most nominated series , only received 8 nominations overall . One of the most critically acclaimed aspects of Doctor Who is its acting quality : Christopher Eccleston , David Tennant and Matt Smith have all won awards playing the Doctor , while Billie Piper , Catherine Tate and Karen Gillan have won awards playing companions , and Carey Mulligan and Alex Kingston won awards playing supporting characters . Both Billie Piper and David Tennant have received awards ; nine ( in two years in the series ) and sixteen ( three regular years , two other years during special episodes ) respectively . The series has earned a broad range of nominations including recognition of its writing quality and its visual effects .", "title": "" }, { "docid": "Ian_Smith_(footballer,_born_1952)", "text": "Ian Lennox Taylor Smith ( born 2 April 1952 ) , sometimes listed as Ian Taylor-Smith , is a Scottish former footballer who played in the Scottish Football League for Queens Park , Heart of Midlothian and Queen of the South , and in the Football League for Birmingham City . He played as a forward . Smith was born in Edinburgh . He studied medicine , and eventually qualified as a doctor , combining this with playing football on an amateur or semi-professional basis . He spent time with several clubs in both Scotland and England , playing league football only where it did not interfere with his medical career . While with Birmingham City , he scored regularly for the reserve team and was highly rated , but his work at the Queen Elizabeth Medical Centre restricted him to only two first-team appearances . His father , Jimmy , played professionally for Clyde and St Mirren in the 1930s , and his son , Matt , turned professional with Oldham Athletic in 2011 .", "title": "" }, { "docid": "Matt_Smith_(guitarist)", "text": "Matt Smith is an Australian jazz guitarist . He is most widely known as the guitarist in the Australian rock pop band Thirsty Merc but also plays guitar for Sydney afrobeat/reggae band The Strides . Matt joined Thirsty Merc in January 2010 after helping record the band 's third album , Mousetrap Heart , in Los Angeles in late 2009 .", "title": "" }, { "docid": "Matt_Smith_(voice_actor)", "text": "Matthew `` Matt '' Smith ( born February 28 , 1968 in Toronto ) is a Canadian voice actor who works with Ocean Productions in Vancouver .", "title": "" }, { "docid": "Gulliver_Smith", "text": "Kevin Gullifer Hopkins-Smith ( born Kevin Gullifer Smith ca. 1950November 2014 ) , who performed as Little Gulliver and Gulliver Smith ( also styled as Gullifer Smith ) , was an Australian singer and songwriter from the early 1960s to mid-2000s . He was the front man and founding mainstay vocalist of Company Caine . In 1976 he and Ross Wilson co-wrote `` A Touch of Paradise '' for Wilson 's group , Mondo Rock , which appeared on their third album , Nuovo Mondo ( July 1982 ) . It was covered by John Farnham on his album , Whispering Jack ( October 1986 ) , and was issued as its third single in February 1987 , which reached the top 30 on the Kent Music Report Singles Chart . Gulliver Smith died on 12 November 2014 from kidney failure , and was survived by his wife Stephanie Hopkins-Smith ( nee Hopkins ) and their three sons . According to Australian musicologist , Ian McFarlane , `` Smith drew on vintage rock 'n' roll , Professor Longhair-styled New Orleans R&B , psychedelia and soul for inspiration . He was known for his outrageous stage act , which incorporated an inventive free-form approach and much evangelist-styled ad-libbing . Later on , he added a satirical Zappaesque component to his on-stage banter and lyrics . ''", "title": "" }, { "docid": "Matt_Smith_(footballer,_born_1989)", "text": "Mathieu James `` Matt '' Smith ( born 7 June 1989 ) is an English professional footballer who plays as a striker for Championship club Queens Park Rangers .", "title": "" }, { "docid": "Matt_Smith_(rugby_union_player_born_1989)", "text": "Matt Smith ( born 26 October 1989 in Hexham ) is a rugby union footballer who plays lock for the Leeds Carnegie and England Students .", "title": "" }, { "docid": "Matt_Smith_(rugby_union_player_born_1996)", "text": "Matt Smith ( born 5 October 1996 in Scotland ) is a Scottish rugby union player who plays for Glasgow Warriors at the Flanker position .", "title": "" }, { "docid": "Broderick_Smith", "text": "Broderick Smith ( born 17 February 1948 in Hertfordshire , England ) a.k.a. Brod Smith is a singer-songwriter , harmonica , guitar and banjo player . He was a member of 1970s bands Carson and The Dingoes , 1980s Broderick Smith 's Big Combo and performed solo . He also acted on stage in the 1973 Australian version of the rock opera Tommy and in minor roles in 1990s Television series Blue Heelers , Snowy River : The McGregor Saga and State Coroner . Smith has been involved in writing about 200 songs and has run workshops on songwriting , harmonica and vocals . He is also the father of King Gizzard and the Lizard Wizard harmonica/keyboard player Ambrose Kenny-Smith .", "title": "" }, { "docid": "The_Crash_of_the_Elysium", "text": "The Crash of the Elysium is a one-hour theatrical work created originally for children by the British company Punchdrunk , centred on the unexplained disappearance of a Victorian steamer named the Elysium and its investigation by the Eleventh Doctor from the television series Doctor Who . It premiered at MediaCityUK in Salford from 1 to 17 July 2011 as part of the Manchester International Festival , with a central narrative idea from Steven Moffat and written by Tom MacRae . It features the Weeping Angels and footage of Matt Smith as the Doctor specially recorded for the show . Its target audience is children from 6 to 12 , with adults allowed in if accompanied by a child on `` family '' shows . A number of adults-only shows were subsequently added following requests from the public . On 16 July 2011 , Matt Smith made a surprise visit to the show , appearing in character in place of the final video sequence . The show was remounted in Ipswich in 2012 as part of London 2012 's Olympics festival . Alfred Hickling of The Guardian awarded the production five out of five stars .", "title": "" }, { "docid": "Matt_Smith_(comics)", "text": "Matt Smith ( born 31 October 1972 ) is the current and longest-serving editor of long-running British science fiction weekly anthology comic 2000 AD , and the sister title Judge Dredd Megazine . He has also written two novels .", "title": "" }, { "docid": "Matt_Smith_(Australian_politician)", "text": "Matthew John `` Matt '' Smith ( born 18 March 1978 ) is an Australian Liberal politician who served in the Tasmanian House of Assembly from 1998 to 2002 . Smith was elected to the Tasmanian House of Assembly in 1998 as a member for the seat of Franklin . He became the youngest member of any parliament in Australia upon election in 1998 at 20 years of age . Smith stepped down shortly before the 2002 election after his father was charged with stealing from his employer and a court was told some of the money may have been used to fund his campaign . His father was later acquitted of all charges .", "title": "" }, { "docid": "Matt_Smith_(footballer,_born_1982)", "text": "Matthew Terence `` Matt '' Smith ( born 14 October 1982 ) is an English-born Australian football ( soccer ) player who plays for Bangkok Glass in the Thai League T1 . Born in England , Smith emigrated to Australia where he started his professional football career with North Queensland Fury during the 2009/10 A-League season and then signed a two-year contract with Brisbane Roar at the start of the A-League 2010/11 season . He has played for the Australian national team .", "title": "" }, { "docid": "Christmas_Eve_(opera)", "text": "Christmas Eve ( Ночь перед Рождеством , Noch ' pered Rozhdestvom ) , is an opera in four acts with music and libretto by Nikolai Rimsky-Korsakov . Composed between 1894 and 1895 , Rimsky-Korsakov based his opera on a short story , `` Christmas Eve '' , from Nikolay Gogol 's Evenings on a Farm Near Dikanka . The story had been used as the basis for an opera at least three times previously , including for Tchaikovsky 's Vakula the Smith ( 1874 ) . Oliver Knussen writes that `` Rimsky is only interested in recreating the atmosphere of the folk-tale , fleshing it out for his stage pageant in a comparable way to Humperdinck in Hansel .", "title": "" }, { "docid": "Matthew_Dow_Smith", "text": "Matthew Dow Smith ( sometimes credited as Matt Smith or Matthew Smith ) is an American comic book artist .", "title": "" }, { "docid": "Matt_Smith_(broadcaster)", "text": "Matt Smith ( born 26 April 1967 ) is a British broadcaster , who worked with ITV Sport between 2001-2015 . He currently presents BT Sport 's Premier League , FA Cup , Champions League , Europa League , Conference Football , England Under 21 .", "title": "" } ]
PLAIN-1513
lima beans
[ { "docid": "MED-4509", "text": "Hypercholesterolemia is a major modifiable risk factor for cardiovascular disease. Some, but not all, studies have shown that soy protein intake decreases total and low-density lipoprotein cholesterol and triglycerides and increases high-density lipoprotein cholesterol. The objective of this meta-analysis was to examine the effect of soy protein supplementation on serum lipid levels in adults. English language articles were retrieved by searching MEDLINE (1966 to February 2005) and the bibliographies of the retrieved articles. A total of 41 randomized controlled trials in which isolated soy protein supplementation was the only intervention and the net changes in serum lipids during intervention were reported. Information on study design, sample size, participant characteristics, intervention, follow-up duration, and treatment outcomes was independently abstracted using a standardized protocol. Using a random-effects model, data from each study were pooled and weighted by the inverse of their variance. Soy protein supplementation was associated with a significant reduction in mean serum total cholesterol (-5.26 mg/dl, 95% confidence interval [CI] -7.14 to -3.38), low-density lipoprotein cholesterol (-4.25 mg/dl, 95% CI -6.00 to -2.50), and triglycerides (-6.26 mg/dl, 95% CI -9.14 to -3.38) and a significant increase in high-density lipoprotein cholesterol (0.77 mg/dl, 95% CI 0.20 to 1.34). Meta-regression analyses showed a dose-response relation between soy protein and isoflavone supplementation and net changes in serum lipids. These results indicate that soy protein supplementation reduces serum lipids among adults with or without hypercholesterolemia. In conclusion, replacing foods high in saturated fat, trans-saturated fat, and cholesterol with soy protein may have a beneficial effect on coronary risk factors.", "title": "A meta-analysis of the effect of soy protein supplementation on serum lipids." }, { "docid": "MED-4510", "text": "Background and Aims Studies evaluating the effect of legume consumption on cholesterol have focused on soybeans, however non-soy legumes, such as a variety of beans, peas, and some seeds, are commonly consumed in Western countries. We conducted a meta-analysis of randomized controlled trials evaluating the effects of non-soy legume consumption on blood lipids. Methods and Results Studies were retrieved by searching MEDLINE (from January 1966 through July 2009), EMBASE (from January 1980 to July 2009), and the Cochrane Collaboration's Central Register of Controlled Clinical Trials using the following terms as medical subject headings and keywords: fabaceae not soybeans not isoflavones and diet or dietary fiber and cholesterol or hypercholesterolemia or triglycerides or cardiovascular diseases. Bibliographies of all retrieved articles were also searched. From 140 relevant reports, 10 randomized clinical trials were selected which compared a non-soy legume diet to control, had a minimum duration of 3 weeks, and reported blood lipid changes during intervention and control. Data on sample size, participant characteristics, study design, intervention methods, duration, and treatment results were independently abstracted by 2 investigators using a standardized protocol. Data from 10 trials representing 268 participants were examined using a random-effects model. Pooled mean net change in total cholesterol for those treated with a legume diet compared to control was −11.8 mg/dL (95% confidence interval [CI], −16.1 to −7.5); mean net change in low density lipoprotein cholesterol was −8.0 mg/dL (95% CI, −11.4 to −4.6). Conclusion These results indicate that a diet rich in legumes other than soy decreases total and LDL cholesterol.", "title": "Non-Soy Legume Consumption Lowers Cholesterol Levels: A Meta-Analysis of Randomized Controlled Trials" } ]
[ { "docid": "MED-3170", "text": "Background Few studies have focused on the cognitive morbidity of neurocysticercosis (NCC), one of the most common parasitic infections of the central nervous system. We longitudinally assessed the cognitive status and quality of life (QoL) of patients with incident symptomatic NCC cases and matched controls. Methodology/Principal Findings The setting of the study was the Sabogal Hospital and Cysticercosis Unit, Department of Transmissible Diseases, National Institute of Neurological Sciences, Lima, Peru. The design was a longitudinal study of new onset NCC cases and controls. Participants included a total of 14 patients with recently diagnosed NCC along with 14 healthy neighborhood controls and 7 recently diagnosed epilepsy controls. A standardized neuropsychological battery was performed at baseline and at 6 months on NCC cases and controls. A brain MRI was performed in patients with NCC at baseline and 6 months. Neuropsychological results were compared between NCC cases and controls at both time points. At baseline, patients with NCC had lower scores on attention tasks (p<0.04) compared with epilepsy controls but no significant differences compared to healthy controls. Six months after receiving anti-parasitic treatment, the NCC group significantly improved on tasks involving psychomotor speed (p<0.02). QoL at baseline suggested impaired mental function and social function in both the NCC and epilepsy group compared with healthy controls. QoL gains in social function (p = 0.006) were noted at 6 months in patients with NCC. Conclusions/Significance Newly diagnosed patients with NCC in this sample had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment. Author Summary Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system. Cognitive changes have been frequently reported with this disease but have not been well studied. Our study team recruited a group of new onset NCC cases and a matched set of healthy neighborhood controls and new onset epilepsy controls in Lima, Peru for this study. A neuropsychological battery was administered at baseline and at 6 months to all groups. Brain MRI studies were also obtained on NCC cases at baseline and at 6 months. Newly diagnosed patients with NCC had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment. This study is the first to assess cognitive status and quality of life longitudinally in patients with NCC and provides new data on an important clinical morbidity outcome.", "title": "Cognitive Changes and Quality of Life in Neurocysticercosis: A Longitudinal Study" }, { "docid": "MED-3584", "text": "Background: A high intake of white rice is associated with the metabolic syndrome and type 2 diabetes. Costa Ricans follow a staple dietary pattern that includes white rice and beans, yet the combined role of these foods on cardiometabolic risk factors has not been studied. Objective: We aimed to determine the association between intake of white rice and beans and the metabolic syndrome and its components in Costa Rican adults (n = 1879) without diabetes. Design: Multivariate-adjusted means were calculated for components of the metabolic syndrome by daily servings of white rice and beans (<1, 1, or >1) and by the ratio of beans to white rice. The OR for the metabolic syndrome was calculated by substituting one serving of beans for one serving of white rice. Results: An increase in daily servings of white rice was positively associated with systolic blood pressure (BP), triglycerides, and fasting glucose and inversely associated with HDL cholesterol (P-trend <0.01 for all). An increase in servings of beans was inversely associated with diastolic BP (P = 0.049). Significant trends for higher HDL cholesterol and lower BP and triglycerides were observed for 1:3, 1:2, 1:1, and 2:1 ratios of beans to white rice. Substituting one serving of beans for one serving of white rice was associated with a 35% (95% CI: 15%, 50%) lower risk of the metabolic syndrome. Conclusion: Increasing the ratio of beans to white rice, or limiting the intake of white rice by substituting beans, may lower cardiometabolic risk factors.", "title": "A higher ratio of beans to white rice is associated with lower cardiometabolic risk factors in Costa Rican adults" }, { "docid": "MED-2140", "text": "Background Around the world, beans and rice are commonly consumed together as a meal. With type 2 diabetes increasing, the effect of this traditional diet pattern on glycemic response has not been studied fully. Methods We evaluated the glycemic response of bean and rice traditional meals compared to rice alone in adults with type 2 diabetes. Seventeen men and women with type 2 diabetes controlled by metformin (n = 14) or diet/exercise (n = 3) aged 35–70 years participated in the randomized 4 × 4 crossover trial. The white long grain rice control, pinto beans/rice, black beans/rice, red kidney beans/rice test meals, matched for 50 grams of available carbohydrate, were consumed at breakfast after a 12 hour fast. Capillary blood glucose concentrations at baseline and at 30 minute intervals up to 180 minutes postprandial were collected. MANOVA for repeated measures established glucose differences between treatments. Paired t tests identified differences between bean types and the rice control following a significant MANOVA. Results Postprandial net glucose values were significantly lower for the three bean/rice treatments in contrast to the rice control at 90, 120 and 150 minutes. Incremental area under the curve values were significantly lower for the pinto and black bean/rice meals compared to rice alone, but not for kidney beans. Conclusions Pinto, dark red kidney and black beans with rice attenuate the glycemic response compared to rice alone. Promotion of traditional foods may provide non-pharmaceutical management of type 2 diabetes and improve dietary adherence with cultural groups. Trial registration Clinical Trials number NCT01241253", "title": "Bean and rice meals reduce postprandial glycemic response in adults with type 2 diabetes: a cross-over study" }, { "docid": "MED-4991", "text": "BACKGROUND: Epidemiological studies have shown positive findings associated with legume consumption and measures of cardiovascular disease and obesity. However, few observational trials have examined beans as a separate food variable when determining associations with health parameters. OBJECTIVE: To determine the association of consuming beans on nutrient intakes and physiological parameters using the National Health and Examination Survey (NHANES) 1999-2002. METHODS: Using data from NHANES 1999-2002, a secondary analysis was completed with a reliable 24-hour dietary recall where three groups of bean consumers were identified (N = 1,475). We determined mean nutrient intakes and physiological values between bean consumers and non-consumers. Least square means, standard errors and ANOVA were calculated using appropriate sample weights following adjustment for age, gender, ethnicity and energy. RESULTS: Relative to non-consumers, bean consumers had higher intakes of dietary fiber, potassium, magnesium, iron, and copper (p's < 0.05). Those consuming beans had a lower body weight (p = 0.008) and a smaller waist size (p = 0.043) relative to non-consumers. Additionally, consumers of beans had a 23% reduced risk of increased waist size (p = 0.018) and a 22% reduced risk of being obese (p = 0.026). Also, baked bean consumption was associated with a lower systolic blood pressure. CONCLUSIONS: Bean consumers had better overall nutrient intake levels, better body weights and waist circumferences, and lower systolic blood pressure in comparison to non-consumers. These data support the benefits of bean consumption on improving nutrient intake and health parameters.", "title": "Bean consumption is associated with greater nutrient intake, reduced systolic blood pressure, lower body weight, and a smaller waist circumference ..." }, { "docid": "MED-3138", "text": "Background Many consumers avoid eating beans because they believe legume consumption will cause excessive intestinal gas or flatulence. An increasing body of research and the 2010 Dietary Guidelines for Americans supports the benefits of a plant-based diet, and legumes specifically, in the reduction of chronic disease risks. The purpose of the current research was to investigate the perception of increased flatulence and gastrointestinal discomfort among participants who consumed a ½ cup of beans daily for 8 or 12 weeks. Methods Participants in three studies to test the effects of beans on heart disease biomarkers completed the same weekly questionnaire to assess gastrointestinal discomfort issues such as increased flatulence, stool changes, and bloating. Studies 1 and 2 were randomized crossover trials. Participants consumed ½ cup of pinto beans, black-eyed peas, and canned carrots as control (n = 17) in Study 1 for three randomized 8-week phases. For Study 2, participants ate ½ cup baked beans or canned carrots as control (n = 29) for two randomized 8-week phases. Study 3 was a parallel arm trial with 40 subjects receiving ½ cup pinto beans and 40 consuming a control soup for 12 weeks. Changes in the frequency of perceived flatulence, stool characteristics, and bloating were the primary outcome measures. Chi-square distributions were examined for the presence or absence of symptoms and demographic characteristics to determine differences by gender, age, body mass index (BMI), and bean type. Results Less than 50% reported increased flatulence from eating pinto or baked beans during the first week of each trial, but only 19% had a flatulence increase with black-eyed peas. A small percentage (3-11%) reported increased flatulence across the three studies even on control diets without flatulence-producing components. Conclusions People's concerns about excessive flatulence from eating beans may be exaggerated. Public health nutritionists should address the potential for gastrointestinal discomfort when increasing fiber intake from beans with clients. It is important to recognize there is individual variation in response to different bean types.", "title": "Perceptions of flatulence from bean consumption among adults in 3 feeding studies" }, { "docid": "MED-1880", "text": "Legumes are the basés diet in several countries. They hold a high nutritional value, but other properties related to human health are nowadays being studied. The aim of this work was to study the influence of processes (boiling or germination) on the phenolic composition of dark beans (Phaseolus vulgaris L. c.v. Tolosana) and their effect on their antioxidant, neuroprotective and anticancer ability. Phenolic composition of raw and processed dark beans was analysed by HPLC-PAD and HPLC-ESI/MS. The antioxidant activity was evaluated by ORAC. Astrocytes cultures (U-373) have been used to test their neuroprotective effect. Anticancer activities were evaluated on three different cell lines (renal adenocarcinoma (TK-10), breast adenocarcinoma (MCF-7) and melanoma (UACC-62)) by sulphorhodamine B method. Qualitative and quantitative differences in phenolic composition have been observed between raw and processed dark beans that influence the antioxidant activity, mainly for germinated samples which show a decrease of antioxidant capacity. Although every assayed extracts decreased reactive oxygen species release and exhibited cytotoxicity activities on cancer cell lines, raw beans proved to be the most active in neuroprotective and antitumoral effects; this sample is especially rich in phenolic compounds, mainly anthocyanins. This study further demonstrated that phenolic composition of dark beans is related with cooking process and so with their neuroprotective and anticancer activity; cooking of dark beans improves their digestion and absorption at intestinal level, while maintaining its protective ability on oxidative process at cellular level. Copyright © 2012 Elsevier Ltd. All rights reserved.", "title": "Effect of cooking and germination on phenolic composition and biological properties of dark beans (Phaseolus vulgaris L.)." }, { "docid": "MED-3141", "text": "OBJECTIVE: To evaluate the associations with chronic disease risk and mortality of the consequences of bean-free diets in Taiwanese adults with regard to gender. DESIGN: A sub-sample of the National Health Interview Survey (NHIS) in 2001 agreed to physical examination in the subsequent year. This group then took part in the Taiwanese Survey of Hyperglycaemia, Hyperlipidaemia and Hypertension (TwSHHH) in 2002. SETTING: Individual records were linked to the eventual death files from 2002 to 2008. SUBJECTS: Up to the end of 2008, a total of 2820 men and 2950 women were tracked by death registry over the 6·8 years of follow-up. RESULTS: Among 38,077 person-years, an average follow-up 6·5 years, 225 all-cause deaths were identified. Generalized linear models showed beans to be favourable for metabolic syndrome (other than for fasting glucose) in men; in women, beans were favourable for waist circumference and HbA1c. Cumulative logistic regression models for the effect of a bean-free diet on metabolic syndrome scores according to the Taiwanese-modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-tw) gave adjusted odds ratios of 1·83 in men and 1·45 in women. Cox regression models for the bean-free diet showed an increased hazard ratio for all-cause mortality among women (1·98, 95% CI 1·03, 3·81) but not men (1·28, 95% CI 0·76, 2·16). CONCLUSIONS: A bean-free diet may play a role in developing the metabolic syndrome in both genders, and is a significant predictor of all-cause mortality in Taiwanese women but not men.", "title": "A bean-free diet increases the risk of all-cause mortality among Taiwanese women: the role of the metabolic syndrome." }, { "docid": "MED-5079", "text": "OBJECTIVE: To determine effects of daily intake of 1/2 cup pinto beans, black-eyed peas or carrots (placebo) on risk factors for coronary heart disease (CHD) and diabetes mellitus (DM) in free-living, mildly insulin resistant adults over an 8 week period. METHODS: Randomized, crossover 3x3 block design. Sixteen participants (7 men, 9 women) received each treatment for eight-weeks with two-week washouts. Fasting blood samples collected at beginning and end of periods were analyzed for total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol, triacylglycerols, high-sensitivity C-reactive protein, insulin, glucose, and hemoglobin A1c. RESULTS: A significant treatment-by-time effect impacted serum TC (p = 0.026) and LDL (p = 0.033) after eight weeks. Paired t-tests indicated that pinto beans were responsible for this effect (p = 0.003; p = 0.008). Mean change of serum TC for pinto bean, black-eyed pea and placebo were -19 +/- 5, 2.5 +/- 6, and 1 +/- 5 mg/dL, respectively (p = 0.011). Mean change of serum LDL-C for pinto bean, black-eyed pea and placebo were -14 +/- 4, 4 +/- 5, and 1 +/- 4 mg/dL, in that order (p = 0.013). Pinto beans differed significantly from placebo (p = 0.021). No significant differences were seen with other blood concentrations across the 3 treatment periods. CONCLUSIONS: Pinto bean intake should be encouraged to lower serum TC and LDL-C, thereby reducing risk for CHD.", "title": "Pinto bean consumption reduces biomarkers for heart disease risk." }, { "docid": "MED-2570", "text": "The functional properties, including antioxidant and chemopreventative capacities as well as the inhibitory effects on angiotensin-converting enzyme (ACE), α-glucosidase and pancreatic lipase, of three Australian-grown faba bean genotypes (Nura, Rossa and TF(Ic*As)*483/13) were investigated using an array of in vitro assays. Chromatograms of on-line post column derivatisation assay coupled with HPLC revealed the existence of active phenolics (hump) in the coloured genotypes, which was lacking in the white-coloured breeding line, TF(Ic*As)*483/13. Roasting reduced the phenolic content, and diminished antioxidant activity by 10-40 % as measured by the reagent-based assays (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and oxygen radical absorbance capacity) in all genotypes. Cell culture-based antioxidant activity assay (cellular antioxidant activity) showed an increase of activity in the coloured genotypes after roasting. Faba bean extracts demonstrated cellular protection ability against H₂O₂-induced DNA damage (assessed using RAW264.7 cells), and inhibited the proliferation of all human cancer cell lines (BL13, AGS, Hep G2 and HT-29) evaluated. However, the effect of faba bean extracts on the non-transformed human cells (CCD-18Co) was negligible. Flow cytometric analyses showed that faba bean extracts successfully induced apoptosis of HL-60 (acute promyelocytic leukaemia) cells. The faba bean extracts also exhibited ACE, α-glucosidase and pancreatic lipase inhibitory activities. Overall, extracts from Nura (buff-coloured) and Rossa (red-coloured) were comparable, while TF(Ic*As)*483/13 (white-coloured) contained the lowest phenolic content and exhibited the least antioxidant and enzyme inhibition activities. These results are important to promote the utilisation of faba beans in human diets for various health benefits.", "title": "In vitro investigations of the potential health benefits of Australian-grown faba beans (Vicia faba L.): chemopreventative capacity and inhibitory ..." }, { "docid": "MED-3136", "text": "The objective of this study was to determine the influence of frequent and long-term consumption of legume seeds on colonic function. Two groups of subjects were studied--one group habitually consumed legume seeds as part of their normal diet, a second group only infrequently consumed legumes. No differences between these groups could be detected for fecal output and frequency, intestinal transit time, VFA excretion or fecal pH during 23-day study periods in which subjects consumed either their usual diet or 100 g red kidney beans, daily. However, the addition of beans to the diets of both groups provided significantly more dietary fiber, and produced greater fecal output and a higher concentration of VFA in feces. Fecal output appeared to be determined by two independent parameters--dietary fiber intake and VFA excretion. Beans provided a physiologically useful source of dietary fiber and favorably influenced colonic function.", "title": "Influence of frequent and long-term bean consumption on colonic function and fermentation." }, { "docid": "MED-2147", "text": "Consumption of Phaseolus vulgaris bean species such as pinto, black, navy or kidney may be beneficial in the prevention and treatment of chronic diseases. In particular, conditions that are promoted by increased glycaemic stress (hyperglycaemia and hyperinsulinaemia) including diabetes, CVD and cancer seem to be reduced in individuals who eat more of these beans. The present paper discusses the influence of P. vulgaris species on glycaemic response and the impact that relationship may have on the risk of developing diabetes, CVD and cancer.", "title": "Phaseolus beans: impact on glycaemic response and chronic disease risk in human subjects." }, { "docid": "MED-2580", "text": "Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial–based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18–0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial–based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence.", "title": "High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial" }, { "docid": "MED-2144", "text": "Bean pods (Phaseolus vulgaris) are among the most widely used traditional remedies against diabetes mellitus. Historical knowledge is summarized and compared to recent study results. Reports dating from the first half of the 20(th) century as well as recent publications show contradictory results. It seems that Phaseolus preparations should not be considered the first choice in phytopharmaceutical treatment of diabetes or lead structure research. To be effective, fairly high doses of aqueous extracts need to be given. Because of their fiber content and an alpha-amylase inhibitory effect, beans might be more useful as food components in preventing or ameliorating type 2 diabetes.", "title": "Beans and diabetes: Phaseolus vulgaris preparations as antihyperglycemic agents." }, { "docid": "MED-2010", "text": "Legumes (including alfalfa, clover, lupins, green beans and peas, peanuts, soybeans, dry beans, broad beans, dry peas, chickpeas, and lentils) represent an important component of the human diet in several areas of the world, especially in the developing countries, where they complement the lack of proteins from cereals, roots, and tubers. In some regions of the world, legume seeds are the only protein supply in the diet. The health benefits of legume consumption have received rising interest from researchers, and their consumption and production extends worldwide. Among European countries, higher legume consumption is observed around the Mediterranean, with per capita daily consumption between 8 and 23 g, while in Northern Europe, the daily consumption is less than 5 g per capita. The physiological effects of different legumes vary significantly. These differences may result from the polysaccharides composition, in particular, the quantity and variety of dietary fibers and starch, protein make-up, and variability in phytochemical content. The majority of legumes contain phytochemicals: bioactive compounds, including enzyme inhibitors, phytohemagglutinins (lectins), phytoestrogens, oligosaccharides, saponins, and phenolic compounds, which play metabolic roles in humans who frequently consume these foods. Dietary intake of phytochemicals may provide health benefits, protecting against numerous diseases or disorders, such as coronary heart disease, diabetes, high blood pressure and inflammation. The synergistic or antagonistic effects of these phytochemical mixtures from food legumes, their interaction with other components of the diet, and the mechanism of their action have remained a challenge with regard to understanding the role of phytochemicals in health and diseases. Their mitigating effects and the mechanism of their action need to be further addressed if we are to understand the role of phytochemicals in health and diseases. This review provides an overview of the nutritional quality of legumes and their potential contribution in cardiometabolic risk prevention.", "title": "Nutritional quality of legumes, and their role in cardiometabolic risk prevention: a review." }, { "docid": "MED-5078", "text": "In this study, solid fermentation of steamed black soybean with various GRAS (Generally recognized as safe) filamentious-fungi including Aspergillus awamori, Aspergillus oryzae BCRC 30222, Aspergillus sojae BCRC 30103, Rhizopus azygosporus BCRC 31158 and Rhizopus sp. No. 2 was performed. Mutagenicity and antimutagenicity of the methanol extracts of unfermented and fermented steamed black soybeans against 4-nitroquinoline-N-oxide (4-NQO), a direct mutagen and Benzo[a]pyrene (B[a]P), an indirect mutagen, on Salmonella Typhimurium TA100 and TA 98, were examined. The methanol extracts of unfermented and fermented steamed black soybeans show no mutagenic activity for either test strains at the doses tested. The extracts inhibited mutagenesis by either 4-NQO or B[a]P in S. Typhimurium TA100 and TA98. Fermentation with fungi also enhanced the antimutagenic effect of black soybean while the antimutagenic effect of the fermented black soybeans extract varied with the starter organism, mutagen, and test strain of S. Typhimurium examined. Generally, the extracts of A. awamori-fermented black soybean exhibited the highest antimutagenic effect. With strain TA100, the inhibitory effects of 5.0 mg of A. awamori-fermented black soybean extract per plate on the mutagenic effects of 4-NQO and B[a]P were 92% and 89%, respectively, while the corresponding rates for extract of unfermented were 41% and 63%, respectively. With strain 98, the inhibition rates were 94 and 81% for the fermented bean extract and 58% and 44% for the unfermented bean extracts. Testing of extracts prepared from black soybean by A. awamori at temperatures 25, 30 and 35 degrees C and for times of 1-5 days revealed that, generally, the extract prepared from beans fermented at 30 degrees C for 3 days exhibited the greatest inhibition against the mutagenic effects of 4-NQO and B[a]P.", "title": "Mutagenic and antimutagenic effects of methanol extracts of unfermented and fermented black soybeans." }, { "docid": "MED-2141", "text": "We investigated the association between dietary patterns and insulin resistance in the 3871 healthy Korean adults from the 2007 to 2008 Korea National Health and Nutrition Examination Survey. The whole grains and beans pattern was associated with lower prevalence of insulin resistance (OR for highest quintile=0.80, 95% CI=0.61-1.03, P for trend=0.013). Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.", "title": "High intake of whole grains and beans pattern is inversely associated with insulin resistance in healthy Korean adult population." }, { "docid": "MED-5080", "text": "Bioactivity-guided fractionation of black bean (Phaseolus vulgaris) seed coats was used to determine the chemical identity of bioactive constituents, which showed potent antiproliferative and antioxidative activities. Twenty-four compounds including 12 triterpenoids, 7 flavonoids, and 5 other phytochemicals were isolated using gradient solvent fractionation, silica gel and ODS columns, and semipreparative and preparative HPLC. Their chemical structures were identified using MS, NMR, and X-ray diffraction analysis. Antiproliferative activities of isolated compounds against Caco-2 human colon cancer cells, HepG2 human liver cancer cells, and MCF-7 human breast cancer cells were evaluated. Among the compounds isolated, compounds 1, 2, 6, 7, 8, 13, 14, 15, 16, 19, and 20 showed potent inhibitory activities against the proliferation of HepG2 cells, with EC50 values of 238.8 +/- 19.2, 120.6 +/- 7.3, 94.4 +/- 3.4, 98.9 +/- 3.3, 32.1 +/- 6.3, 306.4 +/- 131.3, 156.9 +/- 11.8, 410.3 +/- 17.4, 435.9 +/- 47.7, 202.3 +/- 42.9, and 779.3 +/- 37.4 microM, respectively. Compounds 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 14, 15, 19, and 20 showed potent antiproliferative activities against Caco-2 cell growth, with EC50 values of 179.9 +/- 16.9, 128.8 +/- 11.6, 197.8 +/- 4.2, 105.9 +/- 4.7, 13.9 +/- 2.8, 35.1 +/- 2.9, 31.2 +/- 0.5, 71.1 +/- 11.9, 40.8 +/- 4.1, 55.7 +/- 8.1, 299.8 +/- 17.3, 533.3 +/- 126.0, 291.2 +/- 1.0, and 717.2 +/- 104.8 microM, respectively. Compounds 5, 7, 8, 9, 11, 19, 20 showed potent antiproliferative activities against MCF-7 cell growth in a dose-dependent manner, with EC50 values of 129.4 +/- 9.0, 79.5 +/- 1.0, 140.1 +/- 31.8, 119.0 +/- 7.2, 84.6 +/- 1.7, 186.6 +/- 21.1, and 1308 +/- 69.9 microM, respectively. Six flavonoids (compounds 14-19) showed potent antioxidant activity. These results showed the phytochemical extracts of black bean seed coats have potent antioxidant and antiproliferative activities.", "title": "Phytochemicals of black bean seed coats: isolation, structure elucidation, and their antiproliferative and antioxidative activities." }, { "docid": "MED-3132", "text": "Little is known about dietitians current practice in counselling clients about the use of legumes in a low fat, high fibre diet. An exploratory e-mail questionnaire was sent to members of Dietitians of Canada to assess: dietitian use and preferences for legumes, dietitian practice, opinions about clients attitudes and preferences, and resource needs. Counsellors (n=256) had high personal use of legumes (64% > or = 1 serving/week) and frequently recommended legumes in counselling. The legumes most preferred by respondents and their clients were: peanuts, kidney beans, split peas, chickpeas, and lentils. Respondents often recommended canned bean products (76%) and tofu (61%), but other legume grocery products were less often recommended. The most common client issues identified were: flatulence (87% agreed), lack of familiarity (85%), and knowledge of preparation (82%). Dietitians were not satisfied with current resources to support practice, especially those respondents providing primarily clinical counselling services. The most requested resources were: recipes (90%), pamphlets (82%), food demonstrations (75%) and Internet sites (63%). Client level research is now needed to confirm the importance of the issues identified and to develop and test strategies for legume promotion in counselling.", "title": "Legume promotion in counselling: an e-mail survey of dietitians." }, { "docid": "MED-2085", "text": "A diet rich in fruits and vegetables is known to decrease the risk of cardiovascular disease. However, the information regarding the antithrombotic activity (antiplatelet, anticoagulant, and fibrinolytic) of fruits and vegetables is scarce. The aim of this study was to assess the antithrombotic activity of extracts from fruits and vegetables widely consumed in central Chile. The study included samples of 19 fruits and 26 vegetables, representative of the local diet. The extracts prepared from each sample included an aqueous (juice or pressed solubles) and/or methanol-soluble fraction. The extracts were evaluated for antiplatelet, anticoagulant, and fibrinolytic activity in vitro at a final concentration of 1 mg/ml. The antiplatelet activity was assessed by platelet aggregation inhibition; anticoagulant activity was measured by the prothrombin time (PT), diluted prothrombin time (dPT), activated partial thromboplastin time (APTT), kaolin clotting time (KCT), and thrombin time. The fibrinolytic effect was determined with the euglobin clot lysis time and fibrin plate methods. Extracts of green beans and tomatoes inhibited platelet aggregation induced by ADP and arachidonic acid, in a concentration-dependent manner. The methanolic extracts of grapes prolonged the PT and dPT. Finally, extracts of raspberry prolonged the APTT and also presented fibrinolytic activity. In conclusion, from a screening that included a variety of fruits and vegetables, we found antiplatelet activity in green beans and tomatoes, anticoagulant activities in grapes and raspberries, whereas fibrinolytic activity was observed only in raspberries. Further investigations are necessary to advance in knowledge of the active compounds of these fruits and vegetables and their mechanisms of action.", "title": "Antiplatelet, anticoagulant, and fibrinolytic activity in vitro of extracts from selected fruits and vegetables." }, { "docid": "MED-5118", "text": "OBJECTIVE: To compare the effects of two commercially available soy milks (one made using whole soy beans, the other using soy protein isolate) with low-fat dairy milk on plasma lipid, insulin, and glucose responses. DESIGN: Randomized clinical trial, cross-over design. SUBJECTS: Participants were 30-65 years of age, n = 28, with pre-study LDL-cholesterol (LDL-C) concentrations of 160-220 mg/dL, not on lipid lowering medications, and with an overall Framingham risk score of <or=10%. INTERVENTION: Participants were required to consume sufficient milk to provide 25 g protein/d from each source. The protocol included three 4-week treatment phases, each separated from the next by a wash-out period of >or=4 weeks. RESULTS: Mean LDL-C concentration at the end of each phase (+/- SD) was 161 +/- 20, 161 +/- 26 and 170 +/- 24 mg/dL for the whole bean soy milk, the soy protein isolate milk, and the dairy milk, respectively (p = 0.9 between soy milks, p = 0.02 for each soy milk vs. dairy milk). No significant differences by type of milk were observed for HDL-cholesterol, triacylglycerols, insulin, or glucose. CONCLUSION: A 25 g dose of daily soy protein from soy milk led to a modest 5% lowering of LDL-C relative to dairy milk among adults with elevated LDL-C. The effect did not differ by type of soy milk and neither soy milk significantly affected other lipid variables, insulin or glucose.", "title": "Effect of two types of soy milk and dairy milk on plasma lipids in hypercholesterolemic adults: a randomized trial." }, { "docid": "MED-3894", "text": "The purpose of this study was to examine the effects of a natural carbohydrate (CHO) source in the form of sun-dried raisins (SDRs) vs. Sports Jelly Beans™ (SJBs) on endurance performance in trained cyclists and triathletes. Ten healthy men (18-33 years) completed 1 water-only acclimatization exercise trial and 2 randomized exercise trials administered in a crossover fashion. Each trial consisted of a 120-minute constant-intensity glycogen depletion period followed by a 10-km time trial (TT). During each experimental trial, participants consumed isocaloric amounts of SDRs or SJBs in 20-minute intervals. Measurements included time to complete 10-km TT, power output during 10-km TT, blood glucose levels and respiratory exchange ratio during glycogen depletion period, rate of perceived exertion (RPE), 'flow' questionnaire responses, and a hedonic (i.e., pleasantness) sensory acceptance test. There were no significant differences in endurance performance for TT time (SDRs vs. SJBs, 17.3 ± 0.4 vs. 17.3 ± 0.4 seconds) or power (229.3 ± 13.0 vs. 232.0 ± 13.6 W), resting blood glucose levels (5.8 ± 04 mmol·L(-1) for SDRs and 5.4 ± 0.2 mmol·L(-1) for SJBs), RPE, or flow experiences between SDR and SJB trials. However, the mean sensory acceptance scores were significantly higher for the SDRs compared to the SJBs (50.7 ± 1.7 vs. 44.3 ± 2.7). Consuming SDRs or SJBs during 120 minutes of intense cycling results in similar subsequent TT performances and are equally effective in maintaining blood glucose levels during exercise. Therefore, SDRs are a natural, pleasant, cost-effective CHO alternative to commercial SJBs that can be used during moderate- to high-intensity endurance exercise.", "title": "Sun-dried raisins are a cost-effective alternative to Sports Jelly Beans in prolonged cycling." }, { "docid": "MED-4869", "text": "This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, including flavouring agents, with a view to recommending acceptable daily intakes (ADIs) and to preparing specifications for identity and purity. The first part of the report contains a general discussion of the principles governing the toxicological evaluation and assessment of intake of food additives (in particular, flavouring agents). A summary follows of the Committee's evaluations of technical, toxicological and intake data for certain food additives (asparaginase from Aspergillus niger expressed in A. niger, calcium lignosulfonate (40-65), ethyl lauroyl arginate, paprika extract, phospholipase C expressed in Pichia pastoris, phytosterols, phytostanols and their esters, polydimethylsiloxane, steviol glycosides and sulfites [assessment of dietary exposure]) and 10 groups of related flavouring agents (aliphatic branched-chain saturated and unsaturated alcohols, aldehydes, acids and related esters; aliphatic linear alpha,beta-unsaturated aldehydes, acids and related alcohols, acetals and esters; aliphatic secondary alcohols, ketones and related esters; alkoxy-substituted allylbenzenes present in foods and essential oils and used as flavouring agents; esters of aliphatic acyclic primary alcohols with aliphatic linear saturated carboxylic acids; furan-substituted aliphatic hydrocarbons, alcohols, aldehydes, ketones, carboxylic acids and related esters, sulfides, disulfides and ethers; miscellaneous nitrogen-containing substances; monocyclic and bicyclic secondary alcohols, ketones and related esters; hydroxy- and alkoxy-substituted benzyl derivatives; and substances structurally related to menthol). Specifications for the following food additives were revised: canthaxanthin; carob bean gum and carob bean gum (clarified); chlorophyllin copper complexes, sodium and potassium salts; Fast Green FCF; guar gum and guar gum (clarified); iron oxides; isomalt; monomagnesium phosphate; Patent Blue V; Sunset Yellow FCF; and trisodium diphosphate. Re-evaluation of flavouring agents for which estimated intake was based on anticipated poundage data was carried out for 2-isopropyl- N,2,3-trimethylbutyramide (No. 1595) and L-monomenthyl glutarate (No. 1414). Annexed to the report are tables summarizing the Committee's recommendations for intakes and toxicological evaluations of the food additives considered.", "title": "Evaluation of certain food additives." }, { "docid": "MED-2150", "text": "Previous investigations, of adolescent diet recalled in adulthood, found lower risk for benign breast disease (BBD) with higher intakes of vegetable fat and nuts during high school. We investigate whether vegetable protein and fat, derived from diets reported during pre-adolescence and adolescence, are associated with subsequent risk for BBD in young women. The Growing Up Today Study includes 9,039 females, 9–15 years in 1996, who completed questionnaires annually through 2001, and then in 2003, 2005, 2007, and 2010. Food frequency questionnaires (1996–2001) obtained intake data on a variety of foods. Beginning in 2005, women (18–30 years) reported whether they had ever been diagnosed with BBD that was confirmed by breast biopsy (n = 112 cases). Logistic regression estimated associations between intakes of vegetable protein and fat and biopsy-confirmed BBD. Those individual foods that were the largest contributors of protein and fat in this cohort were also investigated. In analyses of intakes from 1996 through 1998, when our cohort was youngest, vegetable fat (OR = 0.72/(10 gm/day), 95 % CI 0.53–0.98; p = 0.04) was inversely associated with BBD risk. The greatest sources of vegetable fat and protein in these girls were peanut butter, peanuts, nuts, beans (beans, lentils, and soybeans), and corn. A daily serving of any one of these was associated with lower risk (OR = 0.32/(serv/day), 95 % CI 0.13–0.79; p = 0.01). Peanut butter (and nuts) at age 11 years was inversely associated with risk (p = 0.01). In analyses of intakes at age 14 years, vegetable protein was associated with lower BBD risk (OR = 0.64/(10 gm/day), 95 % CI 0.43–0.95; p = 0.03). A daily serving at 14 years of any one of the foods was associated with lower risk (OR = 0.34, 95 % CI 0.16–0.75; p = 0.01), as was peanut butter (and nuts) (p = 0.02). Girls with a family history of breast cancer had significantly lower risk if they consumed these foods or vegetable fat. In conclusion, consumption of vegetable protein, fat, peanut butter, or nuts by older girls may help reduce their risk of BBD as young women.", "title": "Vegetable protein and vegetable fat intakes in pre-adolescent and adolescent girls, and risk for benign breast disease in young women" }, { "docid": "MED-719", "text": "In addition to causing embarrassment and unease, flatulence is linked to a variety of symptoms, some of which may be distressing. This review describes the origins of intestinal gas, its composition and methods which have been developed for its analysis. Emphasis is placed upon the effects of legumes in the diet in producing excessive intestinal gas and, particularly, on the role of raffinose-type oligosaccharides, containing alpha-galactosidic groupings. Suggestions for overcoming the problem are presented, including drug treatment, enzyme treatment, food processing and plant breeding. It is emphasised that removal of all raffinose-oligosaccharides from beans does not remove the problem of flatulence in animals and man; the compounds responsible--though assumed to be polysaccharides (or polysaccharide-derived oligomers formed by processing or cooking)--have yet to be characterised.", "title": "Flatulence--causes, relation to diet and remedies." }, { "docid": "MED-724", "text": "In addition to causing embarrassment and unease, flatulence is linked to a variety of symptoms, some of which may be distressing. This review describes the origins of intestinal gas, its composition and methods which have been developed for its analysis. Emphasis is placed upon the effects of legumes in the diet in producing excessive intestinal gas and, particularly, on the role of raffinose-type oligosaccharides, containing alpha-galactosidic groupings. Suggestions for overcoming the problem are presented, including drug treatment, enzyme treatment, food processing and plant breeding. It is emphasised that removal of all raffinose-oligosaccharides from beans does not remove the problem of flatulence in animals and man; the compounds responsible--though assumed to be polysaccharides (or polysaccharide-derived oligomers formed by processing or cooking)--have yet to be characterised.", "title": "Flatulence--causes, relation to diet and remedies." }, { "docid": "MED-890", "text": "A case-control study was carried out in Harbin city to assess the role of diet in the aetiology of colorectal cancer. A total of 336 incident cases of histologically confirmed colorectal cancer (111 colon cancer and 225 rectal cancer) and an equal number of controls with other non-neoplastic diseases were interviewed in hospital wards. Data concerning the average frequency of consumption and amount consumed of single food items were obtained by a dietary history questionnaire. Odds ratios and their confidence limits were computed. Multiple regression for risk status was also used. Vegetables, particularly green vegetables, chives and celery, have a strong protective effect against colorectal cancer. Reduced consumption of meat, eggs, bean products and grain was associated with increasing risk for cancer of the rectum. Alcohol intake was found to be an important risk factor for developing colon cancer and male rectal cancer.", "title": "Diet and cancer of the colon and rectum: a case-control study in China." }, { "docid": "MED-4165", "text": "Ergothioneine is a native membrane-impermeable thiol compound that is specifically accumulated in cells via the organic cation transporter OCTN1. In humans, OCTN1 and ergothioneine have been implicated in the etiopathogenesis of autoimmune disorders. However, available evidence about dietary sources and the functional role of ergothioneine in human physiology is scarce. Here, we analyzed the ergothioneine content in common foods using liquid chromatography tandem-mass spectrometry. Additionally, we assessed the protective potency of ergothioneine against various oxidative stressors in OCTN1-expressing cells in comparison with the main intracellular thiol antioxidant glutathione by evaluating cell viability with the MTT reduction assay. Only some food contained ergothioneine with highest concentrations detected in specialty mushrooms, kidney, liver, black and red beans, and oat bran. Ergothioneine exhibited cell protection only against copper(II)-induced toxicity but was far less potent than glutathione, indicting that ergothioneine is not involved in the intracellular antioxidant thiol defense system.", "title": "Dietary sources and antioxidant effects of ergothioneine." }, { "docid": "MED-875", "text": "AIMS: The purpose of this study was to search for a novel quorum sensing inhibitor and analyse its inhibitory activity. METHODS AND RESULTS: Quorum sensing inhibition was monitored using the Tn-5 mutant, Chromobacterium violaceum CV026. Vanilla beans (Vanilla planifolia Andrews) were extracted using 75% (v/v) aqueous methanol and added to C. violaceum CV026 cultures. Inhibitory activity was measured by quantifying violacein production using a spectrophotometer. The results have revealed that vanilla extract significantly reduced violacein production in a concentration-dependent manner, indicating inhibition of quorum sensing. CONCLUSIONS: Vanilla, a widely used spice and flavour, can inhibit bacterial quorum sensing. SIGNIFICANCE AND IMPACT OF THE STUDY: The results suggest that the intake of vanilla-containing food materials might promote human health by inhibiting quorum sensing and preventing bacterial pathogenesis. Further studies are required to isolate specific substances from vanilla extract acting as quorum sensing inhibitors.", "title": "Inhibition of bacterial quorum sensing by vanilla extract." }, { "docid": "MED-5354", "text": "This review focuses on the possible role in human health of the consumption of lignan-rich foods. Most of the plant lignans in human foods are converted by the intestinal microflora in the upper part of the large bowel to enterolactone and enterodiol, called mammalian or enterolignans. The protective role of these compounds, particularly in chronic Western diseases, is discussed. Evidence suggests that fiber- and lignan-rich whole-grain cereals, beans, berries, nuts, and various seeds are the main protective foods. Many factors, in addition to diet, such as intestinal microflora, smoking, antibiotics, and obesity affect circulating lignan levels in the body. Lignan-rich diets may be beneficial, particularly if consumed for life. Experimental evidence in animals has shown clear anticarcinogenic effects of flaxseed or pure lignans in many types of cancer. Many epidemiological results are controversial, partly because the determinants of plasma enterolactone are very different in different countries. The source of the lignans seems to play a role because other factors in the food obviously participate in the protective effects. The results are promising, but much work is still needed in this area of medicine.", "title": "Lignans and human health." }, { "docid": "MED-2195", "text": "The objective of this study was to evaluate the precursors of acrylamide formation in sweet potato (SP) (Ipomoea batatas L. Lam) chips and to determine the effect of different types of vegetable oils (VOs), that is, palm olein, coconut oil, canola oil, and soya bean oil, on acrylamide formation. The reducing sugars and amino acids in the SP slices were analyzed, and the acrylamide concentrations of SP chips were measured. SP chips that were fried in a lower degree of unsaturation oils contained a lower acrylamide concentration (1443 μg/kg), whereas those fried with higher degree of unsaturated oils contained a higher acrylamide concentration (2019 μg/kg). SP roots were found to contain acrylamide precursors, that is, 4.17 mg/g glucose and 5.05 mg/g fructose, and 1.63 mg/g free asparagine. The type of VO and condition used for frying, significantly influenced acrylamide formation. This study clearly indicates that the contribution of lipids in the formation of acrylamide should not be neglected. © 2013 Institute of Food Technologists®", "title": "The influence of deep frying using various vegetable oils on acrylamide formation in sweet potato (Ipomoea batatas L. Lam) chips." } ]
753
Malaria has a high vectorial capacity.
[ { "docid": "1173667", "text": "Experience gained from the Global Malaria Eradication Program (1955-72) identified a set of shared technical and operational factors that enabled some countries to successfully eliminate malaria. Spatial data for these factors were assembled for all malaria-endemic countries and combined to provide an objective, relative ranking of countries by technical, operational, and combined elimination feasibility. The analysis was done separately for Plasmodium falciparum and Plasmodium vivax, and the limitations of the approach were discussed. The relative rankings suggested that malaria elimination would be most feasible in countries in the Americas and Asia, and least feasible in countries in central and west Africa. The results differed when feasibility was measured by technical or operational factors, highlighting the different types of challenge faced by each country. The results are not intended to be prescriptive, predictive, or to provide absolute assessments of feasibility, but they do show that spatial information is available to facilitate evidence-based assessments of the relative feasibility of malaria elimination by country that can be rapidly updated.", "title": "Ranking of elimination feasibility between malaria-endemic countries" } ]
[ { "docid": "25938221", "text": "A specific retinopathy has been described in African children with cerebral malaria, but in adults this has not been extensively studied. Since the structure and function of the retinal vasculature greatly resembles the cerebral vasculature, study of retinal changes can reveal insights into the pathophysiology of cerebral malaria. A detailed observational study of malarial retinopathy in Bangladeshi adults was performed using high-definition portable retinal photography. Retinopathy was present in 17/27 adults (63%) with severe malaria and 14/20 adults (70%) with cerebral malaria. Moderate or severe retinopathy was more frequent in cerebral malaria (11/20, 55%) than in uncomplicated malaria (3/15, 20%; P=0.039), bacterial sepsis (0/5, 0%; P=0.038) or healthy controls (0/18, 0%; P<0.001). The spectrum of malarial retinopathy was similar to that previously described in African children, but no vessel discolouration was observed. The severity of retinal whitening correlated with admission venous plasma lactate (P=0.046), suggesting that retinal ischaemia represents systemic ischaemia. In conclusion, retinal changes related to microvascular obstruction were common in adults with severe falciparum malaria and correlated with disease severity and coma, suggesting that a compromised microcirculation has important pathophysiological significance in severe and cerebral malaria. Portable retinal photography has potential as a valuable tool to study malarial retinopathy.", "title": "The spectrum of retinopathy in adults with Plasmodium falciparum malaria" }, { "docid": "3929361", "text": "BACKGROUND Malaria elimination requires a variety of approaches individually optimized for different transmission settings. A recent field study in an area of low seasonal transmission in South West Cambodia demonstrated dramatic reductions in malaria parasite prevalence following both mass drug administration (MDA) and high treatment coverage of symptomatic patients with artemisinin-piperaquine plus primaquine. This study employed multiple combined strategies and it was unclear what contribution each made to the reductions in malaria. METHOD AND FINDINGS A mathematical model fitted to the trial results was used to assess the effects of the various components of these interventions, design optimal elimination strategies, and explore their interactions with artemisinin resistance, which has recently been discovered in Western Cambodia. The modelling indicated that most of the initial reduction of P. falciparum malaria resulted from MDA with artemisinin-piperaquine. The subsequent continued decline and near elimination resulted mainly from high coverage with artemisinin-piperaquine treatment. Both these strategies were more effective with the addition of primaquine. MDA with artemisinin combination therapy (ACT) increased the proportion of artemisinin resistant infections, although much less than treatment of symptomatic cases with ACT, and this increase was slowed by adding primaquine. Artemisinin resistance reduced the effectiveness of interventions using ACT when the prevalence of resistance was very high. The main results were robust to assumptions about primaquine action, and immunity. CONCLUSIONS The key messages of these modelling results for policy makers were: high coverage with ACT treatment can produce a long-term reduction in malaria whereas the impact of MDA is generally only short-term; primaquine enhances the effect of ACT in eliminating malaria and reduces the increase in proportion of artemisinin resistant infections; parasite prevalence is a better surveillance measure for elimination programmes than numbers of symptomatic cases; combinations of interventions are most effective and sustained efforts are crucial for successful elimination.", "title": "Optimising Strategies for Plasmodium falciparum Malaria Elimination in Cambodia: Primaquine, Mass Drug Administration and Artemisinin Resistance" }, { "docid": "27841037", "text": "The documented history of malaria in parts of Asia goes back more than 2,000 years, during which the disease has been a major player on the socioeconomic stage in many nation states as they waxed and waned in power and prosperity. On a much shorter time scale, the last half century has seen in microcosm a history of large fluctuations in endemicity and impact of malaria across the spectrum of rice fields and rain forests, mountains and plains that reflect the vast ecological diversity inhabited by this majority aggregation of mankind. That period has seen some of the most dramatic changes in social and economic structure, in population size, density and mobility, and in political structure in history: all have played a part in the changing face of malaria in this extensive region of the world. While the majority of global malaria cases currently reside in Africa, greater numbers inhabited Asia earlier this century before malaria programs savored significant success, and now Asia harbors a global threat in the form of the epicenter of multidrug resistant Plasmodium falciparum which is gradually encompassing the tropical world. The latter reflects directly the vicissitudes of economic change over recent decades, particularly the mobility of populations in search of commerce, trade and personal fortunes, or caught in the misfortunes of physical conflicts. The period from the 1950s to the 1990s has witnessed near \"eradication\" followed by resurgence of malaria in Sri Lanka, control and resurgence in India, the influence of war and postwar instability on drug resistance in Cambodia, increase in severe and cerebral malaria in Myanmar during prolonged political turmoil, the essential disappearance of the disease from all but forested border areas of Thailand where it remains for the moment intractable, the basic elimination of vivax malaria from many provinces of central China. Both positive and negative experiences have lessons to teach in the debate between eradication and control as alternative strategies. China has for years held high the goal of \"basic elimination\", eradication by another name, in sensible semi-defiance of WHO dictates. The Chinese experience makes it clear that, given community organization, exhaustive attention to case detection, management and focus elimination, plus the political will at all levels of society, it is possible both to eliminate malaria from large areas of an expansive nation and to implement surveillance necessary to maintain something approaching eradication status in those areas. But China has not succeeded in the international border regions of the tropical south where unfettered population movement confounds the program. Thailand, Malaysia and to an extent Vietnam have also reached essential elimination in their rice field plains by vigorous vertical programs but fall short at their forested borders. Economics is central to the history of the rise and fall of nations, and to the history of disease in the people who constitute nations. The current love affair with free market economics as the main driving force for advance of national wealth puts severe limitations on the essential involvement of communities in malaria management. The task of malaria control or elimination needs to be clearly related to the basic macroeconomic process that preoccupies governments, not cloistered away in the health sector Historically malaria has had a severe, measurable, negative impact on the productivity of nations. Economic models need rehoning with political aplomb and integrating with technical and demographic strategies. Recent decades in Chinese malaria history carry some lessons that may be relevant in this context.", "title": "Ecology, economics and political will: the vicissitudes of malaria strategies in Asia." }, { "docid": "14337960", "text": "Decisions to eliminate malaria from all or part of a country involve a complex set of factors, and this complexity is compounded by ambiguity surrounding some of the key terminology, most notably \"control\" and \"elimination. \" It is impossible to forecast resource and operational requirements accurately if endpoints have not been defined clearly, yet even during the Global Malaria Eradication Program, debate raged over the precise definition of \"eradication. \" Analogous deliberations regarding the meaning of \"elimination\" and \"control\" are basically nonexistent today despite these terms' core importance to programme planning. To advance the contemporary debate about these issues, this paper presents a historical review of commonly used terms, including control, elimination, and eradication, to help contextualize current understanding of these concepts. The review has been supported by analysis of the underlying mathematical concepts on which these definitions are based through simple branching process models that describe the proliferation of malaria cases following importation. Through this analysis, the importance of pragmatic definitions that are useful for providing malaria control and elimination programmes with a practical set of strategic milestones is emphasized, and it is argued that current conceptions of elimination in particular fail to achieve these requirements. To provide all countries with precise targets, new conceptual definitions are suggested to more precisely describe the old goals of \"control\" - here more exactly named \"controlled low-endemic malaria\" - and \"elimination. \" Additionally, it is argued that a third state, called \"controlled non-endemic malaria,\" is required to describe the epidemiological condition in which endemic transmission has been interrupted, but malaria resulting from onwards transmission from imported infections continues to occur at a sufficiently high level that elimination has not been achieved. Finally, guidelines are discussed for deriving the separate operational definitions and metrics that will be required to make these concepts relevant, measurable, and achievable for a particular environment.", "title": "How absolute is zero? An evaluation of historical and current definitions of malaria elimination" }, { "docid": "3770726", "text": "BACKGROUND Microfluidic platforms for quantitative evaluation of cell biologic processes allow low cost and time efficient research studies of biological and pathological events, such as monitoring cell migration by real-time imaging. In healthy and disease states, cell migration is crucial in development and wound healing, as well as to maintain the body's homeostasis. NEW METHOD The microfluidic chambers allow precise measurements to investigate whether fibroblasts carrying a mutation in the TOR1A gene, underlying the hereditary neurologic disease--DYT1 dystonia, have decreased migration properties when compared to control cells. RESULTS We observed that fibroblasts from DYT1 patients showed abnormalities in basic features of cell migration, such as reduced velocity and persistence of movement. COMPARISON WITH EXISTING METHOD The microfluidic method enabled us to demonstrate reduced polarization of the nucleus and abnormal orientation of nuclei and Golgi inside the moving DYT1 patient cells compared to control cells, as well as vectorial movement of single cells. CONCLUSION We report here different assays useful in determining various parameters of cell migration in DYT1 patient cells as a consequence of the TOR1A gene mutation, including a microfluidic platform, which provides a means to evaluate real-time vectorial movement with single cell resolution in a three-dimensional environment.", "title": "Microfluidic platform to evaluate migration of cells from patients with DYT1 dystonia." }, { "docid": "13959707", "text": "BACKGROUND Plasmodium falciparum malaria remains a major cause of illness and death in sub-Saharan Africa. Young children bear the brunt of the disease and though older children and adults suffer relatively fewer clinical attacks, they remain susceptible to asymptomatic P. falciparum infection. A better understanding of the host factors associated with immunity to clinical malaria and the ability to sustain asymptomatic P. falciparum infection will aid the development of improved strategies for disease prevention. METHODS AND FINDINGS Here we investigate whether full differential blood counts can predict susceptibility to clinical malaria among Kenyan children sampled at five annual cross-sectional surveys. We find that the ratio of monocytes to lymphocytes, measured in peripheral blood at the time of survey, directly correlates with risk of clinical malaria during follow-up. This association is evident among children with asymptomatic P. falciparum infection at the time the cell counts are measured (Hazard ratio (HR) = 2.7 (95% CI 1.42, 5.01, P = 0.002) but not in those without detectable parasitaemia (HR = 1.0 (95% CI 0.74, 1.42, P = 0.9). CONCLUSIONS We propose that the monocyte to lymphocyte ratio, which is easily derived from routine full differential blood counts, reflects an individual's capacity to mount an effective immune response to P. falciparum infection.", "title": "The Ratio of Monocytes to Lymphocytes in Peripheral Blood Correlates with Increased Susceptibility to Clinical Malaria in Kenyan Children" }, { "docid": "18074797", "text": "BACKGROUND Over the past decade malaria intervention coverage has been scaled up across Africa. However, it remains unclear what overall reduction in transmission is achievable using currently available tools. METHODS AND FINDINGS We developed an individual-based simulation model for Plasmodium falciparum transmission in an African context incorporating the three major vector species (Anopheles gambiae s.s., An. arabiensis, and An. funestus) with parameters obtained by fitting to parasite prevalence data from 34 transmission settings across Africa. We incorporated the effect of the switch to artemisinin-combination therapy (ACT) and increasing coverage of long-lasting insecticide treated nets (LLINs) from the year 2000 onwards. We then explored the impact on transmission of continued roll-out of LLINs, additional rounds of indoor residual spraying (IRS), mass screening and treatment (MSAT), and a future RTS,S/AS01 vaccine in six representative settings with varying transmission intensity (as summarized by the annual entomological inoculation rate, EIR: 1 setting with low, 3 with moderate, and 2 with high EIRs), vector-species combinations, and patterns of seasonality. In all settings we considered a realistic target of 80% coverage of interventions. In the low-transmission setting (EIR approximately 3 ibppy [infectious bites per person per year]), LLINs have the potential to reduce malaria transmission to low levels (<1% parasite prevalence in all age-groups) provided usage levels are high and sustained. In two of the moderate-transmission settings (EIR approximately 43 and 81 ibppy), additional rounds of IRS with DDT coupled with MSAT could drive parasite prevalence below a 1% threshold. However, in the third (EIR = 46) with An. arabiensis prevailing, these interventions are insufficient to reach this threshold. In both high-transmission settings (EIR approximately 586 and 675 ibppy), either unrealistically high coverage levels (>90%) or novel tools and/or substantial social improvements will be required, although considerable reductions in prevalence can be achieved with existing tools and realistic coverage levels. CONCLUSIONS Interventions using current tools can result in major reductions in P. falciparum malaria transmission and the associated disease burden in Africa. Reduction to the 1% parasite prevalence threshold is possible in low- to moderate-transmission settings when vectors are primarily endophilic (indoor-resting), provided a comprehensive and sustained intervention program is achieved through roll-out of interventions. In high-transmission settings and those in which vectors are mainly exophilic (outdoor-resting), additional new tools that target exophagic (outdoor-biting), exophilic, and partly zoophagic mosquitoes will be required.", "title": "Reducing Plasmodium falciparum Malaria Transmission in Africa: A Model-Based Evaluation of Intervention Strategies" }, { "docid": "5289038", "text": "Immune clearance and resource limitation (via red blood cell depletion) shape the peaks and troughs of malaria parasitemia, which in turn affect disease severity and transmission. Quantitatively partitioning the relative roles of these effects through time is challenging. Using data from rodent malaria, we estimated the effective propagation number, which reflects the relative importance of contrasting within-host control mechanisms through time and is sensitive to the inoculating parasite dose. Our analysis showed that the capacity of innate responses to restrict initial parasite growth saturates with parasite dose and that experimentally enhanced innate immunity can affect parasite density indirectly via resource depletion. Such a statistical approach offers a tool to improve targeting of drugs or vaccines for human therapy by revealing the dynamics and interactions of within-host regulatory mechanisms.", "title": "Partitioning regulatory mechanisms of within-host malaria dynamics using the effective propagation number." }, { "docid": "1349033", "text": "Based on sensitivity analysis of the MacDonald-Ross model, it has long been argued that the best way to reduce malaria transmission is to target adult female mosquitoes with insecticides that can reduce the longevity and human-feeding frequency of vectors. However, these analyses have ignored a fundamental biological difference between mosquito adults and the immature stages that precede them: adults are highly mobile flying insects that can readily detect and avoid many intervention measures whereas mosquito eggs, larvae and pupae are confined within relatively small aquatic habitats and cannot readily escape control measures. We hypothesize that the control of adult but not immature mosquitoes is compromised by their ability to avoid interventions such as excito-repellant insecticides. We apply a simple model of intervention avoidance by mosquitoes and demonstrate that this can substantially reduce effective coverage, in terms of the proportion of the vector population that is covered, and overall impact on malaria transmission. We review historical evidence that larval control of African malaria vectors can be effective and conclude that the only limitations to the effective coverage of larval control are practical rather than fundamental. Larval control strategies against the vectors of malaria in sub-Saharan Africa could be highly effective, complementary to adult control interventions, and should be prioritized for further development, evaluation and implementation as an integral part of Rolling Back Malaria.", "title": "Advantages of larval control for African malaria vectors: Low mobility and behavioural responsiveness of immature mosquito stages allow high effective coverage" }, { "docid": "8593263", "text": "An observational prospective cohort study assessed malaria risk perception, knowledge and prophylaxis practices among individuals of African ethnicity living in Paris and travelling to their country of origin to visit friends or relatives (VFR). The study compared two groups of VFR who had visited a travel clinic (TC; n=122) or a travel agency (TA; n=69) before departure. Of the 47% of VFR citing malaria as a health concern, 75% knew that malaria is mosquito-borne and that bed nets are an effective preventive measure. Perception of high malaria risk was greater in the TA group (33%) than in the TC group (7%). The availability of a malaria vaccine was mentioned by 35% of VFR, with frequent confusion between yellow fever vaccine and malaria prevention. Twenty-nine percent took adequate chemoprophylaxis with complete adherence, which was higher among the TC group (41%) than the TA group (12%). Effective antivector protection measures used were bed nets (16%), wearing long clothes at night (14%) and air conditioning (8%), with no differences between the study groups except in the use of impregnated bed nets (11% of the TC group and none of the TA group). Media coverage, malaria chemoprophylaxis repayment and cultural adaptation of preventive messages should be improved to reduce the high rate of inadequate malaria prophylaxis in VFR.", "title": "Malaria risk perception, knowledge and prophylaxis practices among travellers of African ethnicity living in Paris and visiting their country of origin in sub-Saharan Africa." }, { "docid": "5710820", "text": "BACKGROUND Following the last major malaria epidemic in 2000, malaria incidence in South Africa has declined markedly. The decrease has been so emphatic that South Africa now meets the World Health Organization (WHO) threshold for malaria elimination. Given the Millennium Development Goal of reversing the spread of malaria by 2015, South Africa is being urged to adopt an elimination agenda. This study aimed to determine the appropriateness of implementing a malaria elimination programme in present day South Africa. METHODS An assessment of the progress made by South Africa in terms of implementing an integrated malaria control programme across the three malaria-endemic provinces was undertaken. Vector control and case management data were analysed from the period of 2000 until 2011. RESULTS Both malaria-related morbidity and mortality have decreased significantly across all three malaria-endemic provinces since 2000. The greatest decline was seen in KwaZulu-Natal where cases decreased from 42,276 in 2000 to 380 in 2010 and deaths dropped from 122 in 2000 to six in 2010. Although there has been a 49.2 % (8,553 vs 4,214) decrease in the malaria cases reported in Limpopo Province, currently it is the largest contributor to the malaria incidence in South Africa. Despite all three provinces reporting average insecticide spray coverage of over 80%, malaria incidence in both Mpumalanga and Limpopo remains above the elimination threshold. Locally transmitted case numbers have declined in all three malaria provinces but imported case numbers have been increasing. Knowledge gaps in vector distribution, insecticide resistance status and drug usage were also identified. CONCLUSIONS Malaria elimination in South Africa is a realistic possibility if certain criteria are met. Firstly, there must be continued support for the existing malaria control programmes to ensure the gains made are sustained. Secondly, cross border malaria control initiatives with neighbouring countries must be strongly encouraged and supported to reduce malaria in the region and the importation of malaria into South Africa. Thirdly, operational research, particularly on vector distribution and insecticide resistance status must be conducted as a matter of urgency, and finally, the surveillance systems must be refined to ensure the information required to inform an elimination agenda are routinely collected.", "title": "The feasibility of malaria elimination in South Africa" }, { "docid": "13948920", "text": "Artemisinin-based combination therapies are the frontline treatment of Plasmodium falciparum malaria. The circulation of falsified and substandard artemisinin-based antimalarials in Southeast Asia has been a major predicament for the malaria elimination campaign. To provide an update of this situation, we purchased 153 artemisinin-containing antimalarials, as convenience samples, in private drug stores from different regions of Myanmar. The quality of these drugs in terms of their artemisinin derivative content was tested using specific dipsticks for these artemisinin derivatives, as point-of-care devices. A subset of these samples was further tested by high-performance liquid chromatography (HPLC). This survey identified that > 35% of the collected drugs were oral artesunate and artemether monotherapies. When tested with the dipsticks, all but one sample passed the assays, indicating that the detected artemisinin derivative content corresponded approximately to the labeled contents. However, one artesunate injection sample was found to contain no active ingredient at all by the dipstick assay and subsequent HPLC analysis. The continued circulation of oral monotherapies and the description, for the first time, of falsified parenteral artesunate provides a worrisome picture of the antimalarial drug quality in Myanmar during the malaria elimination phase, a situation that deserves more oversight from regulatory authorities.", "title": "Quality Testing of Artemisinin-Based Antimalarial Drugs in Myanmar." }, { "docid": "20999249", "text": "BACKGROUND Falciparum malaria or malaria tropica is one of the leading causes of childhood mortality worldwide. Malaria-related deaths occur mainly in sub-Saharan Africa, where an estimated 365 million clinical cases of Plasmodium falciparum malaria occur each year. In Europe, imported malaria cases occur due to returning travellers or immigration mostly from African countries. Children are more at risk than adults. The objective of this study was to identify high risk groups for imported childhood malaria in Europe in order to guide development of strategies for prevention, early recognition and management. METHODS In the period May 2003-January 2005 we reviewed all cases of paediatric malaria in the Netherlands notified by the Dutch Paediatric Surveillance System (Nederland Signalerings Centrum Kindergeneeskunde, NSCK) and the literature on imported malaria in children in Europe published between 1996 and 2006. RESULTS Malaria occurred mainly in children of long-term (n = 15, 47%) and new (n = 8, 25%) immigrants and was mostly acquired in sub-Saharan Africa. The dominant species was P. falciparum. Only one quarter of children had used adequate malaria chemoprophylaxis. Complicated disease occurred in 10 (31%) of cases. We also reviewed the literature and found 6082 reported cases of imported malaria among children in Europe; among these, four died and only one was reported to develop neurological sequelae. CONCLUSION Imported malaria in children remains an important problem and is unlikely to decrease unless the reasons for inadequate prophylaxis are addressed.", "title": "Imported malaria in children: a national surveillance in the Netherlands and a review of European studies." }, { "docid": "40900567", "text": "The multiplication rates and invasiveness of Plasmodium falciparum parasites isolated from adult Thai patients hospitalized with uncomplicated malaria (n=34) were compared with those from persons with severe malaria (n=42). To simulate severe malaria and control for host effects, the in vitro cultures were adjusted to 1% parasitemia and used the same red blood cell donor. P. falciparum isolates from persons with severe malaria had initial cycle multiplication rates in vitro that were 3-fold higher than those from uncomplicated malaria (median [95% confidence interval], 8.3 [7. 1-10.5] vs. 2.8 [1.7-3.9]; P=.001). Parasites causing severe malaria exhibited unrestricted red blood cell invasion, whereas those from uncomplicated malaria were restricted to a geometric mean of 40 (31%-53%) of red blood cells. P. falciparum parasites causing severe malaria were less selective and multiplied more at high parasitemias than those causing uncomplicated malaria.", "title": "Parasite multiplication potential and the severity of Falciparum malaria." }, { "docid": "17433284", "text": "BACKGROUND According to willingness of the Ministry of Health, Iran and presence of appropriate conditions for disease elimination, national malaria control program decided to conduct a research to clarify malaria status in 2007 and to provide required information to perform the elimination program. This review is comprised of the basis of national malaria elimination program in vision of 2025, which was started in 2010. METHODS In this descriptive study, data were analyzed by applications of different variables at district level. All districts in the three south eastern provinces, in which malaria has local transmission, were considered. Malaria cases has been determined and studied based on the national malaria surveillance system. RESULTS Since vivax malaria is predominant in Sistan & Baluchestan Province, number of vivax cases is equal to malaria positive cases approximately. The important point is that Nikshahr contains the maximum number of local vivax cases in this province and the maximum number of falciparum cases is reported from Sarbaz district. Among all districts of Hormozgan Province, no case of autochthonous falciparum was detected except in Bandar Jask and one case in Minab. There was no case of autochthonous falciparum in Kerman Province, except in Kahnoj and Ghale Ganj that each of them had one case in 2007. CONCLUSION It appears that the report of locally transmitted cases in Iran is increasing over the past few years, before starting malaria elimination plan. Since the Afghan refugees started to return to their own country so the main source of reporting of imported malaria cases reduced and local cases would be demonstrated more clearly.", "title": "Determination of Malaria Epidemiological Status in Iran’s Malarious Areas as Baseline Information for Implementation of Malaria Elimination Program in Iran" }, { "docid": "32390525", "text": "CONTEXT Long-term travelers, defined here as those traveling for periods of 6 months or longer, face particular challenges regarding malaria prevention. Current guidelines for malaria prevention primarily address prevention of Plasmodium falciparum infections in short-term travelers. OBJECTIVES To examine the risk of malaria in long-term travelers, recent developments in personal protective measures, and the safety and tolerability of malaria chemoprophylaxis during long-term use and to consider prevention strategies including continuous chemoprophylaxis, stand-by emergency self-treatment, seasonal prophylaxis, and strategies to prevent primary infection and relapses from P vivax malaria. EVIDENCE ACQUISITION Comprehensive search of scientific publications including MEDLINE via both OVID and PubMED for relevant studies and articles with a cutoff date of July 2006, using the search terms long-term travel and malaria prevention, long-term malaria chemoprophylaxis, and insect repellent and malaria. Additional references were obtained from searching the bibliographies of the selected articles, from dissertations, and from the proceedings of relevant conferences on travel medicine. There were no language restrictions. EVIDENCE SYNTHESIS Long-term travelers have a higher risk of malaria than short-term travelers. Long-term travelers underuse personal protective measures and adhere poorly to continuous chemoprophylaxis regimens. A number of strategies are used during long-term stays: discontinuation of chemoprophylaxis after the initial period, sequential regimens with different medications for chemoprophylaxis, stand-by emergency self-treatment, and seasonal chemoprophylaxis targeting high-incidence periods or locations. All strategies have advantages and drawbacks. Counterfeit drugs sold in countries endemic for malaria pose serious concern for long-term travelers who purchase their medications overseas. Vivax malaria causes significant illness in travelers, but relapses of vivax malaria are not prevented with the current first-line chemoprophylaxis regimens. Consensus guidelines are needed for prevention of malaria in long-term travelers. CONCLUSIONS Prevention of malaria in long-term travelers is a complex issue and requires expert advice from travel medicine specialists. Recommendations for prevention of malaria in long-term travelers must be individualized.", "title": "Prevention of malaria in long-term travelers." }, { "docid": "6503185", "text": "Plasmodium falciparum malaria, an infectious disease caused by a parasitic protozoan, claims the lives of nearly a million children each year in Africa alone and is a top public health concern. Evidence is accumulating that resistance to artemisinin derivatives, the frontline therapy for the asexual blood stage of the infection, is developing in southeast Asia. Renewed initiatives to eliminate malaria will benefit from an expanded repertoire of antimalarials, including new drugs that kill circulating P. falciparum gametocytes, thereby preventing transmission. Our current understanding of the biology of asexual blood-stage parasites and gametocytes and the ability to culture them in vitro lends optimism that high-throughput screenings of large chemical libraries will produce a new generation of antimalarial drugs. There is also a need for new therapies to reduce the high mortality of severe malaria. An understanding of the pathophysiology of severe disease may identify rational targets for drugs that improve survival.", "title": "Malaria biology and disease pathogenesis: insights for new treatments" }, { "docid": "25420421", "text": "Little is known about the changes in white blood cells and platelets in children with falciparum malaria in endemic areas. We measured the white cell count (WCC) and platelets of 230 healthy children from the community, 1369 children admitted to hospital with symptomatic malaria, and 1461 children with other medical conditions. Children with malaria had a higher WCC compared with community controls, and leucocytosis was strongly associated with younger age, deep breathing, severe anaemia, thrombocytopenia and death. The WCC was not associated with a positive blood culture. In children with malaria, high lymphocyte and low monocyte counts were independently associated with mortality. A platelet count of less than 150 x 109/l was found in 56.7% of children with malaria, and was associated with age, prostration and parasite density, but not with bleeding problems or mortality. The mean platelet volume was also higher in children with malaria compared with other medical conditions. This may reflect early release from the bone marrow in response to peripheral platelet destruction. Thus, leucocytosis was associated with both severity and mortality in children with falciparum malaria, irrespective of bacteraemia, whereas thrombocytopenia, although very common, was not associated with adverse outcome.", "title": "Changes in white blood cells and platelets in children with falciparum malaria: relationship to disease outcome." }, { "docid": "20931483", "text": "Understanding local variability in malaria transmission risk is critically important when designing intervention or vaccine trials. Using a combination of field data, satellite image analysis, and GIS modeling, we developed a high-resolution map of malaria entomological inoculation rates (EIR) in The Gambia, West Africa. The analyses are based on the variation in exposure to malaria parasites experienced in 48 villages in 1996 and 21 villages in 1997. The entomological inoculation rate (EIR) varied from 0 to 166 infective bites per person per rainy season. Detailed field surveys identified the major Anopheles gambiae s.l. breeding habitats. These habitats were mapped by classification of a LANDSAT TM satellite image with an overall accuracy of 85%. Village EIRs decreased as a power function based on the breeding areas size and proximity. We use this relationship and the breeding habitats to map the variation in EIR over the entire 2500-km(2) study area.", "title": "High spatial resolution mapping of malaria transmission risk in the Gambia, west Africa, using LANDSAT TM satellite imagery." }, { "docid": "37248570", "text": "After a lapse of almost 40 years, malaria eradication is back on the global health agenda. Inspired by the Gates Malaria Forum in October 2007,1,2 key organizations are starting to debate the pros and cons of redefining eradication as an explicit goal of malaria control efforts. Attempts to eliminate malaria in southern Africa3 and Pacific Island states,4 and WHO’s Global Malaria Programme agenda and field manual for malaria elimination,5,6 foreshadow this movement towards another global attempt at eradication. When marking 60 years of WHO’s commitment to fighting malaria, we must ask what has been achieved, but also what can we learn from the past. We now know so much more about the biology of parasite-host responses, the determinants of endemicity and transmission dynamics, the social, economic and cultural implications of malaria at household, community and national levels, and the demands made upon health systems in endemic countries. We do not yet know how to synthesize and integrate this knowledge to achieve elimination in different settings. Regional malaria elimination campaigns were first conducted in the late 1940s, preparing the ground for the Global Malaria Eradication Program in 1955. This campaign succeeded in eliminating malaria from Europe, North America, the Caribbean and parts of Asia and South-Central America.7 But no major success occurred in sub-Saharan Africa, which accounts for 80% of today’s burden of malaria.8 When the aspiration of global eradication was abandoned in 1969, the main reasons for failure were technical challenges of executing the strategy especially in Africa. The post-eradication era from 1969 to 1991 focused on technical issues, and research and development for new tools, leading to advances in drug and vaccine development, vector control and insecticide-treated nets. These decades also brought a better understanding of the social, economic and cultural dimensions of malaria. There was little global support provided specifically for malaria control in the newly independent states of Africa that were struggling to establish broad-based health systems and primary health care. By 1992, the combination of a worsening malaria situation and promising technical developments led to renewed global focus on malaria control. The Roll Back Malaria initiative, launched by WHO in 1998, led to the Abuja Declaration in 2000, which defined progressive intervention coverage targets for control designed to eliminate malaria as a public health problem, while emphasizing that this could only be achieved through vastly strengthened local health systems.9 Increased resources through the Global Fund to Fight AIDS, Tuberculosis and Malaria, the World Bank’s Booster Program, the US President’s Malaria Initiative and many others has meant that this page is finally beginning to turn as intervention coverage is rising.10 It is against this background that we hear this call for elimination/eradication. The challenges remain formidable. We all know that elimination in Africa is not possible with current tools. But efforts must focus beyond simply developing better tools, to include how existing and future tools can be strategically combined for maximum synergistic effectiveness when integrated into different health and social systems prevailing in endemic areas. Aiming at elimination and eradication further implies the need for effective surveillance strategies to monitor progress (again a challenge for health systems). This in turn requires a better understanding of malaria transmission heterogeneity in a globalized world with rapidly changing dynamics in environment, climate, migration and transnational cooperation. Maintaining long-term momentum in the face of success in regional elimination while waiting to achieve final eradication will be a major challenge. Shrinking the map by starting on the malaria margins with the “easy-to-eliminate” settings will boost morale initially but may bring marginal benefits to such areas at the expense of those where the burden of malaria is highest. Any strategic plan – and here we learn again from the past – needs to be a synchronous global effort, locally adapted in all endemic areas. Although we lack sufficient knowledge, systems and tools to eradicate malaria today, we do have a window of political will and financial resources to refocus on the goal of effective control through universal coverage of appropriate interventions. The prerequisites for a successful start are: (i) a process of inclusive discourse to agree on global vision, goals and strategy; and (ii) a global plan for all endemic areas describing how, where and when we move from control towards elimination. What must distinguish the new era, especially in Africa, is a real rather than rhetorical emphasis on health systems. ■", "title": "Malaria eradication back on the table." }, { "docid": "25069745", "text": "OBJECTIVE To describe the epidemiology of urban malaria, an emerging problem in sub-Saharan Africa. METHOD Cross-sectional surveys of communities in Accra and Kumasi, Ghana, determining risk factors for malaria infection and anaemia in children aged 6-60 months. RESULTS Malaria prevalence rates ranged from 2% to 33% between urban communities. 47.1% of children were anaemic (Hb<11.0 g/dl). Factors associated with malaria prevalence were low socio-economic status, age and anaemia. The attributable risks of anaemia and severe anaemia (Hb<8.0 g/dl) caused by malaria were 5% and 23% respectively. CONCLUSIONS Malaria in urban areas displayed a heterogeneity and complexity that differed from the rural environment, which has important implications for malaria control. Marked intra-city variation indicates the importance of targeting specific areas or districts. The most vulnerable group, the urban poor, should be prioritized when designing control measures. This would require careful assessment of the malaria risk pattern in any city to guide an integrated control program.", "title": "Urban malaria and anaemia in children: a cross-sectional survey in two cities of Ghana." }, { "docid": "2264455", "text": "There is no licenced vaccine against any human parasitic disease and Plasmodium falciparum malaria, a major cause of infectious mortality, presents a great challenge to vaccine developers. This has led to the assessment of a wide variety of approaches to malaria vaccine design and development, assisted by the availability of a safe challenge model for small-scale efficacy testing of vaccine candidates. Malaria vaccine development has been at the forefront of assessing many new vaccine technologies including novel adjuvants, vectored prime-boost regimes and the concept of community vaccination to block malaria transmission. Most current vaccine candidates target a single stage of the parasite's life cycle and vaccines against the early pre-erythrocytic stages have shown most success. A protein in adjuvant vaccine, working through antibodies against sporozoites, and viral vector vaccines targeting the intracellular liver-stage parasite with cellular immunity show partial efficacy in humans, and the anti-sporozoite vaccine is currently in phase III trials. However, a more effective malaria vaccine suitable for widespread cost-effective deployment is likely to require a multi-component vaccine targeting more than one life cycle stage. The most attractive near-term approach to develop such a product is to combine existing partially effective pre-erythrocytic vaccine candidates.", "title": "Vaccines against malaria" }, { "docid": "45218443", "text": "The hemoglobinopathies are probably the world's most common genetic diseases: The World Health Organization has estimated that at least 5% of the population are carriers for one or other of the most serious forms, the alpha- and beta-thalassemias and the structural variant hemoglobins S, C, and E, which are found at polymorphic frequencies in many countries. All these hemoglobinopathies are believed to provide protection against malaria, and it is thought that, in malarial regions of the world, natural selection has been responsible for elevating and maintaining their gene frequencies, an idea first proposed 50 years ago by J.B.S. Haldane. Epidemiological studies undertaken in the 1950s on hemoglobin S in Africa provided support for the \"malaria hypothesis,\" but until recently it has proved extremely difficult to verify it for the thalassemias. The application of molecular methods has, however, provided new opportunities to address this old question. Population and molecular genetic analysis of thalassemia variants, and microepidemiological studies of the relationship between alpha-thalassemia and malaria in the southwest Pacific, have provided unequivocal evidence for protection. Surprisingly, some of this protection appears to derive from enhanced susceptibility in very young thalassemic children to both Plasmodium falciparum and, especially, P. vivax, and this early exposure appears to provide the basis for better protection in later life.", "title": "Thalassemia and malaria: new insights into an old problem." }, { "docid": "24721347", "text": "The founding fathers of malariology combined scientific originality, perseverance in research, strong characters, breadth of interest and social concern. A hundred years later research and understanding has made immense progress but the world still bears a huge burden of malaria. For the next century research requires both more specialism and a holistic range if it is to be used in control, requiring multidisciplinary team work. Environmental changes and interventions produce a dynamic and changing pattern of malaria, not the static one of the past. From the original parasite life cycle, research has analysed a series of other cycles at electron microscope, biochemical and genome levels on decreasing size scales and quantitative epidemiological cycles for control. Recent additions to these concepts have been stage-specific antigens, cycles of disease rather than parasites alone, considering populations of parasites rather than just cases, and also genetic variation in each component of the parasite-human host-vector triad. In this volume there emerges for the first time a coherent overall picture of the biomedical aspects of basic malariology as the interacting population genetics of malaria parasites, anophelines and people. This provides a coherent model for the new century dealing with the great biological malaria problems of drug resistance, vaccine development, insecticidal and net control and can feed, with socio-economic work, into the gathering renewal of control efforts. New work on large-scale changes of malaria in space and time enables us to be precise about effects of local and global environmental changes to predict epidemics. Future research will be as much about linking these different scales of understanding as control will be about linking different levels of the health system. The grim situation in poor holoendemic countries also requires practical support of the type that the founders of malariology were involved in. A coherent understanding needs to feed into the new control efforts, from Roll Back Malaria onwards, for the next century.", "title": "The last and the next hundred years of malariology." }, { "docid": "30741007", "text": "The distribution of insecticide-treated bednets to help combat the burden of malaria in sub-Saharan Africa has accelerated in the past 5 years. Additionally, many countries are also considering, or have already begun, indoor residual spraying campaigns. These are positive developments, since vector control has repeatedly proven to be an effective means of reducing malaria transmission. However, the sustainability of these insecticide-based interventions relies on the continuing susceptibility of the anopheles vectors to the limited number of available insecticides. Continual monitoring for early signs of insecticide resistance and the adoption of carefully considered resistance management strategies are therefore required. Regrettably, this essential monitoring component is frequently given a low priority in the push to meet ambitious coverage targets. We outline the key requirements for establishing an insecticide resistance surveillance system and urge all those involved in malaria vector control, either directly or as facilitators, to ensure that these measures are incorporated into control programmes. Failure to act now will inevitably lead to a future breakdown in disease control and jeopardise hopes of eradicating this major public-health problem.", "title": "Lessons from the past: managing insecticide resistance in malaria control and eradication programmes." }, { "docid": "15237660", "text": "BACKGROUND Long-lasting insecticide treated nets (LLINs) and indoor residual house spraying (IRS) are the main interventions for the control of malaria vectors in Zanzibar. The aim of the present study was to assess the susceptibility status of malaria vectors against the insecticides used for LLINs and IRS and to determine the durability and efficacy of LLINs on the island. METHODS Mosquitoes were sampled from Pemba and Unguja islands in 2010-2011 for use in WHO susceptibility tests. One hundred and fifty LLINs were collected from households on Unguja, their physical state was recorded and then tested for efficacy as well as total insecticide content. RESULTS Species identification revealed that over 90% of the Anopheles gambiae complex was An. arabiensis with a small number of An. gambiae s.s. and An. merus being present. Susceptibility tests showed that An. arabiensis on Pemba was resistant to the pyrethroids used for LLINs and IRS. Mosquitoes from Unguja Island, however, were fully susceptible to all pyrethroids tested. A physical examination of 150 LLINs showed that two thirds were damaged after only three years in use. All used nets had a significantly lower (p < 0.001) mean permethrin concentration of 791.6 mg/m2 compared with 944.2 mg/m2 for new ones. Their efficacy decreased significantly against both susceptible An. gambiae s.s. colony mosquitoes and wild-type mosquitoes from Pemba after just six washes (p < 0.001). CONCLUSION The sustainability of the gains achieved in malaria control in Zanzibar is seriously threatened by the resistance of malaria vectors to pyrethroids and the short-lived efficacy of LLINs. This study has revealed that even in relatively well-resourced and logistically manageable places like Zanzibar, malaria elimination is going to be difficult to achieve with the current control measures.", "title": "Challenges for malaria elimination in Zanzibar: pyrethroid resistance in malaria vectors and poor performance of long-lasting insecticide nets" }, { "docid": "42373943", "text": "BACKGROUND Malaria is considered as the main differential diagnosis of acute febrile illness in the tropics, and alteration of various hematological parameters has been observed in patients with malaria. AIM To ascertain if certain hematological parameters increase the probability of malaria in patients with acute febrile illnesses. SETTINGS AND DESIGN Hospital based, prospective cohort study. METHODS AND MATERIAL All consecutive in patients with fever of less than seven days in duration were included in the study. Patients where localizing cause for fever could be determined were excluded. Hematological parameters (Hemoglobin, Red cell distribution width (RDW), Leukocyte count, and platelet counts) were determined by using automated counter, and peripheral smear examination for malarial parasite was taken as gold standard for the diagnosis of malaria. STATISTICAL ANALYSIS USED Diagnostic accuracy was measured by computing sensitivity, specificity, predictive values and likelihood ratios. The precision of these estimates was evaluated using 95% confidence intervals. RESULTS AND CONCLUSIONS A total of 184 patients were included in the study and 70 (38%) had a positive peripheral smear for malarial parasite. Thrombocytopenia alone (platelet countless than 150,000/mm3) was a predictor for malaria (Sn 60%, Sp 88%, LR+ 5.04) and in combination with anemia (Hb < 10 g/dl) it was next best parameter (Sn 69%, Sp 74%, LR+ 2.77). RDW and leukocyte count were not predictive. The conclusion of this study is that the presence of thrombocytopenia in a patient with acute febrile illness increases the probability of malarial infection.", "title": "Can hematological parameters discriminate malaria from nonmalarious acute febrile illness in the tropics?" }, { "docid": "15617866", "text": "Paratransgenesis, the genetic manipulation of insect symbiotic microorganisms, is being considered as a potential method to control vector-borne diseases such as malaria. The feasibility of paratransgenic malaria control has been hampered by the lack of candidate symbiotic microorganisms for the major vector Anopheles gambiae. In other systems, densonucleosis viruses (DNVs) are attractive agents for viral paratransgenesis because they infect important vector insects, can be genetically manipulated and are transmitted to subsequent generations. However, An. gambiae has been shown to be refractory to DNV dissemination. We discovered, cloned and characterized the first known DNV (AgDNV) capable of infection and dissemination in An. gambiae. We developed a flexible AgDNV-based expression vector to express any gene of interest in An. gambiae using a two-plasmid helper-transducer system. To demonstrate proof-of-concept of the viral paratransgenesis strategy, we used this system to transduce expression of an exogenous gene (enhanced green fluorescent protein; EGFP) in An. gambiae mosquitoes. Wild-type and EGFP-transducing AgDNV virions were highly infectious to An. gambiae larvae, disseminated to and expressed EGFP in epidemiologically relevant adult tissues such as midgut, fat body and ovaries and were transmitted to subsequent mosquito generations. These proof-of-principle data suggest that AgDNV could be used as part of a paratransgenic malaria control strategy by transduction of anti-Plasmodium peptides or insect-specific toxins in Anopheles mosquitoes. AgDNV will also be extremely valuable as an effective and easy-to-use laboratory tool for transient gene expression or RNAi in An. gambiae.", "title": "Viral Paratransgenesis in the Malaria Vector Anopheles gambiae" }, { "docid": "26474812", "text": "Malaria parasites and immune responses in an infected human interact on a dynamic landscape, in which a population of replicating parasites depletes a population of replenishing red blood cells (RBCs). These underlying dynamics receive relatively little attention, but they offer unique insights into the processes that control most malaria infections. Here, we focus on the observation that three of the four malaria-parasite species that infect humans are restricted to particular age classes of RBC. We explicitly incorporate this observation in models of infection dynamics to distinguish common from species-specific pressures on host immune responses, and we find that age structuring has profound effects on the course of infection. For all four species conditions exist under which the parasites may persist at low densities, or may clear, even in the absence of an immune response. Catastrophic anemia can occur even with the two species that attack only the youngest RBCs, although only a small fraction of cells are parasitized at any point. Furthermore, with these two, compensatory erythropoetic responses in the host accelerate parasite population growth. A \"basic reproduction rate\" characterizes these differences in outcomes.", "title": "Age-structured red blood cell susceptibility and the dynamics of malaria infections." }, { "docid": "1805641", "text": "BACKGROUND Artemisinin derivatives used in recently introduced combination therapies (ACTs) for Plasmodium falciparum malaria significantly lower patient infectiousness and have the potential to reduce population-level transmission of the parasite. With the increased interest in malaria elimination, understanding the impact on transmission of ACT and other antimalarial drugs with different pharmacodynamics becomes a key issue. This study estimates the reduction in transmission that may be achieved by introducing different types of treatment for symptomatic P. falciparum malaria in endemic areas. METHODS AND FINDINGS We developed a mathematical model to predict the potential impact on transmission outcomes of introducing ACT as first-line treatment for uncomplicated malaria in six areas of varying transmission intensity in Tanzania. We also estimated the impact that could be achieved by antimalarials with different efficacy, prophylactic time, and gametocytocidal effects. Rates of treatment, asymptomatic infection, and symptomatic infection in the six study areas were estimated using the model together with data from a cross-sectional survey of 5,667 individuals conducted prior to policy change from sulfadoxine-pyrimethamine to ACT. The effects of ACT and other drug types on gametocytaemia and infectiousness to mosquitoes were independently estimated from clinical trial data. Predicted percentage reductions in prevalence of infection and incidence of clinical episodes achieved by ACT were highest in the areas with low initial transmission. A 53% reduction in prevalence of infection was seen if 100% of current treatment was switched to ACT in the area where baseline slide-prevalence of parasitaemia was lowest (3.7%), compared to an 11% reduction in the highest-transmission setting (baseline slide prevalence = 57.1%). Estimated percentage reductions in incidence of clinical episodes were similar. The absolute size of the public health impact, however, was greater in the highest-transmission area, with 54 clinical episodes per 100 persons per year averted compared to five per 100 persons per year in the lowest-transmission area. High coverage was important. Reducing presumptive treatment through improved diagnosis substantially reduced the number of treatment courses required per clinical episode averted in the lower-transmission settings although there was some loss of overall impact on transmission. An efficacious antimalarial regimen with no specific gametocytocidal properties but a long prophylactic time was estimated to be more effective at reducing transmission than a short-acting ACT in the highest-transmission setting. CONCLUSIONS Our results suggest that ACTs have the potential for transmission reductions approaching those achieved by insecticide-treated nets in lower-transmission settings. ACT partner drugs and nonartemisinin regimens with longer prophylactic times could result in a larger impact in higher-transmission settings, although their long term benefit must be evaluated in relation to the risk of development of parasite resistance.", "title": "Modelling the Impact of Artemisinin Combination Therapy and Long-Acting Treatments on Malaria Transmission Intensity" } ]
734
MEK inhibitors are effective treatments in RAS-driven mouse models of cancer.
[ { "docid": "4961038", "text": "Somatic mutations that activate phosphoinositide 3-kinase (PI3K) have been identified in the p110-alpha catalytic subunit (encoded by PIK3CA). They are most frequently observed in two hotspots: the helical domain (E545K and E542K) and the kinase domain (H1047R). Although the p110-alpha mutants are transforming in vitro, their oncogenic potential has not been assessed in genetically engineered mouse models. Furthermore, clinical trials with PI3K inhibitors have recently been initiated, and it is unknown if their efficacy will be restricted to specific, genetically defined malignancies. In this study, we engineered a mouse model of lung adenocarcinomas initiated and maintained by expression of p110-alpha H1047R. Treatment of these tumors with NVP-BEZ235, a dual pan-PI3K and mammalian target of rapamycin (mTOR) inhibitor in clinical development, led to marked tumor regression as shown by positron emission tomography-computed tomography, magnetic resonance imaging and microscopic examination. In contrast, mouse lung cancers driven by mutant Kras did not substantially respond to single-agent NVP-BEZ235. However, when NVP-BEZ235 was combined with a mitogen-activated protein kinase kinase (MEK) inhibitor, ARRY-142886, there was marked synergy in shrinking these Kras-mutant cancers. These in vivo studies suggest that inhibitors of the PI3K-mTOR pathway may be active in cancers with PIK3CA mutations and, when combined with MEK inhibitors, may effectively treat KRAS mutated lung cancers.", "title": "Effective Use of PI3K and MEK Inhibitors to Treat Mutant K-Ras G12D and PIK3CA H1047R Murine Lung Cancers" } ]
[ { "docid": "2272614", "text": "Activating mutations in the EGF receptor (EGFR) are associated with clinical responsiveness to EGFR tyrosine kinase inhibitors (TKI), such as erlotinib and gefitinib. However, resistance eventually arises, often due to a second EGFR mutation, most commonly T790M. Through a genome-wide siRNA screen in a human lung cancer cell line and analyses of murine mutant EGFR-driven lung adenocarcinomas, we found that erlotinib resistance was associated with reduced expression of neurofibromin, the RAS GTPase-activating protein encoded by the NF1 gene. Erlotinib failed to fully inhibit RAS-ERK signaling when neurofibromin levels were reduced. Treatment of neurofibromin-deficient lung cancers with a MAP-ERK kinase (MEK) inhibitor restored sensitivity to erlotinib. Low levels of NF1 expression were associated with primary and acquired resistance of lung adenocarcinomas to EGFR TKIs in patients. These findings identify a subgroup of patients with EGFR-mutant lung adenocarcinoma who might benefit from combination therapy with EGFR and MEK inhibitors.", "title": "Reduced NF1 expression confers resistance to EGFR inhibition in lung cancer." }, { "docid": "85665741", "text": "5247 Constitutive ERK signaling is common in human cancer and is often the result of activating mutations of BRAF, RAS and upstream receptor tyrosine kinases. Missense BRAF kinase domain mutations are frequently observed in melanoma, colon and thyroid cancers and less frequently in lung and other cancer types. The vast majority (>90%) involve a glutamic acid for valine substitution at codon 600 (V600E), which results in elevated BRAF kinase activity. BRAF kinase domain mutations with intermediate and impaired kinase activity have also been identified, most frequently in NSCLC. We have previously reported that tumors with V600E BRAF mutation are selectively sensitive to MEK inhibition. Using the potent and selective MEK1/2 inhibitor PD0325901 (Pfizer), we examined a panel of NSCLC cell lines with mutant EGFR, KRAS, and/or low, intermediate and high-activity BRAF kinase domain mutations for MEK dependence. In all but one case, EGFR, KRAS and BRAF mutations were mutually exclusive with the exception being a cell line with concurrent NRAS and intermediate activity BRAF mutations. Consistent with our prior results, NSCLC cells with V600E BRAF mutation were exquisitely sensitive to MEK inhibition (PD0325901 IC50 of 2nM). The proliferation of cells with non-V600E mutations, including those with high (G469A), intermediate (L597V) and impaired (G466V) kinase activities, was also MEK dependent with IC50’s ranging between 2.7 and 80 nM. Inhibition of MEK in these cells resulted in downregulation of cyclin D1 and G1 growth arrest, with variable induction of apoptosis. Despite high basal ERK activity, NSCLC tumor cells with EGFR mutation were uniformly resistant to MEK inhibition (at doses of up to 500nM), despite effective and prolonged inhibition of ERK phosphorylation. Tumor cells with RAS mutation had a more variable response, with some cell lines demonstrating sensitivity, while others were completely resistant. There was no correlation between basal ERK activity and sensitivity to MEK inhibition. A strong inverse correlation between Akt activity and PD0325901 sensitivity was observed. These results suggest that MEK inhibition may be useful therapeutically in tumors with V600E and non-V600E BRAF kinase domain mutations. The results also suggest that inhibition of both MEK and Akt signaling may be required in NSCLC tumors with high basal AKT activity.", "title": "BRAF mutation predicts for MEK-dependence in non-small cell lung cancer (NSCLC)." }, { "docid": "4920376", "text": "Induction of compensatory mechanisms and ERK reactivation has limited the effectiveness of Raf and MEK inhibitors in RAS-mutant cancers. We determined that direct pharmacologic inhibition of ERK suppressed the growth of a subset of KRAS-mutant pancreatic cancer cell lines and that concurrent phosphatidylinositol 3-kinase (PI3K) inhibition caused synergistic cell death. Additional combinations that enhanced ERK inhibitor action were also identified. Unexpectedly, long-term treatment of sensitive cell lines caused senescence, mediated in part by MYC degradation and p16 reactivation. Enhanced basal PI3K-AKT-mTOR signaling was associated with de novo resistance to ERK inhibitor, as were other protein kinases identified by kinome-wide siRNA screening and a genetic gain-of-function screen. Our findings reveal distinct consequences of inhibiting this kinase cascade at the level of ERK.", "title": "Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression." }, { "docid": "28651643", "text": "Activating mutations within the K-ras gene occur in a high percentage of human pancreatic carcinomas. We reported previously that the presence of oncogenic, activated K-ras in human pancreatic carcinoma cell lines did not result in constitutive activation of the extracellular signal-regulated kinases (ERK1 and ERK2). In the present study, we further characterized the ERK signaling pathway in pancreatic tumor cell lines in order to determine whether the ERK pathway is subject to a compensatory downregulation. We found that the attenuation of serum-induced ERK activation was not due to a delay in the kinetics of ERK phosphorylation. Treatment with the tyrosine phosphatase inhibitor orthovanadate increased the level of ERK phosphorylation, implicating a vanadate-sensitive tyrosine phosphatase in the negative regulation of ERK. Furthermore, expression of a dual specificity phosphatase capable of inactivating ERK known as mitogen-activated protein (MAP) kinase phosphatase-2 (MKP-2) was elevated in most of the pancreatic tumor cell lines and correlated with the presence of active MAP kinase kinase (MEK). Taken together, these results suggest that pancreatic tumor cells expressing oncogenic K-ras compensate, in part, by upregulating the expression of MKP-2 to repress the ERK signaling pathway.", "title": "Pancreatic tumor cells with mutant K-ras suppress ERK activity by MEK-dependent induction of MAP kinase phosphatase-2." }, { "docid": "7821634", "text": "Neoadjuvant chemotherapy (NAC) induces a pathological complete response (pCR) in ∼30% of patients with breast cancer. However, many patients have residual cancer after chemotherapy, which correlates with a higher risk of metastatic recurrence and poorer outcome than those who achieve a pCR. We hypothesized that molecular profiling of tumors after NAC would identify genes associated with drug resistance. Digital transcript counting was used to profile surgically resected breast cancers after NAC. Low concentrations of dual specificity protein phosphatase 4 (DUSP4), an ERK phosphatase, correlated with high post-NAC tumor cell proliferation and with basal-like breast cancer (BLBC) status. BLBC had higher DUSP4 promoter methylation and gene expression patterns of Ras-ERK pathway activation relative to other breast cancer subtypes. DUSP4 overexpression increased chemotherapy-induced apoptosis, whereas DUSP4 depletion dampened the response to chemotherapy. Reduced DUSP4 expression in primary tumors after NAC was associated with treatment-refractory high Ki-67 scores and shorter recurrence-free survival. Finally, inhibition of mitogen-activated protein kinase kinase (MEK) synergized with docetaxel treatment in BLBC xenografts. Thus, DUSP4 downregulation activates the Ras-ERK pathway in BLBC, resulting in an attenuated response to anti-cancer chemotherapy.", "title": "Profiling of residual breast cancers after neoadjuvant chemotherapy identifies DUSP4 deficiency as a mechanism of drug resistance" }, { "docid": "9225850", "text": "Neutrophils are peripheral blood leukocytes that represent the first line of immune cell defense against bacterial and fungal infections but are also crucial players in the generation of the inflammatory response. Many neutrophil cell surface receptors regulate important cellular processes via activation of agonist-activated PI3Ks. We show here that activation of human neutrophils with insoluble immune complexes drives a previously uncharacterized, PI3K-dependent, non-canonical, pro-apoptotic signaling pathway, FcγR-PI3Kβ/δ-Cdc42-Pak-Mek-Erk. This is a rare demonstration of Ras/Raf-independent activation of Erk and of PI3K-mediated activation of Cdc42. In addition, comparative analysis of immune-complex- and fMLF-induced signaling uncovers key differences in pathways used by human and murine neutrophils. The non-canonical pathway we identify in this study may be important for the resolution of inflammation in chronic inflammatory diseases that rely on immune-complex-driven neutrophil activation.", "title": "Non-canonical PI3K-Cdc42-Pak-Mek-Erk Signaling Promotes Immune-Complex-Induced Apoptosis in Human Neutrophils" }, { "docid": "3684342", "text": "LIN28B is a RNA-binding protein regulating predominantly let-7 microRNAs with essential functions in inflammation, wound healing, embryonic stem cells, and cancer. LIN28B expression is associated with tumor initiation, progression, resistance, and poor outcome in several solid cancers, including lung cancer. However, the functional role of LIN28B, especially in non-small cell lung adenocarcinomas, remains elusive. Here, we investigated the effects of LIN28B expression on lung tumorigenesis using LIN28B transgenic overexpression in an autochthonous KRASG12V-driven mouse model. We found that LIN28B overexpression significantly increased the number of CD44+/CD326+ tumor cells, upregulated VEGF-A and miR-21 and promoted tumor angiogenesis and epithelial-to-mesenchymal transition (EMT) accompanied by enhanced AKT phosphorylation and nuclear translocation of c-MYC. Moreover, LIN28B accelerated tumor initiation and enhanced proliferation which led to a shortened overall survival. In addition, we analyzed lung adenocarcinomas of the Cancer Genome Atlas (TCGA) and found LIN28B expression in 24% of KRAS-mutated cases, which underscore the relevance of our model.", "title": "LIN28B enhanced tumorigenesis in an autochthonous KRASG12V-driven lung carcinoma mouse model" }, { "docid": "28334217", "text": "Glutaminase (GLS), which converts glutamine to glutamate, plays a key role in cancer cell metabolism, growth, and proliferation. GLS is being explored as a cancer therapeutic target, but whether GLS inhibitors affect cancer cell-autonomous growth or the host microenvironment or have off-target effects is unknown. Here, we report that loss of one copy of Gls blunted tumor progression in an immune-competent MYC-mediated mouse model of hepatocellular carcinoma. Compared with results in untreated animals with MYC-induced hepatocellular carcinoma, administration of the GLS-specific inhibitor bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) prolonged survival without any apparent toxicities. BPTES also inhibited growth of a MYC-dependent human B cell lymphoma cell line (P493) by blocking DNA replication, leading to cell death and fragmentation. In mice harboring P493 tumor xenografts, BPTES treatment inhibited tumor cell growth; however, P493 xenografts expressing a BPTES-resistant GLS mutant (GLS-K325A) or overexpressing GLS were not affected by BPTES treatment. Moreover, a customized Vivo-Morpholino that targets human GLS mRNA markedly inhibited P493 xenograft growth without affecting mouse Gls expression. Conversely, a Vivo-Morpholino directed at mouse Gls had no antitumor activity in vivo. Collectively, our studies demonstrate that GLS is required for tumorigenesis and support small molecule and genetic inhibition of GLS as potential approaches for targeting the tumor cell-autonomous dependence on GLS for cancer therapy.", "title": "Targeted inhibition of tumor-specific glutaminase diminishes cell-autonomous tumorigenesis." }, { "docid": "3981033", "text": "The cellular inhibitors of apoptosis (cIAP) 1 and 2 are amplified in about 3% of cancers and have been identified in multiple malignancies as being potential therapeutic targets as a result of their role in the evasion of apoptosis. Consequently, small-molecule IAP antagonists, such as LCL161, have entered clinical trials for their ability to induce tumor necrosis factor (TNF)-mediated apoptosis of cancer cells. However, cIAP1 and cIAP2 are recurrently homozygously deleted in multiple myeloma (MM), resulting in constitutive activation of the noncanonical nuclear factor (NF)-κB pathway. To our surprise, we observed robust in vivo anti-myeloma activity of LCL161 in a transgenic myeloma mouse model and in patients with relapsed-refractory MM, where the addition of cyclophosphamide resulted in a median progression-free-survival of 10 months. This effect was not a result of direct induction of tumor cell death, but rather of upregulation of tumor-cell-autonomous type I interferon (IFN) signaling and a strong inflammatory response that resulted in the activation of macrophages and dendritic cells, leading to phagocytosis of tumor cells. Treatment of a MM mouse model with LCL161 established long-term anti-tumor protection and induced regression in a fraction of the mice. Notably, combination of LCL161 with the immune-checkpoint inhibitor anti-PD1 was curative in all of the treated mice.", "title": "IAP antagonists induce anti-tumor immunity in multiple myeloma" }, { "docid": "32001951", "text": "Treatment of the cultured human breast-cancer cells BC-M1 with dexamethasone induced a placental-type alkaline phosphatase (ALP). Both the ALP activity and the mRNA level in the cells were increased. The induction of ALP activity by dexamethasone was time- and dose-dependent. The accumulation of ALP mRNA was inhibited by both actinomycin D and cycloheximide, indicating that its induction is a complex event and may involve other regulatory proteins. Retinoic acid showed opposing effects with dexamethasone on the expression of alkaline phosphatase. Retinoic acid (RA) and phorbol 12-myristate 13-acetate also substantially reduced the dexamethasone-induced expression of ALP. Studies on thermostability and sensitivity to various amino acid inhibitors indicated that the BC-M1 ALP is most similar to the placental form. Northern hybridization analysis also revealed that ALP mRNA transcripts in BC-M1 and term placenta are similar in size and are distinct from that of the placental-like mRNA transcript in choriocarcinoma cells. Analysis of the degradation of BC-M1 ALP mRNA showed a similar half-life of 27 h in the untreated and in dexamethasone- or RA-treated cells. These findings demonstrated that the induction of ALP in BC-M1 cells by dexamethasone is mainly due to the increase in the transcription of the ALP gene.", "title": "Regulation of the expression of alkaline phosphatase in a human breast-cancer cell line." }, { "docid": "16119973", "text": "IBD is characterized by uncontrolled immune responses in inflamed mucosa, with dominance of IL-17-producing cells and deficiency of Treg cells. The aim of this study was to explore the effect and mechanisms of RA, the ligand of RARalpha, on immune responses in human and murine colitis. Colonic biopsies from patients with UC were cultured and treated with RA as the agonist of RARalpha or LE135 as the antagonist of RARalpha. Expressions of IL-17 and FOXP3 were detected by immunohistochemistry. Murine colitis was induced by intrarectal administration with TNBS at Day 1. Mice were then i.p.-treated with RA or LE135 daily for 7 days. Cytokine levels in the cultures of mouse LPMCs were measured. Expressions of FOXP3 and IL-17 in colon tissues or MLN were detected by immunohistological analysis. Body weight and colon inflammation were evaluated. RA treatment up-regulated FOXP3 expression and down-regulated IL-17 expression in colon biopsies of patients and in colon tissues and MLN of mice with colitis compared with controls. LPMCs from RA-treated mice produced lower levels of proinflammatory cytokines (TNF-alpha, IL-1beta, IL-17) but more regulatory cytokines (IL-10, TGF-beta) compared with that of untreated mice. LE135 showed the opposite effect of RA. Furthermore, RA ameliorated TNBS-induced colitis in a dose-dependent manner, as seen by improved body weight and colon inflammation. RA down-regulates colon inflammatory responses in patients with IBD in vitro and in murine colitis in vivo, representing a potential therapeutic approach in IBD treatment.", "title": "Article" }, { "docid": "9767444", "text": "Ovarian cancer is the most lethal of all gynecological cancers, and there is an urgent unmet need to develop new therapies. Epithelial ovarian cancer (EOC) is characterized by an immune suppressive microenvironment, and response of ovarian cancers to immune therapies has thus far been disappointing. We now find, in a mouse model of EOC, that clinically relevant doses of DNA methyltransferase and histone deacetylase inhibitors (DNMTi and HDACi, respectively) reduce the immune suppressive microenvironment through type I IFN signaling and improve response to immune checkpoint therapy. These data indicate that the type I IFN response is required for effective in vivo antitumorigenic actions of the DNMTi 5-azacytidine (AZA). Through type I IFN signaling, AZA increases the numbers of CD45+ immune cells and the percentage of active CD8+ T and natural killer (NK) cells in the tumor microenvironment, while reducing tumor burden and extending survival. AZA also increases viral defense gene expression in both tumor and immune cells, and reduces the percentage of macrophages and myeloid-derived suppressor cells in the tumor microenvironment. The addition of an HDACi to AZA enhances the modulation of the immune microenvironment, specifically increasing T and NK cell activation and reducing macrophages over AZA treatment alone, while further increasing the survival of the mice. Finally, a triple combination of DNMTi/HDACi plus the immune checkpoint inhibitor α-PD-1 provides the best antitumor effect and longest overall survival, and may be an attractive candidate for future clinical trials in ovarian cancer.", "title": "Epigenetic therapy activates type I interferon signaling in murine ovarian cancer to reduce immunosuppression and tumor burden." }, { "docid": "9955779", "text": "Combining DNA-demethylating agents (DNA methyltransferase inhibitors [DNMTis]) with histone deacetylase inhibitors (HDACis) holds promise for enhancing cancer immune therapy. Herein, pharmacologic and isoform specificity of HDACis are investigated to guide their addition to a DNMTi, thus devising a new, low-dose, sequential regimen that imparts a robust anti-tumor effect for non-small-cell lung cancer (NSCLC). Using in-vitro-treated NSCLC cell lines, we elucidate an interferon α/β-based transcriptional program with accompanying upregulation of antigen presentation machinery, mediated in part through double-stranded RNA (dsRNA) induction. This is accompanied by suppression of MYC signaling and an increase in the T cell chemoattractant CCL5. Use of this combination treatment schema in mouse models of NSCLC reverses tumor immune evasion and modulates T cell exhaustion state towards memory and effector T cell phenotypes. Key correlative science metrics emerge for an upcoming clinical trial, testing enhancement of immune checkpoint therapy for NSCLC.", "title": "Epigenetic Therapy Ties MYC Depletion to Reversing Immune Evasion and Treating Lung Cancer" }, { "docid": "30658796", "text": "Neoplastic cells are genetically unstable. Strategies that target pathways affecting genome instability can be exploited to disrupt tumor cell growth, potentially with limited consequences to normal cells. Chromosomal instability (CIN) is one type of genome instability characterized by mitotic defects that increase the rate of chromosome mis-segregation. CIN is frequently caused by extra centrosomes that transiently disrupt normal bipolar spindle geometry needed for accurate chromosome segregation. Tumor cells survive with extra centrosomes because of biochemical pathways that cluster centrosomes and promote chromosome segregation on bipolar spindles. Recent work shows that targeted inhibition of these pathways prevents centrosome clustering and forces chromosomes to segregate to multiple daughter cells, an event triggering apoptosis that we refer to as anaphase catastrophe. Anaphase catastrophe specifically kills tumor cells with more than 2 centrosomes. This death program can occur after genetic or pharmacologic inhibition of cyclin dependent kinase 2 (Cdk2) and is augmented by combined treatment with a microtubule inhibitor. This proapoptotic effect occurs despite the presence of ras mutations in cancer cells. Anaphase catastrophe is a previously unrecognized mechanism that can be pharmacologically induced for apoptotic death of cancer cells and is, therefore, appealing to engage for cancer therapy and prevention.", "title": "Anaphase catastrophe is a target for cancer therapy." }, { "docid": "4387494", "text": "PURPOSE Acute myeloid leukemia (AML) is a heterogeneous disease with poor outcomes. Despite increased evidence shows that dysregulation of histone modification contributes to AML, specific drugs targeting key histone modulators are not applied in the clinical treatment of AML. Here, we investigated whether targeting KDM6B, the demethylase of tri-methylated histone H3 lysine 27 (H3K27me3), has a therapeutic potential for AML. METHODS A KDM6B-specific inhibitor, GSK-J4, was applied to treat the primary cells from AML patients and AML cell lines in vitro and in vivo. RNA-sequencing was performed to reveal the underlying mechanisms of inhibiting KDM6B for the treatment of AML. RESULTS Here we observed that the mRNA expression of KDM6B was up-regulated in AML and positively correlated with poor survival. Treatment with GSK-J4 increased the global level of H3K27me3 and reduced the proliferation and colony-forming ability of primary AML cells and AML cell lines. GSK-J4 treatment significantly induced cell apoptosis and cell-cycle arrest in Kasumi-1 cells, and displayed a synergistic effect with cytosine arabinoside. Notably, injection of GSK-J4 attenuated the disease progression in a human AML xenograft mouse model in vivo. Treatment with GSK-J4 predominantly resulted in down-regulation of DNA replication and cell-cycle-related pathways, as well as abrogated the expression of critical cancer-promoting HOX genes. ChIP-qPCR validated an increased enrichment of H3K27me3 in the transcription start sites of these HOX genes. CONCLUSIONS In summary, our findings suggest that targeting KDM6B with GSK-J4 has a therapeutic potential for the treatment of AML.", "title": "Therapeutic potential of GSK-J4, a histone demethylase KDM6B/JMJD3 inhibitor, for acute myeloid leukemia" }, { "docid": "4396105", "text": "Somatic mutations in the small GTPase K-Ras are the most common activating lesions found in human cancer, and are generally associated with poor response to standard therapies. Efforts to target this oncogene directly have faced difficulties owing to its picomolar affinity for GTP/GDP and the absence of known allosteric regulatory sites. Oncogenic mutations result in functional activation of Ras family proteins by impairing GTP hydrolysis. With diminished regulation by GTPase activity, the nucleotide state of Ras becomes more dependent on relative nucleotide affinity and concentration. This gives GTP an advantage over GDP and increases the proportion of active GTP-bound Ras. Here we report the development of small molecules that irreversibly bind to a common oncogenic mutant, K-Ras(G12C). These compounds rely on the mutant cysteine for binding and therefore do not affect the wild-type protein. Crystallographic studies reveal the formation of a new pocket that is not apparent in previous structures of Ras, beneath the effector binding switch-II region. Binding of these inhibitors to K-Ras(G12C) disrupts both switch-I and switch-II, subverting the native nucleotide preference to favour GDP over GTP and impairing binding to Raf. Our data provide structure-based validation of a new allosteric regulatory site on Ras that is targetable in a mutant-specific manner.", "title": "K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions" }, { "docid": "26887439", "text": "To identify cancer-specific targets, we have conducted a synthetic lethal screen using a small interfering RNA (siRNA) library targeting approximately 4,000 individual genes for enhanced killing in the DLD-1 colon carcinoma cell line that expresses an activated copy of the K-Ras oncogene. We found that siRNAs targeting baculoviral inhibitor of apoptosis repeat-containing 5 (survivin) significantly reduced the survival of activated K-Ras-transformed cells compared with its normal isogenic counterpart in which the mutant K-Ras gene had been disrupted (DKS-8). In addition, survivin siRNA induced a transient G(2)-M arrest and marked polyploidy that was associated with increased caspase-3 activation in the activated K-Ras cells. These results indicate that tumors expressing the activated K-Ras oncogene may be particularly sensitive to inhibitors of the survivin protein.", "title": "Survivin depletion preferentially reduces the survival of activated K-Ras-transformed cells." }, { "docid": "5765455", "text": "Myelodysplastic syndromes (MDS) comprise a heterogeneous group of disorders characterized by ineffective hematopoiesis, with an increased propensity to develop acute myelogenous leukemia (AML). The molecular basis for MDS progression is unknown, but a key element in MDS disease progression is loss of chromosomal material (genomic instability). Using our two-step mouse model for myeloid leukemic disease progression involving overexpression of human mutant NRAS and BCL2 genes, we show that there is a stepwise increase in the frequency of DNA damage leading to an increased frequency of error-prone repair of double-strand breaks (DSB) by nonhomologous end-joining. There is a concomitant increase in reactive oxygen species (ROS) in these transgenic mice with disease progression. Importantly, RAC1, an essential component of the ROS-producing NADPH oxidase, is downstream of RAS, and we show that ROS production in NRAS/BCL2 mice is in part dependent on RAC1 activity. DNA damage and error-prone repair can be decreased or reversed in vivo by N-acetyl cysteine antioxidant treatment. Our data link gene abnormalities to constitutive DNA damage and increased DSB repair errors in vivo and provide a mechanism for an increase in the error rate of DNA repair with MDS disease progression. These data suggest treatment strategies that target RAS/RAC pathways and ROS production in human MDS/AML.", "title": "Reactive oxygen species, DNA damage, and error-prone repair: a model for genomic instability with progression in myeloid leukemia?" }, { "docid": "5254463", "text": "Colorectal cancer is one of the major causes of cancer-related deaths. To gain further insights into the mechanisms underlying its development, we investigated the role of Wip1 phosphatase, which is highly expressed in intestinal stem cells, in the mouse model of APC(Min)-driven polyposis. We found that Wip1 removal increased the life span of APC(Min) mice through a significant suppression of polyp formation. This protection was dependent on the p53 tumor suppressor, which plays a putative role in the regulation of apoptosis of intestinal stem cells. Activation of apoptosis in stem cells of Wip1-deficient mice, but not wild-type APC(Min) mice, increased when the Wnt pathway was constitutively activated. We propose, therefore, that the Wip1 phosphatase regulates homeostasis of intestinal stem cells. In turn, Wip1 loss suppresses APC(Min)-driven polyposis by lowering the threshold for p53-dependent apoptosis of stem cells, thus preventing their conversion into tumor-initiating stem cells.", "title": "Wip1 phosphatase regulates p53-dependent apoptosis of stem cells and tumorigenesis in the mouse intestine." }, { "docid": "27428509", "text": "Type 2 diabetes mellitus is becoming a major health problem associated with excess morbidity and mortality. As the prevalence of type 2 diabetes is rapidly increasing, prevention of the disease should be considered as a key objective in the near future. Besides lifestyle changes, various pharmacological treatments have proven their efficacy in placebo-controlled clinical trials, including antidiabetic drugs such as metformin, acarbose and troglitazone, or antiobesity agents such as orlistat. Arterial hypertension, a clinical entity in which insulin resistance is common, is strongly associated with type 2 diabetes and may precede the disease by several years. While antihypertensive agents such as diuretics or β-adrenoceptor antagonists may worsen insulin resistance and impair glucose tolerance, newer antihypertensive agents exert neutral or even slightly positive metabolic effects. Numerous clinical trials have investigated the effects of ACE inhibitors or angiotensin II receptor antagonists (ARAs) on insulin sensitivity in hypertensive patients, with or without diabetes, with no consistent results. Almost half of the studies with ACE inhibitors in hypertensive nondiabetic individuals demonstrated a slight but significant increase in insulin sensitivity as assessed by insulin-stimulated glucose disposal during a euglycaemic hyperinsulinaemic clamp, while the other half failed to reveal any significant change. The effects of ARAs on insulin sensitivity are neutral in most studies. Mechanisms of improvement of glucose tolerance and insulin sensitivity through the inhibition of the renin-angiotensin system (RAS) are complex. They may include improvement of blood flow and microcirculation in skeletal muscles and, thereby, enhancement of insulin and glucose delivery to the insulin-sensitive tissues, facilitating insulin signalling at the cellular level and improvement of insulin secretion by the β cells. Six recent large-scale clinical studies reported a remarkably consistent reduction in the incidence of type 2 diabetes in hypertensive patients treated with either ACE inhibitors or ARAs for 3–6 years, compared with a thiazide diuretic, β-adrenoceptor antagonist, the calcium channel antagonist amlodipine or even placebo. The relative risk reduction averaged 14% (p = 0.034) in the CAPPP (Captopril Prevention Project) with captopril compared with a thiazide or β1-adrenoceptor antagonist, 34% (p < 0.001) in the HOPE (Heart Outcomes Prevention Evaluation) study with ramipril compared with placebo, 30% (p < 0.001) in the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) with lisinopril compared with chlortalidone, 25% (p < 0.001) in the LIFE (Losartan Intervention For Endpoint reduction in hypertension study) with losartan compared with atenolol, and 25% (p = 0.09) in the SCOPE (Study on Cognition and Prognosis in the Elderly) with candesartan cilexetil compared with placebo, and 23% (p < 0.0001) in the VALUE (Valsartan Antihypertensive Long-term Use Evaluation) trial with valsartan compared with amlodipine. All these studies considered the development of diabetes as a secondary endpoint, except the HOPE trial where it was a post hoc analysis. These encouraging observations led to the initiation of two large, prospective, placebo-controlled randomised clinical trials whose primary outcome is the prevention of type 2 diabetes: the DREAM (Diabetes REduction Approaches with ramipril and rosiglitazone Medications) trial with the ACE inhibitor ramipril and the NAVIGATOR (Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research) trial with the ARA valsartan. Finally, ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) will also investigate as a secondary endpoint whether it is possible to prevent the development of type 2 diabetes by blocking the RAS with either an ACE inhibitor or an ARA or a combination of both. Thus, the recent consistent observations of a 14–34% reduction of the development of diabetes in hypertensive patients receiving ACE inhibitors or ARAs are exciting. From a theoretical point of view, they emphasise that there are many aspects of the pathogenesis, prevention and treatment of type 2 diabetes that still need to be uncovered. From a practical point of view, they may offer a new strategy to reduce the ongoing epidemic and burden of type 2 diabetes.", "title": "Prevention of Type 2 Diabetes Mellitus Through Inhibition of the Renin-Angiotensin System" }, { "docid": "33030946", "text": "Summary Hypoxia augments inflammatory responses and osteoclastogenesis by incompletely understood mechanisms. We identified COMMD1 as a cell‐intrinsic negative regulator of osteoclastogenesis that is suppressed by hypoxia. In human macrophages, COMMD1 restrained induction of NF‐&kgr;B signaling and a transcription factor E2F1‐dependent metabolic pathway by the cytokine RANKL. Downregulation of COMMD1 protein expression by hypoxia augmented RANKL‐induced expression of inflammatory and E2F1 target genes and downstream osteoclastogenesis. E2F1 targets included glycolysis and metabolic genes including CKB that enabled cells to meet metabolic demands in challenging environments, as well as inflammatory cytokine‐driven target genes. Expression quantitative trait locus analysis linked increased COMMD1 expression with decreased bone erosion in rheumatoid arthritis. Myeloid deletion of Commd1 resulted in increased osteoclastogenesis in arthritis and inflammatory osteolysis models. These results identify COMMD1 and an E2F‐metabolic pathway as key regulators of osteoclastogenic responses under pathological inflammatory conditions and provide a mechanism by which hypoxia augments inflammation and bone destruction. Graphical Abstract Figure. No Caption available. HighlightsCOMMD1 is a negative regulator of osteoclast differentiationCOMMD1 suppresses bone loss in RA and inflammatory arthritis and osteolysis modelsCOMMD1 negatively regulates E2F1‐dependent metabolic pathways in macrophagesHypoxia suppresses COMMD1 expression to augment osteoclastogenesis &NA; Pathways that promote osteoclastogenesis are well characterized but less is known about negative regulators that suppress pathological bone loss. Murata et al. identify COMMD1 as an inhibitor of osteoclastogenesis that restrains NF‐&kgr;B‐ and E2F1‐CKB‐mediated metabolic pathways in macrophages.", "title": "Hypoxia‐Sensitive COMMD1 Integrates Signaling and Cellular Metabolism in Human Macrophages and Suppresses Osteoclastogenesis" }, { "docid": "12622860", "text": "S-trans,trans-Farnesylthiosalicylic acid (FTS) is a novel farnesylated rigid carboxylic acid derivative. In cell-free systems, it acts as a potent competitive inhibitor (Ki = 2.6 microM) of the enzyme prenylated protein methyltransferase (PPMTase), which methylates the carboxyl-terminal S-prenylcysteine in a large number of prenylated proteins including Ras. In such systems, FTS inhibits Ras methylation but not Ras farnesylation. Inhibition of the PPMTase by FTS in homogenates or membranes of a variety of tissues and cell lines is inferred from a block in the methylation of exogenously added substrates such as N-acetyl-S-trans,trans-farnesyl-L-cysteine and of endogenous substrates including small GTP-binding proteins. FTS can also inhibit methylation of these proteins in intact cells (e.g. in Rat-1 fibroblasts, Ras-transformed Rat-1, and B16 melanoma cells). Unlike in cell-free systems, however, relatively high concentrations of FTS (50-100 microM) are required for partial blocking (10-40%) of protein methylation in the intact cells. Thus, FTS is a weak inhibitor of methylation in intact cells. Because methylation is the last step in the processing of Ras and related proteins, FTS is not likely to affect steps that precede it, e.g. protein prenylation. This may explain why the growth and gross morphology of a variety of cultured cell types (including Chinese hamster ovary, NIH3T3, Rat1, B16 melanoma, and PC12) is not affected by up to 25 microM FTS and is consistent with the observed lack of FTS-induced cytotoxicity. Nevertheless, FTS reduces the levels of Ras in cell membranes and can inhibit Ras-dependent cell growth in vitro, independently of methylation. It inhibits the growth of human Ha-ras-transformed cells (EJ cells) and reverses their transformed morphology in a dose-dependent manner (0.1-10 microM). The drug does not interfere with the growth of cells transformed by v-Raf or T-antigen but inhibits the growth of ErbB2-transformed cells and blocks the mitogenic effects of epidermal and basic fibroblast growth factors, thus implying its selectivity toward Ras growth signaling, possibly via modulation of Ras-Raf communication. Taken together, the results raise the possibility that FTS may specifically interfere with the interaction of Ras with a farnesylcysteine recognition domain in the cell membrane.(ABSTRACT TRUNCATED AT 400 WORDS)", "title": "Selective inhibition of Ras-dependent cell growth by farnesylthiosalisylic acid." }, { "docid": "11200685", "text": "Microtubule nucleation is an essential step in the formation of the microtubule cytoskeleton. We recently showed that androgen and Src promote microtubule nucleation and γ-tubulin accumulation at the centrosome. Here, we explore the mechanisms by which androgen and Src regulate these processes and ask whether integrins play a role. We perturb integrin function by a tyrosine-to-alanine substitution in membrane-proximal NPIY motif in the integrin β1 tail and show that this mutant substantially decreases microtubule nucleation and γ-tubulin accumulation at the centrosome. Because androgen stimulation promotes the interaction of the androgen receptor with Src, resulting in PI3K/AKT and MEK/ERK signaling, we asked whether these pathways are inhibited by the mutant integrin and whether they regulate microtubule nucleation. Our results indicate that the formation of the androgen receptor-Src complex and the activation of downstream pathways are significantly suppressed when cells are adhered by the mutant integrin. Inhibitor studies indicate that microtubule nucleation requires MEK/ERK but not PI3K/AKT signaling. Importantly, the expression of activated RAF-1 is sufficient to rescue microtubule nucleation inhibited by the mutant integrin by promoting the centrosomal accumulation of γ-tubulin. Our data define a novel paradigm of integrin signaling, where integrins regulate microtubule nucleation by promoting the formation of androgen receptor-Src signaling complexes to activate the MEK/ERK signaling pathway.", "title": "Integrins regulate microtubule nucleating activity of centrosome through mitogen-activated protein kinase/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase (MEK/ERK) signaling." }, { "docid": "116792", "text": "Understanding molecular mechanisms mediating epileptogenesis is critical for developing more effective therapies for epilepsy. We recently found that the mammalian target of rapamycin (mTOR) signaling pathway is involved in epileptogenesis, and mTOR inhibitors prevent epilepsy in a mouse model of tuberous sclerosis complex. Here, we investigated the potential role of mTOR in a rat model of temporal lobe epilepsy initiated by status epilepticus. Acute kainate-induced seizures resulted in biphasic activation of the mTOR pathway, as evident by an increase in phospho-S6 (P-S6) expression. An initial rise in P-S6 expression started approximately 1 h after seizure onset, peaked at 3-6 h, and returned to baseline by 24 h in both hippocampus and neocortex, reflecting widespread stimulation of mTOR signaling by acute seizure activity. After resolution of status epilepticus, a second increase in P-S6 was observed in hippocampus only, which started at 3 d, peaked 5-10 d, and persisted for several weeks after kainate injection, correlating with the development of chronic epileptogenesis within hippocampus. The mTOR inhibitor rapamycin, administered before kainate, blocked both the acute and chronic phases of seizure-induced mTOR activation and decreased kainate-induced neuronal cell death, neurogenesis, mossy fiber sprouting, and the development of spontaneous epilepsy. Late rapamycin treatment, after termination of status epilepticus, blocked the chronic phase of mTOR activation and reduced mossy fiber sprouting and epilepsy but not neurogenesis or neuronal death. These findings indicate that mTOR signaling mediates mechanisms of epileptogenesis in the kainate rat model and that mTOR inhibitors have potential antiepileptogenic effects in this model.", "title": "The mammalian target of rapamycin signaling pathway mediates epileptogenesis in a model of temporal lobe epilepsy." }, { "docid": "25915873", "text": "PURPOSE Therapies to target prostate cancer bone metastases have only limited effects. New treatments are focused on the interaction between cancer cells, bone marrow cells and the bone matrix. Osteoclasts play an important role in the development of bone tumors caused by prostate cancer. Since Src kinase has been shown to be necessary for osteoclast function, we hypothesized that dasatinib, a Src family kinase inhibitor, would reduce osteoclast activity and prostate cancer (PC-3) cell-induced osteoclast formation. RESULTS Dasatinib inhibited RANKL-induced osteoclast differentiation of bone marrow-derived monocytes with an EC(50) of 7.5 nM. PC-3 cells, a human prostate cancer cell line, were able to differentiate RAW 264.7 cells, a murine monocytic cell line, into osteoclasts, and dasatinib inhibited this differentiation. In addition, conditioned medium from PC-3 cell cultures was able to differentiate RAW 264.7 cells into osteoclasts and this too, was inhibited by dasatinib. Even the lowest concentration of dasatinib, 1.25 nmol, inhibited osteoclast differentiation by 29%. Moreover, dasatinib inhibited osteoclast activity by 58% as measured by collagen 1 release. EXPERIMENTAL DESIGN We performed in vitro experiments utilizing the Src family kinase inhibitor dasatinib to target osteoclast activation as a means of inhibiting prostate cancer bone metastases. CONCLUSION Dasatinib inhibits osteoclast differentiation of mouse primary bone marrow-derived monocytes and PC-3 cell-induced osteoclast differentiation. Dasatinib also inhibits osteoclast degradation activity. Inhibiting osteoclast differentiation and activity may be an effective targeted therapy in patients with prostate cancer bone metastases.", "title": "Dasatinib inhibits both osteoclast activation and prostate cancer PC-3-cell-induced osteoclast formation." }, { "docid": "46765242", "text": "Cytosine arabinoside (ara-C) is widely used for the treatment of leukemias and displays significant toxicities. Lovastatin, an HMG-CoA reductase inhibitor, is extensively used to treat hypercholesterolemia. To determine whether lovastatin could augment ara-C's activity we have examined their effects in the human erythroleukemia K562 cell line and the ara-C resistant ARAC8D cell line. A synergistic interaction between the two drugs was found. We have demonstrated that the interaction does not occur at the level of RAS but may involve lovastatin's effect of downregulating MAPK activity and preventing ara-C-induced MAPK activation. These studies represent the first description of a potentially beneficial interaction between lovastatin and ara-C that could be applied to the treatment of human leukemia.", "title": "Interaction of cytosine arabinoside and lovastatin in human leukemia cells." }, { "docid": "29124963", "text": "INTRODUCTION The echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion represents a novel target in a subset of non-small cell lung cancer, especially adenocarcinoma. EML4-ALK fusion is mutually exclusive with epidermal growth factor receptor (EGFR) mutations. To understand the impact of EML4-ALK on the prognosis of non-small cell lung cancer, we examined EML4-ALK fusion in lung adenocarcinoma from patients with wild-type EGFR and analyzed their clinical treatment outcomes. METHODS Lung adenocarcinoma patients with malignant pleural effusions having wild-type EGFR and measurable target lesions were enrolled for EML4-ALK analysis by reverse transcription-polymerase chain reaction and direct sequencing. Demographic data, EML4-ALK status, and survival data were analyzed. We also performed fluorescence in situ hybridization on some available tumor samples to validate the PCR result. In addition, K-ras mutation was analyzed for patients without EML4-ALK fusion genes. RESULTS A total of 116 patients with wild-type EGFR sequencing results had complete clinical data for analysis. No patients received ALK inhibitor therapy. There were 39 patients (34%) with the EML4-ALK fusion gene. The concordance rate between reverse transcription-polymerase chain reaction and fluorescence in situ hybridization was 85%. The K-ras mutation rate for patients without EML4-ALK fusion gene was 6.5%. By multivariate analysis, patients who had better performance status (p < 0.001) and EML4-ALK translocation (p = 0.017) had longer overall survival. Comparing patients with tumors harboring variant 1 with those harboring nonvariant 1 EML4-ALK fusion genes, there were no significant differences in clinical factors and survival outcome. CONCLUSION For lung adenocarcinoma patients with wild-type EGFR, EML4-ALK translocation is associated with longer overall survival.", "title": "EML4-ALK translocation predicts better outcome in lung adenocarcinoma patients with wild-type EGFR." }, { "docid": "14819804", "text": "The novel phosphatidylinositol-3-kinase (PI3K) inhibitor PX-866 was tested against 13 experimental human tumor xenografts derived from cell lines of various tissue origins. Mutant PI3K (PIK3CA) and loss of PTEN activity were sufficient, but not necessary, as predictors of sensitivity to the antitumor activity of the PI3K inhibitor PX-866 in the presence of wild-type Ras, whereas mutant oncogenic Ras was a dominant determinant of resistance, even in tumors with coexisting mutations in PIK3CA. The level of activation of PI3K signaling measured by tumor phosphorylated Ser(473)-Akt was insufficient to predict in vivo antitumor response to PX-866. Reverse-phase protein array revealed that the Ras-dependent downstream targets c-Myc and cyclin B were elevated in cell lines resistant to PX-866 in vivo. Studies using an H-Ras construct to constitutively and preferentially activate the three best-defined downstream targets of Ras, i.e., Raf, RalGDS, and PI3K, showed that mutant Ras mediates resistance through its ability to use multiple pathways for tumorigenesis. The identification of Ras and downstream signaling pathways driving resistance to PI3K inhibition might serve as an important guide for patient selection as inhibitors enter clinical trials and for the development of rational combinations with other molecularly targeted agents.", "title": "Mutations in the phosphatidylinositol-3-kinase pathway predict for antitumor activity of the inhibitor PX-866 whereas oncogenic Ras is a dominant predictor for resistance." }, { "docid": "67045088", "text": "Post-translational modification of chemokines mediated by the dipeptidyl peptidase DPP4 (CD26) has been shown to negatively regulate lymphocyte trafficking, and its inhibition enhances T cell migration and tumor immunity by preserving functional chemokine CXCL10. By extending those initial findings to pre-clinical models of hepatocellular carcinoma and breast cancer, we discovered a distinct mechanism by which inhibition of DPP4 improves anti-tumor responses. Administration of the DPP4 inhibitor sitagliptin resulted in higher concentrations of the chemokine CCL11 and increased migration of eosinophils into solid tumors. Enhanced tumor control was preserved in mice lacking lymphocytes and was ablated after depletion of eosinophils or treatment with degranulation inhibitors. We further demonstrated that tumor-cell expression of the alarmin IL-33 was necessary and sufficient for eosinophil-mediated anti-tumor responses and that this mechanism contributed to the efficacy of checkpoint-inhibitor therapy. These findings provide insight into IL-33- and eosinophil-mediated tumor control, revealed when endogenous mechanisms of DPP4 immunoregulation are inhibited. Eosinophils have been described mainly in allergy settings but are increasingly appreciated as being involved in other aspects of immunity. Albert and colleagues use a clinically approved inhibitor of the dipeptidyl peptidase DPP4 to facilitate the recruitment of eosinophils to mouse tumors, where they are essential in tumor destruction.", "title": "Inhibition of the dipeptidyl peptidase DPP4 (CD26) reveals IL-33-dependent eosinophil-mediated control of tumor growth" }, { "docid": "7986878", "text": "We previously reported that intetumumab (CNTO 95), a fully human anti-αv integrin monoclonal antibody, is a radiosensitizer in mice with xenograft tumors. Because intetumumab does not cross-react with mouse integrins, but has cross-reactivity with rat integrins, we next studied the potential combined use of radiation therapy and intetumumab in human cancer xenograft models in nude rats to assess effects on both tumor cells and the tumor microenvironment. Nude rats bearing human head and neck cancer and non-small cell lung cancer (NSCLC) xenografts were treated with intetumumab and fractionated local tumor radiotherapy. Effects on tumor growth and metastasis, blood perfusion, oxygenation, and gastrointestinal toxicity were studied. Intetumumab alone had a moderate effect on tumor growth. When combined with fractionated radiation therapy, intetumumab significantly inhibited tumor growth and produced a tumor response rate that was significantly better than with radiation therapy alone. Treatment with intetumumab also significantly reduced lung metastasis in the A549 NSCLC xenograft model. The oxygenation and blood perfusion in xenograft tumors measured by microbubble-enhanced ultrasound imaging were substantially increased after treatment with intetumumab. The combined use of intetumumab and radiation therapy reduced the microvessel density and increased apoptosis in tumor cells and the tumor microenvironment. Toxicity studies showed that treatment with intetumumab did not cause the histopathologic changes in the lungs and did not sensitize the sensitive gastrointestinal epithelium to the effect of radiation therapy. Intetumumab can potentiate the efficacy of fractionated radiation therapy in human cancer xenograft tumors in nude rats without increased toxicity.", "title": "Anti-alphav integrin monoclonal antibody intetumumab enhances the efficacy of radiation therapy and reduces metastasis of human cancer xenografts in nude rats." } ]
5497
What kinds of exchange-traded funds (ETFs) should specifically be avoided?
[ { "docid": "210257", "text": "\"As with ANY investment the first answer is....do not invest in any that you do not fully understand. ETF's are very versatile and can be used for many different people for many different parts of their portfolio, so I don't think there can be a blanket statement of \"\"this\"\" one is good or bad for all.\"", "title": "" }, { "docid": "86627", "text": "\"Stay away from leveraged or synthetic ETFs. This answer talks about why leveraged ETFs are dangerous. There are numerous articles to be found by searching for \"\"leveraged etf\"\". My answer to this question links to one of the more accessible explanations I've read.\"", "title": "" }, { "docid": "324697", "text": "One of the key things to look for is trading volume. I think the price spread will be better on high volume ETFs, which means you'll be able to sell for more when the time comes. Check Google or Yahoo finance for those stats.", "title": "" } ]
[ { "docid": "332924", "text": "\"I recommend avoiding trading directly in commodities futures and options. If you're not prepared to learn a lot about how futures markets and trading works, it will be an experience fraught with pitfalls and lost money – and I am speaking from experience. Looking at stock-exchange listed products is a reasonable approach for an individual investor desiring added diversification for their portfolio. Still, exercise caution and know what you're buying. It's easy to access many commodity-based exchange-traded funds (ETFs) on North American stock exchanges. If you already have low-cost access to U.S. markets, consider this option – but be mindful of currency conversion costs, etc. Yet, there is also a European-based company, ETF Securities, headquartered in Jersey, Channel Islands, which offers many exchange-traded funds on European exchanges such as London and Frankfurt. ETF Securities started in 2003 by first offering a gold commodity exchange-traded fund. I also found the following: London Stock Exchange: Frequently Asked Questions about ETCs. The LSE ETC FAQ specifically mentions \"\"ETF Securities\"\" by name, and addresses questions such as how/where they are regulated, what happens to investments if \"\"ETF Securities\"\" were to go bankrupt, etc. I hope this helps, but please, do your own due diligence.\"", "title": "" }, { "docid": "161201", "text": "Your assumption that funds sold in GBP trade in GBP is incorrect. In general funds purchase their constituent stocks in the fund currency which may be different to the subscription currency. Where the subscription currency is different from the fund currency subscriptions are converted into the fund currency before the extra money is used to increase holdings. An ETF, on the other hand, does not take subscriptions directly but by creation (and redemption) of shares. The principle is the same however; monies received from creation of ETF shares are converted into the fund currency and then used to buy stock. This ensures that only one currency transaction is done. In your specific example the fund currency will be USD so your purchase of the shares (assuming there are no sellers and creation occurs) will be converted from GBP to USD and held in that currency in the fund. The fund then trades entirely in USD to avoid currency risk. When you want to sell your exposure (supposing redemption occurs) enough holdings required to redeem your money are sold to get cash in USD and then converted to GBP before paying you. This means that trading activity where there is no need to convert to GBP (or any other currency) does not incur currency conversion costs. In practice funds will always have some cash (or cash equivalents) on hand to pay out redemptions and will have an idea of the number and size of redemptions each calendar period so will use futures and swaps to mitigate FX risk. Where the same firm has two funds traded in different currencies with the same objectives it is likely that one is a wrapper for the other such that one simply converts the currency and buys the other currency denominated ETF. As these are exchange traded funds with a price in GBP the amount you pay for the ETF or gain on selling it is the price given and you will not have to consider currency exchange as that should be done internally as explained above. However, there can be a (temporary) arbitrage opportunity if the price in GBP does not reflect the price in USD and the exchange rate put together.", "title": "" }, { "docid": "311192", "text": "\"Bit hesitant to put this in an answer as I don't know if specific investment advice is appropriate, but this has grown way too long for a comment. The typical answer given for people who don't have the time, experience, knowledge or inclination to pick specific stocks to hold should instead invest in ETFs (exchange-traded index funds.) What these basically do is attempt to simulate a particular market or stock exchange. An S&P 500 index fund will (generally) attempt to hold shares in the stocks that make up that index. They only have to follow an index, not try to beat it so are called \"\"passively\"\" managed. They have very low expense ratios (far below 1%) and are considered a good choice for investors who want to hold stock without significant effort or expense and who's main goal is time in the market. It's a contentious topic but on average an index (and therefore an index fund) will go even with or outperform most actively managed funds. With a sufficiently long investment horizon, which you have, these may be ideal for you. Trading in ETFs is also typically cheap because they are traded like stock. There are plenty of low-fee online brokers and virtually all will allow trading in ETFs. My broker even has a list of several hundred popular ETFs that can be traded for free. The golden rule in investing is that you should never buy into something you don't understand. Don't buy individual stock with little information: it's often little more than gambling. The same goes for trading platforms like Loyal3. Don't use them unless you know their business model and what they stand to gain from your custom. As mentioned I can trade certain funds for free with my broker, but I know why they can offer that and how they're still making money.\"", "title": "" }, { "docid": "29184", "text": "\"Does the bolded sentence apply for ETFs and ETF companies? No, the value of an ETF is determined by an exchange and thus the value of the share is whatever the trading price is. Thus, the price of an ETF may go up or down just like other securities. Money market funds can be a bit different as the mutual fund company will typically step in to avoid \"\"Breaking the Buck\"\" that could happen as a failure for that kind of fund. To wit, must ETF companies invest a dollar in the ETF for every dollar that an investor deposited in this aforesaid ETF? No, because an ETF is traded as shares on the market, unless you are using the creation/redemption mechanism for the ETF, you are buying and selling shares like most retail investors I'd suspect. If you are using the creation/redemption system then there are baskets of other securities that are being swapped either for shares in the ETF or from shares in the ETF.\"", "title": "" }, { "docid": "9672", "text": "\"You're talking about money in a savings account, and avoiding the risks posed by an ongoing crisis, and avoiding risk. If you are risk-averse, and likely to need your money in the short term, you should not put your money in the stock market, even in \"\"safe\"\" stocks like P&G/Coca-Cola/etc. Even these safe stocks are at risk of wild price swings in the short- to intermediate-term, especially in the event of international crises such as major European debt defaults and the like. These stocks are suitable for long-term growth objectives, but they are not as a replacement for a savings account. Coca-Cola lost a third of its value between 2007 and 2009. (It's recovered, and is currently doing better than ever.) P&G went from $74/share to $46/share. (It's partially recovered and back at $63). On the other hand, these stocks may indeed be suitable as long-term investments to protect you against local currency inflation. And yes, they even pay dividends. If you're after this investment, a good option is probably a sector-specific exchange-traded fund, such as a consumer-staples ETF. It will likely be more diversified and safer than anything you could come up with using a list of individual stocks. You can also investigate recommendations that show up when you search for a \"\"defensive ETF\"\". If you do not wish to buy the ETF directly, you can also look at listings of the ETF's holdings. Read the prospectus for an idea of the risks associated with these funds. You can buy these funds with any brokerage that gives you access to US stock exchanges.\"", "title": "" }, { "docid": "119819", "text": "\"You seem to be assuming that ETFs must all work like the more traditional closed-end funds, where the market price per share tends—based on supply and demand—to significantly deviate from the underlying net asset value per share. The assumption is simplistic. What are traditionally referred to as closed-end funds (CEFs), where unit creation and redemption are very tightly controlled, have been around for a long time, and yes, they do often trade at a premium or discount to NAV because the quantity is inflexible. Yet, what is generally meant when the label \"\"ETF\"\" is used (despite CEFs also being both \"\"exchange-traded\"\" and \"\"funds\"\") are those securities which are not just exchange-traded, and funds, but also typically have two specific characteristics: (a) that they are based on some published index, and (b) that a mechanism exists for shares to be created or redeemed by large market participants. These characteristics facilitate efficient pricing through arbitrage. Essentially, when large market participants notice the price of an ETF diverging from the value of the shares held by the fund, new units of the ETF can get created or redeemed in bulk. The divergence quickly narrows as these participants buy or sell ETF units to capture the difference. So, the persistent premium (sometimes dear) or discount (sometimes deep) one can easily witness in the CEF universe tend not to occur with the typical ETF. Much of the time, prices for ETFs will tend to be very close to their net asset value. However, it isn't always the case, so proceed with some caution anyway. Both CEF and ETF providers generally publish information about their funds online. You will want to find out what is the underlying Net Asset Value (NAV) per share, and then you can determine if the market price trades at a premium or a discount to NAV. Assuming little difference in an ETF's price vs. its NAV, the more interesting question to ask about an ETF then becomes whether the NAV itself is a bargain, or not. That means you'll need to be more concerned with what stocks are in the index the fund tracks, and whether those stocks are a bargain, or not, at their current prices. i.e. The ETF is a basket, so look at each thing in the basket. Of course, most people buy ETFs because they don't want to do this kind of analysis and are happy with market average returns. Even so, sector-based ETFs are often used by traders to buy (or sell) entire sectors that may be undervalued (or overvalued).\"", "title": "" }, { "docid": "130188", "text": "ETFs trade on specific exchanges. If your broker deals with those exchanges, you should have access to the ETF. If your broker does not deal with that exchange, then you will not have access through that broker. This is different than, say, mutual funds, which don't trade on the exchanges are proprietary to certain brokerages or financial institutions.", "title": "" }, { "docid": "489103", "text": "\"Ask your trading site for their definition of \"\"ETF\"\". The term itself is overloaded/ambiguous. Consider: If \"\"ETF\"\" is interpreted liberally, then any fund that trades on a [stock] exchange is an exchange-traded fund. i.e. the most literal meaning implied by the acronym itself. Whereas, if \"\"ETF\"\" is interpreted more narrowly and in the sense that most market participants might use it, then \"\"ETF\"\" refers to those exchange-traded funds that specifically have a mechanism in place to ensure the fund's current price remains close to its net asset value. This is not the case with closed-end funds (CEFs), which often trade at either a premium or a discount to their underlying net asset value.\"", "title": "" }, { "docid": "304023", "text": "\"ETF Creation and Redemption Process notes the process: While ETF trading occurs on an exchange like stocks, the process by which their shares are created is significantly different. Unless a company decides to issue more shares, the supply of shares of an individual stock trading in the marketplace is finite. When demand increases for shares of an ETF, however, Authorized Participants (APs) have the ability to create additional shares on demand. Through an \"\"in kind\"\" transfer mechanism, APs create ETF units in the primary market by delivering a basket of securities to the fund equal to the current holdings of the ETF. In return, they receive a large block of ETF shares (typically 50,000), which are then available for trading in the secondary market. This ETF creation and redemption process helps keep ETF supply and demand in continual balance and provides a \"\"hidden\"\" layer of liquidity not evident by looking at trading volumes alone. This process also works in reverse. If an investor wants to sell a large block of shares of an ETF, even if there seems to be limited liquidity in the secondary market, APs can readily redeem a block of ETF shares by gathering enough shares of the ETF to form a creation unit and then exchanging the creation unit for the underlying securities. Thus, the in-kind swap to the underlying securities is only done by APs so the outflow would be these individuals taking a large block of the ETF and swapping it for the underlying securities. The APs would be taking advantage of the difference between what the ETF's trading value and the value of the underlying securities.\"", "title": "" }, { "docid": "129070", "text": "You could use a stock-only ISA and invest in Exchange Traded Funds (ETFs). ETFs are managed mutual funds that trade on open exchanges in the same manner as stocks. This changes the specific fund options you have open to you, but there are so many ETFs at this point that any sector you want to invest in is almost certainly represented.", "title": "" }, { "docid": "402046", "text": "Ending up with nothing is an unlikely situation unless you invest 100% in a company stock and the company goes under. In order to give you a good answer we need to see what options your employer gives for 401k investments. The best advice would be to take a list of all options that your employer allows and talk with a financial advisor. Here are a few options that you may or may not have as an option from an employer: Definitions from wikipedia: A target-date fund – also known as a lifecycle, dynamic-risk or age-based fund – is a collective investment scheme, usually a mutual fund, designed to provide a simple investment solution through a portfolio whose asset allocation mix becomes more conservative as the target date (usually retirement) approaches. An index fund or index tracker is a collective investment scheme (usually a mutual fund or exchange-traded fund) that aims to replicate the movements of an index of a specific financial market... An exchange-traded fund (ETF) is an investment fund traded on stock exchanges, much like stocks.[1] An ETF holds assets such as stocks, commodities, or bonds, and trades close to its net asset value over the course of the trading day. Most ETFs track an index, such as a stock index or bond index. ETFs may be attractive as investments because of their low costs, tax efficiency, and stock-like features. The capital stock (or stock) of an incorporated business constitutes the equity stake of its owners. Which one can you lose everything in? You can lose everything in stocks by the company going under. In Index funds the entire market that it follows would have to collapse. The chances are slim here since the index made up of several companies. The S&P 500 is made up of 500 leading companies publicly traded in the U.S. A Pacific-Europe index such as MSCI EAFE Index is made up of 907 companies. The chances of losing everything in an ETF are also slim. The ETF that follows the S&P 500 is made up of 500 companies. An Pacific-Europe ETF such as MSCI EAFE ETF is made up of 871 companies. Target date funds are also slim to lose everything. Target date funds are made up of several companies like indexes and etfs and also mix in bonds and other investments depending on your age. What would I recommend? I would recommend the Index funds and/or ETFs that have the lowest fee that make up the following strategy for your age: Why Not Target Date Funds or Stocks? Target date funds have high fees. Later in life when you are closer to retirement you may want to add bonds to your portfolio. At that time if this is the only option to add bonds then you can change your elections. Stocks are too risky for you with your current knowledge. If your company matches by buying their stock you may want to consider reallocating that stock at certain points to your Index funds or ETFs.", "title": "" }, { "docid": "120059", "text": "\"Generally, ETFs work on the basis that there exists a pair of values that can be taken at any moment in time: A Net Asset Value of each share in the fund and a trading market price of each share in the fund. It may help to picture these in baskets of about 50,000 shares for the creation/redemption process. If the NAV is greater than the market price, then arbitrageurs will buy up shares at the market price and do an \"\"in-kind\"\" transaction that will be worth the NAV value that the arbitrageurs could turn around and sell for an immediate profit. If the market price is greater than the NAV, then the arbitrageurs will buy up the underlying securities that can be exchanged \"\"in-kind\"\" for shares in the fund that can then be sold on the market for an immediate profit. What is the ETF Creation/Redemption Mechanism? would be a source on this though I imagine there are others. Now, in the case of VXX, there is something to be said for how much trading is being done and what impact this can have. From a July 8, 2013 Yahoo Finance article: At big option trade in the iPath S&P 500 VIX Short-Term Futures Note is looking for another jump in volatility. More than 250,000 VXX options have already traded, twice its daily average over the last month. optionMONSTER systems show that a trader bought 13,298 August 26 calls for the ask price of $0.24 in volume that was 6 times the strike's previous open interest, clearly indicating new activity. Now the total returns of the ETF are a combination of changes in share price plus what happens with the distributions which could be held as cash or reinvested to purchase more shares.\"", "title": "" }, { "docid": "349668", "text": "This is more than likely a thing about your financial institution and the exchanges where they trade shares. Some exchanges cannot/will not handle odd lot transactions. Most established brokerages have software and accounting systems that will deal in round lots with the exchanges, but can track your shares individually. Sometimes specific stocks cannot be purchased in odd lots due to circumstances specific to that stock (trading only on a specific exchange, for example). Most brokerages offer dollar-cost averaging programs, but may limit which stocks are eligible, due to odd lot and partial share purchases. Check with your brokerage to see if they can support odd lot and/or DCA purchases. You may find another similar ETF with similar holdings that has better trading conditions, or might consider an open-end mutual fund with similar objectives. Mutual funds allow partial share purchases (you have $100 to invest today, and they issue you 35.2 shares, for example).", "title": "" }, { "docid": "472663", "text": "\"An Exchange-Traded Fund (ETF) is a special type of mutual fund that is traded on the stock exchange like a stock. To invest, you buy it through a stock broker, just as you would if you were buying an individual stock. When looking at a mutual fund based in the U.S., the easiest way to tell whether or not it is an ETF is by looking at the ticker symbol. Traditional mutual funds have ticker symbols that end in \"\"X\"\", and ETFs have ticker symbols that do not end in \"\"X\"\". The JPMorgan Emerging Markets Equity Fund, with ticker symbol JFAMX, is a traditional mutual fund, not an ETF. JPMorgan does have ETFs; the JPMorgan Diversified Return Emerging Markets Equity ETF, with ticker symbol JPEM, is an example. This ETF invests in similar stocks as JFAMX; however, because it is an index-based fund instead of an actively managed fund, it has lower fees. If you aren't sure about the ticker symbol, the advertising/prospectus of any ETF should clearly state that it is an ETF. (In the example of JPEM above, they put \"\"ETF\"\" right in the fund name.) If you don't see ETF mentioned, it is most likely a traditional mutual fund. Another way to tell is by looking at the \"\"investment minimums\"\" of the fund. JFAMX has a minimum initial investment of $1000. ETFs, however, do not have an investment minimum listed; because it is traded like a stock, you simply buy whole shares at whatever the current share price is. So if you look at the \"\"Fees and Investment Minimums\"\" section of the JPEM page, you'll see the fees listed, but not any investment minimums.\"", "title": "" }, { "docid": "367960", "text": "\"I think you are asking about actively managed funds vs. indexes and possibly also vs. diversified funds like target date funds. This is also related to the question of mutual fund vs. ETF. First, a fund can be either actively managed or it can attempt to track an index. An actively managed fund has a fund manager who tries to find the best stocks to invest in within some constraints, like \"\"this fund invests in large cap US companies\"\". An index fund tries to match as closely as possible the performance of an index like the S&P 500. A fund may also try to offer a portfolio that is suitable for someone to put their entire account into. For example, a target date fund is a fund that may invest in a mix of stocks, bonds and foreign stock in a proportion that would be appropriate to someone expecting to retire in a certain year. These are not what people tend to think of as the canonical examples of mutual funds, even though they share the same legal structure and investment mechanisms. Secondly, a fund can either be a traditional mutual fund or it can be an exchange traded fund (ETF). To invest in a traditional mutual fund, you send money to the fund, and they give you a number of shares equal to what that money would have bought of the net asset value (NAV) of the fund at the end of trading on the day they receive your deposit, possibly minus a sales charge. To invest in an ETF, you buy shares of the ETF on the stock market like any other stock. Under the covers, an ETF does have something similar to the mechanism of depositing money to get shares, but only big traders can use that, and it's not used for investing, but only for people who are making a market in the stock (if lots of people are buying VTI, Big Dealer Co will get 100,000 shares from Vanguard so that they can sell them on the market the next day). Historically and traditionally, ETFs are associated with an indexing strategy, while if not specifically mentioned, people assume that traditional mutual funds are actively managed. Many ETFs, notably all the Vanguard ETFs, are actually just a different way to hold the same underlying fund. The best way to understand this is to read the prospectus for a mutual fund and an ETF. It's all there in reasonably plain English.\"", "title": "" }, { "docid": "531180", "text": "You can look into specific market targeted mutual funds or ETF's. For Norway, for example, look at NORW. If you want to purchase specific stocks, then you'd better be ready to trade on local stock exchanges in local currency. ETrade allows trading on some of the international stock exchanges (in Asia they have Hong Kong and Japan, in Europe they have the UK, Germany and France, and in the Americas they have the US and Canada). Some of the companies you're interested in might be trading there.", "title": "" }, { "docid": "39265", "text": "In addition to the higher risk as pointed out by @JamesRoth, you also need to consider that there are regulations against 'naked shorting' so you generally need to either own the security, or have someone that is willing to 'loan' the security to you in order to sell short. If you own a stock you are shorting, the IRS could view the transaction as a Sell followed by a buy taking place in a less than 30 day period and you could be subject to wash-sale rules. This added complexity (most often the finding of someone to loan you the security you are shorting) is another reason such trades are considered more advanced. You should also be aware that there are currently a number of proposals to re-instate the 'uptick rule' or some circuit-breaker variant. Designed to prevent short-sellers from driving down the price of a stock (and conducting 'bear raids etc) the first requires that a stock trade at the same or higher price as prior trades before you can submit a short. In the latter shorting would be prohibited after a stock price had fallen a given percentage in a given amount of time. In either case, should such a rule be (re)established then you could face limitations attempting to execute a short which you would not need to worry about doing simple buys or sells. As to vehicles that would do this kind of thing (if you are convinced we are in a bear market and willing to take the risk) there are a number of ETF's classified as 'Inverse Exchange Traded Funds (ETF's) for a variety of markets that via various means seek to deliver a return similar to that of 'shorting the market' in question. One such example for a common broad market is ticker SH the ProShares Short S&P500 ETF, which seeks to deliver a return that is the inverse of the S&P500 (and as would be predicted based on the roughly +15% performance of the S&P500 over the last 12 months, SH is down roughly -15% over the same period). The Wikipedia article on inverse ETF's lists a number of other such funds covering various markets. I think it should be noted that using such a vehicle is a pretty 'aggressive bet' to take in reaction to the belief that a bear market is imminent. A more conservative approach would be to simply take money out of the market and place it in something like CD's or Treasury instruments. In that case, you preserve your capital, regardless of what happens in the market. Using an inverse ETF OTOH means that if the market went bull instead of bear, you would lose money instead of merely holding your position.", "title": "" }, { "docid": "369266", "text": "A stock, bond or ETF is basically a commodity. Where you bought it does not really matter, and it has a value in USD only inasmuch as there is a current market price quoted at an American exchange. But nothing prevents you from turning around and selling it on a European exchange where it is also listed for an equivalent amount of EUR (arbitrage activities of investment banks ensure that the price will be equivalent in regard to the current exchange rate). In fact, this can be used as a cheap form of currency conversion. For blue chips at least this is trivial; exotic securities might not be listed in Europe. All you need is a broker who allows you to trade on European exchanges and hold an account denominated in EUR. If necessary, transfer your securities to a broker who does, which should not cost more than a nominal fee. Mutual funds are a different beast though; it might be possible to sell shares on an exchange anyway, or sell them back to the issuer for EUR. It depends. In any case, however, transferring 7 figure sums internationally can trigger all kinds of tax events and money laundering investigations. You really need to hire a financial advisor who has international investment experience for this kind of thing, not ask a web forum!", "title": "" }, { "docid": "65663", "text": "\"@sdg's answer is spot-on with the advice to avoid repeated conversions, but I'd like to provide some specifics on the fees involved: Each time you round-trip Canadian dollars (CAD) through a U.S.-dollar (USD) priced security at TD Waterhouse and leave your proceeds in CAD, you're paying a total foreign exchange fee – implied in their rate spread – of about 3%, give or take. That's ~3% per buy & sell combination, or ~1.5% on each end. You can imagine if you trade back & forth frequently, you can quickly lose a lot of money. Do it back and forth ten times in a year and you're out ~30% on the fees alone! The TD U.S. Money Market Fund (TDB166) that TD Waterhouse is referring to has no direct commission to buy or sell, but it does have a Management Expense Ratio (MER) of 0.20% per year – basically a fee which is deducted from the fund's returns (which, today, are also close to zero.) Practically speaking, that's a very slim fee to hold some USD in your Canadian dollar TFSA. While 0.20% is cheap, a point to keep in mind is if you maintain a significant USD balance, you are maintaining currency risk: You can lose money in CAD terms if the CAD appreciates vs. USD. Additional references: Canadian Capitalist describes TD Waterhouse and the use of TDB166 and \"\"wash trades\"\" at How to \"\"Wash\"\" Your Trade? He's referring to RRSPs, but the same applies to TFSAs, which came out after the post was written. Canadian Couch Potato has two relevant articles: Are US-listed ETFs Really Cheaper? and Lowering Your Currency Exchange Fees.\"", "title": "" }, { "docid": "84800", "text": "\"Your broker, Ameritrade, offers a variety of Exchange Traded Funds (ETFs) that you can buy and sell with zero commission. An ETF is like a mutual fund, but you buy and sell shares the same way you buy and sell shares of stocks. From your point of view, the relevance of this is that you can buy and sell as many or as few shares as you like, even down to a single share. Note that to get the commission-free trades on the available ETFs you have to sign up for it in your account profile. Be sure to do that before you enter any buy orders. You'll want to start by looking at the Ameritrade's list of commission-free ETFs. Notice that they are divided into different categories: stocks, bonds, international, and commodities. Which categories you pick from will depend on your personal investing goals, time horizon, risk tolerance, and so on. There are lots of questions and answers on this site that talk about asset allocation. You should read them, as it is the most important decision you will make with your portfolio. The other thing you want to be aware of is the expense ratio for each fund. These expenses reduce the fund's return (they are included in the calculation of the net asset value of the shares), so lower is definitely better. Personally, I wouldn't even consider paying more than about 0.10% (commonly read \"\"10 basis points\"\" or \"\"10 bp\"\") for a broad-based domestic stock fund. For a sectoral fund you might put up with as much as 20 bp in expenses. Bond funds tend to be a little more expensive, so maybe allow as much as 25 bp, and likewise for international funds. I've never invested in commodity funds, so I'll let someone else opine on appropriate expense ratios for those. Once you've decided what funds you want (and have signed up for commission-free trades), all you have to do is enter the trade orders. The website where you manage your account has tutorials on how to do that. After that you should be all set. Good luck with your investing!\"", "title": "" }, { "docid": "224765", "text": "\"An ETF does not track any one individual stock. It \"\"is a marketable security that tracks an index, a commodity, bonds, or a basket of assets like an index fund.\"\" Check out this link to learn more about ETFs. The easiest way see what ETF tracks a stock is to determine what sector and industry that company is in and find some ETF that trade it. The ETF will likely trade that stock, assuming that its market cap and exchange it trades on fits within the parameters of the ETF.\"", "title": "" }, { "docid": "151203", "text": "A derivative in finance is simply any asset whose value is based on the value of another asset or based on the value of a group of assets. A derivative contract is a type of contract (usually a 'standardized contract') with specific payout instruction based on the price changes of a different asset. The basic idea is that it becomes easier to make a claim to an asset or property (and profit from this claim), without needing to physically transfer it (or even the title to said asset), and use much less capital to do so (reduce risk). They become problematic when multiple people may have claims to the real asset, or when the value of the derivatives changes very quickly or are hard to calculate. There are also liquidity problems the further you get from the real asset. This is not a problem for all kinds of derivatives contracts. And you must recognize that derivatives are used colloquially in a way that has nothing to do with reality to cause fear in people/investors that are not financially savvy. Many derivatives also have dubious or no economic purposes such that regulators don't allow them to be traded since they can't see how it is different from gambling. This is seen in financial markets that are less liberalized or cultures with puritanical backgrounds. Typically the trick is to convince regulators that the derivative or financial product helps with reducing risk and hedging and it will get approved. I've mentioned some terminology, but this depends specifically on what kind of derivatives contract you become interested in. Swaps, Credit Default Swaps, Futures, Options, Options on Futures, Leveraged Exchange Traded Funds, Inverse Leveraged Exchange Traded Funds, warrants, and more all have their own terminology. How to trade them in a simulation? It all depends on which financial product you really become interested in.", "title": "" }, { "docid": "276983", "text": "You haven't looked very far if you didn't find index tracking exchange-traded funds (ETFs) on the Toronto Stock Exchange. There are at least a half dozen major exchange-traded fund families that I'm aware of, including Canadian-listed offerings from some of the larger ETF providers from the U.S. The Toronto Stock Exchange (TSX) maintains a list of ETF providers that have products listed on the TSX.", "title": "" }, { "docid": "515643", "text": "So, couple of things. Firstly, every international ETF includes risk disclosure language in the prospectus covering both market disruption events as well as geopolitical risk, so the sponsor would be pretty well insulated from direct liability for anything. If the Russian market were truly shut down there are true-up mechanisms in place but in the scenario you're describing the market is still open, it's just only a few participants can trade in it. First thing to do is shut down creates- that is, allow no new money to come into the fund. This at least prevents your problem from getting bigger. Second you're going to switch all redemptions to in kind only. MV itself can't trade in the underlying so they're kind of jammed here. An ETF sponsor can't really refuse your redemption request (can delay, but only for a short time), but they can control the form in which they respond to it. What theoretically should happen here is an AP not subject to sanctions will step in and handle redemptions. Issue is, they'll probably charge for this so you should expect the fund to start trading at a discount to NAV (you, as an investor, sell to them cheaply, they submit a redemption request, then sell the stocks locally). Someone else has pointed that market makers will start stat arbing the fund using correlated/substitute instruments, which totally will help keep things in line, but my guess is that you'd still see the name trading away from NAV regardless. Driver of this will be the amount of money desperate to get out - if investors are content to wait the sanctions out who knows.", "title": "" }, { "docid": "205280", "text": "\"According to what little information is available currently, this fund is most akin to an actively managed exchange traded fund rather than an investment trust. An investment trust is an actively managed, closed-end fund that is tradeable on the stock market. \"\"Closed-end\"\" means that there are a fixed number of shares available for trading, so if you wish to buy or sell shares in a closed-end fund you need to find someone willing to sell or buy shares. \"\"Actively managed\"\" means that the assets are selected by the fund managers in the belief that they will perform well. This is in contrast to a \"\"passively managed\"\" fund which simply tracks an underlying index. The closed-end nature of investment trusts means that the share price is not well correlated to the value of the underlying assets. Indeed, almost all UK investment trusts trade at a significant discount to their net asset value. This reflects their historic poor performance and relatively weak liquidity. Of course there are some exceptions to this. Examples of open-end funds are unit trust (US = mutual funds) and ETFs (exchange traded funds). They are \"\"open-end\"\" funds in the sense that the number of shares/units available will change according to demand. Most importantly, the price of a share/unit will be strongly correlated to the net asset value of the underlying portfolio. In general, for an open-end fund, if the net asset value of the fund is X and there are Y shares/units outstanding, then the price of a share/unit will be X/Y. Historic data shows that passively managed funds (index trackers) \"\"always\"\" outperform actively managed funds in the long term. One of the big issues with actively managed funds is they have relatively high management fees. The Peoples Trust will be charging about 1% with a promise that this should come down over time. Compare this to a fee of 0.05% on a large, major market index tracking ETF. Further, the 1% headline fee being touted by Peoples Trust is a somewhat misleading, since they are paying their employees bonuses with shares in the fund. This will cause dilution of the net asset value per share and can be read as addition management fees by proxy. Since competent fund managers will demand high incomes, bonus shares could easily double the management fees, depending on the size of the fund. In summary, history has shown that the promises of active fund managers rarely (if ever) come to fruition. Personally, I would not consider this to be an attractive investment and would look more towards a passively managed major market index ETF with low management fees.\"", "title": "" }, { "docid": "479420", "text": "Mutual funds buy (and sell) shares in companies in accordance with the policies set forth in their prospectus, not according to the individual needs of an investor, that is, when you invest money in (or withdraw money from) a mutual fund, the manager buys or sells whatever shares that, in the manager's judgement, will be the most appropriate ones (consistent with the investment policies). Thus, a large-cap mutual fund manager will not buy the latest hot small-cap stock that will likely be hugely profitable; he/she must choose only between various large capitalization companies. Some exchange-traded funds are fixed baskets of stocks. Suppose you will not invest in a company X as a matter of principle. Unless a mutual fund prospectus says that it will not invest in X, you may well end up having an investment in X at some time because the fund manager bought shares in X. With such an ETF, you know what is in the basket, and if the basket does not include stock in X now, it will not own stock in X at a later date. Some exchange-traded funds are constructed based on some index and track the index as a matter of policy. Thus, you will not be investing in X unless X becomes part of the index because Standard or Poor or Russell or somebody changed their minds, and the ETF buys X in order to track the index. Finally, some ETFs are exactly like general mutual funds except that you can buy or sell ETF shares at any time at the price at the instant that your order is executed whereas with mutual funds, the price of the mutual fund shares that you have bought or sold is the NAV of the mutual fund shares for that day, which is established based on the closing prices at the end of the trading day of the stocks, bonds etc that the fund owns. So, you might end up owning stock in X at any time based on what the fund manager thinks about X.", "title": "" }, { "docid": "322725", "text": "In the past 10 years there have been mutual funds that would act as a single bucket of stocks and bonds. A good example is Fidelity's Four In One. The trade off was a management fee for the fund in exchange for having to manage the portfolio itself and pay separate commissions and fees. These days though it is very simple and pretty cheap to put together a basket of 5-6 ETFs that would represent a balanced portfolio. Whats even more interesting is that large online brokerage houses are starting to offer commission free trading of a number of ETFs, as long as they are not day traded and are held for a period similar to NTF mutual funds. I think you could easily put together a basket of 5-6 ETFs to trade on Fidelity or TD Ameritrade commission free, and one that would represent a nice diversified portfolio. The main advantage is that you are not giving money to the fund manager but rather paying the minimal cost of investing in an index ETF. Overall this can save you an extra .5-1% annually on your portfolio, just in fees. Here are links to commission free ETF trading on Fidelity and TD Ameritrade.", "title": "" }, { "docid": "328699", "text": "\"The London Stock Exchange offers a wealth of exchange traded products whose variety matches those offered in the US. Here is a link to a list of exchange traded products listed on the LSE. The link will take you to the list of Vanguard offerings. To view those offered by other managers, click on the letter choices at the top of the page. For example, to view the iShares offerings, click on \"\"I\"\". In the case of Vanguard, the LSE listed S&P500 ETF is traded under the code VUSA. Similarly, the Vanguard All World ETF trades under the code VWRL. You will need to be patient viewing iShares offerings since there are over ten pages of them, and their description is given by the abbreviation \"\"ISH name\"\". Almost all of these funds are traded in GBP. Some offer both currency hedged and currency unhedged versions. Obviously, with the unhedged version you are taking on additional currency risk, so if you wish to avoid currency risk then choose a currency hedged version. Vanguard does not appear to offer currency hedged products in London while iShares does. Here is a list of iShares currency hedged products. As you can see, the S&P500 currency hedged trades under the code IGUS while the unhedged version trades under the code IUSA. The effects of BREXIT on UK markets and currency are a matter of opinion and difficult to quantify currently. The doom and gloom warnings of some do not appear to have materialised, however the potential for near-term volatility remains so longs as the exit agreement is not formalised. In the long-term, I personally believe that BREXIT will, on balance, be a positive for the UK, but that is just my opinion.\"", "title": "" }, { "docid": "454224", "text": "A mutual fund has several classes of shares that are charged different fees. Some shares are sold through brokers and carry a sales charge (called load) that compensates the broker in lieu of a fee that the broker would charge the client for the service. Vanguard does not have sales charge on its funds and you don't need to go through a broker to buy its shares; you can buy directly from them. Admiral shares of Vanguard funds are charged lower annual expenses than regular shares (yes, all mutual funds charge expenses for fund adninistration that reduce the return that you get, and Vanguard has some of the lowest expense ratios) but Admiral shares are available only for large investments, typically $50K or so. If you have invested in a Vanguard mutual fund, your shares can be set to automatically convert to Admiral shares when the investment reaches the right level. A mutual fund manager can buy and sell stocks to achieve the objectives of the fund, so what stockes you are invested in as a share holder in a mutual fund will typically be unknown to you on a day-to-day basis. On the other hand, Exchange-traded funds (ETFs) are fixed baskets of stocks, and you can buy shares in the ETF. These shares are bought and sold through a broker (so you pay a transaction fee each time) but expenses are lower since there is no manager to buy and sell stocks: the basket is fixed. Many ETFs follow specific market indexes (e.g. S&P 500). Another difference between ETFs and mutual funds is that you can buy and sell ETFs at any time of the day just as if you could if you held stocks. With mutual funds, any buy and sell requests made during the day are processed at the end of the day and the value of the shares that you buy or sell is determined by the closing price of the stocks held by the mutual fund. With ETFs, you are getting the intra-day price at the time the buy or sell order is executed by your broker.", "title": "" }, { "docid": "183898", "text": "It is true that this is possible, however, it's very remote in the case of the large and reputable fund companies such as Vanguard. FDIC insurance protects against precisely this for bank accounts, but mutual funds and ETFs do not have an equivalent to FDIC insurance. One thing that does help you in the case of a mutual fund or ETF is that you indirectly (through the fund) own actual assets. In a cash account at a bank, you have a promise from the bank to pay, and then the bank can go off and use your money to make loans. You don't in any sense own the bank's loans. With a fund, the fund company cannot (legally) take your money out of the fund, except to pay the expense ratio. They have to use your money to buy stocks, bonds, or whatever the fund invests in. Those assets are then owned by the fund. Legally, a mutual fund is a special kind of company defined in the Investment Company Act of 1940, and is a separate company from the investment advisor (such as Vanguard): http://www.sec.gov/answers/mfinvco.htm Funds have their own boards, and in principle a fund board can even fire the company advising the fund, though this is not likely since boards aren't usually independent. (a quick google found this article for more, maybe someone can find a better one: http://www.marketwatch.com/story/mutual-fund-independent-board-rule-all-but-dead) If Vanguard goes under, the funds could continue to exist and get a new adviser, or could be liquidated with investors receiving whatever the assets are worth. Of course, all this legal stuff doesn't help you with outright fraud. If a fund's adviser says it bought the S&P 500, but really some guy bought himself a yacht, Madoff-style, then you have a problem. But a huge well-known ETF has auditors, tons of different employees, lots of brokerage and exchange traffic, etc. so to me at least it's tough to imagine a risk here. With a small fund company with just a few people - and there are lots of these! - then there's more risk, and you'd want to carefully look at what independent agent holds their assets, who their auditors are, and so forth. With regular mutual funds (not ETFs) there are more issues with diversifying across fund companies: With ETFs, there probably isn't much downside to diversifying since you could buy them all from one brokerage account. Maybe it even happens naturally if you pick the best ETFs you can find. Personally, I would just pick the best ETFs and not worry about advisor diversity. Update: maybe also deserving a mention are exchange-traded notes (ETNs). An ETN's legal structure is more like the bank account, minus the FDIC insurance of course. It's an IOU from the company that runs the ETN, where they promise to pay back the value of some index. There's no investment company as with a fund, and therefore you don't own a share of any actual assets. If the ETN's sponsor went bankrupt, you would indeed have a problem, much more so than if an ETF's sponsor went bankrupt.", "title": "" } ]
PLAIN-2625
Turmeric Curcumin Reprogramming Cancer Cell Death
[ { "docid": "MED-2781", "text": "Our previous study demonstrated that curcumin, an active compound of Curcuma xanthorrhiza and C. domestica, produces a positive cholekinetic effect. A 20 mg amount of curcumin is capable of contracting the gall bladder by up to 29% within an observation time of 2 h. The aim of the current study was to define the dosage of curcumin capable of producing a 50% contraction of the gall bladder, and to determine if there is a linear relationship between doubling the curcumin dosage and the doubling of gall bladder contraction. A randomised, single-blind, three-phase, crossover-designed examination was carried out on 12 healthy volunteers. Ultrasonography was carried out serially to measure the gall bladder volume. The data obtained was analysed by analysis of variance (ANOVA). The fasting volumes of gall bladders were similar (P > 0.50), with 17.28 +/- 5.47 mL for 20 mg curcumin, 18.34 +/- 3.75 mL for 40 mg and 18.24 +/- 3.72 mL for 80 mg. The percentage decrease in gall bladder volume 2 h after administration of 20, 40 and 80 mg was 34.10 +/- 10.16, 51.15 +/- 8.08 and 72.25 +/- 8.22, respectively, which was significantly different (P < 0.01). On the basis of the present findings, it appears that the dosage of cucumin capable of producing a 50% contraction of the bladder was 40 mg. This study did not show any linear relationship between doubling curcumin dosage and the doubling of gall bladder contraction.", "title": "Effect of different curcumin dosages on human gall bladder." }, { "docid": "MED-2819", "text": "OBJECTIVES: Curcumin (diferuloylmethane) is the principal biochemical component of the spice turmeric and has been shown to possess potent anti-catabolic, anti-inflammatory and antioxidant, properties. This article aims to provide a summary of the actions of curcumin on articular chondrocytes from the available literature with the use of a text-mining tool. We highlight both the potential benefits and drawbacks of using this chemopreventive agent for treating osteoarthritis (OA). We also explore the recent literature on the molecular mechanisms of curcumin mediated alterations in gene expression mediated via activator protein 1 (AP-1)/nuclear factor-kappa B (NF-kappaB) signalling in chondrocytes, osteoblasts and synovial fibroblasts. METHODS: A computer-aided search of the PubMed/Medline database aided by a text-mining tool to interrogate the ResNet Mammalian database 6.0. RESULTS: Recent work has shown that curcumin protects human chondrocytes from the catabolic actions of interleukin-1 beta (IL-1beta) including matrix metalloproteinase (MMP)-3 up-regulation, inhibition of collagen type II and down-regulation of beta1-integrin expression. Curcumin blocks IL-1beta-induced proteoglycan degradation, AP-1/NF-kappaB signalling, chondrocyte apoptosis and activation of caspase-3. CONCLUSIONS: The available data from published in vitro and in vivo studies suggest that curcumin may be a beneficial complementary treatment for OA in humans and companion animals. Nevertheless, before initiating extensive clinical trials, more basic research is required to improve its solubility, absorption and bioavailability and gain additional information about its safety and efficacy in different species. Once these obstacles have been overcome, curcumin and structurally related biochemicals may become safer and more suitable nutraceutical alternatives to the non-steroidal anti-inflammatory drugs that are currently used for the treatment of OA. Copyright 2009 Osteoarthritis Research Society International. All rights reserved.", "title": "Biological actions of curcumin on articular chondrocytes." }, { "docid": "MED-2825", "text": "Turmeric, a dried powder derived from the rhizome of Curcuma longa, has been used for centuries in certain parts of the world and has been linked to numerous biological activities including antioxidant, anti-inflammatory, anticancer, antigrowth, anti-arthritic, anti-atherosclerotic, antidepressant, anti-aging, antidiabetic, antimicrobial, wound healing, and memory-enhancing activities. One component of turmeric is curcumin, which has been extensively studied, as indicated by more than 5600 citations, most of which have appeared within the past decade. Recent research has identified numerous chemical entities from turmeric other than curcumin. It is unclear whether all of the activities ascribed to turmeric are due to curcumin or whether other compounds in turmeric can manifest these activities uniquely, additively, or synergistically with curcumin. However, studies have indicated that turmeric oil, present in turmeric, can enhance the bioavailability of curcumin. Studies over the past decade have indicated that curcumin-free turmeric (CFT) components possess numerous biological activities including anti-inflammatory, anticancer, and antidiabetic activities. Elemene derived from turmeric is approved in China for the treatment of cancer. The current review focuses on the anticancer and anti-inflammatory activities exhibited by CFT and by some individual components of turmeric, including turmerin, turmerone, elemene, furanodiene, curdione, bisacurone, cyclocurcumin, calebin A, and germacrone. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.", "title": "Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric." }, { "docid": "MED-4239", "text": "BACKGROUND: Prostate cancer is the most common solid-tumor cancer in US males but is rare in Asian males. When Asian men adopt the US lifestyle, clinical prostate cancer increases greatly. Epidemiological data from men in the US indicate that regular activity may reduce the risk for prostate cancer. METHODS: Serum was obtained from three groups of similar-aged men, Control, Diet and Exercise, and Exercise alone were used to stimulate LNCaP cells in culture. Growth and apoptosis of tumor cells were measured. Serum samples were also used to measure insulin, IGF-1, IGFBP-1. RESULTS: The Diet and Exercise and the Exercise alone groups had lower serum insulin and IGF-1 but higher IGFBP-1 compared to Controls. LNCaP cell growth was reduced in both groups compared to Control and there was a major increase in apoptosis of tumor cells. CONCLUSIONS: A low-fat diet and/or intensive exercise results in change in serum hormones and growth factors in vivo that can reduce growth and induce apoptosis of LNCaP prostate tumor cells in vitro. Copyright 2003 Wiley-Liss, Inc.", "title": "A low-fat diet and/or strenuous exercise alters the IGF axis in vivo and reduces prostate tumor cell growth in vitro." }, { "docid": "MED-2812", "text": "Curcumin derived from the tropical plant Curcuma longa has a long history of use as a dietary agent, food preservative, and in traditional Asian medicine. It has been used for centuries to treat biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. The preventive and therapeutic properties of curcumin are associated with its antioxidant, anti-inflammatory, and anticancer properties. Extensive research over several decades has attempted to identify the molecular mechanisms of curcumin action. Curcumin modulates numerous molecular targets by altering their gene expression, signaling pathways, or through direct interaction. Curcumin regulates the expression of inflammatory cytokines (e.g., TNF, IL-1), growth factors (e.g., VEGF, EGF, FGF), growth factor receptors (e.g., EGFR, HER-2, AR), enzymes (e.g., COX-2, LOX, MMP9, MAPK, mTOR, Akt), adhesion molecules (e.g., ELAM-1, ICAM-1, VCAM-1), apoptosis related proteins (e.g., Bcl-2, caspases, DR, Fas), and cell cycle proteins (e.g., cyclin D1). Curcumin modulates the activity of several transcription factors (e.g., NF-κB, AP-1, STAT) and their signaling pathways. Based on its ability to affect multiple targets, curcumin has the potential for the prevention and treatment of various diseases including cancers, arthritis, allergies, atherosclerosis, aging, neurodegenerative disease, hepatic disorders, obesity, diabetes, psoriasis, and autoimmune diseases. This review summarizes the molecular mechanisms of modulation of gene expression by curcumin. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.", "title": "Molecular mechanisms of curcumin action: gene expression." }, { "docid": "MED-2604", "text": "Cancer is a hyperproliferative disorder that is usually treated by chemotherapeutic agents that are toxic not only to tumor cells but also to normal cells, so these agents produce major side effects. In addition, these agents are highly expensive and thus not affordable for most. Moreover, such agents cannot be used for cancer prevention. Traditional medicines are generally free of the deleterious side effects and usually inexpensive. Curcumin, a component of turmeric (Curcuma longa), is one such agent that is safe, affordable, and efficacious. How curcumin kills tumor cells is the focus of this review. We show that curcumin modulates growth of tumor cells through regulation of multiple cell signaling pathways including cell proliferation pathway (cyclin D1, c-myc), cell survival pathway (Bcl-2, Bcl-xL, cFLIP, XIAP, c-IAP1), caspase activation pathway (caspase-8, 3, 9), tumor suppressor pathway (p53, p21) death receptor pathway (DR4, DR5), mitochondrial pathways, and protein kinase pathway (JNK, Akt, and AMPK). How curcumin selectively kills tumor cells, and not normal cells, is also described in detail.", "title": "Curcumin and Cancer Cells: How Many Ways Can Curry Kill Tumor Cells Selectively?" }, { "docid": "MED-2605", "text": "Curcumin (diferuloylmethane), the yellow pigment in turmeric (Curcuma longa), is known to inhibit proliferation of cancer cells by arresting them at various phases of the cell cycle and to induce apoptosis in tumor cells. Curcumin-induced apoptosis mainly involves the activation of caspase-3 and mitochondria-mediated pathway in various cancer cells of different tissue origin. In the present study, the induction of apoptosis and cytotoxicity by curcumin in colon cancer colo 205 cells was investigated by using flow cytometry. The results demonstrated that curcumin induced cytotoxicity and apoptosis dose- and time-depedently. Curcumin induced the production of reactive oxygen species (ROS) and Ca+2, decreased the levels of mitochondria membrane potential and induced caspase-3 activity. Curcumin also promoted the expression of Bax, cytochrome C, p53 and p21 but inhibited the expression of Bcl-2. These observations suggest that curcumin may have a possible therapeutic potential in colon cancer patients.", "title": "Curcumin-induced apoptosis of human colon cancer colo 205 cells through the production of ROS, Ca2+ and the activation of caspase-3." }, { "docid": "MED-2826", "text": "Background Curcumin extracts of turmeric are proposed to produce health benefits. To date, human intervention studies have focused mainly on people with existing health problems given high doses of poorly absorbed curcumin. The purpose of the current study was to check whether in healthy people, a low dose of a lipidated curcumin extract could alter wellness-related measures. Methods The present study was conducted in healthy middle aged people (40–60 years old) with a low dose of curcumin (80 mg/day) in a lipidated form expected to have good absorption. Subjects were given either curcumin (N = 19) or placebo (N = 19) for 4 wk. Blood and saliva samples were taken before and after the 4 weeks and analyzed for a variety of blood and saliva measures relevant to health promotion. Results Curcumin, but not placebo, produced the following statistically significant changes: lowering of plasma triglyceride values, lowering of salivary amylase levels, raising of salivary radical scavenging capacities, raising of plasma catalase activities, lowering of plasma beta amyloid protein concentrations, lowering of plasma sICAM readings, increased plasma myeloperoxidase without increased c-reactive protein levels, increased plasma nitric oxide, and decreased plasma alanine amino transferase activities. Conclusion Collectively, these results demonstrate that a low dose of a curcumin-lipid preparation can produce a variety of potentially health promoting effects in healthy middle aged people.", "title": "Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people" }, { "docid": "MED-2794", "text": "Turmeric, a plant rhizome that is often dried, ground and used as a cooking spice, has also been used medicinally for several thousand years. Curcumin, the phytochemical that gives turmeric its golden color, is responsible for most of the therapeutic effects of turmeric. In recent years curcumin has been studied for its effects on chronic diseases such as diabetes, Alzheimer's, and cancer. Though many researchers are investigating turmeric/curcumin in cancer therapy, there is little epidemiologic information on the effects of turmeric consumption. With limited availability of pharmacologic interventions in many areas of the world, use of turmeric in the diet may help to alleviate some of the disease burden through prevention. Here we provide a brief overview of turmeric consumption in different parts of the world, cancer rates in those regions, possible biochemical mechanisms by which turmeric acts and practical recommendations based on the information available.", "title": "Dietary turmeric potentially reduces the risk of cancer." }, { "docid": "MED-2814", "text": "Curcumin (diferuloylmethane), an active constituent of turmeric, is a well-described phytochemical, which has been used since ancient times for the treatment of various diseases. The dysregulation of cell signaling pathways by the gradual alteration of regulatory proteins is the root cause of cancers. Curcumin modulates regulatory proteins through various molecular mechanisms. Several research studies have provided in-depth analysis of multiple targets through which curcumin induces protective effects against cancers including gastrointestinal, genitourinary, gynecological, hematological, pulmonary, thymic, brain, breast, and bone. The molecular mechanisms of action of curcumin in treating different types of cancers remain under investigation. The multifaceted role of this dietary agent is mediated through its inhibition of several cell signaling pathways at multiple levels. Curcumin has the ability to inhibit carcinogenicity through the modulation of the cell cycle by binding directly and indirectly to molecular targets including transcription factors (NF-kB, STAT3, β-catenin, and AP-1), growth factors (EGF, PDGF, and VEGF), enzymes (COX-2, iNOS, and MMPs), kinases (cyclin D1, CDKs, Akt, PKC, and AMPK), inflammatory cytokines (TNF, MCP, IL-1, and IL-6), upregulation of proapoptotic (Bax, Bad, and Bak) and downregulation of antiapoptotic proteins (Bcl(2) and Bcl-xL). A variety of animal models and human studies have proven that curcumin is safe and well tolerated even at very high doses. This study elaborates the current understanding of the chemopreventive effects of curcumin through its multiple molecular pathways and highlights its therapeutic value in the treatment and prevention of a wide range of cancers. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.", "title": "Curcumin in various cancers." }, { "docid": "MED-2810", "text": "Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be \"Curecumin\".", "title": "Curcumin as \"Curecumin\": from kitchen to clinic." }, { "docid": "MED-2599", "text": "Curcumin exhibits anti-inflammatory and antitumor activities. Although its functional mechanism has not been elucidated so far, numerous studies have shown that curcumin induces apoptosis in cancer cells. In the present study, we show that subtoxic concentrations of curcumin sensitize human renal cancer cells to the tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis. This apoptosis induced by the combination of curcumin and TRAIL is not interrupted by Bcl-2 overexpression. We found that treatment with curcumin significantly induces death receptor 5 (DR5) expression both at its mRNA and protein levels, accompanying the generation of the reactive oxygen species (ROS). Not only the pretreatment with N-acetylcystine but also the ectopic expression of peroxiredoxin II, an antioxidative protein, dramatically inhibited the apoptosis induced by curcumin and TRAIL in combination, blocking the curcumin-mediated DR5 upregulation. Taken together, the present study demonstrates that curcumin enhances TRAIL-induced apoptosis by ROS-mediated DR5 upregulation.", "title": "Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through reactive oxygen species-mediated upre..." }, { "docid": "MED-5337", "text": "PURPOSE: Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS AND METHODS: Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group. RESULTS: None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. CONCLUSIONS: Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.", "title": "Intensive lifestyle changes may affect the progression of prostate cancer." }, { "docid": "MED-2805", "text": "Obesity is a significant risk factor for developing osteoarthritis in weight-bearing and non-weight-bearing joints. Although the pathogenesis of obesity-associated osteoarthritis is not completely understood, recent studies indicate that pro-inflammatory metabolic factors contribute to an increase in osteoarthritis risk. Adipose tissue, and in particular infrapatellar fat, is a local source of pro-inflammatory mediators that are increased with obesity and have been shown to increase cartilage degradation in cell and tissue culture models. One adipokine in particular, leptin, may be a critical mediator of obesity-associated osteoarthritis via synergistic actions with other inflammatory cytokines. Biomechanical factors may also increase the risk of osteoarthritis by activating cellular inflammation and promoting oxidative stress. However, some types of biomechanical stimulation, such as physiologic cyclic loading, inhibit inflammation and protect against cartilage degradation. A high percentage of obese individuals with knee osteoarthritis are sedentary, suggesting that a lack of physical activity may increase the susceptibility to inflammation. A more comprehensive approach to understanding how obesity alters daily biomechanical exposures within joint tissues may provide new insight into the protective and damaging effects of biomechanical factors on inflammation in osteoarthritis.", "title": "Pathobiology of obesity and osteoarthritis: integrating biomechanics and inflammation" }, { "docid": "MED-2815", "text": "Curcumin, an active polyphenol of the golden spice turmeric, is a highly pleiotropic molecule with the potential to modulate the biological activity of a number of signaling molecules. Traditionally, this polyphenol has been used in Asian countries to treat such human ailments as acne, psoriasis, dermatitis, and rash. Recent studies have indicated that curcumin can target newly identified signaling pathways including those associated with microRNA, cancer stem cells, and autophagy. Extensive research from preclinical and clinical studies has delineated the molecular basis for the pharmaceutical uses of this polyphenol against cancer, pulmonary diseases, neurological diseases, liver diseases, metabolic diseases, autoimmune diseases, cardiovascular diseases, and numerous other chronic diseases. Multiple studies have indicated the safety and efficacy of curcumin in numerous animals including rodents, monkeys, horses, rabbits, and cats and have provided a solid basis for evaluating its safety and efficacy in humans. To date, more than 65 human clinical trials of curcumin, which included more than 1000 patients, have been completed, and as many as 35 clinical trials are underway. Curcumin is now used as a supplement in several countries including the United States, India, Japan, Korea, Thailand, China, Turkey, South Africa, Nepal, and Pakistan. In this review, we provide evidence for the pharmaceutical uses of curcumin for various diseases. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.", "title": "Curcumin, a component of turmeric: from farm to pharmacy." }, { "docid": "MED-2802", "text": "OBJECTIVE: The objective of this study was to determine the efficacy and safety of Curcuma domestica extracts in pain reduction and functional improvement in patients with knee osteoarthritis. STUDY DESIGN AND SETTING: The design and setting were a randomized controlled study at a university hospital in Bangkok, Thailand. METHODS: One-hundred and seven (107) patients with primary knee osteoarthritis (OA) with pain score of > or =5 were randomized to receive ibuprofen 800 mg per day or C. domestica extracts 2 g per day for 6 weeks. The main outcomes were improvement in pain on level walking, pain on stairs, and functions of knee assessed by time spent during 100-m walk and going up and down a flight of stairs. The adverse events were also recorded. RESULTS: Fifty-two (52) and 55 patients were randomized to C. domestica extracts and ibuprofen groups, respectively. Baseline characteristics of the patients in both groups were not different. The mean scores of the aforementioned outcomes at weeks 0, 2, 4, and 6 were significantly improved when compared with the baseline values in both groups. There was no difference in those parameters between the patients receiving ibuprofen and C. domestica extracts, except pain on stairs (p = 0.016). No significant difference of adverse events between both groups was found (33.3% versus 44.2%, p = 0.36 in C. domestica extracts and ibuprofen groups, respectively). CONCLUSIONS: C. domestica extracts seem to be similarly efficacious and safe as ibuprofen for the treatment of knee OA.", "title": "Efficacy and safety of Curcuma domestica extracts in patients with knee osteoarthritis." }, { "docid": "MED-2813", "text": "The use of turmeric, derived from the root of the plant Curcuma longa, for treatment of different inflammatory diseases has been described in Ayurveda and in traditional Chinese medicine for thousands of years. The active component of turmeric responsible for this activity, curcumin, was identified almost two centuries ago. Modern science has revealed that curcumin mediates its effects by modulation of several important molecular targets, including transcription factors (e.g., NF-kappaB, AP-1, Egr-1, beta-catenin, and PPAR-gamma), enzymes (e.g., COX2, 5-LOX, iNOS, and hemeoxygenase-1), cell cycle proteins (e.g., cyclin D1 and p21), cytokines (e.g., TNF, IL-1, IL-6, and chemokines), receptors (e.g., EGFR and HER2), and cell surface adhesion molecules. Because it can modulate the expression of these targets, curcumin is now being used to treat cancer, arthritis, diabetes, Crohn's disease, cardiovascular diseases, osteoporosis, Alzheimer's disease, psoriasis, and other pathologies. Interestingly, 6-gingerol, a natural analog of curcumin derived from the root of ginger (Zingiber officinalis), exhibits a biologic activity profile similar to that of curcumin. The efficacy, pharmacologic safety, and cost effectiveness of curcuminoids prompt us to \"get back to our roots.\"", "title": "Curcumin: getting back to the roots." }, { "docid": "MED-2583", "text": "Inositol hexaphosphate (IP(6)), a naturally polyphosphorylated carbohydrate, has been reported to have significant in vivo and in vitro anticancer activity against numerous tumours, such as colon, prostate, breast, liver and rhabdomyosarcomas. To confirm this activity in haematological malignancies and to characterize some of the mechanisms of IP(6) action, we analysed its effects on human leukaemic cell lines and fresh chronic myelogenous leukaemia (CML) progenitor cells using a combined cellular and molecular approach. IP(6) had a dose-dependent cytotoxic effect on all of the evaluated cell lines, with accumulation in the G2M phase in two out of five cell lines tested. At the molecular level, cDNA microarray analysis after IP(6) exposure showed an extensive downmodulation of genes involved in transcription and cell cycle regulation and a coherent upregulation of cell cycle inhibitors. Furthermore, IP(6) treatment of fresh leukaemic samples of bone marrow CD34+ CML progenitor cells significantly inhibited granulocyte-macrophage colony-forming unit (CFU-GM) formation (P = 0.0062) in comparison to normal bone marrow specimens, which were not affected. No differentiating effect on HL60 cells was observed. Taken together, our results confirm the antiproliferative activity of IP(6) and suggest that it may have a specific antitumour effect also in chronic myeloid leukaemias, via active gene modulation.", "title": "Effect of inositol hexaphosphate (IP(6)) on human normal and leukaemic haematopoietic cells." }, { "docid": "MED-2786", "text": "Alzheimer's disease (AD) is the most common form of dementia. There is limited choice in modern therapeutics, and drugs available have limited success with multiple side effects in addition to high cost. Hence, newer and alternate treatment options are being explored for effective and safer therapeutic targets to address AD. Turmeric possesses multiple medicinal uses including treatment for AD. Curcuminoids, a mixture of curcumin, demethoxycurcumin, and bisdemethoxycurcumin, are vital constituents of turmeric. It is generally believed that curcumin is the most important constituent of the curcuminoid mixture that contributes to the pharmacological profile of parent curcuminoid mixture or turmeric. A careful literature study reveals that the other two constituents of the curcuminoid mixture also contribute significantly to the effectiveness of curcuminoids in AD. Therefore, it is emphasized in this review that each component of the curcuminoid mixture plays a distinct role in making curcuminoid mixture useful in AD, and hence, the curcuminoid mixture represents turmeric in its medicinal value better than curcumin alone. The progress in understanding the disease etiology demands a multiple-site-targeted therapy, and the curcuminoid mixture of all components, each with different merits, makes this mixture more promising in combating the challenging disease. Copyright © 2013 John Wiley & Sons, Ltd.", "title": "Therapeutic potential of turmeric in Alzheimer's disease: curcumin or curcuminoids?" }, { "docid": "MED-2809", "text": "Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn’s disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin’s pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF–κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E2, prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the effect of curcumin has been investigated.", "title": "Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials" }, { "docid": "MED-4220", "text": "OBJECTIVE: Accumulating evidence indicates that prostate cancer is associated with high levels of serum IGF-I. This study was conducted to determine whether a low-fat diet and exercise (DE) intervention may modulate the IGF axis and reduce prostate cancer cell growth in vitro. METHODS: Fasting serum was obtained from 14 men (age 60 +/- 3 years) participating in an 11-day DE program and from eight similarly aged men who had followed the DE program for 14.2 +/- 1.7 years (long-term). Insulin, IGF-I, IGFBP-1, and IGFBP-3 were measured by ELISA, and serum was used to stimulate LNCaP cell growth in vitro. RESULTS: Serum IGF-I levels decreased by 20% while IGFBP-1 increased by 53% after 11-day DE. In the long-term group, IGF-I was 55% lower, while IGFBP-1 was 150% higher relative to baseline. Serum insulin decreased by 25% after 11-day DE and was 68% lower in the long-term group, relative to baseline. No changes in serum IGFBP-3 were observed. Serum-stimulated LNCaP cell growth was reduced by 30% in post-11-day serum and by 44% in long-term serum relative to baseline. LNCaP cells incubated with post-DE serum showed increased apoptosis/ necrosis, compared to baseline. CONCLUSIONS: A low-fat diet and exercise intervention induces in-vivo changes in the circulating IGF axis and is associated with reduced growth and enhanced apoptosis/necrosis of LNCaP tumor cells in vitro.", "title": "Effect of diet and exercise on serum insulin, IGF-I, and IGFBP-1 levels and growth of LNCaP cells in vitro (United States)." }, { "docid": "MED-2822", "text": "Curcumin is known to possess potent antiinflammatory and antiarthritic properties. This pilot clinical study evaluated the safety and effectiveness of curcumin alone, and in combination with diclofenac sodium in patients with active rheumatoid arthritis (RA). Forty-five patients diagnosed with RA were randomized into three groups with patients receiving curcumin (500 mg) and diclofenac sodium (50 mg) alone or their combination. The primary endpoints were reduction in Disease Activity Score (DAS) 28. The secondary endpoints included American College of Rheumatology (ACR) criteria for reduction in tenderness and swelling of joint scores. Patients in all three treatment groups showed statistically significant changes in their DAS scores. Interestingly, the curcumin group showed the highest percentage of improvement in overall DAS and ACR scores (ACR 20, 50 and 70) and these scores were significantly better than the patients in the diclofenac sodium group. More importantly, curcumin treatment was found to be safe and did not relate with any adverse events. Our study provides the first evidence for the safety and superiority of curcumin treatment in patients with active RA, and highlights the need for future large-scale trials to validate these findings in patients with RA and other arthritic conditions. Copyright © 2012 John Wiley & Sons, Ltd.", "title": "A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis." }, { "docid": "MED-2793", "text": "Piperine, a major active component of black and long peppers, has been reported to enhance drug bioavailability. The present studies were aimed at understanding the interaction of piperine with enzymatic drug biotransforming reactions in hepatic tissue in vitro and in vivo. Piperine inhibited arylhydrocarbon hydroxylation, ethylmorphine-N-demethylation, 7-ethoxycoumarin-O-deethylation and 3-hydroxy-benzo(a)pyrene glucuronidation in rat postmitochondrial supernatant in vitro in a dose-dependent manner. Piperine inhibition of these reactions in postmitochondrial supernatant from 3-methylcholanthrene- and phenobarbital-treated rats was similar to the controls. Inhibition by piperine of arylhydrocarbon hydroxylase (AHH) from 3-methylcholanthrene-treated rats was comparable to that observed with 7,8-benzoflavone. Piperine caused noncompetitive inhibition of hepatic microsomal AHH from the untreated and 3-methylcholanthrene-treated rats with a Ki of 30 microM which was close to the apparent Km of AHH observed in the controls. Similarly, the kinetics of inhibition of ethylmorphine-N-demethylase from control rat liver microsomes exhibited noncompetitive inhibition with an apparent Km of 0.8 mM and Ki of 35 microM. These studies demonstrated that piperine is a nonspecific inhibitor of drug metabolism which shows little discrimination between different cytochrome P-450 forms. Oral administration of piperine in rats strongly inhibited the hepatic AHH and UDP-glucuronyltransferase activities. The maximal inhibition of AHH observed within 1 hr restored to normal value in 6 hr. Pretreatment with piperine prolonged hexobarbital sleeping time and zoxazolamine paralysis time in mice at half the dose of SKF-525A. These results demonstrate that piperine is a potent inhibitor of drug metabolism.", "title": "Biochemical basis of enhanced drug bioavailability by piperine: evidence that piperine is a potent inhibitor of drug metabolism." }, { "docid": "MED-2601", "text": "It has been reported that curcumin inhibited various types of cancer cells in vitro and in vivo. However, mechanisms of curcumin-inhibited cell growth and -induced apoptosis in human non-small cell lung cancer cells (NCI-H460) still remain unclear. In this study, NCI-H460 cells were treated with curcumin to determine its anticancer activity. Different concentrations of curcumin were used for different durations in NCI-H460 cells and the subsequent changes in the cell morphology, viability, cell cycle, mRNA and protein expressions were determined. Curcumin induced apoptotic morphologic changes in NCI-H460 cells in a dose-dependent manner. After curcumin treatment, BAX and BAD were up-regulated, BCL-2, BCL-X(L) and XIAP were down-regulated. In addition, reactive oxygen species (ROS), intracellular Ca(2+) and endoplasmic reticulum (ER) stress were increased in NCI-H460 cells after exposure to curcumin. These signals led to a loss of mitochondrial membrane potential (Delta Psi(m)) and culminated in caspase-3 activation. Curcumin-induced apoptosis was also stimulated through the FAS/caspase-8 (extrinsic) pathway and ER stress proteins, growth arrest- and DNA damage-inducible gene 153 (GADD153) and glucose-regulated protein 78 (GRP78) were activated in the NCI-H460 cells. Apoptotic cell death induced by curcumin was significantly reversed by pretreatment with ROS scavenger or caspase-8 inhibitor. Furthermore, the NCI-H460 cells tended to be arrested at the G(2)/M cell cycle stage after curcumin treatment and down-regulation of cyclin-dependent kinase 1 (CDK1) may be involved. In summary, curcumin exerts its anticancer effects on lung cancer NCI-H460 cells through apoptosis or cell cycle arrest.", "title": "Curcumin induces apoptosis in human non-small cell lung cancer NCI-H460 cells through ER stress and caspase cascade- and mitochondria-dependent pat..." }, { "docid": "MED-4543", "text": "Phyllanthus emblica Linn. (PE) is a medicinal fruit used in many Asian traditional medicine systems for the treatment of various diseases including cancer. The present study tested the potential anticancer effects of aqueous extract of PE in four ways: (1) against cancer cell lines, (2) in vitro apoptosis, (3) mouse skin tumourigenesis and (4) in vitro invasiveness. The PE extract at 50-100 microg/mL significantly inhibited cell growth of six human cancer cell lines, A549 (lung), HepG2 (liver), HeLa (cervical), MDA-MB-231 (breast), SK-OV3 (ovarian) and SW620 (colorectal). However, the extract was not toxic against MRC5 (normal lung fibroblast). Apoptosis in HeLa cells was also observed as PE extract caused DNA fragmentation and increased activity of caspase-3/7 and caspase-8, but not caspase-9, and up-regulation of the Fas protein indicating a death receptor-mediated mechanism of apoptosis. Treatment of PE extract on mouse skin resulted in over 50% reduction of tumour numbers and volumes in animals treated with DMBA/TPA. Lastly, 25 and 50 microg/mL of PE extract inhibited invasiveness of MDA-MB-231 cells in the in vitro Matrigel invasion assay. These results suggest P. emblica exhibits anticancer activity against selected cancer cells, and warrants further study as a possible chemopreventive and antiinvasive agent. Copyright 2010 John Wiley & Sons, Ltd.", "title": "Antitumour effects of Phyllanthus emblica L.: induction of cancer cell apoptosis and inhibition of in vivo tumour promotion and in vitro invasion o..." }, { "docid": "MED-2585", "text": "Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plant and mammalian cells. It was recently recognized to possess multiple biological functions. A striking anticancer effect of IP6 was demonstrated in different experimental models. Inositol is also a natural constituent possessing moderate anticancer activity. The most consistent and best anticancer results were obtained from the combination of IP6 plus inositol. In addition to reducing cell proliferation, IP6 increases differentiation of malignant cells, often resulting in a reversion to normal phenotype. Exogenously administered IP6 is rapidly taken into the cells and dephosphorylated to lower-phosphate inositol phosphates, which further interfere with signal transduction pathways and cell cycle arrest. Enhanced immunity and antioxidant properties can also contribute to tumor cell destruction. However, the molecular mechanisms underlying this anticancer action are not fully understood. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP6 holds great promise in our strategies for the prevention and treatment of cancer. IP6 plus inositol enhances the anticancer effect of conventional chemotherapy, controls cancer metastases, and improves the quality of life, as shown in a pilot clinical trial. The data strongly argue for the use of IP6 plus inositol in our strategies for cancer prevention and treatment. However, the effectiveness and safety of IP6 plus inositol at therapeutic doses needs to be determined in phase I and phase II clinical trials in humans.", "title": "Cancer inhibition by inositol hexaphosphate (IP6) and inositol: from laboratory to clinic." }, { "docid": "MED-2572", "text": "In traditional cultures, balancing health with a balanced lifestyle was a core belief. The diseases of modern civilization were rare. Indigenous people have patterns of illness very different from Western civilization; yet, they rapidly develop diseases once exposed to Western foods and lifestyles. Food and medicine were interwoven. All cultures used special or functional foods to prevent disease. Food could be used at different times either as food or medicine. Foods, cultivation, and cooking methods maximized community health and well-being. With methods passed down through generations, cooking processes were utilized that enhanced mineral and nutrient bioavailability. This article focuses on what researchers observed about the food traditions of indigenous people, their disease patterns, the use of specific foods, and the environmental factors that affect people who still eat traditional foods.", "title": "Traditional non-Western diets." }, { "docid": "MED-2820", "text": "Scope The incidence of cancer is significantly lower in regions where turmeric is heavily consumed. Whether lower cancer incidence is due to turmeric was investigated by examining its effects on tumor cell proliferation, on pro-inflammatory transcription factors NF-κB and STAT3, and on associated gene products. Methods and results Cell proliferation and cell cytotoxicity were measured by the MTT method, NF-κB activity by EMSA, protein expression by Western blot analysis, ROS generation by FACS analysis, and osteoclastogenesis by TRAP assay. Turmeric inhibited NF-κB activation and down-regulated NF-κB-regulated gene products linked to survival (Bcl-2, cFLIP, XIAP, and cIAP1), proliferation (cyclin D1 and c-Myc), and metastasis (CXCR4) of cancer cells. The spice suppressed the activation of STAT3, and induced the death receptors (DR)4 and DR5. Turmeric enhanced the production of ROS, and suppressed the growth of tumor cell lines. Furthermore, turmeric sensitized the tumor cells to chemotherapeutic agents capecitabine and taxol. Turmeric was found to be more potent than pure curcumin for cell growth inhibition. Turmeric also inhibited NF-κB activation induced by RANKL that correlated with the suppression of osteoclastogenesis. Conclusion Our results indicate that turmeric can effectively block the proliferation of tumor cells through the suppression of NF-κB and STAT3 pathways.", "title": "Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis" }, { "docid": "MED-2787", "text": "BACKGROUND: The extract of medicinal plants containing curcumin is traditionally believed to have a positive contraction effect on the human gall-bladder. AIMS: To compare the effect of 20 mg curcumin or placebo on the gall-bladder volume of healthy volunteers. METHODS: A randomized, double blind and crossover design study was carried out in 12 healthy volunteers (seven males and five females). Ultrasonography examination was carried out serially to measure the gall-bladder volume. The data obtained was analysed by paired Student's t-test. RESULTS: The fasting gall-bladder volumes of 15.74 +/- 4.29 mL on curcumin and 15.98 +/- 4.08 mL on placebo were similar (P > 0.20). The gall-bladder volume was reduced within the period after curcumin administration. The percentage of gall-bladder volume reduction at 0.5, 1.0, 1.5 and 2.0 h after 20 mg curcumin administration were 11.8 +/- 6.9, 16.8 +/- 7.4, 22.0 +/- 8.5 and 29. 3 +/- 8.3%, respectively, which was statistically significant compared to placebo. CONCLUSION: On the basis of the present findings, it appears that curcumin induces contraction of the human gall-bladder.", "title": "The effect of curcumin and placebo on human gall-bladder function: an ultrasound study." }, { "docid": "MED-2790", "text": "Vasa (Adhatoda vasica Linn.) is a well known and easily available drug in almost all the seasons. Easy availability of any drug gains popularity among physicians as well as pharmaceuticals and this is the reason why almost every Kalpana of Vasa is found described in the Ayurvedika text. The different dosage forms of Vasa like Kvatha, Avaleha, Sneha, and Sandhana have been used for the treatment of Shwasa Roga. A number of research studies have been performed on different formulations of Vasa and its effect on Shwasa Roga. Therefore, a review study has been carried out on the Vasa extract, Vasa Avaleha (prepared from Svarasa and Kvatha), Vasa Ghrita, Vasarishta, and Vasakasava on Shwasa Roga, to know which formulation is better. It was found in the review that Vasa Ghana, Vasa Ghrita (1), and Vasa Avaleha have shown good results on Tamaka Shwasa.", "title": "A clinical review of different formulations of Vasa (Adhatoda vasica) on Tamaka Shwasa (asthma)" }, { "docid": "MED-2777", "text": "BACKGROUND: Gout, an inflammatory arthritis, reportedly afflicts more than 2 million men and women in the United States. Previous reports have suggested an association between gout and kidney stone disease; however, these studies did not adjust for such important potential confounders as obesity and the presence of hypertension. To our knowledge, no published study has examined the independent association between gout and kidney stone disease. METHODS: We used a national probability sample of the US population to determine the independent association between reported gout and history of kidney stone disease. RESULTS: Among men and women 20 years and older, 5.6% (10 million) reported the previous passage of a kidney stone and 2.7% (5.1 million) reported a diagnosis of gout by a physician. Moreover, 8.6% of individuals who reported the passage of a kidney stone on two or more occasions had a history of gout. Conversely, the prevalence of previous kidney stones in subjects with reported gout was 13.9%. In the age-adjusted model, gout was associated with an increased odds ratio (OR) for previous kidney stones (OR, 1.97; 95% confidence interval [CI], 1.37 to 2.83). After further adjustment for sex, race, body mass index, and presence of hypertension, the OR for previous kidney stones in individuals with gout decreased to 1.49 (95% CI, 1.04 to 2.14). CONCLUSION: Showing an independent association between kidney stone disease and gout strongly suggests that they share common underlying pathophysiological mechanisms. Identification of these mechanisms may lead to improved preventive strategies for both conditions. Copyright 2002 by the National Kidney Foundation, Inc.", "title": "The association between gout and nephrolithiasis: the National Health and Nutrition Examination Survey III, 1988-1994." }, { "docid": "MED-4612", "text": "Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.", "title": "Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity." }, { "docid": "MED-2831", "text": "TNFs are major mediators of inflammation and inflammation-related diseases, hence, the United States Food and Drug Administration (FDA) has approved the use of blockers of the cytokine, TNF-α, for the treatment of osteoarthritis, inflammatory bowel disease, psoriasis and ankylosis. These drugs include the chimeric TNF antibody (infliximab), humanized TNF-α antibody (Humira) and soluble TNF receptor-II (Enbrel) and are associated with a total cumulative market value of more than $20 billion a year. As well as being expensive ($15 000–20 000 per person per year), these drugs have to be injected and have enough adverse effects to be given a black label warning by the FDA. In the current report, we describe an alternative, curcumin (diferuloylmethane), a component of turmeric (Curcuma longa) that is very inexpensive, orally bioavailable and highly safe in humans, yet can block TNF-α action and production in in vitro models, in animal models and in humans. In addition, we provide evidence for curcumin's activities against all of the diseases for which TNF blockers are currently being used. Mechanisms by which curcumin inhibits the production and the cell signalling pathways activated by this cytokine are also discussed. With health-care costs and safety being major issues today, this golden spice may help provide the solution. Linked Articles This article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-8", "title": "Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers" }, { "docid": "MED-2574", "text": "Inositol hexaphosphate (IP(6)) is a naturally occurring polyphosphorylated carbohydrate, abundantly present in many plant sources and in certain high-fiber diets, such as cereals and legumes. In addition to being found in plants, IP(6) is contained in almost all mammalian cells, although in much smaller amounts, where it is important in regulating vital cellular functions such as signal transduction, cell proliferation, and differentiation. For a long time IP(6) has been recognized as a natural antioxidant. Recently IP(6) has received much attention for its role in cancer prevention and control of experimental tumor growth, progression, and metastasis. In addition, IP(6) possesses other significant benefits for human health, such as the ability to enhance immune system, prevent pathological calcification and kidney stone formation, lower elevated serum cholesterol, and reduce pathological platelet activity. In this review we show the efficacy and discuss some of the molecular mechanisms that govern the action of this dietary agent. Exogenously administered IP(6) is rapidly taken up into cells and dephosphorylated to lower inositol phosphates, which further affect signal transduction pathways resulting in cell cycle arrest. A striking anticancer action of IP(6) was demonstrated in different experimental models. In addition to reducing cell proliferation, IP(6) also induces differentiation of malignant cells. Enhanced immunity and antioxidant properties also contribute to tumor cell destruction. Preliminary studies in humans show that IP(6) and inositol, the precursor molecule of IP(6), appear to enhance the anticancer effect of conventional chemotherapy, control cancer metastases, and improve quality of life. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP(6) + inositol holds great promise in our strategies for cancer prevention and therapy. There is clearly enough evidence to justify the initiation of full-scale clinical trials in humans.", "title": "Protection against cancer by dietary IP6 and inositol." }, { "docid": "MED-4114", "text": "Induced apoptosis of autoreactive T-lymphocyte precursors in the thymus is crucial for the prevention of autoimmune disorders. IGF-I and prolactin, which are lymphocyte growth factors, may have the potential to suppress apoptosis in thymocytes and thus encourage autoimmunity; conversely, dietary fish oil rich in omega-3 fats appears to upregulate apoptosis in lymphocytes. Since whole-food vegan diets may downregulate systemic IGF-I activity, it is proposed that such a diet, in conjunction with fish oil supplementation and treatment with dopamine agonists capable of suppressing prolactin secretion, may have utility for treating and preventing autoimmune disorders. This prediction is consistent with the extreme rarity of autoimmune disorders among sub-Saharan black Africans as long as they followed their traditional quasi-vegan lifestyles, and with recent ecologic studies correlating risks for IDDM and for multiple sclerosis mortality with animal product and/or saturated fat consumption. Moreover, there is evidence that vegan or quasi-vegan diets are useful in the management of rheumatoid arthritis, multiple sclerosis, and possibly SLE. The dopamine agonist bromocryptine exerts anti-inflammatory effects in rodent models of autoimmunity, and there is preliminary evidence that this drug may be clinically useful in several human autoimmune diseases; better tolerated D2-specific agonists such as cabergoline may prove to be more practical for use in therapy. The moderate clinical utility of supplemental fish oil in rheumatoid arthritis and certain other autoimmune disorders is documented. It is not unlikely that extra-thymic anti-inflammatory effects contribute importantly to the clinical utility of vegan diets, bromocryptine, and fish oil in autoimmunity. The favorable impact of low latitude or high altitude on autoimmune risk may be mediated by superior vitamin D status, which is associated with decreased secretion of parathyroid hormone; there are theoretical grounds for suspecting that parathyroid hormone may inhibit apoptosis in thymocytes. Androgens appear to up-regulate thymocyte apoptosis, may be largely responsible for the relative protection from autoimmunity enjoyed by men, and merit further evaluation for the management of autoimmunity in women. It will probably prove more practical to prevent autoimmune disorders than to reverse them once established; a whole-food vegan diet, coupled with fish oil and vitamin D supplementation, may represent a practical strategy for achieving this prevention, while concurrently lowering risk for many other life-threatening 'Western' diseases. Copyright 2001 Harcourt Publishers Ltd.", "title": "Upregulation of lymphocyte apoptosis as a strategy for preventing and treating autoimmune disorders: a role for whole-food vegan diets, fish oil an..." }, { "docid": "MED-2816", "text": "Plants contain numerous polyphenols, which have been shown to reduce inflammation and hereby to increase resistance to disease. Examples of such polyphenols are isothiocyanates in cabbage and broccoli, epigallocatechin in green tee, capsaicin in chili peppers, chalones, rutin and naringenin in apples, resveratrol in red wine and fresh peanuts and curcumin/curcuminoids in turmeric. Most diseases are maintained by a sustained discreet but obvious increased systemic inflammation. Many studies suggest that the effect of treatment can be improved by a combination of restriction in intake of proinflammatory molecules such as advanced glycation end products (AGE), advanced lipoperoxidation end products (ALE), and rich supply of antiinflammatory molecules such as plant polyphenols. To the polyphenols with a bulk of experimental documentation belong the curcuminoid family and especially its main ingredient, curcumin. This review summarizes the present knowledge about these turmericderived ingredients, which have proven to be strong antioxidants and inhibitors of cyclooxigenase-2 (COX-2), lipoxygenase (LOX) and nuclear factor kappa B (NF-kappaB) but also AGE. A plethora of clinical effects are reported in various experimental diseases, but clinical studies in humans are few. It is suggested that supply of polyphenols and particularly curcuminoids might be value as complement to pharmaceutical treatment, but also prebiotic treatment, in conditions proven to be rather therapy-resistant such as Crohn's, long-stayed patients in intensive care units, but also in conditions such as cancer, liver cirrhosis, chronic renal disease, chronic obstructive lung disease, diabetes and Alzheimer's disease.", "title": "Plant-derived health: the effects of turmeric and curcuminoids." }, { "docid": "MED-2780", "text": "Spices, such as cinnamon, cloves, cardamom, garlic, ginger, cumin, coriander and turmeric are used all over the world as flavouring and colouring ingredients in Indian foods. Previous studies have shown that spices contain variable amounts of total oxalates but there are few reports of soluble oxalate contents. In this study, the total, soluble and insoluble oxalate contents of ten different spices commonly used in Indian cuisine were measured. Total oxalate content ranged from 194 (nutmeg) to 4,014 (green cardamom) mg/100 g DM, while the soluble oxalate contents ranged from 41 (nutmeg) to 3,977 (green cardamom) mg/100 g DM. Overall, the percentage of soluble oxalate content of the spices ranged from 4.7 to 99.1% of the total oxalate content which suggests that some spices present no risk to people liable to kidney stone formation, while other spices can supply significant amounts of soluble oxalates and therefore should be used in moderation.", "title": "Total and soluble oxalate content of some Indian spices." }, { "docid": "MED-2800", "text": "The management of osteoarthritis represents a real challenge. This complex and multi-factorial disease evolves over decades and requires not only the alleviation of symptoms, i.e. pain and joint function but also the preservation of articular structure without side effects. Nutraceuticals are good candidates for the management of OA due to their safety profile and potential efficacy. However, they are not part of the treatment guidelines and published recommendations. Curcumin is the yellow pigment isolated from the rhizomes of Curcuma longa, commonly known as turmeric. Curcumin is a highly pleiotropic molecule with an excellent safety profile. Strong molecular evidence has been published for its potency to target multiple inflammatory diseases. However, naturally occurring curcumin cannot achieve its optimum therapeutic outcomes due to its low solubility and poor bioavailability. Nevertheless, curcumin presents great potential for treating OA and has been categorized as having preclinical evidence of efficacy. This review aimed at gathering most of the available information to document the potential efficacy of curcumin based on the results obtained in in vitro models of cartilage and osteoarthritis and in other diseases.", "title": "Curcumin: a new paradigm and therapeutic opportunity for the treatment of osteoarthritis: curcumin for osteoarthritis management" }, { "docid": "MED-2582", "text": "Nonstarch polysaccharide (NSP) intake was measured in representative samples of 30 men aged 50-59 in 2 urban and 2 rural Scandinavian populations that exhibited a 3-4 fold difference in incidence of large bowel cancer. Intake was measured by chemical analysis of complete duplicate portions of all food eaten over one day by each individual. NSP intakes showed a rural-urban gradient, with 18.4 +/- 7.8 g/day in rural Finland and 18.0 +/- 6.4 g/day in rural Denmark versus 14.5 +/- 5.4 g/day in urban Finland and 13.2 +/- 4.8 g/day in urban Denmark. NSP intakes were also calculated (using food tables) from weighed food records kept over 4 days, one of which was the day on which the duplicate collection was made. Intakes were 2-2.5 g/day higher with this method than with direct chemical analysis, mainly because published tables of values have become outdated and inaccurate as a result of improved methods for measuring NSP in food. Individual variation from day to day in NSP intake was considerable. Average NSP intake and intake of some of its component sugars were inversely related to colon cancer incidence in this geographical comparison. To show a relationship at the individual level between diet and cancer risk in a prospective study would require detailed and accurate methods for the assessment of NSP consumption.", "title": "Nonstarch polysaccharide consumption in four Scandinavian populations." }, { "docid": "MED-2782", "text": "BACKGROUND & AIMS: Curcumin is a biologically active phytochemical substance present in turmeric and has pharmacologic actions that might benefit patients with ulcerative colitis (UC). The aim in this trial was to assess the efficacy of curcumin as maintenance therapy in patients with quiescent ulcerative colitis (UC). METHODS: Eighty-nine patients with quiescent UC were recruited for this randomized, double-blind, multicenter trial of curcumin in the prevention of relapse. Forty-five patients received curcumin, 1g after breakfast and 1g after the evening meal, plus sulfasalazine (SZ) or mesalamine, and 44 patients received placebo plus SZ or mesalamine for 6 months. Clinical activity index (CAI) and endoscopic index (EI) were determined at entry, every 2 months (CAI), at the conclusion of 6-month trial, and at the end of 6-month follow-up. RESULTS: Seven patients were protocol violators. Of 43 patients who received curcumin, 2 relapsed during 6 months of therapy (4.65%), whereas 8 of 39 patients (20.51%) in the placebo group relapsed (P=.040). Recurrence rates evaluated on the basis of intention to treat showed significant difference between curcumin and placebo (P=.049). Furthermore, curcumin improved both CAI (P=.038) and EI (P=.0001), thus suppressing the morbidity associated with UC. A 6-month follow-up was done during which patients in both groups were on SZ or mesalamine. Eight additional patients in the curcumin group and 6 patients in the placebo group relapsed. CONCLUSIONS: Curcumin seems to be a promising and safe medication for maintaining remission in patients with quiescent UC. Further studies on curcumin should strengthen our findings.", "title": "Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial." }, { "docid": "MED-2785", "text": "Curcumin is extensively used as a spice and pigment and has anticarcinogenic effects that could be linked to its antioxidant properties. However, some studies suggest that this natural compound possesses both pro- and antioxidative effects. In this study, we found that curcumin induced DNA damage to both the mitochondrial and nuclear genomes in human hepatoma G2 cells. Using quantitative polymerase chain reaction and immunocytochemistry staining of 8-hydroxydeoxyguanosine, we demonstrated that curcumin induced dose-dependent damage in both the mitochondrial and nuclear genomes and that the mitochondrial damage was more extensive. Nuclear DNA fragments were also evident in comet assays. The mechanism underlies the elevated level of reactive oxygen species and lipid peroxidation generated by curcumin. The lack of DNA damage at low doses suggested that low levels of curcumin does not induce DNA damage and may play an antioxidant role in carcinogenesis. But at high doses, we found that curcumin imposed oxidative stress and damaged DNA. These data reinforce the hypothesis that curcumin plays a conflicting dual role in carcinogenesis. Also, the extensive mitochondrial DNA damage might be an initial event triggering curcumin-induced cell death.", "title": "Mitochondrial and nuclear DNA damage induced by curcumin in human hepatoma G2 cells." }, { "docid": "MED-2559", "text": "Inositol hexaphosphate (IP6) has anti-cancer properties, but recently other extracellular functions have been observed for IP6, including enhancing superoxide production and phagocytosis by neutrophils in the presence of microbial stimuli. This study investigated other inflammatory functions of IP6 on adherent neutrophils. The effect of IP6 on the release of IL-8, tumour necrosis factor (TNF-alpha) and IL-6 by neutrophils attached to either plastic or laminin for up to 6 hours in response to stimulation with lipopolysaccharide or N-formyl-Met-Leu-Phe (fMLP) was investigated. An increase in IL-8 secretion by stimulated cells occurred in the presence of IP6. The incubation of cells attached to laminin with IP6 alone (100-250 BM) did not effect cell morphology, but in the presence of 10(-7) M fMLP altered cell shape. A direct effect of IP6 on cell function was to trigger a sustained assembly of F-actin. Thus, exposure of neutrophils to low levels of IP6 appears to modulate selective neutrophil functions.", "title": "Effect of IP6 on human neutrophil cytokine production and cell morphology." }, { "docid": "MED-2568", "text": "Inositol hexaphosphate (InsP6 or IP6) is ubiquitous. At 10 microM to 1 mM concentrations, IP6 and its lower phosphorylated forms (IP(1-5)) as well as inositol (Ins) are contained in most mammalian cells, wherein they are important in regulating vital cellular functions such as signal transduction, cell proliferation and differentiation. A striking anti-cancer action of IP6 has been demonstrated both in vivo and in vitro, which is based on the hypotheses that exogenously administered IP6 may be internalized, dephosphorylated to IP(1-5), and inhibit cell growth. There is additional evidence that Ins alone may further enhance the anti-cancer effect of IP6. Besides decreasing cellular proliferation, IP6 also causes differentiation of malignant cells often resulting in a reversion to normal phenotype. These data strongly point towards the involvement of signal transduction pathways, cell cycle regulatory genes, differentiation genes, oncogenes and perhaps, tumor suppressor genes in bringing about the observed anti-neoplastic action of IP6.", "title": "IP6: a novel anti-cancer agent." }, { "docid": "MED-2575", "text": "Introduction Matrix metalloproteinases (MMPs) have repeatedly been shown to play a very active role in extracellular matrix degradation associated with tumor invasion and metastasis. Tissue inhibitors of MMPs (TIMPs) are well-known for their ability to inhibit MMP activity thereby inhibiting malignant progression. Inositol hexaphosphate (IP6 phytic acid) has been recognized to have both preventive and therapeutic effects against various cancers including that of colon. In in vitro studies, IP6 has been demonstrated to inhibit cancer cell adhesion and migration. In the present study, the effect of IP6 on the expression of MMP and TIMP genes was evaluated in unstimulated and IL-1β-stimulated colon cancer cell line Caco-2. Materials and methods Real-time QRT-PCR was used to validate the transcription level of selected MMP and TIMP genes in Caco-2 cells after treatment with 1 ng/ml of IL-1β, 2.5 mM of IP6, and both for 6, 12, and 24 h. Results Stimulation of cells with IL-1β only resulted in an overexpression of MMP and their TIMP mRNAs. A significant decrease in MMP-13, MMP-3, MMP-2, and TIMP-1 basal expression was achieved by IP6. IP6 was also an efficient downregulator of MMP-1, MMP-9, and TIMP-2 genes transcription stimulated by IL-1β in 6 h lasting culture. After 12 h, IL-1β-induced MMP-2 mRNA expression was significantly reduced by IP6. Conclusion Proinflammatory cytokine IL-1β upregulates MMP and TIMP mRNAs expression in colon cancer epithelial cells Caco-2. IP6 (2.5 mM) influences constitutive expression of both MMP and TIMP genes and downregulates IL-1β stimulated transcription of some of these genes. IP6 exerts its anti-metastatic activity through modulation of MMP and TIMP genes expression to prevent cancer cell migration and invasion.", "title": "The effect of inositol hexaphosphate on the expression of selected metalloproteinases and their tissue inhibitors in IL-1β-stimulated colon cancer cells" }, { "docid": "MED-2791", "text": "Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.", "title": "Bioavailability of curcumin: problems and promises." }, { "docid": "MED-2807", "text": "In a previous three-month study of Meriva, a proprietary curcumin-phosphatidylcholine phytosome complex, decreased joint pain and improvement in joint function were observed in 50 osteoarthritis (OA) patients. Since OA is a chronic condition requiring prolonged treatment, the long-term efficacy and safety of Meriva were investigated in a longer (eight months) study involving 100 OA patients. The clinical end points (Western Ontario and McMaster Universities [WOMAC] score, Karnofsky Performance Scale Index, and treadmill walking performance) were complemented by the evaluation of a series of inflammatory markers (interleukin [IL]-1beta, IL-6, soluble CD40 ligand [sCD40L], soluble vascular cell adhesion molecule (sVCAM)-1, and erythrocyte sedimentation rate [ESR]). This represents the most ambitious attempt, to date, to evaluate the clinical efficacy and safety of curcumin as an anti-inflammatory agent. Significant improvements of both the clinical and biochemical end points were observed for Meriva compared to the control group. This, coupled with an excellent tolerability, suggests that Meriva is worth considering for the long-term complementary management of osteoarthritis.", "title": "Efficacy and safety of Meriva®, a curcumin-phosphatidylcholine complex, during extended administration in osteoarthritis patients." }, { "docid": "MED-2578", "text": "The incidence of colonic cancer differs widely between various human populations. It has been suggested that dietary fiber content is of utmost importance and is inversely related to the occurrence of colonic cancer. However, high-fiber diets are not always correlated with low frequency of colonic cancer, suggesting the involvement of additional dietary constituents. Inositol hexaphosphate (phytic acid) is an abundant plant seed component present in many, but not all, fiber-rich diets. The authors have found that phytic acid is a potent inhibitor of iron-mediated generation of the hazardous oxidant, hydroxyl radical. Herein, the authors propose that inhibition of intracolonic hydroxyl radical generation, via the chelation of reactive iron by phytic acid, may help explain the suppression of colonic carcinogenesis and other inflammatory bowel diseases by diets rich in phytic acid.", "title": "Dietary suppression of colonic cancer. Fiber or phytate?" }, { "docid": "MED-2804", "text": "Osteoarthritis (OA) is the most common form of arthritis in the US, and a leading cause of disability. It is typically defined in epidemiologic studies on the basis of radiographic findings and consideration of symptoms. Its incidence and prevalence are rising, likely related to the aging of the population and increasing obesity. Risk factors for OA include a number of person-level factors, such as age, sex, obesity, and genetics, as well as joint-specific factors that are likely reflective of abnormal loading of the joints. A number of methodologic challenges exist in studying OA that can hamper our ability to identify pertinent relationships.", "title": "Epidemiology of OA" }, { "docid": "MED-2797", "text": "Osteoarthritis (OA) has long been considered a \"wear and tear\" disease leading to loss of cartilage. OA used to be considered the sole consequence of any process leading to increased pressure on one particular joint or fragility of cartilage matrix. Progress in molecular biology in the 1990s has profoundly modified this paradigm. The discovery that many soluble mediators such as cytokines or prostaglandins can increase the production of matrix metalloproteinases by chondrocytes led to the first steps of an \"inflammatory\" theory. However, it took a decade before synovitis was accepted as a critical feature of OA, and some studies are now opening the way to consider the condition a driver of the OA process. Recent experimental data have shown that subchondral bone may have a substantial role in the OA process, as a mechanical damper, as well as a source of inflammatory mediators implicated in the OA pain process and in the degradation of the deep layer of cartilage. Thus, initially considered cartilage driven, OA is a much more complex disease with inflammatory mediators released by cartilage, bone and synovium. Low-grade inflammation induced by the metabolic syndrome, innate immunity and inflammaging are some of the more recent arguments in favor of the inflammatory theory of OA and highlighted in this review. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.", "title": "Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!)." }, { "docid": "MED-2788", "text": "Turmeric root has been used medicinally in China and India for thousands of years. The active components are thought to be the curcuminoids, primarily curcumin, which is commonly available worldwide as a standardized extract. This article reviews the pharmacology of curcuminoids, their use and efficacy, potential adverse effects, and dosage and standardization. Preclinical studies point to mechanisms of action that are predominantly anti-inflammatory and antineoplastic, while early human clinical trials suggest beneficial effects for dyspepsia, peptic ulcer, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, uveitis, orbital pseudotumor, and pancreatic cancer. Curcumin is well-tolerated; the most common side effects are nausea and diarrhea. Theoretical interactions exist due to purported effects on metabolic enzymes and transport proteins, but clinical reports do not support any meaningful interactions. Nonetheless, caution, especially with chemotherapy agents, is advised. Late-phase clinical trials are still needed to confirm most beneficial effects.", "title": "Clinical utility of curcumin extract." }, { "docid": "MED-2602", "text": "In this study, we investigated the molecular pathways targeted by curcumin during apoptosis of human melanoma cell lines. We found that curcumin caused cell death in eight melanoma cell lines, four with wild-type and four with mutant p53. We demonstrate that curcumin-induced apoptosis is both dose- and time-dependent. We found that curcumin did not induce p53, suggesting that curcumin activates other apoptosis pathways. Our data show that curcumin activates caspases-3 and -8 but not caspase-9, supporting the rationale that apoptosis occurs via a membrane-mediated mechanism. Both a caspase-8 and broad-based caspase inhibitor, but not a caspase-9 specific inhibitor, suppressed curcumin-induced cell death. To further support our hypothesis that curcumin induces activation of a death receptor pathway, we show that curcumin induces Fas receptor aggregation in a FasL-independent manner and that low-temperature incubation, previously shown to inhibit receptor aggregation, prevented curcumin-induced cell death. Moreover, we demonstrate that expression of dominant negative FADD significantly inhibited curcumin-induced cell death. In addition, our results indicate that curcumin also blocks the NF-kappaB cell survival pathway and suppresses the apoptotic inhibitor, XIAP. Since melanoma cells with mutant p53 are strongly resistant to conventional chemotherapy, curcumin may overcome the chemoresistance of these cells and provide potential new avenues for treatment.", "title": "Curcumin induces apoptosis in human melanoma cells through a Fas receptor/caspase-8 pathway independent of p53." }, { "docid": "MED-5341", "text": "The present study investigated the effects of a diet and exercise intervention on known breast cancer (BCa) risk factors, including estrogen, obesity, insulin, and insulin-like growth factor-I (IGF-I), in overweight/obese, postmenopausal women. In addition, using the subjects' pre- and postintervention serum in vitro, serum-stimulated growth and apoptosis of three estrogen receptor-positive BCa cell lines were studied. The women where placed on a low-fat (10-15% kcal), high-fiber (30-40 g per 1,000 kcal/day) diet and attended daily exercise classes for 2 wk. Serum estradiol was reduced in the women on hormone treatment (HT; n = 28) as well as those not on HT (n = 10). Serum insulin and IGF-I were significantly reduced in all women, whereas IGF binding protein-1 was increased significantly. In vitro growth of the BCa cell lines was reduced by 6.6% for the MCF-7 cells, 9.9% for the ZR-75-1 cells, and 18.5% for the T-47D cells. Apoptosis was increased by 20% in the ZR-75-1 cells, 23% in the MCF-7 cells, and 30% in the T-47D cells (n = 12). These results show that a very-low-fat, high-fiber diet combined with daily exercise results in major reductions in risk factors for BCa while subjects remained overweight/obese. These in vivo serum changes slowed the growth and induced apoptosis in serum-stimulated BCa cell lines in vitro.", "title": "Effects of a low-fat, high-fiber diet and exercise program on breast cancer risk factors in vivo and tumor cell growth and apoptosis in vitro." }, { "docid": "MED-2579", "text": "There are now extensive scientific data suggesting the potential role of dietary and non-dietary phytochemicals in the prevention and control of prostate cancer (PCA) growth and progression. PCA is a disease of elderly male populations with a relatively slower rate of growth and progression as compared to most other cancers and, therefore, is a candidate disease for preventive intervention. Overall, PCA growth and progression involve aberrant mitogenic and survival signaling and deregulated cell cycle progression, accompanied by gradual accumulation of genetic and epigenetic changes over a period of years. Several mechanisms, including overexpression of growth, survival and angiogenic factors and their receptors, together with a loss/decrease of tumor suppressor p53, retinoblastoma and cyclin-dependent kinase inhibitor, have been implicated in PCA growth and progression. Therefore, phytochemicals targeting these molecular events could have a promising role in PCA prevention and/or therapy. Inositol hexaphosphate (IP6) is a major constituent of most cereals, legumes, nuts, oil seeds and soybean. Taken orally as an over-the-counter dietary/nutrient supplement, and is recognised as offering several health benefits without any known toxicity. In vitro anticancer efficacy of IP6 has been observed in many human, mouse and rat prostate cancer cells. Completed studies also show that oral feeding of IP6 inhibits human PCA xenograft growth in nude mice without toxicity. In a recently completed pilot study, we observed similar preventive effects of IP6 on prostate tumorigenesis in the TRAMP model. Mechanistic studies indicate that IP6 targets mitogenic and survival signaling, as well as cell cycle progression, in PCA cells. IP6 is also shown to target molecular events associated with angiogenesis. Moreover, IP6 has pleiotropic molecular targets for its overall efficacy against PCA and, therefore, could be a suitable candidate agent for preventive intervention of this malignancy in humans.", "title": "Prostate cancer and inositol hexaphosphate: efficacy and mechanisms." }, { "docid": "MED-2570", "text": "The functional properties, including antioxidant and chemopreventative capacities as well as the inhibitory effects on angiotensin-converting enzyme (ACE), α-glucosidase and pancreatic lipase, of three Australian-grown faba bean genotypes (Nura, Rossa and TF(Ic*As)*483/13) were investigated using an array of in vitro assays. Chromatograms of on-line post column derivatisation assay coupled with HPLC revealed the existence of active phenolics (hump) in the coloured genotypes, which was lacking in the white-coloured breeding line, TF(Ic*As)*483/13. Roasting reduced the phenolic content, and diminished antioxidant activity by 10-40 % as measured by the reagent-based assays (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and oxygen radical absorbance capacity) in all genotypes. Cell culture-based antioxidant activity assay (cellular antioxidant activity) showed an increase of activity in the coloured genotypes after roasting. Faba bean extracts demonstrated cellular protection ability against H₂O₂-induced DNA damage (assessed using RAW264.7 cells), and inhibited the proliferation of all human cancer cell lines (BL13, AGS, Hep G2 and HT-29) evaluated. However, the effect of faba bean extracts on the non-transformed human cells (CCD-18Co) was negligible. Flow cytometric analyses showed that faba bean extracts successfully induced apoptosis of HL-60 (acute promyelocytic leukaemia) cells. The faba bean extracts also exhibited ACE, α-glucosidase and pancreatic lipase inhibitory activities. Overall, extracts from Nura (buff-coloured) and Rossa (red-coloured) were comparable, while TF(Ic*As)*483/13 (white-coloured) contained the lowest phenolic content and exhibited the least antioxidant and enzyme inhibition activities. These results are important to promote the utilisation of faba beans in human diets for various health benefits.", "title": "In vitro investigations of the potential health benefits of Australian-grown faba beans (Vicia faba L.): chemopreventative capacity and inhibitory ..." }, { "docid": "MED-2817", "text": "Curcumin (diferuloylmethane), a yellow coloring agent extracted from turmeric is also used as a remedy for the treatment and prevention of inflammatory diseases. Acute and chronic inflammation is a major factor in the progression of obesity, type II diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Turmeric has a long history of use in Ayurvedic medicine for the treatment of inflammatory disorders. Recent studies on the efficacy and therapeutic applicability of turmeric have suggested that the active ingredient of tumeric is curcumin. Further, compelling evidence has shown that curcumin has the ability to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the current study, the anti-inflammatory effects of curcumin were evaluated relative to various chronic inflammatory diseases. Based on the available pharmacological data obtained from in vitro and in vivo research, as well as clinical trials, an opportunity exists to translate curcumin into clinics for the prevention of inflammatory diseases in the near future. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.", "title": "Curcumin in inflammatory diseases." }, { "docid": "MED-4113", "text": "Clonal deletion is arguably the most important mechanism of eliminating self-reactive thymocytes from the T-cell repertoire. Recent work has identified new players in this process. On the thymocyte side, several molecules have been newly implicated in the pathway from initial T-cell receptor signaling through to the final result: gene transcription and thymocyte apoptosis. In addition, several proapoptotic molecules have been found to be necessary for the death of self-reactive thymocytes. On the antigen-presenting cell side, the expression of peripheral self-antigens, regulated at least in part by the autoimmune regulator (AIRE) protein, is crucial for complete elimination of autoreactive thymocytes. The importance of thymic peripheral antigen expression and clonal deletion to self-tolerance is demonstrated in the autoimmune diseases autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy and type-1 diabetes mellitus.", "title": "Good riddance: Thymocyte clonal deletion prevents autoimmunity." }, { "docid": "MED-2598", "text": "Death receptors belong to the TNF receptor family and are characterised by an intracellular death domain that serves to recruit adapter proteins such as TRADD and FADD and cysteine proteases such as Caspase-8. Activation of Caspase-8 on the aggregated receptor leads to apoptosis. Triggering of death receptors is mediated through the binding of specific ligands of the TNF family, which are homotrimeric type-2 membrane proteins displaying three receptor binding sites. There are various means of modulating the activation of death receptors. The status of the ligand (membrane-bound vs. soluble) is critical in the activation of Fas and of TRAIL receptors. Cleavage of membrane-bound FasL to a soluble form (sFasL) does not affect its ability to bind to Fas but drastically decreases its cytotoxic activity. Conversely, cross-linking epitope-tagged sFasL with anti-tag antibodies to mimic membrane-bound ligand results in a 1000-fold increase in cytotoxicity. This suggests that more than three Fas molecules need to be aggregated to efficiently signal apoptosis. Death receptors can also be regulated by decoy receptors. The cytotoxic ligand TRAIL interacts with five receptors, only two of which (TRAIL-R1 and -R2) have a death domain. TRAIL-R3 is anchored to the membrane by a glycolipid and acts as a dominant negative inhibitor of TRAIL-mediated apoptosis when overexpressed on TRAIL-sensitive cells. Intracellular proteins interacting with the apoptotic pathway are potential modulators of death receptors. FLIP resembles Caspase-8 in structure but lacks protease activity. It interacts with both FADD and Caspase-8 to inhibits the apoptotic signal of death receptors and, at the same time, can activate other signalling pathways such as that leading to NF-kappa B activation.", "title": "Apoptosis induced by death receptors." }, { "docid": "MED-2803", "text": "Osteoarthritis is a condition caused in part by injury, loss of cartilage structure and function, and an imbalance in inflammatory and anti-inflammatory pathways. It primarily affects the articular cartilage and subchondral bone of synovial joints and results in joint failure, leading to pain upon weight bearing including walking and standing. There is no cure for osteoarthritis, as it is very difficult to restore the cartilage once it is destroyed. The goals of treatment are to relieve pain, maintain or improve joint mobility, increase the strength of the joints and minimize the disabling effects of the disease. Recent studies have shown an association between dietary polyphenols and the prevention of osteoarthritis-related musculoskeletal inflammation. This review discusses the effects of commonly consumed polyphenols, including curcumin, epigallocatechin gallate and green tea extract, resveratrol, nobiletin and citrus fruits, pomegranate, as well as genistein and soy protein, on osteoarthritis with an emphasis on molecular antiosteoarthritic mechanisms. Copyright © 2012 Elsevier Inc. All rights reserved.", "title": "Dietary polyphenols and mechanisms of osteoarthritis." }, { "docid": "MED-2830", "text": "OBJECTIVE: The aim of this work was to determine the bioavailability of herbs and spices after human consumption by measuring the ability to protect lymphocytes from an oxidative injury and by examining the impact on inflammatory biomarkers in activated THP-1 cells. METHODS: Ten to 12 subjects in each of 13 groups consumed a defined amount of herb or spice for 7 days. Blood was drawn from subjects before consumption and 1 hour after taking the final herb or spice capsules. Subject serum and various extractions of the herbs and spices were analyzed for antioxidant capacity by oxygen radical absorbance capacity (ORAC) analysis or by 1,1-diphenyl-2-picrylhydrzyl (DPPH). Subject peripheral blood mononuclear cells (PBMCs) in medium with10% autologous serum were incubated with hydrogen peroxide to induce DNA strand breaks. Subject serum was also used to treat activated THP-1 cells to determine relative quantities of 3 inflammatory cytokine (tumor necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and IL-6) mRNAs. RESULTS: Herbs and spices that protected PBMCs against DNA strand breaks were paprika, rosemary, ginger, heat-treated turmeric, sage, and cumin. Paprika also appeared to protect cells from normal apoptotic processes. Of the 3 cytokine mRNAs studied (TNF-α, IL-1α, and IL-6), TNF-α was the most sensitive responder to oxidized LDL-treated macrophages. Clove, ginger, rosemary, and turmeric were able to significantly reduce oxidized LDL-induced expression of TNF-α. Serum from those consuming ginger reduced all three inflammatory biomarkers. Ginger, rosemary, and turmeric showed protective capacity by both oxidative protection and inflammation measures. CONCLUSIONS: DNA strand breaks and inflammatory biomarkers are a good functional measure of a food's bioavailability.", "title": "Bioavailability of herbs and spices in humans as determined by ex vivo inflammatory suppression and DNA strand breaks." }, { "docid": "MED-4319", "text": "The article gives an overview of phytic acid in food and of its significance for human nutrition. It summarises phytate sources in foods and discusses problems of phytic acid/phytate contents of food tables. Data on phytic acid intake are evaluated and daily phytic acid intake depending on food habits is assessed. Degradation of phytate during gastro-intestinal passage is summarised, the mechanism of phytate interacting with minerals and trace elements in the gastro-intestinal chyme described and the pathway of inositol phosphate hydrolysis in the gut presented. The present knowledge of phytate absorption is summarised and discussed. Effects of phytate on mineral and trace element bioavailability are reported and phytate degradation during processing and storage is described. Beneficial activities of dietary phytate such as its effects on calcification and kidney stone formation and on lowering blood glucose and lipids are reported. The antioxidative property of phytic acid and its potentional anticancerogenic activities are briefly surveyed. Development of the analysis of phytic acid and other inositol phosphates is described, problems of inositol phosphate determination and detection discussed and the need for standardisation of phytic acid analysis in foods argued.", "title": "Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis." }, { "docid": "MED-2821", "text": "The purpose of this review is to summarize the pertinent literature published in the present era regarding the antiulcerogenic property of curcumin against the pathological changes in response to ulcer effectors (Helicobacter pylori infection, chronic ingestion of non-steroidal anti-inflammatory drugs, and exogenous substances). The gastrointestinal problems caused by different etiologies was observed to be associated with the alterations of various physiologic parameters such as reactive oxygen species, nitric oxide synthase, lipid peroxidation, and secretion of excessive gastric acid. Gastrointestinal ulcer results probably due to imbalance between the aggressive and the defensive factors. In 80% of the cases, gastric ulcer is caused primarily due to the use of non-steroidal anti-inflammatory category of drug, 10% by H. pylori, and about 8-10% by the intake of very spicy and fast food. Although a number of antiulcer drugs and cytoprotectants are available, all these drugs have side effects and limitations. In the recent years a widespread search has been launched to identify new antiulcer drugs from synthetic and natural resources. An Indian dietary derivative (curcumin), a yellow pigment found in the rhizome of Curcuma longa, has been widely used for the treatment of several diseases. Epidemiologically, it was suggested that curcumin might reduce the risk of inflammatory disorders, such as cancer and ulcer. These biological effects are attributed to its anti-inflammatory and antioxidant activities. It can, therefore, be reported from the literature that curcumin PRevents gastrointestinal-induced ulcer and can be recommended as a novel drug for ulcer treatment.", "title": "Turmeric (curcumin) remedies gastroprotective action" }, { "docid": "MED-4112", "text": "Co-stimulatory signals through the CD28 receptor enhance the survival of T cells that have their antigen receptor (TCR) engaged. Here we show that stimulation through the CD28 receptor in the absence of TCR engagement with either an anti-CD28 cross-linking antibody or the CD80 ligand transiently increases expression of the insulin-like growth factor-I receptor (IGF-IR) on T cells. Antibodies that block signaling through the IGF-IR decrease the survival of T cells activated through the TCR and CD28 in the presence of IL-2 by more than 50%, and also enhance susceptibility to Fas-induced apoptosis. CD28 stimulation increases IGF-IR expression on Jurkat cells, and exogenously added IGF-I can protect these cells from Fas-induced apoptosis. We conclude that CD28-mediated enhancement of IGF-IR expression provides activated T cells with essential survival signals that are independent of survival mediated by IL-2 and Bcl-xl.", "title": "The insulin-like growth factor-I receptor is regulated by CD28 and protects activated T cells from apoptosis." }, { "docid": "MED-2581", "text": "A hospital-based case-control study of diet and colorectal cancer was conducted among Chinese in Singapore (who constitute 77% of the population). A total of 203 cases and 425 controls were included. A history of the usual dietary intake one year prior to interview was taken using a quantitative food frequency questionnaire. Daily intakes of nutrients and selected food items were computed and stratified by tertiles of the control range, to assess risk in low-, medium- and high-intake categories. Effects were adjusted in analysis for age, sex, Chinese dialect group and occupation. For cancers of colon and rectum combined, significant observations were a protective effect of high cruciferous vegetable intake (OR = 0.50, p less than 0.01) and a predisposing effect of a high meat/vegetable consumption ratio (OR = 1.77, p less than 0.05). Similar results were observed for colon cancer alone. For rectal cancer alone (only 71 cases), significant (p less than 0.05) protective effects were observed for high intakes of protein (OR = 0.61), fibre (OR = 0.46), beta-carotene (OR = 0.54), cruciferous vegetables (OR = 0.51) and total vegetables (OR = 0.51). When further assessed by multiple logistic regression, tests for trend and assessment of risk in the extreme highest and lowest quintiles of the control range, the factors consistently significant were cruciferous vegetable intake and the meat/vegetable ratio. A particularly high relative risk was also noted in association with low coffee consumption (OR = 1.59, with p less than 0.05 for trend). No consistent trends were noted for fat or fibre intakes. For non-dietary variables investigated, a history of cholecystectomy increased the risk of both cancers combined (OR = 3.43, p less than 0.05) and colon cancer alone (OR = 4.39, p less than 0.01). This study in an Asian population of countries of Southern and Eastern Asia newly undergoing industrialization and in which rapid economic change is reflected in changing cancer patterns, suggests that the protective effects of certain dietary constituents, notably the cruciferous vegetables, may be more important than the hitherto stressed carcinogenic potential of fat and protein.", "title": "Colorectal cancer and diet in an Asian population--a case-control study among Singapore Chinese." }, { "docid": "MED-2603", "text": "FAS-associated protein with death domain (FADD) is the key adaptor protein transmitting apoptotic signals mediated by the main death receptors (DRs). Besides being an essential instrument in cell death, FADD is also implicated in proliferation, cell cycle progression, tumor development, inflammation, innate immunity, and autophagy. Recently, many of these new functions of FADD were shown to be independent of DRs. Moreover, FADD function is dictated by protein localization and phosphorylation state. Thus, FADD is a crucial and unique controller of many essential cellular processes. The full understanding of the networks dictating the ultimate function of FADD may provide a new paradigm for other multifaceted proteins. Copyright 2010 Elsevier Ltd. All rights reserved.", "title": "FADD: a regulator of life and death." }, { "docid": "MED-2808", "text": "Chemotherapy remains the core of anticancer treatment. However, despite the tremendous strides made in the development of targeted anticancer therapies, emergence of resistance to chemotherapeutic drugs is still a major obstacle in the successful management of resistant tumours. Therefore, profound investigation into the in-depth molecular mechanisms of drug resistance is essential and may hopefully translate into effective therapies that can flip the switch from drug resistance to susceptibility. Mechanistically, resistance phenomena may be explained by (i) overexpression of drug efflux pumps, (ii) enhanced drug detoxification, (iii) rapid DNA repair efficiency, (iv) defects in apoptosis regulation, and (v) active cell survival signals. Several adverse effects associated with multidrug resistance and the need for safe multi-targeted anticancer drugs instigated the use of the phytochemical, curcumin, the yellow pigment of the spice turmeric, which has pleotropic activities. We performed a structured literature review using PubMed and Medline searches with secondary review of cited publications, identifying studies on the role of curcumin in conquering drug resistance in cancer. This review describes how curcumin sensitizes cancer cells through regulation of multiple multidrug resistance pathways, thus employing one drug for multiple targets. Curcumin helps the cancer cells to regain their 'forgotten' apoptosis, modulates drug-target interaction at different levels, restrains survival pathways when their proteins are overexpressed, and finds an alternate way to carry forward the process of sensitization of different resistant tumours. Additionally, the review dissects the role of curcumin, if any, in targeting the major culprit of drug resistance, cancer stem cells (CSC), thereby circumventing resistance. Taken together, this review strongly suggests that curcumin is a promising chemosensitizing agent and that the unique properties of curcumin may be exploited for successful management of resistant tumours.", "title": "Death by design: where curcumin sensitizes drug-resistant tumours." }, { "docid": "MED-4115", "text": "Cui and associates show that healthy individuals have natural autoantibodies (NAAs) specific for myeloperoxidase, proteinase 3, and glomerular basement membrane (GBM) with the same specificity as anti-neutrophil cytoplasmic antibodies and anti-GBM antibodies that are pathogenic. Although Ehrlich proposed horror autotoxicus and Burnet envisioned elimination of forbidden clones, NAAs are present in all healthy individuals and play beneficial homeostatic roles. Pathogenic autoimmunity is dysregulation of natural homeostatic autoimmunity rather than onset of a previously absent self-recognition.", "title": "The rise and fall of horror autotoxicus and forbidden clones." }, { "docid": "MED-2580", "text": "Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial–based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18–0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial–based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence.", "title": "High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial" }, { "docid": "MED-2823", "text": "Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical which has a variety of biological activities: anti-inflammatory and anti-oxidative. In this review we discuss the biological mechanisms and possible clinical effects of curcumin treatment on cancer therapy, and neurodegenerative diseases such as Alzheimer's Disease, with particular attention to the cell death processes induced by curcumin. Since oxidative stress and inflammation are major determinants of the aging process, we also argue that curcumin can have a more general effect that slows down the rate of aging. Finally, the effects of curcumin can be described as xenohormetic, since it activates a sort of stress response in mammalian cells.", "title": "Curcumin in Cell Death Processes: A Challenge for CAM of Age-Related Pathologies" }, { "docid": "MED-2607", "text": "Numerous natural compounds have been extensively investigated for their potential for cancer prevention over decades. Curcumin, from Curcuma longa, is a highly promising natural compound that can be potentially used for chemoprevention of multiple cancers. Curcumin modulates multiple molecular pathways involved in the lengthy carcinogenesis process to exert its chemopreventive effects through several mechanisms: promoting apoptosis, inhibiting survival signals, scavenging reactive oxidative species (ROS), and reducing the inflammatory cancer microenvironment. Curcumin fulfills the characteristics for an ideal chemopreventive agent with its low toxicity, affordability, and easy accessibility. Nevertheless, the clinical application of curcumin is currently compromised by its poor bioavailability. Here we review the potential of curcumin in cancer prevention, its molecular targets, and action mechanisms. Finally, we suggest specific recommendations to improve its efficacy and bioavailability for clinical applications.", "title": "New perspectives of curcumin in cancer prevention" }, { "docid": "MED-2799", "text": "Objective: To compare selected immunohistological features of inflammation in synovial tissue from patients with early and late osteoarthritis (OA). Methods: Synovial tissue samples were obtained from 10 patients with knee pain, normal radiographs, and arthroscopic manifestations of OA (early OA), and from 15 patients with OA undergoing knee joint arthroplasty (late OA). Conventional immunohistochemical techniques were used to measure microscopic manifestations of inflammation. The inflammatory cell infiltrate, blood vessel formation, and angiogenic factors, NF-κB activation, expression of tumour necrosis factor α (TNFα) and interleukin 1ß (IL1ß), and the presence of cyclo-oxygenase (COX)-1 and COX-2 were quantified. Fibroblast-like synoviocytes (FLS) were isolated from early and late OA tissue samples to compare in vitro production of prostaglandin E2 (PGE2) Results: Synovial tissue from patients with early OA demonstrated significantly greater CD4+ (p = 0.017) and CD68+ (p<0.001) cell infiltration, blood vessel formation (p = 0.01), vascular endothelial growth factor (p = 0.001), and intercellular adhesion molecule-1 expression (p<0.001). Numbers of cells producing TNFα and IL1ß were also significantly greater in early OA (p<0.001). Manifestations of inflammation in early OA were associated with increased expression of the NF-κB1 (p<0.001) and RelA (p = 0.015) subunits, and with increased COX-2 expression (p = 0.04). Cytokine-induced PGE2 production by cultured FLS was similar in both groups. Conclusion: Increased mononuclear cell infiltration and overexpression of mediators of inflammation were seen in early OA, compared with late OA. Isolated FLS were functionally similar in both groups, consistent with microenvironmental differences in the synovial tissue during different phases of OA. These observations may have important therapeutic implications for some patients during the early evolution of OA.", "title": "Synovial tissue inflammation in early and late osteoarthritis" }, { "docid": "MED-2577", "text": "A case-control study probing the role of diet on the incidence of colorectal cancer was undertaken in Athens, Greece, in a population characterized by ethnic homogeneity but substantial heterogeneity with respect to dietary habits. The case series consisted of 100 consecutive patients with histologically confirmed colorectal cancer admitted to two large hospitals of Athens during a 16-month period; the control series consisted of orthopaedic patients, admitted to the same hospitals during the same time period, individually matched to the index cases by age and sex. Dietary histories concerning the frequency of consumption (per month or per week) of about 80 food items were obtained by the same interviewer. Cases reported significantly less frequent consumption of vegetables (particularly beets, spinach, lettuce and cabbage) and, independently, significantly more frequent consumption of meat (notably lamb and beef). Between the two extremes (high-vegetable, low-meat diet versus high-meat, low-vegetable diet) a risk ratio of about 8 appears to exist, sufficient (in size and direction) to explain a substantial part of the international variation in the incidence of colorectal cancer. Significant associations were not found with beer or other alcoholic beverages, and significant interactions were not noted with respect to age, sex and anatomic localization (colon vs. rectum).", "title": "Diet and colorectal cancer: a case-control study in Greece." }, { "docid": "MED-2571", "text": "Background Prospective, randomized, pilot clinical study was conducted to evaluate the beneficial effects of inositol hexaphosphate (IP6) + Inositol in breast cancer patients treated with adjuvant therapy. Patients and methods Patients with invasive ductal breast cancer where polychemotherapy was indicated were monitored in the period from 2005-2007. Fourteen patients in the same stage of ductal invasive breast cancer were involved in the study, divided in two randomized groups. One group was subjected to take IP6 + Inositol while the other group was taking placebo. In both groups of patients the same laboratory parameters were monitored. When the treatment was finished, all patients have filled questionnaires QLQ C30 and QLQ-BR23 to determine the quality of life. Results Patients receiving chemotherapy, along with IP6 + Inositol did not have cytopenia, drop in leukocyte and platelet counts. Red blood cell counts and tumor markers were unaltered in both groups. However, patients who took IP6 + Inositol had significantly better quality of life (p = 0.05) and functional status (p = 0.0003) and were able to perform their daily activities. Conclusion IP6 + Inositol as an adjunctive therapy is valuable help in ameliorating the side effects and preserving quality of life among the patients treated with chemotherapy.", "title": "Efficacy of IP6 + inositol in the treatment of breast cancer patients receiving chemotherapy: prospective, randomized, pilot clinical study" }, { "docid": "MED-2811", "text": "Inflammatory bowel disease (IBD) comprising of ulcerative colitis (UC) and Crohn's disease (CD) is a major ailment affecting the small and large bowel. In clinics, IBD is treated using 5-amninosalicylates, antibiotics, the steroids and immunomodulators. Unfortunately, the long term usages of these agents are associated with undue side effects and compromise the therapeutic advantage. Accordingly, there is a need for novel agents that are effective, acceptable and non toxic to humans. Preclinical studies in experimental animals have shown that curcumin, an active principle of the Indian spice turmeric (Curcuma longa Linn) is effective in preventing or ameliorating UC and inflammation. Over the last few decades there has been increasing interest in the possible role of curcumin in IBD and several studies with various experimental models of IBD have shown it to be effective in mediating the inhibitory effects by scavenging free radicals, increasing antioxidants, influencing multiple signaling pathways, especially the kinases (MAPK, ERK), inhibiting myeloperoxidase, COX-1, COX-2, LOX, TNF-α, IFN-γ, iNOS; inhibiting the transcription factor NF-κB. Clinical studies have also shown that co-administration of curcumin with conventional drugs was effective, to be well-tolerated and treated as a safe medication for maintaining remission, to prevent relapse and improve clinical activity index. Large randomized controlled clinical investigations are required to fully understand the potential of oral curcumin for treating IBD.", "title": "Curcumin, an active component of turmeric in the prevention and treatment of ulcerative colitis: preclinical and clinical observations." }, { "docid": "MED-2818", "text": "Curcumin is a polyphenol derived from the herbal remedy and dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties following oral or topical administration. Apart from curcumin's potent antioxidant capacity at neutral and acidic pH, its mechanisms of action include inhibition of several cell signalling pathways at multiple levels, effects on cellular enzymes such as cyclooxygenase and glutathione S-transferases, immuno-modulation and effects on angiogenesis and cell-cell adhesion. Curcumin's ability to affect gene transcription and to induce apoptosis in preclinical models is likely to be of particular relevance to cancer chemoprevention and chemotherapy in patients. Although curcumin's low systemic bioavailability following oral dosing may limit access of sufficient concentrations for pharmacological effect in certain tissues, the attainment of biologically active levels in the gastrointestinal tract has been demonstrated in animals and humans. Sufficient data currently exist to advocate phase II clinical evaluation of oral curcumin in patients with invasive malignancy or pre-invasive lesions of the gastrointestinal tract, particularly the colon and rectum.", "title": "Curcumin: the story so far." }, { "docid": "MED-2792", "text": "Two populations of immigrants to London and to the West Indies from the Indian subcontinent have higher than expected morbidity and mortality from atherosclerosis but do not show the commonly accepted major risk factors. This study investigated the hypothesis that ghee, a clarified butter product prized in Indian cooking, contains cholesterol oxides and could therefore be an important source of dietary exposure to cholesterol oxides and an explanation for the high atherosclerosis risk. Substantial amounts of cholesterol oxides were found in ghee (12.3% of sterols), but not in fresh butter, by thin-layer and high-performance-liquid chromatography. Dietary exposure to cholesterol oxides from ghee may offer a logical explanation for the high frequency of atherosclerotic complications in these Indian populations.", "title": "Cholesterol oxides in Indian ghee: possible cause of unexplained high risk of atherosclerosis in Indian immigrant populations." }, { "docid": "MED-4390", "text": "The medicinal properties of curcumin obtained from Curcuma longa L. cannot be utilised because of poor bioavailability due to its rapid metabolism in the liver and intestinal wall. In this study, the effect of combining piperine, a known inhibitor of hepatic and intestinal glucuronidation, was evaluated on the bioavailability of curcumin in rats and healthy human volunteers. When curcumin was given alone, in the dose 2 g/kg to rats, moderate serum concentrations were achieved over a period of 4 h. Concomitant administration of piperine 20 mg/kg increased the serum concentration of curcumin for a short period of 1-2 h post drug. Time to maximum was significantly increased (P < 0.02) while elimination half life and clearance significantly decreased (P < 0.02), and the bioavailability was increased by 154%. On the other hand in humans after a dose of 2 g curcumin alone, serum levels were either undetectable or very low. Concomitant administration of piperine 20 mg produced much higher concentrations from 0.25 to 1 h post drug (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h), the increase in bioavailability was 2000%. The study shows that in the dosages used, piperine enhances the serum concentration, extent of absorption and bioavailability of curcumin in both rats and humans with no adverse effects.", "title": "Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers." }, { "docid": "MED-2584", "text": "In a 6-year prospective study, the authors examined the relation between diet and incident colon cancer among 32,051 non-Hispanic white cohort members of the Adventist Health Study (California, 1976-1982) who, at baseline, had no documented or reported history of cancer. The risk of colon cancer was determined from proportional hazards regression with adjustment for age and other covariates. The authors found a positive association with total meat intake (risk ratio (RR) for > or =1 time/week vs. no meat intake = 1.85, 95% confidence interval (CI) 1.19-2.87; p for trend = 0.01) and, among subjects who favored specific types of meat, positive associations with red meat intake (RR for > or =1 time/week vs. no red meat intake = 1.90, 95% CI 1.16-3.11; p for trend = 0.02) and white meat intake (RR for > or =1 time/week vs. no white meat intake = 3.29, 95% CI 1.60-6.75; p for trend = 0.006). An inverse association with legume intake (RR for >2 times/week vs. <1 time/week = 0.53, 95% CI 0.33-0.86; p for trend = 0.03) was observed. Among men, a positive association with body mass index was observed (relative to the RR for tertile III (>25.6 kg/m2) vs. tertile I (<22.5 kg/m2) = 2.63, 95% CI 1.12-6.13; p for trend = 0.05). A complex relation was identified whereby subjects exhibiting a high red meat intake, a low legume intake, and a high body mass experienced a more than threefold elevation in risk relative to all other patterns based on these variables. This pattern of putative risk factors would likely contribute to increases in both insulin resistance (high body mass, high red meat intake) and glycemic load (low legume intake), a synergism that, if causal, implicates hyperinsulinemic exposure in colon carcinogenesis. The overall findings from this cohort identify both red meat intake and white meat intake as important dietary risk factors for colon cancer and raise the possibility that the risk due to red meat intake reflects a more complex etiology.", "title": "Dietary risk factors for colon cancer in a low-risk population." }, { "docid": "MED-2824", "text": "Cancer is primarily a disease of old age, and that life style plays a major role in the development of most cancers is now well recognized. While plant-based formulations have been used to treat cancer for centuries, current treatments usually involve poisonous mustard gas, chemotherapy, radiation, and targeted therapies. While traditional plant-derived medicines are safe, what are the active principles in them and how do they mediate their effects against cancer is perhaps best illustrated by curcumin, a derivative of turmeric used for centuries to treat a wide variety of inflammatory conditions. Curcumin is a diferuloylmethane derived from the Indian spice, turmeric (popularly called \"curry powder\") that has been shown to interfere with multiple cell signaling pathways, including cell cycle (cyclin D1 and cyclin E), apoptosis (activation of caspases and down-regulation of antiapoptotic gene products), proliferation (HER-2, EGFR, and AP-1), survival (PI3K/AKT pathway), invasion (MMP-9 and adhesion molecules), angiogenesis (VEGF), metastasis (CXCR-4) and inflammation (NF-kappaB, TNF, IL-6, IL-1, COX-2, and 5-LOX). The activity of curcumin reported against leukemia and lymphoma, gastrointestinal cancers, genitourinary cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers, and sarcoma reflects its ability to affect multiple targets. Thus an \"old-age\" disease such as cancer requires an \"age-old\" treatment.", "title": "Curcumin and cancer: an \"old-age\" disease with an \"age-old\" solution." }, { "docid": "MED-2783", "text": "Although much has been published about curcumin, which is obtained from turmeric, comparatively little is known about turmeric itself. Turmeric, a golden spice obtained from the rhizome of the plant Curcuma longa, has been used to give color and taste to food preparations since ancient times. Traditionally, this spice has been used in Ayurveda and folk medicine for the treatment of such ailments as gynecological problems, gastric problems, hepatic disorders, infectious diseases, and blood disorders. Modern science has provided the scientific basis for the use of turmeric against such disorders. Various chemical constituents have been isolated from this spice, including polyphenols, sesquiterpenes, diterpenes, triterpenoids, sterols, and alkaloids. Curcumin, which constitutes 2-5% of turmeric, is perhaps the most-studied component. Although some of the activities of turmeric can be mimicked by curcumin, other activities are curcumin-independent. Cell-based studies have demonstrated the potential of turmeric as an antimicrobial, insecticidal, larvicidal, antimutagenic, radioprotector, and anticancer agent. Numerous animal studies have shown the potential of this spice against proinflammatory diseases, cancer, neurodegenerative diseases, depression, diabetes, obesity, and atherosclerosis. At the molecular level, this spice has been shown to modulate numerous cell-signaling pathways. In clinical trials, turmeric has shown efficacy against numerous human ailments including lupus nephritis, cancer, diabetes, irritable bowel syndrome, acne, and fibrosis. Thus, a spice originally common in the kitchen is now exhibiting activities in the clinic. In this review, we discuss the chemical constituents of turmeric, its biological activities, its molecular targets, and its potential in the clinic. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.", "title": "Multitargeting by turmeric, the golden spice: From kitchen to clinic." }, { "docid": "MED-4544", "text": "Emblica officinalis Gaertn. or Phyllanthus emblica Linn, commonly known as Indian gooseberry or amla, is arguably the most important medicinal plant in the Indian traditional system of medicine, the Ayurveda. Various parts of the plant are used to treat a range of diseases, but the most important is the fruit. The fruit is used either alone or in combination with other plants to treat many ailments such as common cold and fever; as a diuretic, laxative, liver tonic, refrigerant, stomachic, restorative, alterative, antipyretic, anti-inflammatory, hair tonic; to prevent peptic ulcer and dyspepsia, and as a digestive. Preclinical studies have shown that amla possesses antipyretic, analgesic, antitussive, antiatherogenic, adaptogenic, cardioprotective, gastroprotective, antianemia, antihypercholesterolemia, wound healing, antidiarrheal, antiatherosclerotic, hepatoprotective, nephroprotective, and neuroprotective properties. In addition, experimental studies have shown that amla and some of its phytochemicals such as gallic acid, ellagic acid, pyrogallol, some norsesquiterpenoids, corilagin, geraniin, elaeocarpusin, and prodelphinidins B1 and B2 also possess antineoplastic effects. Amla is also reported to possess radiomodulatory, chemomodulatory, chemopreventive effects, free radical scavenging, antioxidant, anti-inflammatory, antimutagenic and immunomodulatory activities, properties that are efficacious in the treatment and prevention of cancer. This review for the first time summarizes the results related to these properties and also emphasizes the aspects that warrant future research to establish its activity and utility as a cancer preventive and therapeutic drug in humans.", "title": "Amla (Emblica officinalis Gaertn), a wonder berry in the treatment and prevention of cancer." }, { "docid": "MED-2801", "text": "Turmeric has been long recognized for its anti-inflammatory and health-promoting properties. Curcumin is one of the principal anti-inflammatory and healthful components of turmeric comprising 2-8% of most turmeric preparations. Experimental evidence supports the activity of curcumin in promoting weight loss and reducing the incidence of obesity-related diseases. With the discovery that obesity is characterized by chronic low-grade metabolic inflammation, phytochemicals like curcumin which have anti-inflammatory activity are being intensely investigated. Recent scientific research reveals that curcumin directly interacts with white adipose tissue to suppress chronic inflammation. In adipose tissue, curcumin inhibits macrophage infiltration and nuclear factor κB (NF-κB) activation induced by inflammatory agents. Curcumin reduces the expression of the potent proinflammatory adipokines tumor necrosis factor-α (TNFα), monocyte chemoattractant protein-1 (MCP-1), and plasminogen activator inhibitor type-1 (PAI-1), and it induces the expression of adiponectin, the principal anti-inflammatory agent secreted by adipocytes. Curcumin also has effects to inhibit adipocyte differentiation and to promote antioxidant activities. Through these diverse mechanisms curcumin reduces obesity and curtails the adverse health effects of obesity. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.", "title": "Curcumin and obesity." }, { "docid": "MED-2573", "text": "A significant anticancer activity of the naturally occurring carbohydrate inositol hexaphosphate (IP(6)) has been reported against numerous cancer models. Since tumors require angiogenesis for growth and metastasis, we hypothesize that IP(6) reduces tumor growth by inhibiting angiogenesis. Because angiogenesis depends on the interaction between endothelial and tumor cells, we investigated the effect of IP(6) on both. IP(6) inhibited the proliferation and induced the differentiation of endothelial cells in vitro; the growth of bovine aortic endothelial cells (BAECs) evaluated by MTT proliferation assay was inhibited in a dose-dependent manner (IC(50) = 0.74 mM). The combination of IP(6) and vasostatin, a calreticulin fragment with anti-angiogenic activity, was synergistically superior in growth inhibition than either compound. IP(6) inhibited human umbilical vein endothelial cell (HUVEC) tube formation (in vitro capillary differentiation) on a reconstituted extracellular matrix, Matrigel, and disrupted pre-formed tubes. IP(6) significantly reduced basic fibroblast growth factor (bFGF)-induced vessel formation (P < 0.01) in vivo in Matrigel plug assay. Exposure of HepG2, a human hepatoma cell line, to IP(6) for 8 h, resulted in a dose-dependent decrease in the mRNA levels of vascular endothelial growth factor (VEGF), as assessed by RT-PCR. IP(6) treatment of HepG2 cells for 24 h also significantly reduced the VEGF protein levels in conditioned medium, in a concentration-dependent manner (P = 0.012). Thus, IP(6) has an inhibitory effect on induced angiogenesis.", "title": "Anti-angiogenic activity of inositol hexaphosphate (IP6)." }, { "docid": "MED-2988", "text": "This review describes the present state of knowledge about phytic acid (phytate), which is often present in legume seeds. The antinutritional effects of phytic acid primarily relate to the strong chelating associated with its six reactive phosphate groups. Its ability to complex with proteins and particularly with minerals has been a subject of investigation from chemical and nutritional viewpoints. The hydrolysis of phytate into inositol and phosphates or phosphoric acid occurs as a result of phytase or nonenzymatic cleavage. Enzymes capable of hydrolysing phytates are widely distributed in micro-organisms, plants and animals. Phytases act in a stepwise manner to catalyse the hydrolysis of phytic acid. To reduce or eliminate the chelating ability of phytate, dephosphorylation of hexa- and penta-phosphate forms is essential since a high degree of phosphorylation is necessary to bind minerals. There are several methods of decreasing the inhibitory effect of phytic acid on mineral absorption (cooking, germination, fermentation, soaking, autolysis). Nevertheless, inositol hexaphosphate is receiving increased attention owing to its role in cancer prevention and/or therapy and its hypocholesterolaemic effect.", "title": "The role of phytic acid in legumes: antinutrient or beneficial function?" }, { "docid": "MED-2827", "text": "Alternative and complementary therapeutic approaches, such as the use of a wide array of herbal, nutritional, and physical manipulations, are becoming popular for relieving symptoms of osteoarthritis (OA). The present study evaluated the efficacy of soy protein (SP) supplementation in relieving the pain and discomfort associated with OA. One hundred and thirty-five free-living individuals (64 men and 71 women) with diagnosed OA or with self-reported chronic knee joint pain not attributed to injury or rheumatoid arthritis were recruited for this double-blind, placebo-controlled, parallel design study. Study participants were assigned randomly to consume 40 g of either supplemental SP or milk-based protein (MP) daily for 3 months. Pain, knee range of motion, and overall physical activity were evaluated prior to the start of treatment and monthly thereafter. Serum levels of glycoprotein 39 (YKL-40), a marker of cartilage degradation, and insulin-like growth factor-I (IGF-I), a growth factor associated with cartilage synthesis, were assessed at baseline and at the end of the study. Overall, SP improved OA-associated symptoms such as range of motion and several factors associated with pain and quality of life in comparison to MP. However, these beneficial effects were mainly due to the effect of SP in men rather than women. Biochemical markers of cartilage metabolism further support the efficacy of SP in men as indicated by a significant increase in serum level of IGF-I and a significant decrease in serum level of YKL-40 compared to MP. This study is the first to provide evidence of possible beneficial effects of SP in the management of OA. Examining and verifying the long-term effects of SP on improving symptoms of OA, particularly in men, is warranted.", "title": "Soy protein may alleviate osteoarthritis symptoms." } ]
[ { "docid": "MED-1819", "text": "Gemcitabine is a first line cancer drug widely used for the treatment of pancreatic cancer. However, its therapeutic efficiency is significantly limited by resistance of pancreatic cancer cells to this and other chemotherapeutic drugs. We have investigated the cytotoxic effect of Turmeric Force (TF), a supercritical and hydroethanolic extract of turmeric, alone and in combination with gemcitabine in two pancreatic carcinoma cell lines (BxPC3 and Panc-1). TF is highly cytotoxic to BxPC3 and Panc-1 cell lines with IC50 values of 1.0 and 1.22 microg/ml, respectively with superior cytotoxicity than curcumin. Gemcitabine IC50 value for both of these cell line is 0.03 microg/ml; however, 30-48% of the pancreatic cancer cells are resistant to gemcitabine even at concentrations >100 microg/ml. In comparison, TF induced cell death in 96% of the cells at 50 microg/ml. The combination of gemcitabine and TF was synergistic with IC90 levels achieved in both pancreatic cancer cell lines at lower concentrations. CalcuSyn analysis of cytotoxicity data showed that the Gemcitabine + Turmeric Force combination has strong synergism with combination index (CI) values of 0.050 and 0.183 in BxPC3 and Panc-1 lines, respectively at IC50 level. This synergistic effect is due to the increased inhibitory effect of the combination on nuclear factor-kappaB activity and signal transducer and activator of transcription factor 3 expression as compared to the single agent.", "title": "Potentiation of gemcitabine by Turmeric Force in pancreatic cancer cell lines." }, { "docid": "MED-4999", "text": "Curcumin (Cur), a component of turmeric (Curcuma longa), has been reported to exhibit antimetastatic activities, but the mechanisms remain unclear. Other curcuminoids present in turmeric, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) have not been investigated whether they exhibit antimetastatic activity to the same extent as curcumin. The regulation of matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA) play important role in cancer cell invasion by cleavage of extracellular matrix (ECM). In this line, we comparatively examined the influence of Cur, DMC and BDMC on the expressions of uPA, MMP-2, MMP-9, membrane Type 1 MMP (MT1-MMP), tissue inhibitor of metalloproteinases (TIMP-2), and in vitro invasiveness of human fibrosarcoma cells. The results indicate that the differential potency for inhibition of cancer cell invasion was BDMC> or =DMC>Cur, whereas the cell migration was not affected. Zymography analysis exhibited that curcumin, DMC and BDMC significantly decreased uPA, active-MMP-2 and MMP-9 but not pro-MMP-2 secretion from the cells in a dose-dependent manner, in which BDMC and DMC show higher potency than curcumin. The suppression of active MMP-2 level correlated with inhibition of MT1-MMP and TIMP-2 protein levels involved in pro-MMP-2 activation. Importantly, BDMC and DMC at 10 microM reduced MT1-MMP and TIMP-2 protein expression, but curcumin slightly reduced only MT1-MMP but not TIMP-2. In addition, three forms of curcuminoids significantly inhibited collagenase, MMP-2, and MMP-9 but not uPA activity. In summary, these data demonstrated that DMC and BDMC show higher antimetastasis potency than curcumin by the differentially down-regulation of ECM degradation enzymes.", "title": "Curcumin, demethoxycurcumin and bisdemethoxycurcumin differentially inhibit cancer cell invasion through the down-regulation of MMPs and uPA." }, { "docid": "MED-5001", "text": "We examine the possible evidence that the phytochemical curcumin may overcome resistance to hormonal and cytotoxic agents in breast cancer. We present our observations on MCF-7R, a multidrug-resistant (MDR) variant of the MCF-7 breast cancer cell line. In contrast to MCF-7, MCF-7R lacks aromatase and estrogen receptor alpha (ERalpha) and overexpresses the multidrug transporter ABCB1 and the products of different genes implicated in cell proliferation and survival, like c-IAP-1, NAIP, survivin, and COX-2. Nevertheless, in cytotoxicity and cell death induction assays, we found that the antitumor activity of curcumin is substantial both in MCF-7 and in MCF-7R. We elaborated the diketone system of curcumin into different analogues; the benzyloxime and the isoxazole and pyrazole heterocycles showed remarkable increases in the antitumor potency both in the parental and in the MDR MCF-7 cells. Furthermore, curcumin or, more potently, the isoxazole analogue, produced early reductions in the amounts of relevant gene transcripts that were diverse (i.e., they were relative to Bcl-2 and Bcl-X(L) in MCF-7 and the inhibitory of apoptosis proteins and COX-2 in MCF-7R) in the two cell lines. Thus, the two compounds exhibited the remarkable property of being able to modify their molecular activities according to the distinct characteristics of the parental and MDR cells. We discuss also how curcumin may (1) exert antitumor effects in breast cancer through ER-dependent and ER-independent mechanisms; and (2) act as a drug transporter-mediated MDR reversal agent. Overall, the structure of curcumin may represent the basis for the development of new, effective anticancer agents in hormone-independent MDR breast cancer.", "title": "Curcumin as a possible lead compound against hormone-independent, multidrug-resistant breast cancer." }, { "docid": "MED-2243", "text": "An ethanol extract of turmeric (\"Curcuma longa\") as well as an ointment of curcumin (its active ingredient) were found to produce remarkable symptomatic relief in patients with external cancerous lesions. Reduction in smell were noted in 90% of the cases and reduction in itching in almost all cases. Dry lesions were observed in 70% of the cases, and a small number of patients (10%) had a reduction in lesion size and pain. In many patients the effect continued for several months. An adverse reaction was noticed in only one of the 62 patients evaluated.", "title": "Turmeric and curcumin as topical agents in cancer therapy." }, { "docid": "MED-2239", "text": "OBJECTIVE: Human papillomavirus (HPV) infections remain a leading cause of mortality worldwide. In the U.S. strategies via screening and vaccination prevent HPV-associated cervical neoplasms, but consume immense healthcare costs. The spice component curcumin has potent anticancer and antiviral properties, which have been difficult to harness as a treatment, due to its poor systemic bioavailability. This project tests the possibility of developing a curcumin-based therapy for cervical cancer. METHODS: Using four HPV(+) cervical cancer cell lines and normal fibroblasts we first tested the selectivity and potency of curcumin in eliminating HPV(+) cells. Subsequently, we developed a curcumin-based cervical cream and tested its efficacy in eliminating apposed HPV(+) cells and also its possible side effects on the vaginal epithelium of healthy mice. RESULTS: Curcumin selectively eliminates a variety of HPV(+) cervical cancer cells (HeLa, ME-180, SiHa, and SW756), suppresses the transforming antigen E6, dramatically inhibits the expression of the pro-cancer protein epidermal growth factor receptor (EGFR), and concomitantly induces p53. Additionally, Vacurin, a uniform colloidal solution of curcumin in a clinically used amphipathic vaginal cream, eliminates apposed HeLa cells while suppressing the expression of EGFR. In mice, daily intravaginal application of Vacurin for three weeks produced no change in body weight and when the mice were sacrificed, the vaginal tract epithelium showed no Vacurin-evoked adverse effects. CONCLUSION: We have developed a curcumin-based vaginal cream, which effectively eradicates HPV(+) cancer cells and does not affect non-cancerous tissue. Our preclinical data support a novel approach for the treatment of cervical HPV infection. Copyright © 2012 Elsevier Inc. All rights reserved.", "title": "A novel curcumin-based vaginal cream Vacurin selectively eliminates apposed human cervical cancer cells." }, { "docid": "MED-4998", "text": "Curcumin has been reported to have the potential to prevent obesity as well as cancers. The downstream targets regulated by AMP-activated protein kinase (AMPK) for inhibiting adipocyte differentiation or cancer cell proliferation of curcumin were investigated. The activation of AMPK by curcumin was crucial for the inhibition of differentiation or growth in both adipocytes and cancer cells. Stimulation of AMPK by curcumin resulted in the down-regulation of PPAR (peroxisome proliferator-activated receptor)-gamma in 3T3-L1 adipocytes and the decrease in COX-2 in MCF-7 cells. Application of a synthetic AMPK activator also supported the evidence that AMPK acts as an upstream signal of PPAR-gamma in 3T3-L1 adipocytes. In cancer cells, AMPK was found to act as a regulator of ERK1/2, p38, and COX-2. Regulation of AMPK and its downstream targets such as PPAR-gamma, Mapkinases, and COX-2 by curcumin appears to be important in controlling adipocytes and cancerous cells.", "title": "Curcumin exerts antidifferentiation effect through AMPKalpha-PPAR-gamma in 3T3-L1 adipocytes and antiproliferatory effect through AMPKalpha-COX-2 i..." }, { "docid": "MED-2606", "text": "Curcumin, the active principle of turmeric, is known to act as an anti-oxidant, anti-mutagen and anti-carcinogen in experimental animals. In the present study, anti-mutagenic effects of turmeric were assessed in 16 chronic smokers. It was observed that turmeric, given in doses of 1.5 g/day for 30 days, significantly reduced the urinary excretion of mutagens in smokers. In contrast, in six non-smokers, who served as control, there was no change in the urinary excretion of mutagens after 30 days. Turmeric had no significant effect on serum aspartate aminotransferase and alanine aminotransferase, blood glucose, creatinine and lipid profile. These results indicate that dietary turmeric is an effective anti-mutagen and it may be useful in chemoprevention.", "title": "Effect of turmeric on urinary mutagens in smokers." }, { "docid": "MED-2608", "text": "The effects of curcumin, the yellow pigment of the spice, turmeric (Curcuma longa) on the mutagenicity of several environmental mutagens were investigated in the Salmonella/microsome test with or without Aroclor 1254-induced rat-liver homogenate (S-9 mix). With Salmonella typhimurium strain TA98 in the presence of S-9 mix, curcumin inhibited the mutagenicity of bidi and cigarette smoke condensates, tobacco and masheri extracts, benzo[a]pyrne and dimethyl benzo[a]anthracene in a dose-dependent manner. Curcumin did not influence the mutagenicity without S-9 mix of sodium azide, monoacetylhydrazine and streptozocin in strain TA100 nor of 4-nitrophenylenediamine in strain TA98. Our observations indicate that curcumin may alter the metabolic activation and detoxification of mutagens.", "title": "In vitro antimutagenicity of curcumin against environmental mutagens." }, { "docid": "MED-1507", "text": "Vascular endothelial function is declines with aging and is associated with an increased risk of cardiovascular disease. Lifestyle modification, particularly aerobic exercise and dietary adjustment, has a favorable effect on vascular aging. Curcumin is a major component of turmeric with known anti-inflammatory and anti-oxidative effects. We investigated the effects of curcumin ingestion and aerobic exercise training on flow-mediated dilation as an indicator endothelial function in postmenopausal women. A total of 32 postmenopausal women were assigned to 3 groups: control, exercise, and curcumin groups. The curcumin group ingested curcumin orally for 8 weeks. The exercise group underwent moderate aerobic exercise training for 8 weeks. Before and after each intervention, flow-mediated dilation was measured. No difference in baseline flow-mediated dilation or other key dependent variables were detected among the groups. Flow-mediated dilation increased significantly and equally in the curcumin and exercise groups, whereas no changes were observed in the control group. Our results indicated that curcumin ingestion and aerobic exercise training can increase flow-mediated dilation in postmenopausal women, suggesting that both can potentially improve the age-related decline in endothelial function. Copyright © 2012 Elsevier Inc. All rights reserved.", "title": "Curcumin ingestion and exercise training improve vascular endothelial function in postmenopausal women." }, { "docid": "MED-1813", "text": "PURPOSE: Pancreatic cancer is almost always lethal, and the only U.S. Food and Drug Administration-approved therapies for it, gemcitabine and erlotinib, produce objective responses in <10% of patients. We evaluated the clinical biological effects of curcumin (diferuloylmethane), a plant-derived dietary ingredient with potent nuclear factor-kappaB (NF-kappaB) and tumor inhibitory properties, against advanced pancreatic cancer. EXPERIMENTAL DESIGN: Patients received 8 g curcumin by mouth daily until disease progression, with restaging every 2 months. Serum cytokine levels for interleukin (IL)-6, IL-8, IL-10, and IL-1 receptor antagonists and peripheral blood mononuclear cell expression of NF-kappaB and cyclooxygenase-2 were monitored. RESULTS: Twenty-five patients were enrolled, with 21 evaluable for response. Circulating curcumin was detectable as drug in glucuronide and sulfate conjugate forms, albeit at low steady-state levels, suggesting poor oral bioavailability. Two patients showed clinical biological activity. One had ongoing stable disease for >18 months; interestingly, one additional patient had a brief, but marked, tumor regression (73%) accompanied by significant increases (4- to 35-fold) in serum cytokine levels (IL-6, IL-8, IL-10, and IL-1 receptor antagonists). No toxicities were observed. Curcumin down-regulated expression of NF-kappaB, cyclooxygenase-2, and phosphorylated signal transducer and activator of transcription 3 in peripheral blood mononuclear cells from patients (most of whom had baseline levels considerably higher than those found in healthy volunteers). Whereas there was considerable interpatient variation in plasma curcumin levels, drug levels peaked at 22 to 41 ng/mL and remained relatively constant over the first 4 weeks. CONCLUSIONS: Oral curcumin is well tolerated and, despite its limited absorption, has biological activity in some patients with pancreatic cancer.", "title": "Phase II trial of curcumin in patients with advanced pancreatic cancer." }, { "docid": "MED-2245", "text": "Curcumin (diferuloylmethane) is being considered as a potential chemopreventive agent in humans. In vitro it inhibits transcription by NF-kappaB, and the activity of lipoxygenase or cyclooxygenase enzymes, which facilitate tumor progression. In vivo it is protective in rodent models of chemical carcinogenesis. Curcumin contains an alpha,beta-unsaturated ketone, a reactive chemical substituent that is responsible for its repression of NF-kappaB. In compounds other than curcumin this same electrophilic moiety is associated with inactivation of the tumor suppressor, p53. Here we report that curcumin behaves analogously to these compounds. It disrupts the conformation of the p53 protein required for its serine phosphorylation, its binding to DNA, its transactivation of p53-responsive genes and p53-mediated cell cycle arrest.", "title": "Curcumin impairs tumor suppressor p53 function in colon cancer cells." }, { "docid": "MED-2246", "text": "Curcuma spp. extracts, particularly the dietary polyphenol curcumin, prevent colon cancer in rodents. In view of the sparse information on the pharmacodynamics and pharmacokinetics of curcumin in humans, a dose-escalation pilot study of a novel standardized Curcuma extract in proprietary capsule form was performed at doses between 440 and 2200 mg/day, containing 36-180 mg of curcumin. Fifteen patients with advanced colorectal cancer refractory to standard chemotherapies received Curcuma extract daily for up to 4 months. Activity of glutathione S-transferase and levels of a DNA adduct (M(1)G) formed by malondialdehyde, a product of lipid peroxidation and prostaglandin biosynthesis, were measured in patients' blood cells. Oral Curcuma extract was well tolerated, and dose-limiting toxicity was not observed. Neither curcumin nor its metabolites were detected in blood or urine, but curcumin was recovered from feces. Curcumin sulfate was identified in the feces of one patient. Ingestion of 440 mg of Curcuma extract for 29 days was accompanied by a 59% decrease in lymphocytic glutathione S-transferase activity. At higher dose levels, this effect was not observed. Leukocytic M(1)G levels were constant within each patient and unaffected by treatment. Radiologically stable disease was demonstrated in five patients for 2-4 months of treatment. The results suggest that (a) Curcuma extract can be administered safely to patients at doses of up to 2.2 g daily, equivalent to 180 mg of curcumin; (b) curcumin has low oral bioavailability in humans and may undergo intestinal metabolism; and (c) larger clinical trials of Curcuma extract are merited.", "title": "Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer." }, { "docid": "MED-3724", "text": "Drug resistance remains an on-going challenge in ovarian cancer chemotherapy. The objective of this study was to determine the effect on synergism in activity from the sequenced combinations of cisplatin (Cis) with curcumin (Cur) and epigallocatechin-3-gallate (EGCG) in the human ovarian cancer cell lines. The drugs were added in binary combinations: Cis combined with Cur, and Cis combined with EGCG to the human ovarian A2780 and A2780(cisR) cancer cell lines, using five different sequences of administration: 0/0 h, 4/0 h, 0/4 h, 24/0 h and 0/24 h. The combination index (CI) was used to assess the combined action of the drugs. CIs <1, =1 and >1 indicated synergism, additiveness and antagonism respectively. Cellular accumulation of platinum and platinum-DNA binding levels from Cis and its combination with the phytochemicals were determined using graphite furnace atomic absorption spectrometry. Addition of Cis 4 h before Cur and EGCG (0/4 h combination) produced the most synergistic outcomes in both the A2780 and A2780(cisR) cell lines. The cellular accumulations of platinum and platinum-DNA binding resulting from the 0/4 h combinations were greater as compared to the values using Cis alone, thus providing an explanation for the synergistic action. When sequenced combinations of Cis with Cur and with EGCG are applied to human ovarian A2780 and A2780(cisR) cancer cell lines, lower concentrations and shorter time gap between the two additions seem to produce a higher cytotoxic effect.", "title": "Synergism from sequenced combinations of curcumin and epigallocatechin-3-gallate with cisplatin in the killing of human ovarian cancer cells." }, { "docid": "MED-1112", "text": "Because of the central role of the transcription factor nuclear factor-kappaB (NF-kappaB) in cell survival and proliferation in human multiple myeloma (MM), we explored the possibility of using it as a target for MM treatment by using curcumin (diferuloylmethane), an agent known to have very little or no toxicity in humans. We found that NF-kappaB was constitutively active in all human MM cell lines examined and that curcumin, a chemopreventive agent, down-regulated NF-kappaB in all cell lines as indicated by electrophoretic mobility gel shift assay and prevented the nuclear retention of p65 as shown by immunocytochemistry. All MM cell lines showed consitutively active IkappaB kinase (IKK) and IkappaBalpha phosphorylation. Curcumin suppressed the constitutive IkappaBalpha phosphorylation through the inhibition of IKK activity. Curcumin also down-regulated the expression of NF-kappaB-regulated gene products, including IkappaBalpha, Bcl-2, Bcl-x(L), cyclin D1, and interleukin-6. This led to the suppression of proliferation and arrest of cells at the G(1)/S phase of the cell cycle. Suppression of NF-kappaB complex by IKKgamma/NF-kappaB essential modulator-binding domain peptide also suppressed the proliferation of MM cells. Curcumin also activated caspase-7 and caspase-9 and induced polyadenosine-5'-diphosphate-ribose polymerase (PARP) cleavage. Curcumin-induced down-regulation of NF-kappaB, a factor that has been implicated in chemoresistance, also induced chemosensitivity to vincristine and melphalan. Overall, our results indicate that curcumin down-regulates NF-kappaB in human MM cells, leading to the suppression of proliferation and induction of apoptosis, thus providing the molecular basis for the treatment of MM patients with this pharmacologically safe agent.", "title": "Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-kappa B and IkappaBalpha kinase in human multiple myeloma..." }, { "docid": "MED-4461", "text": "The objective of this study was to investigate, whether the plant-derived isothiocyanate Sulforaphane (SFN) enhances the antitumor activities of the chemotherapeutic agent oxaliplatin (Ox) in a cell culture model of colorectal cancer. Caco-2 cells were cultured under standard conditions and treated with increasing concentrations of SFN [1-20 μM] and/or Ox [100 nM-10 μM]. For co-incubation, cells were pre-treated with SFN for 24 h. Cell growth was determined by BrdU incorporation. Drug interactions were assessed using the combination-index method (CI) (Cl < 1 indicates synergism). Apoptotic events were characterized by different ELISA techniques. Protein levels were examined by Western blot analysis. Annexin V- and propidium iodide (PI) staining followed by FACS analysis was used to differentiate between apoptotic and necrotic events. SFN and Ox alone inhibited cell growth of Caco-2 cells in a dose-dependent manner, an effect, which could be synergistically enhanced, when cells were incubated with the combination of both agents. Co-treated cells further displayed distinctive morphological changes that occurred during the apoptotic process, such as cell surface exposure of phosphatidylserine, membrane blebbing as well as the occurence of cytoplasmic histone-associated DNA fragments. Further observations thereby pointed toward simultaneous activation of both extrinsic and intrinsic apoptotic pathways. With increasing concentrations and treatment duration, a shift from apoptotic to necrotic cell death could be observed. In conclusion, the data suggest that the isothiocyanate SFN sensitizes colon cancer cells to Ox-induced cell growth inhibition via induction of different modes of cell death.", "title": "Sulforaphane potentiates oxaliplatin-induced cell growth inhibition in colorectal cancer cells via induction of different modes of cell death." }, { "docid": "MED-2240", "text": "Curcumin interacts with a large number of extra- and intracellular targets in a biphasic dose-dependent manner. It controls inflammation, oxidative stress, cell survival, cell secretion, homeostasis, and proliferation. Its mechanisms of action are generally directed toward cells that exhibit disordered physiology or blatant mutation-based abnormal states. Optimizing preventative or therapeutic applications require delivering appropriate quantities of curcumin to lesioned cellular targets. Since diseased conditions anatomically are located from topical to systemic sites, efficient application of curcumin requires specific lesion-oriented delivery methods, representatives of which are here reviewed. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.", "title": "Curcumin (diferuloylmethane) delivery methods: a review." }, { "docid": "MED-938", "text": "Saffron (dried stigmas of Crocus sativus L.) has been used as a spice, food colorant and medicinal plant for millennia. In this study cytotoxic effect of saffron extract was evaluated in HepG2 and HeLa cell lines. Meanwhile role of apoptosis and ROS were explored. Malignant and non-malignant cells (L929) were cultured in DMEM medium and incubated with different concentrations of ethanolic saffron extract. Cell viability was quantitated by MTT assay. Apoptotic cells were determined using PI staining of DNA fragmentation by flow cytometry (sub-G1 peak). ROS was measured using DCF-DA by flow cytometry analysis. Saffron could decrease cell viability in malignant cells as a concentration and time-dependent manner. The IC50 values against HeLa and HepG2 were determined 800 and 950 microg/ml after 48 h, respectively. Saffron induced a sub-G1 peak in flow cytometry histogram of treated cells compared to control indicating apoptotic cell death is involved in saffron toxicity. This toxicity was also independent of ROS production. It might be concluded that saffron could cause cell death in HeLa and HepG2 cells, in which apoptosis or programmed cell death plays an important role. Saffron could be also considered as a promising chemotherapeutic agent in cancer treatment in future.", "title": "Study of cytotoxic and apoptogenic properties of saffron extract in human cancer cell lines." }, { "docid": "MED-1942", "text": "Curcumin, from the curry spice turmeric, has been shown to possess potent antioxidant and antiinflammatory properties and to reduce beta-amyloid and plaque burden in experimental studies, but epidemiologic evidence is lacking. The authors investigated the association between usual curry consumption level and cognitive function in elderly Asians. In a population-based cohort (n = 1,010) of nondemented elderly Asian subjects aged 60-93 years in 2003, the authors compared Mini-Mental State Examination (MMSE) scores for three categories of regular curry consumption, taking into account known sociodemographic, health, and behavioral correlates of MMSE performance. Those who consumed curry \"occasionally\" and \"often or very often\" had significantly better MMSE scores than did subjects who \"never or rarely\" consumed curry. The authors reported tentative evidence of better cognitive performance from curry consumption in nondemented elderly Asians, which should be confirmed in future studies.", "title": "Curry consumption and cognitive function in the elderly." }, { "docid": "MED-1811", "text": "BACKGROUND: A growing number of preclinical studies have demonstrated that curcumin could be a promising anticancer drug; however, poor bioavailability has been the major obstacle for its clinical application. To overcome this problem, we developed a new form of curcumin (Theracurmin) and reported high plasma curcumin levels could be safely achieved after a single administration of Theracurmin in healthy volunteers. In this study, we aimed to evaluate the safety of repetitive administration of Theracurmin in cancer patients. METHODS: Pancreatic or biliary tract cancer patients who failed standard chemotherapy were eligible for this study. Based on our previous pharmacokinetic study, we selected Theracurmin containing 200 mg of curcumin (Level 1) as a starting dose, and the dose was safely escalated to Level 2, which contained 400 mg of curcumin. Theracurmin was orally administered every day with standard gemcitabine-based chemotherapy. In addition to safety and pharmacokinetics data, NF-κB activity, cytokine levels, efficacy, and quality-of-life score were evaluated. RESULTS: Ten patients were assigned to level 1 and six were to level 2. Peak plasma curcumin levels (median) after Theracurmin administration were 324 ng/mL (range, 47-1,029 ng/mL) at Level 1 and 440 ng/mL (range, 179-1,380 ng/mL) at Level 2. No unexpected adverse events were observed and 3 patients safely continued Theracurmin administration for >9 months. CONCLUSIONS: Repetitive systemic exposure to high concentrations of curcumin achieved by Theracurmin did not increase the incidence of adverse events in cancer patients receiving gemcitabine-based chemotherapy.", "title": "A phase I study investigating the safety and pharmacokinetics of highly bioavailable curcumin (Theracurmin) in cancer patients." }, { "docid": "MED-1110", "text": "PURPOSE: To determine the effect of curcumin on plasma cells and osteoclasts in patients with MGUS. EXPERIMENTAL DESIGN: Twenty-six patients with MGUS were recruited into the study and administered 4 grams/day oral curcumin. Blood and urine samples were collected at specified visits after initiating therapy. Full blood count, B2 microglobulin, serum paraprotein, and immunoglobulin electrophoresis (IEPG and EPG) were determined for all patients at each visit. Serum calcium, 25 hydroxyvitamin D3, and bone-specific alkaline phosphatase were determined at baseline only. Urine, as a morning second-void sample, was collected at each visit for urinary N-telopeptide of type I collagen. RESULTS: Our results show that oral curcumin is able to decrease paraprotein load in a select group (i.e., those having a paraprotein level of >20 g/L) of patients with MGUS. Fifty percent (5 of 10) of these patients had a 12% to 30% reduction in their paraprotein levels, while on curcumin therapy. In addition, 27% of patients on curcumin had a >25% decrease in urinary N-telopeptide of type I collagen. CONCLUSION: Due to the possible progression of MGUS to multiple myeloma, the potential role of curcumin as a therapeutic intervention for MGUS patients warrants further investigation.", "title": "The potential role of curcumin in patients with monoclonal gammopathy of undefined significance--its effect on paraproteinemia and the urinary N-te..." }, { "docid": "MED-2427", "text": "Lipid rafts/caveolae are membrane platforms for signaling molecules that regulate various cellular functions, including cell survival. To better understand the role of rafts in tumor progression and therapeutics, we investigated the effect of raft disruption on cell viability and compared raft levels in human cancer cell lines versus their normal counterparts. Here, we report that cholesterol depletion using methyl-β cyclodextrin caused anoikis-like apoptosis, which in A431 cells involved decreased raft levels, Bcl-xL down-regulation, caspase-3 activation, and Akt inactivation regardless of epidermal growth factor receptor activation. Cholesterol repletion replenished rafts on the cell surface and restored Akt activation and cell viability. Moreover, the breast cancer and the prostate cancer cell lines contained more lipid rafts and were more sensitive to cholesterol depletion-induced cell death than their normal counterparts. These results indicate that cancer cells contain increased levels of rafts and suggest a potential use of raft-modulating agents as anti-cancer drugs.", "title": "Elevated Levels of Cholesterol-Rich Lipid Rafts in Cancer Cells Are Correlated with Apoptosis Sensitivity Induced by Cholesterol-Depleting Agents" }, { "docid": "MED-3947", "text": "Hibiscus sabdariffa Linne (Malvaceae), an attractive plant believed to be native to Africa, is cultivated in the Sudan and Eastern Taiwan. Anthocyanins exist widely in many vegetables and fruits. Some reports demonstrated that anthocyanins extracted from H. sabdariffa L., Hibiscus anthocyanins (HAs) (which are a group of natural pigments existing in the dried calyx of H. sabdariffa L.) exhibited antioxidant activity and liver protection. Therefore, in this study, we explored the effect of HAs on human cancer cells. The result showed that HAs could cause cancer cell apoptosis, especially in HL-60 cells. Using flow cytometry, we found that HAs treatment (0-4 mg/ml) markedly induced apoptosis in HL-60 cells in a dose- and time-dependent manner. The result also revealed increased phosphorylation in p38 and c-Jun, cytochrome c release, and expression of tBid, Fas, and FasL in the HAs-treated HL-60 cells. We further used SB203580 (p38 inhibitor), PD98059 (MEK inhibitor), SP600125 (JNK inhibitor), and wortmannin (phosphatidylinositol 3-kinase; PI-3K inhibitor) to evaluate their effect on the HAs-induced HL-60 death. The data showed that only SB203580 had strong potential in inhibiting HL-60 cell apoptosis and related protein expression and phosphorylation. Therefore, we suggested that HAs mediated HL-60 apoptosis via the p38-FasL and Bid pathway. According to these results, HAs could be developed as chemopreventive agents. However, further investigations into the specificity and mechanism(s) of HAs are needed.", "title": "Hibiscus anthocyanins rich extract-induced apoptotic cell death in human promyelocytic leukemia cells." }, { "docid": "MED-2044", "text": "Cancer incidence increases with advancing age. Over 60% of new cancers and 70% of cancer deaths occur in individuals aged 65 years or older. One factor that may contribute to this is immunosenescence - a canopy term that is used to describe age-related declines in the normal functioning of the immune system. There are multiple age-related deficits in both the innate and adaptive systems that may play a role in the increased incidence of cancer. These include decreased NK-cell function, impaired antigen uptake and presentation by monocytes and dendritic cells, an increase in 'inflammaging', a decline in the number of naïve T-cells able to respond to evolving tumor cells, and an increase in functionally exhausted senescent cells. There is consensus that habitual physical exercise can offer protection against certain types of cancer; however the evidence linking immunological mechanisms, exercise, and reduced cancer risk remain tentative. Multiple studies published over the last two decades suggest that exercise can mitigate the deleterious effects of age on immune function, thus increasing anti-cancer immunity. The potential ameliorative effect of exercise on these mechanisms include evidence that physical activity is able to stimulate greater NK-cell activity, enhance antigen-presentation, reduce inflammation, and prevent senescent cell accumulation in the elderly. Here we discuss the role played by the immune system in preventing and controlling cancer and how aging may retard these anti-cancer mechanisms. We also propose a pathway by which exercise-induced alterations in immunosenescence may decrease the incidence of cancer and help improve prognosis in cancer patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.", "title": "Can exercise-related improvements in immunity influence cancer prevention and prognosis in the elderly?" }, { "docid": "MED-874", "text": "BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent which selectively kills cancer cells with little effect on normal cells. However, TRAIL resistance is widely found in cancer cells. We have previously reported antimetatstatic and antiangiogenic effects of vanillin, a flavoring agent from vanilla. Here we have evaluated the sensitizing effect of vanillin on a TRAIL-resistant human cervical cancer cell line, HeLa. MATERIALS AND METHODS: Cell viability after treatments was determined by the WST-1 cell counting kit. Apoptosis was demonstrated by detection of caspase-3 activation and cleavage of poly (ADP-ribose) polymerase using immunoblot analysis. Effect of treatments on TRAIL signaling pathway and nuclear factor kappaB (FN-kappaB) activation was studied using immunoblot analysis and luciferase reporter assay. RESULTS: Pretreatment of HeLa cells with vanillin enhanced TRAIL-induced cell death through the apoptosis pathway. Vanillin pretreatment inhibited TRAIL-induced phosphorylation of p65 and transcriptional activity of NF-kappaB. CONCLUSION: Vanillin sensitizes HeLa cells to TRAIL-induced apoptosis by inhibiting NF-kappaB activation.", "title": "Vanillin enhances TRAIL-induced apoptosis in cancer cells through inhibition of NF-kappaB activation." }, { "docid": "MED-865", "text": "Prostate cancer remains the second leading cause of cancer deaths among American men. Earlier diagnosis increases survival rate in patients. However, treatments for advanced disease are limited to hormone ablation techniques and palliative care. Thus, new methods of treatment and prevention are necessary for inhibiting disease progression to a hormone refractory state. One of the approaches to control prostate cancer is prevention through diet, which inhibits one or more neoplastic events and reduces the cancer risk. For centuries, Ayurveda has recommended the use of bitter melon (Momordica charantia) as a functional food to prevent and treat human health related issues. In this study, we have initially used human prostate cancer cells, PC3 and LNCaP, as an in vitro model to assess the efficacy of bitter melon extract (BME) as an anti-cancer agent. We observed that prostate cancer cells treated with BME accumulate during the S phase of the cell cycle, and modulate cyclin D1, cyclin E and p21 expression. Treatment of prostate cancer cells with BME enhanced Bax expression, and induced poly(ADP-ribose) polymerase cleavage. Oral gavage of BME, as a dietary compound, delayed the progression to high grade prostatic intraepithelial neoplasia (PIN) in TRAMP (transgenic adenocarcinoma of mouse prostate) mice (31%). Prostate tissue from BME-fed mice displayed ~51% reduction of PCNA expression. Together, our results suggest for the first time that oral administration of BME inhibits prostate cancer progression in TRAMP mice by interfering cell cycle progression and proliferation.", "title": "Bitter melon extract impairs prostate cancer cell cycle progression and delays prostatic intraepithelial neoplasia in TRAMP model" }, { "docid": "MED-1512", "text": "BACKGROUND: Lifestyle modification (i.e., regular physical activity and diet) is effective in preventing the age-related increase in cardiovascular disease risks. Potential therapeutic effects of curcumin (diferuloylmethane) have been confirmed on various diseases, including cancer and Alzheimer's disease, but the effects of curcumin have not been tested on central arterial hemodynamics. The aim of this pilot study was to test the hypothesis that the regular endurance exercise combined with daily curcumin ingestion lowers the age-related increase in left ventricular (LV) afterload to a greater extent than monotherapy with either intervention alone in postmenopausal women using a randomized, double-blind, placebo-controlled, parallel manner. METHODS: Forty-five women were randomly assigned to four interventions: \"placebo ingestion\" (n = 11), \"curcumin ingestion\" (n = 11), \"exercise training with placebo ingestion\" (n = 11), or \"exercise training with curcumin ingestion\" (n = 12). Curcumin or placebo pills (150 mg/day) were administered for 8 weeks. Aortic blood pressure (BP) and augmentation index (AIx), an index of LV afterload, were evaluated by pulse wave analysis from tonometrically measured radial arterial pressure waveforms. RESULTS: There were no significant differences in baseline hemodynamic variables among four groups. After the interventions, brachial systolic BP (SBP) significantly decreased in both exercise-trained groups (P < 0.05 for both), whereas aortic SBP significantly decreased only in the combined-treatment (e.g., exercise and curcumin) group (P < 0.05). Heart rate (HR) corrected aortic AIx significantly decreases only in the combined-treatment group. CONCLUSIONS: These findings suggest that regular endurance exercise combined with daily curcumin ingestion may reduce LV afterload to a greater extent than monotherapy with either intervention alone in postmenopausal women.", "title": "Effect of endurance exercise training and curcumin intake on central arterial hemodynamics in postmenopausal women: pilot study." }, { "docid": "MED-4711", "text": "Licorice is a common Chinese medicinal herb with antitumor activity. Some components in licorice root have been shown to induce cell cycle arrest or apoptosis in cancer cells. This paper demonstrates for the first time that licorice Glycyrrhiza glabra and its component licochalcone-A (LA) can induce autophagy in addition to apoptosis in human LNCaP prostate cancer cells. Exposure of cells to licorice or LA resulted in several confirmed characteristics of autophagy, including the appearance of autophagic vacuoles revealed by monodansylcadaverine (MDC) staining, formation of acidic vesicular organelles (AVOs), and autophagosome membrane association of microtubule-associated protein 1 light chain 3 (LC3) characterized by cleavage of LC3 and its punctuate redistribution, as well as ultrastructural observation of autophagic vacuoles by transmission electron microscopy. Autophagy induction was accompanied by down-regulation of Bcl-2 and inhibition of the mammalian target of rapamycin (mTOR) pathway. In summary, licorice can induce caspase-dependent and autophagy-related cell death in LNCaP cells.", "title": "Licorice and licochalcone-A induce autophagy in LNCaP prostate cancer cells by suppression of Bcl-2 expression and the mTOR pathway." }, { "docid": "MED-3548", "text": "Cancer metastasis refers to the spread of cancer cells from the primary neoplasm to distant sites, where secondary tumors are formed, and is the major cause of death from cancer. Natural phytochemicals containing phenolic compounds have been widely demonstrated to have the capability to prevent cancer metastasis. Among phenolic compounds, flavonoids are a very large subclass, and they are abundant in food and nutraceuticals. The number of reports demonstrating that flavonoids are an effective natural inhibitor of cancer invasion and metastasis is increasing in the scientific literature. Catechin derivatives, (−)-epigallocatechin-3-gallate, (−)-epigallocatechin, (−)-epicatechin-3-gallate,and (−)-epicatechin, are the most studied compounds in this topic so far; genistein/genistin, silibinin, quercetin, and anthocyanin have also been widely investigated for their inhibitory activities on invasion/metastasis. Other flavonoids in dietary vegetable foods that are responsible for anti-invasive and anti-metastatic activities of tumors include luteolin,apigenin, myricetin, tangeretin, kaempferol, glycitein, licoricidin,daidzein, and naringenin. To effectively overcome the metastatic cascade, including cell-cell attachment, tissue barrier degradation, migration, invasion, cell-matrix adhesion,and angiogenesis, it is essential that a bioactive compound prevent tumor cells from metastasizing. This review summarizes the effects of flavonoids on the metastatic cascade and the related proteins, the in vitro anti-invasive activity of flavonoids against cancer cells, and the effects of flavonoids on antiangiogenic and in vivo anti-metastatic models. The available scientific evidence indicates that flavonoids are a ubiquitous dietary phenolics subclass and exert extensive in vitro anti-invasive and in vivo anti-metastatic activities.", "title": "Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities." }, { "docid": "MED-4907", "text": "Tumor metastasis is the most important cause of cancer death and various treatment strategies have targeted on preventing the occurrence of metastasis. Anthocyanins are natural colorants belonging to the flavonoid family, and are wildly used for their antioxidant properties. Here, we provided molecular evidence associated with the anti-metastatic effects of peonidin 3-glucoside and cyanidin 3-glucoside, major anthocyanins extracted from black rice (Oryza sativa L. indica), by showing a marked inhibition on the invasion and motility of SKHep-1 cells. This effect was associated with a reduced expression of matrix metalloproteinase (MMP)-9 and urokinase-type plasminogen activator (u-PA). Peonidin 3-glucoside and cyanidin 3-glucoside also exerted an inhibitory effect on the DNA binding activity and the nuclear translocation of AP-1. Furthermore, these compounds also exerted an inhibitory effect of cell invasion on various cancer cells (SCC-4, Huh-7, and HeLa). Finally, anthocyanins from O. sativa L. indica (OAs) were evidenced by its inhibition on the growth of SKHep-1 cells in vivo.", "title": "Black rice anthocyanins inhibit cancer cells invasion via repressions of MMPs and u-PA expression." }, { "docid": "MED-2244", "text": "BACKGROUND & AIMS: Familialadenomatous polyposis (FAP) is an autosomal-dominant disorder characterized by the development of hundreds of colorectal adenomas and eventual colorectal cancer. Regression of adenomas in this syndrome occurs with the administration of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors, but these compounds can have considerable side effects. We evaluated the efficacy of the combination of diet-derived nonprescription supplements curcumin and quercetin to regress adenomas in patients with FAP. METHODS: Five FAP patients with prior colectomy (4 with retained rectum and 1 with an ileal anal pouch) received curcumin 480 mg and quercetin 20 mg orally 3 times a day. The number and size of polyps were assessed at baseline and after therapy. The Wilcoxon signed-rank test was used to determine differences in the number and size of polyps. Treatment side effects and medication compliance also were evaluated. RESULTS: All 5 patients had a decreased polyp number and size from baseline after a mean of 6 months of treatment with curcumin and quercetin. The mean percent decrease in the number and size of polyps from baseline was 60.4% (P < .05) and 50.9% (P < .05), respectively. Minimal adverse side effects and no laboratory abnormalities were noted. CONCLUSIONS: The combination of curcumin and quercetin appears to reduce the number and size of ileal and rectal adenomas in patients with FAP without appreciable toxicity. Randomized controlled trials are needed to validate these findings.", "title": "Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis." } ]
211807
Bobby Moore was a professional footballer.
[ { "docid": "Bobby_Moore", "text": "Robert Frederick Chelsea `` Bobby '' Moore OBE ( 12 April 1941 -- 24 February 1993 ) was an English professional footballer . He captained West Ham United for more than ten years and was captain of the England team that won the 1966 World Cup . He is widely regarded as one of the greatest defenders of all time , and was cited by Pelé as the greatest defender that he had ever played against . Moore is a member of the World Team of the 20th Century . He won a total of 108 caps for the England team , which at the time of his international retirement in 1973 was a national record . This record was later broken by 125-cap goalkeeper Peter Shilton . Moore 's total of 108 caps continued as a record for outfield players until 28 March 2009 , when David Beckham gained his 109th cap . Moore was made an inaugural inductee of the English Football Hall of Fame in 2002 in recognition of his impact on the English game as a player . The same year he was named in the BBC 's list of the 100 Greatest Britons .", "title": "" } ]
[ { "docid": "Bobby_Moore_(disambiguation)", "text": "Bobby Moore ( 1941 -- 1993 ) was an English footballer . Bobby Moore is also the name of : Bobby Moore ( pitcher ) ( 1958 -- 2015 ) , former Major League Baseball pitcher for the San Francisco Giants Bobby Moore ( outfielder ) ( born 1965 ) , former Major League Baseball outfielder for the Kansas City Royals Bobby Moore ( motorcyclist ) , former world champion motocross racer Ahmad Rashād ( born Robert Earl Moore , 1949 ) , former American football player and current sportscaster Bobby Moore & the Rhythm Aces ( 1930 -- 2006 ) , 1960s R&B group Statue of Bobby Moore , Wembley , a 2007 statue of the footballer outside Wembley Stadium , London", "title": "" }, { "docid": "Statue_of_Bobby_Moore,_Wembley", "text": "The Bobby Moore statue is a bronze sculpture of the former West Ham and England footballer Bobby Moore , situated outside England 's national stadium , Wembley Stadium , in Wembley Park , north-west London . It commemorates the life of Moore , who captained the only England side ever to win the World Cup , defeating Germany 4-2 in the 1966 FIFA World Cup Final held in England at the old Wembley Stadium , demolished in 2003 . Commissioned by the Football Association , it was unveiled outside the new stadium when it opened in 2007 , fourteen years after Moore 's death from cancer , aged 51 . Standing 20 ft tall on a stone plinth , it looks over spectators as they walk down Wembley Way into the stadium . Sculpted by the Royal Sculptor Philip Jackson , it is Jackson 's second piece featuring Moore , after the World Cup Sculpture unveiled in 2003 .", "title": "" }, { "docid": "Tina_and_Bobby", "text": "Tina and Bobby is a British television series based on the relationship between footballer Bobby Moore and Tina Moore . The three-part series was first broadcast on 13 January 2017 on ITV .", "title": "" }, { "docid": "Escape_to_Victory", "text": "Escape to Victory , known simply as Victory in North America , is a 1981 film about Allied prisoners of war who are interned in a German prison camp during the Second World War who play an exhibition match of football against a German team . The film was directed by John Huston and starred Michael Caine , Sylvester Stallone , Max von Sydow , Daniel Massey , Bobby Moore and Pelé . The film received great attention upon its theatrical release , as it also starred professional footballers Bobby Moore , Osvaldo Ardiles , Kazimierz Deyna , Paul Van Himst , Mike Summerbee , Hallvar Thoresen , Werner Roth and Pelé . Numerous Ipswich Town players were also in the film , including John Wark , Russell Osman , Laurie Sivell , Robin Turner and Kevin O'Callaghan . Further Ipswich Town players stood in for actors in the football scenes -- Kevin Beattie for Michael Caine , and Paul Cooper for Sylvester Stallone . The script was written by Yabo Yablonsky . The film was entered into the 12th Moscow International Film Festival .", "title": "" }, { "docid": "Bobby_Moore_(motorcyclist)", "text": "Bobby Moore is an American former professional motocross racer . He won the 1994 125cc Motocross World Championship . In 1985 , Moore won the A.M.A. 125cc Western Supercross title . He moved on to the F.I.M. world championships , finishing second to Donny Schmit in the 1990 125cc championship . In 1992 , he again finished second to Schmit , this time in the 250cc world championship . He moved back to the 125cc class , and in 1994 , he won the world championship on a Yamaha .", "title": "" }, { "docid": "Bobby_Reid", "text": "Bobby Reid is the name of : Bobby Reid ( American football ) , quarterback Bobby Reid ( footballer , born 1911 ) , Scottish international winger Bobby Reid ( footballer , born 1936 ) , Scottish professional goalkeeper Bobby Reid ( footballer , born 1955 ) , Scottish professional defender Bobby Reid ( footballer , born 1993 ) , English professional midfielder", "title": "" }, { "docid": "Kevin_Lock", "text": "Kevin Lock ( born 27 December 1953 in Plaistow , Essex ) is an English former professional footballer who played as a central defender . Lock played for West Ham United , making his debut against Sheffield United on 29 February 1972 . He took over the number 6 shirt from Bobby Moore , who left for Fulham in 1974 . He played against Moore in the 1975 FA Cup Final victory before joining Fulham himself in 1978 . He won four caps for the England under-23 side . His last game for the Irons was on 17 September 1977 , a 2-3 away win against Bristol City . He later joined Southend United , then managed by Moore , where he played ten League games . He stayed with the Essex club as a coach once he 'd retired from playing . He remained with Southend when David Webb replaced Moore as manager , and followed Webb to Chelsea in 1993 and Brentford from 1993 to 1998 , which was his last job in football .", "title": "" }, { "docid": "Bobby_Wilson", "text": "Bobby Wilson may refer to : Bobby Wilson ( tennis ) ( born 1935 ) , British tennis player of the 1950s and 1960s Bobby Wilson ( Australian rules footballer ) ( 1934 -- 2003 ) , Australian rules footballer for Fitzroy Bobby Wilson ( footballer , born 1943 ) , Scottish footballer ( Dundee FC ) Bobby Wilson ( footballer , born 1944 ) , English footballer Bobby Wilson ( basketball , born 1944 ) , American professional basketball player in the ABA Bobby Wilson ( basketball , born 1951 ) , American professional basketball player in the NBA Bobby Wilson ( defensive tackle ) ( born 1968 ) , American football player Bobby Wilson ( racing driver ) ( born 1981 ) , American racecar driver Bobby Wilson ( baseball ) ( born 1983 ) , American baseball player", "title": "" }, { "docid": "Bobby_Gilfillan", "text": "Bobby Gilfillan may refer to : Bobby Gilfillan ( footballer , born 1926 ) , Scottish professional footballer Bobby Gilfillan ( footballer , born 1938 ) , Scottish professional footballer", "title": "" }, { "docid": "World_Cup_Sculpture", "text": "The World Cup Sculpture , or simply The Champions , is a bronze statue of the 1966 World Cup Final located near West Ham United Football Club 's Boleyn Ground ( Upton Park ) stadium in the London Borough of Newham , England . It depicts a famous victory scene photographed after the final , held at the old Wembley Stadium in London , featuring Bobby Moore , Geoff Hurst , Martin Peters and Ray Wilson . It was the first and only time England had won the World Cup , and England captain Moore is pictured held shoulder high , holding the Jules Rimet Trophy aloft . Jointly commissioned by Newham Council and West Ham United , it stands at the junction of Barking Road and Green Street , near the Boleyn Ground . It commemorates West Ham 's contribution to the victory , with Moore , Hurst and Peters having all been West Ham players at the time of the 1966 World Cup . Sculpted by the Royal Sculptor Philip Jackson , it was unveiled in 2003 by Prince Andrew , president of the Football Association . Jackson went on to also sculpt the statue of Bobby Moore unveiled at the new Wembley when it opened in 2007 .", "title": "" }, { "docid": "Bobby_Moore_(pitcher)", "text": "Robert Devell Moore ( November 8 , 1958 -- April 10 , 2015 ) was a Major League Baseball pitcher , who played briefly during one season at the major league level with the San Francisco Giants , appearing in 16.2 innings through 11 games , compiling a 3.24 ERA . He was originally signed by the Oakland Athletics in the 11th round of the 1976 amateur draft . Bobby Moore played his first professional season with their Class A ( Short Season ) Boise A 's in 1976 , and split his last season between the California Angels ' Double-A Midland Angels and the Cincinnati Reds ' Triple-A Nashville Sounds in 1990 . All together he finished with a career minor league won-lost mark of 55-86 , both as a starter and reliever , with a 5.28 ERA over 1223 innings pitched .", "title": "" }, { "docid": "Luke_Moore_(disambiguation)", "text": "Luke Moore may also refer to : Luke Moore ( born 13 February 1986 ) an English professional footballer striker Luke Moore ( footballer born 1988 ) an English semi-professional footballer Luke Moore ( broadcaster ) Luke Moore , character in 13Hrs", "title": "" }, { "docid": "Bobby_Doyle", "text": "Bobby Doyle may refer to : Bobby Doyle ( Scottish footballer ) ( born 1953 ) , former professional association footballer Bobby Doyle ( Gaelic footballer ) , former Gaelic football player for Dublin Bobby Doyle ( jazz vocalist ) ( 1939 -- 2006 ) , jazz singer from Houston , Texas , who toured with Kenny Rogers", "title": "" }, { "docid": "1972–73_West_Ham_United_F.C._season", "text": "West Ham once again equalled their highest ever league finish of 6th . This was largely due to Hammer of the Year Pop Robson and his prowess in front of goal . Trevor Brooking was runner up as Hammer of the Year . Bobby Moore overtook Jimmy Ruffell 's record number of League Appearances for West Ham , a record that had stood unchallenged since 1936 . Bobby Moore also marked his 100th England cap in the same month . 1972-73 Category : English football clubs 1972 -- 73 season Category :1972 in London Category :1973 in London", "title": "" }, { "docid": "Luke_Moore", "text": "Luke Isaac Hunt Moore ( born 13 February 1986 ) is an English professional footballer striker . Moore has represented England at England U21 level and is the younger brother of former professional footballer , Stefan Moore .", "title": "" }, { "docid": "Bobby_Hill", "text": "Bobby Hill or Bob Hill may refer to : Bob Hill ( footballer ) ( 18671938 ) , Scottish footballer Bob Hill ( American football ) ( born 1891 ) , American football player Bobby Hill ( motorcycle racer ) ( born 1922 ) , American motorcycle racer Bobby Hill ( footballer ) ( born 1938 ) , Scottish footballer Bob Hill ( politician ) ( born 1940 ) , Jersey politician and human rights campaigner Bobby Joe Hill ( 19432002 ) , American basketball player Bob Hill ( born 1948 ) , American basketball coach Bobby Hill ( baseball ) ( born 1978 ) , American professional baseball player Bob Hill ( racing driver ) , American race car driver , see List of ARCA drivers Bobby Hill ( King of the Hill ) , fictional character in the cartoon series King of the Hill Bobby Hill , fictional police officer on the television series Hill Street Blues", "title": "" }, { "docid": "Bobby_Moore_&_the_Rhythm_Aces", "text": "Bobby Moore & the Rhythm Aces is an American soul group from Montgomery , Alabama .", "title": "" }, { "docid": "1964–65_European_Cup_Winners'_Cup", "text": "The season 1964 -- 65 of the European Cup Winners ' Cup football club tournament was won by West Ham United in a final at Wembley Stadium against 1860 Munich . West Ham 's Bobby Moore was captaining a side that also included Geoff Hurst and Martin Peters just one season before all three went on to star in England 's World Cup winning side of 1966 . As a result of their CWC success , Bobby Moore became the only captain to climb the Wembley steps to be presented with three different trophies in three successive seasons ( English FA Cup and European Cup Winners ' Cup with West Ham in 1964 and 1965 respectively , then the World Cup with England in 1966 ) .", "title": "" }, { "docid": "Gillian_Coultard", "text": "Gillian Coultard ( born 22 July 1963 ) is a retired English football player , and former England captain . She is one of England Women 's most capped internationals , with 119 appearances , and was the highest capped outfield England international ever until Rachel Yankey reached 120 caps in 2012 . At the time she was one of only five footballers ( Bobby Moore , Billy Wright and Bobby Charlton were the others ) to have reached over 100 caps for England , and she was the first woman and amateur player to have done so .", "title": "" }, { "docid": "Bobby_Baxter_(footballer,_born_1937)", "text": "Robert Denholm `` Bobby '' Baxter ( born 4 February 1937 ) is an English former professional footballer born in Redcar , Yorkshire , who played in the Football League for Darlington , Brighton & Hove Albion and Torquay United . He is the son and namesake of Scotland and Middlesbrough footballer Bobby Baxter .", "title": "" }, { "docid": "Ron_Pountney", "text": "Ronald Alan Pountney ( born 19 March 1955 ) is an English former professional footballer who played as a midfielder . A West Bromwich Albion supporter , he was named after Ronnie Allen . His style of play was based on `` hard work , graft and unselfishness '' . He was named as Southend United 's Player of the Year three times . He was given a free transfer by manager Bobby Moore in 1985 , however a testimonial match against West Ham United was cancelled after West Ham had a rearranged fixture clash with the event . He eventually received a testimonial game in 2000 . After retiring as a player he worked as a painter and decorator .", "title": "" }, { "docid": "Roy_Moore_(disambiguation)", "text": "Roy Moore is an American judge and politician . Roy Moore may also refer to : Roy Moore ( English footballer ) ( 1923 -- 1991 ) , English former professional soccer player Roy Moore ( Australian footballer ) ( 1914 -- 1973 ) , player of Australian football from the 1930s and 1940s Roy Moore ( baseball ) ( 1898 -- 1951 ) , 1920s Major League Baseball pitcher Roy Moore ( cyclist ) ( born 1932 ) , Australian Olympic cyclist Roy D. Moore ( 1921 -- 2014 ) , American college football head coach Roy K. Moore ( 1914 -- 2008 ) , chief FBI investigator in the Mississippi civil rights workers murders Roy Moore ( wrestler ) , wrestling and judo coach", "title": "" }, { "docid": "Doxie_Moore", "text": "John Doxie Moore ( February 13 , 1911 -- April 23 , 1986 ) was an American basketball player and coach . He attended Delphi High School in Delphi , Indiana , and played college basketball at Purdue University from 1930 to 1934 , playing alongside John Wooden as Purdue laid claim to the 1932 Helms Athletic Foundation National Championship . He coached several professional basketball teams , including the Sheboygan Red Skins , the Anderson Packers and the Milwaukee Hawks in the 1940s and 1950s . Moore was hired to coach Sheboygan for the 1946 -- 47 season . The Red Skins finished with a 26 -- 18 record and qualified for the National Basketball League ( NBL ) playoffs , where they were ousted in the first round . In 1947 -- 48 , Moore began the season as Sheboygan 's head coach , but gave up the duties when the Red Skins obtained player-coach Bobby McDermott , a Hall of Fame guard , from the Chicago American Gears . The Gears players had been distributed among the NBL 's teams when Chicago 's league , the fledgling Professional Basketball League of America , folded in November 1947 after only three weeks in operation . McDermott coached Sheboygan to a 4 -- 5 record in one month of duty before leaving for the Tri-Cities Blackhawks and handing the reins back to Moore . The Red Skins finished a disappointing 23 -- 37 and missed the playoffs . Moore served as the commissioner of the NBL in its final season . Following the NBL-BAA merger , Moore was hired as coach of the Anderson Packers in the middle of the 1949 -- 50 NBA season . When the Packers jumped to the National Professional Basketball League for the 1950 -- 51 season , Moore served as the NPBL 's commissioner as the league struggled to finish its only season . Moore served as coach and vice-president of the Milwaukee Hawks for 1951 -- 52 , their first season in Milwaukee . In the 1950s , he was an administrative assistant to Indiana Governor George N. Craig . Moore was inducted into the Indiana Basketball Hall of Fame in 1978 , and served as the first president of the Hall of Fame Foundation .", "title": "" }, { "docid": "Jeff_Moore", "text": "Jeff or Jeffrey Moore may refer to : Jeff Moore ( basketball ) ( born c. 1966 ) , former American professional basketball player Jeff Moore ( American football ) ( born 1956 ) , former American football running back in the National Football League Jeffrey Moore , Canadian novelist , translator , and educator Jeff Moore ( pioneer ) ( 1780 -- 1835 ) , American pioneer and founder of the town Russell , Kentucky Jeffrey S. Moore ( born 1962 ) , professor of chemistry", "title": "" }, { "docid": "Zeke_Moore", "text": "Zeke Moore ( born in 1943 ) is a former professional American Football player who played defensive back for the American Football League 's Houston Oilers from 1967 -- 1969 , and for the NFL Oilers from 1970 through 1977 . Before his professional career , Moore played for Lincoln University of Missouri . Mr. Moore is currently the president of the Townwood Homeowners Association in Houston , and he is a Texas Registered Peace Officer .", "title": "" }, { "docid": "Bobby_Joe_Green", "text": "Bobby Joe Green ( May 7 , 1936 -- May 28 , 1993 ) was an American college and professional football player who was a punter and running back in the National Football League ( NFL ) for fourteen seasons during the 1960s and early 1970s . Green played college football for the University of Florida , and thereafter , he played professionally for the Pittsburgh Steelers and the Chicago Bears of the NFL .", "title": "" }, { "docid": "Andrew_Moore", "text": "Andrew or Andy Moore may refer to : Andrew Moore ( historian ) , Australian academic and writer Andrew Moore ( Australian footballer ) ( born 1991 ) , Australian footballer Andrew Moore ( politician ) ( 1752 -- 1821 ) , U.S. Representative and Senator from Virginia Andrew Moore ( rugby player ) ( born 1974 ) , Wales international rugby union lock forward Andrew Moore ( baseball ) ( born 1994 ) , American baseball player Andy Moore ( rugby union ) , Wales international rugby union scrum-half Andrew Moore ( musician ) ( born 1979 ) , electronic musician also known as A.M. Andrew B. Moore ( 1807 -- 1873 ) , Governor of the U.S. state of Alabama Andrew L. Moore ( born 1957 ) , American photographer Andrew M. T. Moore , archeologist at the Rochester Institute of Technology Andy Moore ( actor ) , English actor Andy Moore ( footballer ) ( born 1965 ) , English former professional soccer player Andy Moore ( American football ) ( 1902 -- 1971 ) , American football coach at the University of Chattanooga", "title": "" }, { "docid": "Darren_Moore", "text": "Darren Mark Moore ( born 22 April 1974 in Birmingham ) is an English-born Jamaican former professional footballer who played as a defender . During his playing career , he earned three international caps for Jamaica . Moore is also a member of the management committee of the Professional Footballers ' Association .", "title": "" }, { "docid": "Nat_Moore", "text": "Nathaniel Moore ( born September 19 , 1951 ) is an American former college and professional football player who was a wide receiver in the National Football League ( NFL ) for thirteen seasons during the 1970s and 1980s . Moore played college football for the University of Florida , and thereafter , he played professionally for the Miami Dolphins of the NFL . He is best known as a favorite passing target of Dolphins quarterbacks Bob Griese and Dan Marino .", "title": "" }, { "docid": "Bobby_Crawford_(footballer)", "text": "Robert `` Bobby '' Crawford was a Scottish professional footballer . A left half , he played in the Football League for Preston North End , Blackpool and Blackburn Rovers .", "title": "" } ]
4057
What is the effect of a high dollar on the Canadian economy, investors, and consumers?
[ { "docid": "259282", "text": "It depends primarily on how the Canadian economy is designed i.e export oriented or import oriented. If you look at this, it shows more or less equal amount of exports and imports. For the specific case of Canada, the exports would become costlier, because of a costlier dollar, but at the same time imports would become cheaper. This is only a generalization, not specific goodswise, which would require a more detailed ananlysis. But investors have a different dilemma. Canadian investors would find it cheaper to invest abroad so may channel their investments abroad because they may find it costlier to invest in Canada. While foreign investors would find it costlier to invest in Canada and may wait for later or invest somehwre else. Then government may try to boost up investment and start lowering the interest rates, if it sees the rising dollar as detrimental for the Canadian economy and investments flowing abroad instead of Canada. But what would be the final outcome of the whole rigmarole is little difficult to predict, because something is arriving and something is departing and above all goverment is doing something or is going to do. But the basic gist is Canadian exporters will be sad and Canadian importers will be happy, but vice versa for foreign investors intending to invest in Canada.", "title": "" } ]
[ { "docid": "277482", "text": "At the time of writing, the Canadian dollar is worth roughly $0.75 U.S. Now, it's not possible for you to accurately predict what it'll be worth in, say, ten years. Maybe it'll be worth $0.50 U.S. Maybe $0.67. Maybe $1.00. Additionally, you can't know in advance if the Canadian economy will grow faster than the U.S., or slower, or by how much. Let's say you don't want to make a prediction. You just want to invest 50% of your money in Canadian stocks, 50% in U.S. Great. Do that, and don't worry about the current interest rates. Let's say that you do want to make a prediction. You are firmly of the belief that the Canadian dollar will be worth $1.00 U.S. dollar in approximately ten years. And furthermore, the Canadian economy and the U.S. economy will grow at roughly equal rates, in their local currencies. Great. You should put more of your money in Canadian stocks. Let's say that you want to make a prediction. The Canadian economy is tanking. It's going to be worth $0.67 or less in ten years. And on top of that, the U.S. economy is primed for growth. It's going to grow far faster than the Canadian economy. In that case, you want to invest mostly in U.S. stocks. Let's get more complicated. You think the Canadian dollar is going to recover, but boy, maple syrup futures are in trouble. The next decade is all about Micky Mouse. Now what should you do? Well, it depends on how fast the U.S. economy expands, compared to the currency difference. What should you do? I can't tell you that because I can't predict the future. What did I do? I bought 25% Canadian stocks, 25% U.S. stocks, 25% world stocks, and 25% Canadian bonds (roughly), back when the Canadian dollar was stronger. What am I doing now? Same thing. I don't know enough about the respective economies to judge. If I had a firm opinion, though, I'd certainly be happy to change my percentages a little. Not a lot, but a little.", "title": "" }, { "docid": "36272", "text": "There are several possible effects: There isn't much you could do about it. If you had enough money to try to hedge by buying foreign securities, in theory you could be happy no matter what your dollar did: if it goes up, you have pain or gain from local effects (depending on whether imports or exports have a bigger effect on your life) and that is offset by your investment having gain or pain. Ditto if it goes down. In reality the amount you might have to invest to get to this point is probably not a realistic amount for an ordinary person to invest outside their country. I own a Canadian company that bills a number of US clients and I buy very little from the US (I'm big on local food, for example, and very frugal on the consumer-goods front.) When the Canadian dollar falls, I effectively get a raise, so I'm happy while all around me are wringing their hands.", "title": "" }, { "docid": "593820", "text": "Inflation is good for the economy primarily because it is an incentive to invest. If inflation is occurring, then keeping your holdings in cash is a net loser; 5% inflation means that in a year, your $100 is now worth $95.24 (1/1.05), so unless you're getting really good interest, that's a bad thing. On the other hand, if you invested that $100 in a business, you can outgain inflation more easily since inflation should drive the business's profits. Deflation (negative inflation), on the other hand, is bad for investing because it encourages holding cash. If deflation of 5% occurs, then you can get a 5% ROI by simply holding onto twenty dollar bills; why would you invest in a business that was in a deflationary economy (and thus would likely earn less money)? Mild inflation also increases flexibility in the economy, because businesses make a little more money (in terms of denominated money); that allows them more flexibility in expansion. Salaries for some also go up, meaning that spending goes up, and often with more flexibility in how those salaries are spent; inflation doesn't hit all sectors exactly the same, so often this leaves significant portions of the middle class with more money to spend (and thus driving economic growth). More than salary growth, though, inflation seems to drive job creation. From the New York Times, this article quotes a paper by George Akerloff which shows that job creation tends to be more significant than rising salaries during periods of low inflation (ie, what we're talking about here). Salary increases will come here largely from job seeking rather than raises, because businesses don't tend to cut wages and thus are reticent to significantly raise salaries; they'd rather just hire more people, and then cut jobs when the economy weakens (or inflation drops). This is even more true in low wage jobs, such as minimum wage positions, where wages cannot be cut but salary increases have little real effect on job retention; it's easier to change the number of hours for PT employees, or the number of PT/FT employees. Deflation, on the other hand, leads to decreased flexibility, layoffs, and lower consumer spending. While it sounds good to say 'hey, prices are going down!' to your average consumer, you have to keep in mind that those prices are what keep the businesses going that drive our economy and pay your salary (either directly or indirectly). If your employer started making 5% less per year, do you think they'd keep you employed? Maybe not, and at the bottom (service industries, fast food restaurants, grocers, etc.) there would be significant cutbacks if deflation hit them. I would note that 5% inflation is probably a bit high; most economists like 2% to 3%, and the Federal Reserve has said that 2% is the right target. They're mostly concerned with avoiding deflation, as that's a big risk to the economy; the advantages of mild inflation are relatively minor, compared to the damages of deflation, and tend to be more correlations (you get mild inflation in a good economy, as much or more than you need mild inflation for a good economy). Most important, probably, is consistent inflation. Consumers and businesses can act rationally if the inflation rate is relatively stable and predictable. When inflation jumps or drops, it changes the potential outcomes for choices made by investors, consumers, and businesses, meaning choices they made in the past are now suboptimal; if the inflation rate is jumping around (1% one year, 4% another, -1% the next) investors, businesses, and consumers will be relatively conservative in their choices, which leads to a bad economy.", "title": "" }, { "docid": "174002", "text": "Gold is a commodity. It has a tracked price and can be bought and sold as such. In its physical form it represents something real of signifigant value that can be traded for currency or barted. A single pound of gold is worth about 27000 dollars. It is very valuable and it is easily transported as opposed to a car which loses value while you transport it. There are other metals that also hold value (Platinum, Silver, Copper, etc) as well as other commodities. Platinum has a higher Value to weight ratio than gold but there is less of a global quantity and the demand is not as high. A gold mine is an investement where you hope to take out more in gold than it cost to get it out. Just like any other business. High gold prices simply lower your break even point. TIPS protects you from inflation but does not protect you from devaluation. It also only pays the inflation rate recoginized by the Treasury. There are experts who believe that the fed has understated inflation. If these are correct then TIPS is not protecting its investors from inflation as promised. You can also think of treasury bonds as an investment in your government. Your return will be effectively determined by how they run their business of governing. If you believe that the government is doing the right things to help promote the economy then investing in their bonds will help them to be able to continue to do so. And if consumers buy the bonds then the treasury does not have to buy any more of its own.", "title": "" }, { "docid": "147646", "text": "\"To add to MrChrister's answer: Canada also has a Consumer Price Index (CPI) used to measure inflation that is distinct and separate from that maintained by the United States. There are differences in inflation between the U.S. and Canada because our currencies are different, and there may be different items in the \"\"basket\"\" of goods that constitutes the index. You can find current information on the Canadian CPI at Statistics Canada, here: Latest release from the Consumer Price Index. Also, the Bank of Canada – our central bank – maintains a free online Inflation Calculator. The BoC's inflation calculator is handy because you can enter a dollar amount for a past date and it will figure out what that would be in today's dollars. For instance, $100 in 1970 dollars had the same purchasing power (under the CPI) as $561.76 in 2009 dollars! And you're right – if you get a salary increase that is less than the rate of inflation, then in theory you have lost purchasing power. So, anybody really looking for a raise ought to make an effort to get more than the increase in CPI. Of course, some employers are counting on you not knowing that, because any increase that's less than CPI is effectively a salary decrease; which could mean more profit for them, if they are able to increase their prices / revenues at inflation or better. Finally, consider that salary & wage increases also contribute to inflation! Perhaps you've heard of the wage/price inflation spiral. If you haven't, there's more on that here and here.\"", "title": "" }, { "docid": "590840", "text": "It is absolutely feasible to move your savings into Canada. There are a few ways you can do it. However it is unlikely you will benefit or avoid risk by doing so. You could directly hold your savings in the CAD. Investing in Canadian bonds achieves a similar goal as holding your money in the CAD. By doing so you will be getting re-payed with CAD. Some Canadian companies also trade on US markets. In addition some brokerage firms allow you to trade on Canadian markets. The problem with any of the options is the assumption that Canadian banks will fare better then US banks. The entire globe is very dependent on each other, especially the more developed nations. If large US banks were to fail it would create a domino effect which would spiral into a global credit crunch. It wouldn't matter if your invested in Canadian companies or US companies they would all suffer as would the global economy. So it would probably be more valid to refer to your question - enter link description here If you are referring to weather the Canadian bonds would be a safer investment over US Treasuries it would all depend on the scenario at hand. Investors would probably flock to both treasuries.", "title": "" }, { "docid": "577051", "text": "We need to be careful what we are talking about here. Inflation on a economy-level scale at an expected rate will not change consumer habits because the price increase is manageable. You have to realize that prices are not increasing in isolation: wages will have to rise along too. High inflation that is expected will increase consumption of durable goods, as people attempt to 'get rid of their money' before the price changes on them. A good example of this was post-WWI germany, where hyperinflation was so bad that offices began to pay their employees twice daily, so they could adjust their wages, and so that their employees could go out during lunch and after work to buy something with the money before the price changed on them. Unexpected inflation may cause a temporary dip in spending until wages adjust, however consumers still need to buy, so they will likely push for higher wages, leading to consumption to stay about level. There is another effect to inflation as well: People who have savings will have their savings eroded over time if the economy is inflationary. To preserve their wealth, they will invest it. In a deflationary environment, money will increase in value simply by being hoarded, so they will be less willing to invest it. Deflation also increases the cost of interest on a loan, while inflation decreases it. So the overall effect is for an increase in spending under inflation, and a decrease under deflation. The person you have quoted is quite wrong. Price increases in a particular sector will cause consumer spending to decrease but this is a bad example, as it is not inflation, but rather a supply/demand problem of a particular consumer good. They are applying a micro-economic model (price increases of a single good) to a macroeconomic problem (price increases in the entire economy) when price increases at a global scale have the opposite effects. A good theoretical test of this is: what would happen if everyone in the US suddenly had twice as much money? (Ignoring international trade, of course). The answer: prices will double, and nothing else will change. The reason is, people will have more money to spend, but will require more money for their services, so in the end it all cancels out.", "title": "" }, { "docid": "217727", "text": "\"The simplest, most convenient way I know of to \"\"move your savings to Canada\"\" is to purchase an exchange-traded fund like FXC, the CurrencyShares Canadian Dollar Trust, or a similar instrument. (I identify this fund because I know it exists, not because I particularly recommend it.) Your money will be in Canadian currency earning Canadian interest rates. You will pay a small portion of that interest in fees. Since US banks are already guaranteed by the FDIC up to $250,000 per account, I don't really think you avoid any risks associated with the failure of an individual bank, but you might fare better if the US currency is subject to inflation or unfavorable foreign-exchange movements - not that such a thing would be a direct risk of a bank failure, but it could happen as a result of actions taken by the Federal Reserve under the auspices of aiding the economy if the economy worsens in the wake of a financial crisis - or, for that matter, if it worsens as a result of something else, including legislative, regulatory, or executive policies. Read the prospectus to understand additional risks with this investment. One of them is foreign-exchange risk. If the US economy and currency strengthen relative to the Canadian economy and its currency, you may lose substantial amounts of purchasing power. Additionally, one of the possible results of a financial crisis is a \"\"flight to safety\"\"; the global financial markets still seem to think the US dollar is pretty safe, and they may bid it up as they have done in the past, resulting in losses to your position (at least in the short term). I do not personally recommend moving all your savings to Canada, especially if it deprives you of income from more profitable investments over the long term, but moving some of your savings to Canada at least isn't a stupid idea, and it may turn out to be somewhat profitable. Having some Canadian currency is also a good idea if you plan to spend the money that you are saving on Canadian goods in the intermediate future.\"", "title": "" }, { "docid": "89947", "text": "\"I would add to the other excellent answers that another factor besides just high unemployment numbers is the fear people have regarding the \"\"financial\"\" aspects of the country, that is the value of stocks and the value of the dollar. When the economy is sluggish it means people aren't buying enough, therefore companies aren't making enough, therefore their profits are too low and people start to divest from them, and stock prices drop. Or even the fear of this happening can induce people to sell off shares. The point is, people are worried \"\"in this economy\"\" because if--due to unemployment, low spending/consumer confidence--the stock market crashes again as it did in 2008/09, that represents a lot of savings lost, e.g. 40-50% of what one was counting on to retire with, particularly if you panic sell at the bottom. Now suddenly it's as if you had a huge robbery, and you will have to work longer into your retirement years than you'd planned. Similarly, if, due to monetary policy, the U.S. inflates the dollar, what one saved for retirement may not be sufficient. (These arguments are true for shorter periods than just one's retirement, but just taking that as an example). So it's not just unemployment that is worrisome \"\"in this economy\"\". This said, I agree with George Marian that one ought to be careful and plan well regardless of the winds of the economy. I guess for most people (and companies), though, \"\"in this economy\"\" means they can't get away with the kind of carelessness they might have during a boom.\"", "title": "" }, { "docid": "203926", "text": "I haven't read the terms here but the question may not have a good answer. That won't stop me from trying. Call the real rate (interest rate - inflation) and you'll have what is called negative real rates. It's rare for the overnight real rate to be negative. If you check the same sources for historical data you'll find it's usually higher. This is because borrowing money is usually done to gain an economic benefit, ie. make a profit. That is no longer a consideration when borrowing money short term and is IMO a serious problem. This will cause poor investment decisions like you see in housing. Notice I said overnight rate. That is the only rate set by the BoC and the longer rates are set by the market. The central bank has some influence because a longer term is just a series of shorter terms but if you looked up the rate on long Canadian real return bonds, you'd see them with a real rate around 1%. What happens when the central bank raise or lowers rates will depend on the circumstances. The rate in India is so high because they are using it to defend the rupee. If people earn more interest they have a preference to buy that currency rather than others. However these people aren't stupid, they realize it's the real rate that matters. That's why Japan can get away with very low rates and still have demand for the currency - they have, or had, deflation. When that changed, the preference for their currency changed. So if Canada hast forex driven inflation then the BoC will have to raise rates to defend the dollar for the purpose of lowering inflation from imports. Whether it works or not is another story. Note that the Canadian dollar is very dependant on the total dollar value of net oil exports. If Canada has inflation due too an accelerating economy this implies that there are profitable opportunities so businesses and individuals will be more likely to pay a positive real rate of interest. In that scenario the demand for credit money will drive the real rate of return.", "title": "" }, { "docid": "95890", "text": "\"The answer to your question depends on what you mean when you say \"\"growth\"\". If you mean a literal increase in the aggregate market capitalization of companies, across the entire market, then, no, this sort of growth is not possible without concomitant economic growth. The reason why is that the market capitalization of each company is proportional to its gross revenue, and the sum of all revenue from selling \"\"final goods\"\" (i.e., things purchased and used by consumers) is, apart from a few technicalities, the definition of GDP. The exact multiplier might fluctuate up or down depending on investors' expectations about how sales will grow or decline going forward, but in a zero-growth economy this multiplier should be stable over the long run. It might, however, still fluctuate over the short term, but more about that in a minute. Note that all of this applies to aggregate growth across all firms. Individual firms can still grow, of course, but as they must do this by gaining market share from other companies such growth would be balanced by a decline for some other firm. Also, I've assumed zero net exports (that's one of the \"\"technicalities\"\" I mentioned above) because obviously you could have export-driven growth even if the domestic economy were stationary. However, often when people talk about \"\"growth\"\" in the market, what they really mean is \"\"return\"\". That is, how much does your investment earn for you. This isn't really the same thing as growth, but people often think of it that way, particularly in the saving phase of their investing career, when they are reinvesting their returns, and therefore their account balances are growing. It is possible to have a positive return, averaged across the market, even in a stationary economy. The reason why is that there are really only two things a firm can do with its net profits. One possibility is that it could invest it in growing the business. However, there is not much point in doing that in a stationary economy because by assumption no increase in aggregate consumption (and therefore, in the long run, aggregate production) are possible. Therefore, firms are left with only the second option, which is to pay them out to investors as dividends. Those dividends provide a return that is independent of economic growth. Would the stock market still be a good investment in such an economy? Yes. Well, sort of. The rate of return from firms' dividend payouts will depend on investors' demand (in aggregate) for returns on their investments. Stock prices will rise or fall, causing returns to respectively fall or rise, to find that level. If your personal desire for returns is lower than the average across the investing public, then the stock market would look like a good investment. If your desired return is higher than the average, then it will look like a poor investment. The marginal investor will, of course be indifferent. The practical upshot of this is that the people who invest in the stock market in this scenario will be precisely the ones for whom the stock market is a good investment, given their personal propensity to save and desire for returns, and so forth. Finally, you mentioned that in your scenario the GDP stagnation is due to declining population. I am less certain what this means for investment, but my first thought is that you would have a large retired population selling its investments to fund late-life consumption, and you would have a comparatively small (relative to history) working population buying those assets. This would lead to low asset prices, and therefore high rates of return. However, that's assuming that retirees need to sell assets to fund their retirement consumption. If the absolute returns on retirees' assets are large enough to fund their retirement consumption then you would wind up with relatively few sellers, resulting in high prices and therefore relatively low rates of return. It's not obvious to me which effect would dominate, and so it's hard to say whether or not the resulting returns would look attractive to the working-age population.\"", "title": "" }, { "docid": "122018", "text": "Summarized article: The Department of Commerce reported that retail sales increased 1.1% in September, exceeding analysts' expectations. The biggest jump in consumer spending came from car sales, gasoline and electronics. Electronic sales jumped 4.5%, likely due to the debut of Apple's iPhone 5. Additionally, higher gas prices led to 2.5% increase in spending at gas stations. The latest report suggests the economy is expanding as consumer spending drives about 2/3 of the US economy. Other data showed manufacturing activity in New York state shrank for the third straight month as US manufacturers feel the effects of a slowing global economy. Shares rose and yields on government debt increased as the retail sales report bolstered investor sentiment. * For more summarized news, subscribe to the [/r/SkimThat](http://www.reddit.com/r/SkimThat) subreddit", "title": "" }, { "docid": "521233", "text": "\"The short answer is that banking is complicated, but the bank really doesn't need your money because it can get it from the Fed almost free, it can only use 90% of the money you give the bank, it can only make money on that 90% from very low-risk and thus low-return investments, and as it has to show a profit to its shareholders it will take whatever cut it needs to off the top of the returns. All of these things combine to make savings account interest roughly .05% in the US right now. The longer answer: All FDIC-insured banks (which the US requires all \"\"depositor\"\" banks to be) are subject to regulation by the Federal Reserve. The very first rule that all banks must comply with is that depositor money cannot be invested in things the Fed terms \"\"risky\"\". This limits banks from investing your money in things that have high returns, like stocks, commodities and hedges, because along with the high possible returns come high risk. Banks typically can only invest your savings in T-debt and in certain Fed-approved AAA bonds, which have very low risk and so very little return. The investment of bank assets into risky market funds was a major contributor to the financial crisis; with the repeal of the Glass-Steagall Act, banks had been allowed to integrate their FDIC-insured depositor business with their \"\"investment banking\"\" business (not FDIC insured). While still not allowed to bet on \"\"risky\"\" investments with deposits, banks were using their own money (retained profits, corporate equity/bond money) to bet heavily in the markets, and were investing depositor funds in faulty AAA-rated investment objects like CDOs. When the housing market crashed, banks had to pull out of the investment market and cash in hedges like credit-default swaps to cover the depositor losses, which sent a tidal wave through the rest of the market. Banks really can't even loan your money out to people who walk in, like you'd think they would and which they traditionally used to do; that's how the savings and loan crisis happened, when speculators took out huge loans to invest, lost the cash, declared bankruptcy and left the S&Ls (and ultimately the FDIC) on the hook for depositors' money. So, the upshot of all this is that the bank simply won't give you more on your money than it is allowed to make on it. In addition, there are several tools that the Fed has to regulate economic activity, and three big ones play a part. First is the \"\"Federal Funds Rate\"\"; this is the interest rate that the Fed charges on loans made to other banks (which is a primary source of day-to-day liquidity for these banks). Money paid as interest to the Fed is effectively removed from the economy and is a way to reduce the money supply. Right now the FFR is .25% (that's one quarter of one percent) which is effectively zero; borrow a billion dollars ($1,000,000,000) from the Fed for one month and you'll pay them a scant $208,333. Banks lend to other banks at a rate based on the FFR, called the Interbank Rate (usually adding some fraction of a percent so the lending bank makes money on the loan). This means that the banks can get money from the Fed and from other banks very cheaply, which means they don't have to offer high interest rates on savings to entice individual depositors to save their money with the bank. Second is \"\"quantitative easing\"\", which just means the Fed buys government bonds and pays for them with \"\"new\"\" money. This happens all the time; remember those interest charges on bank loans? To keep the money supply stable, the Fed must buy T-debt at least in the amount of the interest being charged, otherwise the money leaves the economy and is not available to circulate. The Fed usually buys a little more than it collects in order to gradually increase the money supply, which allows the economy to grow while controlling inflation (having \"\"too much money\"\" and so making money worth less than what it can buy). What's new is that the Fed is increasing the money supply by a very large amount, by buying bonds far in excess of the (low) rates it's charging, and at fixed prices determined by the yield the Fed wants to induce in the markets. In the first place, with the Fed buying so many, there are fewer for institutions and other investors to buy. This increases the demand, driving down yields as investors besides the Fed are willing to pay a similar price, and remember that T-debt is one of the main things banks are allowed to invest your deposits in. Inflation isn't a concern right now despite the large amount of new money being injected, because the current economy is so lackluster right now that the new cash is just being sat upon by corporations and being used by consumers to pay down debt, instead of what the Fed and Government want us to do (hire, update equipment, buy houses and American cars, etc). In addition, the \"\"spot market price\"\" for a T-bond, or any investment security, is generally what the last guy paid. By buying Treasury debt gradually at a fixed price, the Fed can smooth out \"\"jitters\"\" in the spot price that speculators may try to induce by making low \"\"buy offers\"\" on T-debt to increase yields. Lastly, the Fed can tell banks that they must keep a certain amount of their deposits in \"\"reserve\"\", basically by keeping them in a combination of cash in the vault, and in accounts with the Fed itself. This has a dual purpose; higher reserve rates allow a bank to weather a \"\"run\"\" (more people than usual wanting their money) and thus reduces risk of failure. An increased reserves amount also reduces the amount of money circulating in the economy, because obviously if the banks have to keep a percentage of assets in cash, they can't invest that cash. Banks are currently required to keep 10% of \"\"deposited assets\"\" (the sum of all checking and savings accounts, but not CDs) in cash. This compounds the other problems with banks' investing; not only are they not getting a great return on your savings, they can only use 90% of your savings to get it.\"", "title": "" }, { "docid": "538898", "text": "The Fed sets the overnight borrowing costs by setting its overnight target rate. The markets determine the rates at which the treasury can borrow through the issuance of bonds. The Fed's actions will certainly influence the price of very short term bonds, but the Fed's influence on anything other than very short term bonds in the current environment is very muted. Currently, the most influential factor keeping bond prices high and yields low is the high demand for US treasuries coming from overseas governments and institutions. This is being caused by two factors : sluggish growth in overseas economies and the ongoing strength of the US dollar. With many European government bonds offering negative redemption yields, income investors see US yields as relatively attractive. Those non-US economies which do not have negative bond yields either have near zero yields or large currency risks or both. Political issues such as the survival of the Euro also weigh heavily on market perceptions of the current attractiveness of the US dollar. Italian banks may be about to deliver a shock to the Eurozone, and the Spanish and French banks may not be far behind. Another factor is the continued threat of deflation. Growth is slowing around the world which negatively effects demand. Commodity prices remain depressed. Low growth and recession outside of the US translate into a prolonged period of near zero interest rates elsewhere together with renewed QE programmes in Europe, Japan, and possibly elsewhere. This makes the US look relatively attractive and so there is huge demand for US dollars and bonds. Any significant move in US interest rates risks driving to dollar ever higher which would be very negative for the future earning of US companies which rely on exports and foreign income. All of this makes the market believe that the Fed's hands are tied and low bond yields are here for the foreseeable future. Of course, even in the US growth is relatively slow and vulnerable to a loss of steam following a move in interest rates.", "title": "" }, { "docid": "81897", "text": "\"I have to disagree with you. **Money is a store of value with which you can redeem your accumulated work for a good or service you need, at any time.** Therefore, you don't have to wait until your crop has perished to trade it for what you need. Any store of value that is not purely useful in terms of \"\"I can consume this\"\" or \"\"I can turn this into value directly through labor\"\" is essentially an IOU. It would be more accurate to say, in the context you provide, that for every asset (your apples) there exists an equivalent combination of liability (what you had to borrow to produce the apples) and equity (what you put in of your own in order to get the apples). Since gold in this very simple hypothetical system has absolutely no use other than a **store of value**, it *is* debt. It is the promise that you will at some point in your process of transactions acquire the utility that you require. You can't fertilize with gold, but you can buy fertilizer. **Until you buy that fertilizer, you've only traded your harvest for a promise that you *can* buy your fertilizer.** Something otherwiseyep didn't elaborate on very much, though he mentioned it and it is integral to his story, is the time value of money. That is, if I can borrow 10 gold pieces today for my future work accumulated, I'll pay you back 12 when it's done. This has an effect greater than just injecting value into the economy. It ensures that the negative value experienced by *not* having those 10 gold pieces will be compensated. Credit provides an opportunity for planning for the cyclical nature of markets. It provides an opportunity to make your transaction now - that you don't have to wait until harvest to trade your deer skins for apples. &gt;Economists like Paul Krugman seem to believe that everything can be fixed by increasing demand, but they totally ignore the costs of production. There exists plenty of demand in the US economy right now, but the cooper has died, the barrels must be brought from China. I also disagree with this. Krugman emphasizes the *importance* of demand-side measures, not their exclusivity. Any policy must account for cost curves, and that economic profit for any firm is maximized when marginal revenue (the revenue increase or decrease of a single unit added to production) is equal to marginal cost. The U.S may have some demand right now, but if the cost of production were truly the issue, then these firms would be adjusting their capacity, and not sitting on trillions of dollars of currency that ought to be liquid. If demand was really that high, companies wouldn't be stuffing their mattresses right now to keep the money injected into the economy by QE *out* of circulation. The real problem is that while in the last few decades consumption has been climbing steadily, real wages have flat-lined, and now we have high unemployment. We can't raise wages, we can't hire more workers, and we still want our cars and houses and corn syrup and lead-filled toys. This, I think we can agree, is where credit goes wrong: the gap between consumption and wages was filled with credit. The housing bubble manifested itself thus: not as simply a boom in quantity and a lowering in price, but a lowering in price as a result of faulty (dishonest and misleading) risk assessment - (by the same folks who downgraded US debt), and an implosion as a result of that debt systematically dissolving through defaults and foreclosures (to put it very, very, very, simply). Instead of an increase in consumer credit, we need greater investment by the companies who currently sit on trillions of dollars of frozen cash. Those investments could be better managed, with transparent risk assessment and greater restrictions on lending policy. Or, ideally, that money could be used to hire workers, expand plants and lower marginal costs. To tie it back to your concluding paragraph, credit makes it possible to satisfy the demand for those barrels of apples by buying them at a fair market value from China. If it weren't for China's ability to provide the apples at a \"\"fair\"\" price (you can, for our purposes here, consider this price to be fair market value if you make a transaction - the selling price equals the buying price), there would be an apple shortage, and the price of apples would climb ridiculously high.\"", "title": "" }, { "docid": "220156", "text": "\"What happened was that people would start an \"\"Internet\"\" company without any viable business plan, and investors would pour money. Any company with \"\".COM\"\" or \"\"eSomething\"\" or \"\"netXXX\"\" or whatever would get tons of money from investors, basically selling dreams of getting rich fast. The companies that flourished back than had often no sales and no income, yet they paid high salaries and provided very lucrative benefits to the employees. One of the examples is Mirabilis - company that invented the on-line messenger (ICQ), but provided free service and free products (there were no fees associated with using the ICQ messenger). They got bought for almost half a billion dollars when they had ZERO revenues, by AOL. AOL sold the company, ten years later, for less than 200 million dollars when at that time ICQ (or, as re-branded, AIM) was already providing revenue (from advertisements). Eventually, investors stopped pouring the money in (for various reasons, but amongst others the higher rates and the slower overall economy), and almost immediately companies started going out of business, and then it all blew up.\"", "title": "" }, { "docid": "166412", "text": "\"Quantitative Easing Explained: http://www.npr.org/blogs/money/2010/10/07/130408926/quantitative-easing-explained The short of it is that you're right; the Fed (or another country's Central Bank) is basically creating a large amount of new money, which it then injects into the economy by buying government and institutional debt. This is, in fact, one of the main jobs of the central bank for a currency; to manage the money supply, which in most fiat systems involves slowly increasing the amount of money to keep the economy growing (if there isn't enough money moving around in the economy it's reflected in a slowdown in GDP growth), while controlling inflation (the devaluation of a unit of currency with respect to most or all things that unit will buy including other currencies). Inflation's primary cause is defined quite simply as \"\"too many dollars chasing too few goods\"\". When demand is low for cash (because you have a lot of it) while demand for goods is high, the suppliers of those goods will increase their price for the goods (because people are willing to pay that higher price) and will also produce more. With quantitative easing, the central bank is increasing the money supply by several percentage points of GDP, much higher than is normally needed. This normally would cause the two things you mentioned: Inflation - inflation's primary cause is \"\"too many dollars chasing too few goods\"\"; when money is easy to get and various types of goods and services are not, people \"\"bid up\"\" the price on these things to get them (this usually happens when sellers see high demand for a product and increase the price to take advantage and to prevent a shortage). This often happens across the board in a situation like this, but there are certain key drivers that can cause other prices to increase (things like the price of oil, which affects transportation costs and thus the price to have anything shipped anywhere, whether it be the raw materials you need or the finished product you're selling). With the injection of so much money into the economy, rampant inflation would normally be the result. However, there are other variables at play in this particular situation. Chief among them is that no matter how much cash is in the economy, most of it is being sat on, in the form of cash or other \"\"safe havens\"\" like durable commodities (gold) and T-debt. So, most of the money the Fed is injecting into the economy is not chasing goods; it's repaying debt, replenishing savings and generally being hoarded by consumers and institutions as a hedge against the poor economy. In addition, despite how many dollars are in the economy right now, those dollars are in high demand all around the world to buy Treasury debt (one of the biggest safe havens in the global market right now, so much so that buying T-debt is considered \"\"saving\"\"). This is why the yields on Treasury bonds and notes are at historic lows; it's bad everywhere, and U.S. Government debt is one of the surest things in the world market, especially now that Euro-bonds have become suspect. Currency Devaluation - This is basically specialized inflation; when there are more dollars in the market than people want to have in order to use to buy our goods and services, demand for our currency (the medium of trade for our goods and services) drops, and it takes fewer Euros, Yen or Yuan to buy a dollar. This can happen even if demand for our dollars inside our own borders is high, and is generally a function of our trade situation; if we're buying more from other countries than they are from us, then our dollars are flooding the currency exchange markets and thus become cheaper because they're easy to get. Again, there are other variables at play here that keep our currency strong. First off, again, it's bad everywhere; nobody's buying anything from anyone (relatively speaking) and so the relative trade deficits aren't moving much. In addition, devaluation without inflation is self-stablizing; if currency devalues but inflation is low, the cheaper currency makes the things that currency can buy cheaper, which encourages people to buy them. At the same time, the more expensive foreign currency increases the cost in dollars of foreign-made goods. All of this can be beneficial from a money policy standpoint; devaluation makes American goods cheaper to Americans and to foreign consumers alike than foreign goods, and so a policy that puts downward pressure on the dollar but doesn't make inflation a risk can help American manufacturing and other producer businesses. China knows this just as well as we do, and for decades has been artificially fixing the exchange rate of the Renmin B (Yuan) lower than its true value against the dollar, meaning that no matter how cheap American goods get on the world market, Chinese goods are still cheaper, because by definition the Yuan has greater purchasing power for the same cost in dollars. In addition, dollars aren't only used to buy American-made goods and services. The U.S. has positioned its currency over the years to be an international medium of trade for several key commodities (like oil), and the primary currency for global lenders like the IMF and the World Bank. That means that dollars become necessary to buy these things, and are received from and must be repaid to these institutions, and thus the dollar has a built-in demand pretty much regardless of our trade deficits. On top of all that, a lot of countries base their own currencies on our dollar, by basically buying dollars (using other valuable media like gold or oil) and then holding that cash in their own central banks as the store of value backing their own paper money. This is called a \"\"dollar board\"\". Their money becomes worth a particular fraction of a dollar by definition, and that relationship is very precisely controllable; with 10 billion dollars in the vault, and 20 billion Kabukis issued from Kabukistan's central bank, a Kabuki is worth $.50. Print an additional 20 billion Kabuki and the value of one Kabuki decreases to $.25; buy an additional 10 billion dollars and the Kabuki's value increases again to $.50. Quite a few countries do this, mostly in South America, again creating a built-in demand for U.S. dollars and also tying the U.S. dollar to the value of the exports of that country. If Kabukistan's goods become highly demanded by Europe, and its currency increases relative to the dollar, then the U.S. dollar gets a boost because by definition it is worth an exact, fixed number of Kabukis (and also because a country with a dollar board typically has no problem accepting dollars as payment and then printing Kabukis to maintain the exchange rate)\"", "title": "" }, { "docid": "322049", "text": "I think this question is very nearly off-topic for this site, but I also believe that a basic understanding of the why the tax structure is what it is can help someone new to investing to understand their actual tax liability. The attempt at an answer I provide below is from a Canadian & US context, but should be similar to how this is viewed elsewhere in the world. First note that capital gains today are much more fluid in concept than even 100 years ago. When the personal income tax was first introduced [to pay for WWI], a capital gain was viewed as a very deliberate action; the permanent sale of property. Capital gains were not taxed at all initially [in Canada until 1971], under the view that income taxes would have been paid on income-earning assets all along [through interest, dividends, and rent], and therefore taxing capital gains would be a form of 'double-taxation'. This active, permanent sale was also viewed as an action that an investor would need to work for. Therefore it was seen as foolish to prevent investors from taking positive economic action [redistributing their capital in the most effective way], simply to avoid the tax. However today, because of favourable taxation on capital gains, many financial products attempt to package and sell capital gains to investors. For example, many Canadian mutual funds buy and sell investments to earn capital gains, and distribute those capital gains to the owners of the mutual fund. This is no longer an active action taken by the investor, it is simply a function of passive investing. The line between what is a dividend and what is a capital gain has been blurred by these and similar advanced financial products. To the casual investor, there is no practical difference between receiving dividends or capital gain distributions, except for the tax impact. The notional gain realized on the sale of property includes inflation. Consider a rental property bought in 1930 for $100,000, and sold in 1960 for $180,000, assuming inflation between 1930 and 1960 was 70%. In 1960 dollars, the property was effectively bought for 170k. This means the true gain after accounting for inflation is only $10k. But, the notional gain is $80k, meaning a tax on that capital gain would be almost entirely a tax on inflation. This is viewed by many as being unfair, as it does not actually represent true income. I will pause to note that any tax on any investment at all, taxes inflation; interest, for example, is taxed in full even though it can be almost entirely inflationary, depending on economic conditions. A tax on capital gains may restrict market liquidity. A key difference between capital gains and interest/rent/dividends, is that other forms of investment income are taxed annually. If you hold a bond, you get taxed on interest from that bond. You cannot gain value from a bond, deferring tax until the date it matures [at least in Canada, you are deemed to accrue bond interest annually, even if it is a 0 coupon bond]. However, what if interest rates have gone down, increasing the value of your bond, and you want to sell it to invest in a business? You may choose not to do this, to avoid tax on that capital gain. If it were taxed as much as regular income, you might be even more inclined to never sell any asset until you absolutely have to, thus restricting the flow of capital in the market. I will pause here again, to note that laws could be enacted to minimize capital gains tax, as long as the money is reinvested immediately, thus reducing this impact. Political inertia / lobbying from key interests has a significant impact on the tax structure for investments. The fact remains that the capital gains tax is most significantly an impact on those with accrued wealth. It would take significant public support to increase capital gain tax rates, for any political party to enact such laws. When you get right down to it, tax laws are complex, and hard to push in the public eye. The general public barely understands that their effective tax rate is far lower than their top marginal tax rate. Any tax increases at all are often viewed negatively, even by those who would never personally pay any of that tax due to lack of investment income. Therefore such changes are typically made quietly, and with some level of bi-partisan support. If you feel the capital gains tax rules are illogical, just add it to the pile of such tax laws that exist today.", "title": "" }, { "docid": "123835", "text": "\"Canada would most likely not convert any time in the near future. The challenge for Canada converting to the US Dollar or the fictional \"\"Amero\"\" mentioned by JohnFX is that : Some of the benefits would be: The challenge right now for any government would be to sell the pros over the cons and from that viewpoint the cons would appear to have more negative impact to voters. Considering that Canada currently has a minority government with no expected change to that status for some time the risk would be very high. For more details see Pros and Cons of Canadian Monetary Union and to see the Mexican impact see North American Currency Union It is interesting to note that currency union was first proposed in 1999 when the Canadian Dollar fluctuated between $0.64 to $0.69 US. The Canadian Dollar is closer to par with the US Dollar currently (in fact it rose to $1.10 US in Nov. 2007). Look-up historical rates at the Bank of Canada\"", "title": "" }, { "docid": "290831", "text": "The catch is that you're doing a form of leveraged investing. In other words, you're gambling on the stock market using money that you've borrowed. While it's not as dangerous as say, getting money from a loan shark to play blackjack in Vegas, there is always the chance that markets can collapse and your investment's value will drop rapidly. The amount of risk really depends on what specific investments you choose and how diversified they are - if you buy only Canadian stocks then you're at risk of losing a lot if something happened to our economy. But if your Canadian equities only amount to 3.6% of your total (which is Canada's share of the world market), and you're holding stocks in many different countries then the diversification will reduce your overall risk. The reason I mention that is because many people using the Smith Maneuver are only buying Canadian high-yield dividend stocks, so that they can use the dividends to accelerate the Smith Maneuver process (use the dividends to pay down the mortgage, then borrow more and invest it). They prefer Canadian equities because of preferential tax treatment of the dividend income (in non-registered accounts). But if something happened to those Canadian companies, they stand to lose much of the investment value and suddenly they have the extra debt (the amount borrowed from a HELOC, or from a re-advanceable mortgage) without enough value in the investments to offset it. This could mean that they will not be able to pay off the mortgage by the time they retire!", "title": "" }, { "docid": "180", "text": "Chinese suppliers can quote their price in CNY rather than USD (as has been typical), and thus avoid the exchange risk from US dollar volatility- the CNY has been generally appreciating so committing to receive payments in US dollars when their costs are in CNY means they are typically on the losing end of the equation and they have to pad their prices a bit. Canadian importers will have to buy RMB (typically with CAD) to pay for their orders and Canadian exporters can take payment in RMB if they wish, or set prices in CAD. By avoiding the US dollar middleman the transactions are made less risky and incur less costs. Japan did this many decades ago (they, too, used to price their products in USD). This is important in transactions of large amounts, not so much for the tiny amounts associated with tourism. Two-way annual trade between China and Canada is in excess of $70bn. Of course Forex trading may greatly exceed the actual amounts required for trade- the world Forex market is at least an order of magnitude greater than size of real international trade. All that trading in currency and financial instruments means more jobs on Bay Street and more money flowing into a very vital part of the Canadian economy. Recent article from the (liberal) Toronto Star here.", "title": "" }, { "docid": "305810", "text": "\"I'm not sure what \"\"rents\"\" you are talking about, but corporate profits are completely different from high net worth individuals. And actually, most corporate profits are reinvested (literally) or returned to investors, many of whom are less-than-rich or are institutional investors like pension funds or investment funds who in turn provide those profits to their beneficiaries. If you are suggesting that the financial industry somehow contributes nothing to society, then you must lack an understanding of the importance of liquidity to a modern economy. For an example of what happens when liquidity dries up, look no further than 2008 or Greece today. If you want your cell phone, iPad, internet, etc, then you need a financial system because there is no way a company like Apple is getting enough funding to undertake massive projects like the iPod or iPhone without major multi-national banks who can provide the leverage to make it possible. Though Apple is an admittably poor example of this as they are now so wildly successful that they have a huge pile of cash that they actually are hording. Then again, look at the investor outcry that the Apple horde unleashed. As I said, it's bad business to stockpile cash and the investors let Apple know this. So Apple distributed that cash back to investors in the form of a dividend. Much of Apple stock is owned by non-1%ers and they all now have a sweet check for thousands of dollars (on average) in their mailbox due to evil corporate America.\"", "title": "" }, { "docid": "535340", "text": "\"As user quid states in his answer, all you need to do is open an account with a stock broker in order to gain access to the world's stock markets. If you are currently banking with one of the six big bank, then they will offer stockbroking services. You can shop around for the best commission rates. If you wish to manage your own investments, then you will open a \"\"self-directed\"\" account. You can shelter your investments from all taxation by opening a TFSA account with your stock broker. Currently, you can add $5,500 per year to your TFSA. Unused allowances from previous years can still be used. Thus, if you have not yet made any TFSA contributions, you can add upto $46,500 to your TFSA and enjoy the benefits of tax free investing. Investing in what you are calling \"\"unmanaged index funds\"\" means investing in ETFs (Exchange Traded Funds). Once you have opened your account you can invest in any ETFs traded on the stock markets accessible through your stock broker. Buying shares on foreign markets may carry higher commission rates, but for the US markets commissions are generally the same as they are for Canadian markets. However, in the case of buying foreign shares you will carry the extra cost and risk of selling Canadian dollars and buying foreign currency. There are also issues to do with foreign withholding taxes when you trade foreign shares directly. In the case of the US, you will also need to register with the US tax authorities. Foreign withholding taxes payable are generally treated as a tax credit with respect to Canadian taxation, so you will not be double taxed. In today's market, for most investors there is generally no need to invest directly in foreign market indices since you can do so indirectly on the Toronto stock market. The large Canadian ETF providers offer a wide range of US, European, Asian, and Global ETFs as well as Canadian ETFs. For example, you can track all of the major US indices by trading in Toronto in Canadian dollars. The S&P500, the Dow Jones, and the NASDAQ100 are offered in both \"\"currency hedged\"\" and \"\"unhedged\"\" forms. In addition, there are ETFs on the total US Market, US Small Caps, US sectors such as banks, and more exotic ETFs such as those offering \"\"covered call\"\" strategies and \"\"put write\"\" strategies. Here is a link to the BMO ETF website. Here is a link to the iShares (Canada) ETF website.\"", "title": "" }, { "docid": "480590", "text": "People that argue for an FTT, whether they know it or not, are directly advocating for savers to have reduced stock market returns, making it even harder to save for retirement. Make no mistake - a financial transactions tax would disproportionately hurt middle class savers the most. In almost every article I see advocating an FTT, the authors have a profound misunderstanding about how financial markets work. They focus on jealousy politics (target the rich!) and dismiss the hugely detrimental effects on the market as obscure academic objections. FFTs impose a DIRECT cost on ALL investors in four major ways: (1) larger bid/ask spreads, (2) higher volatility, (3) reduced capital mobility, and obviously (4) the tax itself. All of these things are BAD for any investor. Advocates for FFT essentially want the stock market to be less efficient. Even investors that make NO trades during the year will see the returns drop on their ETFs, mutual funds, index funds, that they are accumulating for retirement. Why? Institutional funds (Vanguard, Fidelity, etc) churn billions of dollars during the normal course of business handling buy/sell orders, portfolio rebalancing, unit creation/elimination. Increased bid/ask spreads make these transactions more expensive, higher volatility makes them more risky, reduced capital mobility reduces volumes available to trade, and the tax adds to the cost. All of these effects show up as reduced returns on a typical fund. Vanguard put the reduced returns on the order of 1% depending on fund style - in other words, hundreds of thousands of dollars in lost savings compounded over a middle class working career. For a middle class saver, that could mean the difference between retiring at a reasonable age or never being able to retire! But don't take my word on it. [There are an extensive number of studies and statements from both academia and industry on this subject, all saying the same thing.](https://modernmarketsinitiative.org/topics/ftt/) When Vanguard says an FTT will hurt investors, people should listen. Vanguard is perhaps the most consumer friendly investment firm in history, single-handedly responsible for bringing investing costs down near zero. They have done more for middle class investors than virtually any other firm.", "title": "" }, { "docid": "128048", "text": "\"When you invest in an S&P500 index fund that is priced in USD, the only major risk you bear is the risk associated with the equity that comprises the index, since both the equities and the index fund are priced in USD. The fund in your question, however, is priced in EUR. For a fund like this to match the performance of the S&P500, which is priced in USD, as closely as possible, it needs to hedge against fluctuations in the EUR/USD exchange rate. If the fund simply converted EUR to USD then invested in an S&P500 index fund priced in USD, the EUR-priced fund may fail to match the USD-priced fund because of exchange rate fluctuations. Here is a simple example demonstrating why hedging is necessary. I assumed the current value of the USD-priced S&P500 index fund is 1,600 USD/share. The exchange rate is 1.3 USD/EUR. If you purchase one share of this index using EUR, you would pay 1230.77 EUR/share: If the S&P500 increases 10% to 1760 USD/share and the exchange rate remains unchanged, the value of the your investment in the EUR fund also increases by 10% (both sides of the equation are multiplied by 1.1): However, the currency risk comes into play when the EUR/USD exchange rate changes. Take the 10% increase in the price of the USD index occurring in tandem with an appreciation of the EUR to 1.4 USD/EUR: Although the USD-priced index gained 10%, the appreciation of the EUR means that the EUR value of your investment is almost unchanged from the first equation. For investments priced in EUR that invest in securities priced in USD, the presence of this additional currency risk mandates the use of a hedge if the indexes are going to track. The fund you linked to uses swap contracts, which I discuss in detail below, to hedge against fluctuations in the EUR/USD exchange rate. Since these derivatives aren't free, the cost of the hedge is included in the expenses of the fund and may result in differences between the S&P500 Index and the S&P 500 Euro Hedged Index. Also, it's important to realize that any time you invest in securities that are priced in a different currency than your own, you take on currency risk whether or not the investments aim to track indexes. This holds true even for securities that trade on an exchange in your local currency, like ADR's or GDR's. I wrote an answer that goes through a simple example in a similar fashion to the one above in that context, so you can read that for more information on currency risk in that context. There are several ways to investors, be they institutional or individual, can hedge against currency risk. iShares offers an ETF that tracks the S&P500 Euro Hedged Index and uses a over-the-counter currency swap contract called a month forward FX contract to hedge against the associated currency risk. In these contracts, two parties agree to swap some amount of one currency for another amount of another currency, at some time in the future. This allows both parties to effectively lock in an exchange rate for a given time period (a month in the case of the iShares ETF) and therefore protect themselves against exchange rate fluctuations in that period. There are other forms of currency swaps, equity swaps, etc. that could be used to hedge against currency risk. In general, two parties agree to swap one quantity, like a EUR cash flow, payments of a fixed interest rate, etc. for another quantity, like a USD cash flow, payments based on a floating interest rate, etc. In many cases these are over-the-counter transactions, there isn't necessarily a standardized definition. For example, if the European manager of a fund that tracks the S&P500 Euro Hedged Index is holding euros and wants to lock in an effective exchange rate of 1.4 USD/EUR (above the current exchange rate), he may find another party that is holding USD and wants to lock in the respective exchange rate of 0.71 EUR/USD. The other party could be an American fund manager that manages a USD-price fund that tracks the FTSE. By swapping USD and EUR, both parties can, at a price, lock in their desired exchange rates. I want to clear up something else in your question too. It's not correct that the \"\"S&P 500 is completely unrelated to the Euro.\"\" Far from it. There are many cases in which the EUR/USD exchange rate and the level of the S&P500 index could be related. For example: Troublesome economic news in Europe could cause the euro to depreciate against the dollar as European investors flee to safety, e.g. invest in Treasury bills. However, this economic news could also cause US investors to feel that the global economy won't recover as soon as hoped, which could affect the S&P500. If the euro appreciated against the dollar, for whatever reason, this could increase profits for US businesses that earn part of their profits in Europe. If a US company earns 1 million EUR and the exchange rate is 1.3 USD/EUR, the company earns 1.3 million USD. If the euro appreciates against the dollar to 1.4 USD/EUR in the next quarter and the company still earns 1 million EUR, they now earn 1.4 million USD. Even without additional sales, the US company earned a higher USD profit, which is reflected on their financial statements and could increase their share price (thus affecting the S&P500). Combining examples 1 and 2, if a US company earns some of its profits in Europe and a recession hits in the EU, two things could happen simultaneously. A) The company's sales decline as European consumers scale back their spending, and B) the euro depreciates against the dollar as European investors sell euros and invest in safer securities denominated in other currencies (USD or not). The company suffers a loss in profits both from decreased sales and the depreciation of the EUR. There are many more factors that could lead to correlation between the euro and the S&P500, or more generally, the European and American economies. The balance of trade, investor and consumer confidence, exposure of banks in one region to sovereign debt in another, the spread of asset/mortgage-backed securities from US financial firms to European banks, companies, municipalities, etc. all play a role. One example of this last point comes from this article, which includes an interesting line: Among the victims of America’s subprime crisis are eight municipalities in Norway, which lost a total of $125 million through subprime mortgage-related investments. Long story short, these municipalities had mortgage-backed securities in their investment portfolios that were derived from, far down the line, subprime mortgages on US homes. I don't know the specific cities, but it really demonstrates how interconnected the world's economies are when an American family's payment on their subprime mortgage in, say, Chicago, can end up backing a derivative investment in the investment portfolio of, say, Hammerfest, Norway.\"", "title": "" }, { "docid": "128676", "text": "EFA must be bought and sold in US dollars. XIN allows people to buy and sell EFA in Canadian dollars without exposing their investment to unpredictable swings in the USD/CAD ratio. This is what's known as a currency-hedged instrument. Now, why the chart sums up to over 100% is anyone's guess. Presumably it's the result of a couple hundred rounding errors from all the components. If you view their most recent report, it also sums up to over 100%, but at least the EFA component is (sensibly) under 100%. P.S. I'm not seeing where it says there's only one holding. There's the primary holding, plus over 100 other cash holdings to effect the currency-hedging.", "title": "" }, { "docid": "32328", "text": "Fundamentally these are my opinions I am expressing. Even though I try to remain as factual as possible, and have significantly modified my opinion over the years as a result of apparently factual information, it's still technically just opinion. &gt; My view is not so much that labour and finance capital returns need to be balanced (although that is probably a great thing to aim for), but that creation of wealth/capital needs to be intrinsically linked with the creation of real value. By the way, when I say capital it's not generally just finance capital, but all operational capital goods. Which includes factories and all means of production. A certain amount of financing is needed to keep it operational, and more is needed to increase the means of production to grow overall wealth. Have you ever heard of the [Bowley's law](http://en.wikipedia.org/wiki/Bowley%27s_law)? Basically you can't really push this ratio very far. If consumer demand dries up then production will get cut back to meat demand. Overproduction of stuff they can't sell is not what they are in business for. Likewise, is demand exceeds the capacity of production to keep up it pushes inflation, which drives up cost to reduce demand. So this ratio remains very nearly a constant. Even though this ratio was at historic highs in the 1970s, and historic lows today. What happens when you artificially dry up labor returns, through excessive supply side policies, is that demand for production falls. Hence production is cut back to meet that demand. This of course reduces employment and increases job competition, which puts more downward on wages exacerbating the situation. Only once labor cost fall low enough it effectively subsidizes inefficient production methods which limits the falling wages at a reduced overall productivity. Note that this is under present circumstances, not those of the 1970s. This adaptive matching between production and demand insures that the Bowley ratio is never too far off of its historical averages, even if productivity is driven well below its potential. More or less the same effect occurs for the opposite reason if capital return ratios are too low. Though with opposite effects on the inflation rate and such. When consumer demand is high enough capital will pay whatever labor cost is required to meet that demand, so long as it remains profitable enough, i.e., they get a reasonable ratio of the market return. Consumer demand with sufficient capital profit margins is what drives full employment, not the sheer volume of capital returns as present policies essentially assume. Yet you can't have a broad based consumer demand, to drive employment, without sufficient labor returns, as those labor returns is what finances that demand needed to drive employment. So not only does labour and capital returns need to be balanced. Economics does NOT allow it to be unbalanced, at least for long. Even if balancing requires the economy to shrink, productivity to fall, etc., that is exactly what it will do to remain balanced. No choice given, no matter how draconian the regulations to force it. This is true under purely agrarian economies of the past, pure communism, and even ecology. This is why I am a capitalist, because nature gives me no choice. But acceptance of that fact does not require me to have an ounce of tolerance for cronyism. The only thing we can do is not push this balance in either direction to destructive levels. Because destruction is what will happen for the balance to remain. Because so much of our productive capacity has been in productivity gains since the 1990s, and wages and demand have as yet not matched these productivity gains, we have a huge latent wealth capacity that continues to grow as we fail to take advantage of it. So far our supply side policies haven't so much destroyed wealth and productivity. Rather it has prevented us from seeing the potential gains from the latent productivity growth from technologies over the few decades. --- The last part you mention about wealth/capital needing to be intrinsically linked with the creation of real value. You are absolute 100% entirely correct. Perhaps even more than you know. Ever heard of planned obsolescence, or [The Light Bulb Conspiracy](http://topdocumentaryfilms.com/light-bulb-conspiracy/)? That link is a documentary on the issue that will make you mad. We could almost certainly pay a flat 90% tax rate on everything and still not come close to what this issue cost us. That's not the only means this issue imposes cost, but it is extreme. Of course just because an appliance still works doesn't mean people will not replace it with newer better models. But the trash pile insures there is a much more limited secondary market for poorer people. Consumption debt cost is also a far bigger issue than people recognize. Debt to finance capital goods for production is fine, as this feeds productivity and wealth in a manner that sustains itself even as the debt is paid. Consumption debt is an entirely different beast. Creating a significant section of the population that feeds on peoples income without producing a thing. Only to let allow people to consume income they haven't earned yet. This generally falls under the category of rent seeking behavior. Yeah, the lack real value creation turns my stomach. That people will knowingly spend money on temporary non-essential novelties and such is all fine and dandy, but underhandedly renting our base appliances for a certain number of uses is outrageous in my book.", "title": "" }, { "docid": "261975", "text": "\"I used to be in research department for big financial data company. Tell your son that there are three factors: Most people think that net sales vs. expectations is the only factor. It might not even be the biggest. It is simply how much money did company make. Note that this is not how many units they sold. For most companies they will have adjustable pricing and incentives in their sector. For example let's talk about a new company selling Superman Kid's Bikes (with a cape the flips out when you hit a certain speed). The company has it in Walmart at one price, Target at another, Toys R' Us even cheaper, Amazon (making more profit there), and other stores. They are doing \"\"OK\"\" come Dec. 1 but holiday season being half way over they slash price from $100 to $80 because they have tons of inventory. What are looking at her is how much money did they make. Note that marketing, advertising, legal (setting up contracts) are a bit fixed. In my opinion consumer sentiment is the #1 thing for a company that sells a product. Incredible consumer sentiment is like millions of dollars in free advertising. So let's say Dec. 15th comes and the reviews on the Superman Bike are through the roof. Every loves it, no major defects. Company can't even supply the retailers now because after slashing the price it became a great buy. A common investor might be pissed that some dummy at the company slashed the prices so they could have had a much better profit margin, but at the same time it wouldn't have led to an onslaught of sales and consumer sentiment. And the last area is product sell-off. This doesn't apply to all product but most. Some products will only have a technology shelf life, some will actually go bad or out of fashion, and even selling Superman bikes you want to get those to the store because the product is so big. So ignoring making a profit can a company sell off inventory at or around cost. If they can't, even if they made a profit, their risk factor goes up. So let's get back to Superman Bikes. This is the only product company ABC has. They had expected holiday sales at 100 million and profits at 40 million. They ended up at 120 million and 44 million. Let's say their stock was $20 before any information was gathered by the public (remember for most companies info is gathered daily now so this is rather simplistic). So you might expect that the stock would rise to maybe $24 - to which if you were an investor is a great profit. However this company has a cult consumer following who are waiting for the Captain America Bike (shoots discs) and the Hulk Bike (turns green when you go fast). Let's say consumer sentiment and projections base off that put next holiday sales at $250 million. So maybe the company is worth $40 a share now. But consumer sentiment is funny because not only does it effect future projections but it also effects perceived present value of company - which may have the stock trading at $60 a share (think earnings and companies like Google). Having a company people feel proud owning or thinking is cool is also a indicator or share worth. I gave you a really good example of a very successful company selling Superman Bikes... There are just as many companies that have the opposite happening. Imagine missing sales goals by a few million with bad consumer feedback and all of a sudden your company goes from $20 to $5 a share.\"", "title": "" }, { "docid": "580757", "text": "If you do not understand the volatility of the fx market, you need to stop trading it, immediately. There are many reasons that fx is riskier than other types of investing, and you bear those risks whether you understand them or not. Below are a number of reasons why fx trading has high levels of risk: 1) FX trades on the relative exchange rate between currencies. That means it is a zero-sum game. Over time, the global fx market cannot 'grow'. If the US economy doubles in size, and the European economy doubles in size, then the exchange rate between the USD and the EUR will be the same as it is today (in an extreme example, all else being equal, yes I know that value of currency /= value of total economy, but the general point stands). Compare that with the stock market - if the US economy doubles in size, then effectively the value of your stock investments will double in size. That means that stocks, bonds, etc. tied to real world economies generally increase when the global economy increases - it is a positive sum game, where many players can be winners. On the long term, on average, most people earn value, without needing to get into 'timing' of trades. This allows many people to consider long-term equity investing to be lower risk than 'day-trading'. With FX, because the value of a currency is in its relative position compared with another currency, 1 player is a winner, 1 player is a loser. By this token, most fx trading is necessarily short-term 'day-trading', which by itself carries inherent risk. 2) Fx markets are insanely efficient (I will lightly state that this is my opinion, but one that I am not alone in holding firmly). This means that public information about a currency [ie: economic news, political news, etc.] is nearly immediately acted upon by many, many people, so that the revised fx price of that currency will quickly adjust. The more efficient a market is, the harder it is to 'time a trade'. As an example, if you see on a news feed that the head of a central bank authority made an announcement about interest rates in that country [a common driver of fx prices], you have only moments to make a trade before the large institutional investors already factor it into their bid/ask prices. Keep in mind that the large fx players are dealing with millions and billions of dollars; markets can move very quickly because of this. Note that some currencies trade more frequently than others. The main currency 'pairs' are typically between USD and / or other G10 country-currencies [JPY, EUR, etc.]. As you get into currencies of smaller countries, trading of those currencies happens less frequently. This means that there may be some additional time before public information is 'priced in' to the market value of that currency, making that currency 'less efficient'. On the flip side, if something is infrequently traded, pricing can be more volatile, as a few relatively smaller trades can have a big impact on the market. 3) Uncertainty of political news. If you make an fx trade based on what you believe will happen after an expected political event, you are taking risk that the event actually happens. Politics and world events can be very hard to predict, and there is a high element of chance involved [see recent 'expected' election results across the world for evidence of this]. For something like the stock market, a particular industry may get hit every once in a while with unexpected news, but the fx market is inherently tied to politics in a way that may impact exchange rates multiple times a day. 4) Leveraging. It is very common for fx traders to borrow money to invest in fx. This creates additional risk because it amplifies the impact of your (positive or negative) returns. This applies to other investments as well, but I mention it because high degrees of debt leveraging is extremely common in FX. To answer your direct question: There are no single individual traders who spike fx prices - that is the impact you see of a very efficient market, with large value traders, reacting to frequent, surprising news. I reiterate: If you do not understand the risks associated with fx trade, I recommend that you stop this activity immediately, at least until you understand it better [and I would recommend personally that any amateur investor never get involved in fx at all, regardless of how informed you believe you are].", "title": "" }, { "docid": "223291", "text": "Common sense was the foundation - the idea that you can't spend more than you take in, indefinitely, without there being negative long term effects. We've been doing that since 1958. With that as the base, then watching what is going on in the economy, not just in the present day, but historically. Looking into how the government has manipulated the economic numbers for decades. Consumer confidence counts for a lot - which is why some of the numbers have been manipulated. Investor confidence counts for a lot too - which explains the others. You can only hide things for so long, though. Borrowing from Peter to pay Paul and then borrowing even more from Paul to pay Peter so Bob thinks you're credit worthy only works until they all figure out you haven't actually got enough money to pay them back, and won't ever. As for confidence, I'm making major life decisions based on it, so I'd say pretty confident. I just hope to be reasonably well prepared by the time it all goes down.", "title": "" } ]
905
Creating a Limited company while still fully employed
[ { "docid": "233702", "text": "Can I apply for limited company now, while fully time employed, and not take any business until I get a contract? Some employment contracts may include non-compete clauses or similar which expressly forbid you engaging in other employment or becoming self-employed while simultaneously working for your current employer. You may want to check this out before making any moves to register as a limited company. You may forfeit long-term benefits (such as a pension) you have built up at your present employer if they catch wind of a conflict of interest. As noted in an earlier answer, the setup process for a limited company is extremely simple in the UK, so there is no reason you need to take these steps in advance of leaving your current employment. During my resignation period scout for contracts... Should I wait weeks before actually deciding to search for contracts? Depending on the type of IT work you intend to be contracting for, you may find yourself shut out from major work if you are not VAT registered. It is a requirement to register for VAT when you breach certain earnings limits (see HMRC's website) but you can voluntarily register with HMRC before these limits if you wish. Being VAT registered increases your bookkeeping and oversight requirements, which makes you appear more attractive to larger enterprises / corporations than a non-VAT registered firm. It also suggests some degree of stability and a plan to stick around for the long haul. This might be a catch-22 situation - if you want to get noticed and land the sizable contracts, you will almost certainly require a VAT registration regardless of your overall yearly earnings. It would be advisable to engage the services of a professional advisor before becoming VAT registered, but this and the subsequent professional advice you may require for putting in VAT claims may not be a fee you wish to pay upfront if you are only attracting a small volume of work.", "title": "" }, { "docid": "442425", "text": "You can register a limited company and leave it dormant, that's no problem. You just need to make sure that later on you notify HMRC within 3 months of any trading activity. As pointed out, you can register a company in a few hours now so I wouldn't worry about that. Your confusion about Private Limited Companies is understandable, it's often not made clear but UK formation services standard packages are always Private Limited by Shares companies. Limited by Guarantee is something else, and normally used by charities or non-profits only. See explanations here. Registering for VAT is optional until you reach the £81,000 turnover threshold but it can make your services more attractive to large companies - especially in your field of business. You should really seek professional advice on whether or not this is the best option for you.", "title": "" }, { "docid": "464385", "text": "I was just thinking ahead, can I apply for Limited company now, while fully time employed, and not take any business until I get a contract. Yes. You can open as many companies you want(assuming you are sane). There is no legal provisions regarding who can open a company. What happens if I create a company and it has no turnover at all? Does this complicate things later? After you open a company, you have to submit your yearly statements to Companies House, whether you have a billion pounds turnover or 0. If you claim VAT that has also to be paid after you register for VAT. VAT registration is another registration different from opening a limited company. Is it the same if I decided to take a 1,2 or x month holiday and the company again will not incur any turnover? Turnover is year end, so at the year end you have to submit your yearly results, whether you took a 12 month holiday or a week's holiday. Is it a OK to do this in foresight or should I wait weeks before actually deciding to search for contracts. No need to open a limited company now, if you are so paranoid. Opening a company in UK takes 5 minutes. So you can open a company after landing a contract.", "title": "" } ]
[ { "docid": "544995", "text": "Yes if you do it as a hobby, as it's still income. But it should be something you can offset against tax Either way, you shouldn't be doing this as you, you should either register as self employed or create a company. You register this income as self-employed income (or income of the company) and offset the expenses of running the server against tax. In the UK, companies (or self employed people, which are basically companies) pay tax on profit not income (unless VAT applies, in which case they're basically just passing the VAT on for their customers). Since you're not making a profit over the whole year (even if some months are profitable) you will pay no tax.", "title": "" }, { "docid": "469043", "text": "\"&gt; There may not be anything shameful about doing that, but that scenario is, indeed, a business **failure**. People do not shutter a profitable (successful) business and then go to work for someone else. Not necessarily. It may very well be a \"\"planned exit\"\" -- not all businesses will (nor should they be expected to or *planned* to) endure into perpetuity... just because the corporate charter sets no specific limit to the duration of the corporate entity does not mean that it is (and certainly not that it needs to be) \"\"immortal\"\". And a business that may be quite profitable to run, even if it's final pre-closing year is less so... is not necessarily a \"\"failure\"\": in fact closing an operation down *while it is (still) slightly profitable*, and BEFORE it begins losing money (and/or selling it's assets off while they still have substantial investment value), may in fact be the **wisest** move (especially financially speaking); which counts as anything BUT a \"\"failure\"\". Plus there are several industries where a \"\"temporary\"\" existence of a firm is heartily recognized as a positive thing: take films as an example, a new \"\"company\"\" (with a pre-planned, limited lifespan) will often be formed to craft and produce the film, and cease to exist once that task has been completed. And I think the hand-wringing about \"\"restaurants\"\" is especially gratuitous... if ever there was/is a business niche that was subject to fad &amp; fashion, and the ephemeral even transitory nature of people's \"\"tastes\"\", it would be the \"\"boutique\"\" segment of the restaurant industry; even the ones (or chains) that do manage to survive, often do so by dramatically changing their menus, brand &amp; character... so that a decade later they barely resemble their former selves. Sure there are also other segments of the industry that are generally \"\"stable\"\" -- but many of them tend to be slow-or-no growth as well. &gt;I believe a key contributor to the confusion is talking about the self-employed and business owners in the same breath. Someone who's self-employed basically owns a job. His income will always be directly proportional to the amount of time spent working and the company does not exist apart from himself. It covers an entire spectrum... and the lines are rather fuzzy. Yes, a lot of self-employed people (whether configured as sole proprietorships, partnerships, LLC's or full \"\"corporations\"\") are by INTENT -- and probably always will be -- simply \"\"job replacement\"\" businesses. (And again, there is NOTHING wrong with that -- whether they endure for a year, 5 years, 10 years or an entire lifetime). How or why people have come to view this as somehow of less \"\"merit\"\" than someone being gainfully employed *for someone else* -- has always puzzled me. But some of those -- just as some of the \"\"part time\"\" or \"\"on the side\"\" businesses -- can take on an (unexpected, unplanned) \"\"life of their own\"\" and grow into substantial enterprises that employ hundreds and even thousands of people over multiple decades. AFTER THE FACT, the owners will often (at least publicly) claim that it was \"\"all part of the plan\"\", but in several cases where I know the founder/owner personally... I know from private conversation that THAT simply wasn't the case. &gt;A business owner, on the other hand, has processes/equipment/staff/IP in place that generates income whether or not she gets out of bed in the morning. You are speaking of someone who has achieved a CERTAIN level of success, and a certain SIZE of operations. &gt;These are different people with different goals and cannot be lumped into the same demographic block. Any and all \"\"blocks\"\" are going to be subjective (and in a very real sense the dividing lines placed at rather arbitrary segments) -- a particular named \"\"block\"\" will be very true from ONE point of view (with lots of things that correlate and appear to be uniformly applicable)... and yet fallacious from another (where there is again a whole spectrum of distinctions).\"", "title": "" }, { "docid": "492428", "text": "An employer can decide that the employee funds are automatically vested. The new company could have had a more aggressive vesting schedule and grandfathered in all the employees of the company they acquired. This could have been part of the purchase negoaitaions. I would be surprised if they did it for employees that left years ago, especially if they were beyond the return period. I wouldn't keep money in a plan with a former employer just in case it happens. Check the plan documents to see all the verbiage regarding vesting here is a paragraph from one: You will receive one year of vesting service for each calendar year during which you complete 850 or more hours of service. Once you have five years of service, your account is fully vested and any future Company contributions made to your account will be immediately vested. Full vesting also occurs at age 59½, total disability or death while employed by the Company. If you leave the Company prior to 100% vesting, any unvested portion of your Plan account will be forfeited.", "title": "" }, { "docid": "416378", "text": "\"Can a company say \"\"StackExchange\"\" donate to a non-profit company say $5,000 in agreement that they will spend that on paying a designer for a new website? And most importantly is this donation still tax deductible? A non-profit would have to typically create a bucket for IT Services or Website design. As long as \"\"StackExchange\"\" specify they employ a profession service to get it done, there would be no issue. If \"\"StackExchange\"\" were to specify an individula/company it would be an issue.\"", "title": "" }, { "docid": "460905", "text": "Defined Benefit Plans: Defined benefit plans are disappearing because of their high cost to the companies that provide them. When an employee retires, the company must pay his pension for the rest of his life, even longer if the pension includes a survivor option. Thus the company's financial burden grows as more employees retire. By law, they must provide a fund that has sufficient resources to pay all present and future pensions. Low interest rates, such as we have now, place a greater burden on the amount that must be in these funds. For these reasons, most companies, including large ones like IBM and Lockheed Martin, have discontinued their pension plans and provide only defined contribution plans. Defined Contribution Plans: These require the company to only make contributions while the employee is working. Once the employee retires, the company's responsibility ends. Usually these plans employ a 401K type savings plan for which the employee contributes and the companies matches some or all of that contribution. Comparison: Although a fully company paid pension plan is the best, it is now almost unavailable. The defined contribution plan, if it includes company matching, can be a viable alternative if the investments are chosen wisely and perform as expected. Of course, this is not guaranteed but is probably the best option that most working people have at this time.", "title": "" }, { "docid": "406561", "text": "\"The limit on SEP IRA is 25%, not 20%. If you're self-employed (filing on Schedule C), then it's taken on net earning, which in your example would be 25% of $90,000. (https://www.irs.gov/retirement-plans/retirement-plans-for-self-employed-people) JoeTaxpayer is correct as regards the 401(k) limits. The elective deferrals are per person - That's a cap in sum across multiple plans and across both traditional and Roth if you have those. In general, it's actually across other retirement plan types too - See below. If you're self-employed and set-up a 401(k) for your own business, the elective deferral is still aggregated with any other 401(k) plans in which you participate that year, but you can still make the employer contribution on your own plan. This IRS page is current a pretty good one on this topic: https://www.irs.gov/retirement-plans/one-participant-401k-plans Key quotes that are relevant: The business owner wears two hats in a 401(k) plan: employee and employer. Contributions can be made to the plan in both capacities. The owner can contribute both: •Elective deferrals up to 100% of compensation (“earned income” in the case of a self-employed individual) up to the annual contribution limit: ◦$18,000 in 2015 and 2016, or $24,000 in 2015 and 2016 if age 50 or over; plus •Employer nonelective contributions up to: ◦25% of compensation as defined by the plan, or ◦for self-employed individuals, see discussion below It continues with this example: The amount you can defer (including pre-tax and Roth contributions) to all your plans (not including 457(b) plans) is $18,000 in 2015 and 2016. Although a plan's terms may place lower limits on contributions, the total amount allowed under the tax law doesn’t depend on how many plans you belong to or who sponsors those plans. EXAMPLE Ben, age 51, earned $50,000 in W-2 wages from his S Corporation in 2015. He deferred $18,000 in regular elective deferrals plus $6,000 in catch-up contributions to the 401(k) plan. His business contributed 25% of his compensation to the plan, $12,500. Total contributions to the plan for 2015 were $36,500. This is the maximum that can be contributed to the plan for Ben for 2015. A business owner who is also employed by a second company and participating in its 401(k) plan should bear in mind that his limits on elective deferrals are by person, not by plan. He must consider the limit for all elective deferrals he makes during a year. Notice in the example that Ben contributed more that than his elective limit in total (his was $24,000 in the example because he was old enough for the $6,000 catch-up in addition to the $18,000 that applies to everyone else). He did this by declaring an employer contribution of $12,500, which was limited by his compensation but not by any of his elective contributions. Beyond the 401(k), keep in mind that elective contributions are capped across different types of retirement plans as well, so if you have a SEP IRA and a solo 401(k), your total contributions across those plans are also capped. That's also mentioned in the example. Now to the extent that you're considering different types of plans, that's a whole question in itself - One that might be worth consulting a dedicated tax advisor. A few things to consider (not extensive list): As for payroll / self-employment tax: Looks like you will end up paying Medicare, including the new \"\"Additional Medicare\"\" tax that came with the ACA, but not SS: If you have wages, as well as self-employment earnings, the tax on your wages is paid first. But this rule only applies if your total earnings are more than $118,500. For example, if you will have $30,000 in wages and $40,000 in selfemployment income in 2016, you will pay the appropriate Social Security taxes on both your wages and business earnings. In 2016, however, if your wages are $78,000, and you have $40,700 in net earnings from a business, you don’t pay dual Social Security taxes on earnings more than $118,500. Your employer will withhold 7.65 percent in Social Security and Medicare taxes on your $78,000 in earnings. You must pay 15.3 percent in Social Security and Medicare taxes on your first $40,500 in self-employment earnings and 2.9 percent in Medicare tax on the remaining $200 in net earnings. https://www.ssa.gov/pubs/EN-05-10022.pdf Other good IRS resources:\"", "title": "" }, { "docid": "478060", "text": "\"The primary advantage of HFTs is their speed to act upon opportunities that exist for only fractions of a second. The reason why they are able to do this is because they invest heavily in hardware, custom software, and custom algorithms. Most of the fleeting advantage, as they all manage to top each other's hardware seemingly every other day, is from the hardware investment. To see the extremes that HFTs will go to invest in hardware, one might view this. It is highly likely that the trader with the market making algorithm could have been ignorant of the \"\"hide not slide\"\" order and missed out on many more opportunities while still being successful. Haim Bodek, who is very much against this order type, was not so lucky. If it was truly an investment bank then it was unlikely that they were actually front running, which is very illegal and easily possible with much more low tech means, since companies like Citadel handle most orders now, and they have not been successful in investment banking. The reality of HFT is slowly coming to light, that while HFT can provide extremely consistent returns with enormous sharpe ratios, the capital investment is equally enormous, and the amount of capital that can be employed is also as enormously limited. After all, the richest people on the planet are not HFT owners. Also, when it comes to time periods longer than 500ms, their results become very human.\"", "title": "" }, { "docid": "561299", "text": "Our Website http://alignmentspinecare.com/ A holistic Chiropractor Queens will treat the client until subluxations are fully resolved and then broaden their attention to include general subluxation correction in the entire spine in order to promote general wellness. Both approaches have real value. While imposing limits on treatment based on the limits of what peer-reviewed research can substantiate is important, holistic chiropractors acknowledge that progress in science occurs by pushing the limits of understanding and treating patients in ways that current best evidence may not fully support. The periphery of science is where progress is usually made - though it is also where quackery finds refuge.", "title": "" }, { "docid": "111354", "text": "From my experience it is much easier to start as a self-employed rather than a limited company. You almost have no paperwork and self assessment can be done online in as little as 20 minutes (from personal experience). On the other hand having a limited company grants you a pile of papers to fill in from the start and almost certainly needing an accountant to do your taxes. Regarding the income tax - if you have no profits, you will pay no tax. And that will leave you only with national insurance that is only about £70 for 3 month (better check with HMRC for the exact figure). So if you don't have a good enough reason to do a Ltd, start as a self-employed, you can always change to limited company later.", "title": "" }, { "docid": "72402", "text": "No, the situation is not different, the roll-over rules are the same. It won't be taxable (as opposed to traditional to Roth roll-over), but other than that it's the same. Whether the 401k allows rolling over or not while you're still employed - you have to check with the plan administrator (ask your payroll/HR for details). Usually, the deferred compensation cannot be rolled over out of the 401k while you're still employed.", "title": "" }, { "docid": "133511", "text": "The reason they have this massive debt is largely (not entirely) because they have been employing Keynes' policies and spending more than they had for so many years as it is. Austerity is not the solution. However, reckless spending is not the solution either. A lot of people arguing for keynesian policies (not a bad idea in most recessions) don't grasp that investors have a limited amount of money to invest and aren't going to place it in a country that has as bad of a debt problem as you pointed out. So many people keep arguing these struggling countries need to spend more. While that would help expand their economies, it is not feasible. Where do you guys going to think the money is going to come from? If investors don't want to provide then they have to print more money, which creates the risk of hyperinflation. Spending could help a little maybe if it was a realistic thing to do. Right now any Keynesian solutions are a fairy tale. Countries like Greece need to do what they can with the resources available to them instead of spending like a bunch of millionaire playboys on crystal meth. Look at the U.S. We have spent trillions and our GDP is still growing at only slightly more than half the rate it has from 1947-2012. If people expect massive government spending to be a fix to these problems, then we are a clear case that it isn't. I acknowledge we could be a lot worse and possibly still be seeing a contraction without the spending, but it clearly isn't fixing our problems and sooner or later we won't be able to take on more debt to fix it. We need real solutions to generate real growth instead of dicking around like this. Other western countries need to do the same. edit:Also what we are doing right now would not be considered keynesian solutions. Keynes would advocate spending money to fix the problems, not just dumping money into the economy. That is something I would agree with. But since our politicians can't grasp that I don't want them in control of the purse strings anymore.", "title": "" }, { "docid": "242654", "text": "Note: I am in the UK. I don't know specifically about australia but I expect the general principles will be much the same everywhere. What banks want is to be reasonablly confident that you have a steady income stream that will continue to pay the mortgate until it completes. In general employed are fairly easy to assess. Most employed people will have a steady basic pay that increases through their career. Payslips will usually seperate-out basic pay, overtime and bonuses. There is little opertunity to cook the books. The self-employed are harder to assess. Income can be bursty and there are far more opertunities for cooking the books to make it look like you are earning more than you really are. So banks are likely to be far more careful about lending to the self-employed, they will likely want to see multiple years of buisness records so that any bursts, whether natural due to the ebbs and flows of buisness or deliberatly created to cook the books average out and they can see the overall pattern. A large deposit will help because it reduces the risk to the bank in the event of a default. Similarly not being anywhere near your limit of affordability will help.", "title": "" }, { "docid": "15270", "text": "Your freelance income will not qualify you for the work-from-home deductions, for that you would need a T2200 form signed by your employer. But, you are allowed to be self employed as a sole-proprietorship while still being an employee of another company. If you take that route, you'll be able to write-off even more expenses than those you linked to. Things like a portion of your internet bill can be claimed, for example. But note that these deductions would only apply to offset the self-employment income, so if you're not earning very much from the freelance work, it might not be worth all the hassle. Filing taxes when self-employed is definitely more complicated, and many people will get professional tax preparation help - at least for the first time.", "title": "" }, { "docid": "106585", "text": "Because BB is really a decentralized marketing company that supports individual retail stores. It would be continuing to use typewriters instead of email; while still employing typists. Xerox had the same problem: they were a copy machine company and the sales workers got paid by each paper copy was made. They R&amp;D the paperless office PARC (mouse, GUI, laser printer, etc...) and can't make it work because it conflicts with their core business. BB would have had to buy back all the franchises. The ONLY thing BB could do was to go out of business.", "title": "" }, { "docid": "187085", "text": "During World War II, the United States (US) instituted wage and price controls. To attract better employees, companies would offer benefits to get around salary limits. Health insurance was one of the more successful benefits. At that time, income taxes were newer and there were many ways to evade them. Companies could generally deduct expenses. So at that time, health care was deductible because everything was. And at that time, only wages were taxable compensation from employer to employee. Since that time, many other benefits have become non-deductible for employers, e.g. housing or the reduced deduction for meals and entertainment. But health care is generally regarded as different, as a necessity. While everyone needs to eat, not everyone needs to eat at a $100 a meal restaurant. People who need expensive health care really need it. People who eat expensive food just prefer it. And of course, health care is more intermittent where food is relatively consistent. You don't need ten thousand calories one day and zero the next. But some families have no health care expenses in a year while another might have cancer or a pregnancy. Note that medical care expenses can be deducted for individuals if they are large enough in aggregate and you itemize. And of course both businesses and workers have incentives to maintain the current system with deductibility. Health insurance is a common benefit. Housing is not (although it's worth noting that travel housing and meals are deductible). So there have been few people impacted by making housing taxable while many people would be impacted by taxable health insurance. You can deduct health insurance costs if self-employed. It's also not true that health insurance is the only benefit with preferential tax treatment. Retirement and child care are also deductible. Even meals and housing can be deducted in certain circumstances. The complex rules about what and how much is deductible. There have been rumbles about normalizing the tax treatment of health insurance and medical care, but there is a lot of opposition. Insurance companies oppose making all healthcare expenses deductible, as that reduces their effective benefit. They would prefer only insurance premiums be deductible. Traditionally employed individuals oppose making health insurance taxable, as that would increase their taxes. So the situation persists. There isn't quite enough support to move in either direction, although the current compromise is economically silly.", "title": "" }, { "docid": "275925", "text": "\"(Real) interest rates are so low because governments want people to use their money to improve the economy by spending or investing rather than saving. Their idea is that by consuming or investing you will help to create jobs that will employ people who will spend or invest their pay, and so on. If you want to keep this money for the future you don't want to spend it and interest rates make saving unrewarding therefore you ought to invest. That was the why, now the how. Inflation protected securities, mentioned in another answer, are the least risk way to do this. These are government guaranteed and very unlikely to default. On the other hand deflation will cause bigger problems for you and the returns will be pitiful compared with historical interest rates. So what else can be done? Investing in companies is one way of improving returns but risk starts to increase so you need to decide what risk profile is right for you. Investing in companies does not mean having to put money into the stock market either directly or indirectly (through funds) although index tracker funds have good returns and low risk. The corporate bond market is lower risk for a lesser reward than the stock market but with better returns than current interest rates. Investment grade bonds are very low risk, especially in the current economic climate and there are exchange traded funds (ETFs) to diversify more risk away. Since you don't mention willingness to take risk or the kind of amounts that you have to save I've tried to give some low risk options beyond \"\"buy something inflation linked\"\" but you need to take care to understand the risks of any product you buy or use, be they a bank account, TIPS, bond investments or whatever. Avoid anything that you don't fully understand.\"", "title": "" }, { "docid": "550643", "text": "If you can afford the cost and risk of 100 shares of stock, then just sell a put option. If you can only afford a few shares, you can still use the information the options market is trying to give you -- see below. A standing limit order to buy a stock is essentially a synthetic short put option position. [1] So deciding on a stock limit order price is the same as valuing an option on that stock. Options (and standing limit orders) are hard to value, and the generally accepted math for doing so -- the Black-Scholes-Merton framework -- is also generally accepted to be wrong, because of black swans. So rather than calculate a stock buy limit price yourself, it's simpler to just sell a put at the put's own midpoint price, accepting the market's best estimate. Options market makers' whole job (and the purpose of the open market) is price discovery, so it's easier to let them fight it out over what price options should really be trading at. The result of that fight is valuable information -- use it. Sell a 1-month ATM put option every month until you get exercised, after which time you'll own 100 shares of stock, purchased at: This will typically give you a much better cost basis (several dollars better) versus buying the stock at spot, and it offloads the valuation math onto the options market. Meanwhile you get to keep the cash from the options premiums as well. Disclaimer: Markets do make mistakes. You will lose money when the stock drops more than the option market's own estimate. If you can't afford 100 shares, or for some reason still want to be in the business of creating synthetic options from pure stock limit orders, then you could maybe play around with setting your stock purchase bid price to (approximately): See your statistics book for how to set ndev -- 1 standard deviation gives you a 30% chance of a fill, 2 gives you a 5% chance, etc. Disclaimer: The above math probably has mistakes; do your own work. It's somewhat invalid anyway, because stock prices don't follow a normal curve, so standard deviations don't really mean a whole lot. This is where market makers earn their keep (or not). If you still want to create synthetic options using stock limit orders, you might be able to get the options market to do more of the math for you. Try setting your stock limit order bid equal to something like this: Where put_strike is the strike price of a put option for the equity you're trading. Which option expiration and strike you use for put_strike depends on your desired time horizon and desired fill probability. To get probability, you can look at the delta for a given option. The relationship between option delta and equity limit order probability of fill is approximately: Disclaimer: There may be math errors here. Again, do your own work. Also, while this method assumes option markets provide good estimates, see above disclaimer about the markets making mistakes.", "title": "" }, { "docid": "308255", "text": "Let me first start off by saying that you need to be careful with an S-Corp and defined contribution plans. You might want to consider an LLC or some other entity form, depending on your state and other factors. You should read this entire page on the irs site: S-Corp Retirement Plan FAQ, but here is a small clip: Contributions to a Self-Employed Plan You can’t make contributions to a self-employed retirement plan from your S corporation distributions. Although, as an S corporation shareholder, you receive distributions similar to distributions that a partner receives from a partnership, your shareholder distributions aren’t earned income for retirement plan purposes (see IRC section 1402(a)(2)). Therefore, you also can’t establish a self-employed retirement plan for yourself solely based on being an S corporation shareholder. There are also some issues and cases about reasonable compensation in S-Corp. I recommend you read the IRS site's S Corporation Compensation and Medical Insurance Issues page answers as I see them, but I recommend hiring CPA You should be able to do option B. The limitations are in place for the two different types of contributions: Elective deferrals and Employer nonelective contributions. I am going to make a leap and say your talking about a SEP here, therefore you can't setup one were the employee could contribute (post 1997). If your doing self employee 401k, be careful to not make the contributions yourself. If your wife is employed the by company, here calculation is separate and the company could make a separate contribution for her. The limitation for SEP in 2015 are 25% of employee's compensation or $53,000. Since you will be self employed, you need to calculate your net earnings from self-employment which takes into account the eductible part of your self employment tax and contributions business makes to SEP. Good read on SEPs at IRS site. and take a look at chapter 2 of Publication 560. I hope that helps and I recommend hiring a CPA in your area to help.", "title": "" }, { "docid": "457549", "text": "\"I appreciate the detailed responses, truthfully however I feel like at least half of your points are either just argumentative for its sake alone, display a deep lack of understanding of unions, collective bargaining, and the histories of both, or ignore pragmatism and cling to an uncompromising and ultimately self-defeating ideology. &gt; Collective bargaining is an ambiguous term that could refer to many concepts. There is voluntarily agreed to collective bargaining, which has nothing wrong with it, and then there are laws that FORCE the employer to collectively bargain with a union if a union requests it, which is a mandate and violates the employer's contract liberty. The law forces the two parties to sit at a table. The law forces the two parties to discuss a few core things, like wages. The law *doesn't* force anyone to agree to anything, and very often they don't. I don't see how this is a violation of anyone's \"\"contract liberty\"\" (a term I've actually never heard before). The idea is since these worker-employer disputes exist naturally, making them at least sit at a table together and talking is helpful in avoiding ego and testosterone fueled disruptions where no one benefits. If this you see this as a violation of one's liberty, I really don't know what to say to that. &gt; The prevalence of child labor was decreasing long before any law was created prohibiting it. Child labor is necessary in poor countries because people are far less productive per hour worked. I'm not saying I don't believe you, but citation needed. &gt; As productivity increases, parents can afford to send their children off to school instead of working, since their own work is enough to support the family. Wouldn't educating children first lead to an increase in productivity? Also, what if the owners of the means of production, only a few in an given area, have incomes 100x greater than the workers? They seem to be producing enough wealth to support themselves, only they're not the beneficiaries. What's the solution here? I understand that in a poor country child labor is seen as a necessity; however I think there is a moral issue when someone from a developed nation opens a factory in a third-world country with conditions that they would not want someone in their own family subjected to. Maybe these conditions are standard in the third-world country, but just because they're standard that doesn't mean the people there are happy with them. &gt; In other words, no government mandate created due to union-pressure can possibly lead to beneficial change, since laws that limit people's economic rights, under the assumption that 51% knows what's better for the minority than they themselves do, generally do much more harm than good. This is quite a leap. Problem is you always assume that a company is always paying workers as much as it can instead of having a net income that can absorb an uptick in overhead. &gt; As history over the last century has shown, it's no hyperbole. Labor unions-backed regulations (soft-socialism) has succeeded in spite of the resistance of employers. And you owe this to violence or the threat of violence? Citation needed. &gt; Because unions have destroyed nearly every major industry where they had a natural tendency to form (large scale capital intensive manufacturing operations where large numbers of workers were concentrated in one place). This is typical anti-union propaganda, and it's funny you pull it out since it ignores your own ideology. What interest would a union have in destroying the very industry it needs to exist? Answer: none. This is just a way for a business to deflect criticism when they want to outsource, killing US jobs just to increase their net income. Unions make concessions when they have to. &gt; The force of government prevents companies from refusing to collectively bargain with a labor union. Threat of violence? Violent strikes? This is a straw-man if I've ever seen one. Who is threatening violence here? This existed before government laws were created that made legal threats on behalf of employees that want to keep unionized employees employed and force companies to collectively bargain with a union. Now of course the strikers themselves are not directly threatening violence, since they are backed by the force of government. This is just showing a tremendous amount of ignorance regarding the way things actually happen. &gt; Collectively bargaining doesn't benefit workers in general. It benefits in the short-term, those workers who are employed and unionized, at the expense of long-term wage growth and employment opportunities for the unemployed and non-unionized employees. I have no idea how one could come to this conclusion. I can only assume it stems from the same old idea that employers are always paying out the most that they can afford. I happen to have first-hand knowledge that it's false however - when my workplace unionized recently, one of around a dozen locations nationally and the only one to organize, the company responded by increasing wages and benefits to all locations. Have any locations closed? No. Has anyone been laid off? No. Is the company still mad profitable? Yes.\"", "title": "" }, { "docid": "510373", "text": "When getting a mortgage it always depends on the bank and each bank may be more or less strict. With that being said there are rules and general guidelines which can help you understand how you fit in the world of mortgage approvals. If you can provide the same paper work as an employee of your company that you would normally provide from any other company then a bank may just accept that alone. However to me it seems like you will be looking at a new variation of what was known as a Self-certification mortgage A self-certification mortgage is basically a mortgage for those who cannot prove their income. As a result of the housing collapse, the rules on a traditional self-cert mortgages have changed. As someone who is self employed, it is more difficult today to get a mortgage but is still possible. This article provides some good information: Can the self employed still get a mortgage? I advise doing some research on this topic and speaking with a professional mortgage broker. Some Resources: Compare Self Cert Mortgages How to beat the mortgage famine in 2012 Can the self employed still get a mortgage?", "title": "" }, { "docid": "134497", "text": "\"Both models understand that the value of a company is the sum total of all cashflows in the future, discounted back to the present. They vary in their definition of \"\"cash\"\". The Gordon Growth model uses dividends as a proxy for cashflow, under the assumption that this is the only true cash received by shareholders. (In theory, counting cash is meaningless if there's no eventual end-game where the accumulated cash is divvied up amongst the owners.) The Gordon model is best used to value companies that have an established, reliable dividend. The company should be stable, and the payout ratio high. GG will underestimate the value of firms that consistently maintain a low payout ratio, and instead accumulate cash. There are multiple DCF models. A firm valuation measures all cash available to both equity and debt holders. A traditional equity valuation measures all cash that can be claimed by shareholders. While the latter seems most intuitive and pertinent to a shareholder, the former is very good at showing what a company can do regardless of their choice of capital structure. A small add-on to a firm valuation is the concept of EVA, or economic value add, where the return on capital (all capital -- both debt and equity) is compared to the blended cost of capital. The DCF model is more flexible (optimistic?) than the Gordon in its approach to cash. The approach can be applied to many types of companies, at every stage in their maturity, even if they don't pay a dividend. A simplistic, or single-stage DCF is similar to the Gordon. The assumption is that the company is fully mature, growing at a rate perhaps just slightly above inflation, forever. For younger companies a multi-stage DCF can be employed, where you forecast fairly confident numbers for the next 3-5 years, then 3-5 years beyond that the forecast is less certain, but assumed to be slowing growth, and a generally maturing, stabilizing company. And then the steady-state stage is tacked on to the end. You'll want to check out Professor Aswath Damodaran's website: http://pages.stern.nyu.edu/~adamodar/ . He addresses all this and so much more, and has a big pile of spreadsheets freely downloadable to get you started. I also highly recommend his book \"\"Investment Valuation\"\". It's the bible on the topic.\"", "title": "" }, { "docid": "387574", "text": "\"BYOD is one of the problems [VMWare Octopus](http://www.vmwareoctopus.com/) will hopefully solve. I went to a demo of it last month and it looks promising because it creates a virtual \"\"work phone\"\" that can have all the security and limitations a company demands while leaving the normal phone in tact and unlimited as far as dropbox, etc.\"", "title": "" }, { "docid": "434196", "text": "\"Unfortunately, not directly. For IRAs and HSAs, we have an annual maximum contribution limit. What you can do (which doesn't \"\"initially seed\"\" it) is to put the money aside in a savings account that you want to contribute to your HSA or IRA and then put it in the IRA or HSA when the timing is right for you. The key here though is that the contribution cannot exceed the maximum limit for the year. Another \"\"way around\"\" this (which really isn't because it just means that you'll have a new higher limit) is to become self employed, see this from the IRS about SEPs: Contribute as much as 25% of your net earnings from self-employment (not including contributions for yourself), up to $51,000 for 2013 ($52,000 for 2014). Still, none of these methods are pre-seeding an account, as the maximum contribution limit is never exceeded.\"", "title": "" }, { "docid": "94653", "text": "I don't think you're missing anything. Many modern trading systems actually warn you when trying to enter a market order, asking if you are sure that you wouldn't prefer to set a limit. I fully agree with you that it is usually just better to define a limit even 20% higher than just doing a market trade. Let me give you some examples when you still might prefer to use a market order instead of a limit: But even in those two examples a (wide) limit order might just be the safer thing to do. So, what it really comes down to is speed: A market order has no other criterias to be defined, is thus entered faster and saves you a few seconds that might be crucial.", "title": "" }, { "docid": "162630", "text": "Firstly if you've formed a limited company you don't need to register as self-employed. You're an employee and shareholder of the company and your taxes will be handled that way. Registering as self-employed is only necessary if you're operating as a sole trader (i.e. without a company). Secondly you absolutely do want to get set-up correctly with HMRC as soon as possible, whether you're a company or a sole trader. Ignoring the legal question your worry about paying taxes when you have no income is groundless - if you're not making any money there won't be any tax to pay. Furthermore it seems likely that the business is currently losing money. Those losses, if correctly recorded, can be carried forward and offset against future profits so not only do you not have to pay tax now, but you can reduce the tax you pay later when the money does start rolling in.", "title": "" }, { "docid": "528361", "text": "You will be categorized as self employed. Will I have to register myself as a company or can go on unregistered and work You can register a company or can use an umbrella company or work as a sole trader. Remember as a sole trader you are legally responsible for you company's activities, an if a company sues you for your work he can take compensation from your personal assets. As a company your liability ends with the company, if your company is sued. Your personal assets are outside the purview of the lawsuit, but the court can attach that also but those are rare. This doesn't matter if you use an umbrella company. If you intend to be doing this for a short time(maybe a year or so), go for an umbrella company. Else register a company. will take you 5 minutes to form one. Depending on your earning you might need to register for VAT too. A comprehensive guide for self employed on HMRC. what would i need to be sound in uk and to be fit to work online as a freelancer? The same as above. Will it include paying any tax or paying any insurance Yes you have register for National Insurance(NI), before you can pay yourself a salary. The benefit of a company is you pay yourself a minimum salary, below the limit above which you have to contribute for NI, and take the rest as dividends. And pay no tax on it, till you don't exceed the limits. When the money comes in my account, will i be accountable to government of uk, to tell the source of income? If you are operating through a company, yes you would need to show your income(including source) and expenditure when you do your annual returns. What should i be knowing, like health insurance and things that are necessities in uk for a freelancer ? No health insurance as NHS exists. You can take out health insurance if you don't want to get into queues in NHS.", "title": "" }, { "docid": "428671", "text": "\"Your question asks \"\"how\"\" but \"\"if\"\" may be your issue. Most companies will not permit an external transfer while still employed, or under a certain age, 55 or so. If yours is one of the rare companies that permits a transfer, you simply open an IRA with the broker of your choice. Schwab, Fidelity, eTrade, or a dozen others. That broker will give you the paperwork you need to fill out, and they initiate the transfer. I assume you want an IRA in which you can invest in stocks or funds of your choosing. A traditional IRA. The term \"\"self-directed\"\" has another meaning, often associated with the account that permits real estate purchases inside the account. The brokers I listed do not handle that, those custodians have a different business model and are typically smaller firms with fewer offices, not country-wide.\"", "title": "" }, { "docid": "514357", "text": "You cannot withdraw funds from a 401(k) while still employed with your company. To access your contributions, that would be treated as a loan against the 401(k), in which case you'd pay an upfront fee, and then have to repay the amount loaned, plus interest, over a set period of time. (In essence, you are paying back yourself.) Typically, there is also a minimum amount you must take out as a loan. Should you leave the job and still have an outstanding loan against your 401(k), it will be treated as a withdrawal after a certain date, at which point a 10% penalty plus taxes applies, unless you pay back the full amount of the loan remaining before that certain date. Your friends should seriously consider contributing the minimum amount necessary to get that full 50% matching amount. It's free money. As you said, it's like leaving money on the table.", "title": "" }, { "docid": "82874", "text": "If you know you will have a big bill, like braces. and you fully expect to hit the deductible then it can make sense. The deductible can trip some people up, because if they put too much into the limited purpose FSA and don't hit the deductible for the regular insurance policy, they can't get to all the money in the FSA. Because you have the ability to spend the potential money in the FSA before all the money has been contributed, it can allow you to make that payment for the braces in January. I did this the first year we had the HSA. I knew I needed to pay a dental bill early in the year. But the HSA would only have a few hundred dollars at that time, so I used the limited purpose FSA to be able to make that payment. This could also work if you spent a lot of money in the previous year. Because you have the ability to adjust how much money goes into the HSA each each pay period, this idea does keep the option open to fully fund the HSA if your finances improve. Regarding the deductible. The law limits what you can use the limited purpose FSA for: dental and vision only. There is an exception. If you hit the deductible for the high deductible insurance policy, then you can use the funds in the limited purpose FSA for ANY medical reason. When I did this a few years ago, I needed to send extensive paperwork to the company holding the funds before they would release the funds for dental. Once I sent them proof that I had met the deductible, then any medical expense after that date could use the FSA with minimal paperwork. If you fully fund the FSA beyond the cost of the braces, and then have a light year medical expense wise, you might not be able to spend all money in the FSA by the deadline. Regarding state taxes. I saw no difference in my states (Virginia) treatment of the funds. The state taxable income number was exactly the same as the federal taxable income number. It did not treat the money in the FSA differently than the money in the HSA.", "title": "" }, { "docid": "576931", "text": "\"They're not at all the same. A Ponzi scheme is a fraudulent investment method that pays off early investors with deposits from later ones. Fractional reserve banking is the practice of keeping only a fraction of a bank's demand deposits on reserve, while lending out the rest. The reserve requirement is how central banks limit the amount of money that can float around in commercial banks. In the latter case, there is no \"\"later investor\"\" somewhere down near the bottom of a money food chain. Every dollar, regardless of whether it was created fresh from one of the federal reserve banks or created via several chained loans, is worth the same. If the dollars depreciate for whatever reason, they do so for everyone. Now, if you want a good example of a Ponzi scheme that is actually legal, look at Social Security. Edit: A \"\"debt-based society\"\" is separate from fractional-reserve banking. If the Fed creates $1,000,000, the total amount of money that can float around is still capped based on whatever the reserve requirement is. (For a 10% reserve requirement, it's something like $10,000,000.) We have unsustainable debt increases because of lack of self-control on the part of our leaders. The fractional-reserve process helps it along, but it's not the culprit. It's an enabler.\"", "title": "" } ]
PLAIN-678
beta glucan
[ { "docid": "MED-1292", "text": "There has been enormous interest in the biologic activity of mushrooms and innumerable claims have been made that mushrooms have beneficial effects on immune function with subsequent implications for inhibition of tumor growth. The majority of these observations are anecdotal and often lack standardization. However, there remains considerable data on both in vitro and in vivo effects that reflect on the potential of mushroom compounds to influence human immunity. A number of these effects are beneficial but, unfortunately, many responses are still characterized based on phenomenology and there is more speculation than substance. With respect to tumor biology, although many neoplastic lesions are immunogenic, tumor antigens frequently are self antigens and induce tolerance and many patients with cancer exhibit suppressed immune responses, including defective antigen presentation. Therefore, if and when mushroom extracts are effective, they more likely function as a result of improved antigen presentation by dendritic cells than by a direct cytopathic effect. In this review we attempt to place these data in perspective, with a particular focus on dendritic cell populations and the ability of mushroom extracts to modulate immunity. There is, at present, no scientific basis for the use of either mushrooms or mushroom extracts in the treatment of human patients but there is significant potential for rigorous research to understand the potential of mushrooms in human disease and thence to focus on appropriate clinical trials to demonstrate effectiveness and/ or potential toxicity.", "title": "The immunobiology of mushrooms." }, { "docid": "MED-1296", "text": "Natural immunomodulators are getting more and more popular. The popularity, however, often brings over-optimistic claims and mediocre effects. The purpose of the present study was to directly compare eleven most commonly used immunomodulators. Through testing both cellular and humoral branches of immune reactions, we found that most of the immunomodulators tested have limited, if any, effects, with glucan being consistently the most active molecule strongly stimulating every reaction evaluated. These data were also confirmed using a Lewis lung cancer model, where only glucan and resveratrol lowered the number of metastases.", "title": "Natural immunomodulators and their stimulation of immune reaction: true or false?" }, { "docid": "MED-1291", "text": "There is significant interest in the use of mushrooms and/or mushroom extracts as dietary supplements based on theories that they enhance immune function and promote health. To some extent, select mushrooms have been shown to have stimulatory action on immune responsiveness, particularly when studied in vitro. However, despite their widespread use for potential health benefits, there is a surprising paucity of epidemiologic and experimental studies that address the biologic activities of mushrooms after oral administration to animals or humans. There have been a number of studies that have addressed the ability of mushrooms to modulate mononuclear cell activation and the phenotypic expression of cytokines and their cognate receptors. There have also been a number of attempts to determine antitumor activities of mushrooms. Such studies are important because many of the components of mushrooms do potentially have significant biologic activity. All data, however, should be tempered by the possibility that there are toxic levels of metals, including arsenic, lead, cadmium, and mercury as well as the presence of radioactive contamination with 137Cs. In this review, we will present the comparative biology with respect to both immunological and antitumor activities of mushroom extracts and also highlight the need for further evidence-based research.", "title": "Mushrooms, tumors, and immunity: an update." }, { "docid": "MED-3153", "text": "This was a placebo-controlled, double-blind study designed to evaluate the effect of a commercially available dietary supplement on upper-respiratory tract symptoms (URTI) and mood state. Seventy-five marathon runners (35 men, 40 women) ranging in age from 18-53 years, mean age: 36 ± 9, self-administered placebo, 250 mg or 500 mg of BETA 1,3/1,6 GLUCAN (commercial name Wellmune WGP®) daily during the 4 week post-marathon trial period following the 2007 Carlsbad Marathon. Subjects filled out the profile of mood state (POMS) assessment and a questionnaire style health log measuring health status and URTI symptoms after 2- and 4-week treatment administrations. During the course of the 4-week study, subjects in the treatment groups (250 mg and 500 mg BETA-GLUCAN per day) reported significantly fewer URTI symptoms, better overall health and decreased confusion, fatigue, tension, and anger, and increased vigor based on the POMS survey compared to placebo. BETA-GLUCAN may prevent URTI symptoms, and improve overall health and mood following a competitive marathon. Key points", "title": "Effect of BETA 1, 3/1, 6 GLUCAN on Upper Respiratory Tract Infection Symptoms and Mood State in Marathon Athletes" }, { "docid": "MED-1293", "text": "In the domain of nutrition, exploring the diet-health linkages is major area of research. The outcomes of such interventions led to widespread acceptance of functional and nutraceutical foods; however, augmenting immunity is a major concern of dietary regimens. Indeed, the immune system is incredible arrangement of specific organs and cells that enabled humans to carry out defense against undesired responses. Its proper functionality is essential to maintain the body homeostasis. Array of plants and their components hold immunomodulating properties. Their possible inclusion in diets could explore new therapeutic avenues to enhanced immunity against diseases. The review intended to highlight the importance of garlic (Allium sativum), green tea (Camellia sinensis), ginger (Zingiber officinale), purple coneflower (Echinacea), black cumin (Nigella sativa), licorice (Glycyrrhiza glabra), Astragalus and St. John's wort (Hypericum perforatum) as natural immune boosters. These plants are bestowed with functional ingredients that may provide protection against various menaces. Modes of their actions include boosting and functioning of immune system, activation and suppression of immune specialized cells, interfering in several pathways that eventually led to improvement in immune responses and defense system. In addition, some of these plants carry free radical scavenging and anti-inflammatory activities that are helpful against cancer insurgence. Nevertheless, interaction between drugs and herbs/botanicals should be well investigated before recommended for their safe use, and such information must be disseminated to the allied stakeholders.", "title": "Immunity: plants as effective mediators." }, { "docid": "MED-1298", "text": "Obesity-induced insulin resistance has been suggested to be a systemic inflammatory condition with activation of the innate immune system. Animal studies indicate that certain dietary fibers such as (1,3)(1,6)-beta-D-glycans (BDG) have potent effects on immune activity such as increasing the antiinflammatory cytokine interleukin-10 (IL-10) and reducing the secretion of inflammatory factors. Therefore, we hypothesized that BDG consumption improves inflammatory markers and insulin sensitivity in overweight and obese subjects with moderately increased levels of C-reactive protein, indicating subclinical inflammation. We screened 180 overweight and obese subjects for moderately increased C-reactive protein levels on 2 or more occasions, in the absence of any signs of acute infection. Twelve of the subjects met all inclusion criteria and were investigated in a randomized, double-blind, placebo-controlled, crossover design for 2 x 4 weeks (washout > or =4 weeks). Subjects ingested capsules containing 3 x 0.5 g of highly purified BDG or 3 x 0.5 g of placebo (waxy maize starch) daily. Maintenance of the normal diet of the participants and the correct intake of the capsules were monitored, using 6 x 3-day food recording and counting of the provided capsules. Predefined outcome measures were BDG-induced changes in pro and antiinflammatory markers in circulating blood and gene expression in adipose tissue and peripheral insulin sensitivity expressed as M value. The BDG consumption for 4 weeks significantly increased both circulating levels and adipose tissue messenger RNA (mRNA) expression of the antiinflammatory cytokine IL-10 in overweight and obese humans. Insulin sensitivity as well as circulating levels and mRNA expression of proinflammatory cytokines were unaffected by BDG treatment. Increased IL-10 after BDG consumption might be a contributing factor to the known beneficial effects of dietary fiber intake.", "title": "Increased interleukin-10 but unchanged insulin sensitivity after 4 weeks of (1, 3)(1, 6)-beta-glycan consumption in overweight humans." }, { "docid": "MED-3150", "text": "Background Exercise can alter health in children in both beneficial (eg reduced long‐term risk of atherosclerosis) and adverse (eg exercise‐induced asthma) ways. The mechanisms linking exercise and health are not known, but may rest, partly, on the ability of exercise to increase circulating immune cells. Little is known about the effect of brief exercise, more reflective of naturally occurring patterns of physical activity in children, on immune cell responses. Objectives To determine whether (1) a 6‐min bout of exercise can increase circulating inflammatory cells in healthy children and (2) the effect of brief exercise is greater in children with a history of asthma. Methods Children with mild–moderate persistent asthma and age‐matched controls (n = 14 in each group, mean age 13.6 years) performed a 6‐min bout of cycle‐ergometer exercise. Spirometry was performed at baseline and after exercise. Blood was drawn before and after exercise, leucocytes were quantified and key lymphocyte cell surface markers were assessed by flow cytometry. Results Exercise decreased spirometry only in children with asthma, but increased (p<0.001) most types of leucocytes (eg lymphocytes (controls, mean (SD) 1210 (208) cells/μl; children with asthma, 1119 (147) cells/μl) and eosinophils (controls, 104 (22) cells/μl; children with asthma, 88 (20) cells/μl)) to the same degree in both groups. Similarly, exercise increased T helper cells (controls, 248 (60) cells/μl; children with asthma, 232 (53) cells/μl) and most other lymphocyte subtypes tested. By contrast, although basophils (16 (5) cells/μl) and CD4+ CD45RO+ RA+ lymphocytes (19 (4) cells/μl) increased in controls, no increase in these cell types was found in children with asthma. Conclusions Exercise increased many circulating inflammatory cells in both children with asthma and controls. Circulating inflammatory cells did increase in children with asthma, but not to a greater degree than in controls. In fact, basophils and T helper lymphocyte memory transition cells did not increase in children with asthma, whereas they did increase in controls. Even brief exercise in children and adolescents robustly mobilises circulating immune cells.", "title": "Do circulating leucocytes and lymphocyte subtypes increase in response to brief exercise in children with and without asthma?" }, { "docid": "MED-1295", "text": "A number of polysaccharides with beta-glycosidic linkage are widespread in nature in a variety of sources. All have a common structure and the (1-->3)-beta-D-glucan backbone is essential. They have attracted attention over the years because of their bioactive and medicinal properties. In many cases their functional role is a mystery, in others it is well established. Because of their insoluble chemical nature, particulate (1-->3)-beta-D-glucans are not suitable for many medical applications. Various methods of changing or modifying the beta-D-glucan chemical structure and transforming it to a soluble form have been published. The beta-D-glucan bioactive properties can be affected positively or negatively by such modifications. This review examines beta-glucan sources in nature, health effects and structure-activity relationships. It presents the current state of beta-D-glucan solubilization methods and discusses their effectiveness and application possibilities for the future.", "title": "Natural and modified (1-->3)-beta-D-glucans in health promotion and disease alleviation." }, { "docid": "MED-1300", "text": "Purpose The effect of brewers’ yeast (1,3)-(1,6)-beta-d-glucan consumption on the number of common cold episodes in healthy subject was investigated. Methods In a placebo-controlled, double-blind, randomized, multicentric clinical trial, 162 healthy participants with recurring infections received 900 mg of either placebo (n = 81) or an insoluble yeast (1,3)-(1,6)-beta-d-glucan preparation (n = 81) per day over a course of 16 weeks. Subjects were instructed to document each occurring common cold episode in a diary and to rate ten predefined infection symptoms during an infections period, resulting in a symptom score. The subjects were examined by the investigator during the episode visit on the 5th day of each cold episode. Results In the per protocol population, supplementation with insoluble yeast (1,3)-(1,6)-beta-glucan reduced the number of symptomatic common cold infections by 25 % as compared to placebo (p = 0.041). The mean symptom score was 15 % lower in the beta-glucan as opposed to the placebo group (p = 0.125). Beta-glucan significantly reduced sleep difficulties caused by cold episode as compared to placebo (p = 0.028). Efficacy of yeast beta-glucan was rated better than the placebo both by physicians (p = 0.004) participants (p = 0.012). Conclusion The present study demonstrated that yeast beta-glucan preparation increased the body’s potential to defend against invading pathogens.", "title": "Yeast (1,3)-(1,6)-beta-glucan helps to maintain the body’s defence against pathogens: a double-blind, randomized, placebo-controlled, multicentric study in healthy subjects" }, { "docid": "MED-1299", "text": "OBJECTIVE: Several studies have shown a baker's yeast beta-1,3/1,6-d-glucan, extracted from Saccharomyces cerevisiae, is effective in reducing the incidence of cold and flu symptoms. This study evaluated the effect of a specific beta-glucan supplement (Wellmune) on upper respiratory tract symptoms and psychological well-being in women with moderate levels of psychological stress. METHODS: Healthy women (38 ± 12 years old) prescreened for moderate levels of psychological stress, self-administered a placebo (n = 38) or 250 mg of Wellmune (n = 39) daily for 12 weeks. We used the Profile of Mood States (POMS) psychological survey to assess changes in mental/physical energy levels (vigor) and overall well-being (global mood state). A quantitative health perception log was used to track upper respiratory symptoms. RESULTS: Subjects in the Wellmune group reported fewer upper respiratory symptoms compared to placebo (10% vs 29%), better overall well-being (global mood state: 99 ± 19 vs 108 ± 23, p < 0.05), and superior mental/physical energy levels (vigor: 19.9 ± 4.7 vs 15.8 ± 6.3, p < 0.05). CONCLUSIONS: These data show that daily dietary supplementation with Wellmune reduces upper respiratory symptoms and improves mood state in stressed subjects, and thus it may be a useful approach for maintaining immune protection against daily stressors.", "title": "Baker's yeast beta-glucan supplement reduces upper respiratory symptoms and improves mood state in stressed women." }, { "docid": "MED-3155", "text": "Senescent T-cells accumulate with age, lowering the naïve T-cell repertoire and increasing host infection risk. As this response is likely to be influenced by certain lifestyle factors, we examined the association between aerobic fitness (VO(2max)) and the age-related accumulation of senescent T-cells. Blood lymphocytes from 102 healthy males (18-61 yr) were analyzed for KLRG1, CD57, CD28, CD45RA, CD45RO surface expression on CD4+ and CD8+ T-cells by 4-color flow cytometry. Advancing age (yr) was positively associated with the proportion (%) of senescent (KLRG1+/CD57+; KLRG1+/CD28-) CD4+ (B=1.00; 1.02) and CD8+ (B=0.429; 1.02) T-cells and inversely associated with naïve (KLRG1-/CD28+) CD4+ (B=-1.000) and CD8+ (B=-0.993) T-cells. VO(2max) was inversely associated with senescent CD4+ (B=-0.97) and CD8+ (B=-0.240). Strikingly, age was no longer associated with the proportions of senescent or naïve T-cells after adjusting for VO(2max), while the association between VO(2max) and these T-cell subsets withstood adjustment for age, BMI and percentage body fat. Ranking participants by age-adjusted VO(2max) revealed that the highest tertile had 17% more naïve CD8+ T-cells and 57% and 37% less senescent CD4+ and CD8+ T-cells, respectively, compared to the lowest tertile. VO(2max) was not associated with latent cytomegalovirus (CMV), Epstein-Barr virus (EBV) or herpes simplex virus-1 (HSV-1) infection, indicating that the moderating associations of VO(2max) were not confounded by persistent viral infections. This is the first study to show that aerobic fitness is associated with a lower age-related accumulation of senescent T-cells, highlighting the beneficial effects of maintaining a physically active lifestyle on the aging immune system. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Aerobic fitness is associated with lower proportions of senescent blood T-cells in man." }, { "docid": "MED-1294", "text": "Beta-glucans are a heterogeneous group of natural polysaccharides mostly investigated for their immunological effects. Due to the low systemic availability of oral preparations, it has been thought that only parenterally applied beta-glucans can modulate the immune system. However, several in vivo and in vitro investigations have revealed that orally applied beta-glucans also exert such effects. Various receptor interactions, explaining possible mode of actions, have been detected. The effects mainly depend on the source and structure of the beta-glucans. In the meantime, several human clinical trials with dietary insoluble yeast beta-glucans have been performed. The results confirm the previous findings of in vivo studies. The results of all studies taken together clearly indicate that oral intake of insoluble yeast beta-glucans is safe and has an immune strengthening effect.", "title": "Immune-modulatory effects of dietary Yeast Beta-1,3/1,6-D-glucan" }, { "docid": "MED-3154", "text": "Anecdotal, survey, and epidemiological data suggest that endurance athletes are at an increased risk for upper respiratory tract infection (URTI) during periods of heavy training and the 1 - to 2-wk period after race events. The majority of athletes, however, who participate in endurance race events do not experience illness. Of greater public health importance is the consistent finding of a reduction in URTI risk reported by fitness enthusiasts and athletes who engage in regular exercise training while avoiding overreaching/overtraining. Although it naturally follows that infection risk should in some way be linked to acute and chronic exercise-induced alterations in immunity, attempts thus far to measure this association have been unsuccessful. There is growing evidence that for several hours subsequent to heavy exertion, several components of both the innate and adaptive immune system exhibit suppressed function. The immune response to heavy exertion is transient, however, and further research on the mechanisms underlying the immune response to prolonged and intensive endurance exercise is necessary before meaningful clinical applications can be drawn. Some attempts have been made through chemical or nutritional means (e.g., indomethacin, glutamine, vitamin C, and carbohydrate supplementation) to attenuate immune changes after intensive exercise to lower the risk of infection. No consistent relationship between nutritional interventions, exercise immunology, and alteration in URTI risk has yet been established.", "title": "Is infection risk linked to exercise workload?" }, { "docid": "MED-3151", "text": "Strenuous aerobic exercise is known to weaken the immune system, and while many nutritional supplements have been proposed to boost post-exercise immunity, few are known to be effective. The purpose of the present study was to evaluate whether 10 d of supplementation with a defined source of baker's yeast β-glucan (BG, Wellmune WGP®) could minimise post-exercise immunosuppression. Recreationally active men and women (n 60) completed two 10 d trial conditions using a cross-over design with a 7 d washout period: placebo (rice flour) and baker's yeast BG (250 mg/d of β-1,3/1,6-glucans derived from Saccharomyces cerevisiae) before a bout of cycling (49 ± 6 min) in a hot (38 ± 2°C), humid (45 ± 2 % relative humidity) environment. Blood was collected at baseline (before supplement), pre- (PRE), post- (POST) and 2 h (2H) post-exercise. Total and subset monocyte concentration was measured by four-colour flow cytometry. Plasma cytokine levels and lipopolysaccharide (LPS)-stimulated cytokine production were measured using separate multiplex assays. Total (CD14⁺) and pro-inflammatory monocyte concentrations (CD14⁺/CD16⁺) were significantly greater at POST and 2H (P<0·05) with BG supplementation. BG supplementation boosted LPS-stimulated production of IL-2, IL-4, IL-5 and interferon-γ (IFN-γ) at PRE and POST (P<0·05). Plasma IL-4, IL-5 and IFN-γ concentrations were greater at 2H following BG supplementation. It appears that 10 d of supplementation with BG increased the potential of blood leucocytes for the production of IL-2, IL-4, IL-5 and IFN-γ. The key findings of the present study demonstrate that BG may have potential to alter immunity following a strenuous exercise session.", "title": "Baker's yeast β-glucan supplementation increases monocytes and cytokines post-exercise: implications for infection risk?" }, { "docid": "MED-3164", "text": "Prolonged exercise and heavy training are associated with depressed immune cell function. To maintain immune function, athletes should eat a well-balanced diet sufficient to meet their energy, carbohydrate, protein, and micronutrient requirements. Consuming carbohydrate during prolonged strenuous exercise attenuates rises in stress hormones and appears to limit the degree of exercise-induced immune depression. Recent evidence suggests that antioxidant vitamin supplementation may also reduce exercise stress and impairment of leukocyte functions. Further research is needed to evaluate the effects of other antioxidants and dietary immunostimulants such as probiotics and echinacea on exercise-induced immune impairment.", "title": "Can nutrition limit exercise-induced immunodepression?" } ]
[ { "docid": "MED-1309", "text": "Obesity is associated with a great diversity of diseases including non-alcoholic fatty liver disease. Our recent report suggested that oat, rich in beta-glucan, had a metabolic-regulating and liver-protecting effect in an animal model. In this study, we performed a clinical trial to further confirm the effect of oat. Subjects with BMI ≥27 and aged 18-65, were randomly divided into a control (n=18) and an oat-treated (n=16) group, taking a placebo or beta glucan-containing oat cereal, respectively, for 12 weeks. Our data showed that consumption of oat reduced body weight, BMI, body fat and the waist-to-hip ratio. Profiles of hepatic function, including AST, but especially ALT, were useful resources to help in the evaluation of the liver, since both showed decrements in patients with oat consumption. Nevertheless, anatomic changes were still not observed by ultrasonic image analysis. Ingestion of oat was well tolerated and there was no adverse effect during the trial. In conclusion, consumption of oat reduced obesity, abdominal fat, and improved lipid profiles and liver functions. Taken as a daily supplement, oat could act as an adjuvant therapy for metabolic disorders.", "title": "Oat prevents obesity and abdominal fat distribution, and improves liver function in humans." }, { "docid": "MED-1316", "text": "Oatmeal has been used for centuries as a soothing agent to relieve itch and irritation associated with various xerotic dermatoses. In 1945, a ready to use colloidal oatmeal, produced by finely grinding the oat and boiling it to extract the colloidal material, became available. Today, colloidal oatmeal is available in various dosage forms from powders for the bath to shampoos, shaving gels, and moisturizing creams. Currently, the use of colloidal oatmeal as a skin protectant is regulated by the U.S. Food and Drug Administration (FDA) according to the Over-The-Counter Final Monograph for Skin Protectant Drug Products issued in June 2003. Its preparation is also standardized by the United States Pharmacopeia. The many clinical properties of colloidal oatmeal derive from its chemical polymorphism. The high concentration in starches and beta-glucan is responsible for the protective and water-holding functions of oat. The presence of different types of phenols confers antioxidant and anti-inflammatory activity. Some of the oat phenols are also strong ultraviolet absorbers. The cleansing activity of oat is mostly due to saponins. Its many functional properties make colloidal oatmeal a cleanser, moisturizer, buffer, as well as a soothing and protective anti-inflammatory agent.", "title": "Colloidal oatmeal: history, chemistry and clinical properties." }, { "docid": "MED-4099", "text": "OBJECTIVE: A meta-analysis was performed on epidemiologic studies to assess the relation between β-glucan consumption from oats and from barley on blood cholesterol level, triglyceride/triacylglycerol (TGL/TAG) level, and blood glucose level (BGL) in humans. In addition, the effect of β-glucan on total cholesterol (TC) and BGL was translated into an empirical dose-response model. METHODS: Thirty research articles that evaluated the effect of different exposure levels of β-glucan on blood cholesterol and BGL were analyzed, yielding 126 clinical studies. RESULTS: There was a significant inverse relation in TC (-0.60 mmol/L, 95% confidence interval [CI] -0.85 to -0.34), low-density lipoprotein (-0.66 mmol/L, 95% CI -0.96 to -0.36), and TGL/TAG (-0.04 mmol/L, 95% CI -0.15 to 0.07) after consumption of β-glucan. In contrast, an increase in high-density lipoprotein cholesterol was noted (0.03 mmol/L, 95% CI -0.06 to 0.13) with the random-effect model. The analysis showed a significant change in BGL (-2.58 mmol/L, 95% CI -3.22 to -1.84) with high heterogeneity between (I(2) = 97%) and across (τ(2) = 5.88) the studies. The fixed-effect model showed a significant change in TC, low-density lipoprotein, and BGL, whereas it showed no significant changes in high-density lipoprotein and TGL/TAG. The dose-response model showed that a 3-g/d dose of oat or barley β-glucan was sufficient to decrease TC. CONCLUSION: Consumption of 3 g/d of oat or barley β-glucan is sufficient to decrease blood cholesterol, whereas the effect on BGL is still inconclusive, with high heterogeneity, and requires further clinical research studies with longer intervention periods. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Meta-analysis of the effect of β-glucan intake on blood cholesterol and glucose levels." }, { "docid": "MED-4833", "text": "Effective diets reduce blood lipids and oxidative damage, both of which have been linked to the complications of diabetes and coronary heart disease. Our objective was to assess the effect of adding strawberries, as a source of antioxidants, to improve the antioxidant effect of a cholesterol-lowering diet (dietary portfolio). To this end, 28 hyperlipidemic subjects who had followed the dietary portfolio consisting of soy, viscous fiber, plant sterol, and nuts for a mean of 2.5 years were randomized to receive supplements of strawberries (454 g/d, 112 kcal) or additional oat bran bread (65 g/d, 112 kcal, approximately 2 g beta-glucan) (control) in a randomized 1-month crossover study with a 2-week washout. Strawberry supplementation resulted in a greater reduction in oxidative damage to low-density lipoprotein (LDL) measured as thiobarbituric acid-reactive substances in the LDL fraction (P = .014). At the end of the strawberry period, reductions in LDL cholesterol and in the ratio of total to high-density lipoprotein cholesterol were maintained close to 1-year values at -13.4% +/- 2.1% and -15.2% +/- 1.7%, respectively (P < .001), and were similar to the post-oat bran bread values. Strawberries also improved the palatability of the diet. We conclude that strawberry supplementation reduced oxidative damage to LDL while maintaining reductions in blood lipids and enhancing diet palatability. Added fruit may improve the overall utility of diets designed to lower coronary heart disease risk.", "title": "The effect of strawberries in a cholesterol-lowering dietary portfolio." }, { "docid": "MED-4858", "text": "BACKGROUND/OBJECTIVE: beta-Carotene is often used as a marker for the amount of fruit and vegetables consumed, but little is known about plasma beta-carotene concentrations in subjects whose habitual (long-term) diets are characterized by different amounts of foods of plant origin. We compared dietary beta-carotene intake and plasma concentrations in women on habitual diets differing in the consumed amounts of foods of plant origin. METHODS: A comparison of dietary beta-carotene intakes and plasma beta-carotene concentrations in women adhering to an average Western diet (n = 172), wholesome nutrition (following preventive recommendations) (n = 238) or a raw food diet (n = 104). RESULTS: Dietary beta-carotene intake was 5.5, 9.3, 14.7 mg/day for women adhering to an average Western diet, wholesome nutrition and raw food diet, respectively (p < 0.001). Corresponding multivariate adjusted plasma beta-carotene concentrations were 1.07, 1.65, and 1.16 micromol/l, respectively (p < 0.001). Comparable dietary beta-carotene intake resulted in lower multivariate adjusted plasma beta-carotene in women adhering to a raw food diet and average Western diet compared to those on wholesome nutrition (p < 0.001 for all intake groups up to 20 mg/day). The amount of fruit and vegetable intake did not predict plasma beta-carotene levels in women consuming a raw food diet. CONCLUSIONS: Plasma beta-carotene concentrations differed among the diet groups, with highest plasma levels in women adhering to wholesome nutrition. Plasma beta-carotene concentrations may not reflect beta-carotene intake and the amount of fruit and vegetables consumed. 2009 S. Karger AG, Basel.", "title": "Plasma beta-carotene is not a suitable biomarker of fruit and vegetable intake in german subjects with a long-term high consumption of fruits and v..." }, { "docid": "MED-1070", "text": "AIMS/HYPOTHESIS: Defects in pancreatic beta cell turnover are implicated in the pathogenesis of type 2 diabetes by genetic markers for diabetes. Decreased beta cell neogenesis could contribute to diabetes. The longevity and turnover of human beta cells is unknown; in rodents <1 year old, a half-life of 30 days is estimated. Intracellular lipofuscin body (LB) accumulation is a hallmark of ageing in neurons. To estimate the lifespan of human beta cells, we measured beta cell LB accumulation in individuals aged 1-81 years. METHODS: LB content was determined by electron microscopical morphometry in sections of beta cells from human (non-diabetic, n = 45; type 2 diabetic, n = 10) and non-human primates (n = 10; 5-30 years) and from 15 mice aged 10-99 weeks. Total cellular LB content was estimated by three-dimensional (3D) mathematical modelling. RESULTS: LB area proportion was significantly correlated with age in human and non-human primates. The proportion of human LB-positive beta cells was significantly related to age, with no apparent differences in type 2 diabetes or obesity. LB content was low in human insulinomas (n = 5) and alpha cells and in mouse beta cells (LB content in mouse <10% human). Using 3D electron microscopy and 3D mathematical modelling, the LB-positive human beta cells (representing aged cells) increased from >or=90% (<10 years) to >or=97% (>20 years) and remained constant thereafter. CONCLUSIONS/INTERPRETATION: Human beta cells, unlike those of young rodents, are long-lived. LB proportions in type 2 diabetes and obesity suggest that little adaptive change occurs in the adult human beta cell population, which is largely established by age 20 years.", "title": "The long lifespan and low turnover of human islet beta cells estimated by mathematical modelling of lipofuscin accumulation." }, { "docid": "MED-1303", "text": "The aim of the present review article is to summarize the available information related to the availability, production, chemical composition, pharmacological activity, and traditional uses of Avena sativa to highlight its potential to contribute to human health. Oats are now cultivated worldwide and form an important dietary staple for the people in number of countries. Several varieties of oats are available. It is a rich source of protein, contains a number of important minerals, lipids, β-glucan, a mixed-linkage polysaccharide, which forms an important part of oat dietary fiber, and also contains various other phytoconstituents like avenanthramides, an indole alkaloid-gramine, flavonoids, flavonolignans, triterpenoid saponins, sterols, and tocols. Traditionally oats have been in use since long and are considered as stimulant, antispasmodic, antitumor, diuretic, and neurotonic. Oat possesses different pharmacological activities like antioxidant, anti-inflammatory, wound healing, immunomodulatory, antidiabetic, anticholesterolaemic, etc. A wide spectrum of biological activities indicates that oat is a potential therapeutic agent.", "title": "Avena sativa (Oat), a potential neutraceutical and therapeutic agent: an overview." }, { "docid": "MED-2185", "text": "Orange fleshed sweet potato (OFSP) has been identified as a good source of beta-carotene but the beta-carotene bioaccessibility is affected by processing. In this study, the effect of traditional heat processing methods on the microstructure and in vitro bioaccessibility of beta-carotene from OFSP were investigated. Bioaccessibility was determined using simulated in vitro digestion model followed by membrane filtration to separate the micellar fraction containing bioaccessible beta-carotene. Processing led to decrease in the amount of all-trans-beta-carotene and increase in 13-cis-beta-carotene. Processed OFSP had significantly higher (P < 0.05) bioaccessible beta-carotene compared to the raw forms. Bioaccessibility varied with processing treatments in the order; raw < baked < steamed/boiled < deep fried. Light microscopy showed that the microstructure of OFSP was disrupted by the processing methods employed. The cell walls of OFSP were sloughed by the traditional heat processing methods applied. The findings show that heat processing improves bioaccessibility of beta-carotene in OFSP and this was probably due to disruption of the tissue microstructure.", "title": "Microstructure and in vitro beta carotene bioaccessibility of heat processed orange fleshed sweet potato." }, { "docid": "MED-1062", "text": "The prevalence of Type 2 diabetes is increasing dramatically as a result of the obesity epidemic, and poses a major health and socio-economic burden. Type 2 diabetes develops in individuals who fail to compensate for insulin resistance by increasing pancreatic insulin secretion. This insulin deficiency results from pancreatic beta-cell dysfunction and death. Western diets rich in saturated fats cause obesity and insulin resistance, and increase levels of circulating NEFAs [non-esterified ('free') fatty acids]. In addition, they contribute to beta-cell failure in genetically predisposed individuals. NEFAs cause beta-cell apoptosis and may thus contribute to progressive beta-cell loss in Type 2 diabetes. The molecular pathways and regulators involved in NEFA-mediated beta-cell dysfunction and apoptosis are beginning to be understood. We have identified ER (endoplasmic reticulum) stress as one of the molecular mechanisms implicated in NEFA-induced beta-cell apoptosis. ER stress was also proposed as a mechanism linking high-fat-diet-induced obesity with insulin resistance. This cellular stress response may thus be a common molecular pathway for the two main causes of Type 2 diabetes, namely insulin resistance and beta-cell loss. A better understanding of the molecular mechanisms contributing to pancreatic beta-cell loss will pave the way for the development of novel and targeted approaches to prevent Type 2 diabetes.", "title": "Fatty acids and glucolipotoxicity in the pathogenesis of Type 2 diabetes." }, { "docid": "MED-3251", "text": "CONTEXT: Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established. OBJECTIVE: To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n = 868) were compared with untreated contemporary (n = 829) and historical (n = 959) cohorts. MAIN OUTCOME MEASURES: The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication. RESULTS: The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta-treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P = .14) or the historical control cohort (hazard ratio, 0.77; 95% CI, 0.58-1.02; P = .07) were considered. Further adjustment for comorbidities and socioeconomic status, where possible, did not change interpretations, and propensity score adjustment did not substantially change the results. CONCLUSION: Among patients with relapsing-remitting MS, administration of interferon beta was not associated with a reduction in progression of disability.", "title": "Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis." }, { "docid": "MED-4402", "text": "Sudden infant death syndrome (SIDS) is the most common cause of death in infants and its pathogenesis is complex and multifactorial. The aim of this review is to summarize recent novel findings regarding the possible association of beta-casomorphin (beta-CM) to apnea in SIDS, which has not been widely appreciated by pediatricians and scientists. beta-CM is an exogenous bioactive peptide derived from casein, a major protein in milk and milk products, which has opioid activity. Mechanistically, circulation of this peptide into the infant's immature central nervous system might inhibit the respiratory center in the brainstem leading to apnea and death. This paper will review the possible relationship between beta-CM and SIDS in the context of passage of beta-CM through the gastrointestinal tract and the blood-brain barrier (BBB), permeability of the BBB to peptides in infants, and characterization of the casomorphin system in the brain.", "title": "Relation of beta-casomorphin to apnea in sudden infant death syndrome." }, { "docid": "MED-2362", "text": "The study of the expression of Gal alpha 1----3Gal beta 1----4GlcNAc residues on mammalian glycoconjugates is of particular interest since as many as 1% of circulating IgG antibodies in man (the natural anti-Gal antibody) interact specifically with this carbohydrate residue. In recent studies, we have found that Gal alpha 1----3Gal beta 1----4GlcNAc residues are abundant on red cells and nucleated cells of nonprimate mammals, prosimians, and New World monkeys, but their expression is diminished in Old World monkeys, apes, and humans. In the present work, we have analyzed the expression of these residues on secreted mammalian glycoproteins. For this purpose, we have developed a radioimmunoassay (RIA) which enables the quantification of Gal alpha 1----3Gal beta 1----4GlcNAc residues on the secreted glycoproteins. Purified biotinylated anti-Gal was used as the antibody in the RIA, and bovine thyroglobulin enriched for Gal alpha 1----3Gal beta 1----4GlcNAc residues served as a solid-phase antigen. In this study, it is reported for the first time that the evolutionary pattern of Gal alpha 1----3Gal beta 1----4GlcNAc residue distribution in in vivo secreted glycoproteins is similar to that observed in membranes of cell lines and of red cells. Thyroglobulin, fibrinogen, or IgG molecules from nonprimate mammals and from New World monkeys express varying amounts of Gal alpha 1----3Gal beta 1----4GlcNAc residues ranging between 0.01 and 11 residues per molecule, whereas no such residues are present on any of these glycoproteins of human or Old World monkey origin.(ABSTRACT TRUNCATED AT 250 WORDS)", "title": "Distribution of Gal alpha 1----3Gal beta 1----4GlcNAc residues on secreted mammalian glycoproteins (thyroglobulin, fibrinogen, and immunoglobulin G..." }, { "docid": "MED-4677", "text": "Excessive milk consumption has a long association with increased respiratory tract mucus production and asthma. Such an association cannot be explained using a conventional allergic paradigm and there is limited medical evidence showing causality. In the human colon, beta-casomorphin-7 (beta-CM-7), an exorphin derived from the breakdown of A1 milk, stimulates mucus production from gut MUC5AC glands. In the presence of inflammation similar mucus overproduction from respiratory tract MUC5AC glands characterises many respiratory tract diseases. beta-CM-7 from the blood stream could stimulate the production and secretion of mucus production from these respiratory glands. Such a hypothesis could be tested in vitro using quantitative RT-PCR to show that the addition of beta-CM-7 into an incubation medium of respiratory goblet cells elicits an increase in MUC5AC mRNA and by identifying beta-CM-7 in the blood of asthmatic patients. This association may not necessarily be simply cause and effect as the person has to be consuming A1 milk, beta-CM-7 must pass into the systemic circulation and the tissues have to be actively inflamed. These prerequisites could explain why only a subgroup of the population, who have increased respiratory tract mucus production, find that many of their symptoms, including asthma, improve on a dairy elimination diet. (c) 2009 Elsevier Ltd. All rights reserved.", "title": "Does milk increase mucus production?" }, { "docid": "MED-2169", "text": "Norharman and harman are two heterocyclic beta-carboline (9H-pyrido[3,4-b]indole) alkaloids with biological and potential toxicological activity that appear in foodstuffs and environmental sources. To assess the occurrence and distribution of these compounds and to estimate the exposure levels based on the detected amounts, numerous samples of foodstuffs and cigarette smoke were analysed by solid-phase extraction and high-performance liquid chromatography-fluorescence. The levels found of beta-carbolines were highly variable. Low processed foodstuffs (i.e. milk, yoghurt, uncooked meats and fish) did not contain norharman and harman above the detection limit. Others, however, contained relatively high concentrations (at the tens of ng g(-1) or microg l(-1) level) depending on the processing conditions as, for example, 'well-done' cooked meat and fish. The highest amounts of norharman and harman were found in brewed coffee (29-207 microg l(-1)), sauces (soy sauce and Tabasco, among others; 4-252 microg l(-1)), 'well done' cooked meat and fish (57-160 ng g(-1)), toasted bread (42-160 ng g(-1)), and fermented alcoholic beverages (n.d.-41 mug l(-1)). beta-Carbolines also occurred in a high amount in the mainstream of cigarette smoke (207-2780 ng/cigarette), which is an important contributor to daily exposure to these compounds. Based on these results, it is concluded that the daily exposure to beta-carbolines in humans might be from tens to hundreds of micrograms, with cigarette smoke, coffee, certain seasonings, cooked foods and alcoholic beverages, in this order, being the major contributors. Many other foodstuffs might also contribute with minor amounts of norharman and harman. Foods and tobacco smoke might be potential contributors to the reported endogenous presence of beta-carbolines in humans.", "title": "Relative exposure to beta-carbolines norharman and harman from foods and tobacco smoke." }, { "docid": "MED-2546", "text": "BACKGROUND: We have shown that inositol hexaphosphate (IP6), a natural compound and a potent anti-cancer agent, inhibited cancer cell adhesion to the extracellular matrix (ECM) proteins, thereby leading to inhibition of cell migration and invasion. Cell adhesion to ECM is mediated by specific cell surface integrins, which transduce intracellular signals through their interaction and activation of other proteins that are recruited to the focal adhesion. We hypothesize that IP6 decreases cell adhesion by suppressing the integrin receptors and their subsequent signaling pathway. MATERIALS AND METHODS: We analyzed integrin expressions of the highly invasive estrogen receptor-negative human breast cancer MDA-MB 231 cells exposed to IP6 by flow cytometry. The expression of focal adhesion proteins was investigated by immunocytochemistry and Western blotting. RESULTS: IP6 treatment caused a significant (P < 0.005) decrease in the expression of integrin heterodimers alpha 2 beta 1 (collagen receptor), alpha 5 beta 1 (fibronectin receptor) and alpha v beta 3 (vitronectin receptor); flow cytometry showed that it was the alpha 5 subunit that was down-regulated ( < 0.001). However, the expression of the alpha 2, alpha v, beta 1 and beta 3 subunits were not affected by IP6 treatment. When the expression of integrins on the cell surface was assessed, there was a dramatic 82% decrease in the expression of alpha 5 beta 1 on IP6-treated cells (P < 0.0001), indicating a decrease in cell surface expression of the heterodimers. No effect was seen when inositol hexasulfate (IS6), an analogue of IP6, was used as a control. Immunocytochemistry showed a lack of clustering of paxillin; tyrosine-phosphorylated proteins in IP6-treated cells were discontinuous and scattered around the cell periphery, whereas the patterns were more dense and localized in control cells. Consistent with these observations, focal adhesion kinase (FAK) autophosphorylation at tyrosine-397 residue was suppressed, albeit modestly, by IP6 treatment, suggesting a down-regulation in the integrin-mediated signaling pathway. CONCLUSION: The results of this study indicate that IP6-induced inhibition of cancer cell adhesion, migration and invasion may be mediated through the modulation of integrin dimerization, cell surface expression and integrin-associated signaling pathway.", "title": "Inositol hexaphosphate (IP6) inhibits key events of cancer metastasis: II. Effects on integrins and focal adhesions." }, { "docid": "MED-2176", "text": "The aromatic beta-carbolines norharman and harman have been implicated in a number of human diseases including Parkinson's disease, tremor, addiction and cancer. It has been shown that these compounds are normal body constituents formed endogenously but external sources have been identified. Here, we summarise literature data on levels of norharman and harman in fried meat and fish, meat extracts, alcoholic drinks, and coffee brews. Other sources include edible and medicinal plants but tobacco smoke has been identified as a major source. Exposure levels from these different dietary sources are estimated to a maximum of 4 microg norharman per kg body weight (bw) per day and 1 microg harman per kg bw per day. Exposure via tobacco smoke depends on smoking habits and type of cigarettes but can be estimated to 1.1 microg/kg bw for norharman and 0.6 microg/kg bw for harman per package of cigarettes smoked. Studies on toxicokinetics indicate that inhalative exposure leads to a rapid increase in plasma levels and high bioavailability of norharman and harman. Oral bioavailability is lower but there are indications that sublingual absorption may increase dietary uptake of beta-carbolines. Endogenous formation can be estimated to be 50-100 ng/kg bw per day for norharman and about 20 ng/kg bw per day for harman but these rates may increase with high intake of precursors. Biomarker studies on plasma levels of beta-carbolines reported on elevated levels of norharman, harman or both in diseased patients, alcoholics and following tobacco smoking or consumption of beta-carboline-containing food. Cigarette smoking has been identified as major influence but dietary exposure may contribute to exposure.", "title": "Exposure to beta-carbolines norharman and harman." }, { "docid": "MED-118", "text": "The aims of this study were to determine the concentrations of 4-nonylphenol (NP) and 4-octylphenol (OP) in 59 human milk samples and to examine related factors including mothers' demographics and dietary habits. Women who consumed over the median amount of cooking oil had significantly higher OP concentrations (0.98 ng/g) than those who consumed less (0.39 ng/g) (P < 0.05). OP concentration was significantly associated with the consumption of cooking oil (beta = 0.62, P < 0.01) and fish oil capsules (beta = 0.39, P < 0.01) after adjustment for age and body mass index (BMI). NP concentration was also significantly associated with the consumption of fish oil capsules (beta = 0.38, P < 0.01) and processed fish products (beta = 0.59, P < 0.01). The food pattern of cooking oil and processed meat products from factor analysis was strongly associated with OP concentration in human milk (P < 0.05). These determinations should aid in suggesting foods for consumption by nursing mothers in order to protect their infants from NP/OP exposure. 2010 Elsevier Ltd. All rights reserved.", "title": "Alkylphenols in human milk and their relations to dietary habits in central Taiwan." }, { "docid": "MED-2651", "text": "The aims of this study were to determine the concentrations of 4-nonylphenol (NP) and 4-octylphenol (OP) in 59 human milk samples and to examine related factors including mothers' demographics and dietary habits. Women who consumed over the median amount of cooking oil had significantly higher OP concentrations (0.98 ng/g) than those who consumed less (0.39 ng/g) (P < 0.05). OP concentration was significantly associated with the consumption of cooking oil (beta = 0.62, P < 0.01) and fish oil capsules (beta = 0.39, P < 0.01) after adjustment for age and body mass index (BMI). NP concentration was also significantly associated with the consumption of fish oil capsules (beta = 0.38, P < 0.01) and processed fish products (beta = 0.59, P < 0.01). The food pattern of cooking oil and processed meat products from factor analysis was strongly associated with OP concentration in human milk (P < 0.05). These determinations should aid in suggesting foods for consumption by nursing mothers in order to protect their infants from NP/OP exposure. 2010 Elsevier Ltd. All rights reserved.", "title": "Alkylphenols in human milk and their relations to dietary habits in central Taiwan." }, { "docid": "MED-1794", "text": "Nonstarch polysaccharides (NSPs) occur naturally in many foods. The physiochemical and biological properties of these compounds correspond to dietary fiber. Nonstarch polysaccharides show various physiological effects in the small and large intestine and therefore have important health implications for humans. The remarkable properties of dietary NSPs are water dispersibility, viscosity effect, bulk, and fermentibility into short chain fatty acids (SCFAs). These features may lead to diminished risk of serious diet related diseases which are major problems in Western countries and are emerging in developing countries with greater affluence. These conditions include coronary heart disease, colo-rectal cancer, inflammatory bowel disease, breast cancer, tumor formation, mineral related abnormalities, and disordered laxation. Insoluble NSPs (cellulose and hemicellulose) are effective laxatives whereas soluble NSPs (especially mixed-link β-glucans) lower plasma cholesterol levels and help to normalize blood glucose and insulin levels, making these kinds of polysaccharides a part of dietary plans to treat cardiovascular diseases and Type 2 diabetes. Moreover, a major proportion of dietary NSPs escapes the small intestine nearly intact, and is fermented into SCFAs by commensal microflora present in the colon and cecum and promotes normal laxation. Short chain fatty acids have a number of health promoting effects and are particularly effective in promoting large bowel function. Certain NSPs through their fermented products may promote the growth of specific beneficial colonic bacteria which offer a prebiotic effect. Various modes of action of NSPs as therapeutic agent have been proposed in the present review. In addition, NSPs based films and coatings for packaging and wrapping are of commercial interest because they are compatible with several types of food products. However, much of the physiological and nutritional impact of NSPs and the mechanism involved is not fully understood and even the recommendation on the dose of different dietary NSPs intake among different age groups needs to be studied.", "title": "Dietary roles of non-starch polysaccharides in human nutrition: a review." }, { "docid": "MED-1752", "text": "The transforming growth factor-beta (TGF-beta) superfamily encompasses a large group of growth and differentiation factors playing important roles in regulating embryonic development and in maintaining tissue homeostasis in adult animals. Using degenerate polymerase chain reaction, we have identified a new murine TGF-beta family member, growth/differentiation factor-8 (GDF-8), which is expressed specifically in developing and adult skeletal muscle. During early stages of embryogenesis, GDF-8 expression is restricted to the myotome compartment of developing somites. At later stages and in adult animals, GDF-8 is expressed in many different muscles throughout the body. To determine the biological function of GDF-8, we disrupted the GDF-8 gene by gene targeting in mice. GDF-8 null animals are significantly larger than wild-type animals and show a large and widespread increase in skeletal muscle mass. Individual muscles of mutant animals weigh 2-3 times more than those of wild-type animals, and the increase in mass appears to result from a combination of muscle cell hyperplasia and hypertrophy. These results suggest that GDF-8 functions specifically as a negative regulator of skeletal muscle growth.", "title": "Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member." }, { "docid": "MED-4928", "text": "Background Observational studies suggested that a diet high in fruits and vegetables, both of which are rich with antioxidants, may prevent cancer development. However, findings from randomized trials of the association between antioxidant use and cancer risk have been mostly negative. Methods From 8171 women who were randomly assigned in the Women's Antioxidant Cardiovascular Study, a double-blind, placebo-controlled 2 × 2 × 2 factorial trial of vitamin C (500 mg of ascorbic acid daily), natural-source vitamin E (600 IU of α-tocopherol every other day), and beta carotene (50 mg every other day), 7627 women who were free of cancer before random assignment were selected for this study. Diagnoses and deaths from cancer at a specific site were confirmed by use of hospital reports and the National Death Index. Cox proportional hazards regression models were used to assess hazard ratios (represented as relative risks [RRs]) of common cancers associated with use of antioxidants, either individually or in combination. Subgroup analyses were conducted to determine if duration of use modified the association of supplement use with cancer risk. All statistical tests were two-sided. Results During an average 9.4 years of treatment, 624 women developed incident invasive cancer and 176 women died from cancer. There were no statistically significant effects of use of any antioxidant on total cancer incidence. Compared with the placebo group, the RRs were 1.11 (95% confidence interval [CI] = 0.95 to 1.30) in the vitamin C group, 0.93 (95% CI = 0.79 to 1.09) in the vitamin E group, and 1.00 (95% CI = 0.85 to 1.17) in the beta carotene group. Similarly, no effects of these antioxidants were observed on cancer mortality. Compared with the placebo group, the RRs were 1.28 (95% CI = 0.95 to 1.73) in the vitamin C group, 0.87 (95% CI = 0.65 to 1.17) in the vitamin E group, and 0.84 (95% CI = 0.62 to 1.13) in the beta carotene group. Duration and combined use of the three antioxidants also had no effect on cancer incidence and cancer death. Conclusions Supplementation with vitamin C, vitamin E, or beta carotene offers no overall benefits in the primary prevention of total cancer incidence or cancer mortality.", "title": "Vitamins C and E and Beta Carotene Supplementation and Cancer Risk: A Randomized Controlled Trial" }, { "docid": "MED-3639", "text": "Several foods have been shown to contain natural components (especially polyphenols) which display anti-adhesive properties against Streptococcus mutans, the aetiological agent responsible for dental crown caries, as well as inhibition of glucosyltransferases, which are the S. mutans enzymes involved in the synthesis of an adherent, water-insoluble glucan from sucrose. Other studies have demonstrated an in vitro action on oral plaque biofilm formation and desorption. This study evaluated whether the activity displayed in vitro by food compounds could affect the microbiological composition of saliva and dental plaque of subjects with a diet rich in these foods, comparing the results with those obtained from subjects with a different diet. The foods considered were: coffee, barley coffee, tea and wine. A total of 93 subjects were recruited into the study. Six samples of both plaque and saliva were collected from each subject at roughly one-monthly intervals. Total bacteria, total streptococci, S. mutans and lactobacilli counts were determined by culture in both saliva and dental plaque. The highest bacterial titres were recorded for the control population, while each drinking habit subgroup showed counts roughly one log lower than the controls. These differences in bacterial counts proved statistically significant (P<0.05). As far as dental plaque was concerned, while total counts did not significantly vary per mg of plaque in the subjects belonging to the different drinking habit subgroups, a significant decrease (P<0.05) was observed in those subjects drinking coffee, tea, barley coffee and wine when mutans streptococci and lactobacilli were evaluated. In several cases a more than one log decrease was observed. Plaque indices were also determined, and a significant (P<0.05) reduction in values was recorded in the subjects belonging the specific drinking habit subgroups compared to the control group. This study indicates that there is a correlation between consumption of specific foods and oral health in terms of reduced plaque deposition and lower counts of odontopathogens.", "title": "Differences in microbiological composition of saliva and dental plaque in subjects with different drinking habits." }, { "docid": "MED-1514", "text": "OBJECTIVE: Total sedentary (absence of whole-body movement) time is associated with obesity, abnormal glucose metabolism, and the metabolic syndrome. In addition to the effects of total sedentary time, the manner in which it is accumulated may also be important. We examined the association of breaks in objectively measured sedentary time with biological markers of metabolic risk. RESEARCH DESIGN AND METHODS: Participants (n = 168, mean age 53.4 years) for this cross-sectional study were recruited from the 2004-2005 Australian Diabetes, Obesity and Lifestyle study. Sedentary time was measured by an accelerometer (counts/minute(-1) < 100) worn during waking hours for seven consecutive days. Each interruption in sedentary time (counts/min > or = 100) was considered a break. Fasting plasma glucose, 2-h plasma glucose, serum triglycerides, HDL cholesterol, weight, height, waist circumference, and resting blood pressure were measured. MatLab was used to derive the breaks variable; SPSS was used for the statistical analysis. RESULTS: Independent of total sedentary time and moderate-to-vigorous intensity activity time, increased breaks in sedentary time were beneficially associated with waist circumference (standardized beta = -0.16, 95% CI -0.31 to -0.02, P = 0.026), BMI (beta = -0.19, -0.35 to -0.02, P = 0.026), triglycerides (beta = -0.18, -0.34 to -0.02, P = 0.029), and 2-h plasma glucose (beta = -0.18, -0.34 to -0.02, P = 0.025). CONCLUSIONS: This study provides evidence of the importance of avoiding prolonged uninterrupted periods of sedentary (primarily sitting) time. These findings suggest new public health recommendations regarding breaking up sedentary time that are complementary to those for physical activity.", "title": "Breaks in sedentary time: beneficial associations with metabolic risk." }, { "docid": "MED-2460", "text": "BACKGROUND: Elevated oxidative stress and impaired antioxidant defences are increasingly recognised features of asthma. Carotenoids are potent dietary antioxidants that may protect against asthma by reducing oxidative damage. OBJECTIVES: This study aimed firstly, to characterise circulating and airway levels of carotenoids in asthma compared to healthy controls, in relation to dietary intake. Secondly, the study aimed to test whether airway lycopene defences can be improved using oral supplements. METHODS: Induced sputum and peripheral blood samples were collected from subjects with asthma (n = 15) and healthy controls (n = 16). Dietary carotenoid intakes were estimated using the 24-hour recall method and analysed using a modified version of the Foodworks 210 Nutrient Calculation Software. Another group of healthy controls (n = 9) were supplemented with 20 mg/day lycopene for 4 weeks. Carotenoids (beta-carotene, lycopene, alpha-carotene, beta-cryptoxanthin, lutein/zeaxanthin) were measured by HPLC. RESULTS: Despite similar dietary intake, whole blood levels of total carotenoids, lycopene, lutein, beta-cryptoxanthin, alpha-carotene and beta-carotene were significantly lower in asthma than controls. However, there were no differences in plasma or sputum carotenoid levels. Induced sputum carotenoid levels were significantly lower than plasma and whole blood levels, but correlated strongly with plasma levels (r = 0.798, p < 0.001). Although there were no overall increases in either plasma or sputum lycopene levels following supplementation, changes in airway lycopene levels correlated with changes in plasma levels (r = 0.908, p < 0.002). CONCLUSIONS: Whole blood, but not plasma or sputum, carotenoid levels are deficient in asthma. Plasma carotenoid levels reflect airway carotenoid levels and when plasma levels are improved using oral supplements this is reflected in the airways.", "title": "Airway and circulating levels of carotenoids in asthma and healthy controls." }, { "docid": "MED-2702", "text": "BACKGROUND: Oxidative stress can cause cancer. Our aim was to establish whether antioxidant supplements reduce the incidence of gastrointestinal cancer and mortality. METHODS: With the Cochrane Collaboration methodology, we reviewed all randomised trials comparing antioxidant supplements with placebo for prevention of gastrointestinal cancers. We searched electronic databases and reference lists (February, 2003). Outcome measures were incidence of gastrointestinal cancers, overall mortality, and adverse effects. Outcomes were analysed with fixed-effect and random-effects model meta-analyses and were reported as relative risk with 95% CIs. FINDINGS: We identified 14 randomised trials (n=170,525). Trial quality was generally high. Heterogeneity of results was low to moderate. Neither the fixed-effect (relative risk 0.96, 95% CI 0.88-1.04) nor random-effects meta-analyses (0.90, 0.77-1.05) showed significant effects of supplementation with beta-carotene, vitamins A, C, E, and selenium (alone or in combination) versus placebo on oesophageal, gastric, colorectal, pancreatic, and liver cancer incidences. In seven high-quality trials (n=131727), the fixed-effect model showed that antioxidant significantly increased mortality (1.06, 1.02-1.10), unlike the random-effects meta-analysis (1.06, 0.98-1.15). Low-quality trials showed no significant effect of antioxidant supplementation on mortality. The difference between the mortality estimates in high-quality and low-quality trials was significant (Z=2.10, p=0.04 by test of interaction). beta-carotene and vitamin A (1.29, 1.14-1.45) and beta-carotene and vitamin E (1.10, 1.01-1.20) significantly increased mortality, whereas beta-carotene alone only tended to increase mortality (1.05, 0.99-1.11). In four trials (three with unclear or inadequate methodology), selenium showed significant beneficial effect on the incidence of gastrointestinal cancer. INTERPRETATION: We could not find evidence that antioxidant supplements can prevent gastrointestinal cancers; on the contrary, they seem to increase overall mortality. The potential preventive effect of selenium should be studied in adequate randomised trials.", "title": "Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis." }, { "docid": "MED-4726", "text": "The aim of these studies was to evaluate the potential of some nutritional approaches to prevent or reduce the body load of organochlorines (OC) in humans. Study 1 compared plasma OC concentrations between vegans and omnivores while study 2 verified if the dietary fat substitute olestra could prevent the increase in OC concentrations that is generally observed in response to a weight-reducing programme. In study 1, nine vegans and fifteen omnivores were recruited and the concentrations of twenty-six OC (beta-hexachlorocyclohexane (beta-HCH), p, p'-dichlorodiphenyldichloroethane (p, p'-DDE), p, p'-dichlorodiphenyltrichloroethane (p, p'-DDT), hexachlorobenzene, mirex, aldrin, alpha-chlordane, gamma-chlordane, oxychlordane, cis-nonachlor, trans-nonachlor, polychlorinated biphenyl (PCB) nos. 28, 52, 99, 101, 105, 118, 128, 138, 153, 156, 170, 180, 183 and 187, and aroclor 1260) were determined. In study 2, the concentrations of these twenty-six OC were measured before and after weight loss over 3 months in thirty-seven obese men assigned to one of the following treatments: standard group (33 % fat diet; n 13), fat-reduced group (25 % fat diet; n 14) or fat-substituted group (1/3 of dietary lipids substituted by olestra; n 10). In study 1, plasma concentrations of five OC compounds (aroclor 1260 and PCB 99, PCB 138, PCB 153 and PCB 180) were significantly lower in vegans compared with omnivores. In study 2, beta-HCH was the only OC which decreased in the fat-substituted group while increasing in the other two groups (P = 0.045). In conclusion, there was a trend toward lesser contamination in vegans than in omnivores, and olestra had a favourable influence on beta-HCH but did not prevent plasma hyperconcentration of the other OC during ongoing weight loss.", "title": "Impact of adopting a vegan diet or an olestra supplementation on plasma organochlorine concentrations: results from two pilot studies." }, { "docid": "MED-5020", "text": "Bioactivity-guided fractionation of Red Delicious apple peels was used to determine the chemical identity of bioactive constituents, which showed potent antiproliferative and antioxidant activities. Twenty-nine compounds, including triterpenoids, flavonoids, organic acids and plant sterols, were isolated using gradient solvent fractionation, Diaion HP-20, silica gel, and ODS columns, and preparative HPLC. Their chemical structures were identified using HR-MS and 1D and 2D NMR. Antiproliferative activities of isolated pure compounds against HepG2 human liver cancer cells and MCF-7 human breast cancer cells were evaluated. On the basis of the yields of isolated flavonoids (compounds 18- 23), the major flavonoids in apple peels are quercetin-3-O-beta-D-glucopyranoside (compound 20, 82.6%), then quercetin-3-O-beta-D-galactopyranoside (compound 19, 17.1%), followed by trace amounts of quercetin (compound 18, 0.2%), (-)-catechin (compound 22), (-)-epicatechin (compound 23), and quercetin-3-O-alpha-L-arabinofuranoside (compound 21). Among the compounds isolated, quercetin (18) and quercetin-3-O-beta-D-glucopyranoside (20) showed potent antiproliferative activities against HepG2 and MCF-7 cells, with EC 50 values of 40.9 +/- 1.1 and 49.2 +/- 4.9 microM to HepG2 cells and 137.5 +/- 2.6 and 23.9 +/- 3.9 microM to MCF-7 cells, respectively. Six flavonoids (18-23) and three phenolic compounds (10, 11, and 14) showed potent antioxidant activities. Caffeic acid (10), quercetin (18), and quercetin-3-O-beta-D-arabinofuranoside (21) showed higher antioxidant activity, with EC 50 values of <10 microM. Most tested flavonoids and phenolic compounds had high antioxidant activity when compared to ascorbic acid and might be responsible for the antioxidant activities of apples. These results showed apple peel phytochemicals have potent antioxidant and antiproliferative activities.", "title": "Phytochemicals of apple peels: isolation, structure elucidation, and their antiproliferative and antioxidant activities." }, { "docid": "MED-2172", "text": "Co-mutagenic beta-carbolines, such as norharman and harman, were quantified in mainstream and sidestream smoke condensates of six Japanese brands of cigarettes, and also in 13 kinds of cooked foods, using a combination of blue cotton treatment and HPLC. Norharman and harman were detected in all the cigarette smoke condensate samples. Their levels in the mainstream smoke case were 900-4240 ng per cigarette for norharman, and 360-2240 ng for harman, and in sidestream smoke, 4130-8990 ng for norharman and 2100-3000 ng for harman. These beta-carbolines were also found to be present in all the cooked food samples, at levels of 2.39-795 ng for norharman and 0.62-377 ng for harman per gram of cooked food. The observed concentrations are much higher than those found for mutagenic and carcinogenic heterocyclic amines (HCAs), suggesting that humans are exposed to norharman and harman in daily life to a larger extent than to HCAs.", "title": "Quantification of the co-mutagenic beta-carbolines, norharman and harman, in cigarette smoke condensates and cooked foods." }, { "docid": "MED-2165", "text": "Death of dopaminergic neurons in Parkinson's disease (PD) may partially be caused by synthesis and accumulation of endogenous and exogenous toxins. Because of structural similarity to MPTP, beta-carbolines, like norharman and harman, have been proposed as putative neurotoxins. In vivo they may easily be formed by cyclization of indoleamines with e.g. aldehydes. For further elucidation of the role of beta-carbolines in neurodegenerative disorders harman and norharman levels in cerebrospinal fluid (CSF) were measured in 14 patients with PD and compared to an age- and sex-matched control group (n = 14). CSF levels of norharman and harman in PD were significantly higher compared to controls. These results may suggest a possible role of harman and norharman or its N-methylated carbolinium ions in the pathophysiological processes initiating PD. However the origin of increased levels of these beta-carbolines remains unclear. On the one hand one may speculate, that unknown metabolic processes induce the increased synthesis of harman and norharman in PD. On the other hand a possible impact of exogenous sources may also be possible.", "title": "Elevated levels of harman and norharman in cerebrospinal fluid of parkinsonian patients." }, { "docid": "MED-3720", "text": "Black raspberries are a rich natural source of chemopreventive phytochemicals. Recent studies have shown that freeze-dried black raspberries inhibit the development of oral, esophageal, and colon cancer in rodents, and extracts of black raspberries inhibit benzo(a)pyrene-induced cell transformation of hamster embryo fibroblasts. However, the molecular mechanisms and the active components responsible for black raspberry chemoprevention are unclear. In this study, we found that 2 major chemopreventive components of black raspberries, ferulic acid and beta-sitosterol, and a fraction eluted with ethanol (RO-ET) during silica column chromatography of the organic extract of freeze-dried black raspberries inhibit the growth of premalignant and malignant but not normal human oral epithelial cell lines. Another fraction eluted with CH2Cl2/ethanol (DM:ET) and ellagic acid inhibited the growth of normal as well as premalignant and malignant human oral cell lines. We investigated the molecular mechanisms by which ferulic acid and beta-sitosterol and the RO-ET fraction selectively inhibited the growth of premalignant and malignant oral cells using flow cytometry and Western blotting of cell cycle regulatory proteins. There was no discernable change in the cell cycle distribution following treatment of cells with the RO-ET fraction. Premalignant and malignant cells redistributed to the G2/M phase of the cell cycle following incubation with ferulic acid. beta-sitosterol treated premalignant and malignant cells accumulated in the G0/G1 and G2/M phases, respectively. The RO-ET fraction reduced the levels of cyclin A and cell division cycle gene 2 (cdc2) in premalignant cells and cyclin B1, cyclin D1, and cdc2 in the malignant cell lines. This fraction also elevated the levels of p21waf1/cip1 in the malignant cell line. Ferulic acid treatment led to increased levels of cyclin B1 and cdc2 in both cell lines, and p21waf1/cip1 was induced in the malignant cell line. beta-sitosterol reduced the levels of cyclin B1 and cdc2 while increasing p21waf1/cip1 in both the premalignant and malignant cell lines. These results show for the first time that the growth inhibitory effects of black raspberries on premalignant and malignant human oral cells may reside in specific components that target aberrant signaling pathways regulating cell cycle progression.", "title": "Inhibition of the growth of premalignant and malignant human oral cell lines by extracts and components of black raspberries." } ]
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Jerry Maguire was produced by James L. Brooks in 2001.
[ { "docid": "Jerry_Maguire", "text": "Jerry Maguire is a 1996 American romantic comedy-drama sports film written , produced and directed by Cameron Crowe , and stars Tom Cruise , Cuba Gooding Jr. and Renée Zellweger . Produced in part by long time Simpsons producer James L. Brooks , it was inspired by sports agent Leigh Steinberg , who acted as Technical Consultant on the crew . It was released in North American theaters on December 13 , 1996 , produced by Gracie Films and distributed by TriStar Pictures . The film received critical acclaim , with critics praising its acting and writing . The film was a financial success , bringing in more than $ 273 million worldwide , against its $ 50 million budget . It was the ninth top-grossing film of 1996 . The film was nominated for five Academy Awards , including Best Picture and Best Actor for Tom Cruise , with Cuba Gooding Jr. winning the Academy Award for Best Supporting Actor . The film was also nominated for three Golden Globes , with Tom Cruise winning for Best Actor , and three Screen Actors Guild Awards , with Cuba Gooding Jr. winning Best Supporting Actor .", "title": "" } ]
[ { "docid": "Richard_Sakai", "text": "Richard Sakai ( born January 28 , 1954 ) is an American television and film producer . He is best known for his work on the animated sitcom The Simpsons , for which he is one of the original producers . In 1997 , Sakai was nominated for an Academy Award for Best Picture for his work on the film Jerry Maguire ( 1996 ) . Sakai began his career as an assistant to James L. Brooks in 1977 . In 1984 , Brooks invited Sakai to become a producer in his new film production company , Gracie Films . Sakai ultimately produced many of Brooks ' films , such as Jerry Maguire , As Good as It Gets ( 1997 ) , and Spanglish ( 2004 ) . Sakai also produced Bottle Rocket ( 1996 ) and Riding in Cars with Boys ( 2001 ) . Additionally , he was a producer for The Simpsons Movie ( 2007 ) . As a television producer and director , Sakai has worked on many different shows . He has directed episodes of Taxi , Newhart , and Who 's the Boss ? . He has also produced episodes of The Tracey Ullman Show , The Critic , Phenom , and What About Joan ? in addition to his work on The Simpsons , for which he has won several Emmy Awards . On The Simpsons , Sakai has been animated several times , most notably as : a karaoke singer in the episode One Fish , Two Fish , Blowfish , Blue Fish ; an escaping prisoner in a commercial about `` revolving door prisons '' in Sideshow Bob Roberts ; and a jazz vibraphone player in Jazzy and the Pussycats . Sakai is currently president of Gracie Films .", "title": "" }, { "docid": "Gracie_Films", "text": "Gracie Films is a California-based film and television production company , created by James L. Brooks in 1986 . The company has produced many award-winning films and television series , including Big , Broadcast News , Jerry Maguire , and most notably The Simpsons . The company is primarily associated with film studio and distributor Sony Pictures Entertainment , but it still has an office at the 20th Century Fox lot as The Simpsons is still produced there .", "title": "" }, { "docid": "Jared_Jussim", "text": "Jared Jussim ( born 1935 ) is the Deputy General Counsel and Executive Vice President of the Intellectual Property Department of Sony Pictures Entertainment Inc. , a division of the Sony Corporation , where he has worked since 1971 . Jussim attended City College of the City University of New York , graduating in 1958 , and Harvard Law School , graduating in 1961 and is admitted to the bar in California and New York . His professional activities include participation in New York State Bar Association 's Committee on Legislation , on which he held the position of Chairman from 1986 - 1990 . Jussim appeared in TriStar Pictures ' Jerry Maguire in 1996 as Dicky Fox , mentor to Tom Cruise 's Jerry Maguire . TriStar was a subsidiary of Columbia Pictures , which was renamed Sony Pictures Entertainment in 1991 . Cameron Crowe had initially asked director Billy Wilder to play the role of Dicky Fox but Wilder told him to get an actor . Jussim , who had no prior acting experience , was cast for the role after walking into a production meeting with Crowe and James L. Brooks . Jussim was asked to say one line and was thereafter selected .", "title": "" }, { "docid": "James_Brooks", "text": "James , Jim , or Jimmy Brooks may refer to : James Brooks ( American football ) ( born 1958 ) , American football player James Brooks ( architect ) ( 1825 -- 1901 ) , English architect James Brooks ( bishop ) ( 1512 -- 1560 ) , Bishop of Gloucester James Brooks ( civil servant ) KCB ( 1863 -- 1941 ) , British Admiralty Director of Victualling James Brooks ( painter ) ( 1906 -- 1992 ) , American painter James Brooks ( politician ) ( 1810 -- 1873 ) , United States Representative from New York James Brooks ( rugby union ) ( born 1980 ) , English rugby player James Brooks ( Texas Ranger ) ( 1855 -- 1944 ) , American lawman James Brooks , guitarist with British post-rock band Appliance James Brooks , Jr. ( 1942 -- 1999 ) , American actor , known by his stage name of Stephen Brooks James F. Brooks ( born 1955 ) , American historian James L. Brooks ( born 1940 ) , American producer , writer and film director Jim Brooks ( actor ) ( born 1980 ) , American actor Jim Brooks , co-owner of the Lehigh Valley Phantoms ice hockey team Jimmy Brooks , fictional character on Degrassi : The Next Generation", "title": "" }, { "docid": "What_About_Joan?", "text": "What About Joan ? is an ABC sitcom that aired in 2001 for 2 seasons ( 21 episodes ) . It starred Joan Cusack as Joan Gallagher , a Chicago schoolteacher and the comedy of her day-to-day life . It co-starred Kyle Chandler . It was produced by James L. Brooks , Richard Sakai , David Richardson , and Ed Weinberger .", "title": "" }, { "docid": "James_Maguire", "text": "James Maguire may refer to : James G. Maguire , American politician James Maguire ( basketball ) , basketball player for Canada at the 1964 Summer Olympics James Rochfort Maguire ( 1855 -- 1925 ) , British imperialist and Irish Nationalist politician and MP James Maguire ( rugby union ) ( 1886 -- 1966 ) , New Zealand rugby union player Jim Maguire , Irish footballer Jamie Maguire , character of the British television drama series Shameless", "title": "" }, { "docid": "The_Simpsons_(season_1)", "text": "The Simpsons ' first season originally aired on the Fox network between December 17 , 1989 and May 13 , 1990 , beginning with the Christmas special `` Simpsons Roasting on an Open Fire '' . The executive producers for the first production season were Matt Groening , James L. Brooks , and Sam Simon . The series was originally set to debut in autumn 1989 with the episode `` Some Enchanted Evening '' , which was meant to introduce the main characters ; during the first screening of the episode , the producers discovered that the animation was so appalling that 70 % of the episode needed to be redone . The producers considered aborting the series if the next episode turned out as bad , but it only suffered from easily fixable problems . The producers convinced Fox to move the debut to December 17 , and aired `` Simpsons Roasting on an Open Fire '' as the first episode of the series . The first season won one Emmy Award , and received four additional nominations . The DVD boxset was released on September 25 , 2001 in Region 1 and September 24 , 2001 in both Region 2 and Region 4", "title": "" }, { "docid": "James_L._Brooks", "text": "James Lawrence `` Jim '' Brooks ( born May 9 , 1940 ) is an Academy Award - , Emmy - and Peabody Award-winning American television and movie director , producer and screenwriter . Growing up in North Bergen , New Jersey , Brooks endured a fractured family life and passed the time by reading and writing . After dropping out of New York University , he got a job as an usher at CBS , going on to write for the CBS News broadcasts . He moved to Los Angeles in 1965 to work on David L. Wolper 's documentaries . After being laid off he met producer Allan Burns who secured him a job as a writer on the series My Mother the Car . Brooks wrote for several shows before being hired as a story editor on My Friend Tony and later created the series Room 222 . Grant Tinker hired Brooks and Burns at MTM Productions to create The Mary Tyler Moore Show in 1970 . The show , one of the first to feature an independent working woman as its lead character , was critically acclaimed and won Brooks several Primetime Emmy Awards . Brooks and Burns then created two successful spin-offs from Mary Tyler Moore in the shape of Rhoda ( a comedy ) and Lou Grant ( a drama ) . Brooks left MTM Productions in 1978 to co-create the sitcom Taxi which , despite winning multiple Emmys , suffered from low ratings and was canceled twice . Brooks moved into feature film work when he wrote and co-produced the 1979 film Starting Over . His next project was the critically acclaimed film Terms of Endearment , which he produced , directed and wrote , winning an Academy Award for all three roles . Basing his next film , Broadcast News , on his journalistic experiences , the film earned him a further two Academy Award nominations . Although his 1994 work I 'll Do Anything was hampered by negative press attention due to the cutting of all of its recorded musical numbers , As Good as It Gets ( co-written with Mark Andrus ) earned further praise . It was seven years until his next film , 2004 's Spanglish . His sixth film , How Do You Know , was released in 2010 . Brooks also produced and mentored Cameron Crowe on Say Anything ... ( 1989 ) and Wes Anderson and Owen Wilson on Bottle Rocket ( 1996 ) . In 1984 , Brooks founded the television and film company , Gracie Films . Although he did not intend to do so , Brooks returned to television in 1987 as the producer of The Tracey Ullman Show . He hired cartoonist Matt Groening to create a series of shorts for the show , which eventually led to The Simpsons in 1989 . The Simpsons won numerous awards and is still running . Brooks also co-produced and co-wrote the 2007 film adaptation of the show , The Simpsons Movie . In total , Brooks has received 47 Emmy nominations , winning 20 of them .", "title": "" }, { "docid": "Broadcast_News_(film)", "text": "Broadcast News is a 1987 romantic comedy-drama film written , produced and directed by James L. Brooks . The film concerns a virtuoso television news producer ( Holly Hunter ) , who has daily emotional breakdowns , a brilliant yet prickly reporter ( Albert Brooks ) and his charismatic but far less seasoned rival ( William Hurt ) . It also stars Robert Prosky , Lois Chiles , Joan Cusack , and Jack Nicholson ( billed only in the end credits ) as the evening news anchor .", "title": "" }, { "docid": "Chris_Lee_(producer)", "text": "Chris Lee ( born c. 1956 ) is a film producer who was formerly the head of Columbia/TriStar . During his tenure , he oversaw films such as Jerry Maguire , As Good As It Gets and Philadelphia . After leaving Columbia , he has produced films such as Valkyrie and Superman Returns . Lee is the founder of the University of Hawaii 's Academy for Creative Media .", "title": "" }, { "docid": "Laurence_Mark", "text": "Laurence Mark is an Academy Award-nominated , Emmy-nominated , Golden Globe-winning producer of such acclaimed hit films as Julie & Julia , Dreamgirls , I , Robot , As Good as It Gets and Jerry Maguire .", "title": "" }, { "docid": "Democratic_nominees_for_Governor_of_California", "text": "1849 Peter Hardeman Burnett 1851 John Bigler 1853 John Bigler 1855 John Bigler 1857 John B. Weller 1859 Milton Latham 1861 John Conness 1863 John G. Downey , 1867 H. H. Haight 1871 H. H. Haight 1875 William Irwin 1879 Hugh J. Glenn 1882 George Stoneman 1886 Washington Bartlett1890 Edward B. Pond1894 James Budd 1898 James G. Maguire 1902 Franklin K. Lane1906 Theodore A. Bell1910 Theodore A. Bell1914 J. B. Curtin1918 1922 Thomas Lee Woolwine1926 Justus S. Wardell1930 Milton K. Young1934 Upton Sinclair1938 Culbert Olson 1942 Culbert Olson 1946 Earl Warren , 1950 James Roosevelt 1954 Richard P. Graves1958 Edmund G. `` Pat '' Brown 1962 Edmund G. `` Pat '' Brown 1966 Edmund G. `` Pat '' Brown 1970 Jess Unruh 1974 Jerry Brown 1978 Jerry Brown 1982 Tom Bradley1986 Tom Bradley1990 Dianne Feinstein 1994 Kathleen Brown1998 Gray Davis 2002 Gray Davis 2006 Phil Angelides 2010 Jerry Brown All except those in italics '' won the general election and were elected Governor of California .", "title": "" }, { "docid": "My_Mother_the_Car", "text": "My Mother the Car is an American fantasy sitcom which aired for a single season on NBC between September 14 , 1965 and April 5 , 1966 . A total of 30 episodes were produced by United Artists Television . Critics and adult viewers generally panned the show , often savagely . In 2002 , TV Guide proclaimed it to be the second-worst of all time , just behind The Jerry Springer Show . In 2010 The O'Reilly Factor recorded its viewers as listing it as the worst show of all time . In the context of its time , however , My Mother the Car was an original variation on then-popular `` gimmick '' shows like Bewitched , My Favorite Martian , The Flying Nun , I Dream of Jeannie , and especially Mister Ed , all of which depended on a fantastic , quirky premise for their comedy . Allan Burns , co-creator of My Mother the Car , went on to create several critically acclaimed shows , including The Mary Tyler Moore Show , Rhoda , and Lou Grant . Television producer James L. Brooks , who later collaborated with Burns on these series , created , among others , Room 222 and Taxi , and served as executive producer of The Simpsons ( which later parodied the show in the `` Lovematic Grandpa '' segment of `` The Simpsons Spin-Off Showcase '' ) , got his start in television sitcoms when he was called upon to rewrite a script for an episode of the series . The other co-creator , Chris Hayward , produced and wrote for Barney Miller during its first several seasons . The show is currently in syndication in the digital television subchannel Antenna TV .", "title": "" }, { "docid": "Sibs", "text": "Sibs is an American sitcom broadcast by ABC from September 17 , 1991 until May 6 , 1992 . The series chronicled the relationship of three sisters , and the support the youngest two especially needed from their eldest married sister . Sibs was created by Heide Perlman and executived produced by Perlman , James L. Brooks and Sam Simon , all of whom had been showrunners of Fox 's The Tracey Ullman Show . The series was backed by Brooks ' Gracie Films company and Columbia Pictures Television .", "title": "" }, { "docid": "Theo_Greenly", "text": "Theo Greenly ( born March 27 , 1985 in Laguna Beach , California ) is an American actor . He is perhaps best known for role as Elliott Rifkin on the Disney Channel series The Jersey . In 1997 , he co-starred with Pauly Shore in Shore 's self-titled Fox sitcom Pauly . His other television credits include Profiler , Judging Amy and the animated series Fillmore ! . His film credits include Jerry Maguire ( 1996 ) , Touch ( 1997 ) , Chump Change ( 2001 ) and A.I. Artificial Intelligence ( 2001 ) .", "title": "" }, { "docid": "The_Producers_(musical)", "text": "The Producers is a musical adapted by Mel Brooks and Thomas Meehan from Brooks ' 1968 film of the same name , with lyrics written by Brooks and music composed by Brooks and arranged by Glen Kelly and Doug Besterman . As in the film , the story concerns two theatrical producers who scheme to get rich by overselling interests in a Broadway flop . Complications arise when the show unexpectedly turns out to be successful . The humor of the show draws on ridiculous accents , caricatures of homosexuals and Nazis , and many show business in-jokes . After 33 previews , the original Broadway production opened at the St. James Theatre on April 19 , 2001 , starring Nathan Lane and Matthew Broderick , and ran for 2,502 performances , winning a record-breaking 12 Tony Awards . It spawned a successful London production running for just over two years , national tours in the US and UK , many productions worldwide and a 2005 film version .", "title": "" }, { "docid": "Jerry_Ross", "text": "Jerry Ross may refer to : Jerry Ross ( painter ) ( born 1944 ) , Gerald , American painter Jerry Ross ( composer ) ( 1926 -- 1955 ) , Jerold , American lyricist and composer Jerry L. Ross ( born 1948 ) , U.S. Air Force officer and former NASA astronaut Jerry Ross ( record producer ) ( born 1933 ) , American songwriter and producer , founder of Heritage Records", "title": "" }, { "docid": "Allan_Burns", "text": "Allan Burns ( born May 18 , 1935 ) is an American screenwriter and television producer . Burns is best known for , alongside James L. Brooks , creating and writing for the television sitcoms The Munsters , The Mary Tyler Moore Show and Rhoda .", "title": "" }, { "docid": "A_Star_Is_Burns", "text": "`` A Star Is Burns '' is the eighteenth episode of The Simpsons ' sixth season . It first aired on the Fox network in the United States on March 5 , 1995 . In the episode , Springfield decides to hold a film festival , and famed critic Jay Sherman is invited to be a judge . The story involves a crossover with the short-lived animated series The Critic . Jay Sherman was the main character on the show . The Critic was created by Al Jean and Mike Reiss , who had previously written for The Simpsons but left following the fourth season , and produced by James L. Brooks , who was also a producer for The Simpsons . The show had premiered on the American Broadcasting Company ( ABC ) network in January 1994 but was canceled despite positive critical reception . The series was switched over to Fox , and put in the timeslot directly after The Simpsons . Brooks pitched a crossover episode as a way to promote The Critic and decided that a film festival would be a good way to introduce Sherman . Matt Groening , creator of The Simpsons , reacted negatively when he heard about this episode , feeling that it was just an advertisement for The Critic , and that people would incorrectly associate the show with him . When he was unsuccessful in getting the program pulled , he had his name removed from the credits and went public with his concerns , openly criticizing James L. Brooks . The episode was directed by Susie Dietter and was the first episode to be written by Ken Keeler . Jon Lovitz , the star of The Critic , guest stars as Jay Sherman , while Maurice LaMarche ( who was also a regular on The Critic ) has a few minor roles . The episode received mixed reviews from critics , many of whom felt the crossover was out of place on the show , although Barney 's film festival entry was well received .", "title": "" }, { "docid": "Jay_Mohr", "text": "Jon Ferguson Cox `` Jay '' Mohr ( born Jon Ferguson Mohr ; August 23 , 1970 ) is an American actor , comedian and radio host . He is known for his role as Professor Rick Payne in the TV series Ghost Whisperer ( 2006 -- 2008 ) , the title role in the CBS sitcom Gary Unmarried ( 2008 -- 2010 ) , as a featured cast member on the sketch comedy show Saturday Night Live ( 1993 -- 1995 ) and the back-stabbing sports agent Bob Sugar in Jerry Maguire ( 1996 ) . Since making his cinema debut with Jerry Maguire , he has appeared in many more high-profile films , including Picture Perfect ( 1997 ) , Paulie ( 1998 ) , Small Soldiers ( 1998 ) , The Adventures of Pluto Nash ( 2002 ) , Are We There Yet ? ( 2005 ) , Street Kings ( 2008 ) , Hereafter ( 2010 ) and The Incredible Burt Wonderstone ( 2013 ) . Mohr hosts his own podcast Mohr Stories on the SModcast Network and , since September 2015 , hosted Jay Mohr Sports , a daily midday sports radio talk show on Fox Sports Radio . Mohr left Fox Sports Radio in January of 2016 to pursue acting ventures . He was nominated for a Primetime Emmy Award as the inaugural host and executive producer of Last Comic Standing ( 2003 -- 2006 ) .", "title": "" }, { "docid": "Lilac_Wine", "text": "`` Lilac Wine '' is a song written by James Shelton ( lyrics and music ) in 1950 . It was introduced by Hope Foye in the short-lived theater musical revue , Dance Me a Song . The song has since been covered by many famous artists including Eartha Kitt , Nina Simone , Elkie Brooks , Katie Melua , Jeff Buckley , Clare Maguire , Jeff Beck , Fanny Ardant , John Legend , Miley Cyrus , Emily Keener , and The Cinematic Orchestra .", "title": "" }, { "docid": "James_Maguire_(rugby_union)", "text": "James Richard Maguire ( 6 February 1886 -- 1 December 1966 ) was a New Zealand rugby union player . Mainly a backrow forward , Maguire represented at a provincial level between 1905 and 1910 . He was a member of the New Zealand national side , the All Blacks , on their 1910 tour of Australia . He played six matches for the All Blacks on that tour -- five of them at hooker -- including three internationals . Maguire was also a noted rower , being a part of the Waitemata four that won a national title in 1909 . Maguire died in Lower Hutt on 1 December 1966 , and was buried at Karori Cemetery .", "title": "" }, { "docid": "Terms_of_Endearment", "text": "Terms of Endearment is a 1983 American comedy-drama film adapted from Larry McMurtry 's eponymous 1975 novel , directed , written , and produced by James L. Brooks and starring Shirley MacLaine , Debra Winger , Jack Nicholson , Danny DeVito , Jeff Daniels , and John Lithgow . The film covers 30 years of the relationship between Aurora Greenway ( MacLaine ) and her daughter Emma ( Winger ) . The film received eleven Academy Award nominations and won five . Brooks won the Academy Awards for Best Picture , Best Director , and Best Writing ( Adapted Screenplay ) while MacLaine won the Academy Award for Best Actress and Nicholson won the Academy Award for Best Supporting Actor . In addition , it won four Golden Globes : Best Motion Picture -- Drama , Best Actress in a Drama ( MacLaine ) , Best Supporting Actor ( Nicholson ) , and Best Screenplay ( Brooks ) .", "title": "" }, { "docid": "John_Maguire", "text": "John Maguire may refer to : John Maguire ( archbishop of Glasgow ) ( 1851 -- 1920 ) , Scottish Roman Catholic prelate John Maguire ( coadjutor archbishop of New York ) ( 1904 -- 1989 ) , American Roman Catholic prelate John Maguire ( cricketer ) ( born 1956 ) , Australian cricketer John Maguire ( fighter ) ( born 1983 ) , English mixed martial artist John Maguire ( Irish politician ) ( died 1872 ) , Irish politician John Maguire ( Irish senator ) , Irish senator John A. Maguire ( 1870 -- 1939 ) , American politician John M. Maguire , CEO of Friendly 's Jack Maguire ( 1925 -- 2001 ) , American baseball player", "title": "" }, { "docid": "Michael_Maguire_(actor)", "text": "Michael L. Maguire ( born February 20 , 1955 ) is an American actor , best known for his role as Enjolras in the original Broadway production of the musical Les Misérables . This role won him a Tony Award in 1987 . It also won him a Drama Desk Award and a Theatre World Award . In 1995 he was chosen to reprise the role in Les Misérables : The Dream Cast in Concert at the Royal Albert Hall in London , produced to celebrate the musical 's 10th anniversary . His voice type is baritone . Maguire was born in Newport News , Virginia , and , as a teenager , worked as a strolling troubadour in Williamsburg , Virginia , before going on to study opera at the Oberlin Conservatory and the University of Michigan . One of his sisters is Linda Maguire , a renowned classical and operatic vocalist . He worked as a stockbroker for several years before making his Broadway debut in 1987 with Les Misérables . He appeared in the films L.A. Pictures , Cadillac , Go Fish , The Deep End of the Ocean , Busted , and Where The Day Takes You , as well as in a variety of television shows . In 2008 he received a law degree from Southwestern Law School in Los Angeles . He now practices family law in Beverly Hills .", "title": "" }, { "docid": "Jerry_DeGregorio", "text": "Gennaro L. `` Jerry '' DeGregorio ( born February 20 , 1962 ) is an American basketball coach . He was the former head basketball coach of the University of Rhode Island , where he coached the Rams from 1999 to 2001 .", "title": "" }, { "docid": "James_Brooks_(rugby_union)", "text": "James Brooks ( born 6 April 1980 in Henley-on-Thames , Oxfordshire , England ) is a rugby union footballer who plays at fly-half for Leeds Carnegie . Brooks began his playing career in rugby league , spending two seasons with London Broncos . In 2001 he then joined Northampton Saints , signing for Wasps in the summer of 2004 . He joined Leeds Carnegie at the beginning of the 2007-08 . Brooks was a regular in the England sevens squad between 2003 and 2005 .", "title": "" }, { "docid": "Bryan_Maguire,_1st_Baron_of_Enniskillen", "text": "Bryan Roe Maguire , 1st Baron of Enniskillen ( Brian Rua Mag Uidhir 1589 -- 1633 ) , was a Gaelic Irish nobleman from Magherastephana , County Fermanagh . He was the son of Connor Roe Maguire , nicknamed `` the Queen 's Maguire '' for his support of Elizabeth I 's campaign in the Nine Years ' War . Bryan was knighted on 2 February 1626 and made `` Lord Maguire , Baron of Enniskillen '' by James I on 3 March 1627 . The Annals of the Four Masters was compiled under his patronage . His sons Connor Maguire , 2nd Baron and Colonel Rory Maguire died as officers of Confederate Ireland .", "title": "" }, { "docid": "The_Longest_Daycare", "text": "Maggie Simpson in `` The Longest Daycare '' , or simply The Longest Daycare , is a 2012 American traditionally animated 3D comedy short film based on the animated television series The Simpsons . In the film , Maggie Simpson is enrolled at a new daycare facility where she squares off with the foul-tempered Baby Gerald when she befriends a caterpillar . The short originated with Simpsons producer James L. Brooks , who enlisted long-time veteran of the series , David Silverman , to direct the film . The picture was written by producers Brooks , Al Jean , David Mirkin , writers Michael Price and Joel H. Cohen , as well as show creator Matt Groening . The film premiered on July 13 , 2012 , where it was attached to screenings of the 20th Century Fox release Ice Age : Continental Drift . The film is the second Simpsons theatrical release . Reception has been positive , praising the storytelling and animation . The film was nominated for an Academy Award for Best Animated Short Film in 2013 , losing to Paperman .", "title": "" }, { "docid": "David_Davis_(TV_producer)", "text": "David Davis ( born 1937 ) is an American television producer and television writer . He is best known for work on the sitcoms The Bob Newhart Show , a series he co-created with Lorenzo Music , and Taxi , a series he co-created with James L. Brooks , Stan Daniels and Ed . Weinberger . In 1979 , he won a Primetime Emmy Award for his producing work on Taxi . He also produced for the series O.K. Crackerby ! , My Mother the Car , He & She , The Good Guys , Get Smart and wrote episodes for The Mary Tyler Moore Show and its spin-off Rhoda . Since 1976 , Davis has been in a relationship with actress Julie Kavner , they met on the set on Rhoda , a series Kavner co-starred in .", "title": "" } ]
PLAIN-3369
The Healthiest Beverage
[ { "docid": "MED-2827", "text": "Alternative and complementary therapeutic approaches, such as the use of a wide array of herbal, nutritional, and physical manipulations, are becoming popular for relieving symptoms of osteoarthritis (OA). The present study evaluated the efficacy of soy protein (SP) supplementation in relieving the pain and discomfort associated with OA. One hundred and thirty-five free-living individuals (64 men and 71 women) with diagnosed OA or with self-reported chronic knee joint pain not attributed to injury or rheumatoid arthritis were recruited for this double-blind, placebo-controlled, parallel design study. Study participants were assigned randomly to consume 40 g of either supplemental SP or milk-based protein (MP) daily for 3 months. Pain, knee range of motion, and overall physical activity were evaluated prior to the start of treatment and monthly thereafter. Serum levels of glycoprotein 39 (YKL-40), a marker of cartilage degradation, and insulin-like growth factor-I (IGF-I), a growth factor associated with cartilage synthesis, were assessed at baseline and at the end of the study. Overall, SP improved OA-associated symptoms such as range of motion and several factors associated with pain and quality of life in comparison to MP. However, these beneficial effects were mainly due to the effect of SP in men rather than women. Biochemical markers of cartilage metabolism further support the efficacy of SP in men as indicated by a significant increase in serum level of IGF-I and a significant decrease in serum level of YKL-40 compared to MP. This study is the first to provide evidence of possible beneficial effects of SP in the management of OA. Examining and verifying the long-term effects of SP on improving symptoms of OA, particularly in men, is warranted.", "title": "Soy protein may alleviate osteoarthritis symptoms." }, { "docid": "MED-5052", "text": "OBJECTIVE: Habitual green tea consumption has long been associated with health benefits including chemoprevention and cardiovascular protection. This non-systematic literature review presents the clinical evidence to date. METHOD: A literature review of peer-reviewed articles on observational and interventional studies was conducted to include green tea, its extract or its purified polyphenol (-)-epigallocatechin-3-gallate (EGCG). Electronic databases searched included PubMed (1966-2009) and the Cochrane Library (Issue 4, 2008). RESULTS: Observational studies are inconclusive on the benefits of habitual consumption of green tea in the prevention of most cancers. However, there are trends towards prevention in breast and prostate cancers. Interventional studies have demonstrated reduction in relapses following surgical resection in colorectal adenomas and increased survival rates in epithelial ovarian cancer. Observational studies indicate that green tea may provide protection against hypertension and reduce the risk for stroke, and interventional studies are providing biochemical and physiological evidence. CONCLUSION: Although the overall clinical evidence is inconclusive, habitual green tea consumption may be providing some level of chemoprevention in prostate and breast cancer. Green tea may also attenuate the risk factors association with the development of atherosclerosis thus reducing the incidence of cardiovascular events and stoke.", "title": "Can green tea do that? A literature review of the clinical evidence." }, { "docid": "MED-2826", "text": "Background Curcumin extracts of turmeric are proposed to produce health benefits. To date, human intervention studies have focused mainly on people with existing health problems given high doses of poorly absorbed curcumin. The purpose of the current study was to check whether in healthy people, a low dose of a lipidated curcumin extract could alter wellness-related measures. Methods The present study was conducted in healthy middle aged people (40–60 years old) with a low dose of curcumin (80 mg/day) in a lipidated form expected to have good absorption. Subjects were given either curcumin (N = 19) or placebo (N = 19) for 4 wk. Blood and saliva samples were taken before and after the 4 weeks and analyzed for a variety of blood and saliva measures relevant to health promotion. Results Curcumin, but not placebo, produced the following statistically significant changes: lowering of plasma triglyceride values, lowering of salivary amylase levels, raising of salivary radical scavenging capacities, raising of plasma catalase activities, lowering of plasma beta amyloid protein concentrations, lowering of plasma sICAM readings, increased plasma myeloperoxidase without increased c-reactive protein levels, increased plasma nitric oxide, and decreased plasma alanine amino transferase activities. Conclusion Collectively, these results demonstrate that a low dose of a curcumin-lipid preparation can produce a variety of potentially health promoting effects in healthy middle aged people.", "title": "Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people" }, { "docid": "MED-2830", "text": "OBJECTIVE: The aim of this work was to determine the bioavailability of herbs and spices after human consumption by measuring the ability to protect lymphocytes from an oxidative injury and by examining the impact on inflammatory biomarkers in activated THP-1 cells. METHODS: Ten to 12 subjects in each of 13 groups consumed a defined amount of herb or spice for 7 days. Blood was drawn from subjects before consumption and 1 hour after taking the final herb or spice capsules. Subject serum and various extractions of the herbs and spices were analyzed for antioxidant capacity by oxygen radical absorbance capacity (ORAC) analysis or by 1,1-diphenyl-2-picrylhydrzyl (DPPH). Subject peripheral blood mononuclear cells (PBMCs) in medium with10% autologous serum were incubated with hydrogen peroxide to induce DNA strand breaks. Subject serum was also used to treat activated THP-1 cells to determine relative quantities of 3 inflammatory cytokine (tumor necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and IL-6) mRNAs. RESULTS: Herbs and spices that protected PBMCs against DNA strand breaks were paprika, rosemary, ginger, heat-treated turmeric, sage, and cumin. Paprika also appeared to protect cells from normal apoptotic processes. Of the 3 cytokine mRNAs studied (TNF-α, IL-1α, and IL-6), TNF-α was the most sensitive responder to oxidized LDL-treated macrophages. Clove, ginger, rosemary, and turmeric were able to significantly reduce oxidized LDL-induced expression of TNF-α. Serum from those consuming ginger reduced all three inflammatory biomarkers. Ginger, rosemary, and turmeric showed protective capacity by both oxidative protection and inflammation measures. CONCLUSIONS: DNA strand breaks and inflammatory biomarkers are a good functional measure of a food's bioavailability.", "title": "Bioavailability of herbs and spices in humans as determined by ex vivo inflammatory suppression and DNA strand breaks." }, { "docid": "MED-2831", "text": "TNFs are major mediators of inflammation and inflammation-related diseases, hence, the United States Food and Drug Administration (FDA) has approved the use of blockers of the cytokine, TNF-α, for the treatment of osteoarthritis, inflammatory bowel disease, psoriasis and ankylosis. These drugs include the chimeric TNF antibody (infliximab), humanized TNF-α antibody (Humira) and soluble TNF receptor-II (Enbrel) and are associated with a total cumulative market value of more than $20 billion a year. As well as being expensive ($15 000–20 000 per person per year), these drugs have to be injected and have enough adverse effects to be given a black label warning by the FDA. In the current report, we describe an alternative, curcumin (diferuloylmethane), a component of turmeric (Curcuma longa) that is very inexpensive, orally bioavailable and highly safe in humans, yet can block TNF-α action and production in in vitro models, in animal models and in humans. In addition, we provide evidence for curcumin's activities against all of the diseases for which TNF blockers are currently being used. Mechanisms by which curcumin inhibits the production and the cell signalling pathways activated by this cytokine are also discussed. With health-care costs and safety being major issues today, this golden spice may help provide the solution. Linked Articles This article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-8", "title": "Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers" } ]
[ { "docid": "MED-4994", "text": "BACKGROUND: The cardioprotective properties of moderate alcohol consumption, compared with abstinence or heavy drinking, are widely reported, but whether the benefits are experienced equally by all moderate drinkers is less well known. AIMS: To examine the association between average alcohol intake per week and the incidence of fatal and non-fatal myocardial infarction during 17 years of follow-up for 9655 men and women without prevalent disease in the general population; and to test whether the level of cardioprotection differs according to subjects' other health behaviours (healthy, moderately healthy, unhealthy) at entry to the study. METHOD: A longitudinal, British civil service-based cohort study, baseline in 1985-8. RESULTS: A significant benefit of moderate drinking compared with abstinence or heavy drinking was found among those with poor health behaviours (little exercise, poor diet and smokers). No additional benefit from alcohol was found among those with the healthiest behaviour profile (> or =3 hours of vigorous exercise per week, daily fruit or vegetable consumption and non-smokers). CONCLUSION: The cardioprotective benefit from moderate drinking does not apply equally to all drinkers, and this variability should be emphasised in public health messages.", "title": "Who benefits most from the cardioprotective properties of alcohol consumption--health freaks or couch potatoes?" }, { "docid": "MED-1743", "text": "This article describes the nutrient and elemental composition, including residues of herbicides and pesticides, of 31 soybean batches from Iowa, USA. The soy samples were grouped into three different categories: (i) genetically modified, glyphosate-tolerant soy (GM-soy); (ii) unmodified soy cultivated using a conventional \"chemical\" cultivation regime; and (iii) unmodified soy cultivated using an organic cultivation regime. Organic soybeans showed the healthiest nutritional profile with more sugars, such as glucose, fructose, sucrose and maltose, significantly more total protein, zinc and less fibre than both conventional and GM-soy. Organic soybeans also contained less total saturated fat and total omega-6 fatty acids than both conventional and GM-soy. GM-soy contained high residues of glyphosate and AMPA (mean 3.3 and 5.7 mg/kg, respectively). Conventional and organic soybean batches contained none of these agrochemicals. Using 35 different nutritional and elemental variables to characterise each soy sample, we were able to discriminate GM, conventional and organic soybeans without exception, demonstrating \"substantial non-equivalence\" in compositional characteristics for 'ready-to-market' soybeans. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.", "title": "Compositional differences in soybeans on the market: glyphosate accumulates in Roundup Ready GM soybeans." }, { "docid": "MED-1646", "text": "The Beverage Guidance Panel was assembled to provide guidance on the relative health and nutritional benefits and risks of various beverage categories. The beverage panel was initiated by the first author. The Panel's purpose is to attempt to systematically review the literature on beverages and health and provide guidance to the consumer. An additional purpose of the Panel is to develop a deeper dialog among the scientific community on overall beverage consumption patterns in the United States and on the great potential to change this pattern as a way to improve health. Over the past several decades, levels of overweight and obesity have increased across all population groups in the United States. Concurrently, an increased daily intake of 150-300 kcal (for different age-sex groups) has occurred, with approximately 50% of the increased calories coming from the consumption of calorically sweetened beverages. The panel ranked beverages from the lowest to the highest value based on caloric and nutrient contents and related health benefits and risks. Drinking water was ranked as the preferred beverage to fulfill daily water needs and was followed in decreasing value by tea and coffee, low-fat (1.5% or 1%) and skim (nonfat) milk and soy beverages, noncalorically sweetened beverages, beverages with some nutritional benefits (fruit and vegetable juices, whole milk, alcohol, and sports drinks), and calorically sweetened, nutrient-poor beverages. The Panel recommends that the consumption of beverages with no or few calories should take precedence over the consumption of beverages with more calories.", "title": "A new proposed guidance system for beverage consumption in the United States." }, { "docid": "MED-1710", "text": "Sugar intake in the United States has increased by >40 fold since the American Revolution. The health concerns that have been raised about the amounts of sugar that are in the current diet, primarily as beverages, are the subject of this review. Just less than 50% of the added sugars (sugar and high-fructose corn syrup) are found in soft drinks and fruit drinks. The intake of soft drinks has increased 5-fold between 1950 and 2000. Most meta-analyses have shown that the risk of obesity, diabetes, cardiovascular disease, and metabolic syndrome are related to consumption of beverages sweetened with sugar or high-fructose corn syrup. Calorically sweetened beverage intake has also been related to the risk of nonalcoholic fatty liver disease, and, in men, gout. Calorically sweetened beverages contribute to obesity through their caloric load, and the intake of beverages does not produce a corresponding reduction in the intake of other food, suggesting that beverage calories are “add-on” calories. The increase in plasma triglyceride concentrations by sugar-sweetened beverages can be attributed to fructose rather than glucose in sugar. Several randomized trials of sugar-containing soft drinks versus low-calorie or calorie-free beverages show that either sugar, 50% of which is fructose, or fructose alone increases triglycerides, body weight, visceral adipose tissue, muscle fat, and liver fat. Fructose is metabolized primarily in the liver. When it is taken up by the liver, ATP decreases rapidly as the phosphate is transferred to fructose in a form that makes it easy to convert to lipid precursors. Fructose intake enhances lipogenesis and the production of uric acid. By worsening blood lipids, contributing to obesity, diabetes, fatty liver, and gout, fructose in the amounts currently consumed is hazardous to the health of some people.", "title": "Energy and Fructose From Beverages Sweetened With Sugar or High-Fructose Corn Syrup Pose a Health Risk for Some People" }, { "docid": "MED-1858", "text": "As a hard tissue dental disease, dental erosion has a multifactorial etiology. The majority of dental erosion that originates from extrinsic sources is the result of dietary intake, particularly acidic beverages. Several preventive means have been proposed to minimize the damage to the dentition, including a reduction in the consumption of causative beverages and the adoption of a specific method of drinking, utilizing a straw instead of a cup. This article presents two cases involving the clinical and radiographic features of erosion lesions associated with chronic and excessive intake of acidic carbonated beverages. These examples embody how drinking patterns influence the formation of erosion lesions in various anatomic locations within the dentition. The clinical and radiographic evidence presented in this report cautions against the use of nonspecific terms, such as \"cup versus straw,\" and instead suggests implementing a more precise description of the suggested method. In view of the extensive damage inflicted by the chronic, excessive intake of carbonated beverages, preventive measures are considered to be the only effective course of management. This article offers illustrative examples of erosion lesions associated with long-term excessive intake of carbonated beverages. The influence of the drinking method--that is, a straw positioned into the labial vestibule versus a cup--on the anatomic location of the erosion lesions will be demonstrated through clinical and radiographic evidence.", "title": "Influence of drinking patterns of carbonated beverages on dental erosion." }, { "docid": "MED-713", "text": "The effect of beverages prepared from the dried calyx of the flowers of Hibiscus sabdariffa on the excretion of diclofenac was investigated using a controlled study in healthy human volunteers. A high pressure liquid chromatographic method was used to analyse the 8 h urine samples collected after the administration of diclofenac with 300 mL (equivalent to 8.18 mg anthocyanins) of the beverage administered daily for 3 days. An unpaired two-tailed t-test was used to analyse for significant difference observed in the amount of diclofenac excreted before and after administration of the beverage. There was a reduction in the amount of diclofenac excreted and the wide variability observed in the control with the water beverage of Hibiscus sabdariffa (p < 0.05). There is an increasing need to counsel patients against the use of plant beverages with drugs.", "title": "Effects of water extract of Hibiscus sabdariffa, Linn (Malvaceae) 'Roselle' on excretion of a diclofenac formulation." }, { "docid": "MED-1627", "text": "Sweetened beverages, coffee, and tea are the most consumed non-alcoholic beverages and may have important health consequences. We prospectively evaluated the consumption of various types of beverages assessed in 1995–1996 in relation to self-reported depression diagnosis after 2000 among 263,923 participants of the NIH-AARP Diet and Health Study. Odds ratios (OR) and 95% confidence intervals (CI) were derived from multivariate logistic regressions. The OR (95% CI) comparing ≥4 cans/cups per day with none were 1.30 (95%CI: 1.17–1.44) for soft drinks, 1.38 (1.15–1.65) for fruit drinks, and 0.91 (0.84–0.98) for coffee (all P for trend<0.0001). Null associations were observed for iced-tea and hot tea. In stratified analyses by drinkers of primarily diet versus regular beverages, the ORs were 1.31 (1.16–1.47) for diet versus 1.22 (1.03–1.45) for regular soft drinks, 1.51 (1.18–1.92) for diet versus 1.08 (0.79–1.46) for regular fruit drinks, and 1.25 (1.10–1.41) for diet versus 0.94 (0.83–1.08) for regular sweetened iced-tea. Finally, compared to nondrinkers, drinking coffee or tea without any sweetener was associated with a lower risk for depression, adding artificial sweeteners, but not sugar or honey, was associated with higher risks. Frequent consumption of sweetened beverages, especially diet drinks, may increase depression risk among older adults, whereas coffee consumption may lower the risk.", "title": "Sweetened Beverages, Coffee, and Tea and Depression Risk among Older US Adults" }, { "docid": "MED-897", "text": "The effects of different polyphenol-containing beverages on Fe absorption from a bread meal were estimated in adult human subjects from the erythrocyte incorporation of radio-Fe. The test beverages contained different polyphenol structures and were rich in either phenolic acids (chlorogenic acid in coffee), monomeric flavonoids (herb teas, camomile (Matricaria recutita L.), vervain (Verbena officinalis L.), lime flower (Tilia cordata Mill.), pennyroyal (Mentha pulegium L.) and peppermint (Mentha piperita L.), or complex polyphenol polymerization products (black tea and cocoa). All beverages were potent inhibitors of Fe absorption and reduced absorption in a dose-dependent fashion depending on the content of total polyphenols. Compared with a water control meal, beverages containing 20-50 mg total polyphenols/serving reduced Fe absorption from the bread meal by 50-70%, whereas beverages containing 100-400 mg total polyphenols/serving reduced Fe absorption by 60-90%. Inhibition by black tea was 79-94%, peppermint tea 84%, pennyroyal 73%, cocoa 71%, vervain 59%, lime flower 52% and camomile 47%. At an identical concentration of total polyphenols, black tea was more inhibitory than cocoa, and more inhibitory than herb teas camomile, vervain, lime flower and pennyroyal, but was of equal inhibition to peppermint tea. Adding milk to coffee and tea had little or no influence on their inhibitory nature. Our findings demonstrate that herb teas, as well as black tea, coffee and coca can be potent inhibitors of Fe absorption. This property should be considered when giving dietary advice in relation to Fe nutrition.", "title": "Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages." }, { "docid": "MED-3763", "text": "The aim of this study was to explore oral exposure to carcinogenic (group 1) acetaldehyde after single sips of strong alcoholic beverages containing no or high concentrations of acetaldehyde. Eight volunteers tasted 5 ml of ethanol diluted to 40 vol.% with no acetaldehyde and 40 vol.% calvados containing 2400 μM acetaldehyde. Salivary acetaldehyde and ethanol concentrations were measured by gas chromatography. The protocol was repeated after ingestion of ethanol (0.5 g/kg body weight). Salivary acetaldehyde concentration was significantly higher after sipping calvados than after sipping ethanol at 30s both with (215 vs. 128 μmol/l, p<0.05) and without (258 vs. 89 μmol/l, p<0.05) alcohol ingestion. From 2 min onwards there were no significant differences in the decreasing salivary acetaldehyde concentration, which remained above the level of carcinogenicity still at 10 min. The systemic alcohol distribution from blood to saliva had no additional effect on salivary acetaldehyde after sipping of the alcoholic beverages. Carcinogenic concentrations of acetaldehyde are produced from ethanol in the oral cavity instantly after a small sip of strong alcoholic beverage, and the exposure continues for at least 10 min. Acetaldehyde present in the beverage has a short-term effect on total acetaldehyde exposure. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "A single sip of a strong alcoholic beverage causes exposure to carcinogenic concentrations of acetaldehyde in the oral cavity." }, { "docid": "MED-918", "text": "Consumption of a large amount of dietary fructose induces gastrointestinal intolerance, and glucose has been known as an enhancer of fructose absorption. Erythritol is a nonglycemic sugar alcohol, and it has been suggested that erythritol is absorbed paracellularly. It was hypothesized that paracellular absorption of erythritol could also enhance paracellular absorption of fructose in healthy adults. This is one of the proposed pathways for how additional glucose enhances the absorption of fructose. Thirty-seven nondiabetic, healthy adults participated in a randomized, double-masked, controlled crossover study. After an overnight fast, participants consumed beverages containing either 50 g fructose and 50 g glucose, 50 g fructose and 33.3 g erythritol (an equimolar concentration of fructose), or 50 g fructose alone. Breath hydrogen response was determined for 8 hours postprandially. Gastrointestinal intolerance symptoms and the number and consistency of bowel movements were recorded for 24 hours postprandially. The breath hydrogen area under the curve (AUC) of the fructose and erythritol beverage was 2 times the AUC of the fructose beverage and 8.75 times the AUC of the fructose and glucose beverage (P < .001, respectively). Compared with fructose and glucose beverage and fructose alone, frequency of watery stools increased (P < .05) and gastrointestinal tolerance worsened (P < .05) when participants consumed fructose and erythritol. These data suggest that coingestion of equimolar concentrations of fructose and erythritol increased carbohydrate malabsorption. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Combination of erythritol and fructose increases gastrointestinal symptoms in healthy adults." }, { "docid": "MED-1637", "text": "Epidemiologic studies suggest that tea consumption decreases the risk for cardiovascular events. However, there has been no clinical report examining the effects of tea consumption on coronary circulation. The purpose of this study was to evaluate the effects of black tea on coronary flow velocity reserve (CFVR) using transthoracic Doppler echocardiography (TTDE). This was a double-blind crossover study of 10 healthy male volunteers conducted to compare the effects of black tea and caffeine on coronary circulation. The coronary flow velocity of the left anterior descending coronary artery was measured at baseline and at hyperemia during adenosine triphosphate infusion by TTDE to determine CFVR. The CFVR ratio was defined as the ratio of CFVR after beverage consumption to CFVR before beverage consumption. All data were divided into 2 groups according to beverage type: group T (black tea) and group C (caffeine). Two-way analysis of variance showed a significant group effect and interaction in CFVR before and after beverage consumption (p = 0.001). CFVR significantly increased after tea consumption in group T (4.5 +/- 0.9 vs 5.2 +/- 0.9, p <0.0001). The CFVR ratio of group T was larger than that of group C (1.18 +/- 0.07 vs 1.04 +/- 0.08, p = 0.002). Acute black tea consumption improves coronary vessel function, as determined by CFVR.", "title": "Black tea increases coronary flow velocity reserve in healthy male subjects." }, { "docid": "MED-1707", "text": "Sugar-sweetened drinks have been associated with several health problems. In the point narrative as presented below, we provide our opinion and review of the data to date that we need to reconsider consumption of dietary sugar based on the growing concern of obesity and type 2 diabetes. In the counterpoint narrative following our contribution, Drs. Kahn and Sievenpiper provide a defense and suggest that dietary sugar is not the culprit. Data from the National Health and Nutrition Examination Survey and U.S. Department of Agriculture dietary surveys along with commercial Homescan data on household purchases were used to understand changes in sugar and fructose consumption. Meta-analyses and randomized clinical trials were used to evaluate outcomes of beverage and fructose intake. About 75% of all foods and beverages contain added sugar in a large array of forms. Consumption of soft drinks has increased fivefold since 1950. Meta-analyses suggest that consumption of sugar-sweetened beverages (SSBs) is related to the risk of diabetes, the metabolic syndrome, and cardiovascular disease. Drinking two 16-ounce SSBs per day for 6 months induced features of the metabolic syndrome and fatty liver. Randomized controlled trials in children and adults lasting 6 months to 2 years have shown that lowering the intake of soft drinks reduced weight gain. Recent studies suggest a gene-SSB potential relationship. Consumption of calorie-sweetened beverages has continued to increase and plays a role in the epidemic of obesity, the metabolic syndrome, and fatty liver disease. Reducing intake of soft drinks is associated with less weight gain.", "title": "Dietary sugar and body weight: have we reached a crisis in the epidemic of obesity and diabetes?: health be damned! Pour on the sugar." }, { "docid": "MED-3533", "text": "This study ascertained whether a proprietary tart cherry juice blend (CherryPharm, Inc., Geneva, NY, USA) associated with anecdotal reports of sleep enhancement improves subjective reports of insomnia compared to a placebo beverage. The pilot study used a randomized, double-blind, crossover design where each participant received both treatment and placebo for 2 weeks with an intervening 2-week washout period. Sleep continuity (sleep onset, wake after sleep onset, total sleep time, and sleep efficiency) was assessed by 2-week mean values from daily sleep diaries and disease severity by the Insomnia Severity Index in a cohort of 15 older adults with chronic insomnia who were otherwise healthy. The tart cherry juice beverage was associated with statistically significant pre- to post-treatment improvements on all sleep variables. When compared to placebo, the study beverage produced significant reductions in insomnia severity (minutes awake after sleep onset); no such improvements were observed for sleep latency, total sleep time, or sleep efficiency compared to placebo. Effect sizes were moderate and in some cases negligible. The results of this pilot study suggest that CherryPharm, a tart cherry juice blend, has modest beneficial effects on sleep in older adults with insomnia with effect sizes equal to or exceeding those observed in studies of valerian and in some, but not all, studies of melatonin, the two most studied natural products for insomnia. These effects, however, were considerably less than those for evidence-based treatments of insomnia: hypnotic agents and cognitive-behavioral therapies for insomnia.", "title": "Effects of a Tart Cherry Juice Beverage on the Sleep of Older Adults with Insomnia: A Pilot Study" }, { "docid": "MED-4822", "text": "Objective We examined the associations between sweets, sweetened and unsweetened beverages, and sugars and pancreatic cancer risk. Methods We conducted a population-based case–control study (532 cases, 1,701 controls) and used multivariate logistic regression models to calculate odds ratios (OR) and 95% confidence intervals (CI). Because associations were often different by sex, we present results for men and women combined and separately. Results Among men, greater intakes of total and specific sweets were associated with pancreatic cancer risk (total sweets: OR = 1.9, 95% CI: 1.0, 3.6; sweet condiments: OR = 1.9, 95% CI: 1.2, 3.1; chocolate candy: OR = 2.4, 95% CI: 1.1, 5.0; other mixed candy bars: OR = 3.3, 95% CI: 1.5, 7.3 for 1 + servings/day versus none/rarely). Sweets were not consistently associated with risk among women. Sweetened beverages were not associated with increased pancreatic cancer risk. In contrast, low-calorie soft drinks were associated with increased risk among men only; while other low-/non-caloric beverages (e.g., coffee, tea, and water) were unassociated with risk. Of the three sugars assessed (lactose, fructose, and sucrose), only the milk sugar lactose was associated with pancreatic cancer risk (OR = 2.0, 95% CI: 1.5, 2.7 comparing extreme quartiles). Conclusion These results provide limited support for the hypothesis that sweets or sugars increase pancreatic cancer risk.", "title": "Sweets, sweetened beverages, and risk of pancreatic cancer in a large population-based case–control study" }, { "docid": "MED-5046", "text": "Epidemiological evidence suggests a role for tea catechins in reduction of chronic disease risk. However, stability of catechins under digestive conditions is poorly understood. The objective of this study was to characterize the effect of common food additives on digestive recovery of tea catechins. Green tea water extracts were formulated in beverages providing 4.5, 18, 23, and 3.5 mg per 100 mL epicatechin (EC), epigallocatechin (EGC), epigallocatechin-gallate (EGCG), and epicatechin-gallate (ECG), respectively. Common commercial beverage additives; citric acid (CA), BHT, EDTA, ascorbic acid (AA), milk (bovine, soy, and rice), and citrus juice (orange, grapefruit, lemon, and lime) were formulated into finished tea beverages at incremental dosages. Samples were then subjected to in vitro digestion simulating gastric and small intestinal conditions with pre- and post-digestion catechin profiles assessed by HPLC. Catechin stability in green tea was poor with <20% total catechins remaining post-digestion. EGC and EGCG were most sensitive with less, not double equals 10% recovery. Teas formulated with 50% bovine, soy, and rice milk increased total catechin recovery significantly to 52, 55, and 69% respectively. Including 30 mg AA in 250 mL of tea beverage significantly (p<0.05) increased catechin recovery of EGC, EGCG, EC, and ECG to 74, 54, 82, and 45% respectively. Juice preparation resulted in the highest recovery of any formulation for EGC (81-98%), EGCG (56-76%), EC (86-95%), and ECG (30-55%). These data provide evidence that tea consumption practices and formulation factors likely impact catechin digestive recovery and may result in diverse physiological profiles.", "title": "Common tea formulations modulate in vitro digestive recovery of green tea catechins." }, { "docid": "MED-2219", "text": "Our laboratory recently reported that a 3-month exposure of rats to cola-like beverages induced sex hormone changes. The aim of the study was to investigate the effects of various types of Coca-cola intake with different composition for 6 months on oxidative status in testes and testosterone in adult male rats. Fifty adult male Wistar rats were divided into control group drinking water, and groups drinking different Coca-cola beverages (regular Coca-cola, Coca-cola caffeine-free, Coca-cola Light and Coca-cola Zero). Oxidative and carbonyl stress markers were measured in the testicular tissue to assess oxidative status together with testicular and plasma testosterone. StAR expression in testes as a marker of steroidogenesis was quantified. No significant differences were found between the groups in any of the measured parameters. In conclusion, oxidative and carbonyl stress in testicular tissue were not influenced by drinking any type of Coca-cola. Additionally, testosterone in testes and in plasma, as well as testicular StAR expression were comparable among the groups. Copyright © 2013 Elsevier Ltd. All rights reserved.", "title": "No harmful effect of different Coca-cola beverages after 6 months of intake on rat testes." }, { "docid": "MED-3375", "text": "OBJECTIVE: To describe food and beverage types offered and consumed during classroom celebrations at an elementary school in a low-income, urban community. In addition, to report student intake of fresh fruit provided alongside other party foods. METHODS: Observations held during 4 classroom celebrations. Food and beverage items were measured and counted before and after each celebration. Consumption data were recorded in aggregate for the entire classroom and later adjusted to mean intake per student. RESULTS: Majority of items offered were low-nutrient, energy-dense foods. Mean caloric intake during celebrations ranged from 259 to 455 cal. Fruit provided during 2 of the 4 classroom celebrations resulted in a mean intake of 1 full serving per student. CONCLUSIONS AND IMPLICATIONS: Caloric intake from low-nutrient, energy-dense foods and beverages offered during classroom celebrations contributed 20% or more of daily caloric needs. However, fresh fruit may be a reasonable addition to the party food table. Copyright © 2012 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.", "title": "Classroom \"cupcake\" celebrations: observations of foods offered and consumed." }, { "docid": "MED-2461", "text": "This study aimed to evaluate the association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan. An in-class interview survey elicited experiences of asthma and respiratory symptoms and consumption frequencies of the major food categories in 2290 fifth graders. Respiratory symptoms surveyed included persistent cough, chest tightness, wheezing with cold, wheezing without cold, dyspnea-associated wheezing, and exercise-induced cough or wheezing. Results showed that the consumption of sweetened beverages had the strongest association with respiratory symptoms and was positively associated with six of the seven respiratory symptoms (all p < 0.05). The adjusted odds ratios (aOR) ranged from 1.05 (95% confidence interval (CI = 1.01-1.09) for exercise-induced cough to 1.09 (95% CI = 1.03-1.16) for wheezing without cold. Egg consumption was associated with 5 of the 7 respiratory symptoms. Consumptions of seafood, soy products, and fruits were each negatively associated with one of the seven respiratory symptoms (all p < 0.05). Consumption of seafood was negatively associated with physician-diagnosed asthma and consumptions of sweetened beverages and eggs were positively associated with suspected asthma (p < 0.05). In conclusion, the study suggests that diet is associated with the respiratory symptoms in schoolchildren in Taipei. Consumptions of sweetened beverages and eggs are associated with increased risk of respiratory symptoms and asthma whereas consumptions of soy products and fruits are associated with reduced risk of respiratory symptoms.", "title": "The association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan." }, { "docid": "MED-4318", "text": "Preliminary data in the literature indicate that iron absorption from a meal may be increased when consumed with low-pH beverages such as cola, and it is also possible that sugar iron complexes may alter iron availability. A randomized, crossover trial was conducted to compare the bioavailability of nonheme iron from a vegetarian pizza meal when consumed with 3 different beverages (cola, diet cola, and mineral water). Sixteen women with serum ferritin concentrations of 11-54 µg/L were recruited and completed the study. The pizza meal contained native iron and added ferric chloride solution as a stable isotope extrinsic label; the total iron content of the meal was ~5.3 mg. Incorporation of iron from the meal into RBC was not affected by the type of drink (9.9% with cola, 9.4% with diet cola, and 9.6% with water). Serum ferritin and plasma hepcidin were correlated (r = 0.66; P<0.001) and both were significant predictors of iron bioavailability, but their combined effect explained only 30% of the inter-individual variation (P<0.001) and illustrates the current lack of understanding of mechanisms responsible for the fine-tuning of iron absorption. Although there was no effect of low-pH drinks on iron bioavailability in healthy women, their effect on absorption of fortification iron that requires solubilization in dilute acid, such as reduced iron, and in individuals with low gastric acid production, such as older people and individuals with Helicobacter pylori infection, warrants further investigation.", "title": "Low-pH cola beverages do not affect women's iron absorption from a vegetarian meal." }, { "docid": "MED-2226", "text": "BACKGROUND: Studies of cocoa suggest an array of cardiovascular benefits; however, the effects of daily intake of sugar-free and sugar-sweetened cocoa beverages on endothelial function (EF) have yet to be established. METHODS: 44 adults (BMI 25-35 kg/m2) participated in a randomized, controlled, crossover trial. Participants were randomly assigned to a treatment sequence: sugar-free cocoa beverage, sugar-sweetened cocoa beverage, and sugar-sweetened cocoa-free placebo. Treatments were administered daily for 6 weeks, with a 4-week washout period. RESULTS: Cocoa ingestion improved EF measured as flow-mediated dilation (FMD) compared to placebo (sugar-free cocoa: change, 2.4% [95% CI, 1.5 to 3.2] vs. -0.8% [95% CI, -1.9 to 0.3]; difference, 3.2% [95% CI, 1.8 to 4.6]; p<0.001 and sugar-sweetened cocoa: change, 1.5% [95% CI, 0.6 to 2.4] vs. -0.8% [95% CI, -1.9 to 0.3]; difference, 2.3% [95% CI, 0.9 to 3.7]; p=0.002). The magnitude of improvement in FMD after consumption of sugar-free versus sugar-sweetened cocoa was greater, but not significantly. Other biomarkers of cardiac risk did not change appreciably from baseline. BMI remained stable throughout the study. CONCLUSIONS: Daily cocoa ingestion improves EF independently of other biomarkers of cardiac risk, and does not cause weight gain. Sugar-free preparations may further augment endothelial function. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.", "title": "Effects of sugar-sweetened and sugar-free cocoa on endothelial function in overweight adults." }, { "docid": "MED-2155", "text": "Coffee, after water, is the most widely consumed beverage in the United States, and is the principal source of caffeine intake among adults. The biological effects of coffee may be substantial and are not limited to the actions of caffeine. Coffee is a complex beverage containing hundreds of biologically active compounds, and the health effects of chronic coffee intake are wide ranging. From a cardiovascular (CV) standpoint, coffee consumption may reduce the risk of type 2 diabetes mellitus and hypertension, as well as other conditions associated with CV risk such as obesity and depression; but it may adversely affect lipid profiles depending on how the beverage is prepared. Regardless, a growing body of data suggests that habitual coffee consumption is neutral to beneficial regarding the risks of a variety of adverse CV outcomes including coronary heart disease, congestive heart failure, arrhythmias, and stroke. Moreover, large epidemiological studies suggest that regular coffee drinkers have reduced risks of mortality, both CV and all-cause. The potential benefits also include protection against neurodegenerative diseases, improved asthma control, and lower risk of select gastrointestinal diseases. A daily intake of ∼2 to 3 cups of coffee appears to be safe and is associated with neutral to beneficial effects for most of the studied health outcomes. However, most of the data on coffee's health effects are based on observational data, with very few randomized, controlled studies, and association does not prove causation. Additionally, the possible advantages of regular coffee consumption have to be weighed against potential risks (which are mostly related to its high caffeine content) including anxiety, insomnia, tremulousness, and palpitations, as well as bone loss and possibly increased risk of fractures. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.", "title": "Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause mortality." }, { "docid": "MED-4878", "text": "Background Telomere length reflects biological aging and may be influenced by environmental factors, including those that affect inflammatory processes. Objective With data from 840 white, black, and Hispanic adults from the Multi-Ethnic Study of Atherosclerosis, we studied cross-sectional associations between telomere length and dietary patterns and foods and beverages that were associated with markers of inflammation. Design Leukocyte telomere length was measured by quantitative polymerase chain reaction. Length was calculated as the amount of telomeric DNA (T) divided by the amount of a single-copy control DNA (S) (T/S ratio). Intake of whole grains, fruit and vegetables, low-fat dairy, nuts or seeds, nonfried fish, coffee, refined grains, fried foods, red meat, processed meat, and sugar-sweetened soda were computed with responses to a 120-item food-frequency questionnaire completed at baseline. Scores on 2 previously defined empirical dietary patterns were also computed for each participant. Results After adjustment for age, other demographics, lifestyle factors, and intakes of other foods or beverages, only processed meat intake was associated with telomere length. For every 1 serving/d greater intake of processed meat, the T/S ratio was 0.07 smaller (β ± SE: −0.07 ± 0.03, P = 0.006). Categorical analysis showed that participants consuming ≥1 serving of processed meat each week had 0.017 smaller T/S ratios than did nonconsumers. Other foods or beverages and the 2 dietary patterns were not associated with telomere length. Conclusions Processed meat intake showed an expected inverse association with telomere length, but other diet features did not show their expected associations.", "title": "Dietary patterns, food groups, and telomere length in the Multi-Ethnic Study of Atherosclerosis (MESA)" }, { "docid": "MED-5244", "text": "Coffee, after water, is the most widely consumed beverage in the United States, and is the principal source of caffeine intake among adults. The biological effects of coffee may be substantial and are not limited to the actions of caffeine. Coffee is a complex beverage containing hundreds of biologically active compounds, and the health effects of chronic coffee intake are wide ranging. From a cardiovascular (CV) standpoint, coffee consumption may reduce the risk of type 2 diabetes mellitus and hypertension, as well as other conditions associated with CV risk such as obesity and depression; but it may adversely affect lipid profiles depending on how the beverage is prepared. Regardless, a growing body of data suggests that habitual coffee consumption is neutral to beneficial regarding the risks of a variety of adverse CV outcomes including coronary heart disease, congestive heart failure, arrhythmias, and stroke. Moreover, large epidemiological studies suggest that regular coffee drinkers have reduced risks of mortality, both CV and all-cause. The potential benefits also include protection against neurodegenerative diseases, improved asthma control, and lower risk of select gastrointestinal diseases. A daily intake of ∼2 to 3 cups of coffee appears to be safe and is associated with neutral to beneficial effects for most of the studied health outcomes. However, most of the data on coffee's health effects are based on observational data, with very few randomized, controlled studies, and association does not prove causation. Additionally, the possible advantages of regular coffee consumption have to be weighed against potential risks (which are mostly related to its high caffeine content) including anxiety, insomnia, tremulousness, and palpitations, as well as bone loss and possibly increased risk of fractures. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.", "title": "Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause mortality." }, { "docid": "MED-2491", "text": "Exposure limits for arsenic and lead in drinking water have long been established by the U.S. Environmental Protection Agency and new regulations regarding the presence of these contaminants in bottled water went into effect in California in 2009. No comparable exposure limits or regulations are available, however, for juices and other beverages that may contain arsenic and lead. In the study described in this article, 20 apple juices (or ciders), 15 apple-containing juices, one grape, and one citrus juice were analyzed for arsenic and lead. Arsenic was detected in all juices while lead was detected in more than 94% of juices analyzed. Twelve samples (32%) demonstrated arsenic levels nearly at or above the drinking water exposure limit of 10 parts per billion. No juices contained lead above drinking water exposure limits. Expanding drinking water limits to include juices (and other frequently consumed beverages) would better protect consumers while regular testing of these juices would better inform consumers of the risks posed by specific juices and brands.", "title": "Arsenic and lead in juice: apple, citrus, and apple-base." }, { "docid": "MED-5123", "text": "The present paper explores the level of evidence required to justify giving dietary advice to the public. There are important practical differences between the development of public health nutrition guidelines and guidelines for clinical practice. While the gold standard for evidence for clinical practice guidelines is a meta-analysis of a number of randomised controlled trials, this is often unrealistic and sometimes unethical for the evaluation of public health nutrition interventions. Hence, epidemiological studies make up the bulk of evidence for nutrition guidelines. Tea and coffee are an interesting case study in relation to this issue. They are two of the most commonly consumed beverages worldwide, yet there is little dietary advice on their use. The evidence for a relationship between coffee or tea consumption and several diseases is discussed. The available studies, predominantly epidemiological, together with animal and in vitro studies, indicate that coffee and tea are both safe beverages. However, tea is the healthier option because it has a possible role in the prevention of several cancers and CVD. While the evidence for such relationships is not strong, the public will continue to drink both tea and coffee, and will continue to ask nutritionists to make recommendations. It is therefore argued that advice should be given on the best available data, as waiting for complete data to become available could have severe consequences for public health.", "title": "Tea or coffee? A case study on evidence for dietary advice." }, { "docid": "MED-1621", "text": "Except for conflicting evidence about coffee and risk of coronary disease, coffee and tea are not linked to major causes of death. Because of widespread use of both beverages and limitations of prior studies, concern persists. Using Cox models (ten covariates) we studied relations in 128,934 persons to 4501 subsequent deaths. Except for slightly increased risk from acute myocardial infarction among heavier (> or = 4 cups/d) coffee users (relative risk versus nondrinkers = 1.4, 95% confidence interval = 1.0 to 1.9, P = 0.07), there was no increased risk of mortality for all deaths (relative risk per cup of coffee per day = 0.99, 95% confidence interval = 0.97 to 1.01; relative risk per cup of tea per day = 0.98, 95% confidence interval = 0.96 to 1.00) or major causes in adjusted analyses. Coffee was related to lower risk of liver cirrhosis death (relative risk per cup of coffee per day = 0.77, 95% confidence interval = 0.67 to 0.89). Use of both beverages was related to a lower risk of suicide, progressively lower at higher coffee intake (relative risk per cup of coffee per day = 0.87, 95% confidence interval = 0.77 to 0.98). We conclude that coffee and tea have no overall relation to mortality risk. If coffee increases coronary risk, this is balanced by an unexplained lower risk of other conditions, notably cirrhosis and suicide.", "title": "Coffee, tea, and mortality." }, { "docid": "MED-2677", "text": "Population differences in age-related diseases and cancer could stem from differences in diet. To characterize DNA strand-breaking activities in selected foods/beverages, flavorings, and some of their constituent chemicals, we used p53R cells, a cellular assay sensitive to such breaks. Substances testing positive included reference chemicals: quinacrine (peak response, 51X) and etoposide (33X); flavonoids: EGCG (19X), curcumin (12X), apigenin (9X), and quercetin (7X); beverages: chamomile (11X), green (21X), and black tea (26X) and coffee (3 to 29X); and liquid smoke (4 to 28X). Damage occurred at dietary concentrations: etoposide near 5 μg/ml produced responses similar to a 1:1000 dilution of liquid smoke, a 1:20 dilution of coffee, and a 1:5 dilution of tea. Pyrogallol-related chemicals and tannins are present in dietary sources and individually produced strong activity: pyrogallol (30X), 3-methoxycatechol (25X), gallic acid (21X), and 1,2,4-benzenetriol (21X). From structure-activity relationships, high activities depended on specific orientations of hydroxyls on the benzene ring. Responses accompanied cellular signals characteristic of DNA breaks such as H2AX phosphorylation. Breaks were also directly detected by comet assay. Cellular toxicological effects of foods and flavorings could guide epidemiologic and experimental studies of potential disease risks from DNA strand-breaking chemicals in diets.", "title": "Biological Clues to Potent DNA-Damaging Activities in Food and Flavoring" }, { "docid": "MED-3588", "text": "Background Many studies have examined whether caffeine, alcohol, or specific beverages containing these affect fertility in women. However most of these studies have retrospectively collected information on alcohol and caffeine intake, making the results susceptible to biases. Methods We followed 18,555 married women without a history of infertility for 8 years as they attempted to become (or became) pregnant. Diet was measured twice during this period and prospectively related to the incidence of ovulatory disorder infertility. Results There were 438 incident report of ovulatory disorder infertility during follow-up. Intakes of alcohol and caffeine were unrelated to the risk of ovulatory disorder infertility. The multivariate-adjusted relative risk (RR), 95% confidence interval (CI), P for trend comparing the highest to lowest categories of intake were 1.11 (0.76–1.64; 0.78) for alcohol and 0.86 (0.61–1.20; 0.44) for total caffeine. However, intake of caffeinated soft drinks was positively related to ovulatory disorder infertility. The multivariate-adjusted RR 95% CI, and P for trend comparing the highest to lowest categories of caffeinated soft drink consumption were 1.47 (1.09–1.98; 0.01). Similar associations were observed for noncaffeinated, sugared, diet and total soft drinks. Conclusions Our findings do not support the hypothesis that alcohol and caffeine impair ovulation to the point of decreasing fertility. The association between soft drinks and ovulatory disorder infertility appears not to be attributable to their caffeine or sugar content, and deserves further investigation.", "title": "Caffeinated and alcoholic beverage intake in relation to ovulatory disorder infertility" }, { "docid": "MED-1185", "text": "Endogenous sulfite is generated as a consequence of the body's normal processing of sulfur-containing amino acids. Sulfites occur as a consequence of fermentation and also occur naturally in a number of foods and beverages. As food additives, sulfiting agents were first used in 1664 and approved in the United States as long ago as the 1800s. With such long experience with their use, it is easy to understand why these substances have been regarded as safe. They are currently used for a variety of preservative properties, including controlling microbial growth, preventing browning and spoilage, and bleaching some foods. It is estimated that up to 500,000 (< .05% of the population) sulfite-sensitive individuals live in the United States. Sulfite sensitivity occurs most often in asthmatic adults--predominantly women; it is uncommonly reported in preschool children. Adverse reactions to sulfites in nonasthmatics are extremely rare. Asthmatics who are steroid-dependent or who have a higher degree of airway hyperreactivity may be at greater risk of experiencing a reaction to sulfite-containing foods. Even within this limited population, sulfite sensitivity reactions vary widely, ranging from no reaction to severe. The majority of reactions are mild. These manifestations may include dermatologic, respiratory, or gastrointestinal signs and symptoms. Severe nonspecific signs and symptoms occur less commonly. Broncho-constriction is the most common sensitivity response in asthmatics. The precise mechanisms of the sensitivity responses have not been completely elucidated. Inhalation of sulfur dioxide (SO2) generated in the stomach following ingestion of sulfite-containing foods or beverages, a deficiency in a mitochondrial enzyme, and an IgE-mediated immune response have all been implicated.(ABSTRACT TRUNCATED AT 250 WORDS)", "title": "Sulfite sensitivity: significance in human health." }, { "docid": "MED-1640", "text": "Coffee is one of the most widely used pharmacologically active beverages. The present study was designed to evaluate the acute effect of coffee ingestion on endothelial function in healthy individuals, and the potential role of caffeine. We studied 17 healthy young adults (28.9+/-3.0 years old; nine men), who were regular non-heavy coffee drinkers. The endothelial performance was estimated by endothelium-dependent FMD (flow-mediated dilatation) of the brachial artery before and 30, 60, 90 and 120 min after ingestion of a cup of caffeinated coffee (80 mg of caffeine) or the corresponding decaffeinated beverage (< 2 mg of caffeine) in two separate sessions, following a randomized single-blind cross-over design. There was no difference in baseline FMD values between the two sessions [7.78 compared with 7.07% after caffeinated and decaffeinated coffee respectively; P = NS (not significant)]. Caffeinated coffee led to a decline of FMD (7.78, 2.86, 2.12, 4.44 and 4.57% at baseline, 30, 60, 90 and 120 min respectively; P < 0.001). This adverse effect was focused at 30 (P = 0.004) and 60 min (P < 0.001). No significant effect on FMD was found with the decaffeinated coffee session (7.07, 6.24, 5.21, 7.41 and 5.20%; P = NS). The composite effect of the type of coffee consumed over time on FMD was significantly different (P = 0.021). In conclusion, coffee exerts an acute unfavourable effect on the endothelial function in healthy adults, lasting for at least 1 h after intake. This effect might be attributed to caffeine, given that decaffeinated coffee was not associated with any change in the endothelial performance.", "title": "Effect of coffee on endothelial function in healthy subjects: the role of caffeine." } ]
PLAIN-1502
lentil effect
[ { "docid": "MED-3580", "text": "The effects of the glycemic index (GI) of carbohydrate eaten the previous night on the glycemic response to a standard test meal eaten subsequently in the morning (breakfast) was studied. On separate evenings normal subjects ate low- or high-GI test meals of the same nutrient composition. The dinners consisted of single foods in two experiments and mixed meals containing several foods in the third. The differences between the observed glycemic responses to low- and high-GI dinners were predicted by their GIs. The glycemic responses to breakfast were significantly lower on mornings after low-GI dinners than after high-GI dinners. Eating, at dinner, foods with different fiber contents but the same GI had no effect on postbreakfast glycemia. We conclude that the GI predicts the difference between glycemic responses of mixed dinner meals; breakfast carbohydrate tolerance is improved when low-GI foods are eaten the previous evening.", "title": "Second-meal effect: low-glycemic-index foods eaten at dinner improve subsequent breakfast glycemic response." }, { "docid": "MED-3582", "text": "Breakfasts of lentils or wholemeal bread of identical carbohydrate content were taken by seven healthy volunteers. The lentils produced a significant 71% (p less than 0.001) reduction in the blood glucose area and flattened the plasma insulin and gastric inhibitory polypeptide responses by comparison with the bread. In addition, the lentil breakfast was followed by a significantly flatter blood glucose response to the standard bread lunch which followed 4 h later (by 38%, p less than 0.01). The blood glucose pattern was mimicked by feeding the bread breakfast slowly over the 4 h before lunch. Giving a bread breakfast containing a quarter of the carbohydrate reduced the breakfast glucose profile but resulted in a significantly impaired blood glucose response to lunch (168% of control, p less than 0.01). These results, together with breath hydrogen studies, performed on a separate group of four volunteers, indicate that the flattened response to lentils is not due to carbohydrate malabsorption. Slow release or \"lente\" carbohydrate foods such as lentils may form a useful part of the diets of those with impaired carbohydrate tolerance.", "title": "Slow release dietary carbohydrate improves second meal tolerance." }, { "docid": "MED-3584", "text": "Background: A high intake of white rice is associated with the metabolic syndrome and type 2 diabetes. Costa Ricans follow a staple dietary pattern that includes white rice and beans, yet the combined role of these foods on cardiometabolic risk factors has not been studied. Objective: We aimed to determine the association between intake of white rice and beans and the metabolic syndrome and its components in Costa Rican adults (n = 1879) without diabetes. Design: Multivariate-adjusted means were calculated for components of the metabolic syndrome by daily servings of white rice and beans (<1, 1, or >1) and by the ratio of beans to white rice. The OR for the metabolic syndrome was calculated by substituting one serving of beans for one serving of white rice. Results: An increase in daily servings of white rice was positively associated with systolic blood pressure (BP), triglycerides, and fasting glucose and inversely associated with HDL cholesterol (P-trend <0.01 for all). An increase in servings of beans was inversely associated with diastolic BP (P = 0.049). Significant trends for higher HDL cholesterol and lower BP and triglycerides were observed for 1:3, 1:2, 1:1, and 2:1 ratios of beans to white rice. Substituting one serving of beans for one serving of white rice was associated with a 35% (95% CI: 15%, 50%) lower risk of the metabolic syndrome. Conclusion: Increasing the ratio of beans to white rice, or limiting the intake of white rice by substituting beans, may lower cardiometabolic risk factors.", "title": "A higher ratio of beans to white rice is associated with lower cardiometabolic risk factors in Costa Rican adults" }, { "docid": "MED-3581", "text": "BACKGROUND: Low postprandial blood glucose is associated with low risk of metabolic diseases. A meal's ability to diminish the glucose response to carbohydrates eaten during the following meal is known as the \"second-meal effect\" (SME). The reduced glycemia elicited by low-glycemic-index (LGI) foods consumed during the first meal has been suggested as the main mechanism for SME. However, LGI foods often increase colonic fermentation because of the presence of fiber and resistant starch. OBJECTIVE: The objective was to study the SME of greater fermentation of high-glycemic-index (HGI) and LGI carbohydrates eaten during a previous meal. DESIGN: Ten healthy volunteers ate 3 breakfast test meals consisting of sponge cakes made with rapidly digestible, nonfermentable amylopectin starch plus cellulose (HGI meal), amylopectin starch plus the fermentable disaccharide lactulose (HGI-Lac meal), or slowly digestible, partly fermentable amylose starch plus cellulose (LGI meal). Five hours later, subjects were fed the same standard lunch containing 93 g available carbohydrates. Blood was collected for measurement of glucose, insulin, and nonesterified fatty acids (NEFAs). Breath hydrogen was measured as a marker of colonic fermentation. Postlunch gastric emptying was measured by using ultrasonography. RESULTS: Both the HGI-Lac and LGI meals improved glucose tolerance at lunch. In the case of the HGI-Lac meal, this effect was concomitant with low NEFA concentrations and delayed gastric emptying. CONCLUSION: Fermentable carbohydrates, independent of their effect on a food's glycemic index, have the potential to regulate postprandial responses to a second meal by reducing NEFA competition for glucose disposal and, to a minor extent, by affecting intestinal motility.", "title": "Colonic fermentation of indigestible carbohydrates contributes to the second-meal effect." }, { "docid": "MED-3583", "text": "Pulses are low-glycemic appetite-suppressing foods, but it is not known whether these properties persist after being consumed as part of a meal and after a second meal. The objective of this study was to determine the effects of a fixed-size pulse meal on appetite and blood glucose (BG) before and after an ad libitum test meal (pizza) and on food intake (FI) at the test meal. Males (n = 25; 21.3 ± 0.5 years; 21.6 ± 0.3 kg·m(-2)) randomly consumed 4 isocaloric meals: chickpea; lentil; yellow split pea; and macaroni and cheese (control). Commercially available canned pulses provided 250 kcal, and were consumed with macaroni and tomato sauce. FI was measured at a pizza meal 260 min after consumption of the isocaloric meal. BG and appetite were measured from 0 to 340 min. The lentil and yellow pea, but not chickpea, treatments led to lower appetite ratings during the 260 min prepizza meal period, and less FI at the pizza meal, compared with macaroni and cheese (p < 0.05). All pulse treatments lowered BG immediately following consumption (at 20 min) (p < 0.05), but there was no effect of treatment on prepizza meal BG AUC (p = 0.07). Immediately after the pizza meal, BG was lower following the chickpea and lentil treatments, but not the yellow pea treatment (p < 0.05). Postpizza meal BG AUC was lower following the chickpea and lentil treatments than in the yellow pea treatment (p < 0.05). The beneficial effects of consuming a pulse meal on appetite, FI at a later meal, and the BG response to a later meal are dependent on pulse type.", "title": "First and second meal effects of pulses on blood glucose, appetite, and food intake at a later meal." } ]
[ { "docid": "MED-4863", "text": "Chemical and cellular antioxidant activities and phenolic profiles of 11 lentil cultivars grown in the cool northern parts of the United States were investigated. Individual phenolic compounds, including phenolic acids, flavan-3-ols, flavones, and anthocyanins, were further quantitatively investigated by HPLC. Cellular antioxidant activities (CAA) and peroxyl radical scavenging capacity (PRSC) were evaluated by fluorescence microplate reader. Cultivar Morton exhibited the highest individual flavan-3-ols (catechin and epicatechin) and total flavonoids, as well as the highest antioxidant properties (PRSC and CAA) among all lentils tested. Five phenolic acids of the benzoic types and their derivates (gallic, protocatechuic, 2,3,4-trihydroxybenzoic, p-hydroxybenzoic acid, and protocatechualdehyde) and four phenolic acids of the cinnamic type (chlorogenic, p-coumaric, m-coumaric, and sinapic acid) were detected in all lentil cultivars. Two flavan-3-ols [(+)-catechin and (-)-epicatechin] and one flavone (luteolin) were detected in all lentil cultivars. Among all phenolic compounds detected, sinapic acid was the predominant phenolic acid, and (+)-catechin and (-)-epicatechin were the predominant flavonoids. These results showed that different phenotype lentils possessed considerable variations in their individual phenolic compounds, as well as chemical and cellular antioxidant activities. Caffeic acid, catechin, epicatechin, and total flavonoids significantly (p < 0.05) correlated with peroxyl radical scavenging assay. Cellular antioxidant assay significantly correlated with chemical antioxidant assay ORAC. The results from this study could be very interesting for breeding programs to improve lentils for use as functional foods.", "title": "Phenolic substance characterization and chemical and cell-based antioxidant activities of 11 lentils grown in the northern United States." }, { "docid": "MED-2010", "text": "Legumes (including alfalfa, clover, lupins, green beans and peas, peanuts, soybeans, dry beans, broad beans, dry peas, chickpeas, and lentils) represent an important component of the human diet in several areas of the world, especially in the developing countries, where they complement the lack of proteins from cereals, roots, and tubers. In some regions of the world, legume seeds are the only protein supply in the diet. The health benefits of legume consumption have received rising interest from researchers, and their consumption and production extends worldwide. Among European countries, higher legume consumption is observed around the Mediterranean, with per capita daily consumption between 8 and 23 g, while in Northern Europe, the daily consumption is less than 5 g per capita. The physiological effects of different legumes vary significantly. These differences may result from the polysaccharides composition, in particular, the quantity and variety of dietary fibers and starch, protein make-up, and variability in phytochemical content. The majority of legumes contain phytochemicals: bioactive compounds, including enzyme inhibitors, phytohemagglutinins (lectins), phytoestrogens, oligosaccharides, saponins, and phenolic compounds, which play metabolic roles in humans who frequently consume these foods. Dietary intake of phytochemicals may provide health benefits, protecting against numerous diseases or disorders, such as coronary heart disease, diabetes, high blood pressure and inflammation. The synergistic or antagonistic effects of these phytochemical mixtures from food legumes, their interaction with other components of the diet, and the mechanism of their action have remained a challenge with regard to understanding the role of phytochemicals in health and diseases. Their mitigating effects and the mechanism of their action need to be further addressed if we are to understand the role of phytochemicals in health and diseases. This review provides an overview of the nutritional quality of legumes and their potential contribution in cardiometabolic risk prevention.", "title": "Nutritional quality of legumes, and their role in cardiometabolic risk prevention: a review." }, { "docid": "MED-2148", "text": "Pulses are low in energy density, supporting their inclusion in the diet for the management of risk factors of the metabolic syndrome (MetSyn). The aim of the present study was to describe the effects of frequent consumption (five cups/week over 8 weeks) of pulses (yellow peas, chickpeas, navy beans and lentils), compared with counselling to reduce energy intake by 2093 kJ/d (500 kcal/d), on risk factors of the MetSyn in two groups (nineteen and twenty-one subjects, respectively) of overweight or obese (mean BMI 32·8 kg/m2) adults. Body weight, waist circumference, blood pressure, fasting blood parameters and 24 h food intakes were measured at weeks 1, 4 and 8. Blood glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1) and ghrelin were measured after a 75 g oral glucose load at weeks 1 and 8. At week 8, both groups reported reductions in energy intake, waist circumference, systolic blood pressure, glycosylated Hb (HbA1c) and glucose AUC and homeostasis model of insulin resistance (HOMA-IR) following the glucose load (P < 0·05). However, HDL, fasting C-peptide and insulin AUC responses were dependent on diet (P < 0·05). HDL and C-peptide increased by 4·5 and 12·3 %, respectively, in the pulse group, but decreased by 0·8 and 7·6 %, respectively, in the energy-restricted group. Insulin AUC decreased in both females and males on the energy-restricted diet by 24·2 and 4·8 %, respectively, but on the pulse diet it decreased by 13·9 % in females and increased by 27·3 % in males (P < 0·05). In conclusion, frequent consumption of pulses in an ad libitum diet reduced risk factors of the MetSyn and these effects were equivalent, and in some instances stronger, than counselling for dietary energy reduction.", "title": "Regular consumption of pulses for 8 weeks reduces metabolic syndrome risk factors in overweight and obese adults." }, { "docid": "MED-2008", "text": "Our purpose was to determine the effects of a pulse-based diet in individuals 50 years or older for reducing CVD risk factors. A total of 108 participants were randomised to receive pulse-based foods (two servings daily of beans, chickpeas, peas or lentils; about 150 g/d dry weight) or their regular diet for 2 months, followed by a washout of 1 month and a cross-over to the other diet for 2 months. Anthropometric measures, body composition and biochemical markers (i.e. serum LDL-cholesterol (LDL-C), as the primary outcome, and other lipids, glucose, insulin and C-reactive protein) were assessed before and after each diet phase. A total of eighty-seven participants (thirty males and fifty-seven females; 59·7 (sd 6·3) years, body mass 76 (sd 16) kg) completed the study. Compared with the regular diet, the pulse-based diet decreased total cholesterol by 8·3 % (pulse, 4·57 (sd 0·93) to 4·11 (sd 0·91) mmol/l; regular, 4·47 (sd 0·94) to 4·39 (sd 0·97) mmol/l; P < 0·001) and LDL-C by 7·9 % (pulse, 2·93 (sd 0·84) to 2·55 (sd 0·75) mmol/l; regular, 2·96 (sd 0·86) to 2·81 (sd 0·83) mmol/l; P = 0·01). In a sub-analysis of individuals with high lipid levels at baseline (twenty individuals with high cholesterol), the pulse-based diet reduced cholesterol by 6 % compared with the regular diet (pulse, 5·62 (sd 0·78) to 5·26 (sd 0·68) mmol/l; regular, 5·60 (sd 0·91) to 5·57 (sd 0·85) mmol/l; P = 0·05). A pulse-based diet is effective for reducing total cholesterol and LDL-C in older adults and therefore reduces the risk of CVD.", "title": "A pulse-based diet is effective for reducing total and LDL-cholesterol in older adults." }, { "docid": "MED-2145", "text": "AIMS/HYPOTHESIS: Dietary non-oil-seed pulses (chickpeas, beans, peas, lentils, etc.) are a good source of slowly digestible carbohydrate, fibre and vegetable protein and a valuable means of lowering the glycaemic-index (GI) of the diet. To assess the evidence that dietary pulses may benefit glycaemic control, we conducted a systematic review and meta-analysis of randomised controlled experimental trials investigating the effect of pulses, alone or as part of low-GI or high-fibre diets, on markers of glycaemic control in people with and without diabetes. METHODS: We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Library for relevant controlled trials of >or=7 days. Two independent reviewers (A. Esfahani and J. M. W. Wong) extracted information on study design, participants, treatments and outcomes. Data were pooled using the generic inverse variance method and expressed as standardised mean differences (SMD) with 95% CIs. Heterogeneity was assessed by chi (2) and quantified by I (2). Meta-regression models identified independent predictors of effects. RESULTS: A total of 41 trials (39 reports) were included. Pulses alone (11 trials) lowered fasting blood glucose (FBG) (-0.82, 95% CI -1.36 to -0.27) and insulin (-0.49, 95% CI -0.93 to -0.04). Pulses in low-GI diets (19 trials) lowered glycosylated blood proteins (GP), measured as HbA(1c) or fructosamine (-0.28, 95% CI -0.42 to -0.14). Finally, pulses in high-fibre diets (11 trials) lowered FBG (-0.32, 95% CI -0.49 to -0.15) and GP (-0.27, 95% CI -0.45 to -0.09). Inter-study heterogeneity was high and unexplained for most outcomes, with benefits modified or predicted by diabetes status, pulse type, dose, physical form, duration of follow-up, study quality, macronutrient profile of background diets, feeding control and design. CONCLUSIONS/INTERPRETATION: Pooled analyses demonstrated that pulses, alone or in low-GI or high-fibre diets, improve markers of longer term glycaemic control in humans, with the extent of the improvements subject to significant inter-study heterogeneity. There is a need for further large, well-designed trials.", "title": "Effect of non-oil-seed pulses on glycaemic control: a systematic review and meta-analysis of randomised controlled experimental trials in people wi..." }, { "docid": "MED-4347", "text": "BACKGROUND: The nutritional composition of the dietary intake could produce specific effects on metabolic variables and inflammatory marker concentrations. This study assessed the effects of two hypocaloric diets (legume-restricted- vs. legume-based diet) on metabolic and inflammatory changes, accompanying weight loss. METHODS: Thirty obese subjects (17 M/13F; BMI: 32.5 ± 4.5 kg/m(2); 36 ± 8 years) were randomly assigned to one of the following hypocaloric treatments (8 weeks): Calorie-restricted legume-free diet (Control: C-diet) or calorie-restricted legume-based diet (L-diet), prescribing 4 weekly different cooked-servings (160-235 g) of lentils, chickpeas, peas or beans. Body composition, blood pressure (BP), blood biochemical and inflammatory marker concentrations as well as dietary intake were measured at baseline and after the nutritional intervention. RESULTS: The L-diet achieved a greater body weight loss, when compared to the C-diet (-7.8 ± 2.9% vs. -5.3 ± 2.7%; p = 0.024). Total and LDL cholesterol levels and systolic BP were improved only when consuming the L-diet (p < 0.05). L-diet also resulted in a significant higher reduction in C-reactive protein (CRP) and complement C3 (C3) concentrations (p < 0.05), compared to baseline and C-diet values. Interestingly, the reduction in the concentrations of CRP and C3 remained significantly higher to L-diet group, after adjusting by weight loss (p < 0.05). In addition, the reduction (%) in CRP concentrations was positively associated with decreases (%) in systolic BP and total cholesterol concentration specifically in the L-diet group, independent from weight loss (p < 0.05). CONCLUSION: The consumption of legumes (4 servings/week) within a hypocaloric diet resulted in a specific reduction in proinflammatory markers, such as CRP and C3 and a clinically significant improvement of some metabolic features (lipid profile and BP) in overweight/ obese subjects, which were in some cases independent from weight loss.", "title": "A legume-based hypocaloric diet reduces proinflammatory status and improves metabolic features in overweight/obese subjects." }, { "docid": "MED-3132", "text": "Little is known about dietitians current practice in counselling clients about the use of legumes in a low fat, high fibre diet. An exploratory e-mail questionnaire was sent to members of Dietitians of Canada to assess: dietitian use and preferences for legumes, dietitian practice, opinions about clients attitudes and preferences, and resource needs. Counsellors (n=256) had high personal use of legumes (64% > or = 1 serving/week) and frequently recommended legumes in counselling. The legumes most preferred by respondents and their clients were: peanuts, kidney beans, split peas, chickpeas, and lentils. Respondents often recommended canned bean products (76%) and tofu (61%), but other legume grocery products were less often recommended. The most common client issues identified were: flatulence (87% agreed), lack of familiarity (85%), and knowledge of preparation (82%). Dietitians were not satisfied with current resources to support practice, especially those respondents providing primarily clinical counselling services. The most requested resources were: recipes (90%), pamphlets (82%), food demonstrations (75%) and Internet sites (63%). Client level research is now needed to confirm the importance of the issues identified and to develop and test strategies for legume promotion in counselling.", "title": "Legume promotion in counselling: an e-mail survey of dietitians." }, { "docid": "MED-1812", "text": "Epidemiologic studies of diet and pancreas cancer are few, and include ecologic comparisons and a limited number of prospective and case-control studies. Foods and/or nutrients that have been suggested to be associated with increased risk of this cancer include total fat intake, eggs, animal protein, sugar, meat, coffee and butter. Consumption of raw fruits and vegetables has been consistently associated with decreased risk. Dietary habits and medical history variables were evaluated in a prospective study of fatal pancreas cancer among 34,000 California Seventh-day Adventists between 1976 and 1983. Forty deaths from pancreas cancer occurred during the follow-up period. Compared to all US whites, Adventists experienced decreased risk from pancreas cancer death (standardized mortality ratio [SMR] = 72 for men; 90 for women), which was not statistically significant. Although there was a suggestive relationship between increasing meat, egg, and coffee consumption and increased pancreatic cancer risk, these variables were not significantly related to risk after controlling for cigarette smoking. However, increasing consumption of vegetarian protein products, beans, lentils, and peas as well as dried fruit was associated with highly significant protective relationships to pancreas cancer risk. A prior history of diabetes was associated with increased risk of subsequent fatal pancreas cancer, as was a history of surgery for peptic or duodenal ulcer. A history of tonsillectomy was associated with a slight, nonsignificant protective relationship as was history of various allergic reactions. These findings suggest that the protective relationships associated with frequent consumption of vegetables and fruits high in protease-inhibitor content are more important than any increase in pancreas cancer risk attendant on frequent consumption of meat or other animal products. Furthermore, the previously reported positive associations between diabetes and abdominal surgery and pancreas cancer risk are supported in these data.", "title": "Dietary habits and past medical history as related to fatal pancreas cancer risk among Adventists." }, { "docid": "MED-2150", "text": "Previous investigations, of adolescent diet recalled in adulthood, found lower risk for benign breast disease (BBD) with higher intakes of vegetable fat and nuts during high school. We investigate whether vegetable protein and fat, derived from diets reported during pre-adolescence and adolescence, are associated with subsequent risk for BBD in young women. The Growing Up Today Study includes 9,039 females, 9–15 years in 1996, who completed questionnaires annually through 2001, and then in 2003, 2005, 2007, and 2010. Food frequency questionnaires (1996–2001) obtained intake data on a variety of foods. Beginning in 2005, women (18–30 years) reported whether they had ever been diagnosed with BBD that was confirmed by breast biopsy (n = 112 cases). Logistic regression estimated associations between intakes of vegetable protein and fat and biopsy-confirmed BBD. Those individual foods that were the largest contributors of protein and fat in this cohort were also investigated. In analyses of intakes from 1996 through 1998, when our cohort was youngest, vegetable fat (OR = 0.72/(10 gm/day), 95 % CI 0.53–0.98; p = 0.04) was inversely associated with BBD risk. The greatest sources of vegetable fat and protein in these girls were peanut butter, peanuts, nuts, beans (beans, lentils, and soybeans), and corn. A daily serving of any one of these was associated with lower risk (OR = 0.32/(serv/day), 95 % CI 0.13–0.79; p = 0.01). Peanut butter (and nuts) at age 11 years was inversely associated with risk (p = 0.01). In analyses of intakes at age 14 years, vegetable protein was associated with lower BBD risk (OR = 0.64/(10 gm/day), 95 % CI 0.43–0.95; p = 0.03). A daily serving at 14 years of any one of the foods was associated with lower risk (OR = 0.34, 95 % CI 0.16–0.75; p = 0.01), as was peanut butter (and nuts) (p = 0.02). Girls with a family history of breast cancer had significantly lower risk if they consumed these foods or vegetable fat. In conclusion, consumption of vegetable protein, fat, peanut butter, or nuts by older girls may help reduce their risk of BBD as young women.", "title": "Vegetable protein and vegetable fat intakes in pre-adolescent and adolescent girls, and risk for benign breast disease in young women" }, { "docid": "MED-1483", "text": "CONTEXT: Most medical interventions have modest effects, but occasionally some clinical trials may find very large effects for benefits or harms. OBJECTIVE: To evaluate the frequency and features of very large effects in medicine. DATA SOURCES: Cochrane Database of Systematic Reviews (CDSR, 2010, issue 7). STUDY SELECTION: We separated all binary-outcome CDSR forest plots with comparisons of interventions according to whether the first published trial, a subsequent trial (not the first), or no trial had a nominally statistically significant (P < .05) very large effect (odds ratio [OR], ≥5). We also sampled randomly 250 topics from each group for further in-depth evaluation. DATA EXTRACTION: We assessed the types of treatments and outcomes in trials with very large effects, examined how often large-effect trials were followed up by other trials on the same topic, and how these effects compared against the effects of the respective meta-analyses. RESULTS: Among 85,002 forest plots (from 3082 reviews), 8239 (9.7%) had a significant very large effect in the first published trial, 5158 (6.1%) only after the first published trial, and 71,605 (84.2%) had no trials with significant very large effects. Nominally significant very large effects typically appeared in small trials with median number of events: 18 in first trials and 15 in subsequent trials. Topics with very large effects were less likely than other topics to address mortality (3.6% in first trials, 3.2% in subsequent trials, and 11.6% in no trials with significant very large effects) and were more likely to address laboratory-defined efficacy (10% in first trials,10.8% in subsequent, and 3.2% in no trials with significant very large effects). First trials with very large effects were as likely as trials with no very large effects to have subsequent published trials. Ninety percent and 98% of the very large effects observed in first and subsequently published trials, respectively, became smaller in meta-analyses that included other trials; the median odds ratio decreased from 11.88 to 4.20 for first trials, and from 10.02 to 2.60 for subsequent trials. For 46 of the 500 selected topics (9.2%; first and subsequent trials) with a very large-effect trial, the meta-analysis maintained very large effects with P < .001 when additional trials were included, but none pertained to mortality-related outcomes. Across the whole CDSR, there was only 1 intervention with large beneficial effects on mortality, P < .001, and no major concerns about the quality of the evidence (for a trial on extracorporeal oxygenation for severe respiratory failure in newborns). CONCLUSIONS: Most large treatment effects emerge from small studies, and when additional trials are performed, the effect sizes become typically much smaller. Well-validated large effects are uncommon and pertain to nonfatal outcomes.", "title": "Empirical evaluation of very large treatment effects of medical interventions." }, { "docid": "MED-2706", "text": "AIM: This systematic review was aimed at critically evaluating the evidence regarding the adverse effects associated with aromatherapy. METHOD: Five electronic databases were searched to identify all relevant case reports and case series. RESULTS: Forty two primary reports met our inclusion criteria. In total, 71 patients experienced adverse effects of aromatherapy. Adverse effects ranged from mild to severe and included one fatality. The most common adverse effect was dermatitis. Lavender, peppermint, tea tree oil and ylang-ylang were the most common essential oils responsible for adverse effects. CONCLUSION: Aromatherapy has the potential to cause adverse effects some of which are serious. Their frequency remains unknown. Lack of sufficiently convincing evidence regarding the effectiveness of aromatherapy combined with its potential to cause adverse effects questions the usefulness of this modality in any condition.", "title": "Adverse effects of aromatherapy: a systematic review of case reports and case series." }, { "docid": "MED-2702", "text": "BACKGROUND: Oxidative stress can cause cancer. Our aim was to establish whether antioxidant supplements reduce the incidence of gastrointestinal cancer and mortality. METHODS: With the Cochrane Collaboration methodology, we reviewed all randomised trials comparing antioxidant supplements with placebo for prevention of gastrointestinal cancers. We searched electronic databases and reference lists (February, 2003). Outcome measures were incidence of gastrointestinal cancers, overall mortality, and adverse effects. Outcomes were analysed with fixed-effect and random-effects model meta-analyses and were reported as relative risk with 95% CIs. FINDINGS: We identified 14 randomised trials (n=170,525). Trial quality was generally high. Heterogeneity of results was low to moderate. Neither the fixed-effect (relative risk 0.96, 95% CI 0.88-1.04) nor random-effects meta-analyses (0.90, 0.77-1.05) showed significant effects of supplementation with beta-carotene, vitamins A, C, E, and selenium (alone or in combination) versus placebo on oesophageal, gastric, colorectal, pancreatic, and liver cancer incidences. In seven high-quality trials (n=131727), the fixed-effect model showed that antioxidant significantly increased mortality (1.06, 1.02-1.10), unlike the random-effects meta-analysis (1.06, 0.98-1.15). Low-quality trials showed no significant effect of antioxidant supplementation on mortality. The difference between the mortality estimates in high-quality and low-quality trials was significant (Z=2.10, p=0.04 by test of interaction). beta-carotene and vitamin A (1.29, 1.14-1.45) and beta-carotene and vitamin E (1.10, 1.01-1.20) significantly increased mortality, whereas beta-carotene alone only tended to increase mortality (1.05, 0.99-1.11). In four trials (three with unclear or inadequate methodology), selenium showed significant beneficial effect on the incidence of gastrointestinal cancer. INTERPRETATION: We could not find evidence that antioxidant supplements can prevent gastrointestinal cancers; on the contrary, they seem to increase overall mortality. The potential preventive effect of selenium should be studied in adequate randomised trials.", "title": "Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis." }, { "docid": "MED-5070", "text": "Polyphenol-rich berry extracts were screened for their antiproliferative effectiveness using human cervical cancer (HeLa) cells grown in microtiter plates. Rowan berry, raspberry, lingonberry, cloudberry, arctic bramble, and strawberry extracts were effective but blueberry, sea buckthorn, and pomegranate extracts were considerably less effective. The most effective extracts (strawberry > arctic bramble > cloudberry > lingonberry) gave EC 50 values in the range of 25-40 microg/(mL of phenols). These extracts were also effective against human colon cancer (CaCo-2) cells, which were generally more sensitive at low concentrations but conversely less sensitive at higher concentrations. The strawberry, cloudberry, arctic bramble, and the raspberry extracts share common polyphenol constituents, especially the ellagitannins, which have been shown to be effective antiproliferative agents. However, the components underlying the effectiveness of the lingonberry extracts are not known. The lingonberry extracts were fractionated into anthocyanin-rich and tannin-rich fractions by chromatography on Sephadex LH-20. The anthocyanin-rich fraction was considerably less effective than the original extract, whereas the antiproliferative activity was retained in the tannin-rich fraction. The polyphenolic composition of the lingonberry extract was assessed by liquid chromatography-mass spectrometry and was similar to previous reports. The tannin-rich fraction was almost entirely composed of procyanidins of linkage type A and B. Therefore, the antiproliferative activity of lingonberry was caused predominantly by procyanidins.", "title": "Berry extracts exert different antiproliferative effects against cervical and colon cancer cells grown in vitro." }, { "docid": "MED-3620", "text": "Dietary factors such as fruit and vegetables are thought to reduce the risk of cancer incidence and mortality. We investigated the effect of a diet rich in fruit and vegetables against the long-term effects of radiation exposure on the risk of cancer. A cohort of 36,228 atomic-bomb survivors of Hiroshima and Nagasaki, for whom radiation dose estimates were currently available, had their diet assessed in 1980. They were followed for a period of 20 years for cancer mortality. The joint-effect of fruit and vegetables intake and radiation exposure on risk of cancer death was examined, in additive (sum of effects of diet alone and radiation alone) and multiplicative (product of effects of diet alone and radiation alone) models. In the additive model, a daily intake of fruit and vegetables significantly reduced the risk of cancer deaths by 13%, compared to an intake of once or less per week. Radiation exposure of 1 Sievert (Sv) increased significantly the risk of cancer death by 48-49%. The additive joint-effects showed a lower risk of cancer among those exposed to 1 Sv who had a diet rich in vegetables (49%-13%=36%) or fruit (48%-13%=35%). The multiplicative model gave similar results. The cancer risk reduction by vegetables in exposed persons went from 52% (effect of radiation alone) to 32% (product of effect of vegetables and radiation), and cancer risk reduction by fruit was 52% (radiation alone) to 34% (product of effect of fruit and radiation). There was no significant evidence to reject either the additive or the multiplicative model. A daily intake of fruit and vegetables was beneficial to the persons exposed to radiation in reducing their risks of cancer death.", "title": "Dietary factors and cancer mortality among atomic-bomb survivors." }, { "docid": "MED-4262", "text": "Satiety, which is the inhibition of eating following the end of a meal, is influenced by a number of food characteristics, including compositional and structural factors. An increased understanding of these factors and the mechanisms whereby they exert their effects on satiety may offer a food-based approach to weight management. Water and gas, which are often neglected in nutrition, are major components of many foods and contribute to volume, and to sensory and other characteristics. A review of previous short-term studies that evaluated the effects of water or gas in foods on satiety showed that while satiety was generally increased, effects on subsequent intakes were not always apparent. These studies were diverse in terms of design, timings and food matrices, which precludes definitive conclusions. However, the results indicate that solids may be more effective at increasing satiety than liquids, but gas may be as effective as water. Although increased gastric distension may be the main mechanism underlying these effects, pre-ingestive and ingestive impacts on cognitive, anticipatory and sensory responses also appear to be involved. Furthermore, there is limited evidence that water on its own may be effective at increasing satiety and decreasing intakes when drunk before, but not with, a meal. Longer-term extrapolation suggests that increasing food volumes with water or gas may offer weight-management strategies. However, from a practical viewpoint, the effects of water and gas on satiety may be best exploited by using these non-nutrients to manipulate perceived portion sizes, without increasing energy contents.", "title": "Satiety: have we neglected dietary non-nutrients?" }, { "docid": "MED-4678", "text": "The aim of this study was to obtain a better understanding of the role of hormonal factors in breast cancer risk and to determine whether the effect of reproductive events differs according to age at diagnosis. It analysed the effect of age at menarche, age at first full-term pregnancy, number of full-term pregnancies and number of spontaneous abortions both on the overall risk of breast cancer and on its pre- or postmenopausal onset, using the data on 1718 breast cancer cases, obtained from a large sample of around 100 000 French women participating in the E3N cohort study. The results provide further evidence that the overall risk of breast cancer increases with decreasing age at menarche, increasing age at first pregnancy and low parity. No overall effect of spontaneous abortions was observed. The effect of these reproductive factors differed according to menopausal status. Age at menarche had an effect on premenopausal breast cancer risk, with a decrease in risk with increasing age of 7% per year (P<0.05). Compared to those who had their first menstrual periods at 11 or before, women experiencing menarche at 15 or after had an RR of 0.66 (95% CI 0.45–0.97) in the premenopausal group. Age at first full-term pregnancy had an effect on both pre- and postmenopausal breast cancer risk, with significant tests showing increasing risk per year of increasing age (P=0.001 and P<0.05 respectively). A first full-term pregnancy above age 30 conveyed a risk of 1.63 (95% CI 1.12–2.38) and 1.35 (95% CI 1.02–1.78) in the pre- and postmenopausal groups respectively. A protective effect of high parity was observed only for postmenopausal breast cancer risk (P for trend test =0.001), with point estimates of 0.79 (95% CI 0.60–1.04), 0.69 (95% CI 0.54–0.88), 0.66 (95% CI 0.51–0.85) and 0.64 (95% CI 0.48–0.86) associated to a one, two, three and four or more full-term pregnancies. A history of spontaneous abortion had no significant effect on the risk of breast cancer diagnosed before or after menopause. Our results suggest that reproductive events have complex effects on the risk of breast cancer. British Journal of Cancer (2002) 86, 723–727. DOI: 10.1038/sj/bjc/6600124 www.bjcancer.com © 2002 Cancer Research UK", "title": "Differential effects of reproductive factors on the risk of pre- and postmenopausal breast cancer. Results from a large cohort of French women" }, { "docid": "MED-5305", "text": "Since the time of Lavoisier it has been known that the ingestion of food in animals and man produces an increase in oxygen consumption. This increase in metabolic rate was originally called 'specific dynamic action' (SDA) and is now widely referred to as the thermic effect (TE) of food or diet-induced thermogenesis (DIT) (Rothwell & Stock, 1981). Much of the early work on the thermic effect was confined to the type and amount of food, notably the macronutrients--proteins, fats and carbohydrates. Later, it was shown that certain minor constituents of the diet such as caffeine and associated methylxanthines (Zahorska-Markrewicz, 1980; Jung et al., 1981) in tea and coffee could also have a profound effect on metabolic rate. The consumption of alcohol was also shown to increase metabolic rate (Rosenberg & Durnin, 1978). The work described in this paper reports the effect of another minor constituent of food, spices, on metabolic rate. Although the use of spices in our food has steadily increased with time little information exists on their effect on the metabolic rate. It has been estimated that approximately 40 different spices are used in our diet today. This communication reports the effect of chilli (red pepper, capsicum annuum) and mustard (Brassica juncea).", "title": "Effect of spiced food on metabolic rate." }, { "docid": "MED-3012", "text": "The fish ingredient N3-docosahexaenoic acid 22:6 n-3 (DHA) stimulates brain development. On the other hand methylmercury (MeHg) in fish disturbs the developing central nervous system. In this Context the IQ score in children is considered as an aggregate measure of in utero brain development. To determine the effect of DHA exposure on prenatal neurodevelopment the maternal DHA intake during pregnancy was compared with its epidemiologically observed effect on the IQ score of children. For MeHg the maternal intake was converted into its accumulation in the maternal body. The maternal body burden then was compared with its epidemiologically observed relationship with the IQ score. Taking the MeHg and DHA content of 33 fish species the net effect of these compounds on the IQ score was quantified. For most fish species the adverse effect of MeHg on the IQ score exceeded the beneficial effect of DHA. In the case of long-living predators a negative effect up to 10 points on the IQ score was found. The results of this study indicate that food interventions aiming at the beneficial effects of fish consumption should focus on fish species with a high DHA content, while avoiding fish species with a high MeHg content. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Fish consumption during child bearing age: a quantitative risk-benefit analysis on neurodevelopment." }, { "docid": "MED-2712", "text": "PURPOSE: We reviewed studies from 1990 to 2010 on using aromatherapy for people with anxiety or anxiety symptoms and examined their clinical effects. METHODS: The review was conducted on available electronic databases to extract journal articles that evaluated the anxiolytic effects of aromatherapy for people with anxiety symptoms. RESULTS: The results were based on 16 randomized controlled trials examining the anxiolytic effects of aromatherapy among people with anxiety symptoms. Most of the studies indicated positive effects to quell anxiety. No adverse events were reported. CONCLUSIONS: It is recommended that aromatherapy could be applied as a complementary therapy for people with anxiety symptoms. Further studies with better quality on methodology should be conducted to identify its clinical effects and the underlying biologic mechanisms.", "title": "A systematic review on the anxiolytic effects of aromatherapy in people with anxiety symptoms." }, { "docid": "MED-2228", "text": "BACKGROUND: There is substantial interest in chocolate and flavan-3-ols for the prevention of cardiovascular disease (CVD). OBJECTIVE: The objective was to systematically review the effects of chocolate, cocoa, and flavan-3-ols on major CVD risk factors. DESIGN: We searched Medline, EMBASE, and Cochrane databases for randomized controlled trials (RCTs) of chocolate, cocoa, or flavan-3-ols. We contacted authors for additional data and conducted duplicate assessment of study inclusion, data extraction, validity, and random-effects meta-analyses. RESULTS: We included 42 acute or short-term chronic (≤18 wk) RCTs that comprised 1297 participants. Insulin resistance (HOMA-IR: -0.67; 95% CI: -0.98, -0.36) was improved by chocolate or cocoa due to significant reductions in serum insulin. Flow-mediated dilatation (FMD) improved after chronic (1.34%; 95% CI: 1.00%, 1.68%) and acute (3.19%; 95% CI: 2.04%, 4.33%) intakes. Effects on HOMA-IR and FMD remained stable to sensitivity analyses. We observed reductions in diastolic blood pressure (BP; -1.60 mm Hg; 95% CI: -2.77, -0.43 mm Hg) and mean arterial pressure (-1.64 mm Hg; 95% CI: -3.27, -0.01 mm Hg) and marginally significant effects on LDL (-0.07 mmol/L; 95% CI: -0.13, 0.00 mmol/L) and HDL (0.03 mmol/L; 95% CI: 0.00, 0.06 mmol/L) cholesterol. Chocolate or cocoa improved FMD regardless of the dose consumed, whereas doses >50 mg epicatechin/d resulted in greater effects on systolic and diastolic BP. GRADE (Grading of Recommendations, Assessment, Development and Evaluation, a tool to assess quality of evidence and strength of recommendations) suggested low- to moderate-quality evidence of beneficial effects, with no suggestion of negative effects. The strength of evidence was lowered due to unclear reporting for allocation concealment, dropouts, missing data on outcomes, and heterogeneity in biomarker results in some studies. CONCLUSIONS: We found consistent acute and chronic benefits of chocolate or cocoa on FMD and previously unreported promising effects on insulin and HOMA-IR. Larger, longer-duration, and independently funded trials are required to confirm the potential cardiovascular benefits of cocoa flavan-3-ols.", "title": "Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials." }, { "docid": "MED-1359", "text": "Previous meta-analyses investigating the effect of exercise on depression have included trials where the control condition has been categorized as placebo despite the fact that this particular placebo intervention (e.g., meditation, relaxation) has been recognized as having an antidepressant effect. Because meditation and mindfulness-based interventions are associated with depression reduction, it is impossible to separate the effect of the physical exercise from the meditation-related parts. The present study determined the efficacy of exercise in reducing symptoms of depression compared with no treatment, placebo conditions or usual care among clinically defined depressed adults. Of 89 retrieved studies, 15 passed the inclusion criteria of which 13 studies presented sufficient information for calculating effect sizes. The main result showed a significant large overall effect favoring exercise intervention. The effect size was even larger when only trials that had used no treatment or placebo conditions were analyzed. Nevertheless, effect size was reduced to a moderate level when only studies with high methodological quality were included in the analysis. Exercise may be recommended for people with mild and moderate depression who are willing, motivated, and physically healthy enough to engage in such a program. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.", "title": "Physical exercise intervention in depressive disorders: meta-analysis and systematic review." }, { "docid": "MED-5115", "text": "The potential health benefits of soy-derived phytoestrogens include their reported utility as anticarcinogens, cardioprotectants and as hormone replacement alternatives in menopause. Although there is increasing popularity of dietary phytoestrogen supplementation and of vegetarian and vegan diets among adolescents and adults, concerns about potential detrimental or other genotoxic effects persist. While a variety of genotoxic effects of phytoestrogens have been reported in vitro, the concentrations at which such effects occurred were often much higher than the physiologically relevant doses achievable by dietary or pharmacologic intake of soy foods or supplements. This review focuses on in vitro studies of the most abundant soy phytoestrogen, genistein, critically examining dose as a crucial determinant of cellular effects. In consideration of levels of dietary genistein uptake and bioavailability we have defined in vitro concentrations of genistein >5 microM as non-physiological, and thus \"high\" doses, in contrast to much of the previous literature. In doing so, many of the often-cited genotoxic effects of genistein, including apoptosis, cell growth inhibition, topoisomerase inhibition and others become less obvious. Recent cellular, epigenetic and microarray studies are beginning to decipher genistein effects that occur at dietarily relevant low concentrations. In toxicology, the well accepted principle of \"the dose defines the poison\" applies to many toxicants and can be invoked, as herein, to distinguish genotoxic versus potentially beneficial in vitro effects of natural dietary products such as genistein.", "title": "Genistein genotoxicity: critical considerations of in vitro exposure dose." }, { "docid": "MED-5285", "text": "High blood pressure is an important risk factor for cardiovascular disease and cardiovascular events worldwide. Clinical and epidemiological studies suggest that cocoa-rich products reduce the risk of cardiovascular disease. According to this, cocoa has a high content in polyphenols, especially flavanols. Flavanols have been described to exert favorable effects on endothelium-derived vasodilation via the stimulation of nitric oxide-synthase, the increased availability of l-arginine, and the decreased degradation of NO. Cocoa may also have a beneficial effect by protecting against oxidative stress alterations and via decreased platelet aggregation, decreased lipid oxidation, and insulin resistance. These effects are associated with a decrease of blood pressure and a favorable trend toward a reduction in cardiovascular events and strokes. Previous meta-analyses have shown that cocoa-rich foods may reduce blood pressure. Long-term trials investigating the effect of cocoa products are needed to determine whether or not blood pressure is reduced on a chronic basis by daily ingestion of cocoa. Furthermore, long-term trials investigating the effect of cocoa on clinical outcomes are also needed to assess whether cocoa has an effect on cardiovascular events. A 3 mmHg systolic blood pressure reduction has been estimated to decrease the risk of cardiovascular and all-cause mortality. This paper summarizes new findings concerning cocoa effects on blood pressure and cardiovascular health, focusing on putative mechanisms of action and \"nutraceutical \" viewpoints.", "title": "Cocoa, Blood Pressure, and Cardiovascular Health." }, { "docid": "MED-3975", "text": "Background In Japan, gargling is a generally accepted way of preventing upper respiratory tract infection (URTI). The effectiveness of gargling for preventing URTI has been shown in a randomized controlled trial that compared incidences of URTI between gargling and control groups. From the perspective of the third-party payer, gargling is dominant due to the fact that the costs of gargling are borne by the participant. However, the cost-effectiveness of gargling from a societal perspective should be considered. In this study, economic evaluation alongside a randomized controlled trial was performed to evaluate the cost-effectiveness of gargling for preventing URTI from a societal perspective. Methods Among participants in the gargling trial, 122 water-gargling and 130 control subjects were involved in the economic analysis. Sixty-day cumulative follow-up costs and effectiveness measured by quality-adjusted life days (QALD) were compared between groups on an intention-to-treat basis. Incremental cost-effectiveness ratio (ICER) was converted to dollars per quality-adjusted life years (QALY). The 95% confidence interval (95%CI) and probability of gargling being cost-effective were estimated by bootstrapping. Results After 60 days, QALD was increased by 0.43 and costs were $37.1 higher in the gargling group than in the control group. ICER of the gargling group was $31,800/QALY (95%CI, $1,900–$248,100). Although this resembles many acceptable forms of medical intervention, including URTI preventive measures such as influenza vaccination, the broad confidence interval indicates uncertainty surrounding our results. In addition, one-way sensitivity analysis also indicated that careful evaluation is required for the cost of gargling and the utility of moderate URTI. The major limitation of this study was that this trial was conducted in winter, at a time when URTI is prevalent. Care must be taken when applying the results to a season when URTI is not prevalent, since the ICER will increase due to decreases in incidence. Conclusion This study suggests gargling as a cost-effective preventive strategy for URTI that is acceptable from perspectives of both the third-party payer and society.", "title": "Cost-effectiveness of gargling for the prevention of upper respiratory tract infections" }, { "docid": "MED-5172", "text": "The prevalence of allergic rhinitis is increasing globally due to various causes. It affects the quality life of a large group of people in all around the world. Allergic rhinitis still remains inadequately controlled with present medical means. The need of continuous medical therapy makes individuals anxious about the side effects of the drugs. So there is a need for an alternative strategy. Effects of spirulina, tinospora cordifolia and butterbur were investigated recently on allergic rhinitis in just very few investigations. Spirulina represents a blue-green alga that is produced and commercialized as a dietary supplement for modulating immune functions, as well as ameliorating a variety of diseases. This double blind, placebo controlled study, evaluated the effectiveness and tolerability of spirulina for treating patients with allergic rhinitis. Spirulina consumption significantly improved the symptoms and physical findings compared with placebo (P < 0.001***) including nasal discharge, sneezing, nasal congestion and itching. Spirulina is clinically effective on allergic rhinitis when compared with placebo. Further studies should be performed in order to clarify the mechanism of this effect.", "title": "The effects of spirulina on allergic rhinitis." }, { "docid": "MED-1640", "text": "Coffee is one of the most widely used pharmacologically active beverages. The present study was designed to evaluate the acute effect of coffee ingestion on endothelial function in healthy individuals, and the potential role of caffeine. We studied 17 healthy young adults (28.9+/-3.0 years old; nine men), who were regular non-heavy coffee drinkers. The endothelial performance was estimated by endothelium-dependent FMD (flow-mediated dilatation) of the brachial artery before and 30, 60, 90 and 120 min after ingestion of a cup of caffeinated coffee (80 mg of caffeine) or the corresponding decaffeinated beverage (< 2 mg of caffeine) in two separate sessions, following a randomized single-blind cross-over design. There was no difference in baseline FMD values between the two sessions [7.78 compared with 7.07% after caffeinated and decaffeinated coffee respectively; P = NS (not significant)]. Caffeinated coffee led to a decline of FMD (7.78, 2.86, 2.12, 4.44 and 4.57% at baseline, 30, 60, 90 and 120 min respectively; P < 0.001). This adverse effect was focused at 30 (P = 0.004) and 60 min (P < 0.001). No significant effect on FMD was found with the decaffeinated coffee session (7.07, 6.24, 5.21, 7.41 and 5.20%; P = NS). The composite effect of the type of coffee consumed over time on FMD was significantly different (P = 0.021). In conclusion, coffee exerts an acute unfavourable effect on the endothelial function in healthy adults, lasting for at least 1 h after intake. This effect might be attributed to caffeine, given that decaffeinated coffee was not associated with any change in the endothelial performance.", "title": "Effect of coffee on endothelial function in healthy subjects: the role of caffeine." }, { "docid": "MED-2229", "text": "BACKGROUND/OBJECTIVES: In vitro and animal studies have reported that young broccoli sprouts improve oxidative stress status in diabetic condition. The objective of this double-blind, placebo-controlled, randomized clinical trial was to investigate the effects of broccoli sprouts powder (BSP) on some oxidative stress parameters in type 2 diabetes patients. SUBJECTS/METHODS: A total of 81 patients with type 2 diabetes were randomly assigned to one of three treatment groups for 4 weeks. The groups received either 10 g/d BSP (n=27), 5 g/d BSP (n=29) or placebo (n=25). Serum total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), malondialdehyde (MDA) and oxidized low density lipoprotein (LDL) cholesterol were measured at baseline and at 4 weeks after treatment. RESULTS: In all, 63 patients in three groups were included in the analysis: 10 g/d BSP (n=21), 5 g/d (n=22) and placebo (n=20). After 4 weeks, consumption of BSP resulted in significant decrease in MDA (P=0.001 for treatment effect), oxidized low density lipoprotein cholesterol (P=0.03 for treatment effect), OSI (P=0.001 for treatment effect) and significant increase in TAC (P=0.001 for treatment effect). No effects were found on TOS. CONCLUSION: BSP had favorable effects on oxidative stress status in type 2 diabetes patients.", "title": "Broccoli sprouts reduce oxidative stress in type 2 diabetes: a randomized double-blind clinical trial." }, { "docid": "MED-2400", "text": "The early effects of 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) exposure in the population involved in the Seveso, Italy, incident in 1976, have been examined in numerous studies. Chloracne was the only effect linked with sufficient certainty to dioxin exposure. The possible long-term consequences were investigated with mortality and cancer incidence studies. Mortality and morbidity findings during the 20-year period following the accident showed increased risk from lymphoemopoietic neoplasm, digestive system cancer (rectum in males, and biliary tract among females, in particular) and respiratory system cancer (lung, among males). In the incidence analyses, also thyroid gland and pleura cancer appeared suggestively increased. Soft tissue sarcomas showed an increase in the largest, yet least exposed, exposure sub-cohort. Several hypotheses associating non-cancer effects with dioxin exposure were corroborated by findings in the Seveso population: this was the case with cardiovascular effects (possibly linked to both chemical exposure and stressful disaster experience), endocrine effects (diabetes among females) and reproductive effects: exposure of men to TCDD was linked to a lowered male/female sex ratio in their offspring. The results of many Seveso studies point to possible gender effects, in accordance with animal models. Notwithstanding the acknowledged study limitations (lack of individual exposure markers, short latency, and small population size for certain cancer types), results of previous experimental and epidemiological studies, along with mechanistic knowledge on dioxin toxicity, support the hypotheses that the observed excesses might be associated with dioxin exposure. The mortality and cancer incidence follow-up of the Seveso cohort are continuing.", "title": "Short- and long-term morbidity and mortality in the population exposed to dioxin after the \"Seveso accident\"." }, { "docid": "MED-5050", "text": "Tea is the most widely consumed beverage in the world after water. Tea is known to be a rich source of flavonoid antioxidants. However tea also contains a unique amino acid, L-theanine that may modulate aspects of brain function in humans. Evidence from human electroencephalograph (EEG) studies show that it has a direct effect on the brain (Juneja et al. Trends in Food Science & Tech 1999;10;199-204). L-theanine significantly increases activity in the alpha frequency band which indicates that it relaxes the mind without inducing drowsiness. However, this effect has only been established at higher doses than that typically found in a cup of black tea (approximately 20mg). The aim of the current research was to establish this effect at more realistic dietary levels. EEG was measured in healthy, young participants at baseline and 45, 60, 75, 90 and 105 minutes after ingestion of 50mg L-theanine (n=16) or placebo (n=19). Participants were resting with their eyes closed during EEG recording. There was a greater increase in alpha activity across time in the L-theanine condition (relative to placebo (p+0.05). A second study replicated this effect in participants engaged in passive activity. These data indicate that L-theanine, at realistic dietary levels, has a significant effect on the general state of mental alertness or arousal. Furthermore, alpha activity is known to play an important role in critical aspects of attention, and further research is therefore focussed on understanding the effect of L-theanine on attentional processes.", "title": "L-theanine, a natural constituent in tea, and its effect on mental state." }, { "docid": "MED-4301", "text": "BACKGROUND: Epidemiological studies have consistently associated nut consumption with reduced risk for coronary heart disease. Subsequently, many dietary intervention trials investigated the effects of nut consumption on blood lipid levels. The objectives of this study were to estimate the effects of nut consumption on blood lipid levels and to examine whether different factors modify the effects. METHODS: We pooled individual primary data from 25 nut consumption trials conducted in 7 countries among 583 men and women with normolipidemia and hypercholesterolemia who were not taking lipid-lowering medications. In a pooled analysis, we used mixed linear models to assess the effects of nut consumption and the potential interactions. RESULTS: With a mean daily consumption of 67 g of nuts, the following estimated mean reductions were achieved: total cholesterol concentration (10.9 mg/dL [5.1% change]), low-density lipoprotein cholesterol concentration (LDL-C) (10.2 mg/dL [7.4% change]), ratio of LDL-C to high-density lipoprotein cholesterol concentration (HDL-C) (0.22 [8.3% change]), and ratio of total cholesterol concentration to HDL-C (0.24 [5.6% change]) (P < .001 for all) (to convert all cholesterol concentrations to millimoles per liter, multiply by 0.0259). Triglyceride levels were reduced by 20.6 mg/dL (10.2%) in subjects with blood triglyceride levels of at least 150 mg/dL (P < .05) but not in those with lower levels (to convert triglyceride level to millimoles per liter, multiply by 0.0113). The effects of nut consumption were dose related, and different types of nuts had similar effects on blood lipid levels. The effects of nut consumption were significantly modified by LDL-C, body mass index, and diet type: the lipid-lowering effects of nut consumption were greatest among subjects with high baseline LDL-C and with low body mass index and among those consuming Western diets. CONCLUSION: Nut consumption improves blood lipid levels in a dose-related manner, particularly among subjects with higher LDL-C or with lower BMI.", "title": "Nut consumption and blood lipid levels: a pooled analysis of 25 intervention trials." } ]
3328
Are tax deductions voluntary?
[ { "docid": "293920", "text": "\"What kind of \"\"deductions\"\" are you talking about? Many deductions, like the standard/itemized deductions, come after the AGI, and do not affect the AGI, so I don't see how this would make any difference. Maybe you are talking about deductions that come before the AGI? If you want to increase your AGI legitimately, here's a way: Every year, itemize deductions on your federal return, and over-withhold your state income tax (assuming your state has income tax) by a lot, and/or make voluntary extra payments to your state income tax. As a result, you will get a huge refund on your state taxes the following year. Then you will need to include this refund as income on line 10 of the federal return that year, which will be included in the AGI. (Of course, you will also be able to deduct a lot of state income tax paid every year in the federal itemized deductions, but those come after the AGI.)\"", "title": "" }, { "docid": "580379", "text": "\"I did a little research and found this article from 2006 by a Villanova law professor, titled \"\"No Thanks, Uncle Sam, You Can Keep Your Tax Break\"\". The final paragraph of the article says: Under these circumstances, it is reasonable to conclude that a taxpayer is not required to claim a allowable deduction unless a statutory provision so requires, or a binding judicial precedent so specifies. It would be unwise, of course, to forego a deduction that the IRS considers mandatory such as those claimed by self-employed individuals with respect to their self-employment, whether for purposes of the self-employment tax or the earned income tax credit. Until the statute is changed or some other binding authority is issued, there is no reason taxpayers who wish to forego deductions, such as the dependency exemption deduction, should hesitate in doing so. (The self-employment tax issues in the quote cited by CQM are explicitly discussed in the article as one of a few special kinds of deduction which are mandatory.) This is not a binding statement: it's not law or even official IRS policy. You could never use it as a defense in the event that this professor turned out to be wrong and the IRS decided to go after you anyway. However, it is a clear statement from a credible, qualified source.\"", "title": "" }, { "docid": "240643", "text": "\"Legally: gods know. I would strongly recommend asking the Law asre of Stack Exchange to advise on that. Practically: What's the worst that happens? They audit, you say \"\"Yeah, I could probably have claimed these deductions but I didn't want to; is that a problem?\"\", they decide and either nothing happens or they issue you the unwanted refunnd. They aren't going to fine you for overpaying. Unless this would expose something criminal -- or you're a public figure and it would be embarassing -- this strikes me as falling firmly within the bounds of \"\"no harm, no foul\"\".\"", "title": "" }, { "docid": "331925", "text": "\"There are many people who have deductions far above the standard deduction, but still don't itemize. That's their option even though it comes at a cost. It may be foolish, but it's not illegal. If @littleadv citation is correct, the 'under penalty of perjury' type issue, what of those filers who file a Schedule A but purposely leave off their donations? I've seen many people discuss charity, and write that they do not want to benefit in any way from their donation, yet, still Schedule A their mortgage and property tax. Their returns are therefore fraudulent. I am curious to find a situation in which the taxpayer benefits from such a purposeful oversight, or, better still, a cited case where they were charged with doing so. I've offered advice on filings return that wasn't \"\"truthful\"\". When you own a stock and cannot find cost basis, there are times that you might realize the basis is so low that just entering zero will cost you less than $100 in extra tax. You are not truthful, of course, but this kind of false statement isn't going to lead to any issue. If it gets noticed within an audit, no agent is going to give it more than a moment of time and perhaps suggest, \"\"you didn't even know the year it was bought?\"\" but there would be no consequence. My answer is for personal returns, I'm sure for business, accuracy to the dollar is actually important.\"", "title": "" } ]
[ { "docid": "262358", "text": "How is taxing them preventing a donation to their charity of choice? It isn't one or the other. You can be taxed and voluntarily charitable. The whole GOP point, though, is to make it ALL voluntary charity so if they give, they get to decide who deserves their money and they deserve a big fat tax deduction.", "title": "" }, { "docid": "290862", "text": "My basic rule of thumb is that if the the bill come from a government office of taxation, and that if you fail to pay the amount they can put a tax lien on the property it is a tax. for you the complication is in Pub530: Assessments for local benefits. You cannot deduct amounts you pay for local benefits that tend to increase the value of your property. Local benefits include the construction of streets, sidewalks, or water and sewer systems. You must add these amounts to the basis of your property. You can, however, deduct assessments (or taxes) for local benefits if they are for maintenance, repair, or interest charges related to those benefits. An example is a charge to repair an existing sidewalk and any interest included in that charge. If only a part of the assessment is for maintenance, repair, or interest charges, you must be able to show the amount of that part to claim the deduction. If you cannot show what part of the assessment is for maintenance, repair, or interest charges, you cannot deduct any of it. An assessment for a local benefit may be listed as an item in your real estate tax bill. If so, use the rules in this section to find how much of it, if any, you can deduct. I have never seen a tax bill that said this amount is for new streets, and the rest i for things the IRS says you can deduct. The issue is that if the Center City tax bill is a separate line or a separate bill then does it count. I would go back to the first line of the quote from Pub 530: You cannot deduct amounts you pay for local benefits that tend to increase the value of your property. Then I would look at the quote from the CCD web site: The Center City District (CCD) is a business improvement district. Our mission is to keep Philadelphia's downtown, called Center City, clean, safe, beautiful and fun. We provide security, cleaning and promotional services that supplement, but do not replace, basic services provided by the City of Philadelphia and the fundamental responsibilities of property owners. CCD also makes physical improvements to the downtown, installing and maintaining lighting, > signs, banners, trees and landscape elements. and later on the same page: CCD directly bills and collects mandatory payments from properties in the district. CCD also receives voluntary contributions from the owners of tax-exempt properties that benefit from our services. The issues is that it is a business improvement district (BID), and you aren't a business: I did find this document from the city of Philadelphia explain how to establish a BID: If the nature of the BID is such that organizers wish to include residential properties within the district and make these properties subject to the assessment, it may make sense to assess these properties at a lower level than a commercial property, both because BID services and benefits are business-focused, and because owner-occupants often cannot treat NID assessments as tax-deductible business expenses, like commercial owners do. Care must be taken to ensure that the difference in commercial and residential assessment rates is equitable, and complies with the requirements of the CEIA. from the same document: Funds for BID programs and services are generated from a special assessment paid by the benefited property owners directly to the organization that manages the BID’s activities. (Note: many leases have a clause that allows property owners to pass the BID assessment on to their tenants.) Because they are authorized by the City of Philadelphia, the assessment levied by the BID becomes a legal obligation of the property owner and failure to pay can result in the filing of a lien. I have seen discussion that some BIDS can accept tax deductible donations. This means if a person itemizes they can deduct the donation. I would then feel comfortable deducting the tax because: If you can't deduct it that would mean the only people who can't deduct it are home owners. So deduct it. (keep in mind I am not a tax professional)", "title": "" }, { "docid": "547401", "text": "Yes, you are generally allowed to make contributions yourself to your HSA, even if your employer also made contributions. Let me explain further. The contribution limit for tax year 2015 is $3350 for individual coverage. (It is higher for family coverage, or for account holders age 55+.) The limit is for everything contributed to the HSA, whether it is an employer contribution or an account holder contribution. (In other words, if your limit is $3350, and your employer contributed $3000, you can only contribute $350.) As far as the IRS is concerned, anything that your employer sends in is considered an employer contribution. This might be money from the company as part of a benefit, or it might be money deducted from your salary as part of a voluntary contribution on your part. Either way, if the employer sends it in, it is an employer contribution. None of this employer contribution shows up on your W-2 as taxable income, so you don't get to deduct it on your tax return. It has already been taken off of your income. Money that you send in yourself with your after-tax dollars is your account holder contribution. This is money that you can deduct on your tax return, so that you aren't paying tax on this money. So here is what you need to do: Determine your total HSA contribution limit for tax year 2015. Find out how much your employer has already contributed for 2015. The difference is how much you can still contribute for 2015. Contact your HSA provider and find out how to make a 2015 contribution. Don't just send money in, because there is probably a form they want you to fill out to make a prior year contribution. Get all this done by April 15, the deadline for making a prior year contribution. Actually, get it done before April 15, because often there will be some sort of delay of a day or two that will prevent you from doing this on the last day.", "title": "" }, { "docid": "101764", "text": "\"When you give a gift to another person or receive a gift from another person there is no impact on your taxes. You do not have to report certain amounts in your income, including the following: ... -most gifts and inheritances; http://www.cra-arc.gc.ca/tx/ndvdls/tpcs/ncm-tx/rtrn/cmpltng/rprtng-ncm/nttxd-eng.html If you give a gift to a charity or similar organization you can reduce your taxes. It is my recollection that when a family member gives a large amount of money to a child, tax on the income that money earns (typically interest) should be paid by the giver, not the child, but I can't find any publications to that effect on the CRA Site. There is a bit of language about \"\"Gifts\"\" from an employer that are really employment income: Gifts and other voluntary payments 1.3 The term gift is not defined in the Act. In common law jurisdictions, the courts have said that a bona fide gift exists when: •There is a voluntary transfer of property, •A donor freely disposes of his or her property to a donee, and •The donee confers no right, privilege, material benefit, or advantage on the donor or on a person designated by the donor. 1.4 Whether a transfer of property has been made voluntarily is a question of fact. In order for a transfer to be considered voluntary, there must be no obligation to make such a transfer. Amounts received as gifts, that is, voluntary transfers without consideration and which cannot be attributed to an income-earning source, are not subject to tax in the hands of the recipient. 1.5 However, sometimes individuals receive a voluntary payment or other valuable transfer or benefit by virtue of an office or employment from an employer, or from some other person. In such cases, the amount of the payment or the value of the transfer or benefit is generally included in employment income pursuant to subsection 5(1) or paragraph 6(1)(a). (See also Guide T4130, Employers’ Guide - Taxable Benefits and Allowances.) Similarly, voluntary payments (or other transfers or benefits) received by virtue of a profession or in the course of carrying on a business are taxable receipts. http://www.cra-arc.gc.ca/tx/tchncl/ncmtx/fls/s3/f9/s3-f9-c1-eng.html#N10244 If the people in question are adults who are not related to each other and don't have a business or employment relationship, then you should find that regardless of the amount of the gift, neither giver nor recipient will have a tax consequence.\"", "title": "" }, { "docid": "80664", "text": "By the time you've earned the income, it is basically too late to decide who it belongs to[*]. If the assets belong to one person, income from those assets must be declared by that person. If you earn interest on a shared account, you must declare 50% of it each. And so on. (If you're tempted to fudge it bear in mind that banks report to the ATO about interest paid and account ownership.) I don't think Family Tax Benefits are taxable income, but I don't get them myself so I don't know. What you can do is think about how you want things arranged going forward. That means making a prediction about who will have the higher income; it sounds like that's going to be you, and she will be working at most part time. Therefore she should hold anything that generates taxable income (bank accounts etc) and you should hold anything that generates losses (negatively-geared investments, charitable deductions, etc). You could look into making a voluntary super contribution into her account which (imbw) will be deductible for you and get it into a lower-tax area. If you're earning on the order of $30k per annum in interest you're looking at paying $11500 tax on it if it's in your name vs $5k if it's in hers, so it's not a moot point. $420k in cash is arguably quite a lot, and perhaps you want to look at putting some of it into a low-cost balanced managed fund, such as those from Vanguard. That will be somewhat more tax effective, though less stable. If you're looking to buy a new house within a few years perhaps cash is the best place for it. [*] One kind-of exception is that if you have a family trust, the trust can decide at the end of the year to whom it will distribute its income. However, you still have to decide to establish a trust in advance.", "title": "" }, { "docid": "392484", "text": "You would report the overall income on your T1 general income tax return, and use form T2125 to report income and expenses for your business. Form T2125 is like a mini income-statement where you report your gross revenue and subtract off expenses. Being able to claim legitimate expenses as a deduction is an important tax benefit for businesses big and small. In terms of your second question, you generally need to register for a business number at least once you cross the threshold for GST / HST. If you earn $30,000/year (or spread over four consecutive quarters) then charging GST / HST is mandatory; see GST/HST Mandatory registration. There are other conditions as well, but the threshold is the principal one. You can also register voluntarily for GST / HST even if you're below that threshold; see GST/HST Voluntary registration. The advantage of registering voluntarily is that you can claim input tax credits (ITC) on any GST that your business pays, and remit only the difference. That saves your business money, especially if you have a lot of expenses early on. Finally, in terms of Ontario specifically (saw that on your profile), you might want to check out Ontario Sole Proprietorship. There are specific cases in which you need to register a business: e.g. specific types of businesses, or if you plan on doing business under a name other than your own. Finally, you may want to consider whether incorporating might be better for you. Here's an interesting article that compares Sole Proprietorship Versus Incorporation. Here's another article, Choosing a business structure, from the feds.", "title": "" }, { "docid": "239780", "text": "\"&gt;SS is not an investment. It is a Tax. Learn the difference. Thus you pay for it with the Federal Insurance Contributions Act tax (FICA). It is not an investment, you do not have an account with your money, it has always been a pay as you go plan, just like medicare, funds for schools, and all the other programs. SS is collected like a tax, but if it is infact a tax, why can I opt out of it? Come on, you really aren't trying to win an arguement about SS by saying its a \"\"tax\"\" and not a \"\"investment\"\". That's seriously the weakest bullshit, who the fuck cares the symantics of how its \"\"collected\"\".. The arguement is still the same, with no USA no SS. It is, therefore, a ponzi by definition. &gt;The US government wrote the laws that specify exactly who can opt out. Most people cannot just opt out because they don't meet the criteria. Again you're wrong. Joining and quitting Obtaining a Social Security number for a child is voluntary.[26] Further, there is no general legal requirement that individuals join the Social Security program (although, under normal circumstances, FICA taxes must be collected anyway). Although the Social Security Act itself does not require a person to have a Social Security Number (SSN) to live and work in the United States,[27] the Internal Revenue Code does generally require the use of the social security number by individuals for federal tax purposes: The social security account number issued to an individual for purposes of section 205(c)(2)(A) of the Social Security Act shall, except as shall otherwise be specified under regulations of the Secretary [of the Treasury or his delegate], be used as the identifying number for such individual for purposes of this title.[28] Importantly, most parents apply for Social Security numbers for their dependent children in order to[29] include them on their income tax returns as a dependent. Everyone filing a tax return, as taxpayer or spouse, must have a Social Security Number or Taxpayer Identification Number (TIN) since the IRS is unable to process returns or post payments for anyone without an SSN or TIN. The FICA taxes are imposed on all workers and self-employed persons. Employers are required[30] to report wages for covered employment to Social Security for processing Forms W-2 and W-3. There are some specific wages which are not a part of the Social Security program (discussed below). Internal Revenue Code provisions section 3101[31] imposes payroll taxes on individuals and employer matching taxes. Section 3102[32] mandates that employers deduct these payroll taxes from workers' wages before they are paid. Generally, the payroll tax is imposed on everyone in employment earning \"\"wages\"\" as defined in 3121[33] of the Internal Revenue Code.[34] and also taxes[35] net earnings from self-employment.[36] **Seriously, you need to learn how to use google asshole. Stop looking like an idiot and posting blatent lies.**\"", "title": "" }, { "docid": "566005", "text": "He should look into the Voluntary Disclosures Program. He will have to keep up to date with his taxes thereafter, but the outcome will likely be better than if they discover he hasn't been filing before he discloses it.", "title": "" }, { "docid": "301485", "text": "\"The tax bracket is the point where you start paying for the \"\"services\"\" the government \"\"offers\"\" it's not so voluntary membership. I know there is \"\"brackets\"\". We have been talking about how some people think it is OK to discriminate based on your assigned \"\"bracket\"\".\"", "title": "" }, { "docid": "258175", "text": "But the tax isn't paid for in a commodity, like the one you're describing. It's paid for in paper, that the government has a monopoly on printing. Private roads in the past were built using silver and gold as compensation, and the tolls were that, as well. Taxation is mass-extortion, not a voluntary contractual interaction.", "title": "" }, { "docid": "477001", "text": "Again, it is paid for in paper because the people have decided that the paper has value. Taxes have to buy things (services, materials, etc.), and if nobody wants said currency, that tax pool is completely worthless. &gt; Taxation is mass-extortion, not a voluntary contractual interaction. I'm not sure where you come from, but in any reasonably democratic country this is simply not true. It is the collective population deciding to pool some of their wealth to share certain costs of living and working together. You may disagree with the collective, but that doesn't change the collective.", "title": "" }, { "docid": "14478", "text": "\"For many people, giving to charity will have minimal effect on their taxes. Non-profits love to attract donations by saying the money is tax deductible, but for most people, it doesn't work out that way. You will only itemize deductions if they exceed your standard deduction. The IRS allows you to either \"\"itemize\"\" your deductions (where you list each deduction you can take) or take the \"\"standard deduction\"\". Consider a married couple filing jointly in 2011. Their standard deduction is $11,400. They are in the 28% tax bracket. They donate $100 of old clothes to the Goodwill, and are looking forward to deducting that on your taxes, and getting $28 of that back. If that's their only deduction, though, they'd have to give up the standard deduction to take the itemized deduction. Not worth it. Suppose instead they have $11,500 of deductions in 2011. Now we're talking, right? No. The tax impact of itemizing is only $28, since they only exceeded the standard deduction by $100. The cost of having a tax accountant fill out the itemization form probably offsets that small gain. There's also all the time that went in to tracking those deductions over the year. Not worth it. Tax deductions only become worthwhile when they significantly exceed the standard deduction. You need some big ticket items to get past the itemized deduction threshold. For most people, this only happens when they have a mortgage, as the interest on a residence is deductible. Folks love to suggest that having a mortgage is a good deal, because the interest is deductible. However, since you have to exceed the standard deduction before it makes sense to itemize, it's not likely to be a big win. For most people: TL;DR: Give to charity because you want that charity to have your money. Tax implications are minimal; let your accountant sort it out. Disclaimer: I am not an accountant.\"", "title": "" }, { "docid": "51497", "text": "Those choices aren't mutually exclusive. Yes, most discussion of the mortgage interest deduction ignores the fact that for a standard itemizer, much, if not all of this deduction can be lost. For 2011, the std deduction for a single is $5,800. It's not just mortgage interest that's deductible, state income tax, realestate tax, and charitable contributions are among the other deductions. If this house is worth $350K, the property tax is about $5K, and since it's not optional, I'd be inclined to assume that it's the deduction that offsets the std deduction. Most states have an income tax, which tops off the rest. You are welcome to toss this aside as sophistry, but I view it as these other deductions as 'lost' first. I'm married, and our property tax is more than our standard deduction, so when doing the math, the mortgage is fully deductible, as are our contributions. In your case, the numbers may play out differently. No state tax? Great, so it's the property tax and deductions you'd add up first and decide on the value the mortgage deduction brings. Last, I don't have my mortgage for the deduction, I just believe that long term my other investments will exceed, after tax, the cost of that mortgage.", "title": "" }, { "docid": "55666", "text": "I don't think there's much you can do. Losses from the sale of personal-use automobiles (used for pleasure, commuting, etc) are not deductible as capital losses. See IRS Tax Topic 409, end of the first paragraph. The expenses you incurred in owning and operating the car (insurance, fuel, maintenance, service plans, etc) are not deductible either. If you used it partly for business, then some of your expenses might be deductible; see IRS Tax Topic 510. This includes depreciation (decline in value), but only according to a standard schedule; you don't generally just get to deduct the difference between your buying and selling price. Also, you'd need to have records to verify your business use. But anyway, these deductions would apply (or not) regardless of whether you sell the car. You don't get your sales tax refunded when you resell the vehicle. That's why it's a sales tax, not a value-added tax. Note, however, that if you do sell it, the sales tax on this new transaction will be the buyer's responsibility, not yours. You do have the option on your federal income tax return to deduct the state sales tax you paid when you bought the car; in fact, you can deduct all the sales taxes you paid in that year. (If you have already filed your taxes for that year, you can go back and amend them.) However, this takes the place of your state income tax deduction for the year; you can't deduct both. See Tax Topic 503. So this is only useful if your sales taxes for that year exceeded the state income tax you paid in that year. Also, note that state taxes are not deductible on your state income tax return. Again, this deduction applies whether you sell the car or not.", "title": "" }, { "docid": "462831", "text": "In the US there's no significant difference between what a business can deduct and what an individual can deduct. However, you can only deduct what is an expense to produce income. Businesses are allowed to write off salaries, but individuals can't write off what they pay their gardener or maid (at least in the US) If you're a sole proprietor in the business of managing properties - you can definitely deduct payments to gardeners or maids. Business paying for a gardener on a private property not related to producing the income (like CEO's daughter's house) cannot deduct that expense for tax purposes (although it is still recorded in the business accounting books as an expense - with no tax benefit). Businesses are allowed to deduct utility expenses as overhead, individuals cannot Same thing exactly. I can deduct utility expenses for my rental property, but not for my primary residence. Food, shelter, clothing and medical care are fundamental human needs, but we still pay for them with after-tax money, and pay additional sales tax. Only interest (and not principal) on a mortgage is deductible in the US, which is great for people who take out mortgages (and helps banks get more business, I'm sure), but you're out of luck if you pay cash for your house, or are renting. Sales taxes are deductible. You can deduct sales taxes you paid during the year if you itemize your deduction. You can chose - you either deduct the sales taxes or the State income taxes, whatever is more beneficial for you. BTW in many states food and medicine are exempt from sales tax. Medical expenses are deductible if they're significant compared to your total income. You can deduct medical expenses in excess of 10% of your AGI. With the ACA kicking in - I don't see how would people even get to that. If your AGI is low you get subsidies for insurance, and the insurance keeps your expenses capped. For self-employed and employed, insurance premiums are pre-tax (i.e.: not even added to your AGI). Principle for mortgage is not deductible because it is not an expense - it is equity. You own an asset, don't you? You do get the standard deduction, even if your itemized (real) deductions are less - business don't get that. You also get an exemption amount (for your basic living needs), which businesses don't get. You can argue about the amounts - but it is there. In some States (like California) renters get tax breaks for renting, depending on the AGI. CA renters credit is phasing out at AGI of about $60K, which is pretty high.", "title": "" }, { "docid": "470215", "text": "&gt; Its a no, there should be no taxes on anyone, only service providers and voluntary customers. Last time you made this claim I pointed you to [a video on the US's Articles of Confederation](https://www.youtube.com/watch?v=C6rHSiN0vKk) and you never responded. Perhaps you'll muster up the courage this time. The Articles of Confederation was set up very similar to what you are proposing. Why do you think that government failed?", "title": "" }, { "docid": "312493", "text": "When you itemize your deductions, you get to deduct all the state income tax that was taken out of your paycheck last year (not how much was owed, but how much was withheld). If you deducted this last year, then you need to add in any amount that you received in state income tax refunds last year to your taxes this year, to make up for the fact that you ended up deducting more state income tax than was really due to the state. If you took the standard deduction last year instead of itemizing, then you didn't deduct your state income tax withholding last year and you don't need to claim your refund as income this year. Also, if you itemized, but chose to take the state sales tax deduction instead of the state income tax deduction, you also don't need to add in the refund as income. For whatever reason, Illinois decided that you don't get a 1099-G. It might be that the amount of the refund was too small to warrant the paperwork. It might be that they screwed up. But if you deducted your state income tax withholding on last year's tax return, then you need to add the state tax refund you got last year on line 10 of this year's 1040, whether or not the state issued you a form or not. Take a look at the Line 10 instructions starting on page 22 of the 1040 instructions to see if you have any unusual situations covered there that you didn't mention here. (For example, if you received a refund check for multiple years last year.) Then check your tax return from last year to verify that you deducted your state income tax withholding on Schedule A. If you did, then this year add the refund you got from the state to line 10 of this year's 1040.", "title": "" }, { "docid": "500705", "text": "\"First of all, it is absolutely **not** constitutional for any branch of the US government to outsource its primary functions to a private corporation. But, more to your point, the constitution provides that \"\"no state shall make any thing but gold and silver coin a tender in payment of debts.\"\" They will argue that Federal Reserve notes are unbacked, that taxes are voluntary, that Washington D.C. is not a state, that the FED is not private, or even (sometimes) that the gold standard is still in force. But each of those is contradicted by their actions.\"", "title": "" }, { "docid": "510413", "text": "\"This is the best tl;dr I could make, [original](https://www.bloomberg.com/news/articles/2017-07-06/-voluntary-tax-plan-as-expected-fails-miserably-in-norway) reduced by 75%. (I'm a bot) ***** &gt; &amp;quot;The tax scheme was set up to allow those who want to pay more taxes to do so in a simple and straightforward way,&amp;quot; Finance Minister Siv Jensen said in an emailed comment. &gt; The government responded by aggressively cutting taxes and tapping into the country&amp;#039;s massive wealth fund for the first time. &gt; Ironically, it was Store, whose net worth is $8 million, who prodded the government into action by complaining earlier this year that he had ended up paying less taxes under the current administration. ***** [**Extended Summary**](http://np.reddit.com/r/autotldr/comments/6m0s27/liberals_dont_want_to_pay_for_their_hobbies_they/) | [FAQ](http://np.reddit.com/r/autotldr/comments/31b9fm/faq_autotldr_bot/ \"\"Version 1.65, ~162232 tl;drs so far.\"\") | [Feedback](http://np.reddit.com/message/compose?to=%23autotldr \"\"PM's and comments are monitored, constructive feedback is welcome.\"\") | *Top* *keywords*: **government**^#1 **taxes**^#2 **pay**^#3 **tax**^#4 **more**^#5\"", "title": "" }, { "docid": "135202", "text": "I feel like the economics based on slave labor should have a name but I can't think of one. It's not really capitalist because that would require a voluntary trade and slave labor is not voluntary. But in economic theory slavery can be powerful. The Nazi's really surprised the allied planners with how effective their use of slave labor really was.", "title": "" }, { "docid": "115884", "text": "For a 401(k), only contributions that you make for the current tax year through payroll deduction are tax-deductible. Those contributions are subtracted off of your income for your W-2 Box 1 income amount. If you make a manual contribution to your 401(k) outside of that, it is not tax deductible, and there is nowhere on your Form 1040 to deduct it. Your commuter benefits are also paid for out of payroll deduction and deducted on your W-2, so this is not an option, either. You could contribute to a traditional IRA for last year up to your tax return deadline, and deduct the amount on Form 1040 Line 32. However, because you have access to a retirement plan at work, your IRA contribution is only tax deductible if your income is below certain limits.", "title": "" }, { "docid": "262960", "text": "You can always reduce the income by the direct expenses required to earn it, and figure out whether it is ultimately a net profit or loss. The net profit is taxable income. The loss may be tax deductible if the underlying thing is tax deductible. For the book, the $50 revenue required a $100 expense, so that's a $50 net loss. You don't owe any income tax since it's a loss. You could take the loss as a tax deduction if you have a business trading books, or if buying the book would be tax deductible for some reason. Note that in the latter case you can only deduct the $50 not the $100. For the airline ticket, it is to compensate you for the losses you took as a result if the delayed flight. So you tally up the $22 meal you had in the airport waiting for news, the $110 on the motel room you rented or forfeited, any other way you can peg a cash value to any losses you took. Total them up, again, a net loss is only deductible if the travel is already deductible. Note that if the actual expenses (book, flight) were tax deductible for some reason, the cash-back reduces the amount of your tax deduction, so it has the same effect as the sale/gift being taxable income.", "title": "" }, { "docid": "144751", "text": "\"There's currently not much reason to keep around a long-term non-deductible Traditional IRA in my opinion -- a Roth IRA is almost strictly better. Think about it: a non-deductible Traditional IRA vs. a Roth IRA of the same amount. In both cases, contributions are after-tax (so no tax deduction). But when you withdraw, for the Roth IRA you don't have to pay tax, and for the non-deductible Traditional IRA, you have to pay tax on the \"\"earnings\"\". A Roth IRA can be contributed to at pretty much any income level, thanks to the backdoor Roth IRA process (which uses a temporary non-deductible Traditional IRA in the process). So there is not much reason for a long-term non-deductible Traditional IRA. As for your question, a non-deductible Traditional IRA vs. a taxable account. Well, a non-deductible Traditional IRA is contributed to with after-tax money, and taxed on the earnings only on withdrawal. So the taxation is almost identical to things like stocks and homes, where the gain is not realized until the thing is sold. However, compared to things like savings accounts and bonds, where you get taxed on the interest yearly, it is much better. Every time you get taxed on gains like this, it is taxing gains earned from after-tax money, so if you think of an amount of money as being equivalent to the amount of money it grows to over time (time value of money), then it is taxing money that is (or grown from money that is) already taxed. So it is better to have this only happen at the end at withdrawal than every year.\"", "title": "" }, { "docid": "139059", "text": "\"Summary: It's because you are effectively contributing more money in the second case, so you have more money at the end. The effect of being covered by an employer retirement plan (in the case of a 401(k), that means either you or your employer contributed to it during the year) is that it prevents you from deducting Traditional IRA contributions unless your income is below a very low level (for Single filing status, it phases out at an MAGI of between $62k and $72k). Since you are unable to deduct the Traditional IRA contribution, but you entered that you are still making the full $5500 contribution every year, that means you are making a non-deductible contribution of $5500 every year instead of a deductible contribution. Nondeductible contributions are \"\"after-tax\"\", whereas deductible contributions are \"\"pre-tax\"\" (because your taxable income is reduced by the amount of the contribution, so you effectively don't pay income tax on the income you used to contribute). $1 of pre-tax money is not the same as $1 of after-tax money. If your marginal tax rate is 25%, then $1 of pre-tax money is equivalent to $0.75 of after-tax money. However, since in both cases you are putting in the same nominal amount of contribution ($5500), but one is pre-tax and one is after-tax, in the after-tax case you are effectively contributing more money, i.e. more money is taken out from your bank account that year. The $5500 pre-tax contribution is equivalent to only $5500 * 0.75 = $4125 after-tax, i.e. you are only short $4125 from your bank account at the end of the year after making a $5500 deductible contribution, whereas you are short $5500 after making a $5500 non-deductible contribution, so it's not a fair comparison. The non-deductible Traditional IRA contributions are not taxed when withdrawn (though the earnings earned from those contributions are still taxed), so that's why you are left with a greater amount. This is a similar situation to what happens when you try to compare a $5500 deductible Traditional IRA contribution to a $5500 Roth IRA contribution -- it will look like the Roth IRA case leaves you with much more money, but that's again because you are effectively contributing more money, because the Roth IRA contribution is after-tax, so it's not a fair comparison. (The Roth IRA case will produce a much greater \"\"advantage\"\" than the non-deductible Traditional IRA contribution case, because for a Roth IRA, both the contributions and earnings will not be taxed at withdrawal.)\"", "title": "" }, { "docid": "343766", "text": "In the US, mortgage payments are not deductible. What is deductible is the mortgage interest (to a limit). That, as well, is not deductible unconditionally, but rather as part of your itemized deductions on Schedule A of your yearly tax return. So if you're married and have a standard deduction of $12600 a year, live in a state with no state income tax, and your property tax and the mortgage interest are less than your standard deduction - you will not be getting any tax benefit whatsoever. That is, in fact, the case for many, if not majority, of the US mortgage payers. So in order to get a proper estimate, you need to take into account all the aspects of your tax calculations, which are by nature quite personal, and simulate the changes with the mortgage interest deduction. Most tax preparation software will allow you creating multiple files, so you can run the numbers for different scenarios.", "title": "" }, { "docid": "62281", "text": "\"Click on the ? icon next to \"\"Employer Plan\"\". This is used to determine if you can deduct your annual contributions from your taxes. For more information on how an employer plan can affect your IRA tax deduction, see the definition for non-deductible contributions. So, we look there: The total of your Traditional IRA contributions that were deposited without a tax deduction. Traditional IRA contributions are normally tax deductible. However, if you have an employer-sponsored retirement plan, such as a 401(k), your tax deduction may be limited. The $20K difference between $272K and $252K just happens to be $15% of $132,500 which is the amount of your non-deductible contributions.\"", "title": "" }, { "docid": "105264", "text": "\"Actually, the other answer isn't strictly correct. It's an estimate, giving a lower bound that gets less accurate as income increases. Consider: U.S. income tax is based on a progressive tax system where there are income bracket levels with increasing tax rates. Example: Given U.S. 2009 federal tax rates for an individual filing as \"\"single\"\": Imagine somebody making $100000. Assuming no other credits, deductions, or taxes, then income tax based on the above brackets & rates would be calculated as follows: Meaning the average tax rate for the single individual earning $100,000 is 21.72%. However, a pre-tax deduction from that income actually comes off at the top marginal tax rate. Consider the same calculation but with taxable income reduced to $99,000 instead (i.e. simulating a pre-tax $1000 deduction): That's a difference of $280, which is more than the $217.20 savings that would have been estimated if just using the average tax rate method. Consequently, when trying to determine how much money would be saved by a tax deduction, it makes better sense to estimate using the marginal tax rate, which in this case was 28%. It gets a little trickier if the deduction crosses a bracket boundary. (Left as an exercise to the reader :-) Finally, in the case of the deduction being discussed, it also looks like payroll FICA taxes paid by the employee (Social Security's 6.2%, and Medicare's 1.45%) would be avoided as well; so add that to the marginal tax rate savings. The surest way to know how much would be saved, though, would be to do one's income tax return calculation without the deduction, and then with, and compare the numbers. Tax software can make this very easy to do.\"", "title": "" }, { "docid": "401146", "text": "\"There are tax free bonds in the United States. They are for things like public housing and other urban projects. They are tax free for everyone but only rich people buy them. Why? The issue is that the tax free nature of the bond is included in its yield. So rather than yielding say a 5% return, they figure that the owner is getting 20% off due to not paying taxes. As a result, they only give a 4% return but are as risky as a 5% return investment. Net result, only rich people invest in tax free bonds. \"\"Rich\"\" is defined here to mean people paying a 20% tax on long term investment returns. Or take the State and Local Tax (SALT) deduction, which has been in the news recently. Again, it is technically open to everyone. But there is also a standard deduction that is open to everyone. For the typical family, state and local taxes might be 5% of income. So for a family making $100k a year, that's $5k. The same family can take a $13k or so standard deduction instead of itemizing. So why would they take the smaller deduction? As a practical matter, two groups take the SALT deduction. People rich enough to pay more than $13k in state and local taxes and people who also take the mortgage interest deduction. So it helps a lot of people who are rich quite a bit. And it helps a few middle class people some. But if you are lower middle class with a $30k mortgage on a tiny house and paying 4% interest, then that's only $1200 a year. Add in property taxes of $3000 and SALT of $2.8k and that's only $7k. Even if the person gives $3k to charity, the $13k deduction is a lot better and requires less paperwork. Contrast that with someone who has $500k mortgage at 3.6% interest. That's $18k in interest alone. Add in a SALT of $7k and property taxes of $50k, and there's $75k of itemized deductions, much better than $13k. Now a $7k donation to charity is entirely deductible. And even after the mortgage interest deduction goes away, the other $64k remains.\"", "title": "" }, { "docid": "404587", "text": "The general idea of the PRPP is so that small business who cannot afford to offer a plan alone will be able to pool resources with others along with self-employed to create voluntary, defined-contribution pension plans that would be managed by private sector financial institutions. The PRPP concept would offer more options to individuals as well as small and medium-sized businesses - Tax Rules for Pooled Registered Pension Plans You can also find an overview here THE NEW PRPP – A Pension for the Pension-Less", "title": "" }, { "docid": "277353", "text": "If you have multiple accounts, you have to empty them all before you can deduct any losses. Your loss is not a capital loss, its a deduction. It is calculated based on the total amount you have withdrawn from all your Roth IRA's, minus the total basis. It will be subject to the 2% AGI treshhold (i.e.: if your AGI is > 100K, none of it is deductible, and you have to itemize to get it). Bottom line - think twice. Summarizing the discussion in comments: If you have a very low AGI, I would guess that your tax liability is pretty low as well. Even if you deduct the whole $2K, and all of it is above the other deductions you have (which in turn is above the standard deduction of almost $6K), you save say $300 if you're in 15% tax bracket. That's the most savings you have. However I'm assuming something here: I'm assuming that you're itemizing your deductions already and they're above the standard deduction. This is very unlikely, with such a low income. You don't have state taxes to deduct, you probably don't spend a lot to deduct sales taxes, and I would argue that with the low AGI you probably don't own property, and if you do - you don't have a mortgage with a significant interest on it. You can be in 15% bracket with AGI between (roughly) $8K and $35K, i.e.: you cannot deduct between $160 and $750 of the $2K, so it's already less than the maximum $300. If your AGI is $8K, the deduction doesn't matter, EIC might cover all of your taxes anyway. If your AGI is $30K, you can deduct only $1400, so if you're in the 15% bracket - you saved $210. That, again, assuming it's above your other deductions, which in turn are already above the standard deduction. Highly unlikely. As I said in the comments - I do not think you can realistically save on taxes because of this loss in such a manner.", "title": "" } ]
631
Inhibiting HDAC6 increases survival of mice with ARID1A mutated tumors.
[ { "docid": "5468807", "text": "ARID1A, encoding a subunit of the SWI/SNF chromatin-remodelling complex, is the most frequently mutated epigenetic regulator across all human cancers. ARID1A and TP53 mutations are typically mutually exclusive. Therapeutic approaches that correlate with this genetic characteristic remain to be explored. Here, we show that HDAC6 activity is essential in ARID1A-mutated ovarian cancers. Inhibition of HDAC6 activity using a clinically applicable small-molecule inhibitor significantly improved the survival of mice bearing ARID1A-mutated tumours. This correlated with the suppression of growth and dissemination of ARID1A-mutated, but not wild-type, tumours. The dependence on HDAC6 activity in ARID1A-mutated cells correlated with a direct transcriptional repression of HDAC6 by ARID1A. HDAC6 inhibition selectively promoted apoptosis of ARID1A-mutated cells. HDAC6 directly deacetylates Lys120 of p53, a pro-apoptotic post-translational modification. Thus, ARID1A mutation inactivates the apoptosis-promoting function of p53 by upregulating HDAC6. Together, these results indicate that pharmacological inhibition of HDAC6 is a therapeutic strategy for ARID1A-mutated cancers.", "title": "ARID1A-mutated ovarian cancers depend on HDAC6 activity" } ]
[ { "docid": "9211173", "text": "BACKGROUND Ovarian clear-cell and endometrioid carcinomas may arise from endometriosis, but the molecular events involved in this transformation have not been described. METHODS We sequenced the whole transcriptomes of 18 ovarian clear-cell carcinomas and 1 ovarian clear-cell carcinoma cell line and found somatic mutations in ARID1A (the AT-rich interactive domain 1A [SWI-like] gene) in 6 of the samples. ARID1A encodes BAF250a, a key component of the SWI–SNF chromatin remodeling complex. We sequenced ARID1A in an additional 210 ovarian carcinomas and a second ovarian clear-cell carcinoma cell line and measured BAF250a expression by means of immunohistochemical analysis in an additional 455 ovarian carcinomas. RESULTS ARID1A mutations were seen in 55 of 119 ovarian clear-cell carcinomas (46%), 10 of 33 endometrioid carcinomas (30%), and none of the 76 high-grade serous ovarian carcinomas. Seventeen carcinomas had two somatic mutations each. Loss of the BAF250a protein correlated strongly with the ovarian clear-cell carcinoma and endometrioid carcinoma subtypes and the presence of ARID1A mutations. In two patients, ARID1A mutations and loss of BAF250a expression were evident in the tumor and contiguous atypical endometriosis but not in distant endometriotic lesions. CONCLUSIONS These data implicate ARID1A as a tumor-suppressor gene frequently disrupted in ovarian clear-cell and endometrioid carcinomas. Since ARID1A mutation and loss of BAF250a can be seen in the preneoplastic lesions, we speculate that this is an early event in the transformation of endometriosis into cancer. (Funded by the British Columbia Cancer Foundation and the Vancouver General Hospital–University of British Columbia Hospital Foundation.).", "title": "ARID1A mutations in endometriosis-associated ovarian carcinomas." }, { "docid": "33370", "text": "Glioblastomas are deadly cancers that display a functional cellular hierarchy maintained by self-renewing glioblastoma stem cells (GSCs). GSCs are regulated by molecular pathways distinct from the bulk tumor that may be useful therapeutic targets. We determined that A20 (TNFAIP3), a regulator of cell survival and the NF-kappaB pathway, is overexpressed in GSCs relative to non-stem glioblastoma cells at both the mRNA and protein levels. To determine the functional significance of A20 in GSCs, we targeted A20 expression with lentiviral-mediated delivery of short hairpin RNA (shRNA). Inhibiting A20 expression decreased GSC growth and survival through mechanisms associated with decreased cell-cycle progression and decreased phosphorylation of p65/RelA. Elevated levels of A20 in GSCs contributed to apoptotic resistance: GSCs were less susceptible to TNFalpha-induced cell death than matched non-stem glioma cells, but A20 knockdown sensitized GSCs to TNFalpha-mediated apoptosis. The decreased survival of GSCs upon A20 knockdown contributed to the reduced ability of these cells to self-renew in primary and secondary neurosphere formation assays. The tumorigenic potential of GSCs was decreased with A20 targeting, resulting in increased survival of mice bearing human glioma xenografts. In silico analysis of a glioma patient genomic database indicates that A20 overexpression and amplification is inversely correlated with survival. Together these data indicate that A20 contributes to glioma maintenance through effects on the glioma stem cell subpopulation. Although inactivating mutations in A20 in lymphoma suggest A20 can act as a tumor suppressor, similar point mutations have not been identified through glioma genomic sequencing: in fact, our data suggest A20 may function as a tumor enhancer in glioma through promotion of GSC survival. A20 anticancer therapies should therefore be viewed with caution as effects will likely differ depending on the tumor type.", "title": "Targeting A20 Decreases Glioma Stem Cell Survival and Tumor Growth" }, { "docid": "3173489", "text": "DNA replication stress promotes genome instability in cancer. However, the contribution of the replication stress response to the development of malignancies remains unresolved. The DNA replication stress response protein SMARCAL1 stabilizes DNA replication forks and prevents replication fork collapse, a cause of DNA breaks and apoptosis. While the fork regression/remodeling functions of SMARCAL1 have been investigated, its in vivo functions in replication stress and cancer are unclear. Using a gamma radiation (IR)-induced replication stress T-cell lymphoma mouse model, we observed a significant inhibition of lymphomagenesis in mice lacking one or both alleles of Smarcal1. Notably, a quarter of the Smarcal1-deficient mice did not develop tumors. Moreover, hematopoietic stem/progenitor cells (HSPCs) and developing thymocytes in Smarcal1-deficient mice showed increased DNA damage and apoptosis during the proliferation burst following IR and an impaired ability to repopulate the thymus after IR. Additionally, mice lacking Smarcal1 showed significant HSPC defects when challenged to respond to other replication stress stimuli. Thus, our data reveal the critical function of the DNA replication stress response and, specifically, Smarcal1 in hematopoietic cell survival and tumor development. Our results also provide important insight into the immunodeficiency observed in individuals with mutations in SMARCAL1 by suggesting that it is an HSPC defect.", "title": "Defective replication stress response inhibits lymphomagenesis and impairs lymphocyte reconstitution" }, { "docid": "9638032", "text": "Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common genetic cause of Parkinson's disease. LRRK2 is a multifunctional protein affecting many cellular processes and has been described to bind microtubules. Defective microtubule-based axonal transport is hypothesized to contribute to Parkinson's disease, but whether LRRK2 mutations affect this process to mediate pathogenesis is not known. Here we find that LRRK2 containing pathogenic Roc-COR domain mutations (R1441C, Y1699C) preferentially associates with deacetylated microtubules, and inhibits axonal transport in primary neurons and in Drosophila, causing locomotor deficits in vivo. In vitro, increasing microtubule acetylation using deacetylase inhibitors or the tubulin acetylase αTAT1 prevents association of mutant LRRK2 with microtubules, and the deacetylase inhibitor trichostatin A (TSA) restores axonal transport. In vivo knockdown of the deacetylases HDAC6 and Sirt2, or administration of TSA rescues both axonal transport and locomotor behavior. Thus, this study reveals a pathogenic mechanism and a potential intervention for Parkinson's disease.", "title": "Increasing microtubule acetylation rescues axonal transport and locomotor deficits caused by LRRK2 Roc-COR domain mutations" }, { "docid": "2727303", "text": "Stromal-interaction molecule 1 (STIM1) is an endoplasmic reticulum Ca(2+) storage sensor that promotes cell growth, migration, and angiogenesis in breast and cervical cancers. Here, we report that the microtubule-associated histone deacetylase 6 (HDAC6) differentially regulates activation of STIM1-mediated store-operated Ca(2+) entry (SOCE) between cervical cancer cells and normal cervical epithelial cells. Confocal microscopy of living cells indicated that microtubule integrity was necessary for STIM1 trafficking to the plasma membrane and interaction with Orai1, an essential pore subunit of SOCE. Cancer cells overexpressed both STIM1 and Orai1 compared with normal cervical epithelial cells. HDAC6 upregulation in cancer cells was accompanied by hypoacetylated α-tubulin. Tubastatin-A, a specific HDAC6 inhibitor, inhibited STIM1 translocation to plasma membrane and blocked SOCE activation in cancer cells but not normal epithelial cells. Genetic or pharmacologic inhibition of HDAC6 blocked STIM1 membrane trafficking and downstream Ca(2+) influx, as evidenced by total internal reflection fluorescent images and intracellular Ca(2+) determination. In contrast, HDAC6 inhibition did not affect interactions between STIM1 and the microtubule plus end-binding protein EB1. Analysis of surgical specimens confirmed that most cervical cancer tissues overexpressed STIM1 and Orai1, accompanied by hypoacetylated α-tubulin. Together, our results identify HDAC6 as a candidate target to disrupt STIM1-mediated SOCE as a general strategy to block malignant cell behavior.", "title": "Microtubule-associated histone deacetylase 6 supports the calcium store sensor STIM1 in mediating malignant cell behaviors." }, { "docid": "15435343", "text": "The inflammasome is a proteolysis complex that generates the active forms of the proinflammatory cytokines interleukin (IL)-1β and IL-18. Inflammasome activation is mediated by NLR proteins that respond to microbial and nonmicrobial stimuli. Among NLRs, NLRP3 senses the widest array of stimuli and enhances adaptive immunity. However, its role in antitumor immunity is unknown. Therefore, we evaluated the function of the NLRP3 inflammasome in the immune response using dendritic cell vaccination against the poorly immunogenic melanoma cell line B16-F10. Vaccination of Nlrp3(-/-) mice led to a relative 4-fold improvement in survival relative to control animals. Immunity depended on CD8(+) T cells and exhibited immune specificity and memory. Increased vaccine efficacy in Nlrp3(-/-) hosts did not reflect differences in dendritic cells but rather differences in myeloid-derived suppressor cells (MDSC). Although Nlrp3 was expressed in MDSCs, the absence of Nlrp3 did not alter either their functional capacity to inhibit T cells or their presence in peripheral lymphoid tissues. Instead, the absence of Nlrp3 caused a 5-fold reduction in the number of tumor-associated MDSCs found in host mice. Adoptive transfer experiments also showed that Nlrp3(-/-) MDSCs were less efficient in reaching the tumor site. Depleting MDSCs with an anti-Gr-1 antibody increased the survival of tumor-bearing wild-type mice but not Nlrp3(-/-) mice. We concluded that Nlrp3 was critical for accumulation of MDSCs in tumors and for inhibition of antitumor T-cell immunity after dendritic cell vaccination. Our findings establish an unexpected role for Nlrp3 in impeding antitumor immune responses, suggesting novel approaches to improve the response to antitumor vaccines by limiting Nlrp3 signaling.", "title": "The inflammasome component NLRP3 impairs antitumor vaccine by enhancing the accumulation of tumor-associated myeloid-derived suppressor cells." }, { "docid": "982650", "text": "BACKGROUND & AIMS Tumor cells survive hypoxic conditions by inducing autophagy. We investigated the roles of microRNAs (miRNAs) in regulating autophagy of hepatocellular carcinoma (HCC) cells under hypoxic conditions. METHODS We used gain- and loss-of-function methods to evaluate the effect of miRNAs on autophagy in human HCC cell lines (Huh7 and Hep3B) under hypoxic conditions. Autophagy was quantified by immunoblot, immunofluoresence, and transmission electron microscopy analyses, and after incubation of cells with bafilomycin A1. We used a luciferase reporter assay to confirm associations between miRNAs and their targets. We analyzed growth of HCC xenograft tumors in nude mice. RESULTS miR-375 was down-regulated in HCC cells and tissues; it inhibited autophagy under hypoxic conditions by suppressing the conversion of LC3I to LC3II and thereby autophagic flux. The ability of miR-375 to inhibit autophagy was independent of its ability to regulate 3'-phosphoinositide-dependent protein kinase-1-AKT-mammalian target of rapamycin signaling, but instead involved suppression of ATG7, an autophagy-associated gene. miR-375 bound directly to a predicted site in the 3' untranslated region of ATG7. Up-regulating miR-375 or down-regulating ATG7 inhibited mitochondrial autophagy of HCC cells, reduced the elimination of damaged mitochondria under hypoxia, increased release of mitochondrial apoptotic proteins, and reduced viability of HCC cells. In mice, xenograft tumors that expressed miR-375 had fewer autophagic cells, larger areas of necrosis, and grew more slowly than tumors from HCC cells that expressed lower levels of miR-375. CONCLUSIONS miR-375 inhibits autophagy by reducing expression of ATG7 and impairs viability of HCC cells under hypoxic conditions in culture and in mice. miRNAs that inhibit autophagy of cancer cells might be developed as therapeutics.", "title": "miR-375 inhibits autophagy and reduces viability of hepatocellular carcinoma cells under hypoxic conditions." }, { "docid": "2266471", "text": "Lymphangioleiomyomatosis (LAM), a multisystem disease of women, is manifest by the proliferation of smooth muscle-like cells in the lung resulting in cystic lung destruction. Women with LAM can also develop renal angiomyolipomas. LAM is caused by mutations in the tuberous sclerosis complex genes (TSC1 or TSC2), resulting in hyperactive mammalian Target of Rapamycin (mTOR) signaling. The mTOR inhibitor, Rapamycin, stabilizes lung function in LAM and decreases the volume of renal angiomyolipomas, but lung function declines and angiomyolipomas regrow when treatment is discontinued, suggesting that factors induced by mTORC1 inhibition may promote the survival of TSC2-deficient cells. Whether microRNA (miRNA, miR) signaling is involved in the response of LAM to mTORC1 inhibition is unknown. We identified Rapamycin-dependent miRNA in LAM patient angiomyolipoma-derived cells using two separate screens. First, we assayed 132 miRNA of known significance to tumor biology. Using a cut-off of >1.5-fold change, 48 microRNA were Rapamycin-induced, while 4 miRs were downregulated. In a second screen encompassing 946 miRNA, 18 miRs were upregulated by Rapamycin, while eight were downregulated. Dysregulation of miRs 29b, 21, 24, 221, 106a and 199a were common to both platforms and were classified as candidate \"RapamiRs. \" Validation by qRT-PCR confirmed that these microRNA were increased. miR-21, a pro-survival miR, was the most significantly increased by mTOR-inhibition (p<0.01). The regulation of miR-21 by Rapamycin is cell type independent. mTOR inhibition promotes the processing of the miR-21 transcript (pri-miR-21) to a premature form (pre-miR-21). In conclusion, our findings demonstrate that Rapamycin upregulates multiple miRs, including pro-survival miRs, in TSC2-deficient patient-derived cells. The induction of miRs may contribute to the response of LAM and TSC patients to Rapamycin therapy.", "title": "MicroRNA-21 is Induced by Rapamycin in a Model of Tuberous Sclerosis (TSC) and Lymphangioleiomyomatosis (LAM)" }, { "docid": "8133180", "text": "Germline mutations in the RET tyrosine kinase gene are responsible for the development of multiple endocrine neoplasia 2A and 2B (MEN2A and MEN2B). However, knowledge of the fundamental principles that determine the mutant RET-mediated signaling remains elusive. Here, we report increased expression of mitogen-activated protein kinase phosphatase-2 (MKP-2) in carcinomas developed in transgenic mice carrying RET with the MEN2A mutation (RET-MEN2A). The expression of MKP-2 was not only induced by RET-MEN2A or RET-MEN2B mutant proteins but also by the activation of endogenous RET by its ligand, glial cell line-derived neurotrophic factor (GDNF). MKP-2 expression was also evident in the MKK-f cell line, which was established from a mammary tumor developed in a RET-MEN2A transgenic mouse. Inhibition of MKP-2 attenuated the in vitro and in vivo proliferation of MKK-f cells, which was mediated by the suppression of cyclin B1 expression. Furthermore, we found that MKP-2 is highly expressed in medullary thyroid carcinomas derived from MEN2A patients. These findings suggest that the increased expression of MKP-2 may play a crucial role in oncogenic signaling downstream of mutant RET, leading to deregulation of cell cycle.", "title": "Roles of induced expression of MAPK phosphatase-2 in tumor development in RET-MEN2A transgenic mice" }, { "docid": "30658796", "text": "Neoplastic cells are genetically unstable. Strategies that target pathways affecting genome instability can be exploited to disrupt tumor cell growth, potentially with limited consequences to normal cells. Chromosomal instability (CIN) is one type of genome instability characterized by mitotic defects that increase the rate of chromosome mis-segregation. CIN is frequently caused by extra centrosomes that transiently disrupt normal bipolar spindle geometry needed for accurate chromosome segregation. Tumor cells survive with extra centrosomes because of biochemical pathways that cluster centrosomes and promote chromosome segregation on bipolar spindles. Recent work shows that targeted inhibition of these pathways prevents centrosome clustering and forces chromosomes to segregate to multiple daughter cells, an event triggering apoptosis that we refer to as anaphase catastrophe. Anaphase catastrophe specifically kills tumor cells with more than 2 centrosomes. This death program can occur after genetic or pharmacologic inhibition of cyclin dependent kinase 2 (Cdk2) and is augmented by combined treatment with a microtubule inhibitor. This proapoptotic effect occurs despite the presence of ras mutations in cancer cells. Anaphase catastrophe is a previously unrecognized mechanism that can be pharmacologically induced for apoptotic death of cancer cells and is, therefore, appealing to engage for cancer therapy and prevention.", "title": "Anaphase catastrophe is a target for cancer therapy." }, { "docid": "25726838", "text": "The role of immune responses in tumor development is a central issue for tumor biology and immunology. IL-17 is an important cytokine for inflammatory and autoimmune diseases. Although IL-17-producing cells are detected in cancer patients and tumor-bearing mice, the role of IL-17 in tumor development is controversial, and mechanisms remain to be fully elucidated. In the current study, we found that the development of tumors was inhibited in IL-17R-deficient mice. A defect in IFN-gammaR increased tumor growth, whereas tumor growth was inhibited in mice that were deficient in both IL-17R and IFN-gammaR compared with wild-type animals. Further experiments showed that neutralization of IL-17 by Abs inhibited tumor growth in wild-type mice, whereas systemic administration of IL-17 promoted tumor growth. The IL-17R deficiency increased CD8 T cell infiltration, whereas it reduced the infiltration of myeloid-derived suppressor cells (MDSCs) in tumors. In contrast, administration of IL-17 inhibited CD8 T cell infiltration and increased MDSCs in tumors. Further analysis indicated that IL-17 was required for the development and tumor-promoting activity of MDSCs in tumor-bearing mice. These data demonstrate that IL-17-mediated responses promote tumor development through the induction of tumor-promoting microenvironments at tumor sites. IL-17-mediated regulation of MDSCs is a primary mechanism for its tumor-promoting effects. The study provides novel insights into the role of IL-17 in tumor development and has major implications for targeting IL-17 in treatment of tumors.", "title": "IL-17 promotes tumor development through the induction of tumor promoting microenvironments at tumor sites and myeloid-derived suppressor cells." }, { "docid": "14874811", "text": "Oxygen (O2) deprivation, or hypoxia, has profound effects on cell metabolism and growth. Cells can adapt to low O2 in part through activation of hypoxia-inducible factor (HIF). We report here that hypoxia inhibits mRNA translation by suppressing multiple key regulators, including eIF2alpha, eEF2, and the mammalian target of rapamycin (mTOR) effectors 4EBP1, p70S6K, and rpS6, independent of HIF. Hypoxia results in energy starvation and activation of the AMPK/TSC2/Rheb/mTOR pathway. Hypoxic AMP-activated protein kinase (AMPK) activation also leads to eEF2 inhibition. Moreover, hypoxic effects on cellular bioenergetics and mTOR inhibition increase over time. Mutation of the TSC2 tumor suppressor gene confers a growth advantage to cells by repressing hypoxic mTOR inhibition and hypoxia-induced G1 arrest. Together, eIF2alpha, eEF2, and mTOR inhibition represent important HIF-independent mechanisms of energy conservation that promote survival under low O2 conditions.", "title": "Hypoxia-induced energy stress regulates mRNA translation and cell growth." }, { "docid": "8671456", "text": "BACKGROUND Interleukin-24 (IL-24) is a cytokine that belongs to the IL-10 family. It can selectively induce cancer cell apoptosis which has been utilized as a cancer gene therapy strategy. METHODS A recombinant type five adenovirus containing IL-24 gene (designated CNHK600-IL24) was constructed, whose replication is activated only in tumor cells. The replication of CNHK600-IL24 in breast tumor cells and fibroblasts were assessed by TCID50 and MTT assay; the secretion of IL-24 was measured by ELISA and western blotting. The in vivo anti-tumor effect of CNHK600-IL24 was investigated in nude mice carrying orthotopic or metastatic breast tumor. RESULTS We observed that CNHK600-IL24 could replicate efficiently and resulted in high level IL-24 expression and massive cell death in human breast cancer cell MDA-MB-231 but not in normal fibroblast cell MRC-5. In addition, orthotopic breast tumor growth in the nude mice model was significantly suppressed when CNHK600-IL24 was administered. In the metastatic model generated by tail vein injection, CNHK600-IL24 virotherapy significantly improved survival compared with the same virus expressing EGFP (median survival CNHK600-IL24, 55 days vs. CNHK600-EGFP, 41 day, p < 0.05 Mantal-Cox test). A similar phenomenon was observed in the metastatic model achieved by left ventricular injection as suggested by in vivo luminescence imaging of tumor growth. CONCLUSION The oncolytic adenovirus armed with IL-24, which exhibited enhanced anti-tumor activity and improved survival, is a promising candidate for virotherapy of breast cancer.", "title": "Oncolytic adenovirus armed with IL-24 Inhibits the growth of breast cancer in vitro and in vivo" }, { "docid": "17755060", "text": "Tumor cells have high-energetic and anabolic needs and are known to adapt their metabolism to be able to survive and keep proliferating under conditions of nutrient stress. We show that PKCζ deficiency promotes the plasticity necessary for cancer cells to reprogram their metabolism to utilize glutamine through the serine biosynthetic pathway in the absence of glucose. PKCζ represses the expression of two key enzymes of the pathway, PHGDH and PSAT1, and phosphorylates PHGDH at key residues to inhibit its enzymatic activity. Interestingly, the loss of PKCζ in mice results in enhanced intestinal tumorigenesis and increased levels of these two metabolic enzymes, whereas patients with low levels of PKCζ have a poor prognosis. Furthermore, PKCζ and caspase-3 activities are correlated with PHGDH levels in human intestinal tumors. Taken together, this demonstrates that PKCζ is a critical metabolic tumor suppressor in mouse and human cancer.", "title": "Control of Nutrient Stress-Induced Metabolic Reprogramming by PKCζ in Tumorigenesis" }, { "docid": "43014661", "text": "Xeroderma pigmentosum variant (XPV) patients with mutations in the DNA polymerase eta (pol eta) gene are hypersensitive to sunlight and have greatly increased susceptibility to sunlight-induced skin cancer. Consistent with the ability of Pol eta to efficiently bypass UV light-induced cyclobutane pyrimidine dimers, XPV cells lacking Pol eta have diminished capacity to replicate UV-damaged DNA and are sensitive to UV light-induced killing and mutagenesis. To better understand these and other Pol eta functions, we generated Pol eta-deficient mice. Mice homozygous for a null mutation in pol eta are viable, fertile, and do not show any obvious spontaneous defects during the first year of life. However, fibroblasts derived from these mutant mice are sensitive to killing by exposure to UV light, and all Pol eta-deficient mice develop skin tumors after UV irradiation, in contrast to the wild-type littermate controls that did not develop such tumors. These results and biochemical studies of translesion synthesis by mouse Pol eta indicate that Pol eta-dependent bypass of cyclobutane pyrimidine dimers suppresses UV light-induced skin cancer in mice. Moreover, 37.5% of pol eta heterozygous mice also developed skin cancer during 5 months after a 5-month exposure to UV light, suggesting that humans who are heterozygous for mutations in pol eta may also have an increased risk of skin cancer.", "title": "Increased susceptibility to UV-induced skin carcinogenesis in polymerase eta-deficient mice." }, { "docid": "7317051", "text": "Pancreatic ductal adenocarcinoma (PDA) represents an unmet therapeutic challenge. PDA is addicted to the activity of the mutated KRAS oncogene which is considered so far an undruggable therapeutic target. We propose an approach to target KRAS effectively in patients using RNA interference. To meet this challenge, we have developed a local prolonged siRNA delivery system (Local Drug EluteR, LODER) shedding siRNA against the mutated KRAS (siG12D LODER). The siG12D LODER was assessed for its structural, release, and delivery properties in vitro and in vivo. The effect of the siG12D LODER on tumor growth was assessed in s.c. and orthotopic mouse models. KRAS silencing effect was further assessed on the KRAS downstream signaling pathway. The LODER-encapsulated siRNA was stable and active in vivo for 155 d. Treatment of PDA cells with siG12D LODER resulted in a significant decrease in KRAS levels, leading to inhibition of proliferation and epithelial-mesenchymal transition. In vivo, siG12D LODER impeded the growth of human pancreatic tumor cells and prolonged mouse survival. We report a reproducible and safe delivery platform based on a miniature biodegradable polymeric matrix, for the controlled and prolonged delivery of siRNA. This technology provides the following advantages: (i) siRNA is protected from degradation; (ii) the siRNA is slowly released locally within the tumor for prolonged periods; and (iii) the siG12D LODER elicits a therapeutic effect, thereby demonstrating that mutated KRAS is indeed a druggable target.", "title": "Mutant KRAS is a druggable target for pancreatic cancer." }, { "docid": "32852283", "text": "BACKGROUND Although zoledronic acid (ZOL), a third-generation nitrogen-containing bisphosphonate, has been identified as an attractive therapeutic agent against breast cancer, prostate cancer, multiple myeloma as well as small-cell lung cancer (SCLC), as best as we are aware, the anti-tumor effect of ZOL upon non-small-cell lung cancer (NSCLC) remains to be effectively investigated. This study examined the effects of ZOL upon the line-1 tumor cell, using a murine lung adenocarcinoma cell line similar to the behavior of human lung adenocarcinoma. METHODS We investigated the anti-tumor effects of ZOL (3-100 microM) on line-1 tumor cells in vitro, including cellular proliferation, by means of an MTT assay, cell-cycle analysis by flow cytometry and by assessing the level of apoptosis by annexin V/propidium iodide (PI) and 4'-6-diamidino-2-phenylindole (DAPI) staining. Further, we evaluated the growth and survival of line-1 tumor cells following ZOL treatment (1 microg/kg/week) using an animal model. We also examined the in vivo cell-cycle pattern using lacZ-expressing line-1 cells (line-1/lacZ). RESULTS ZOL significantly slowed the line-1 tumor growth in a dose-dependent manner in vitro. The treated line-1 tumor cells typically arrested at the S/G2/M-phase of the cell-cycle following ZOL exposure, but no apoptotic cells could be detected by either annexin V/PI or DAPI staining. When the ZOL was washed out, the drug-inhibited cells continued to proliferate again and the cell-cycle prolongation elicited earlier by the drug, then disappeared. Within 72-96 h following drug removal, the cell-cycle of the treated cells revealed a similar distribution to that of the untreated controls. In vivo studies demonstrated that ZOL significantly slowed the line-1 tumor growth. Indeed, mice lived significantly longer when they had been ZOL-treated than was the case for untreated mice (p<0.05). Using line-1/lacZ cells, the in vivo cell-cycle distribution of line-1 tumor cells subsequent to ZOL exposure revealed S/G2/M-phase arrest that was identical to the in vitro culture. CONCLUSIONS ZOL maintains the potential to reduce tumor burden and prolong survival for murine pulmonary adenocarcinoma. The flow cytometrical analysis of cell-cycle demonstrated that ZOL induces no apoptosis but is able to arrest line-1 tumor cells at the S/G2/M-phase. Although the clinical relevance of these results warrants verification for human lung cancer patients, ZOL combined with chemotherapy and/or radiotherapy appears to be a new therapeutic strategy for the effective treatment of NSCLC.", "title": "Zoledronic acid is unable to induce apoptosis, but slows tumor growth and prolongs survival for non-small-cell lung cancers." }, { "docid": "33677323", "text": "MicroRNAs are frequently deregulated in cancer. Here we show that miR-22 is upregulated in myelodysplastic syndrome (MDS) and leukemia and its aberrant expression correlates with poor survival. To explore its role in hematopoietic stem cell function and malignancy, we generated transgenic mice conditionally expressing miR-22 in the hematopoietic compartment. These mice displayed reduced levels of global 5-hydroxymethylcytosine (5-hmC) and increased hematopoietic stem cell self-renewal accompanied by defective differentiation. Conversely, miR-22 inhibition blocked proliferation in both mouse and human leukemic cells. Over time, miR-22 transgenic mice developed MDS and hematological malignancies. We also identify TET2 as a key target of miR-22 in this context. Ectopic expression of TET2 suppressed the miR-22-induced phenotypes. Downregulation of TET2 protein also correlated with poor clinical outcomes and miR-22 overexpression in MDS patients. Our results therefore identify miR-22 as a potent proto-oncogene and suggest that aberrations in the miR-22/TET2 regulatory network are common in hematopoietic malignancies.", "title": "The oncogenic microRNA miR-22 targets the TET2 tumor suppressor to promote hematopoietic stem cell self-renewal and transformation." }, { "docid": "28334217", "text": "Glutaminase (GLS), which converts glutamine to glutamate, plays a key role in cancer cell metabolism, growth, and proliferation. GLS is being explored as a cancer therapeutic target, but whether GLS inhibitors affect cancer cell-autonomous growth or the host microenvironment or have off-target effects is unknown. Here, we report that loss of one copy of Gls blunted tumor progression in an immune-competent MYC-mediated mouse model of hepatocellular carcinoma. Compared with results in untreated animals with MYC-induced hepatocellular carcinoma, administration of the GLS-specific inhibitor bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) prolonged survival without any apparent toxicities. BPTES also inhibited growth of a MYC-dependent human B cell lymphoma cell line (P493) by blocking DNA replication, leading to cell death and fragmentation. In mice harboring P493 tumor xenografts, BPTES treatment inhibited tumor cell growth; however, P493 xenografts expressing a BPTES-resistant GLS mutant (GLS-K325A) or overexpressing GLS were not affected by BPTES treatment. Moreover, a customized Vivo-Morpholino that targets human GLS mRNA markedly inhibited P493 xenograft growth without affecting mouse Gls expression. Conversely, a Vivo-Morpholino directed at mouse Gls had no antitumor activity in vivo. Collectively, our studies demonstrate that GLS is required for tumorigenesis and support small molecule and genetic inhibition of GLS as potential approaches for targeting the tumor cell-autonomous dependence on GLS for cancer therapy.", "title": "Targeted inhibition of tumor-specific glutaminase diminishes cell-autonomous tumorigenesis." }, { "docid": "9737083", "text": "We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.", "title": "The Somatic Genomic Landscape of Glioblastoma" }, { "docid": "41650417", "text": "PURPOSE To evaluate the effect of KRAS and epidermal growth factor receptor (EGFR) genotype on the response to erlotinib treatment in the BR.21, placebo-controlled trial. PATIENTS AND METHODS We analyzed 206 tumors for KRAS mutation, 204 tumors for EGFR mutation, and 159 tumors for EGFR gene copy by fluorescent in situ hybridization (FISH). We reanalyzed EGFR deletion/mutation using two highly sensitive techniques that detect abnormalities in samples with 5% to 10% tumor cellularity. KRAS mutation was analyzed by direct sequencing. RESULTS Thirty patients (15%) had KRAS mutations, 34 (17%) had EGFR exon 19 deletion or exon 21 L858R mutations, and 61 (38%) had high EGFR gene copy (FISH positive). Response rates were 10% for wild-type and 5% for mutant KRAS (P = .69), 7% for wild-type and 27% for mutant EGFR (P = .03), and 5% for EGFR FISH-negative and 21% for FISH-positive patients (P = .02). Significant survival benefit from erlotinib therapy was observed for patients with wild-type KRAS (hazard ratio [HR] = 0.69, P = .03) and EGFR FISH positivity (HR = 0.43, P = .004) but not for patients with mutant KRAS (HR = 1.67, P = .31), wild-type EGFR (HR = 0.74, P = .09), mutant EGFR (HR = 0.55, P = .12), and EGFR FISH negativity (HR = 0.80, P = .35). In multivariate analysis, only EGFR FISH-positive status was prognostic for poorer survival (P = .025) and predictive of differential survival benefit from erlotinib (P = .005). CONCLUSION EGFR mutations and high copy number are predictive of response to erlotinib. EGFR FISH is the strongest prognostic marker and a significant predictive marker of differential survival benefit from erlotinib.", "title": "Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21." }, { "docid": "85665741", "text": "5247 Constitutive ERK signaling is common in human cancer and is often the result of activating mutations of BRAF, RAS and upstream receptor tyrosine kinases. Missense BRAF kinase domain mutations are frequently observed in melanoma, colon and thyroid cancers and less frequently in lung and other cancer types. The vast majority (>90%) involve a glutamic acid for valine substitution at codon 600 (V600E), which results in elevated BRAF kinase activity. BRAF kinase domain mutations with intermediate and impaired kinase activity have also been identified, most frequently in NSCLC. We have previously reported that tumors with V600E BRAF mutation are selectively sensitive to MEK inhibition. Using the potent and selective MEK1/2 inhibitor PD0325901 (Pfizer), we examined a panel of NSCLC cell lines with mutant EGFR, KRAS, and/or low, intermediate and high-activity BRAF kinase domain mutations for MEK dependence. In all but one case, EGFR, KRAS and BRAF mutations were mutually exclusive with the exception being a cell line with concurrent NRAS and intermediate activity BRAF mutations. Consistent with our prior results, NSCLC cells with V600E BRAF mutation were exquisitely sensitive to MEK inhibition (PD0325901 IC50 of 2nM). The proliferation of cells with non-V600E mutations, including those with high (G469A), intermediate (L597V) and impaired (G466V) kinase activities, was also MEK dependent with IC50’s ranging between 2.7 and 80 nM. Inhibition of MEK in these cells resulted in downregulation of cyclin D1 and G1 growth arrest, with variable induction of apoptosis. Despite high basal ERK activity, NSCLC tumor cells with EGFR mutation were uniformly resistant to MEK inhibition (at doses of up to 500nM), despite effective and prolonged inhibition of ERK phosphorylation. Tumor cells with RAS mutation had a more variable response, with some cell lines demonstrating sensitivity, while others were completely resistant. There was no correlation between basal ERK activity and sensitivity to MEK inhibition. A strong inverse correlation between Akt activity and PD0325901 sensitivity was observed. These results suggest that MEK inhibition may be useful therapeutically in tumors with V600E and non-V600E BRAF kinase domain mutations. The results also suggest that inhibition of both MEK and Akt signaling may be required in NSCLC tumors with high basal AKT activity.", "title": "BRAF mutation predicts for MEK-dependence in non-small cell lung cancer (NSCLC)." }, { "docid": "15570691", "text": "Activation of cyclin-dependent kinases 4 and 6 (cdk4/6) occurs in the majority of glioblastoma multiforme (GBM) tumors, and represents a promising molecular target for the development of small molecule inhibitors. In the current study, we investigated the molecular determinants and in vivo response of diverse GBM cell lines and xenografts to PD-0332991, a cdk4/6-specific inhibitor. In vitro testing of PD-0332991 against a panel of GBM cell lines revealed a potent G(1) cell cycle arrest and induction of senescence in each of 16 retinoblastoma protein (Rb)-proficient cell lines regardless of other genetic lesions, whereas 5 cell lines with homozygous inactivation of Rb were completely resistant to treatment. Short hairpin RNA depletion of Rb expression conferred resistance of GBM cells to PD-0332991, further demonstrating a requirement of Rb for sensitivity to cdk4/6 inhibition. PD-0332991 was found to efficiently cross the blood-brain barrier and proved highly effective in suppressing the growth of intracranial GBM xenograft tumors, including those that had recurred after initial therapy with temozolomide. Remarkably, no mice receiving PD-0332991 died as a result of disease progression while on therapy. Additionally, the combination of PD-0332991 and radiation therapy resulted in significantly increased survival benefit compared with either therapy alone. In total, our results support clinical trial evaluation of PD-0332991 against newly diagnosed as well as recurrent GBM, and indicate that Rb status is the primary determinant of potential benefit from this therapy.", "title": "Pharmacologic inhibition of cyclin-dependent kinases 4 and 6 arrests the growth of glioblastoma multiforme intracranial xenografts." }, { "docid": "15113221", "text": "Pathway-specific therapy is the future of cancer management. The oncogenic phosphatidylinositol 3-kinase (PI3K) pathway is frequently activated in solid tumors; however, currently, no reliable test for PI3K pathway activation exists for human tumors. Taking advantage of the observation that loss of PTEN, the negative regulator of PI3K, results in robust activation of this pathway, we developed and validated a microarray gene expression signature for immunohistochemistry (IHC)-detectable PTEN loss in breast cancer (BC). The most significant signature gene was PTEN itself, indicating that PTEN mRNA levels are the primary determinant of PTEN protein levels in BC. Some PTEN IHC-positive BCs exhibited the signature of PTEN loss, which was associated to moderately reduced PTEN mRNA levels cooperating with specific types of PIK3CA mutations and/or amplification of HER2. This demonstrates that the signature is more sensitive than PTEN IHC for identifying tumors with pathway activation. In independent data sets of breast, prostate, and bladder carcinoma, prediction of pathway activity by the signature correlated significantly to poor patient outcome. Stathmin, encoded by the signature gene STMN1, was an accurate IHC marker of the signature and had prognostic significance in BC. Stathmin was also pathway-pharmacodynamic in vitro and in vivo. Thus, the signature or its components such as stathmin may be clinically useful tests for stratification of patients for anti-PI3K pathway therapy and monitoring therapeutic efficacy. This study indicates that aberrant PI3K pathway signaling is strongly associated with metastasis and poor survival across carcinoma types, highlighting the enormous potential impact on patient survival that pathway inhibition could achieve.", "title": "Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity." }, { "docid": "9767444", "text": "Ovarian cancer is the most lethal of all gynecological cancers, and there is an urgent unmet need to develop new therapies. Epithelial ovarian cancer (EOC) is characterized by an immune suppressive microenvironment, and response of ovarian cancers to immune therapies has thus far been disappointing. We now find, in a mouse model of EOC, that clinically relevant doses of DNA methyltransferase and histone deacetylase inhibitors (DNMTi and HDACi, respectively) reduce the immune suppressive microenvironment through type I IFN signaling and improve response to immune checkpoint therapy. These data indicate that the type I IFN response is required for effective in vivo antitumorigenic actions of the DNMTi 5-azacytidine (AZA). Through type I IFN signaling, AZA increases the numbers of CD45+ immune cells and the percentage of active CD8+ T and natural killer (NK) cells in the tumor microenvironment, while reducing tumor burden and extending survival. AZA also increases viral defense gene expression in both tumor and immune cells, and reduces the percentage of macrophages and myeloid-derived suppressor cells in the tumor microenvironment. The addition of an HDACi to AZA enhances the modulation of the immune microenvironment, specifically increasing T and NK cell activation and reducing macrophages over AZA treatment alone, while further increasing the survival of the mice. Finally, a triple combination of DNMTi/HDACi plus the immune checkpoint inhibitor α-PD-1 provides the best antitumor effect and longest overall survival, and may be an attractive candidate for future clinical trials in ovarian cancer.", "title": "Epigenetic therapy activates type I interferon signaling in murine ovarian cancer to reduce immunosuppression and tumor burden." }, { "docid": "381602", "text": "UNLABELLED Immune cells promote the initial metastatic dissemination of carcinoma cells from primary tumors. In contrast to their well-studied functions in the initial stages of metastasis, the specific roles of immunocytes in facilitating progression through the critical later steps of the invasion-metastasis cascade remain poorly understood. Here, we define novel functions of neutrophils in promoting intraluminal survival and extravasation at sites of metastatic dissemination. We show that CD11b(+)/Ly6G(+) neutrophils enhance metastasis formation via two distinct mechanisms. First, neutrophils inhibit natural killer cell function, which leads to a significant increase in the intraluminal survival time of tumor cells. Thereafter, neutrophils operate to facilitate extravasation of tumor cells through the secretion of IL1β and matrix metalloproteinases. These results identify neutrophils as key regulators of intraluminal survival and extravasation through their cross-talk with host cells and disseminating carcinoma cells. SIGNIFICANCE This study provides important insights into the systemic contributions of neutrophils to cancer metastasis by identifying how neutrophils facilitate intermediate steps of the invasion-metastasis cascade. We demonstrate that neutrophils suppress natural killer cell activity and increase extravasation of tumor cells. Cancer Discov; 6(6); 630-49. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 561.", "title": "Neutrophils Suppress Intraluminal NK Cell-Mediated Tumor Cell Clearance and Enhance Extravasation of Disseminated Carcinoma Cells." }, { "docid": "9831859", "text": "Pancreatic stellate cells (PSC) produce the stromal reaction in pancreatic cancer, but their role in cancer progression is not fully elucidated. We examined the influence of PSCs on pancreatic cancer growth using (a) an orthotopic model of pancreatic cancer and (b) cultured human PSCs (hPSC) and human pancreatic cancer cell lines MiaPaCa-2 and Panc-1. Athymic mice received an intrapancreatic injection of saline, hPSCs, MiaPaCa-2 cells, or hPSCs + MiaPaCa-2. After 7 weeks, tumor size, metastases, and tumor histology were assessed. In vitro studies assessed the effect of cancer cell secretions on PSC migration and the effect of hPSC secretions on cancer cell proliferation, apoptosis, and migration. Possible mediators of the effects of hPSC secretions on cancer cell proliferation were examined using neutralizing antibodies. Compared with mice receiving MiaPaCa-2 cells alone, mice injected with hPSCs + MiaPaCa-2 exhibited (a) increased tumor size and regional and distant metastasis, (b) fibrotic bands (desmoplasia) containing activated PSCs within tumors, and (c) increased tumor cell numbers. In vitro studies showed that, in the presence of pancreatic cancer cells, PSC migration was significantly increased. Furthermore, hPSC secretions induced the proliferation and migration, but inhibited the apoptosis, of MiaPaCa-2 and Panc-1 cells. The proliferative effect of hPSC secretions on pancreatic cancer cells was inhibited in the presence of neutralizing antibody to platelet-derived growth factor. Our studies indicate a significant interaction between pancreatic cancer cells and stromal cells (PSCs) and imply that pancreatic cancer cells recruit stromal cells to establish an environment that promotes cancer progression.", "title": "Pancreatic stellate cells: partners in crime with pancreatic cancer cells." }, { "docid": "4325398", "text": "Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.", "title": "Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes" }, { "docid": "33387953", "text": "Activating mutations in genes encoding G protein α (Gα) subunits occur in 4-5% of all human cancers, but oncogenic alterations in Gβ subunits have not been defined. Here we demonstrate that recurrent mutations in the Gβ proteins GNB1 and GNB2 confer cytokine-independent growth and activate canonical G protein signaling. Multiple mutations in GNB1 affect the protein interface that binds Gα subunits as well as downstream effectors and disrupt Gα interactions with the Gβγ dimer. Different mutations in Gβ proteins clustered partly on the basis of lineage; for example, all 11 GNB1 K57 mutations were in myeloid neoplasms, and seven of eight GNB1 I80 mutations were in B cell neoplasms. Expression of patient-derived GNB1 variants in Cdkn2a-deficient mouse bone marrow followed by transplantation resulted in either myeloid or B cell malignancies. In vivo treatment with the dual PI3K-mTOR inhibitor BEZ235 suppressed GNB1-induced signaling and markedly increased survival. In several human tumors, mutations in the gene encoding GNB1 co-occurred with oncogenic kinase alterations, including the BCR-ABL fusion protein, the V617F substitution in JAK2 and the V600K substitution in BRAF. Coexpression of patient-derived GNB1 variants with these mutant kinases resulted in inhibitor resistance in each context. Thus, GNB1 and GNB2 alterations confer transformed and resistance phenotypes across a range of human tumors and may be targetable with inhibitors of G protein signaling.", "title": "Mutations in G protein beta subunits promote transformation and kinase inhibitor resistance" }, { "docid": "25513319", "text": "Metabolic pathway reprogramming is a hallmark of cancer cell growth and survival and supports the anabolic and energetic demands of these rapidly dividing cells. The underlying regulators of the tumor metabolic program are not completely understood; however, these factors have potential as cancer therapy targets. Here, we determined that upregulation of the oncogenic transcriptional coregulator steroid receptor coactivator 2 (SRC-2), also known as NCOA2, drives glutamine-dependent de novo lipogenesis, which supports tumor cell survival and eventual metastasis. SRC-2 was highly elevated in a variety of tumors, especially in prostate cancer, in which SRC-2 was amplified and overexpressed in 37% of the metastatic tumors evaluated. In prostate cancer cells, SRC-2 stimulated reductive carboxylation of α-ketoglutarate to generate citrate via retrograde TCA cycling, promoting lipogenesis and reprogramming of glutamine metabolism. Glutamine-mediated nutrient signaling activated SRC-2 via mTORC1-dependent phosphorylation, which then triggered downstream transcriptional responses by coactivating SREBP-1, which subsequently enhanced lipogenic enzyme expression. Metabolic profiling of human prostate tumors identified a massive increase in the SRC-2-driven metabolic signature in metastatic tumors compared with that seen in localized tumors, further implicating SRC-2 as a prominent metabolic coordinator of cancer metastasis. Moreover, SRC-2 inhibition in murine models severely attenuated the survival, growth, and metastasis of prostate cancer. Together, these results suggest that the SRC-2 pathway has potential as a therapeutic target for prostate cancer.", "title": "Coactivator SRC-2-dependent metabolic reprogramming mediates prostate cancer survival and metastasis." } ]
12700
Dwight D. Eisenhower worked with the Chinese government.
[ { "docid": "Dwight_D._Eisenhower", "text": "Dwight David `` Ike '' Eisenhower ( -LSB- ˈaɪzənˌhaʊ.ər -RSB- ; October 14 , 1890 -- March 28 , 1969 ) was an American politician and Army general who served as the 34th President of the United States from 1953 until 1961 . He was a five-star general in the United States Army during World War II and served as Supreme Commander of the Allied Expeditionary Forces in Europe . He was responsible for planning and supervising the invasion of North Africa in Operation Torch in 1942 -- 43 and the successful invasion of France and Germany in 1944 -- 45 from the Western Front . Eisenhower was born in Denison , Texas , and raised in Kansas in a large family of mostly Pennsylvania Dutch ancestry by parents with a strong religious background . His mother was born a Lutheran , married as a River Brethren and later converted to Jehovah 's Witnesses . Eisenhower did not belong to any denomination until he was President . He graduated from West Point in 1915 and later married Mamie Doud , with whom he had two sons . During World War I , he was denied a request to serve in Europe , instead commanding a unit training tank crews . Following the war , he served under several notable generals , and was promoted to the rank of brigadier general in 1941 . After the U.S. entered World War II , Eisenhower oversaw the successful invasions of North Africa and Sicily before supervising the invasions of France and Germany . After the war , Eisenhower served as Army Chief of Staff and then in an uncomfortable role as president of Columbia University . In 1951 -- 52 , he served as the first Supreme Commander of NATO . Eisenhower entered the 1952 presidential race as a Republican , in order to block the foreign policies of Senator Robert A. Taft . He won two landslide elections , becoming the first Republican winner to do so since 1928 . Eisenhower 's main goals in office were to contain the expansion of the Soviet Union and reduce federal deficits . In 1953 , he threatened the use of nuclear weapons until China agreed to terms regarding POWs in the Korean War . An armistice ended the stalemated conflict . His New Look policy of nuclear deterrence prioritized inexpensive nuclear weapons while reducing funding for expensive Army divisions . He continued Truman 's policy of recognizing the Republic of China as the legitimate government of China , and he won congressional approval of the Formosa Resolution . His administration provided major aid to help the French fight off Vietnamese Communists in the First Indochina War . After the French left he gave strong financial support to the new state of South Vietnam . He supported local military coups against hostile governments in Iran and Guatemala . During the Suez Crisis of 1956 , Eisenhower condemned the Israeli , British and French invasion of Egypt , and forced them to withdraw . He also condemned the Soviet invasion during the Hungarian Revolution of 1956 but took no action . After the Soviet Union launched Sputnik in 1957 , Eisenhower authorized the establishment of NASA , which led to the space race . During the Syrian Crisis of 1957 he approved a CIA-MI6 plan to stage fake border incidents as an excuse for an invasion by Syria 's pro-western neighbours . He deployed 15,000 soldiers during the 1958 Lebanon crisis . Near the end of his term , his efforts to set up a summit meeting with the Soviets collapsed when an American spy plane was shot down over Russia . On the domestic front , Eisenhower was a moderate conservative who continued New Deal agencies and expanded Social Security . He covertly opposed Joseph McCarthy and contributed to the end of McCarthyism by openly invoking executive privilege . Eisenhower was reluctant to support civil rights but signed the Civil Rights Act of 1957 and sent Army troops to enforce federal court orders that integrated schools in Little Rock , Arkansas . His largest program was the Interstate Highway System . He promoted the establishment of strong science education via the National Defense Education Act . Eisenhower 's two terms saw widespread economic prosperity except for a minor recession in 1958 . In his farewell address to the nation , Eisenhower expressed his concerns about the dangers of massive military spending , particularly deficit spending and government contracts to private military manufacturers . Voted Gallup 's most admired man twelve times , he achieved widespread popular esteem both in and out of office . Since the late 20th century , consensus among Western scholars has consistently held Eisenhower as one of the greatest U.S. Presidents .", "title": "" } ]
[ { "docid": "Eisenhower_(surname)", "text": "Eisenhower is a surname derived from the German word Eisenhauer , meaning `` iron hewer '' . Notable people with the surname include : David Eisenhower ( born 1948 ) , historian , son of John Eisenhower Doud Eisenhower ( 1917 -- 1921 ) , infant son of future-President Dwight D. Eisenhower and Mamie Eisenhower Dwight D. Eisenhower ( 1890 -- 1969 ) , five-star general and 34th President of the United States Earl D. Eisenhower ( 1898 -- 1968 ) , American electrical engineer and politician , brother of President Dwight D. Eisenhower Edgar N. Eisenhower ( 1889 -- 1971 ) , American lawyer , brother of President Dwight D. Eisenhower Jennie Elizabeth Eisenhower ( born 1978 ) , actress , daughter of David and Julie Eisenhower John Eisenhower ( 1922 -- 2013 ) , U.S. Army officer , son of President Dwight D. Eisenhower and Mamie Eisenhower Julie Nixon Eisenhower ( born 1948 ) , daughter of Richard Nixon and wife of David Eisenhower Mamie Eisenhower ( 1896 -- 1979 ) , wife of President Dwight D. Eisenhower Mary Jean Eisenhower ( born 1955 ) , international charity worker , daughter of John Eisenhower Milton S. Eisenhower ( 1899 -- 1985 ) , American University President , brother of President Dwight D. Eisenhower Susan Eisenhower ( born 1951 ) , author and expert on international security , daughter of John Eisenhower", "title": "" }, { "docid": "Inauguration_of_Dwight_D._Eisenhower", "text": "Inauguration of Dwight D. Eisenhower may refer to : First inauguration of Dwight D. Eisenhower , 1953 Second inauguration of Dwight D. Eisenhower , 1957", "title": "" }, { "docid": "Eisenhower_Park_(disambiguation)", "text": "Eisenhower Park or Dwight D. Eisenhower Park may refer to : Eisenhower Park , in East Meadow , New York Eisenhower State Park ( Kansas ) , a Kansas state park in Osage County , Kansas Eisenhower State Park ( Texas ) , a Texas state park near Denison , Texas Eisenhower National Historic Site , in Gettysburg , Pennsylvania Eisenhower Birthplace State Historic Site , a historic site in Denison , Texas ( Dwight D. Eisenhower 's birthplace ) Dwight D. Eisenhower Park ( Houston ) , a Harris County public park in Houston , Texas Dwight D. Eisenhower Park ( San Antonio ) , a city park in San Antonio , Texas Category : Place name disambiguation pages", "title": "" }, { "docid": "Timeline_of_the_presidency_of_Dwight_D._Eisenhower", "text": "The presidency of Dwight D. Eisenhower began on January 20 , 1953 when Dwight D. Eisenhower was inaugurated as President of the United States , and ended on January 20 , 1961 .", "title": "" }, { "docid": "Dwight_D._Eisenhower_Memorial", "text": "The Dwight D. Eisenhower Memorial is a planned United States presidential memorial to honor Dwight D. Eisenhower , the Supreme Commander of the Allied Forces in Europe during World War II and the 34th President of the United States . On October 25 , 1999 , the United States Congress created the Dwight D. Eisenhower Memorial Commission , and charged it with creating '' ... an appropriate permanent memorial to Dwight D. Eisenhower ... to perpetuate his memory and his contributions to the United States . '' A preliminary design by architect Frank Gehry proved highly controversial . After several years of hearings and several design changes , a revised preliminary design won approval from the United States Commission of Fine Arts in the summer of 2013 . After additional changes , another revised preliminary design was approved by the National Capital Planning Commission in October 2014 . Final detailed design approvals were given in June and July 2015 , but funding for the memorial remains in doubt despite the recent implementation of a private fundraising effort .", "title": "" }, { "docid": "Arthur_S._Nevins", "text": "Brigadier General Arthur Seymour Nevins ( July 19 , 1891 -- January 19 , 1979 ) was a career army officer ; a close friend of Dwight D. Eisenhower ; and the manager of the Eisenhower 's Gettysburg Farm . Nevins was born in Illinois , and was a brother of Allan Nevins , the noted historian . He joined the Army in 1917 and served under Dwight D. Eisenhower in the Philippines in the 1930s and in North Africa and Europe during World War II . Nevins retired from the Army in 1946 but continued to have frequent contacts with Dwight D. Eisenhower . In 1950 Dwight D. and Mamie Eisenhower bought a 189 acre farm adjacent to the Gettysburg Battlefield , intending to use it as a place to live when they retired . Eisenhower was preparing to leave for Europe where he had been appointed Supreme Commander of NATO forces , so he hired Nevins to manage the farm for him . Nevins moved to Gettysburg in April 1951 and managed Eisenhower 's farm until Eisenhower retired from the presidency in 1961 . Nevins settled on an adjoining farm and remained a close friend of Eisenhower until Eisenhower 's death in 1969 . Soon after Eisenhower 's death , General Nevins began to write a book about their friendship . In 1972 he provided the Eisenhower Presidential Library with a copy of the rough draft of the manuscript , which he had titled `` Looking Back Over More Than Fifty Years of Friendship With General Eisenhower . '' The book was eventually published in 1977 by Carlton Press of New York City under the title `` Gettysburg 's Five-Star Farmer . ''", "title": "" }, { "docid": "Second_inauguration_of_Dwight_D._Eisenhower", "text": "The second inauguration of Dwight D. Eisenhower as President of the United States was held privately on Sunday , January 20 , 1957 and publicly the following day , January 21 , 1957 . The inauguration marked the commencement of the second four-year term of Dwight D. Eisenhower as President and Richard Nixon as Vice President . Chief Justice Earl Warren administered the Oath of office .", "title": "" }, { "docid": "USS_Dwight_D._Eisenhower", "text": "USS Dwight D. Eisenhower ( CVN-69 ) ( `` Ike '' ) is a nuclear-powered aircraft carrier currently in service with the United States Navy . Commissioned in 1977 , the ship is the second of the ten s currently in service , and is the first ship named after the 34th President of the United States , Dwight D. Eisenhower . The vessel was initially named simply as USS Eisenhower , much like the lead ship of the class , , but the name was changed to its present form on 25 May 1970 . The carrier , like all others of her class , was constructed at Newport News Shipbuilding Company in Virginia , with the same design as the lead ship , although the ship has been overhauled twice to bring her up to the standards of those constructed more recently . Since commissioning , Dwight D. Eisenhower has participated in deployments including Operation Eagle Claw during the Iran hostage crisis in 1980 , as well as the Gulf War in the 1990s , and more recently in support of U.S. military operations in Iraq and Afghanistan .", "title": "" }, { "docid": "Eisenhower_High_School_(Rialto,_California)", "text": "Dwight D. Eisenhower High School ( est. 1959 ) , is located in Rialto , California , United States on the corner of Baseline Avenue and Lilac Ave. The school is named for U.S. President Dwight D. Eisenhower . Eisenhower High School is located in Rialto , California , which lies north of Interstate 10 , between the cities of San Bernardino and Fontana . It is one of three comprehensive high schools in the Rialto Unified School District and serves a student population of approximately 2,200 in grades 9-12 . Established in 1959 , Eisenhower has served more than four generations of the community 's members and prides itself on its outstanding programs . Dwight D. Eisenhower High School has been awarded National Blue Ribbon School 1993 and California Distinguished School 1994", "title": "" }, { "docid": "Dwight_D._Eisenhower_School_for_National_Security_and_Resource_Strategy", "text": "The Dwight D. Eisenhower School for National Security and Resource Strategy ( Eisenhower School ) , formerly known as the Industrial College of the Armed Forces ( ICAF ) , is a part of the National Defense University . It was renamed on 6 September 2012 in honor of Dwight D. Eisenhower who graduated from this school when it was previously known as the Army Industrial College . The Eisenhower School is a United States military educational institution tasked with preparing selected military officers and civilians for senior national security leadership positions dealing with the resource component of national power . The college conducts postgraduate , executive-level courses of study and associated research , awarding a Master of Science degree in national resource strategy to its graduates . Special emphasis is placed on materiel acquisition , joint logistics , and their integration into national security strategy .", "title": "" }, { "docid": "First_inauguration_of_Dwight_D._Eisenhower", "text": "The first inauguration of Dwight D. Eisenhower as the 34th President of the United States was held on January 20 , 1953 , at the east portico of the United States Capitol in Washington , D.C. . The inauguration marked the commencement of the first four-year term of Dwight D. Eisenhower as President and of Richard Nixon as Vice President . Chief Justice Fred M. Vinson administered the presidential oath of office to Eisenhower . The vice presidential oath was administered to Nixon by Senator William Knowland ( R -- CA ) . Eisenhower placed his hand upon on two Bibles when he recited the oath : the Bible used by George Washington in 1789 , opened to II Chronicles 7:14 ; and his own personal `` West Point Bible , '' opened to Psalm 33:12 . Afterward , he recited his own prayer , rather than kissing the Bible .", "title": "" }, { "docid": "List_of_memorials_to_Dwight_D._Eisenhower", "text": "This is a list of places in the United States named for Dwight D. Eisenhower :", "title": "" }, { "docid": "Dwight_D._Eisenhower_Park_(San_Antonio)", "text": "Dwight D. Eisenhower Park , also known as Eisenhower City Park is a park located in the Texas Hill Country outside San Antonio . It is managed by the City of San Antonio Parks and Recreation Department .", "title": "" }, { "docid": "Doud_Eisenhower", "text": "Doud Dwight `` Icky '' Eisenhower ( September 24 , 1917 -- January 2 , 1921 ) was the first son of Dwight D. Eisenhower and Mamie Eisenhower . He was named `` Doud '' in honor of his mother ( her maiden name was Doud ) and `` Dwight '' in honor of his father . He was commonly called `` Icky '' amongst his family members .", "title": "" }, { "docid": "Military_career_of_Dwight_D._Eisenhower", "text": "The military career of Dwight D. Eisenhower encompassed over forty six years of active service .", "title": "" }, { "docid": "William_R._Gruber", "text": "William Rudolph Gruber , ( December 17 , 1890 -- January 27 , 1979 ) Brigadier general , was an instructor at the Army Command and General Staff School at Fort Leavenworth when Dwight D. Eisenhower was a student there . Following Eisenhower 's graduation , Gruber and his wife Helen Drennan Gruber were joined by Dwight D. and Mamie Eisenhower on a 17-day , 1800 mile motor trip through Belgium , Germany , Switzerland and France in 1929 . They left Paris on August 28 , 1929 , and drove to Brussels , Belgium . Their route then took them to Bonn , Germany , south along the Rhine River to Coblenz , Heidelberg and through the Black Forest . They then went to Switzerland , spending seven days and visiting Zürich , Lucerne , Interlaken , Montreux , and Geneva , and surviving a harrowing crossing of the Furka Pass high in the Alps . From Switzerland the travelers went to Besançon , then to Romagne in France . While the ladies stayed there to visit with a mutual friend , Gruber and Eisenhower toured the World War I battlefields in the area . Eisenhower was an expert guide having just completed work on a guidebook for the Battle Monuments Commission . The Grubers and Eisenhowers returned to Paris on September 13 .", "title": "" }, { "docid": "List_of_executive_actions_by_Dwight_D._Eisenhower", "text": "Executive Orders numbered 10432 -- 10913 signed by President Dwight D. Eisenhower ( 1953 -- 1961 ) . Category : United States federal policy", "title": "" }, { "docid": "Wichita_Dwight_D._Eisenhower_National_Airport", "text": "Wichita Dwight D. Eisenhower National Airport is a commercial airport located about 7 mi west of downtown Wichita , Kansas , United States . It is the largest and busiest airport in the state of Kansas . The airport is commonly referred to as Eisenhower National Airport although most locals call it Wichita Airport . The airport was previously Wichita Mid-Continent Airport . The name was to be changed on March 31 , 2015 by the city of Wichita , but the official change occurred within the Federal Aviation Administration ( FAA ) on November 13 , 2014 for a deadline to publish new aeronautical charts and airport directories . The new terminal opened on Wednesday , June 3 , 2015 . The airport is named for Dwight Eisenhower , the 34th President of the United States from 1953 to 1961 . His boyhood home , museum , and Presidential Library are at the Eisenhower Presidential Center in Abilene , Kansas .", "title": "" }, { "docid": "List_of_federal_judges_appointed_by_Dwight_D._Eisenhower", "text": "Following is a list of all United States federal judges appointed by President Dwight D. Eisenhower during his presidency . In total Eisenhower appointed five Justices to the Supreme Court of the United States ( including one Chief Justice ) , 45 judges to the United States Courts of Appeals , and 129 judges to the United States district courts .", "title": "" }, { "docid": "Dwight_D._Eisenhower_Park_(Houston)", "text": "Dwight D. Eisenhower Park is a park located in Harris County , Texas on the south coast of Lake Houston It is owned and managed by Harris County Precinct One , which acquired the park from the City of Houston in 1995 .", "title": "" }, { "docid": "LNER_Class_A4_4496_Dwight_D_Eisenhower", "text": "60008 Dwight D Eisenhower is an LNER Class A4 steam locomotive named after the United States General of the Army . Built for the London & North Eastern Railway in 1937 , this locomotive was originally numbered 4496 and named Golden Shuttle . It was renamed Dwight D. Eisenhower after World War II and renumbered 8 on 23 November 1946 under Edward Thompson 's LNER 1946 renumbering scheme . After nationalisation in 1948 British Railways renumbered it 60008 on 29 October 1948 . It was retired from service in 1963 , and was moved to the National Railroad Museum in Ashwaubenon , a suburb of Green Bay , Wisconsin , United States , where it is currently on display . It returned to England in 2012 for display at the National Railway Museum in York when all surviving A4s were reunited . It returned to Green Bay in 2014 .", "title": "" }, { "docid": "Dwight_D._Eisenhower_High_School_(Blue_Island,_Illinois)", "text": "Dwight D. Eisenhower High School ( Eisenhower , DDE , EHS or Ike ) is a public four-year high school located in Blue Island , Illinois , a southern suburb of Chicago , Illinois , in the United States . It is part of Community High School District 218 along with sister schools Alan B. Shepard High School and Harold L. Richards High School . Eisenhower is a diverse school with a balanced student body of Caucasian , Hispanic and African American students . Eisenhower serves students from the communities of Blue Island , Calumet Park , Robbins , Alsip , Merrionette Park , Posen , Deer Pointe & Garden Homes . The current enrollment is over 2,500 students .", "title": "" }, { "docid": "Julie_Nixon_Eisenhower", "text": "Julie Nixon Eisenhower ( born July 5 , 1948 ) is the daughter of Richard M. Nixon , 37th President of the United States , and Pat Nixon , First Lady of the United States . She is the younger sister to Patricia Nixon Cox . While her father served as President of the United States , she wrote several books and worked as Assistant Managing Editor of The Saturday Evening Post . Since her father left the White House in 1974 , she has written additional books and works to support her parents ' legacy . In 1968 , she married David Eisenhower , grandson of President Dwight D. Eisenhower . She is the mother of two daughters , Jennie Eisenhower and Melanie Catherine Eisenhower , and a son , Alexander Richard Eisenhower .", "title": "" }, { "docid": "Eisenhower_High_School_(Houston)", "text": "Dwight D. Eisenhower High School is a Title I public secondary school located in Near Northwest and in Houston , Texas , United States . Eisenhower is a part of the Aldine Independent School District . The main campus is located at 7922 Antoine Drive , while the Eisenhower 9th Grade School is located at 3550 West Gulfbank Road . The Inwood Forest community and the western portion of the Acres Homes community are served by Eisenhower . In addition , the unincorporated Harris County communities of Bammel Trace , Mount Royal Village , Parkland Place , Greensfield Village , and Willow Springs Villas are zoned to Eisenhower . Eisenhower offers Advanced Placement courses , including World History , Calculus ( AB and BC ) , Macroeconomics , Statistics , U.S. Government and Politics , English , Spanish , French , US History , Visual Arts and Psychology . . Eisenhower also offers the International Baccalaureate Programme with courses including Higher Level English , Higher Level Spanish , Standard Level Spanish , Standard Level French , Higher Level History of the Americas , Standard Level Chemistry , Standard Level Physics , Higher Level Biology , Standard Level Mathematical Studies , Standard Level Mathematics , Higher Level Visual Arts , Higher Level Music , In the past , Eisenhower sent at least two projects each year to the National History Day competition in Washington D.C. , while having a top-tiered Academic Decathlon team that has progressed to the state competition three years in a row . In 1991 , 1998 and 2009 the school hosted Texas French Symposium . In 2016 Eisenhower will house another program for advanced students named YES Prep Eisenhower.The purpose of the partnership is to increase student achievement . Working under a shared-campus model , Aldine and YES Prep are united behind the commitment to provide outstanding educational options for all students . Together Aldine and YES Prep will create a cooperative environment that is focused on developing a strong culture in the building and sharing best practices between teachers , building leaders , and the organizations . The partnership reflects a distinct move from the long-standing competitive relationship between traditional public schools and public charter schools to a powerful , collaborative association . The school is nicknamed `` Big Ike '' and `` Ike , '' after Dwight D. Eisenhower 's nickname . The school was named a National Blue Ribbon School in 1988-89 .", "title": "" }, { "docid": "Dwight_D._Eisenhower_Supreme_Court_candidates", "text": "During his two terms in office , President Dwight D. Eisenhower appointed five members of the Supreme Court of the United States : Chief Justice Earl Warren , and Associate Justices John Marshall Harlan , William Brennan , Charles Evans Whittaker , and Potter Stewart .", "title": "" }, { "docid": "Dwight_D._Eisenhower_Presidential_Library,_Museum_and_Boyhood_Home", "text": "The Dwight D. Eisenhower Presidential Library , Museum and Boyhood Home is the presidential library and museum of Dwight David Eisenhower , the 34th President of the United States ( 1953 -- 1961 ) , located in his hometown of Abilene , Kansas . The museum also includes his boyhood home , where he lived from 1898 until being appointed to West Point in 1911 , and his final resting place . It is one of the thirteen presidential libraries under the auspices of the National Archives and Records Administration ( NARA ) . Admission to the Visitor Center , Place of Meditation ( gravesite ) , and the archives is free . Admission to the museum is $ 12 for adults and includes a tour of the Boyhood Home . The complex is open every day except New Year 's Day , Thanksgiving and Christmas .", "title": "" }, { "docid": "Kenneth_S._Davis", "text": "Kenneth Sydney Davis ( September 29 , 1912 -- June 10 , 1999 ) was a historian and university professor , most renowned for his series of biographies of Franklin Delano Roosevelt . Davis also wrote biographies of Charles Lindbergh , Adlai Stevenson , and authored the first biography of General Dwight D. Eisenhower , entitled Dwight D. Eisenhower : Soldier of Democracy .", "title": "" }, { "docid": "James_Lambie", "text": "James M. Lambie , Jr. ( September 19 , 1914 -- November 30 , 1999 ) served in the Eisenhower Administration ( 1953 -- 1961 ) as Special Assistant and Assistant Staff Secretary coordinating public information programs between the Advertising Council and the U.S. government . Lambie was born in Washington , Pennsylvania and attended Washington and Jefferson College , the University of Michigan at Ann Arbor , and Pennsylvania State College . Before joining Dwight D. Eisenhower 's campaign staff in 1952 he worked for the National Committee for a Free Europe , Inc. , and Crusade for Freedom . In 1953 President Eisenhower assigned him the job of Special Assistant in the White House where he served as the coordinator of public information programs between the Advertising Council and the U.S. government and arbitrated conflicting government claims for the use of the Advertising Council 's facilities for public service campaigns . In 1960 he was appointed the Assistant Staff Secretary on the White House staff . From September 1954 to January 1961 Lambie also served in an unofficial capacity as Deputy Chairman of the Interagency Committee for Agricultural Surplus Disposal . The purpose of this committee , chaired by Clarence Francis , was to carry out the provisions of P.L. 480 by coordinating the various agricultural surplus disposal activities of the U.S. government .", "title": "" }, { "docid": "David_Eisenhower", "text": "Dwight David Eisenhower II ( born March 31 , 1948 ) is an American author , public policy fellow , professor at the University of Pennsylvania , and eponym of the U.S. Presidential retreat , Camp David . He is the only grandson of 34th President of the United States , Dwight D. Eisenhower , and the son-in-law of the 37th President of the United States Richard Nixon .", "title": "" }, { "docid": "Lester_W._Bentley", "text": "Lester W. Bentley ( 1908 -- 1972 ) was an American artist from Wisconsin . He is most well known for painting portraits and murals . The two portraits he is most famous for painting are of President Dwight D. Eisenhower and U.S. Supreme Court Chief Justice William O. Douglas . Bentley painted the portrait of President Dwight D. Eisenhower in 1954 for Columbia University .", "title": "" } ]
86
Adult tissue-resident macrophages are seeded before birth.
[ { "docid": "22406695", "text": "Macrophages are distributed in tissues throughout the body and contribute to both homeostasis and disease. Recently, it has become evident that most adult tissue macrophages originate during embryonic development and not from circulating monocytes. Each tissue has its own composition of embryonically derived and adult-derived macrophages, but it is unclear whether macrophages of distinct origins are functionally interchangeable or have unique roles at steady state. This new understanding also prompts reconsideration of the function of circulating monocytes. Classical Ly6c(hi) monocytes patrol the extravascular space in resting organs, and Ly6c(lo) nonclassical monocytes patrol the vasculature. Inflammation triggers monocytes to differentiate into macrophages, but whether resident and newly recruited macrophages possess similar functions during inflammation is unclear. Here, we define the tools used for identifying the complex origin of tissue macrophages and discuss the relative contributions of tissue niche versus ontological origin to the regulation of macrophage functions during steady state and inflammation.", "title": "Origin and functions of tissue macrophages." }, { "docid": "7521113", "text": "Mononuclear phagocytes, including monocytes, macrophages, and dendritic cells, contribute to tissue integrity as well as to innate and adaptive immune defense. Emerging evidence for labor division indicates that manipulation of these cells could bear therapeutic potential. However, specific ontogenies of individual populations and the overall functional organization of this cellular network are not well defined. Here we report a fate-mapping study of the murine monocyte and macrophage compartment taking advantage of constitutive and conditional CX(3)CR1 promoter-driven Cre recombinase expression. We have demonstrated that major tissue-resident macrophage populations, including liver Kupffer cells and lung alveolar, splenic, and peritoneal macrophages, are established prior to birth and maintain themselves subsequently during adulthood independent of replenishment by blood monocytes. Furthermore, we have established that short-lived Ly6C(+) monocytes constitute obligatory steady-state precursors of blood-resident Ly6C(-) cells and that the abundance of Ly6C(+) blood monocytes dynamically controls the circulation lifespan of their progeny.", "title": "Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis." } ]
[ { "docid": "2604063", "text": "The intestinal microbiota has become a relevant aspect of human health. Microbial colonization runs in parallel with immune system maturation and plays a role in intestinal physiology and regulation. Increasing evidence on early microbial contact suggest that human intestinal microbiota is seeded before birth. Maternal microbiota forms the first microbial inoculum, and from birth, the microbial diversity increases and converges toward an adult-like microbiota by the end of the first 3-5 years of life. Perinatal factors such as mode of delivery, diet, genetics, and intestinal mucin glycosylation all contribute to influence microbial colonization. Once established, the composition of the gut microbiota is relatively stable throughout adult life, but can be altered as a result of bacterial infections, antibiotic treatment, lifestyle, surgical, and a long-term change in diet. Shifts in this complex microbial system have been reported to increase the risk of disease. Therefore, an adequate establishment of microbiota and its maintenance throughout life would reduce the risk of disease in early and late life. This review discusses recent studies on the early colonization and factors influencing this process which impact on health.", "title": "The composition of the gut microbiota throughout life, with an emphasis on early life" }, { "docid": "12827098", "text": "Despite accumulating evidence suggesting local self-maintenance of tissue macrophages in the steady state, the dogma remains that tissue macrophages derive from monocytes. Using parabiosis and fate-mapping approaches, we confirmed that monocytes do not show significant contribution to tissue macrophages in the steady state. Similarly, we found that after depletion of lung macrophages, the majority of repopulation occurred by stochastic cellular proliferation in situ in a macrophage colony-stimulating factor (M-Csf)- and granulocyte macrophage (GM)-CSF-dependent manner but independently of interleukin-4. We also found that after bone marrow transplantation, host macrophages retained the capacity to expand when the development of donor macrophages was compromised. Expansion of host macrophages was functional and prevented the development of alveolar proteinosis in mice transplanted with GM-Csf-receptor-deficient progenitors. Collectively, these results indicate that tissue-resident macrophages and circulating monocytes should be classified as mononuclear phagocyte lineages that are independently maintained in the steady state.", "title": "Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes." }, { "docid": "22973574", "text": "Macrophages and dendritic cells (DCs) are key components of cellular immunity and are thought to originate and renew from hematopoietic stem cells (HSCs). However, some macrophages develop in the embryo before the appearance of definitive HSCs. We thus reinvestigated macrophage development. We found that the transcription factor Myb was required for development of HSCs and all CD11b(high) monocytes and macrophages, but was dispensable for yolk sac (YS) macrophages and for the development of YS-derived F4/80(bright) macrophages in several tissues, such as liver Kupffer cells, epidermal Langerhans cells, and microglia--cell populations that all can persist in adult mice independently of HSCs. These results define a lineage of tissue macrophages that derive from the YS and are genetically distinct from HSC progeny.", "title": "A lineage of myeloid cells independent of Myb and hematopoietic stem cells." }, { "docid": "16863359", "text": "Inflammasomes are multiprotein complexes that link pathogen recognition and cellular stress to the processing of the proinflammatory cytokine interleukin-1β (IL-1β). Whereas inflammasome-mediated activation is heavily studied in hematopoietic macrophages and dendritic cells, much less is known about microglia, resident tissue macrophages of the brain that originate from a distinct progenitor. To directly compare inflammasome-mediated activation in different types of macrophages, we isolated primary microglia and hematopoietic macrophages from adult, healthy rhesus macaques. We analyzed the expression profile of NOD (nucleotide-binding oligomerization domain)-like receptors, adaptor proteins, and caspases and characterized inflammasome activation and regulation in detail. We here demonstrate that primary microglia can respond to the same innate stimuli as hematopoietic macrophages. However, microglial responses are more persistent due to lack of negative regulation on pro-IL-1β expression. In addition, we show that while caspase 1, 4, and 5 activation is pivotal for inflammasome-induced IL-1β secretion by hematopoietic macrophages, microglial secretion of IL-1β is only partially dependent on these inflammatory caspases. These results identify key cell type-specific differences that may aid the development of strategies to modulate innate immune responses in the brain.", "title": "Inflammasome-induced IL-1β secretion in microglia is characterized by delayed kinetics and is only partially dependent on inflammatory caspases." }, { "docid": "12966719", "text": "CD8 tissue-resident memory T (TRM) cells provide efficient local control of viral infection, but the role of CD4 TRM is less clear. Here, by using parabiotic mice, we show that a preexisting pool of CD4 TRM cells in the genital mucosa was required for full protection from a lethal herpes simplex virus 2 (HSV-2) infection. Chemokines secreted by a local network of macrophages maintained vaginal CD4 TRM in memory lymphocyte clusters (MLCs), independently of circulating memory T cells. CD4 TRM cells within the MLCs were enriched in clones that expanded in response to HSV-2. Our results highlight the need for vaccine strategies that enable establishment of TRM cells for protection from a sexually transmitted virus and provide insights as to how such a pool might be established.", "title": "A local macrophage chemokine network sustains protective tissue-resident memory CD4 T cells" }, { "docid": "43192375", "text": "Adipose tissue macrophages (ATMs) infiltrate adipose tissue during obesity and contribute to insulin resistance. We hypothesized that macrophages migrating to adipose tissue upon high-fat feeding may differ from those that reside there under normal diet conditions. To this end, we found a novel F4/80(+)CD11c(+) population of ATMs in adipose tissue of obese mice that was not seen in lean mice. ATMs from lean mice expressed many genes characteristic of M2 or \"alternatively activated\" macrophages, including Ym1, arginase 1, and Il10. Diet-induced obesity decreased expression of these genes in ATMs while increasing expression of genes such as those encoding TNF-alpha and iNOS that are characteristic of M1 or \"classically activated\" macrophages. Interestingly, ATMs from obese C-C motif chemokine receptor 2-KO (Ccr2-KO) mice express M2 markers at levels similar to those from lean mice. The antiinflammatory cytokine IL-10, which was overexpressed in ATMs from lean mice, protected adipocytes from TNF-alpha-induced insulin resistance. Thus, diet-induced obesity leads to a shift in the activation state of ATMs from an M2-polarized state in lean animals that may protect adipocytes from inflammation to an M1 proinflammatory state that contributes to insulin resistance.", "title": "Obesity induces a phenotypic switch in adipose tissue macrophage polarization." }, { "docid": "4928057", "text": "Organ-specific functions of tissue-resident macrophages in the steady-state heart are unknown. Here, we show that cardiac macrophages facilitate electrical conduction through the distal atrioventricular node, where conducting cells densely intersperse with elongated macrophages expressing connexin 43. When coupled to spontaneously beating cardiomyocytes via connexin-43-containing gap junctions, cardiac macrophages have a negative resting membrane potential and depolarize in synchrony with cardiomyocytes. Conversely, macrophages render the resting membrane potential of cardiomyocytes more positive and, according to computational modeling, accelerate their repolarization. Photostimulation of channelrhodopsin-2-expressing macrophages improves atrioventricular conduction, whereas conditional deletion of connexin 43 in macrophages and congenital lack of macrophages delay atrioventricular conduction. In the Cd11bDTR mouse, macrophage ablation induces progressive atrioventricular block. These observations implicate macrophages in normal and aberrant cardiac conduction.", "title": "Macrophages Facilitate Electrical Conduction in the Heart" }, { "docid": "25068298", "text": "Distribution and fine structure of macrophages were studied in 10 human embryos in the 6th and 7th week of gestation, 5.5 to 12 mm in crown-rump length. The yolk sac macrophages were found in the extravascular mesenchymal tissues and intravascular spaces long before the first appearance of bone marrow and lymphatic tissues in the embryos. In addition to the macrophages, the fibroblastic cells and the cells of erythropoietic series were also present in the extravascular space. The macrophages showed a variety of cellular structures suggesting transition from immature cell type with no heterophagolysosomes to mature cell type in phagocytosis. The mature macrophages avidly phagocytized the primitive erythroblasts and occasionally platelets. They were positively stained for lysosomal enzymes and were characterized by numerous pleomorphic heterophagolysosomes which exhibited various stages of digestion of phagocytized blood cells. The origin of intravascular macrophages may be in either migrated extravascular macrophages or phagocytic endothelial cells. The phagocytosis and degradation of erythroblasts appear to be one of the main functions of yolk sac macrophages. The presence of the macrophages in mitosis indicates their proliferation in situ.", "title": "Electron microscopic studies of macrophages in early human yolk sacs." }, { "docid": "7489663", "text": "A current paradigm states that monocytes circulate freely and patrol blood vessels but differentiate irreversibly into dendritic cells (DCs) or macrophages upon tissue entry. Here we show that bona fide undifferentiated monocytes reside in the spleen and outnumber their equivalents in circulation. The reservoir monocytes assemble in clusters in the cords of the subcapsular red pulp and are distinct from macrophages and DCs. In response to ischemic myocardial injury, splenic monocytes increase their motility, exit the spleen en masse, accumulate in injured tissue, and participate in wound healing. These observations uncover a role for the spleen as a site for storage and rapid deployment of monocytes and identify splenic monocytes as a resource that the body exploits to regulate inflammation.", "title": "Identification of splenic reservoir monocytes and their deployment to inflammatory sites." }, { "docid": "12205576", "text": "OBJECTIVE The aim was to describe the sex and socioeconomic differences in patterns of physical activity at work and in leisure time of men and women aged 36 years, and to investigate factors in childhood and adolescence which predict high rates of participation in sports and recreational activities in later life. DESIGN Data collected in childhood, adolescence, and at 36 years on members of a national prospective birth cohort study were used. SETTING The population sample was resident in England, Scotland, and Wales. SUBJECTS A stratified sample of about 3500 men and women was studied regularly from birth until 43 years. MEASUREMENTS AND MAIN RESULTS More men than women reported high rates of sports and recreational activities, gardening, and do-it-yourself. In contrast women reported higher rates of bicycling and walking. Higher levels of education were associated with frequent participation in sports. Individuals often engaged in one type of activity without necessarily engaging in other types. Those who were most active in sport had been above average at sports in school, more outgoing socially in adolescence, had fewer health problems in childhood, were better educated, and had more mothers with a secondary education than those who were less active. CONCLUSIONS Studies that examine the relationship between physical activity and chronic disease should consider a broad range of pursuits rather than extrapolating from only one area of physical activity, and in their explanations should take account of the possible role of childhood characteristics. The findings suggest the importance of developing skills and habits in childhood as well as of encouraging healthier exercise habits in adults who may have had few opportunities or low motivation previously.", "title": "Physical activity at 36 years: patterns and childhood predictors in a longitudinal study." }, { "docid": "9629682", "text": "The field of macro-imaging has grown considerably with the appearance of innovative clearing methods and confocal microscopes with lasers capable of penetrating increasing tissue depths. The ability to visualize and model the growth of whole organs as they develop from birth, or with manipulation, disease or injury, provides new ways of thinking about development, tissue-wide signaling, and cell-to-cell interactions. The zebrafish (Danio rerio) has ascended from a predominantly developmental model to a leading adult model of tissue regeneration. The unmatched neurogenic and regenerative capacity of the mature central nervous system, in particular, has received much attention, however tools to interrogate the adult brain are sparse. At present there exists no straightforward methods of visualizing changes in the whole adult brain in 3-dimensions (3-D) to examine systemic patterns of cell proliferation or cell populations of interest under physiological, injury, or diseased conditions. The method presented here is the first of its kind to offer an efficient step-by-step pipeline from intraperitoneal injections of the proliferative marker, 5-ethynyl-2'-deoxyuridine (EdU), to whole brain labeling, to a final embedded and cleared brain sample suitable for 3-D imaging using optical projection tomography (OPT). Moreover, this method allows potential for imaging GFP-reporter lines and cell-specific antibodies in the presence or absence of EdU. The small size of the adult zebrafish brain, the highly consistent degree of EdU labeling, and the use of basic clearing agents, benzyl benzoate, and benzyl alcohol, makes this method highly tractable for most laboratories interested in understanding the vertebrate central nervous system in health and disease. Post-processing of OPT-imaged adult zebrafish brains injected with EdU illustrate that proliferative patterns in EdU can readily be observed and analyzed using IMARIS and/or FIJI/IMAGEJ software. This protocol will be a valuable tool to unlock new ways of understanding systemic patterns in cell proliferation in the healthy and injured brain, brain-wide cellular interactions, stem cell niche development, and changes in brain morphology.", "title": "A Whole Brain Staining, Embedding, and Clearing Pipeline for Adult Zebrafish to Visualize Cell Proliferation and Morphology in 3-Dimensions" }, { "docid": "22815457", "text": "OBJECTIVE To compare the outcome of pregnancy in cohorts of women with singleton pregnancy and history of preterm birth and sonographic short cervix managed with different treatment protocols, namely cerclage, vaginal progesterone or cervical pessary. METHODS This was a comparison of three management protocols for women with singleton pregnancy and a high risk of preterm birth because of a prior spontaneous preterm birth before 34 weeks and a shortened cervical length detected by transvaginal ultrasound. The study included 142 women who were initially treated with cerclage (USA), 59 with vaginal progesterone (UK) and 42 with cervical pessary (Spain). Perinatal outcomes were compared between the three cohorts. RESULTS There were no statistically significant differences in perinatal losses, neonatal morbidity and preterm births among the three groups, apart from a higher rate of preterm birth before 34 weeks' gestation after treatment with vaginal progesterone in comparison with treatment with cervical pessary (32% vs 12%; relative risk (RR) = 2.70; 95% CI, 1.10-6.67). When only the subgroups of women with cervical length < 25 mm, irrespective of gestational age, were compared, the difference between these two cohorts was not statistically significant (RR = 2.21; 95% CI, 0.83-5.89). CONCLUSION Cerclage, vaginal progesterone and pessary appear to have similar effectiveness as management strategies in women with singleton pregnancy, previous spontaneous preterm birth and short cervix. Direct randomized comparisons of these strategies, or combinations thereof, are needed to determine optimal management.", "title": "Vaginal progesterone, cerclage or cervical pessary for preventing preterm birth in asymptomatic singleton pregnant women with a history of preterm birth and a sonographic short cervix." }, { "docid": "5511240", "text": "Kupffer cells, the phagocytes of fetal origin that line the liver sinusoids, are key contributors of host defense against enteroinvasive bacteria. Here, we found that infection by Listeria monocytogenes induced the early necroptotic death of Kupffer cells, which was followed by monocyte recruitment and an anti-bacterial type 1 inflammatory response. Kupffer cell death also triggered a type 2 response that involved the hepatocyte-derived alarmin interleukin-33 (IL-33) and basophil-derived interleukin-4 (IL-4). This led to the alternative activation of the monocyte-derived macrophages recruited to the liver, which thereby replaced ablated Kupffer cells and restored liver homeostasis. Kupffer cell death is therefore a key signal orchestrating type 1 microbicidal inflammation and type-2-mediated liver repair upon infection. This indicates that beyond the classical dichotomy of type 1 and type 2 responses, these responses can develop sequentially in the context of a bacterial infection and act interdependently, orchestrating liver immune responses and return to homeostasis, respectively.", "title": "Liver-resident macrophage necroptosis orchestrates type 1 microbicidal inflammation and type-2-mediated tissue repair during bacterial infection." }, { "docid": "27567994", "text": "The generation of tumor-directed cytotoxic T lymphocytes is considered crucial for the induction of antitumor immunity. To activate these CD8(+) T cells, antigen-presenting cells (APCs) must initially acquire tumor cell-associated antigens. The major source of tumor antigens is dead tumor cells, but little is known about how APCs in draining lymph nodes acquire and crosspresent these antigens. Here we show that CD169(+) macrophages phagocytose dead tumor cells transported via lymphatic flow and subsequently crosspresent tumor antigens to CD8(+) T cells. Subcutaneous immunization with irradiated tumor cells protects mice from syngenic tumor. However, tumor antigen-specific CD8(+) T cell activation and subsequent antitumor immunity are severely impaired in mice depleted with CD169(+) macrophages. Neither migratory dendritic cells (DCs) nor lymph node-resident conventional DCs are essential for the crosspresentation of tumor antigens. Thus, we have identified CD169(+) macrophages as lymph node-resident APCs dominating early activation of tumor antigen-specific CD8(+) T cells.", "title": "CD169-positive macrophages dominate antitumor immunity by crosspresenting dead cell-associated antigens." }, { "docid": "5487448", "text": "Birth weight is a significant predictor of breast cancer risk in adult life and mammary gland mass could be an intermediate stage in this long process. We have studied the association of birth size measurements with mammographic density, a marker of mammary gland mass. For a population-based sample of 893 postmenopausal women without previous cancer in Sweden, we retrieved information on birth size from birth records and their most recent mammography. Film mammograms of the medio-lateral oblique view were digitized and the Cumulus software was used for computer-assisted semi-automated thresholding of mammographic density. Results were analyzed using generalized linear models controlling for possible confounders. Mean percent mammographic density increased when comparing the extreme categories of birth weight (from 15.6% to 18.6%) and head circumference (from 15.5% to 20.4%), and the corresponding linear trends were statistically significant (p values 0.02 and 0.007, respectively). The associations were particularly strong when the cutoff for high versus low mammographic density was set at the relatively high value of 50%. Compared to women weighing 3001-3500 grams at birth, women with birth weights >4000g were at almost 3-fold risk of developing high mammographic density (odds ratio: 2.9, 95% confidence interval 1.1 to 7.9). No association with mammographic density was evident with respect to birth length which, however, is known to be less accurately measured. These results indicate that adult breast density, a powerful predictor of breast cancer risk, has intrauterine roots, as reflected in birth size.", "title": "Birth weight and mammographic density among postmenopausal women in Sweden." }, { "docid": "2605032", "text": "We investigated if whether intrauterine protein restriction in combination with overfeeding during lactation would cause adult-onset obesity and metabolic disorders. After birth, litters from dams fed with control (17% protein) and low protein (6% protein) diets were adjusted to a size of four (CO and LO groups, respectively) or eight (CC and LC groups, respectively) pups. All of the offspring were fed a diet containing 12% protein from the time of weaning until they were 90 d old. Compared to the CC and LC groups, the CO and LO groups had higher relative and absolute food intakes, oxygen consumption and carbon dioxide production; lower brown adipose tissue weight and lipid content and greater weight gain and absolute and relative white adipose tissue weight and absolute lipid content. Compared with the CO and CC rats, the LC and LO rats exhibited higher relative food intake, brown adipose tissue weight and lipid content, reduced oxygen consumption, carbon dioxide production and spontaneous activity, increased relative retroperitoneal adipose tissue weight and unaltered absolute white adipose tissue weight and lipid content. The fasting serum glucose was similar among the groups. The area under the glucose curve was higher in the LO and CO rats than in the LC and CC rats. The basal insulinemia and homeostasis model assessment of insulin resistance (HOMA-IR) were lower in the LO group than in the other groups. The total area under the insulin curve for the LO rats was similar to the CC rats, and both were lower than the CO and LC rats. Kitt was higher in the LO, LC and CO groups than in the CC group. Thus, intrauterine protein restriction followed by overfeeding during lactation did not induce obesity, but produced glucose intolerance by impairing pancreatic function in adulthood.", "title": "Intrauterine protein restriction combined with early postnatal overfeeding was not associated with adult-onset obesity but produced glucose intolerance by pancreatic dysfunction" }, { "docid": "12411274", "text": "Skeletal muscle in vertebrates is derived from somites, epithelial structures of the paraxial mesoderm, yet many unrelated reports describe the occasional appearance of myogenic cells from tissues of nonsomite origin, suggesting either transdifferentiation or the persistence of a multipotent progenitor. Here, we show that clonable skeletal myogenic cells are present in the embryonic dorsal aorta of mouse embryos. This finding is based on a detailed clonal analysis of different tissue anlagen at various developmental stages. In vitro, these myogenic cells show the same morphology as satellite cells derived from adult skeletal muscle, and express a number of myogenic and endothelial markers. Surprisingly, the latter are also expressed by adult satellite cells. Furthermore, it is possible to clone myogenic cells from limbs of mutant c-Met-/- embryos, which lack appendicular muscles, but have a normal vascular system. Upon transplantation, aorta-derived myogenic cells participate in postnatal muscle growth and regeneration, and fuse with resident satellite cells. The potential of the vascular system to generate skeletal muscle cells may explain observations of nonsomite skeletal myogenesis and raises the possibility that a subset of satellite cells may derive from the vascular system.", "title": "Skeletal Myogenic Progenitors Originating from Embryonic Dorsal Aorta Coexpress Endothelial and Myogenic Markers and Contribute to Postnatal Muscle Growth and Regeneration" }, { "docid": "30468386", "text": "The olfactory epithelium houses chemosensory neurons, which transmit odor information from the nose to the brain. In adult mammals, the olfactory epithelium is a uniquely robust neuroproliferative zone, with the ability to replenish its neuronal and non-neuronal populations due to the presence of germinal basal cells. The stem and progenitor cells of these germinal layers, and their regulatory mechanisms, remain incompletely defined. Here we show that progenitor cells expressing c-Kit, a receptor tyrosine kinase marking stem cells in a variety of embryonic tissues, are required for maintenance of the adult neuroepithelium. Mouse genetic fate-mapping analyses show that embryonically, a c-Kit(+) population contributes to olfactory neurogenesis. In adults under conditions of normal turnover, there is relatively sparse c-Kit(+) progenitor cell (ckPC) activity. However, after experimentally induced neuroepithelial injury, ckPCs are activated such that they reconstitute the neuronal population. There are also occasional non-neuronal cells found to arise from ckPCs. Moreover, the selective depletion of the ckPC population, utilizing temporally controlled targeted diphtheria toxin A expression, results in failure of neurogenesis after experimental injury. Analysis of this model indicates that most ckPCs reside among the globose basal cell populations and act downstream of horizontal basal cells, which can serve as stem cells. Identification of the requirement for olfactory c-Kit-expressing progenitors in olfactory maintenance provides new insight into the mechanisms involved in adult olfactory neurogenesis. Additionally, we define an important and previously unrecognized site of adult c-Kit activity.", "title": "Adult c-Kit(+) progenitor cells are necessary for maintenance and regeneration of olfactory neurons." }, { "docid": "15274349", "text": "Almost immediately after a human being is born, so too is a new microbial ecosystem, one that resides in that person's gastrointestinal tract. Although it is a universal and integral part of human biology, the temporal progression of this process, the sources of the microbes that make up the ecosystem, how and why it varies from one infant to another, and how the composition of this ecosystem influences human physiology, development, and disease are still poorly understood. As a step toward systematically investigating these questions, we designed a microarray to detect and quantitate the small subunit ribosomal RNA (SSU rRNA) gene sequences of most currently recognized species and taxonomic groups of bacteria. We used this microarray, along with sequencing of cloned libraries of PCR-amplified SSU rDNA, to profile the microbial communities in an average of 26 stool samples each from 14 healthy, full-term human infants, including a pair of dizygotic twins, beginning with the first stool after birth and continuing at defined intervals throughout the first year of life. To investigate possible origins of the infant microbiota, we also profiled vaginal and milk samples from most of the mothers, and stool samples from all of the mothers, most of the fathers, and two siblings. The composition and temporal patterns of the microbial communities varied widely from baby to baby. Despite considerable temporal variation, the distinct features of each baby's microbial community were recognizable for intervals of weeks to months. The strikingly parallel temporal patterns of the twins suggested that incidental environmental exposures play a major role in determining the distinctive characteristics of the microbial community in each baby. By the end of the first year of life, the idiosyncratic microbial ecosystems in each baby, although still distinct, had converged toward a profile characteristic of the adult gastrointestinal tract.", "title": "Development of the Human Infant Intestinal Microbiota" }, { "docid": "36618603", "text": "The differentiation in vitro of murine embryonic stem cells to embryoid bodies mimics events that occur in vivo shortly before and after embryonic implantation. We have used this system, together with differential cDNA cloning, to identify genes the expression of which is regulated during early embryogenesis. Here we describe the isolation of several such cDNA clones, one of which corresponds to the gene H19. This gene is activated in extraembryonic cell types at the time of implantation, suggesting that it may play a role at this stage of development, and is subsequently expressed in all of the cells of the mid-gestation embryo with the striking exception of most of those of the developing central and peripheral nervous systems. After birth, expression of this gene ceases or is dramatically reduced in all tissues.", "title": "The murine H19 gene is activated during embryonic stem cell differentiation in vitro and at the time of implantation in the developing embryo." }, { "docid": "37480103", "text": "CONTEXT During pregnancy, serum levels of estrogen, progesterone, and other hormones are markedly higher than during other periods of life. Pregnancy hormones primarily are produced in the placenta, and signs of placental impairment may serve as indirect markers of hormone exposures during pregnancy. During pregnancy, these markers have been inconsistently associated with subsequent risk of breast cancer in the mother. OBJECTIVE To examine associations between indirect markers of hormonal exposures, such as placental weight and other pregnancy characteristics, and maternal risk of developing breast cancer. DESIGN AND SETTING Population-based cohort study using data from the Swedish Birth Register, the Swedish Cancer Register, the Swedish Cause of Death Register, and the Swedish Register of Population and Population Changes. PARTICIPANTS Women included in the Sweden Birth Register who delivered singletons between 1982 and 1989, with complete information on date of birth and gestational age. Women were followed up until the occurrence of breast cancer, death, or end of follow-up (December 31, 2001). Cox proportional hazards models were used to estimate associations between hormone exposures and risks of breast cancer. MAIN OUTCOME MEASURE Incidence of invasive breast cancer. RESULTS Of 314,019 women in the cohort, 2216 (0.7%) developed breast cancer during the follow-up through 2001, of whom 2100 (95%) were diagnosed before age 50 years. Compared with women who had placentas weighing less than 500 g in 2 consecutive pregnancies, the risk of breast cancer was increased among women whose placentas weighed between 500 and 699 g in their first pregnancy and at least 700 g in their second pregnancy (or vice versa) (adjusted hazard ratio, 1.82; 95% confidence interval [CI], 1.07-3.08), and the corresponding risk was doubled among women whose placentas weighed at least 700 g in both pregnancies (adjusted hazard ratio, 2.05; 95% CI, 1.15-3.64). A high birth weight (> or =4000 g) in 2 successive births was associated with an increased risk of breast cancer before but not after adjusting for placental weight and other covariates (adjusted hazard ratio, 1.10; 95% CI, 0.76-1.59). CONCLUSIONS Placental weight is positively associated with maternal risk of breast cancer. These results further support the hypothesis that pregnancy hormones are important modifiers of subsequent maternal breast cancer risk.", "title": "Pregnancy characteristics and maternal risk of breast cancer." }, { "docid": "25148216", "text": "Several members of the Kruppel-like factor (KLF) family of transcription factors play important roles in differentiation, survival, and trafficking of blood and immune cell types. We demonstrate in this study that hematopoietic cells from KLF4(-/-) fetal livers (FL) contained normal numbers of functional hematopoietic progenitor cells, were radioprotective, and performed as well as KLF4(+/+) cells in competitive repopulation assays. However, hematopoietic \"KLF4(-/-) chimeras\" generated by transplantation of KLF4(-/-) fetal livers cells into lethally irradiated wild-type mice completely lacked circulating inflammatory (CD115(+)Gr1(+)) monocytes, and had reduced numbers of resident (CD115(+)Gr1(-)) monocytes. Although the numbers and function of peritoneal macrophages were normal in KLF4(-/-) chimeras, bone marrow monocytic cells from KLF4(-/-) chimeras expressed lower levels of key trafficking molecules and were more apoptotic. Thus, our in vivo loss-of-function studies demonstrate that KLF4, previously shown to mediate proinflammatory signaling in human macrophages in vitro, is essential for differentiation of mouse inflammatory monocytes, and is involved in the differentiation of resident monocytes. In addition, inducible expression of KLF4 in the HL60 human acute myeloid leukemia cell line stimulated monocytic differentiation and enhanced 12-O-tetradecanoylphorbol 13-acetate induced macrophage differentiation, but blocked all-trans-retinoic acid induced granulocytic differentiation of HL60 cells. The inflammation-selective effects of loss-of-KLF4 and the gain-of-KLF4-induced monocytic differentiation in HL60 cells identify KLF4 as a key regulator of monocytic differentiation and a potential target for translational immune modulation.", "title": "Kruppel-like factor 4 is essential for inflammatory monocyte differentiation in vivo." }, { "docid": "16905344", "text": "Injured axons of the adult CNS undergo lengthy retraction from the initial site of axotomy after spinal cord injury. Macrophage infiltration correlates spatiotemporally with this deleterious phenomenon, but the direct involvement of these inflammatory cells has not been demonstrated. In the present study, we examined the role of macrophages in axonal retraction within the dorsal columns after spinal cord injury in vivo and found that retraction occurred between days 2 and 28 after lesion and that the ends of injured axons were associated with ED-1+ cells. Clodronate liposome-mediated depletion of infiltrating macrophages resulted in a significant reduction in axonal retraction; however, we saw no evidence of regeneration. We used time-lapse imaging of adult dorsal root ganglion neurons in an in vitro model of the glial scar to examine macrophage-axon interactions and observed that adhesive contacts and considerable physical interplay between macrophages and dystrophic axons led to extensive axonal retraction. The induction of retraction was dependent on both the growth state of the axon and the activation state of the macrophage. Only dystrophic adult axons were susceptible to macrophage \"attack. \" Unlike intrinsically active cell line macrophages, both primary macrophages and microglia required activation to induce axonal retraction. Contact with astrocytes had no deleterious effect on adult dystrophic axons, suggesting that the induction of extensive retraction was specific to phagocytic cells. Our data are the first to indicate a direct role of activated macrophages in axonal retraction by physical cell-cell interactions with injured axons.", "title": "Another Barrier to Regeneration in the CNS: Activated Macrophages Induce Extensive Retraction of Dystrophic Axons through Direct Physical Interactions" }, { "docid": "9412420", "text": "Mesenchymal stem cells (MSCs) commonly defined by in vitro functions have entered clinical application despite little definition of their function in residence. Here, we report genetic pulse-chase experiments that define osteoblastic cells as short-lived and nonreplicative, requiring replenishment from bone-marrow-derived, Mx1(+) stromal cells with \"MSC\" features. These cells respond to tissue stress and migrate to sites of injury, supplying new osteoblasts during fracture healing. Single cell transplantation yielded progeny that both preserve progenitor function and differentiate into osteoblasts, producing new bone. They are capable of local and systemic translocation and serial transplantation. While these cells meet current definitions of MSCs in vitro, they are osteolineage restricted in vivo in growing and adult animals. Therefore, bone-marrow-derived MSCs may be a heterogeneous population with the Mx1(+) population, representing a highly dynamic and stress responsive stem/progenitor cell population of fate-restricted potential that feeds the high cell replacement demands of the adult skeleton.", "title": "Endogenous bone marrow MSCs are dynamic, fate-restricted participants in bone maintenance and regeneration." }, { "docid": "3155731", "text": "T cells have crucial roles in protection against infection and cancer. Although the trafficking of memory T cells around the body is integral to their capacity to provide immune protection, studies have shown that specialization of some memory T cells into unique tissue-resident subsets gives the host enhanced regional immunity. In recent years, there has been considerable progress in our understanding of tissue-resident T cell development and function, revealing mechanisms for enhanced protective immunity that have the potential to influence rational vaccine design. This Review discusses the major advances and the emerging concepts in this field, summarizes what is known about the differentiation and the protective functions of tissue-resident memory T cells in different tissues in the body and highlights key unanswered questions.", "title": "Tissue-resident memory T cells: local specialists in immune defence" }, { "docid": "36708463", "text": "A major question is whether genes encoded on the sex chromosomes act directly in non-gonadal tissues to cause sex differences in development or function, or whether all sex differences in somatic tissues are induced by gonadal secretions. As part of this question we asked whether mouse X-Y homologous gene pairs are expressed in brain in a sex-specific fashion. Using RT-PCR and northern blot analysis, we assessed mRNA expression in brain of eight Y-linked genes as well as their X-linked homologues, at three ages: 13.5 days post coitum, the day of birth (P1) and adult. Transcripts of six Y genes were expressed at one or more ages: Usp9y, Ube1y, Smcy, Eif2s3y, Uty and Dby. Their expression also occurred in XY female brain, and therefore does not require testicular secretions. Six X-linked homologues (Usp9x, Ube1x, Smcx, Eif2s3x, Utx and Dbx) were also expressed in brain, and in adulthood all of these transcripts were expressed at significantly higher levels in brains of females than in brains of males, irrespective of their X-inactivation status. For five of these gene pairs, the expression of the Y-linked homologue in males was not sufficient to compensate for the female bias in X gene expression. Three X-Y gene pairs, Usp9x/y, Ube1x/y and Eif2s3x/y, appeared to be differentially regulated (expressed in brain in a different age- or tissue-dependent pattern), and hence may not be functionally equivalent. These sex differences in X-Y gene expression suggest several mechanisms by which these genes may participate in sex differences in brain development and function.", "title": "Sex differences in sex chromosome gene expression in mouse brain." }, { "docid": "8698208", "text": "Rett syndrome (RTT) is an inherited neurodevelopmental disorder of females that occurs once in 10,000–15,000 births. Affected females develop normally for 6–18 months, but then lose voluntary movements, including speech and hand skills. Most RTT patients are heterozygous for mutations in the X-linked gene MECP2 (refs. 3–12), encoding a protein that binds to methylated sites in genomic DNA and facilitates gene silencing. Previous work with Mecp2-null embryonic stem cells indicated that MeCP2 is essential for mouse embryogenesis. Here we generate mice lacking Mecp2 using Cre-loxP technology. Both Mecp2-null mice and mice in which Mecp2 was deleted in brain showed severe neurological symptoms at approximately six weeks of age. Compensation for absence of MeCP2 in other tissues by MeCP1 (refs. 19,20) was not apparent in genetic or biochemical tests. After several months, heterozygous female mice also showed behavioral symptoms. The overlapping delay before symptom onset in humans and mice, despite their profoundly different rates of development, raises the possibility that stability of brain function, not brain development per se, is compromised by the absence of MeCP2.", "title": "A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome" }, { "docid": "16322674", "text": "BACKGROUND Birth size, perhaps a proxy for prenatal environment, might be a correlate of subsequent breast cancer risk, but findings from epidemiological studies have been inconsistent. We re-analysed individual participant data from published and unpublished studies to obtain more precise estimates of the magnitude and shape of the birth size-breast cancer association. METHODS AND FINDINGS Studies were identified through computer-assisted and manual searches, and personal communication with investigators. Individual participant data from 32 studies, comprising 22,058 breast cancer cases, were obtained. Random effect models were used, if appropriate, to combine study-specific estimates of effect. Birth weight was positively associated with breast cancer risk in studies based on birth records (pooled relative risk [RR] per one standard deviation [SD] [= 0.5 kg] increment in birth weight: 1.06; 95% confidence interval [CI] 1.02-1.09) and parental recall when the participants were children (1.02; 95% CI 0.99-1.05), but not in those based on adult self-reports, or maternal recall during the woman's adulthood (0.98; 95% CI 0.95-1.01) (p for heterogeneity between data sources = 0.003). Relative to women who weighed 3.000-3.499 kg, the risk was 0.96 (CI 0.80-1.16) in those who weighed < 2.500 kg, and 1.12 (95% CI 1.00-1.25) in those who weighed > or = 4.000 kg (p for linear trend = 0.001) in birth record data. Birth length and head circumference from birth records were also positively associated with breast cancer risk (pooled RR per one SD increment: 1.06 [95% CI 1.03-1.10] and 1.09 [95% CI 1.03-1.15], respectively). Simultaneous adjustment for these three birth size variables showed that length was the strongest independent predictor of risk. The birth size effects did not appear to be confounded or mediated by established breast cancer risk factors and were not modified by age or menopausal status. The cumulative incidence of breast cancer per 100 women by age 80 y in the study populations was estimated to be 10.0, 10.0, 10.4, and 11.5 in those who were, respectively, in the bottom, second, third, and top fourths of the birth length distribution. CONCLUSIONS This pooled analysis of individual participant data is consistent with birth size, and in particular birth length, being an independent correlate of breast cancer risk in adulthood.", "title": "Birth Size and Breast Cancer Risk: Re-analysis of Individual Participant Data from 32 Studies" }, { "docid": "21489324", "text": "Located in the Kassena-Nankana districts of northern Ghana, the Navrongo health and demographic surveillance system (NHDSS) was established in 1992 by the Navrongo health research centre (NHRC). The NHRC is one of three research centres of the Ghana health service. The activities and potential of the NHDSS for collaborative research are described. The NHDSS monitors health and demographic dynamics of the two Kassena-Nankana districts of northern Ghana and facilitates evaluation of the morbidity and mortality impact of health and social interventions. The total population currently under surveillance is 152 000 residing in 32 000 households. Events monitored routinely include pregnancies, births, morbidity, deaths, migration, marriages and vaccination coverage. Data updates are done every 4 months by trained fieldworkers. The NHRC also undertakes biomedical and socio-economic studies. Additional features of the NHDSS include the community key informant system where trained volunteers routinely report key events, such as births and deaths as they occur in their locality and the verbal autopsy (VA) system for determining the probable causes of deaths that occur at the community level. Data from the NHDSS are shared with funders and collaborators and partners in the INDEPTH Network. The Director of the NHDSS is the contact person for potential collaboration with the NHDSS and the use of its data.", "title": "Profile of the Navrongo Health and Demographic Surveillance System." }, { "docid": "19489351", "text": "Somatic stem cells have been identified in multiple adult tissues. Whether self-renewal occurs symmetrically or asymmetrically is key to understanding long-term stem cell maintenance and generation of progeny for cell replacement. In the adult mouse brain, neural stem cells (NSCs) (B1 cells) are retained in the walls of the lateral ventricles (ventricular-subventricular zone [V-SVZ]). The mechanism of B1 cell retention into adulthood for lifelong neurogenesis is unknown. Using multiple clonal labeling techniques, we show that the vast majority of B1 cells divide symmetrically. Whereas 20%-30% symmetrically self-renew and can remain in the niche for several months before generating neurons, 70%-80% undergo consuming divisions generating progeny, resulting in the depletion of B1 cells over time. This cellular mechanism decouples self-renewal from the generation of progeny. Limited rounds of symmetric self-renewal and consuming symmetric differentiation divisions can explain the levels of neurogenesis observed throughout life.", "title": "Adult Neurogenesis Is Sustained by Symmetric Self-Renewal and Differentiation." } ]
4606
How do I bring money overseas?
[ { "docid": "507983", "text": "I'm an Australian who just got back from a trip to Malaysia for two weeks over the New Year, so this feels a bit like dejavu! I set up a 28 Degrees credit card (my first ever!) because of their low exchange rate and lack of fees on credit card transactions. People say it's the best card for travel and I was ready for it. However, since Malaysia is largely a cash economy (especially in the non-city areas), I found myself mostly just withdrawing money from my credit card and thus getting hit with a cash advance fee ($4) and instant application of the high interest rate (22%) on the money. Since I was there already and had no other alternatives, I made five withdrawals over the two weeks and ended up paying about $21 in fees. Not great! But last time I travelled I had a Commonwealth Bank Travel Money Card (not a great idea), and if I'd used that instead on this trip and given up fees for a higher exchange rate, I would have been charged an extra $60! Presumably my Commonwealth debit card would have been the same. This isn't even including mandatory ATM fees. If I've learned anything from this experience and these envelope calculations I'm doing now, it's these:", "title": "" }, { "docid": "511647", "text": "\"This page from TripAdvisor may be of interest. Look at what fees are charged on your ATM cards and credit cards, and consider overpaying your credit card so you have a credit balance that you can draw on for cash \"\"advances\"\" from ATMs that will dispense in local currency. Depending on what fees your bank charges, you may get a better rate than the forex cash traders at the airport. Edit: Cards may not always have the best rate. I recently heard from a traveler who was able to use a locally but not globally dominant currency to buy cash of a major currency at a shopping mall (with competitive forex traders) at rates even better than the mid-market rates posted at xe.com and similar places; I don't think you'll have that experience going from Australia to Malaysia (but another traveler reading this might have a different pair). In my experience the card rates are slightly worse than those and the airport forex traders significantly worse.\"", "title": "" } ]
[ { "docid": "576270", "text": "\"That's a very clear explanation, thanks! So a few additional things if anyone will humor my curiosity... 1. By \"\"one-time\"\" tax, does that mean a company that has, say, $5B overseas could bring that back into the US and just be taxed $500M, then keep the remaining $4.5B? 2. Could a company choose a percentage of their overseas money to transfer into the US? Like, only bring in 8% of that $5B ($400M) and be taxed $40M, while keeping all the rest outside the US? Or would it be mandatory to bring it all over? 3. Would most companies just start that same practice of routing to tax havens again after this tax is implented?\"", "title": "" }, { "docid": "403184", "text": "&gt; Our corporations pay some of the lowest taxes in the world, with some of the larger ones actually paying none. No, they don't. The top marginal rate for income taxes is 38%. Meanwhile, in the Republic of Ireland, rates vary from 12.5 - 25% depending on the exact source of the income. So, no, 'our' corporations do not pay the lowest taxes in the world. As far as them paying 'none', that stems from one of two things: one, corporations that pay out all their money in salaries and therefore have no retained earnings (hence, all their money is taxed at the individual level, and workers get socked at a full 35%), and two, corporations that create a price-transfer agreement with a foreign corporation so that income is shifted to a low-tax region where they end up paying nothing to Uncle Sam. That money will still be taxed if they ever try to bring it home and distribute it ... but as long as it stays overseas then no one can touch it because, technically, it hasn't been earned as income yet. That's how companies avoid greedy bastards trying to take their money -- because contrary to your opinion, you're not actually entitled to any of their money, or anyone else's money either. It's not 'your' money, or 'our' money, its 'their' money -- and they have an effective method to make sure it stays that way. &gt; Btw, if wanting decent opportunity to take care of me and mine is greed, then yes, I'm greedy. You can already do that -- it's called getting a fucking job and living within your means. You don't **DESERVE** anything in life -- you have to earn it. No one is obligated to just **GIVE** you things just because you want them. Ultimately, this whole 'lets sock it to the rich' attitude doesn't actually take any money out of their pockets ... the only people harmed are workers who can't take advantage of the methods they use to shift income overseas. In short: you're not simply wrong, you're criminally ignorant.", "title": "" }, { "docid": "408078", "text": "According to the US government a percent of your income from all over the world, whether or not any part of it happened in the US. You sold a burger made of US meat on a US bun in a US city? Yeah pay taxes to the US on it. You sell a burger made of Canadian meat on a Canadian bun in a Canadian city? You should pay Canadian taxes. In a reasonable world you should pay US taxes on a single burger and Canadian taxes on a single burger. In the real world you pay Canadian taxes on a single burger and US taxes on two burgers. Unless of course you keep your Canadian income overseas and never bring it to the US. Though you'll have to deal with a million articles about how you are hiding money from the US gov in overseas tax havens.", "title": "" }, { "docid": "401174", "text": "&gt; Tax rates do make a difference between whether to invest here or in Ireland. Not actual investment, but if you have the discretion to chanel profits to a lower taxed jurisdiction (necessarily a loophole that can be closed), then you may structure transactions accordingly. &gt; he money that American businesses profit overseas stays overseas instead of being repatriated because the taxes are too high to justify paying them before reinvesting the money in the economy. That is an issue that is also independent of tax rates. Providing incentives to bring money back is unlikely to finance any new investment though. There are loopholes that allow using foreign assets (cash especially) to fund foreign loans that can finance any desired investment. Still, even if repatriation is used for stock buybacks and dividends that would be more money flowing into the US, though not really money flowing to people who spend a high portion of flows (rich investors). But just because there are reasonable arguments for tax reform encouraging repatriation and HQ locations as at least not being harful, does not support also including the genuinely directly harmful effects of cuts to tax rates.", "title": "" }, { "docid": "363178", "text": "\"&gt; A corporation should be taxed based on where it does business and not where the corporate headquarters are located. But... but.. that's the whole point of the inversions. The US government tries to claim taxes on income from revenue generated overseas. So right now if BK repatariates it's overseas earnings, the US government will double dip beyond it's fair share and tax already taxed revenue just because it was taxed by non-US governments. All BK is doing is moving their headquarters to to a more business friendly economy that doesn't do similar double dipping. That way when they repatriate overseas money they are not being forced to pay taxes unjustly like they would be in the US. They will still pay taxes in the US for earnings in the US, they just won't pay US taxes on earnings foreign earnings. I don't think you Americans get just how fucked up and hostile your tax structure is. It has nothing to do with \"\"fair share\"\".\"", "title": "" }, { "docid": "462164", "text": "\"The economics in this are pretty, let's just say weird/off. US looks richer because of borrowing money therefore it's currency appreciates in relation to other countries? I don't see the logic in this one. The outsourcing jobs overseas phenomenon is a long term one. Firms don't do it cyclically with recessions. Recessions might force the hand of some firms to outsource but I don't see businesses suddenly bringing those jobs back en mass when a boom occurs. It also ignores the fact that when firms outsource, they can provide goods at a cheaper rate domestically thereby bringing down some costs. The decrease in costs might even make it cheaper for businesses to operate thereby allowing enough savings to hire more people. Who knows, the whole effect is somewhat ambiguous. To simply select the worst possible scenario and explain only that is pretty obvious bias. \"\"... When Uncle Sam can no longer pay it's bills\"\" The video says it like it's a certainty. Somehow he knows for a fact that the US will default soon yet the Investment Banks with teams of analysts don't.\"", "title": "" }, { "docid": "123511", "text": "\"What can I do to help him out, but at the same time protect myself from any potential scams? Find out why he can't do this himself. Whether your relative is being sincere or not, if he owns both accounts then he should be able to transfer money between them by himself. If you can find a way to solve that issue without involving your bank account, so much the better. Don't settle for \"\"something about authorized payees and expired cards.\"\" Get details, write them down. If possible, get documents. Then go to a bank or financial adviser you can trust and run those details by them to see what they have to say. Even if there's no scam, if what he's trying to do is illegal (even if he doesn't realize it himself) then you want to know before you get involved. You say you're willing to deal with \"\"other issues\"\" separately, but keep in mind that, even if there's no external scam here, those \"\"other issues\"\" could include hefty fees, censures on your own account, or jail time. Ask yourself: Does it make sense that this relative has an account overseas? I don't have any overseas accounts, because I don't do business in other countries. Is your relative a dual-citizen? Does he travel a lot? What country is the overseas account in? How long has he had this account? What bank is it with? Where the money is going is just as important as how it gets there (ie: through your account.) Arguably more so. Keep in mind that many scammers tell their marks not to share what's going on with anyone else. (Because doing so increases the odds of someone telling them to snap out of it.) It's entirely possible he's being scammed himself and just not telling you the whole story because the 419er is telling him to keep it quiet. (Check out that link for more details on common scams that your relative may be unwittingly part of, btw.) Get as many details as possible about what he's doing and why. If he's communicating with anyone else regarding this transfer, find out who. If there are emails, ask his permission to read them and watch for anything suspicious (ie: people who can't spell their own name consistently, constant pressure to act quickly, etc.)\"", "title": "" }, { "docid": "585494", "text": "\"Pay off the credit cards. From now on, pay off the credit cards monthly. Under no circumstances should you borrow money. You have net worth but no external income. Borrowing is useless to you. $200,000 in two bank accounts, because if one bank collapses, you want to have a spare while you wait for the government to pay off the guarantee. Keep $50,000 in checking and another $50k in savings. The remainder put into CDs. Don't expect interest income beyond inflation. Real interest rates (after inflation) are often slightly negative. People ask why you might keep money in the bank rather than stocks/bonds. The problem is that stocks/bonds don't always maintain their value, much less go up. The bank money won't gain, but it won't suddenly lose half its value either. It can easily take five years after a stock market crash for the market to recover. You don't want to be withdrawing from losses. Some people have suggested more bonds and fewer stocks. But putting some of the money in the bank is better than bonds. Bonds sometimes lose money, like stocks. Instead, park some of the money in the bank and pick a more aggressive stock/bond mixture. That way you're never desperate for money, and you can survive market dips. And the stock/bond part of the investment will return more at 70/30 than 60/40. $700,000 in stock mutual funds. $300,000 in bond mutual funds. Look for broad indexes rather than high returns. You need this to grow by the inflation rate just to keep even. That's $20,000 to $30,000 a year. Keep the balance between 70/30 and 75/25. You can move half the excess beyond inflation to your bank accounts. That's the money you have to spend each year. Don't withdraw money if you aren't keeping up with inflation. Don't try to time the market. Much better informed people with better resources will be trying to do that and failing. Play the odds instead. Keep to a consistent strategy and let the market come back to you. If you chase it, you are likely to lose money. If you don't spend money this year, you can save it for next year. Anything beyond $200,000 in the bank accounts is available for spending. In an emergency you may have to draw down the $200,000. Be careful. It's not as big a cushion as it seems, because you don't have an external income to replace it. I live in southern California but would like to move overseas after establishing stable investments. I am not the type of person that would invest in McDonald's, but would consider other less evil franchises (maybe?). These are contradictory goals, as stated. A franchise (meaning a local business of a national brand) is not a \"\"stable investment\"\". A franchise is something that you actively manage. At minimum, you have to hire someone to run the franchise. And as a general rule, they aren't as turnkey as they promise. How do you pick a good manager? How will you tell if they know how the business works? Particularly if you don't know. How will you tell that they are honest and won't just embezzle your money? Or more honestly, give you too much of the business revenues such that the business is not sustainable? Or spend so much on the business that you can't recover it as revenue? Some have suggested that you meant brand or stock rather than franchise. If so, you can ignore the last few paragraphs. I would be careful about making moral judgments about companies. McDonald's pays its workers too little. Google invades privacy. Exxon is bad for the environment. Chase collects fees from people desperate for money. Tesla relies on government subsidies. Every successful company has some way in which it can be considered \"\"evil\"\". And unsuccessful companies are evil in that they go out of business, leaving workers, customers, and investors (i.e. you!) in the lurch. Regardless, you should invest in broad index funds rather than individual stocks. If college is out of the question, then so should be stock investing. It's at least as much work and needs to be maintained. In terms of living overseas, dip your toe in first. Rent a small place for a few months. Find out how much it costs to live there. Remember to leave money for bigger expenses. You should be able to live on $20,000 or $25,000 a year now. Then you can plan on spending $35,000 a year to do it for real (including odd expenses that don't happen every month). Make sure that you have health insurance arranged. Eventually you may buy a place. If you can find one that you can afford for something like $100,000. Note that $100,000 would be low in California but sufficient even in many places in the US. Think rural, like the South or Midwest. And of course that would be more money in many countries in South America, Africa, or southern Asia. Even southern and eastern Europe might be possible. You might even pay a bit more and rent part of the property. In the US, this would be a duplex or a bed and breakfast. They may use different terms elsewhere. Given your health, do you need a maid/cook? That would lean towards something like a bed and breakfast, where the same person can clean for both you and the guests. Same with cooking, although that might be a second person (or more). Hire a bookkeeper/accountant first, as you'll want help evaluating potential purchases. Keep the business small enough that you can actively monitor it. Part of the problem here is that a million dollars sounds like a lot of money but isn't. You aren't rich. This is about bare minimum for surviving with a middle class lifestyle in the United States and other first world countries. You can't live like a tourist. It's true that many places overseas are cheaper. But many aren't (including much of Europe, Japan, Australia, New Zealand, etc.). And the ones that aren't may surprise you. And you also may find that some of the things that you personally want or need to buy are expensive elsewhere. Dabble first and commit slowly; be sure first. Include rarer things like travel in your expenses. Long term, there will be currency rate worries overseas. If you move permanently, you should certainly move your bank accounts there relatively soon (perhaps keep part of one in the US for emergencies that may bring you back). And move your investments as well. Your return may actually improve, although some of that is likely to be eaten up by inflation. A 10% return in a country with 12% inflation is a negative real return. Try to balance your investments by where your money gets spent. If you are eating imported food, put some of the investment in the place from which you are importing. That way, if exchange rates push your food costs up, they will likely increase your investments at the same time. If you are buying stuff online from US vendors and having it shipped to you, keep some of your investments in the US for the same reason. Make currency fluctuations work with you rather than against you. I don't know what your circumstances are in terms of health. If you can work, you probably should. Given twenty years, your million could grow to enough to live off securely. As is, you would be in trouble with another stock market crash. You'd have to live off the bank account money while you waited for your stocks and bonds to recover.\"", "title": "" }, { "docid": "209776", "text": "Reading about the [Bring Jobs Home Act](http://thehill.com/blogs/floor-action/senate/239029-republicans-blocked-the-democrats-insourcing-bill) it talks about how the (filibustered in July) bill would end the ability of companies to take a tax deduction for the costs of off-shoring labor(moving people and equipment overseas). The blog/newspaper articles don't really say much more than that.", "title": "" }, { "docid": "438038", "text": "\"You don't want to do that. DON'T LIE TO THE IRS!!! We live overseas as well and have researched this extensively. You cannot make $50k overseas and then say you only made $45k to put $5k into retirement. I have heard from some accountants and tax attorneys who interpret the law as saying that the IRS considers Foreign Earned Income as NOT being compensation when computing IRA contribution limits, regardless of whether or not you exclude it. Publication 590-A What is Compensation (scroll down a little to the \"\"What Is Not Compensation\"\" section). Those professionals say that any amounts you CAN exclude, not just ones you actually do exclude. Then there are others that say the 'can' is not implied. So be careful trying to use any foreign-earned income to qualify for retirement contributions. I haven't ran across anyone yet who has gotten caught doing it and paid the price, but that doesn't mean they aren't out there. AN ALTERNATIVE IN CERTAIN CASES: There are two things you can do that we have found to have some sort of taxable income that is preferably not foreign so that you can contribute to a retirement account. We do this by using capital gains from investments as income. Since our AGI is always zero, we pay no short or long term capital gains taxes (as long as we keep short term capital gains lower than $45k) Another way to contribute to a Roth IRA when you have no income is to do an IRA Rollover. Of course, you need money in a tax-deferred account to do this, but this is how it works: I always recommend those who have tax-deferred IRA's and no AGI due to the FEIE to roll over as much as they can every year to a Roth IRA. That really is tax free money. The only tax you'll pay on that money is sales tax when you SPEND IT!! =)\"", "title": "" }, { "docid": "470879", "text": "So how is it that American citizens working overseas get taxed, but American companies holding profits overseas don't? Or foreign companies making profits within the US for that matter. I don't really think we should be protectionist, but I do think corporations should be paying a fair share of taxes needed to support infrastructure, social and legal framework.", "title": "" }, { "docid": "562191", "text": "\"The elephant in the room is the research. From the article it seems to conclude that the majority of the research happened in the US, but Microsoft is claiming it happened overseas. From what I've seen a lot of *initial* research does happen in Microsoft international offices, all further development to bring it to market might be done in the US but the idea sprung elsewhere. From a taxation perspective you can argue that the patent was invented offshore and profits should be allocated there, or you can argue that it was the US development investment that made it profitable and so profits should be allocated in the US. Both are right - and this makes the US so interesting to invest in. If you invest in the US and then license offshore to sell back to a US entity - thats just exploiting a loophole. If it was invented offshore, thats what the laws are trying to protect. Personally I think Microsoft is doing pretty well here, like the demo of translations from chinese sign language to english - MSR Asia invented it, but it will be US teams transform it to a feature that derives income. Where should it be taxed if it does become a real product? How many other areas of Windows, Visual Studio, Office, Azure were \"\"invented\"\" by non-US teams and should also be taxed offshore?\"", "title": "" }, { "docid": "469993", "text": "This is stupid. Change the US tax law, that will fix it. Apple is avoiding taxes by playing an overseas card, are you getting rid of your iPhone, too, if you are about to boycott Burger King? Microsoft, is doing it, all the multinationals are playing games like this. I am not blaming them, I am just saying. More and more of the largest companies are leaving because of our excessive tax laws, we end up with lower net tax income as a result (fewer and fewer companies to pay the large taxes). These taxes also make us less and less competitive. Articles like this aren't going to cut it, waving a flag won't either. Oh, and don't get me started on the total stupidity on taxing US citizens living overseas for overseas income, even if they haven't lived or worked in the US for years. They have to pay whatever taxes of the country they are in, plus have to file and declare income to the US government, to also pay US taxes. I think only USA is doing that, btw. Look up how many people are force to give up their US citizenship because of these laws. That, too, has to be changed. The sooner the better.", "title": "" }, { "docid": "541126", "text": "&gt;**Firms responded to this act by significantly increasing repatriations from foreign affiliates.** This paper analyzes the impact of the tax holiday on firm behavior. It controls for endogeneity and omitted variable bias by using instruments that identify the firms likely to receive the largest tax benefits from the holiday. Repatriations did not lead to an increase in investment, employment or R&amp;D—even for the firms that lobbied for the tax holiday stating these intentions. Instead, a $1 increase in repatriations was associated with an increase of approximately $1 in payouts to shareholders. Offhand, that's all I would think that they were going to do. If you remove a tax from something, you effectively get more of it. You're removing a tax on *bringing capital home to the US.* This is a good thing no matter what is done with it, because it means our money isn't being used to build up another country. With the dividend being returned to stock holders, you have to realize that retirement plans are the biggest holders of dividend paying stock. Your parents, your grandma, just got a raise. Since they're living on fixed income, this has a very high stimulative effect. They buy something nicer at the grocery. They give their kids and grandkids a $20. This improves the economy from the bottom up. This is undoubtedly a good thing, and certainly much better than keeping that money overseas.", "title": "" }, { "docid": "269646", "text": "I find that there are two violation of law , prima facie , if someone earns money by depositing in the online account and then not reporting it ( including in his total income for the year ) and not bringing in India. Income Tax Act violation 1. It is simply comcealment liable for penalty & prosecution under I.T.Act. 2. You should know that anyone who is resident of India as per income Tax Act and having taxable income ( gross total income exceeding exemption limit) will have to fill up the column in his/her income tax return whether Previously these column were not in the Income Tax Return. So , now anyone who is liable to file return of Income can be tried for false return if he has hiddne assets aborad. 2. FEMA violation RBI permits remittance under Liberalized Remittance Scheme. However this scheme can not be used for certain purpose . It is important to examine whether RBI prohibits use of remittance for any entity or business you have described. You can read following FAQ on RBI site Q. 30. What are the prohibited items under the Scheme? Ans. The remittance facility under the Scheme is not available for the following: i) Remittance for any purpose specifically prohibited under Schedule-I (like purchase of lottery tickets/sweep stakes, proscribed magazines, etc.) or any item restricted under Schedule II of Foreign Exchange Management (Current Account Transactions) Rules, 2000; ii) Remittance from India for margins or margin calls to overseas exchanges / overseas counter-party; iii) Remittances for purchase of FCCBs issued by Indian companies in the overseas secondary market; iv) Remittance for trading in foreign exchange abroad; v) Remittance by a resident individual for setting up a company abroad; vi) Remittances directly or indirectly to Bhutan, Nepal, Mauritius and Pakistan; vii) Remittances directly or indirectly to countries identified by the Financial Action Task Force (FATF) as “non co-operative countries and territories”, from time to time; and viii) Remittances directly or indirectly to those individuals and entities identified as posing significant risk of committing acts of terrorism as advised separately by the Reserve Bank to the banks. You will have to examine , if the remittance was NOT done for purpose not allowed by RBI under LRS . If you clear this , you can say there is no violation and your violation is restricted to I.T.Act only.", "title": "" }, { "docid": "290857", "text": "\"Just addressing the sending side: you should be able to make the transfer out of the UK tax-free, if you transfer to a \"\"Recognised Overseas Pension Scheme\"\" (ROPS). These were formerly called QROPS (\"\"Qualifying...\"\") and a lot of online resources will talk about those. The basic idea is that as long as the overseas pension scheme guarantees to follow broadly similar rules to the UK system - e.g. not allowing you to withdraw your money before retirement age - then you can transfer to it. There's a list of these schemes on the HMRC website, but in theory you still have to check for yourself that they actually follow the relevant rules. I'm not sure how to do that in practice. There are only two USA providers listed, which suggests that transferring there isn't actually very common. The Wikipedia page suggests that in practice most people transfer to a scheme in a low-tax place like Gibraltar, rather than where they actually move to. I suspect that any move will be quite expensive in fees, and from your own answer it seems the USA won't recognise it as a transfer in anyway.\"", "title": "" }, { "docid": "529731", "text": "There is no limit on how much money you can bring into the USA, in Cash or through electronic transfer. You only need to be able to proof or convincingly show that you earned it legally and paid all potential US taxes that you had to pay. If you chose to bring it in cash, you need to tell customs when arriving (and again, be prepared to proof the legal sources). Wire transfer, cash in the suitcase, whatever you like. There is no tax for bringing the money, and the tax for making that money supposedly is already paid. Once the money is in the US, and earns more money, you will owe taxes on the gain (not on the capital itself, just on the amounts it increases by) I hope you understand that if you live in the US, and you have money anywhere in the world, you might need to report it to the IRS; and if your money makes interest anywhere in the world (including of course in India), you might be are required to pay US taxes on the gains. That is independent of your question; but if you don't do it, you are cheating the IRS, and they will ask this when you bring the money back.", "title": "" }, { "docid": "536374", "text": "\"Re: Specifically, am I right in that everything I put on these is deducted from tax, or are there other rules? and Am I correctly understanding this as \"\"anything above £3,600 per year will not be deducted from your tax\"\"? Neither interpretation seems quite right… Unless what you mean is this: The contributions (to a pension, or to the share-save scheme) are deducted from your pay before it is taxed. That's how it works for employer-run pension schemes. In other words, you are paying the gross amount you earn into the pension, not the amount after tax. It's a tax-efficient way to save, because: compared to other forms of saving: (The bit about the £3,600: you can ignore this assuming you're earning more than £3,600 a year.) What happens to the pension if you decide to move back to France or another country? In some cases you can transfer tax free. Worst case, you'd pay some tax on the transfer but not more than 25%. [See here for the current rules: https://www.gov.uk/transferring-your-pension/transferring-to-an-overseas-pension-scheme. Re: the share scheme, if by 'salary exchange' you mean salary sacrifice (where your gross pay is officially reduced by that amount e.g. £150 a month), that's even more tax-efficient, because it saves you paying the National Insurance contribution too (approx 9% of the pay packet). Conclusion: Saving into pension and company share save schemes is supremely tax-efficient and, provided you're OK with your money being locked away until you're 57 (pension) or tied up in company shares, it's understandably many people's priority to make use of these schemes before considering other forms of saving where you pay into them from your salary after tax. Now, about this: I am trying to understand how much I should put into it Should I put money into these, or should look for another way to save (how will this work out if I go back to France or another country)? Nobody here can advise you what to do since individuals' goals and circumstances are different and we don't know enough of the picture. That said: FWIW, I'll tell you what I might do based solely on what you've told us in the question… First, I'd definitely contribute 6% to the company pension. This gets you the full employer match. That's free money (plus, remember the tax relief = more free money). If you're 27, a total of 12% salary into a pension a year is a decent rate to start saving for retirement. Actually, 14% would be generally advisable, and maybe more still – it's generally a case of 'the more the better' especially while young, as you have time for growth and you don't know what later priorities might change / financial needs might arise. Nevertheless, you said you might move overseas. So in your position I would then:\"", "title": "" }, { "docid": "350315", "text": "Do I report it as income? Is it subject to just the same amount of taxes (~30%) as regular income? Are there any restrictions on how it can be used? It is income. You can deduct the costs of maintaining the web page and producing the software from it (have an accountant do that for you, there are strict rules on how to do that, and you can only deduct up to the income if its a hobby and not a for-profit business), but otherwise it's earned income like any other self employment income. It is reported on your schedule C or on line 21 of your 1040 (miscellaneous income), and you're also liable for self-employment taxes on this income. There are no restrictions, it's your money. Technically, who is the donation even being made to? Me, just because I own the webpage? Yes. This is for the United States, but is there any difference if the donations come from overseas? No, unless you paid foreign taxes on the money (in which case you should fill form 1116 and ask for credit). If you create an official 501(c) organization to which the donations are given, instead of you getting it directly, the tax treatment will be different. But of course, you have to have a real charitable organization for that. To avoid confusion - I'm not a licensed tax professional and this is not a tax advice. If in doubt - talk to a EA/CPA licensed in your State.", "title": "" }, { "docid": "145299", "text": "I was thinking down the road about what may happen as some countries pile on debt and others are more responsible. I've spent a lot of time oversea and talented people in the capital cities are really mobile these days. Right now there's a small brain drain to the benefit of Switzerland which has some really innovative people moving there. What if a large country like Germany were to do on a larger scale? Educated workforce, innovative and if you overlook a really ugly period, a great history of innovation. It seems they could bring in a lot of people from Japan and (increasingly) the US as they head slowly toward debt of 200% of GDP. Why would talented people who are highly mobile want to stay in a country where the debt will take 30 years to repay mostly on the back of the talented high earning people?", "title": "" }, { "docid": "521491", "text": "\"Maybe I am a bit jaded but I don't spend a lot of time trying to convince friends or family members to avoid MLM schemes even though I personally see them as scams. If they specifically ask for my advice I will walk them through the economics of the particular MLM that they are interested in. I have found that if you get to pushy in showing your friends or family members that their new \"\"business\"\" is actually a fraud they tend to get defensive and it becomes counter productive to continue trying to convince them of their mistake. You waste your time and anger your friend or family member. It's just not worth it. There are a few key questions I like to ask people about their MLM \"\"business\"\". What does the business do? How do you make money? How do they make money? You would be amazed at the number of people that sign up and pay money to get into a business and they don't even have the slightest clue what the business actually does. Even fewer have an idea about how they can actually make money because the entire sales presentation focuses on what they could with all of the money they \"\"are going to make\"\". Why does this business need you? What do you bring to the table that the business doesn't already have (skills, contacts, money)? Most MLM's and especially the pyramid schemes focus more on recruiting people than selling products because they make their money on over priced initiation fees, and their products are mediocre at best.\"", "title": "" }, { "docid": "121543", "text": "My wife and I meet in the first few days of each month to create a budget for the coming month. During that meeting we reconcile any spending for the previous month and make sure the amount money in our accounts matches the amount of money in our budget record to the penny. (We use an excel spreadsheet, how you track it matters less than the need to track it and see how much you spent in each category during the previous month.) After we have have reviewed the previous month's spending, we allocate money we made during that previous month to each of the categories. What categories you track and how granular you are is less important than regularly seeing how much you spend so that you can evaluate whether your spending is really matching your priorities. We keep a running total for each category so if we go over on groceries one month, then the following month we have to add more to bring the category back to black as well as enough for our anticipated needs in the coming month. If there is one category that we are consistently underestimating (or overestimating) we talk about why. If there are large purchases that we are planning in the coming month, or even in a few months, we talk about them, why we want them, and we talk about how much we're planning to spend. If we want a new TV or to go on a trip, we may start adding money to the category with no plans to spend in the coming month. The biggest benefit to this process has been that we don't make a lot of impulse purchases, or if we do, they are for small dollar amounts. The simple need to explain what I want and why means I have to put the thought into it myself, and I talk myself out of a lot of purchases during that train of thought. The time spent regularly evaluating what we get for our money has cut waste that wasn't really bringing much happiness. We still buy what we want, but we agree that we want it first.", "title": "" }, { "docid": "207354", "text": "I think that is the wrong approach. You certainly need to teach the value of work, but you cannot tie it to income levels as a hard and fast rule. If you do, how do you then explain athletes making millions per year and only 'working' half a year, at most. And, then comparing that person to a person working hard in a factory, 40-50 hours per week, 50 weeks per year, bringing home $50K per year? I've always taught my kids to work hard and with integrity. And, most importantly, you better enjoy the work you do because no matter how much money you make, if you dread getting up in the morning to go to work, your money won't make you happy. I've never focused on the amount of money they should be making.", "title": "" }, { "docid": "236441", "text": "Tax rates do make a difference between whether to invest here or in Ireland. The rate of return would be lower in a place where you pay higher taxes, as taxes are a cost. The investment is going to happen, sure, it just depends on where that occurs. And then secondly, the money that American businesses profit overseas stays overseas instead of being repatriated because the taxes are too high to justify paying them before reinvesting the money in the economy. This is a problem because it means jobs for everyday Americans going to another country, where due to Balassa-Samuelson, the other country is already more attractive in terms of labor costs due to our high price levels here in the US.", "title": "" }, { "docid": "421575", "text": "Are financial institutions less likely to lend me money because of my age Yes. But they are especially unlikely to loan you money because you have little income. or because they know I avoid interest by paying things off aggressively? This won't affect them. But you might ask yourself how much credit history you have. Credit history can include all of loans, credit cards, rent, utilities, etc. You mention three loans. But you don't mention rent or utilities. You may simply not have much credit history, even if what you do have is good. But again, the biggest thing that they will look at is your income history. If you have a small income, then it doesn't matter what your payment history is. They don't want to loan money to people who need money. They want to loan money to people who don't need to borrow but are instead bringing a future purchase into the present. The ideal recipient is someone who has a high income and spends it all every month. Such a person is likely to borrow heavily but be able to keep up the payments. Obsessing about your ability to borrow is probably the wrong approach. Instead focus on how you can meet your goals without borrowing. Eventually your ability to pay will catch up. Then they'll offer you money. Of course, you might not need it then. Note that when I say little income, I'm talking about their perspective. You may be fully on track and making decent money or even very good money for your age. But they're looking for people who are mature in their careers and regularly bringing home large sums but who spend it faster than they can get it.", "title": "" }, { "docid": "544630", "text": "\"Designed by Apple in California, manufactured in China. At this point in time Apple has more employees in the US than in the past. They never really moved jobs overseas, mostly they just spun up work overseas because that's where all of the components of the supply chain were. When you say \"\"hey... I want to start cranking out devices. I need to know how fast you can turn if there's a design change late in the pre-production stage\"\" and the best answers you get are from makers in China, that's where your work goes.\"", "title": "" }, { "docid": "197910", "text": "\"Absolutely. You can trace all of it back to Reagan. His awful Tax Reform Act of 1986 made corporate profits from operations in foreign countries tax exempt, unless and until the corporations chose to \"\"repatriate\"\" those profits [i.e. bring them back to the U.S.], in which case they were subject only to a sharply reduced tax. This provision created the huge impetus for U.S. corporations to move their operations, and their jobs, overseas. Reagan initiated the huge increase in income and wealth inequality.\"", "title": "" }, { "docid": "559357", "text": "After reading your back and forth with geerussell, its interesting seeing you bring up WWII, where the concern was full output and employment, just as he is suggesting. If the government wants to, it can take a country mired in depression, with women mostly out of the work force and men unemployed in great numbers, and have near full employment and the addition of women in the work force in a few short years. *And they were shipping a lot of their best laborers and much of their output overseas to be simply destroyed.*", "title": "" }, { "docid": "226625", "text": "I expect it goes back long before Eisenhower. I expect it goes back long before Washington. I expect it goes back long before Julius Caesar. That shouldn't mean I can express my disgust at it. I'm weary of politics, and a company that wants my money doesn't need to pander to any ideology they think I hold. More specific to this particular story, I don't particularly care how my employees vote. I pay them for the value they bring to our company; what they do with THEIR money is up to them.", "title": "" }, { "docid": "586272", "text": "\"The real question is what can you NOT do! If you track all your monetary actions, you know everything about your monetary situation. That means you have the tools to ask and answer \"\"what if\"\" questions, such as: \"\"If I get a 10% raise, could I take longer vacations?\"\" You could calculate how much you spend per day on vacation and then consider the amount of your raise and how much of it you'd need to allocate to vacations to, say, be able to take a two-week vacation instead of a one-week vacation. \"\"How much more would I have to earn to move to this nicer apartment?\"\" This may seem like a simple question, but a surprising number of people can't answer it in a reliable way, because they don't have a clear understanding of how much money they make and how much of it they can afford to spend on housing. If you find you have lots of spare income, maybe you can move to the nicer place right away; if not, at least you can get a sense of how much more money you'd need to make it happen. \"\"If I started taking the bus to work, how much would I save?\"\" You can look at how much you spend on gas and compare that to the price of a bus pass. By separating out categories like gas, repairs, and car insurance, you can also calculate different scenarios, like if you still kept your car but only used it for occasional trips, versus if you sold the car and used only public transportation. \"\"If I want to take a trip to Tahiti, what can I cut back on to save the money?\"\" Using your table you can pencil out scenarios like \"\"Suppose I stop eating out for lunch at work and just bring my lunch, how long would I have to do that to save enough to pay for a plane ticket?\"\" These are just a few random examples. The general idea is that with a record of hard numbers, you can start to consider potential tradeoffs in an objective way --- that is, you can ask \"\"how much in category X would I have to give up to gain this thing I want in category Y?\"\" The real trick in making use of your data is not so much \"\"what\"\" you can do, but \"\"how\"\" exactly to do it. You may have to become more of a spreadsheet wizard to really delve into these questions. Also, if you have programming expertise, you can even use something like Python to do calculations that might be laborious in a spreadsheet.\"", "title": "" } ]
44181
T-Pain's debut album was Chocolate and Cheese.
[ { "docid": "T-Pain", "text": "Faheem Rashad Najm ( born September 30 , 1985 ) , better known by his stage name T-Pain , is an American rapper , singer , songwriter and record producer from Tallahassee , Florida . His debut album , Rappa Ternt Sanga , was released in 2005 . In 2007 , T-Pain released his second album Epiphany , which reached number one on the US Billboard 200 chart . His third album , Thr33 Ringz , was released in 2008 . T-Pain has also released a string of hit singles , including `` I 'm Sprung '' , `` I 'm 'n Luv ( Wit a Stripper ) '' , `` Buy U a Drank ( Shawty Snappin ' ) '' , `` Bartender '' , `` Ca n't Believe It '' , `` 5 O'Clock '' and more . T-Pain has earned two Grammy Awards , alongside artists Kanye West and Jamie Foxx respectively . T-Pain is the founder of the record label imprint Nappy Boy Entertainment , established in 2005 . Throughout his career as a singer , T-Pain is best known for using and popularizing the creative use of the Auto-Tune pitch correction effect , used with extreme parameter settings to create distinctive vocal sounds . From 2006 to 2010 , T-Pain was featured on more than 50 chart topping singles , his most successful feature to date was on Flo Rida 's debut single `` Low '' , which has since been certified 6x platinum by the Recording Industry Association of America ( RIAA ) .", "title": "" } ]
[ { "docid": "T-Pain_discography", "text": "The discography of T-Pain , an American R&B singer , songwriter record producer and rapper , consists of four studio albums , forty-two singles ( as lead artist , and featured artist ) , five mixtapes , and thirty-six music videos . On December 6 , 2005 , his debut studio album , Rappa Ternt Sanga , is where it first appeared on the charts , when it debuted at number 33 on the US Billboard 200 . Both singles , `` I 'm Sprung '' and `` I 'm 'n Luv ( Wit a Stripper ) '' , peaked in the top ten on the US Billboard Hot 100 . After that , he collaborated with fellow rapper E-40 , along with an singer Kandi Burruss on the single `` U and Dat '' , which it peaked at number 13 in the United States . In 2007 , his second album , titled Epiphany ( 2007 ) , which debuted at number 1 in the United States . The lead single `` Buy U a Drank ( Shawty Snappin ' ) '' , peaked at number one in the United States , the follow-up single `` Bartender '' which peaked at number 5 , and the album 's third single `` Church '' . During 2007 , T-Pain made several guest appearances on songs by other performing artists , the most commercially successful of these being `` Low '' by Flo Rida , which peaked at number one in the United States , and on several national singles charts worldwide . In November 2008 , T-Pain released his third studio album , Three Ringz , debuted at number 4 in the United States , and its consists by all 3 singles -- `` Chopped 'n' Skrewed '' , `` Ca n't Believe It '' and `` Freeze '' . In 2008 , T-Pain appeared on several other singles by other performing artists , including `` Got Money '' by Lil Wayne , `` The Boss by Rick Ross and `` One More Drink '' by Ludacris , among several others . T-Pain 's fourth studio album , Revolver , was released in December 2011 . The album has been preceded by the release of the promotional singles `` Take Your Shirt Off '' , `` Reverse Cowgirl '' and `` Rap Song '' , as well as the single `` Booty Wurk ( One Cheek at a Time ) '' , which attained mixed success on worldwide charts . On May 4 , 2011 , T-Pain released a mixtape , PrEVOLVEr , in promotion of the album . The first official single from Revolver was `` Best Love Song '' , which features Chris Brown . The album 's second single was `` 5 O'Clock '' , which features Wiz Khalifa and Lily Allen . The album 's third single was `` Turn All the Lights On '' , which features Ne-Yo .", "title": "" }, { "docid": "Epiphany_(T-Pain_album)", "text": "Epiphany is the second studio album by American record producer and recording artist T-Pain . It was released on June 5 , 2007 , by his record label Nappy Boy Entertainment , distributed by Akon 's label Konvict Muzik and Jive Records . The album marks as a first for T-Pain ; who launched his own record label Nappy Boy Entertainment . Critics gave the album positive reviews for T-Pain 's production and his use of various characters throughout its track listing . Epiphany debuted at number one on the Billboard 200 and spawned three singles : `` Buy U a Drank ( Shawty Snappin ' ) '' , `` Bartender '' and `` Church '' .", "title": "" }, { "docid": "Time_To_Make_Love", "text": "Time To Make Love was R&B singer T-Pain 's first song which features a rapper named Sarge on the second verse . It was the start of T-Pain 's solo singing career . It was released in his mixtape and did n't make it to the official track list of T-Pain 's debut album Rappa Ternt Sanga . T-Pain stated it was his first song to be played on the radio as a solo artist , yet was asleep & was n't able to enjoy that mini moment of success . Category : T-Pain songs", "title": "" }, { "docid": "Chocolate_and_Cheese", "text": "Chocolate and Cheese is the fourth studio album by Ween , originally released by Elektra Records in 1994 . It was the first Ween album to be recorded in a professional studio , in contrast to the crude four-track home recordings of their first three albums . However , most of the instruments were still played by Dean and Gene Ween , including their drum machine .", "title": "" }, { "docid": "Shawty_Get_Loose", "text": "`` Shawty Get Loose '' is the third single from hip hop artist Lil Mama 's debut album , VYP : Voice of the Young People . The single is the remix version , where it features Chris Brown singing the chorus , and T-Pain rapping on the second verse . In the original , T-Pain originally sings the chorus , while Lil Mama raps on the second verse . Instead of T-Pain using the Auto-Tune effect , Chris Brown uses it , like he did in his other collaboration with T-Pain , `` Kiss Kiss '' .", "title": "" }, { "docid": "I'm_Sprung", "text": "`` I 'm Sprung '' is the debut single by American singer T-Pain from his debut album Rappa Ternt Sanga . The song is dedicated to his wife , Amber . T-Pain thanked DJ Felli Fel for being the first person to play the song on the radio .", "title": "" }, { "docid": "T_Lopez", "text": "Christina T. Lopez ( born April 18 , 1981 ) , better known by her stage name T Lopez , is a Mexican American actress and singer from Ontario , California . T Lopez was a former member of the Latina group known as Soluna , signed to DreamWorks Records , whose musical debut album `` For All Time '' and debut single of the same name was released in 2002 . The group opened for the international tours of Enrique Iglesias and Marc Anthony . Now a solo artist , T Lopez signed a record label deal with Cash Money Records and Universal Republic Records and is currently working on both an English album and a Spanish album . The English album is expected to feature Lil Wayne , Birdman , Daddy Yankee , T-Pain , Flo Rida , Glasses Malone and Colby O'Donis . The Spanish Album is expected to feature A.B. Quintanilla , Jon Secada , The D.E.Y. , and Kinky .", "title": "" }, { "docid": "Bartender_(T-Pain_song)", "text": "`` Bartender '' is an R&B / hip-hop song by T-Pain , Co-written by Ali Noordin and the official second single from his second album , Epiphany . The song debuted on the Billboard Hot 100 chart on the issue date of June 16 , 2007 at # 97 and has since peaked at # 5 , making the single T-Pain 's 4th consecutive top 10 hit single on the Billboard Hot 100 as well as Akon 's 9th top 10 hit single on the same chart . In 2008 the song was nominated for a Grammy for Best R&B Performance by a Duo or Group .", "title": "" }, { "docid": "A.D.I.D.A.S._(Killer_Mike_song)", "text": "`` A.D.I.D.A.S. '' is a song by American rapper Killer Mike , released as the second single from his debut studio album Monster ( 2003 ) . The song features guest appearances from fellow rapper Big Boi and singer Sleepy Brown , and is produced by Mr. DJ , who helped write the song along with the two rappers . The lead hook that continues throughout the song is sampled from the Ween song `` Roses are Free '' , from their 1994 album Chocolate and Cheese .", "title": "" }, { "docid": "Low_(Flo_Rida_song)", "text": "`` Low '' is the debut single by American rapper Flo Rida , featured on his debut studio album Mail on Sunday and also featured on the soundtrack to the 2008 film Step Up 2 : The Streets . The song features and was co-written by fellow American rapper T-Pain . There is also a remix in which the hook is sung by Flo Rida rather than T-Pain . An official remix was made which features Pitbull and T-Pain . With its catchy , up-tempo and club-oriented Southern hip hop rhythms , the song peaked at the summit of the U.S. Billboard Hot 100 . The song was a massive success worldwide and was the longest-running number-one single of 2008 in the United States , spending ten consecutive weeks atop the Billboard Hot 100 . With over six million digital downloads , it has been certified 8 × Platinum by the RIAA , and was the most downloaded single of the 2000s decade , measured by paid digital downloads . The song was named third on the Billboard Hot 100 Songs of the Decade .", "title": "" }, { "docid": "The_Instrumentals_(T-Pain_album)", "text": "The Instrumentals is a compilation album containing instrumentals of select songs composed and performed by musician T-Pain . It was first released for digital download at Amazon.com on August 21 , 2009 . The tracks were available for purchase on iTunes just four days later . The songs that are released as instrumentals come from all albums by T-Pain , including Rappa Ternt Sanga , Epiphany , and Thr33 Ringz . The songs are uploaded on T-Pain 's official MySpace profile .", "title": "" }, { "docid": "I_Can't_Wait_(Akon_song)", "text": "`` I Ca n't Wait '' is the seventh single from Senegalese singer-songwriter Akon 's second studio album , Konvicted . The song was released as a digital download only single on April 14 , 2008 . The song features additional vocals from R&B singer and rapper T-Pain . The song was added to and peaked at the C-list on BBC Radio 1 's playlist . The song reached # 116 on the UK Singles Chart . The original version of the song was entitled `` You and Me '' , and is unreleased track from T-Pain 's debut album , Rappa Ternt Sanga .", "title": "" }, { "docid": "Revolver_(T-Pain_album)", "text": "Revolver ( stylized as REVOLVEЯ ) , is the fourth studio album by American rapper T-Pain , released through Konvict Muzik , RCA Records and his own label Nappy Boy Entertainment on December 6 , 2011 . It is his first album released after the dissolution of his previous label , Jive Records . Recording sessions for the album have taken place from 2009 to 2011 . T-Pain stated that the two R 's in the word , RevolveЯ have been capitalized so that in the middle , it says `` evolve '' , indicating that T-Pain has evolved as an artist , and as a person in the period from Thr33 Ringz up till RevolveЯ . He later stated that the R 's were put to show how people can be deceived , and precept incorrectly without looking at the inside of things , and he then said that this will be the scheme of the album . T-Pain announced that the album would be released on December 6 in the United States in an interview with Lady Jade on the F.A.M.E. tour bus , coincidentally this is the same release date of his first album , Rappa Ternt Sanga back in 2005 . At the end of 2009 , and throughout the early part of 2010 , several singles were released from the album ; however , the poor chart performance of these songs caused them to re-dubbed as promotional singles .", "title": "" }, { "docid": "Rick_Ross_discography", "text": "The discography of Rick Ross , an American rapper , consists of nine studio albums , one compilation album , eighty-five singles ( including sixty-five as a featured artist ) , one soundtrack , and forty music videos . Ross 's debut album , Port of Miami , was released in 2006 , which features the singles , `` Hustlin ' '' and `` Push It '' . Ross 's second album , Trilla was released in 2008 , which spawned the singles , `` The Boss '' which features T-Pain and `` Here I Am '' which features Nelly and Avery Storm . Ross 's third studio album , Deeper Than Rap was released on April 21 , 2009 . Deeper Than Rap which included the singles , `` Magnificent '' , which features John Legend and `` Maybach Music 2 '' , which features Kanye West , Lil Wayne and T-Pain . On July 20 , 2010 , Ross released his fourth studio album , Teflon Don , which includes the hit single , `` Aston Martin Music '' , which features Drake and Chrisette Michele . Ross has also appeared in many other artist 's singles and tracks , including `` All I Do Is Win '' by DJ Khaled also featuring Ludacris , Snoop Dogg and T-Pain , and `` I 'm On One '' also by Khaled featuring Drake and Lil Wayne . The latter peaked at number 10 on the Hot 100 , becoming Ross ' most successful song to date , and was also nominated at the 54th Annual Grammy Awards .", "title": "" }, { "docid": "We_Global", "text": "We Global is the third studio album by Miami based mixtape DJ and Terror Squad member , DJ Khaled . The album was released on September 16 , 2008 . This was his third album distributed by Koch Records ( now Entertainment One Music ) , and the first released on his We the Best Music Group label . The album 's guest appearances from Game , T-Pain , Bun B , Rick Ross , Ace Hood , Plies , Akon , Trick Daddy , Lil Boosie , Nas , Kanye West , Fabolous , Fat Joe , Sean Paul , Busta Rhymes , Pitbull , Casely and Flo Rida among others . The album 's first single , `` Out Here Grindin '' leaked on May 5 , 2008 . The song features Akon , Rick Ross , Lil Boosie , Trick Daddy , Ace Hood and Plies . The single debuted and peaked at number 38 on the US Billboard Hot 100 . The album 's second single was `` Go Hard '' featuring Kanye West and T-Pain . The song peaked at number 69 on the US Billboard Hot 100 .", "title": "" }, { "docid": "Uncle_Charlie", "text": "Uncle Charlie is the fourth studio album by Charlie Wilson and was released on February 17 , 2009 . It features production from Gregg Pagani , The Underdogs , Bigg D , T-Pain and L.O.S. da Maestro . It features guest appearances from Snoop Dogg , Jamie Foxx and T-Pain . The first two singles from the album are `` Supa Sexxy '' and `` There Goes My Baby '' , the latter receiving major airplay on the Urban and Adult R&B radio stations as well being named Billboard Magazine 's number one Urban Adult Song for 2009 . It debuted and peaked at number two on the Billboard 200 with sales of 58,000 copies in its first week . This was his highest peak on the Billboard 200 to date and so far has sold 362,355 copies . At the 52nd Grammy Awards the album was nominated for Best R&B Album and the song `` There Goes My Baby '' was nominated for Best Male R&B Vocal Performance .", "title": "" }, { "docid": "Can't_Believe_It_(T-Pain_song)", "text": "`` Ca n't Believe It '' is a single by American producer/singer-songwriter T-Pain . It was released on July 29 , 2008 . The song is the first official single from T-Pain 's album Thr33 Ringz . The song also features rapper Lil Wayne . This is the second collaboration between T-Pain & Lil Wayne released as a single .", "title": "" }, { "docid": "Freeze_(T-Pain_song)", "text": "`` Freeze '' is the third and final single from R&B singer T-Pain from his third album , Thr33 Ringz . The song features singer Chris Brown . The song was released on iTunes on October 10 and was added to T-Pain 's MySpace on October 17 . A version that features Omarion was originally on the album , but was changed to Chris Brown .", "title": "" }, { "docid": "Who_the_Fuck_Is_That?", "text": "`` Who the Fuck Is That ? '' or the edited version known as `` Who the Heck Is That ? '' or the BET version known as `` Who the Heck ... '' is the first single off slain rapper Dolla 's unreleased debut album A Dolla and a Dream , as well as his mixtape Another Day Another Dolla . The song features T-Pain and Tay Dizm . The official remix of the song features labelmates T-Pain , Akon and Klepto . It is produced by DJ Montay and Akon . The edited version of the original makes a sound of glass breaking to censor out the word `` fuck '' . The edited version of the remix makes a blur-like sound when `` fuck '' is said , making it sound like `` funk '' . At the end of Dolla 's second verse , he says `` Album comin ' soon , bitch , get ready for the summa '' , referring to the late release of the single as to when the song was officially leaked around July 2007 . The song was originally for rapper Klepto featuring Bravo with T-Pain on the chorus , because of label disputes and distribution agreements the rights for the song were passed to rapper Loon , Later , Loon 's verses was replaced by verses by Dolla and finally Tay Dizm 's verse was added on the final version . Later releasing a version featuring Klepto and Bravo The Vulgar Basterd as a Freestyle Remix .", "title": "" }, { "docid": "Cash_Flow_(Ace_Hood_song)", "text": "`` Cash Flow '' is the debut single from rapper Ace Hood 's debut album Gutta . It features T-Pain , Rick Ross and DJ Khaled with a quick intro . DJ Khaled 's not credited in `` Cash Flow '' . It is produced by The Runners .", "title": "" }, { "docid": "Young_Fyre", "text": "Tramaine Winfrey ( born March 9 , 1986 ) , professionally known as Young Fyre , is an American record producer signed to T-Pain 's record label , Nappy Boy Entertainment . He has worked extensively with T-Pain and produced most of the album Revolver , T-Pain 's fourth studio album . Young Fyre has also worked with Britney Spears , Tech N9ne , Krizz Kaliko , Lil Wayne , Ace Hood , Chris Brown , Mario , Busta Rhymes , Big Time Rush , Nicholas RAS Furlong , Rico Love , The Writing Camp , and many others . Among the notable songs credited to him are T-Pain 's `` Best Love Song '' featuring Chris Brown , Britney Spears ' `` Private Show '' and `` What You Need '' , `` Rap Song '' featuring Rick Ross , and `` Booty Wurk ( One Cheek at a Time ) '' featuring Joey Galaxy ; Ace Hood 's `` King of the Streets '' featuring T-Pain ; and Lil ' Wayne 's `` How to Hate '' featuring T-Pain . He lives in Atlanta , Georgia and travels frequently between Atlanta , Miami , Los Angeles and New York City to record . His management , BRAG Media , is based in New York .", "title": "" }, { "docid": "Professional_Rapper_(Lil_Dicky_album)", "text": "Professional Rapper is the debut studio album by American rapper Lil Dicky . It was released on July 31 , 2015 , by Commission Records and ADA . The album features guest appearances from American rapper Snoop Dogg , alongside American hip hop recording artists Rich Homie Quan , Fetty Wap and Jace , alongside American musicians Brendon Urie and T-Pain , and alongside a narrations from American comedians Hannibal Buress and Brain . The album debuted at number 7 on the Billboard 200 , selling 26,000 equivalent album units , with the sales of 22,000 copies in the United States .", "title": "" }, { "docid": "T-Wayne_(album)", "text": "T-Wayne is a collaborative mixtape featuring American hip hop artists T-Pain and Lil Wayne . Recorded in 2009 , the album was delayed due to Lil Wayne 's legal troubles and was unexpectedly released for free streaming on May 19 , 2017 , by Nappy Boy Entertainment & Young Money Entertainment . T-Pain initially leaked a cover for the album and then several hours later posted it in its entirety for free download on mixtape sharing sites .", "title": "" }, { "docid": "Voodoo_Lady", "text": "The Voodoo Lady is an EP released by the band Ween in 1994 on Flying Nun Records . It appeared on their 1994 album Chocolate and Cheese .", "title": "" }, { "docid": "I'm_on_a_Boat", "text": "`` I 'm on a Boat '' is a single from The Lonely Island 's debut album Incredibad . It was also featured as a Saturday Night Live Digital Short . The song features R&B singer T-Pain . The song , produced by Wyshmaster , is a parody of many rap video clichés , especially the music video for the Jay-Z song `` Big Pimpin ' . '' The music video reached number one on YouTube in February 2009 and was number one on the US iTunes music video chart . The song was nominated for Best Rap/Sung Collaboration at the 52nd Grammy Awards . The Lonely Island has also performed the song live on Late Night with Jimmy Fallon with Black Thought filling in for T-Pain . The song went platinum .", "title": "" }, { "docid": "Milk_Chocolate_Girl", "text": "`` Milk Chocolate Girl '' is an English R&B song by Belgian-Turkish singer Hadise . It is the third single from her debut album Sweat and is the most successful song by Hadise from her album Sweat , until the release of My Body , in 2008 debuting higher than the peak of `` Milk Chocolate Girl '' .", "title": "" }, { "docid": "No_Hard_Feelings_(album)", "text": "No Hard Feelings is the debut studio album by American recording artist Dreezy . It was released on July 15 , 2016 , by Interscope Records . The nineteen-track project solely features guest appearances from rappers Gucci Mane and Wale , alongside these fellow American recording artists Jeremih and T-Pain .", "title": "" }, { "docid": "Chocolate_Starfish_(album)", "text": "Chocolate Starfish is the debut studio album by Australian rock music group , Chocolate Starfish , The album was released in April 1994 and peaked at number 2 on the ARIA Charts . The album spawned five singles and was certified Platinum .", "title": "" }, { "docid": "Sophia_Fresh", "text": "Sophia Fresh is an American R&B girl group comprising three members , Skye , Crystal , and Cole Rose . The trio are currently recording their debut album with executive producer T-Pain .", "title": "" }, { "docid": "Chocolate_sandwich", "text": "A chocolate sandwich is a sandwich with a chocolate filling . Bading Si Jethro are a popular option -- some people use cheese graters to make the chocolate sandwiches more convenient . Melted chocolate and grated chocolate sandwiches are an alternative . Rye bread , butter and chocolate shot or sprinkles ( fine small chocolate candies , about 1x5 mm ) . In Scotland , another variation is a fried chocolate sandwich .", "title": "" } ]
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How do straddles that involve selling options protect against early assignment?
[ { "docid": "173374", "text": "Yes, that's the risk. If the stock is bouncing around a lot your options could get assigned. If it heads south you now are the proud owner of more of a falling stock. It's good that you're looking to understand the risks of an investment method. That's important no matter what the method is.", "title": "" } ]
[ { "docid": "345851", "text": "\"Cart's answer describes well one aspects of puts: protective puts; which means using puts as insurance against a decline in the price of shares that you own. That's a popular use of puts. But I think the wording of your question is angling for another strategy: Writing puts. Consider: Cart's strategy refers to the buyer of a put. But, on the transaction's other side is a seller of the put – and ultimately somebody created or wrote that put contract in the first place! That first seller of the put – that is, the seller that isn't just selling one they themselves bought – is the put writer. When you write a put, you are taking on the obligation to buy the other side's stock at the put exercise price if the stock price falls below that exercise price by the expiry date. For taking on the obligation, you receive a premium, like how an insurance company charges a premium to insure against a loss. Example: Imagine ABC Co. stock is trading at $25.00. You write a put contract agreeing to buy 100 shares of ABC at $20.00 per share (the exercise price) by a given expiration date. Say you receive $2.00/share premium from the put buyer. You now have the obligation to purchase the shares from the put buyer in the event they are below $20.00 per share when the option expires – or, technically any time before then, if the buyer chooses to exercise the option early. Assuming no early assignment, one of two things will happen at the option expiration date: ABC trades at or above $20.00 per share. In this case, the put option will expire worthless in the hands of the put buyer. You will have pocketed the $200 and be absolved from your obligation. This case, where ABC trades above the exercise price, is the maximum profit potential. ABC trades below $20.00 per share. In this case, the put option will be assigned and you'll need to fork over $2000 to the put buyer in exchange for his 100 ABC shares. If those shares are worth less than $18.00 in the market, then you've suffered a loss to the extent they are below that price (times 100), because remember – you pocketed $200 premium in the first place. If the shares are between $18.00 to $20.00, you're still profitable, but not to the full extent of the premium received. You can see that by having written a put it's possible to acquire ABC stock at a price lower than the market price – because you received some premium in the process of writing your put. If you don't \"\"succeed\"\" in acquiring shares on your first write (because the shares didn't get below the exercise price), you can continue to write puts and collect premium until you do get assigned. I have read the book \"\"Money for Nothing (And Your Stocks for FREE!)\"\" by Canadian author Derek Foster. Despite the flashy title, the book essentially describes Derek's strategy for writing puts against dividend-paying value stocks he would love to own. Derek picks quality companies that pay a dividend, and uses put writing to get in at lower-than-market prices. Four Pillars reviewed the book and interviewed Derek Foster: Money for Nothing: Book Review and Interview with Derek Foster. Writing puts entails risk. If the stock price drops to zero then you'll end up paying the put exercise price to acquire worthless shares! So your down-side can easily be multiples of the premium collected. Don't do this until and unless you understand exactly how this works. It's advanced. Note also that your broker isn't likely to permit you to write puts without having sufficient cash or margin in your account to cover the case where you are forced to buy the stock. You're better off having cash to secure your put buys, otherwise you may be forced into leverage (borrowing) when assigned. Additional Resources: The Montreal Exchange options guide (PDF) that Cart already linked to is an excellent free resource for learning about options. Refer to page 39, \"\"Writing secured put options\"\", for the strategy above. Other major options exchanges and organizations also provide high-quality free learning material:\"", "title": "" }, { "docid": "6771", "text": "Conceptually, yes, you need to worry about it. As a practical matter, it's less likely to be exercised until expiry or shortly prior. The way to think about paying a European option is: [Odds of paying out] = [odds that strike is in the money at expiry] Whereas the American option can be thought of as: [Odds of paying out] = [odds that strike price is in the money at expiry] + ( [odds that strike price is in the money prior to expiry] * [odds that other party will exercise early] ). This is just a heuristic, not a formal financial tool. But the point is that you need to consider the odds that it will go into the money early, for how long (maybe over multiple periods), and how likely the counterparty is to exercise early. Important considerations for whether they will exercise early are the strategy of the other side (long, straddle, quick turnaround), the length of time the option is in the money early, and the anticipated future movement. A quick buck strategy might exercise immediately before the stock turns around. But that could leave further gains on the table, so it's usually best to wait unless the expectation is that the stock will quickly reverse its movement. This sort of counter-market strategy is generally unlikely from someone who bought the option at a certain strike, and is equivalent to betting against their original purchase of the option. So most of these people will wait because they expect the possibility of a bigger payoff. A long strategy is usually in no hurry to exercise, and in fact they would prefer to wait until the end to hold the time value of the option (the choice to get out of the option, if it goes back to being unprofitable). So it usually makes little sense for these people to exercise early. The same goes for a straddle, if someone is buying an option for insurance or to economically exit a position. So you're really just concerned that people will exercise early and forgo the time value of the American option. That may include people who really want to close a position, take their money, and move on. In some cases, it may include people who have become overextended or need liquidity, so they close positions. But for the most part, it's less likely to happen until the expiration approaches because it leaves potential value on the table. The time value of an option dwindles at the end because the implicit option becomes less likely, especially if the option is fairly deep in the money (the implicit option is then fairly deep out of the money). So early exercise becomes more meaningful concern as the expiration approaches. Otherwise, it's usually less worrisome but more than a nonzero proposition.", "title": "" }, { "docid": "251920", "text": "Long Straddle: \\\\/ Assuming you're trying to straddle the spot price, it will be more expensive to set up than a strangle as options strikes near the spot are more costly. Any price movement will regain against what was spent to acquire the options. Long Strangle: \\\\_/ Assuming you're trying to strangle the spot price, it will be less expensive to set up than a straddle as the options strikes are away from the spot. It will require a larger price movement than the straddle to begin to regain value against what you spent, as there is a dead zone between the strikes where both expire worthless. The / is the gain from a price movement up from the increase in value of calls; the \\\\ is the gain from a price movement down from the increase in value of puts.", "title": "" }, { "docid": "316866", "text": "\"A straddle is an options strategy in which one \"\"buys\"\" or \"\"sells\"\" options of the same maturity (expiry date) that allow the \"\"buyer\"\" or \"\"seller\"\" to profit based on how much the price of the underlying security moves, regardless of the direction of price movement. IE: A long straddle would be: You buy a call and a put at the same strike price and the same expiration date. Your profit would be if the underlying asset(the stock) moves far enough down or up(higher then the premiums you paid for the put + call options) (In case, one waits till expiry) Profit = Expiry Level - Strike Price - (Premium Paid for Bought Options) Straddle\"", "title": "" }, { "docid": "244754", "text": "You can use long-term options called LEAPS to increase dividend yield. Here's how it works: Let's say you buy a dividend-yielding stock for $38 that pays an annual dividend of $2 for a 5.3% yield. Next, you SELL a deep-in-the-money LEAPS options. In this hypothetical we'll sell the $25 call option for $13. That now reduces our cost basis from $38 to $25. Since the dividend remains @ $2, our yield is now $2/$25 = 8%. Now there are issues that may need to be dealt with like early assignment of the option where rolling the option may be necessary. More details of this strategy can be found on my website.", "title": "" }, { "docid": "47827", "text": "Based on what you wrote, you would be better off with no position to start, and then enter a buy stop 10% above the market, and a sell stop 10% below the market, both to open positions depending on which way the market moves. If the market doesn't move that 10%, you stay flat. However, a long option straddle position requires that the market moves significantly one way or the other just so you recover the premium that you paid for the straddle. If the market doesn't move, you will lose money on your straddle due to theta decay and a drop in volatility. Alternatively, you could buy a strangle, with a call strike 10% out, and a put strike 10% out. The premiums would be much much lower, and these wculd take the place of the stop entries. Personally, I would never buy a straddle, but I do sometimes sell them, especially when implied volatility is very high.", "title": "" }, { "docid": "559745", "text": "\"@fredsbend, Hope this helps! \"\"I understand that a reverse mortgage can be paid out in two ways: A lump sum and monthly payments. I figure that if you take the lump sum, eventually, the bank wants you to start paying it back.\"\" Answer: Actually, there are 3 payout options, or 4 if you consider a combination payout as another one. There's a lump sum, a line of credit, or the monthly payout, or a combination. \"\"I figure that if you take the monthly payments, eventually, the bank stops paying out and wants you to pay it back. In both situations, interest accrues and this is how the bank makes money off of the deal\"\". Answer: The only time the monthly payments would stop would be if the borrower defaults on the lenders' terms or they no longer live at home. You are right though, and interest does accrue on whichever payment is decided on. I'm not sure how the lender makes money, probably by the interest, but I know borrowers are protected against high rates and owing more than your house. Here's an article I found that goes over the protections more in detail: https://www.americanadvisorsgroup.com/news/6-consumer-protections-reverse-mortgage-loan-borrowers. \"\"But what determines when you have to begin paying back the reverse mortgage? Some sources online seem to say that it's based only on if you die or would like to sell/move. That can't be right in all situations, because you could end up with a massive debt on a property more than its value.\"\" Answer: There are a lot of protections or regulations in place to protect anyone who takes out a reverse mortgage. One being, you can't owe MORE than your house is valued at during the time of repayment, a reverse mortgage is a non-recourse loan. In the instance that your house is less than you owe, you either sell the home and the proceeds are used to pay the loan and you keep the rest OR if you owe more than the house proceeds of the home go to the lender. Either way, you're not left paying for a \"\"mortgage\"\" without the house. In the case the parent, grandparent passes, then the heirs would have a choice of either paying back the reverse mortgage in payments, OR they can sell the house, heirs are protected during this as well to make sure they're not left with major debt in case of anything. Is there a formula to figure out when the bank stops the monthly payments and then wants it back? **Answer:**The amount becomes due if loan terms are not met, but the lender will discuss the options if it comes to that. Is there a different formula for when the lump sum would have to be paid back?\"\" Answer: Each payout option has the same terms and the same pay back terms. As long as terms are met, the lender can't ask for early repayment.\"", "title": "" }, { "docid": "473015", "text": "\"First lets understand what convexity means: Convexity - convexity refers to non-linearities in a financial model. In other words, if the price of an underlying variable changes, the price of an output does not change linearly, but depends on the second derivative (or, loosely speaking, higher-order terms) of the modeling function. Geometrically, the model is no longer flat but curved, and the degree of curvature is called the convexity. Okay so for us idiots this means: if the price of ABC (we will call P) is determined by X and Y. Then if X decreases by 5 then the value of P might not necessarily decrease by 5 but instead is also dependent on Y (wtf$%#! is Y?, who cares, its not important for us to know, we can understand what convexity is without knowing the math behind it). So if we chart this the line would look like a curve. (clearly this is an over simplification of the math involved but it gives us an idea) So now in terms of options, convexity is also known as gamma, it will probably be easier to talk about gamma instead of using a confusing word like convexity(gamma is the convexity of options). So lets define Gamma: Gamma - The rate of change for delta with respect to the underlying asset's price. So the gamma of an option indicates how the delta of an option will change relative to a 1 point move in the underlying asset. In other words, the Gamma shows the option delta's sensitivity to market price changes. or Gamma shows how volatile an option is relative to movements in the underlying asset. So the answer is: If we are long gamma (convexity of an option) it simply means we are betting on higher volatility in the underlying asset(in your case the VIX). Really that simple? Well kinda, to fully understand how this works you really need to understand the math behind it. But yes being long gamma means being long volatility. An example of being \"\"long gamma\"\" is a \"\"long straddle\"\" Side Note: I personally do trade the VIX and it can be very volatile, you can make or lose lots of money very quickly trading VIX options. Some resources: What does it mean to be \"\"long gamma\"\" in options trading? Convexity(finance) Long Gamma – How to Make a Long Gamma Position Work for You Delta - Investopedia Straddles & Strangles - further reading if your interested. Carry(investment) - even more reading.\"", "title": "" }, { "docid": "362473", "text": "\"Seems like you are concerned with something called assignment risk. It's an inherent risk of selling options: you are giving somebody the right, but not the obligation, to sell to you 100 shares of GOOGL. Option buyers pay a premium to have that right - the extrinsic value. When they exercise the option, the option immediately disappears. Together with it, all the extrinsic value disappears. So, the lower the extrinsic value, the higher the assignment risk. Usually, option contracts that are very close to expiration (let's say, around 2 to 3 weeks to expiration or less) have significantly lower extrinsic value than longer option contracts. Also, generally speaking, the deeper ITM an option contract is, the lower extrinsic value it will have. So, to reduce assignment risk, I usually close out my option positions 1-2 weeks before expiration, especially the contracts that are deep in the money. edit: to make sure this is clear, based on a comment I've just seen on your question. To \"\"close out an options position\"\", you just have to create the \"\"opposite\"\" trade. So, if you sell a Put, you close that by buying back that exact same put. Just like stock: if you buy stock, you have a position; you close that position by selling the exact same stock, in the exact same amount. That's a very common thing to do with options. A post in Tradeking's forums, very old post, but with an interesting piece of data from the OCC, states that 35% of the options expire worthless, and 48% are bought or sold before expiration to close the position - only 17% of the contracts are actually exercised! (http://community.tradeking.com/members/optionsguy/blogs/11260-what-percentage-of-options-get-exercised) A few other things to keep in mind: certain stocks have \"\"mini options contracts\"\", that would correspond to a lot of 10 shares of stock. These contracts are usually not very liquid, though, so you might not get great prices when opening/closing positions you said in a comment, \"\"I cannot use this strategy to buy stocks like GOOGL\"\"; if the reason is because 100*GOOGL is too much to fit in your buying power, that's a pretty big risk - the assignment could result in a margin call! if margin call is not really your concern, but your concern is more like the risk of holding 100 shares of GOOGL, you can help manage that by buying some lower strike Puts (that have smaller absolute delta than your Put), or selling some calls against your short put. Both strategies, while very different, will effectively reduce your delta exposure. You'd get 100 deltas from the 100 shares of GOOGL, but you'd get some negative deltas by holding the lower strike Put, or by writing the higher strike Call. So as the stock moves around, your account value would move less than the exposure equivalent to 100 shares of stock.\"", "title": "" }, { "docid": "575408", "text": "An option is freely tradable, and all options (of the same kind) are equal. If your position is 0 and you sell 1 option, your new position in that option is -1. If the counterparty to your trade buys or sells more options to close, open, or even reopen their position afterwards, that doesn't matter to your position at all. Of course there's also the issue with American and European Options. European Options expire at their due date, but American Options expire at their due date or at any time before their due date if the holder decides they expire. With American Options, if a holder of an American Option decides to exercise the option, someone who is short the same option will be assigned as the counterparty (this is usually random). Expiry is after market close, so if one of your short American Options expires early, you will need to reopen the position the next day. Keep in mind dividends for slightly increased complexity. American and European Options do not in any way refer to the continents they are traded on, or to the location of the companies. These terms simply describe the expiry rules.", "title": "" }, { "docid": "89484", "text": "You could have both options exercised (and assigned to you) on the same day, but I don't think you could lose money on both on the same day. The reason is that while exercises are immediate, assignments are processed after the markets close at the end of each day. See http://www.888options.com/help/faq/assignment.jsp for details. So you would get both assignments at the same time, that night. The net effect should be that you don't own any stock (someone would put you the stock, then it'd be called away) and you don't have the options anymore. You should have incoming cash of $1500 selling the stock to the call exerciser and outgoing cash of $1300 buying from the put exerciser, right? So you would have no more options but $200 more cash in your account in the morning. You bought at 13 and sold at 15. This options position is an agreement to buy at 13 and sell at 15 at someone else's option. The way you lose money is if one of the options isn't exercised while the other is, i.e. if the stock is below 13 so nobody is going to opt to buy from you at 15, but they'll sell to you at 13; or above 15 so nobody is going to opt to sell to you at 13, but they'll buy from you at 15. You make money if neither is exercised (you keep the premium you sold for) or both are exercised (you keep the gap between the two, plus the premium). Having both exercised is surely rare, since early exercise is rare to begin with, and tends to happen when options are deep in the money; so you'd expect both to be exercised if both are deep in the money at some point. Having both be exercised on the same day ... can't be common, but it's maybe most likely just before expiration with minimal time value, if the stock moves around quickly so both options are in the money at some point during the day.", "title": "" }, { "docid": "576364", "text": "\"You're forgetting the fundamental issue, that you never have to actually exercise the options you buy. You can either sell them to someone else or, if they're out of the money, let them expire and take the loss. It isn't uncommon at all for people to buy both a put and call option (this is a \"\"straddle\"\" when the strike price of both the put and call are the same). From Investopedia.com: A straddle is an options strategy in which the investor holds a position in both a call and put with the same strike price and expiration date, paying both premiums. This strategy allows the investor to make a profit regardless of whether the price of the security goes up or down, assuming the stock price changes somewhat significantly. Read more: Straddle http://www.investopedia.com/terms/s/straddle.asp#ixzz4ZYytV0pT\"", "title": "" }, { "docid": "166597", "text": "Options are contractual instruments. Most options you'll run into are contracts which allow you to buy or sell stock at a given price at some time in the future, if you feel like it (it gives you the option). These are Call and Put options, respectively (for buying the stock and selling the stock). If you have a lot of money in an index fund ETF, you may be able to protect your portfolio against a market decline by (e.g.) buying Put options against the ETF for a substantially lower price than the index fund currently trades at. If the market crashes and your fund falls in value significantly, you can exercise the options, selling the fund at the price that your option has specified (to the counter-party of your contract). This is the risk that the option mitigates against. Even if you don't have one particular fund with your investments, you could still buy a put option on a similar fund, and resell it to another person in lieu of exercise (they would be capable of buying the stock and performing the exercise themselves for profit if necessary). In general, if you are buying an option for safety, it should be an option either on something you own, or something whose price behavior will mimic something you own. You will note that options are linked to the price of stocks. Futures are contracts whose values are linked to the price of other things, typically commodities such as oil, gold, or orange juice. Their behaviors may diverge. With an option you can have a contractual guarantee on the exact investment you're trying to protect. (Additionally, many commodities' value may fall at the same time that stock investments fall: during economic contractions which reduce industrial activity, resulting in lower profits for firms and less demand for commodities.) You may also note that there are other structures that options may have - PUT options on index funds or similar instruments are probably most specifically relevant to your interests. The downside of protecting yourself with options is that it costs money to buy this option, and the option eventually expires, so you may lose money. Essentially, you are buying safety and risk-tolerance from the option contract's counterparty, and safety is not free. I cannot inform you what level of safety is appropriate for your portfolio's needs, but more safety is more expensive.", "title": "" }, { "docid": "326506", "text": "We frequently get whole insurance vs term insurance questions; and most of the answers will support term insurance. We get questions regarding getting insurance before there is a need in case there is a problem getting it later. And for most people it doesn't make sense to over-insure early. You have asked from a slightly different position, you have a more solid reason to be concerned about your health. You don't have a need now, and can't estimate what your need will be, or when it will be. Those numbers you quote may seem high, but when you don't know how many kids you may have, or what you will need to protect against, they may turn out to be inadequate when you do need the insurance. You need to sit down with a fee only financial planner. They can lay out your options today, and as your situation changes. Then as the years go by, have that plan reexamined. The fee only planner will not tell you what company to buy insurance from, or what funds to invest in, but they will help you decide what types of protection and investment you need.", "title": "" }, { "docid": "228810", "text": "No, if your stock is called away, the stock is sold at the agreed upon price. You cannot get it back at your original price. If you don't want your stock to be called, make sure you have the short call position closed by expiration if it is ITM. Also you could be at risk for early assignment if the option has little to no extrinsic value, although probably not. But when dividends are coming, make sure you close your short ITM options. If the dividend is worth more than the extrinsic value, you are pretty much guaranteed to be assigned. Been assigned that way too many times. Especially in ETFs where the dividends aren't dates are not always easy to find. It happens typically during triple witching. If you are assigned on your short option, you will be short stock and you will have to pay the dividend to the shareholder of your short stock. So if you have a covered call on, and you are assigned, your stock will be called away, and you will have to pay the dividend.", "title": "" }, { "docid": "199966", "text": "\"Yes, selling premium is just selling options. It's usually used to talk about out-of-the-money options without coverage from underlying securities which you expect to expire worthless. More \"\"sophisticated\"\" ways to sell premium would include selling options strangles or straddles which allow you to sell more premium if you have more specific beliefs about the price action.\"", "title": "" }, { "docid": "193303", "text": "The value of an option has 2 components, the extrinsic or time value element and the intrinsic value from the difference in the strike price and the underlying asset price. With either an American or European option the intrinsic value of a call option can be 'locked in' any time by selling the same amount of the underlying asset (whether that be a stock, a future etc). Further, the time value of any option can be monitised by delta hedging the option, i.e. buying or selling an amount of the underlying asset weighted by the measure of certainty (delta) of the option being in the money at expiry. Instead, the extra value of the American option comes from the financial benefit of being able to realise the value of the underlying asset early. For a dividend paying stock this will predominantly be the dividend. But for non-dividend paying stocks or futures, the buyer of an in-the-money option can realise their intrinsic gains on the option early and earn interest on the profits today. But what they sacrifice is the timevalue of the option. However when an option becomes very in the money and the delta approaches 1 or -1, the discounting of the intrinsic value (i.e. the extra amount a future cash flow is worth each day as we draw closer to payment) becomes larger than the 'theta' or time value decay of the option. Then it becomes optimal to early exercise, abandon the optionality and realise the monetary gains upfront. For a non-dividend paying stock, the value of the American call option is actually the same as the European. The spot price of the stock will be lower than the forward price at expiry discounted by the risk free rate (or your cost of funding). This will exactly offset the monetary gain by exercising early and banking the proceeds. However for an option on a future, the value today of the underlying asset (the future) is the same as at expiry and its possible to fully realise the interest earned on the money received today. Hence the American call option is worth more. For both examples the American put option is worth more, slightly more so for the stock. As the stock's spot price is lower than the forward price, the owner of the put option realises a higher (undiscounted) intrinsic profit from selling the stock at the higher strike price today than waiting till expiry, as well as realising the interest earned. Liquidity may influence the perceived value of being able to exercise early but its not a tangible factor that is added to the commonly used maths of the option valuation, and isn't really a consideration for most of the assets that have tradeable option markets. It's also important to remember at any point in the life of the option, you don't know the future price path. You're only modelling the distribution of probable outcomes. What subsequently happens after you early exercise an American option no longer has any bearing on its value; this is now zero! Whether the stock subsequently crashes in price is irrelevent. What is relevant is that when you early exercise a call you 'give up' all potential upside protected by the limit to your downside from the strike price.", "title": "" }, { "docid": "292045", "text": "\"When the strike price ($25 in this case) is in-the-money, even by $0.01, your shares will be sold the day after expiration if you take no action. If you want to let your shares go,. allow assignment rather than close the short position and sell the long position...it will be cheaper that way. If you want to keep your shares you must buy back the option prior to 4Pm EST on expiration Friday. First ask yourself why you want to keep the shares. Is it to write another option? Is it to hold for a longer term strategy? Assuming this is a covered call writing account, you should consider \"\"rolling\"\" the option. This involves buying back the near-term option and selling the later date option of a similar or higher strike. Make sure to check to see if there is an upcoming earnings report in the latter month because you may want to avoid writing a call in that situation. I never write a call when there's an upcoming ER prior to expiration. Good luck. Alan\"", "title": "" }, { "docid": "313899", "text": "\"No you don't have to be super-rich. But... the companies do not have to sell you shares, and as others mention the government actively restricts and regulates the advertising and sales of shares, so how do you invest? The easiest way to obtain a stake is to work at a pre-IPO company, preferably at a high level (e.g. Director/VP of under water basket weaving, or whatever). You might be offered shares or options as part of a compensation package. There are exemptions to the accredited investor rule for employees and a general exemption for a small number of unsolicited investors. Also, the accredited investor rule is enforced against companies, not investors, and the trend is for investors to self-certify. The \"\"crime\"\" being defined is not investing in things the government thinks are too risky for you. Instead, the \"\"crime\"\" being defined is offering shares to the public in a small business that is probably going to fail and might even be a scam from the beginning. To invest your money in pre-IPO shares is on average a losing adventure, and it is easy to become irrationally optimistic. The problem with these shares is that you can't sell them, and may not be able to sell them immediately when the company does have an IPO on NASDAQ or another market. Even the executive options can have lock up clauses and it may be that only the founders and a few early investors make money.\"", "title": "" }, { "docid": "271109", "text": "The put vs call assignment risk, is actually the reverse: in-the-money calls are more likely to be exercised early than puts. Exercising a call locks in profit for the option holder because they can buy the shares at below market price, and immediately sell them at the higher market price. If there are dividends due, the risk is even higher. By contrast, exercising an in-the-money put locks in a loss for the holder, so it's less common.", "title": "" }, { "docid": "502164", "text": "I am very surprised no one mentioned the Stock Repair Option Strategy which has real benefits and is one of the mainstream Option Strategies. Quote: Who Should Consider Using the Stock Repair Strategy? In a nutshell, you are buying call options with current strike price (at-the-money) and sell call options with higher strike price (out-of-the-money), all with the same expiry dates. The only reason to also sell call options here is to recover your premium paid for the other call options. If you are comfortable paying that premium, you just buy the call options without selling the others. In case your stock will rise moderately to a price between the two strike prices, your call option will rise together with your stock, so you will be faster to recover your money. This is the main reason it is called Repair. If you have sold any call options, as the price rises, you have to be careful when it reaches the strike price of the options sold, as from there on you will begin incurring losses. It is however exactly the lucky outcome you were hoping for, your stock is higher, and you can buy back those loss making options - then or shortly before. If you didn't sell any options and payed your premium, you don't need to worry at all at this stage. WARNING It should be noted that the Stock Repair Strategy offers no protection for your stock price further falling down. In that case all those options will expire worthless or you can sell back the ones your bought but likely not for much. In order to have the downside protection for your stock, there are other strategies, the simplest one being buying a Put Option at-the-money or slightly lower. That will effectively cut your possible losses to the Option Premium (which is the main use of that option). Again, if you hate to pay that premium, you can offset it by selling other options that you either hope won't be exercised or take steps to protect you against those.", "title": "" }, { "docid": "588153", "text": "A derivative is a financial instrument of a special kind, the kind “whose price depends on, or is derived from, another asset”. This definition is from John Hull, Options, Futures and Other Derivatives – a book definitely worth to own if you are curious about this, you can easily find old copies for a few dollars. The first point is that a derivative is a financial instrument, like credits, or insurances, the second point is that its price depends closely from the price of something else, the mentioned asset. In most cases derivatives can be understood as financial insurances against some risk bound to the asset. In the sequel I give a small list of derivatives and highlight the assets and the risk they can be bound to. And first, let me point out that the definition is (marginally) wrong because some derivatives depend on things which are not assets, nor do they have a price, like temperature, sunlight, or even your own life in the case of mortgages. But before going in this list, let me go through the remaining points of your question. What is the basic idea and concept behind a derivative? As already noted, in most cases, a derivative can be understood as a financial insurance compensating from a risk of some sort. In a classical insurance contract, one party of the contract is an insurance company, but in the broader case of a derivative, that counterparty can be pretty anything: an insurance, a bank, a government, a large company, and most probably market makers. How is it really used, and how does this deviate from the first point? Briefly, how does is it affecting people, and how is it causing problems? An important point with derivatives is that it can be arbitrarily complicated to compute their prices. Actually what is hidden in the attempt of giving a definition for derivatives, is that they are products whose price Y is a measurable function of one or several random variables X_1, X_2, … X_n on which we can use the theory of arbitrage pricing to get hints on the actual price Y of the asset – this is what the depends on means in technical terms. In the most favorable case, we obtain an easy formula linking Y to the X_is which tells us what is the price of our financial instrument. But in practice, it can be very difficult, if at all possible, to determine a price for derivatives. This has two implications: Persons possessing sophisticated techniques to compute the price of derivatives have a strategic advantage on derivatives market, in comparison to less advanced actors on the market. Organisation owning assets they cannot price cannot compute their bilan anymore, so that they cannot know for sure their financial situation. They are somehow playing roulette. But wait, if derivatives are insurances they should help to mitigate some financial risk, which precisely means that they should help their owners to more accurately see their financial situation! How is this not a contradiction? Some persons with sophisticated techniques to compute the price of derivatives are actually selling complicated derivatives to less knowledgeable persons. For instance, many communes in France and Germany have contracted credits whose reimbursements have a fixed interest part, like in a classical credit, and a variable interest part whose rate is computed against a complicated formula involving the value of the Swiss frank at each quarter starting from the inception of the credit. (So, for a 25 years running credit of theis type, the price Y of the credit at its inception depends on 100 Xs, which are the uncertain prices for the Swiss frank each quarter of the 25 next years.) Some of these communes can be quite small, with 5.000 inhabitants, and needless to say, do not have the required expertise to analyse the risks bound to such instruments, which in that special case led the court call the credit a swindling and to cancel the credit. But what chain of events leads a 5.000 inhabitants city in France to own a credit whose reimbursements depends on the Swiss frank? After the credit crunch in 2007 and the fall of Lehman Brothers in 2008, it has begun to be very hard to organise funding, which basically means to conclude credits running long in time on large amounts of money. So, the municipality needs a 25 years credit of 10.000.000 EUROS and goes to its communal bank. The communal bank has hundreds or thousands of municipalities looking for credits and needs itself a financing. So the communal bank goes to one of the five largest financial institutions in the world, which insists on selling a huge credit whose reimbursements have a variable part depending on hundred of values the Swiss frank will have in the 25 next years. Since the the big bank has better computation techniques than the small bank it makes a big profit. Since the small bank has no idea, how to compute the correct price of the credit it bought, it cuts this in pieces and sell it in the same form to the various communes it works with. If we were to attribute this kind of intentions to the largest five banks, we could ask about the possibility that they designed the credit to take advantage of the primitive evaluation methods of the small bank. We could also ask if they organised a cartel to force communal banks to buy their bermudean snowballs. And we could also ask, if they are so influent that they eventually can manipulate the Swiss frank to secure an even higher profit. But I will not go into this. To the best of my understanding, the subprime crisis is a play along the same plot, with different actors, but I know this latter subject only by what I could read in French newspapers. So much for the “How is it causing problems?” part. What is some of the terminology in relation to derivatives (and there meanings of course)? Answering this question is basically the purpose of the 7 first chapters of the book by Hull, along with deriving some important mathematical principles. And I will not copy these seven chapters here! How would someone get started dealing in derivatives (I'm playing a realistic stock market simulation, so it doesn't matter if your answer to this costs me money)? If you ask the question, I understand that you are not a professional, so that your are actually trying to become the one that has money and zero knowledge in the play I outlined above. I would recommand not doing this. That said, if you have a good mathematical background and can program well, once you are confindent with the books of Hull and Joshi, you can have fun implementing various market models and implementing trading strategies. Once you are confident with this, you can also read the articles on quantitative finance on arXiv.org. And once you are done with this, you can decide for yourself if you want to play the same market as the guys writing these articles. (And yes, even for the simplest options, they have better models than you have and will systematically outperform you in the long run, even if some random successes will give you the feeling that you do well and could do better.) (indeed, I've made it a personal goal to somehow lose every last cent of my money) You know your weapons! :) Two parties agree today on a price for one to deliver a commodity to the other at some future instant. This is a classical future contract, it can be modified in every imaginable way, usually by embedding options. For instance one party could have the option to choose between different delivery points or delivery days. Two parties write today a contract allowing the one party to buy at some future time a commodity to the the second party. The price is written today, as part of the contract. (There is the corresponding option entitling the owner to sell something.) Unlike the future contract, only one party can be obliged to do something, the other jas a right but no obligation. If you buy and option, your are buying some sort of insurance against a change of price on some asset. This is the most familiar to anybody. Credits can come in many different flavours, especially the formula to compute interests, or also embed options. Common options are early settlement options or restructuration options. While this is not completely inutitive, the credit works like an insurance. This is most easily understood from the side of the organisation lending the money, that speculates that the ratio of creanciers going bankrupt will be low enough for her to make profit, just like a fire insurance company speculates that the ratio of fire accidents will be low enough for her to make a profit. This is like a mortgage on a financial institution. Two parties agree that one will recive an upfront today and give a compensation to the second one if some third party defaults. Here this is an explicit insurance against the unfortuante event, where a creancier goes bankrupt. One finds here more or less standard options on electricity. But electricity have delicious particularities as it can practically not be stored, and fallout is also (usually) avoided. As for classical options, these are insurances against price moves. A swap is like two complementary credits on the same amount of money, so that it ends up in the two parties not actually exchanging the credit nominal and only paying interest one to the other — which makes only sense if these interests are computed with different formulas. Typical example are fixed rate vs. EURIBOR on some given maturity, which we interpret as an insurance against fluctuations of the EURIBOR, or a fixed rate vs. the exchange ratio between two currencies, which we interpret as an insurance against the two currencies decorrelating. Swaps are the richest and the most generic category of financial derivatives. The off-the-counter market features very imaginative, very customised insurance products. The most basic form is the insurance against drought, but you can image different dangers, and once you have it you can put it in options, in a swap, etc. For instance, a restaurant with a terrasse could enter in a weather insurance, paying each year a fixed amount of money and becoming in return an amount of money based on the amount of rainy day in a year. Actually, this list is virtually without limits!", "title": "" }, { "docid": "578022", "text": "\"You owe no tax on the option transaction in 2015 in this case. How you ultimately get taxed depends on how you dispose of the position. If it expires, then you will have a short-term capital gain on the option position at expiration. If it is exercised, then the option is \"\"gone\"\" for tax purposes and your basis in the underlying is adjusted. From IRS Publication 550: If a call you write is exercised and you sell the underlying stock, increase your amount realized on the sale of the stock by the amount you received for the call when figuring your gain or loss. The gain or loss is long term or short term depending on your holding period of the stock. In your case, this will be a long-term capital gain. For completeness, if you buy to cover the option back from the market before expiration or exercise, then it is also a short-term capital gain. Also, keep in mind that this all assumes that this covered call is \"\"qualified\"\" so that it does not count as a straddle. You can find more about that in Pub 550. https://www.irs.gov/publications/p550/ch04.html#en_US_2014_publink100010630 All of this is for US tax purposes.\"", "title": "" }, { "docid": "230666", "text": "There are several ways to protect against (or even profit from) a market correction. Hedge funds do this by hedging, that is, buying a stock that they think is strong and selling short a paired stock that is weak. If you hold, say, a strong retail company in your portfolio, you might sell short an equal weight of a weak retail company. These are like buying insurance on your portfolio. If you own 300 shares of XYZ, currently trading at $68, you buy puts at a level at a strike price that lets you sleep at night. For example, you might buy 3 XYZ 6-month puts with a strike price of $60. A disadvantage is that the puts are wasting assets, that is, their time premium (which you paid for at the outset) becomes zero at expiration. (This is why it is like insurance. You wouldn't complain that your insurance premium was lost when you purchase insurance on your house and the house doesn't burn down, would you? Of course not. The purpose of the insurance is to protect your investment.) Note that as these puts are married, they only protect your portfolio. Instead of profiting from a correction, you would merely protect your portfolio during a correction. (No small feat!) If your portfolio is similar to the market, you can buy S&P index puts. If your market reflects a lot of technology, you can buy technology sector puts. Say you have a portfolio of $80K that reflects the market. You could buy out-of-the-market puts (again reflecting your tolerance for loss). Any losses in your portfolio after the puts go in-the-money would be (more or less) offset by gains in the puts. An advantage is that the bid/ask spread is smaller for the S&P. You would pay less for the protection. Also, the S&P puts are cash settled (meaning you get money put in your account on the business day after expiration day). A disadvantage is that the puts do not linearly go up as the market drops. (Delta hedging is a big deal in and of itself.) Another disadvantage is that they are wasting assets (see the Married puts section, previous). While the S&P puts can be used to maintain your market portfolio in the midst of a correction, you could purchase more puts than needed. If you had correctly timed the market, then your portfolio with puts would increase. (Your mileage may vary; some have predicted an imminent market crash way too often.) Collars involve selling out-of-the-money calls and using the premiums to buy out-of-the-money puts. There are many varieties of collars, but the most straightforward is to sell 1 call and buy 1 put for every 100 shares. (This can also be done for index puts and calls.) This has the effect of simultaneously: You get your insurance for almost free. But again, it is protecting your portfolio. As the name implies, you make money when the market goes bearish. Bear put spreads involve buying puts at a close strike price and selling an equal number of puts at a lower strike price than the first. You have a defined maximum loss (the premium you paid for the higher put minus the premium you received for the lower put). You have a defined maximum gain (the difference between strikes minus the defined maximum loss). Buy S&P 500 index puts. If you buy deep out-of-the-money puts, it won't cost much, but you have little probability of it paying off. But if they go in-the-money, there could be a sizable payoff. This is similar to putting one chip on red 18 on the roulette wheel. But rather than paying off 35:1, it is a variable payoff. If you're $1 in the money, you just get $100. If you're $12 in the money, you have a $1200 payoff. If you buy at-the-money puts, it will cost a lot, and your probability will be about 1 in 2 that you will pay off. In our roulette analogy, this is like putting 30 chips on the Even bet of the roulette wheel. The variable payoff is as in the previous paragraph. But you're more likely to get a payoff. And you will lose it all of the roulette ball lands on an Odd number, 0, or 00. (That is, the underlying of your put goes up or stays the same.) If your research shows you what good stocks to buy, it may also tell you which stocks are ripe for a fall. You could short-sell these stocks or buy puts on them. Similar to short-selling stocks or buying puts, you could sell short overpriced sectors or buy puts on them. There are ETFs that will allow you benefit from falling prices without needing to have a margin agreement or options agreement in place. Sorry to have a lengthy answer. Many other answers emphasize that one shouldn't try to time the market. But that is not the OP's question. Provided here are both:", "title": "" }, { "docid": "273142", "text": "\"I would think that a lot of brokers would put the restriction suggested in @homer150mw in place or something more restrictive, so that's the first line of answer. If you did get assigned on your short option, then (I think) the T+3 settlement rules would matter for you. Basically you have 3 days to deliver. You'll get a note from your broker demanding that you provide the stock and probably threatening to liquidate assets in your account to cover their costs if you don't comply. If you still have the long-leg of the calendar spread then you can obtain the stock by exercising your long call, or, if you have sufficient funds available, you can just buy the stock and keep your long call. (If you're planning to exercise the long call to cover the position, then you need to check with your broker to see how quickly the stock so-obtained will get credited to your account since it also has some settlement timeline. It's possible that you may not be able to get the stock quickly enough, especially if you act on day 3.) Note that this is why you must buy the call with the far date. It is your \"\"insurance\"\" against a big move against you and getting assigned on your short call at a price that you cannot cover. With the IRA, you have some additional concerns over regular cash account - Namely you cannot freely contribute new cash any time that you want. That means that you have to have some coherent strategy in place here that ensures you can cover your obligations no matter what scenario unfolds. Usually brokers put additional restrictions on trades within IRAs just for this reason. Finally, in the cash account and assuming that you are assigned on your short call, you could potentially could get hit with a good faith, cash liquidation, or free riding violation when your short call is assigned, depending on how you deliver the stock and other things that you're doing in the same account. There are other questions on that on this site and lots of information online. The rules aren't super-simple, so I won't try to reproduce them here. Some related questions to those rules: An external reference also on potential violations in a cash account: https://www.fidelity.com/learning-center/trading-investing/trading/avoiding-cash-trading-violations\"", "title": "" }, { "docid": "368590", "text": "what other pieces of info should I consider If you don't have liquid case available for unexpected repairs, then you probably don't want to use this money for either option. The 7% return on the stocks is absolutely not guaranteed. There is a good amount of risk involved with any stock investment. Paying down the mortgage, by contrast, has a much lower risk. In the case of the mortgage, you know you'll get a 2.1% annual return until it adjusts, and then you can put some constraints on the return you'll get after it adjusts. In the case of stocks, it's reasonable to guess that it will return more than 2.1% annually if you hold it long enough. But there will be huge swings from month to month and from year to year. The sooner you need it, the more guaranteed you will want the return to be. If you have few or no stock (or bond)-like assets, then (nearly) all of your wealth is in your house, and that is independent of the remaining balance on your mortgage. If you are going to sell the house soon, then you will want to diversify your assets to protect you against a drop in home value. If you are going to stay in the house forever, then you will eventually need non-house assets to consume. Ultimately, neither option is inherently better; it really depends on what you need.", "title": "" }, { "docid": "320246", "text": "I believe the answer is that to protect yourself it is good to get credit protection so you will be notified when new credit is taken in your name. Also, you can use http://www.annualcreditreport.com/ to look at your credit report. HINT: While you do that, and while you are in the TransUnion report, you will have the option to DISPUTE adverse items. I always suggest that people dispute everything adverse. That puts the onus on the other parties to produce evidence to TransUnion within 30 days attesting to the validity of the adverse item. You would be surprised how many will simply drop off your report after doing that. Everybody should do this Here is a direct address for TransUnion: https://dispute.transunion.com/dp/dispute/landingPage.jsp ==> Once the disputes are finalized, the results get communicated to the other two bureaus. It is amazing how well it works. It can raise your credit score significantly. It really helps to watch your credit report yourself, and also to get whatever protection is offered that may help protect you against others opening new accounts in your name.", "title": "" }, { "docid": "39376", "text": "Kudos to you on having money in a retirement account as early as after college. Many people don't start investing towards retirement until far to late and compound interest makes a major difference in those early years. Ideally, neither withdraw nor borrow from these accounts. Withdrawing from your 403b will incur a 10% penalty unless you are over the minimum age on top of the normal tax on that income. With a 401K loan you're putting yourself at risk if you run into a situation where you can't pay the loan back of incurring the same penalties as an early withdrawal. This article covers the concerns well. In general, you want to view your retirement money as untouchable until the distributions need to start coming in retirement. It's your future in there. Of course, this doesn't help the short term cash need. Do you have money in an emergency fund somewhere? Could a relative loan you money? Can you move to a less expensive place in advance and squirrel away some of what would have been your rent cash? Can you cut back to bare necessities and do the same? Do you have some nice stuff sitting around that you could sell to make up that needed cash? Will your current employer pay out unused vacation or are you getting any severance from this situation? Will you qualify for unemployment? I other words, think about what you would do to get the money if your retirement accounts weren't there. Then do that - as long as it's legal and doesn't involve running up debt on high interest lines of credit - instead of borrowing against your future.", "title": "" }, { "docid": "69395", "text": "\"Your plan already answers your own question in the best possible way: If you want to be able to make the most possible profit from a large downward move in a stock (in this case, a stock that tracks gold), with a limited, defined risk if there is an upward move, the optimal strategy is to buy a put option. There are a few Exchange Traded Funds (ETFs) that track the price of gold. think of them as stocks that behave like gold, essentially. Two good examples that have options are GLD and IAU. (When you talk about gold, you'll hear a lot about futures. Forget them, for now. They do the same essential thing for your purposes, but introduce more complexity than you need.) The way to profit from a downward move without protection against an upward move is by shorting the stock. Shorting stock is like the opposite of buying it. You make the amount of money the stock goes down by, or lose the amount it goes up by. But, since stocks can go up by an infinite amount, your possible loss is unlimited. If you want to profit on a large downward move without an unlimited loss if you're wrong and it goes up, you need something that makes money as the stock drops, but can only lose so much if it goes up. (If you want to be guaranteed to lose nothing, your best investment option is buying US Treasuries, and you're technically still exposed to the risk that US defaults on its debt, although if you're a US resident, you'll likely have bigger problems than your portfolio in that situation.) Buying a put option has the exact asymmetrical exposure you want. You pay a limited premium to buy it, and at expiration you essentially make the full amount that the stock has declined below the strike price, less what you paid for the option. That last part is important - because you pay a premium for the option, if it's down just a little, you might still lose some or all of what you paid for it, which is what you give up in exchange for it limiting your maximum loss. But wait, you might say. When I buy an option, I can lose all of my money, cant I? Yes, you can. Here's the key to understanding the way options limit risk as compared to the corresponding way to get \"\"normal\"\" exposure through getting long, or in your case, short, the stock: If you use the number of options that represent the number of shares you would have bought, you will have much, much less total money at risk. If you spend the same \"\"bag 'o cash\"\" on options as you would have spent on stock, you will have exposure to way more shares, and have the same amount of money at risk as if you bought the stock, but will be much more likely to lose it. The first way limits the total money at risk for a similar level of exposure; the second way gets you exposure to a much larger amount of the stock for the same money, increasing your risk. So the best answer to your described need is already in the question: Buy a put. I'd probably look at GLD to buy it on, simply because it's generally a little more liquid than IAU. And if you're new to options, consider the following: \"\"Paper trade\"\" first. Either just keep track of fake buys and sells on a spreadsheet, or use one of the many online services where you can track investments - they don't know or care if they're real or not. Check out www.888options.com. They are an excellent learning resource that isn't trying to sell you anything - their only reason to exist is to promote options education. If you do put on a trade, don't forget that the most frustrating pitfall with buying options is this: You can be basically right, and still lose some or all of what you invest. This happens two ways, so think about them both before you trade: If the stock goes in the direction you think, but not enough to make back your premium, you can still lose. So you need to make sure you know how far down the stock has to be to make back your premium. At expiration, it's simple: You need it to be below the strike price by more than what you paid for the option. With options, timing is everything. If the stock goes down a ton, or even to zero - free gold! - but only after your option expires, you were essentially right, but lose all your money. So, while you don't want to buy an option that's longer than you need, since the premium is higher, if you're not sure if an expiration is long enough out, it isn't - you need the next one. EDIT to address update: (I'm not sure \"\"not long enough\"\" was the problem here, but...) If the question is just how to ensure there is a limited, defined amount you can lose (even if you want the possible loss to be much less than you can potentially make, the put strategy described already does that - if the stock you use is at $100, and you buy a put with a 100 strike for $5, you can make up to $95. (This occurs if the stock goes to zero, meaning you could buy it for nothing, and sell it for $100, netting $95 after the $5 you paid). But you can only lose $5. So the put strategy covers you. If the goal is to have no real risk of loss, there's no way to have any real gain above what's sometimes called the \"\"risk-free-rate\"\". For simplicity's sake, think of that as what you'd get from US treasuries, as mentioned above. If the goal is to make money whether the stock (or gold) goes either up or down, that's possible, but note that you still have (a fairly high) risk of loss, which occurs if it fails to move either up or down by enough. That strategy, in its most common form, is called a straddle, which basically means you buy a call and a put with the same strike price. Using the same $100 example, you could buy the 100-strike calls for $5, and the 100-strike puts for $5. Now you've spent $10 total, and you make money if the stock is up or down by more than $10 at expiration (over 110, or under 90). But if it's between 90 and 100, you lose money, as one of your options will be worthless, and the other is worth less than the $10 total you paid for them both.\"", "title": "" }, { "docid": "62047", "text": "\"I think this question is perfectly on topic, and probably has been asked and answered many times. However, I cannot help myself. Here are some basics however: Personal Finance is not only about math. As a guy who \"\"took vector calculus just for fun\"\", I have learned that superior math skills do not translate into superior net worth. Personal finance is about 50% behavior. Take a look at the housing crisis, car loans, or payday lenders and you will understand that the desire to be accepted by others often trumps the math surrounding a transaction. Outline your goals What is it that you want in life? A pile of money or to retire early? What does your business look like? How much cash will you need? Do you want to own a ton of rental properties? How does all this happen (set intermediate goals). Then get on a budget A budget is a plan to spend your money in advance. Stick to it. From there you can see how much money you have to implement various goals. Are your goals to aggressive? This is really important as people have a tendency to spend more money then they have. Often times when people receive a bonus at work, they spend that one bonus on two or three times over. A budget will prevent this from happening. Get an Emergency Fund Without an emergency fund, you be subject to the financial whims of people involved in your own life and that of the broader marketplace. Once you have one, you are free to invest with impunity and have less stress in a world that deals out plenty. Bad things will happen to you financially, protect against them. The best first investments are simple: Invest in yourself. Find a way to make a very healthy income with upward mobility. Also get out and stay out of debt. These things are not sexy, but they pay off in the long run. The next best investment is also simple: Index funds. These become the bench mark for all other investments. If you do not stand a good chance of beating the S&P 500 index fund, why bother? Just dump the money in the fund and sleep well at night.\"", "title": "" } ]
7148
Are wash sale rules different for stocks and ETFs / Mutual Funds?
[ { "docid": "590010", "text": "What JoeTaxpayer means is that you can sell one ETF and buy another that will perform substantially the same during the 30 day wash sale period without being considered substantially the same from a wash sale perspective more easily than you could with an individual stock. For example, you could sell an S&P 500 index ETF and then temporarily buy a DJIA index ETF. As these track different indexes, they are not considered to be substantially the same for wash sale purposes, but for a short term investing period, their performance should still be substantially the same.", "title": "" }, { "docid": "261902", "text": "\"The IRS rules are actually the same. 26 U.S. Code § 1091 - Loss from wash sales of stock or securities In the case of any loss claimed to have been sustained from any sale or other disposition of shares of stock or securities where it appears that, within a period beginning 30 days before the date of such sale or disposition and ending 30 days after such date, the taxpayer has acquired (by purchase or by an exchange on which the entire amount of gain or loss was recognized by law), or has entered into a contract or option so to acquire, substantially identical stock or securities, then no deduction shall be allowed... What you should take away from the quote above is \"\"substantially identical stock or securities.\"\" With stocks, one company may happen to have a high correlation, Exxon and Mobil come to mind, before their merger of course. With funds or ETFs, the story is different. The IRS has yet to issue rules regarding what level of overlap or correlation makes two funds or ETFs \"\"substantially identical.\"\" Last month, I wrote an article, Tax Loss Harvesting, which analyses the impact of taking losses each year. I study the 2000's which showed an average loss of 1% per year, a 9% loss for the decade. Tax loss harvesting made the decade slightly positive, i.e. an annual boost of approx 1%.\"", "title": "" }, { "docid": "275340", "text": "No, there's nothing special in mutual funds or ETFs. Wash sale rules apply to any asset.", "title": "" } ]
[ { "docid": "195767", "text": "@BlackJack does a good answer of addressing the gains and when you are taxed on them and at what kind of rate. Money held in a brokerage account will usually be in a money-market fund, so you would own taxes on the interest it earned. There is one important consideration that must be understood for capitol Losses. This is called the Wash Sale Rule. This rule comes into affect if you sell a stock at a LOSS, and buy shares of the same stock within 30 days (before or after) the sale. A common tactic used to minimize taxes paid is to 'capture losses' when they occur, since these can be used to offset gains and lower your taxes. This is normally done by selling a stock in which you have a LOSS, and then either buying another similar stock, or waiting and buying back the stock you sold. However, if you are intending to buy back the same stock, you must not 'trigger' the Wash Sale Rule or you are forbidden to take the loss. Examples. Lets presume you own 1000 shares of a stock and it's trading 25% below where you bought it, and you want to capture the loss to use on your taxes. This can be a very important consideration if trading index ETF's if you have a loss in something like a S&P500 ETF, you would likely incur a wash sale if you sold it and bought a different S&P500 ETF from another company since they are effectively the same thing. OTOH, if you sold an S&P500 ETF and bought something like a 'viper''total stock market' ETF it should be different enough to not trigger the wash sale rule. If you are trying to minimize the taxes you pay on stocks, there are basically two rules to follow. 1) When a gain is involved, hold things at least a year before selling, if at all possible. 2) Capture losses when they occur and use to offset gains, but be sure not to trigger the wash sale rule when doing so.", "title": "" }, { "docid": "530631", "text": "\"It sounds like this is an entirely unsettled question, unfortunately. In the examples you provide, I think it is safe to say that none of those are 'substantially identical'; a small overlap or no overlap certainly should not be considered such by a reasonable interpretation of the rule. This article on Kitces goes into some detail on the topic. A few specifics. First, Former publication 564 explains: Ordinarily, shares issued by one mutual fund are not considered to be substantially identical to shares issued by another mutual fund. Of course, what \"\"ordinarily\"\" means is unspecified (and this is no longer a current publication, so, who knows). The Kitces article goes on to explain that the IRS hasn't really gone after wash sales for mutual funds: Over the years, the IRS has not pursued wash sale abuses against mutual funds, perhaps because it just wasn’t very feasible to crack down on them, or perhaps because it just wasn’t perceived as that big of an abuse. After all, while the rules might allow you to loss-harvest a particular stock you couldn’t have otherwise, it also limits you from harvesting ANY losses if the overall fund is up in the aggregate, since losses on individual stocks can’t pass through to the mutual fund shareholders. But then goes to explain about ETFs being very different: sell SPY, buy IVV or VTI, and you're basically buying/selling the identical thing (99% or so correlation in stocks owned). The recommendation by the article is to look at the correlation in owned stocks, and stay away from things over 95%; that seems reasonable in my book as well. Ultimately, there will no doubt be a large number of “grey” and murky situations, but I suspect that until the IRS provides better guidance (or Congress rewrites/updates the wash sale rules altogether!), in the near term the easiest “red flag” warning is simply to look at the correlation between the original investment being loss-harvested, and the replacement security; at correlations above 0.95, and especially at 0.99+, it’s difficult to argue that the securities are not ”substantially identical” to each other in performance. Basically - use common sense, and don't do anything you think would be hard to defend in an audit, but otherwise you should be okay.\"", "title": "" }, { "docid": "207929", "text": "I agree, one should not let the tax tail wag the investing dog. The only question should be whether he'd buy the stock at today's price. If he wishes to own it long term, he keeps it. To take the loss this year, he'd have to sell soon, and can't buy it back for 30 days. If, for whatever reason, the stock comes back a bit, he's going to buy in higher. To be clear, the story changes for ETFs or mutual funds. You can buy a fund to replace one you're selling, capture the loss, and easily not run afoul of wash sale rules.", "title": "" }, { "docid": "454224", "text": "A mutual fund has several classes of shares that are charged different fees. Some shares are sold through brokers and carry a sales charge (called load) that compensates the broker in lieu of a fee that the broker would charge the client for the service. Vanguard does not have sales charge on its funds and you don't need to go through a broker to buy its shares; you can buy directly from them. Admiral shares of Vanguard funds are charged lower annual expenses than regular shares (yes, all mutual funds charge expenses for fund adninistration that reduce the return that you get, and Vanguard has some of the lowest expense ratios) but Admiral shares are available only for large investments, typically $50K or so. If you have invested in a Vanguard mutual fund, your shares can be set to automatically convert to Admiral shares when the investment reaches the right level. A mutual fund manager can buy and sell stocks to achieve the objectives of the fund, so what stockes you are invested in as a share holder in a mutual fund will typically be unknown to you on a day-to-day basis. On the other hand, Exchange-traded funds (ETFs) are fixed baskets of stocks, and you can buy shares in the ETF. These shares are bought and sold through a broker (so you pay a transaction fee each time) but expenses are lower since there is no manager to buy and sell stocks: the basket is fixed. Many ETFs follow specific market indexes (e.g. S&P 500). Another difference between ETFs and mutual funds is that you can buy and sell ETFs at any time of the day just as if you could if you held stocks. With mutual funds, any buy and sell requests made during the day are processed at the end of the day and the value of the shares that you buy or sell is determined by the closing price of the stocks held by the mutual fund. With ETFs, you are getting the intra-day price at the time the buy or sell order is executed by your broker.", "title": "" }, { "docid": "367960", "text": "\"I think you are asking about actively managed funds vs. indexes and possibly also vs. diversified funds like target date funds. This is also related to the question of mutual fund vs. ETF. First, a fund can be either actively managed or it can attempt to track an index. An actively managed fund has a fund manager who tries to find the best stocks to invest in within some constraints, like \"\"this fund invests in large cap US companies\"\". An index fund tries to match as closely as possible the performance of an index like the S&P 500. A fund may also try to offer a portfolio that is suitable for someone to put their entire account into. For example, a target date fund is a fund that may invest in a mix of stocks, bonds and foreign stock in a proportion that would be appropriate to someone expecting to retire in a certain year. These are not what people tend to think of as the canonical examples of mutual funds, even though they share the same legal structure and investment mechanisms. Secondly, a fund can either be a traditional mutual fund or it can be an exchange traded fund (ETF). To invest in a traditional mutual fund, you send money to the fund, and they give you a number of shares equal to what that money would have bought of the net asset value (NAV) of the fund at the end of trading on the day they receive your deposit, possibly minus a sales charge. To invest in an ETF, you buy shares of the ETF on the stock market like any other stock. Under the covers, an ETF does have something similar to the mechanism of depositing money to get shares, but only big traders can use that, and it's not used for investing, but only for people who are making a market in the stock (if lots of people are buying VTI, Big Dealer Co will get 100,000 shares from Vanguard so that they can sell them on the market the next day). Historically and traditionally, ETFs are associated with an indexing strategy, while if not specifically mentioned, people assume that traditional mutual funds are actively managed. Many ETFs, notably all the Vanguard ETFs, are actually just a different way to hold the same underlying fund. The best way to understand this is to read the prospectus for a mutual fund and an ETF. It's all there in reasonably plain English.\"", "title": "" }, { "docid": "364735", "text": "I think that assuming that you're not looking to trade the fund, an index Mutual Fund is a better overall value than an ETF. The cost difference is negligible, and the ability to dollar-cost average future contributions with no transaction costs. You also have to be careful with ETFs; the spreads are wide on a low-volume fund and some ETFs are going more exotic things that can burn a novice investor. Track two similar funds (say Vanguard Total Stock Market: VTSMX and Vanguard Total Stock Market ETF: VTI), you'll see that they track similarly. If you are a more sophisticated investor, ETFs give you the ability to use options to hedge against declines in value without having to incur capital gains from the sale of the fund. (ie. 20 years from now, can use puts to make up for short-term losses instead of selling shares to avoid losses) For most retail investors, I think you really need to justify using ETFs versus mutual funds. If anything, the limitations of mutual funds (no intra-day trading, no options, etc) discourage speculative behavior that is ultimately not in your best interest. EDIT: Since this answer was written, many brokers have begun offering a suite of ETFs with no transaction fees. That may push the cost equation over to support Index ETFs over Index Mutual Funds, particularly if it's a big ETF with narrow spreads..", "title": "" }, { "docid": "285135", "text": "\"The IRS has been particularly vague about the \"\"substantially identical\"\" investment part of the wash rule. Many brokers, Schwab for instance, say that only identical CUSIPs (exactly the same ETF) matter for the wash rule in their internal calculations, but warn that the IRS might consider two ETFs over the same index to be substantially identical. In your case, the broker has chosen to call these a wash despite even having different underlying indices. Talking to the broker is the first step as they will report it to the IRS. Though technically you have the final say in your taxes about the cost basis, discussing this with the IRS could be rather painful. First though it is probably worth checking with your broker about exactly what happened. There are other wash sale triggers that frequently trip people up that may have been in play here.\"", "title": "" }, { "docid": "132111", "text": "\"Yes- you do not realize gains or losses until you actually sell the stock. After you sell the initial stocks/bonds you have realized the gain. When you buy the new, different stocks you haven't realized anything until you then sell those. There is one exception to this, called the \"\"Wash-Sale Rule\"\". From Investopedia.com: With the wash-sale rule, the IRS disallows a loss deduction from the sale of a security if a ‘substantially identical security' was purchased within 30 days before or after the sale. The wash-sale period is actually 61 days, consisting of the 30 days before and the 30 days after the date of the sale. For example, if you bought 100 shares of IBM on December 1 and then sold 100 shares of IBM on December 15 at a loss, the loss deduction would not be allowed. Similarly, selling IBM on December 15 and then buying it back on January 10 of the following year does not permit a deduction. The wash-sale rule is designed to prevent investors from making trades for the sole purpose of avoiding taxes.\"", "title": "" }, { "docid": "153660", "text": "\"For a non-ETF mutual fund, you can only buy shares of the mutual fund from the mutual fund itself (at a price that the mutual fund will reveal only at the end of the day) and can only shares back to the mutual fund (again at a price that the mutual fund will reveal only at the end of the day). There is no open market in the sense that you cannot put in a bid to buy, say, 100 shares of VFINX at $217 per share through a brokerage, and if there is a seller willing to sell 100 shares of VFINX to you at $217, then the sale is consummated and you are now the proud owner of 100 shares of VFINX. The only buyer or seller of VFINX is the mutual find itself, and you tell it that you \"\"want to buy 100 shares of VFINX and please take the money out of my checking account\"\". If this order is entered before the markets close at 4 pm, the mutual fund determines its share price as of the end of the day, opens a new account for you and puts 100 shares of VFINX in it (or adds 100 shares of VFINX to your already existing pile of shares) and takes the purchase price out of your checking account via an ACH transfer. Similarly for redeeming/selling shares of VFINX that you own (and these are held in an account at the mutual fund itself, not by your brokerage): you tell the mutual fund to that you \"\"wish to redeem 100 shares and please send the proceeds to my bank account\"\" and the mutual fund does this at the end of the day, and the money appears in your bank account via ACH transfer two or three days later. Generally, these transactions do not need to be for round lots of multiples of 100 shares for efficiency; most mutual fund will gladly sell you fractional shares down to a thousandth of a share. In contrast, shares of an exchange-traded fund (ETF) are just like stock shares in that they can be bought and sold on the open market and your broker will charge you fees for buying and selling them. Selling fractional shares on the open market is generally not possible, and trading in round lots is less expensive. Also, trades occur at all times of the stock exchange day, not just at the end of the day as with non-ETF funds, and the price can fluctuate during the day too. Many non-ETF mutual funds have an ETF equivalent: VOO is the symbol for Vanguard's S&P 500 Index ETF while VFINX is the non-ETF version of the same index fund. Read more about the differences between ETFs and mutual funds, for example, here.\"", "title": "" }, { "docid": "254230", "text": "The issue with trading stocks vs. mutual funds (or ETFs) is all about risk. You trade Microsoft you now have a Stock Risk in your portfolio. It drops 5% you are down 5%. Instead if you want to buy Tech and you buy QQQ if MSFT fell 5% the QQQs would not be as impacted to the downside. So if you want to trade a mutual fund, but you want to be able to put in stop sell orders trade ETFs instead. Considering mutual funds it is better to say Invest vs. Trade. Since all fund families have different rules and once you sell (if you sell it early) you will pay a fee and will not be able to invest in that same fund for x number of days (30, 60...)", "title": "" }, { "docid": "370244", "text": "Behind the scenes, mutual funds and ETFs are very similar. Both can vary widely in purpose and policies, which is why understanding the prospectus before investing is so important. Since both mutual funds and ETFs cover a wide range of choices, any discussion of management, assets, or expenses when discussing the differences between the two is inaccurate. Mutual funds and ETFs can both be either managed or index-based, high expense or low expense, stock or commodity backed. Method of investing When you invest in a mutual fund, you typically set up an account with the mutual fund company and send your money directly to them. There is often a minimum initial investment required to open your mutual fund account. Mutual funds sometimes, but not always, have a load, which is a fee that you pay either when you put money in or take money out. An ETF is a mutual fund that is traded like a stock. To invest, you need a brokerage account that can buy and sell stocks. When you invest, you pay a transaction fee, just as you would if you purchase a stock. There isn't really a minimum investment required as there is with a traditional mutual fund, but you usually need to purchase whole shares of the ETF. There is inherently no load with ETFs. Tax treatment Mutual funds and ETFs are usually taxed the same. However, capital gain distributions, which are taxable events that occur while you are holding the investment, are more common with mutual funds than they are with ETFs, due to the way that ETFs are structured. (See Fidelity: ETF versus mutual funds: Tax efficiency for more details.) That having been said, in an index fund, capital gain distributions are rare anyway, due to the low turnover of the fund. Conclusion When comparing a mutual fund and ETF with similar objectives and expenses and deciding which to choose, it more often comes down to convenience. If you already have a brokerage account and you are planning on making a one-time investment, an ETF could be more convenient. If, on the other hand, you have more than the minimum initial investment required and you also plan on making additional regular monthly investments, a traditional no-load mutual fund account could be more convenient and less expensive.", "title": "" }, { "docid": "138383", "text": "Bond ETFs are just another way to buy a bond mutual fund. An ETF lets you trade mutual fund shares the way you trade stocks, in small share-size increments. The content of this answer applies equally to both stock and bond funds. If you are intending to buy and hold these securities, your main concerns should be purchase fees and expense ratios. Different brokerages will charge you different amounts to purchase these securities. Some brokerages have their own mutual funds for which they charge no trading fees, but they charge trading fees for ETFs. Brokerage A will let you buy Brokerage A's mutual funds for no trading fee but will charge a fee if you purchase Brokerage B's mutual fund in your Brokerage A account. Some brokerages have multiple classes of the same mutual fund. For example, Vanguard for many of its mutual funds has an Investor class (minimum $3,000 initial investment), Admiral class (minimum $10,000 initial investment), and an ETF (share price as initial investment). Investor class has the highest expense ratio (ER). Admiral class and the ETF generally have much lower ER, usually the same number. For example, Vanguard's Total Bond Market Index mutual fund has Investor class (symbol VBMFX) with 0.16% ER, Admiral (symbol VBTLX) with 0.06% ER, and ETF (symbol BND) with 0.06% ER (same as Admiral). See Vanguard ETF/mutual fund comparison page. Note that you can initially buy Investor class shares with Vanguard and Vanguard will automatically convert them to the lower-ER Admiral class shares when your investment has grown to the Admiral threshold. Choosing your broker and your funds may end up being more important than choosing the form of mutual fund versus ETF. Some brokers charge very high purchase/redemption fees for mutual funds. Many brokers have no ETFs that they will trade for free. Between funds, index funds are passively managed and are just designed to track a certain index; they have lower ERs. Actively managed funds are run by managers who try to beat the market; they have higher ERs and tend to actually fall below the performance of index funds, a double whammy. See also Vanguard's explanation of mutual funds vs. ETFs at Vanguard. See also Investopedia's explanation of mutual funds vs. ETFs in general.", "title": "" }, { "docid": "436530", "text": "\"From Pub 550: More or less stock bought than sold. If the number of shares of substantially identical stock or securities you buy within 30 days before or after the sale is either more or less than the number of shares you sold, you must determine the particular shares to which the wash sale rules apply. You do this by matching the shares bought with an equal number of the shares sold. Match the shares bought in the same order that you bought them, beginning with the first shares bought. The shares or securities so matched are subject to the wash sale rules. You must match \"\"beginning with the first shares bought.\"\" If only activity 1 & 4 happened, you'd have bought and sold stock with no wash sale. If you remove activity 1 & 4 from consideration because they are a \"\"normal\"\" or non-wash sale transaction, then the Activity 2 or Activity 3 trigger a wash sale. The shares in lot 1 are sold for disallowed loss, so the disallowed basis would be added to shares in lot 2 because lot 2 was purchased before lot 3. (hat tip to user662852 who had much better wording) Second example: Activity 5, 7, and 8 all together would not be a wash sale. The addition of activity 6 creates a wash sale. The shares in Activity 5 are sold for a disallowed loss in Activity 7 & 8 because of the wash sale triggering purchase in Activity 6. Activity 6 is where you add the disallowed basis because they are the \"\"first shares bought\"\" that cause the wash sale rule to be triggered.\"", "title": "" }, { "docid": "358997", "text": "What is your time horizon? Over long horizons, you absolutely want to minimise the expense ratio – a seemingly puny 2% fee p.a. can cost you a third of your savings over 35 years. Over short horizons, the cost of trading in and trading out might matter more. A mutual fund might be front-loaded, i.e. charge a fixed initial percentage when you first purchase it. ETFs, traded daily on an exchange just like a stock, don't have that. What you'll pay there is the broker commission, and the bid-ask spread (and possibly any premium/discount the ETF has vis-a-vis the underlying asset value). Another thing to keep in mind is tracking error: how closely does the fond mirror the underlying index it attempts to track? More often than not it works against you. However, not sure there is a systematic difference between ETFs and funds there. Size and age of a fund can matter, indeed - I've had new and smallish ETFs that didn't take off close down, so I had to sell and re-allocate the money. Two more minor aspects: Synthetic ETFs and lending to short sellers. 1) Some ETFs are synthetic, that is, they don't buy all the underlying shares replicating the index, actually owning the shares. Instead, they put the money in the bank and enter a swap with a counter-party, typically an investment bank, that promises to pay them the equivalent return of holding that share portfolio. In this case, you have (implicit) credit exposure to that counter-party - if the index performs well, and they don't pay up, well, tough luck. The ETF was relying on that swap, never really held the shares comprising the index, and won't necessarily cough up the difference. 2) In a similar vein, some (non-synthetic) ETFs hold the shares, but then lend them out to short sellers, earning extra money. This will increase the profit of the ETF provider, and potentially decrease your expense ratio (if they pass some of the profit on, or charge lower fees). So, that's a good thing. In case of an operational screw up, or if the short seller can't fulfil their obligations to return the shares, there is a risk of a loss. These two considerations are not really a factor in normal times (except in improving ETF expense ratios), but during the 2009 meltdown they were floated as things to consider. Mutual funds and ETFs re-invest or pay out dividends. For a given mutual fund, you might be able to choose, while ETFs typically are of one type or the other. Not sure how tax treatment differs there, though, sorry (not something I have to deal with in my jurisdiction). As a rule of thumb though, as alex vieux says, for a popular index, ETFs will be cheaper over the long term. Very low cost mutual funds, such as Vanguard, might be competitive though.", "title": "" }, { "docid": "161019", "text": "Your tax efficient reasoning is solid for where you want to distribute your assets. ETFs are often more tax efficient than their equivalent mutual funds but the exact differences would depend on the comparison between the fund and ETF you were considering. The one exception to this rule is Vanguard funds and ETFs which have the exact same tax-efficiency because ETFs are a share class of the corresponding mutual fund.", "title": "" }, { "docid": "270992", "text": "The main difference between an ETF and a Mutual Fund is Management. An ETF will track a specific index with NO manager input. A Mutual Fund has a manager that is trying to choose securities for its fund based on the mandate of the fund. Liquidity ETFs trade like a stock, so you can buy at 10am and sell at 11 if you wish. Mutual Funds (most) are valued at the end of each business day, so no intraday trading. Also ETFs are similar to stocks in that you need a buyer/seller for the ETF that you want/have. Whereas a mutual fund's units are sold back to itself. I do not know of many if any liquity issues with an ETF, but you could be stuck holding it if you can not find a buyer (usually the market maker). Mutual Funds can be closed to trading, however it is rare. Tax treatment Both come down to the underlying holdings in the fund or ETF. However, more often in Mutual Funds you could be stuck paying someone else's taxes, not true with an ETF. For example, you buy an Equity Mutual Fund 5 years ago, you sell the fund yourself today for little to no gain. I buy the fund a month ago and the fund manager sells a bunch of the stocks they bought for it 10 years ago for a hefty gain. I have a tax liability, you do not even though it is possible that neither of us have any gains in our pocket. It can even go one step further and 6 months from now I could be down money on paper and still have a tax liability. Expenses A Mutual Fund has an MER or Management Expense Ratio, you pay it no matter what. If the fund has a positive return of 12.5% in any given year and it has an MER of 2.5%, then you are up 10%. However if the fund loses 7.5% with the same MER, you are down 10%. An ETF has a much smaller management fee (typically 0.10-0.95%) but you will have trading costs associated with any trades. Risks involved in these as well as any investment are many and likely too long to go into here. However in general, if you have a Canadian Stock ETF it will have similar risks to a Canadian Equity Mutual Fund. I hope this helps.", "title": "" }, { "docid": "39265", "text": "In addition to the higher risk as pointed out by @JamesRoth, you also need to consider that there are regulations against 'naked shorting' so you generally need to either own the security, or have someone that is willing to 'loan' the security to you in order to sell short. If you own a stock you are shorting, the IRS could view the transaction as a Sell followed by a buy taking place in a less than 30 day period and you could be subject to wash-sale rules. This added complexity (most often the finding of someone to loan you the security you are shorting) is another reason such trades are considered more advanced. You should also be aware that there are currently a number of proposals to re-instate the 'uptick rule' or some circuit-breaker variant. Designed to prevent short-sellers from driving down the price of a stock (and conducting 'bear raids etc) the first requires that a stock trade at the same or higher price as prior trades before you can submit a short. In the latter shorting would be prohibited after a stock price had fallen a given percentage in a given amount of time. In either case, should such a rule be (re)established then you could face limitations attempting to execute a short which you would not need to worry about doing simple buys or sells. As to vehicles that would do this kind of thing (if you are convinced we are in a bear market and willing to take the risk) there are a number of ETF's classified as 'Inverse Exchange Traded Funds (ETF's) for a variety of markets that via various means seek to deliver a return similar to that of 'shorting the market' in question. One such example for a common broad market is ticker SH the ProShares Short S&P500 ETF, which seeks to deliver a return that is the inverse of the S&P500 (and as would be predicted based on the roughly +15% performance of the S&P500 over the last 12 months, SH is down roughly -15% over the same period). The Wikipedia article on inverse ETF's lists a number of other such funds covering various markets. I think it should be noted that using such a vehicle is a pretty 'aggressive bet' to take in reaction to the belief that a bear market is imminent. A more conservative approach would be to simply take money out of the market and place it in something like CD's or Treasury instruments. In that case, you preserve your capital, regardless of what happens in the market. Using an inverse ETF OTOH means that if the market went bull instead of bear, you would lose money instead of merely holding your position.", "title": "" }, { "docid": "457059", "text": "\"There are different schools of thought. You can ask the IRS - and it would not surprise me if you got different answers on different phone calls. One interpretation is that a put is not \"\"substantially identical\"\" to the disposed stock, therefore no wash is triggered by that sale. However if that put is exercised, then you automatically purchase the security, and that is identical. As to whether the IRS (or your brokerage firm) recognizes the identical security when it falls out of an option, I can't say; but technically they could enforce it because the rule is based on 30 days and a \"\"substantially identical\"\" stock or security. In this interpretation (your investor) would probably at least want to stay out of the money in choosing a strike price, to avoid exercise; however, options are normally either held or sold, rather than be exercised, until at or very close to the expiration date (because time value is left on the table otherwise). So the key driver in this interpretation would be expiration date, which should be at least 31 days out from the stock sale; and it would be prudent to sell an out of the money put as well, in order to avoid the wash sale trigger. However there is also a more unfavorable opinion - see fairmark.com/capgain/wash/wsoption.htm where they hold that a \"\"deep in the money\"\" option is an immediate trigger (regardless of exercise). This article is sage, in that they say that the Treasury (IRS) may interpret an option transaction as a wash if it's ballpark to being exercisable. And, if the IRS throws paper, it always beats each of paper, rock and scissors :( A Schwab article (\"\"A Primer on Wash Sales\"\") says, if the CUSIPs match, bang, wash. This is the one that they may interpret unfavorably on in any case, supporting Schwab's \"\"play it safe\"\" position: \"\"3. Acquire a contract or option to buy substantially identical stock or securities...\"\" . This certainly nails buying a call. As to selling a put, well, it is at least conceivable that an IRS official would call that a contract to buy! SO it's simply not a slam dunk; there are varying opinions that you might describe as ranging from \"\"hell no\"\" to \"\"only if blatant.\"\" If you can get an \"\"official\"\" predetermination, or you like to go aggressive in your tax strategy, there's that; they may act adversely, so Caveat Taxfiler!\"", "title": "" }, { "docid": "113948", "text": "Yes, an overall $500 loss on the stock can be claimed. Since the day trader sold both lots she acquired, the Wash Sale rule has no net impact on her taxes. The Wash Sale rule would come into play if within thirty days of second sale, she purchased the stock a third time. Then she would have to amend her taxes because claiming the $500 loss would no longer be a valid under the Wash Sale rule. It would have to be added to the cost basis of the most recent purchase.", "title": "" }, { "docid": "589957", "text": "In a situation like this, I presume you'd invest in the child company if you thought that the child company would increase in value at a higher rate than the parent. You'd invest in the parent company if you thought the parent company would perform well as a whole, but you did not want to assume the risk of an individual company underneath it. Say the child company is worth 100 million, and the parent company is worth 500 million. You've invested a sum of money in the child company. The child company performs very well, and increases in value by, say, 20 million. As the parent company owns the child, we could say it also increases in value by roughly 20 million. The difference is proportional - Your investment in the child sees a 20% gain in value, whereas your investment in the parent sees a 4% gain in total value, as in this example the parent company, which owns nearly 100% of the child company, is worth 5x more and thus proportionally sees 1/5 the increase in value, due to it being worth more as a whole. Think of it similarly to a mutual fund or ETF that invests in many different stocks on the market. As the market does well, that mutual fund or ETF does well, too. As the mutual fund is made up of many individual stocks, one stock performing very well, say at a 10-20% increase in value, does not raise the value of the ETF or mutual fund by 10-20%. The etf / mutual fund will perform slightly better (Assuming all other components remain equal for this example), but only proportionally to the fraction of it that's made up of the stock that's performing well.", "title": "" }, { "docid": "571124", "text": "\"According to Wikipedia this is still a wash sale: In the USA wash sale rules are codified in \"\"26 USC § 1091 - Loss from wash sales of stock or securities.\"\" Under Section 1091, a wash sale occurs when a taxpayer sells or trades stock or securities at a loss, and within 30 days before or after the sale:\"", "title": "" }, { "docid": "49168", "text": "The creation mechanism for ETF's ensures that the value of the underlying stocks do not diverge significantly from the Fund's value. Authorized participants have a strong incentive to arbitrage any pricing differences and create/redeem blocks of stock/etf until the prices are back inline. Contrary to what was stated in a previous answer, this mechanism lowers the cost of management of ETF's when compared to mutual funds that must access the market on a regular basis when any investors enter/exit the fund. The ETF only needs to create/redeem in a wholesale basis, this allows them to operate with management fees that are much lower than those of a mutual fund. Expenses Due to the passive nature of indexed strategies, the internal expenses of most ETFs are considerably lower than those of many mutual funds. Of the more than 900 available ETFs listed on Morningstar in 2010, those with the lowest expense ratios charged about .10%, while those with the highest expenses ran about 1.25%. By comparison, the lowest fund fees range from .01% to more than 10% per year for other funds. (For more on mutual fund feeds, read Stop Paying High Fees.)", "title": "" }, { "docid": "350555", "text": "Capital gain distribution is not capital gain on sale of stock. If you have stock sales (Schedule D) you should be filing 1040, not 1040A. Capital gain distributions are distributions from mutual funds/ETFs that are attributed to capital gains of the funds (you may not have actually received the distribution, but you still may have gain attributed to you). It is reported on 1099-DIV, and if it is 0 - then you don't have any. If you sold a stock, your broker should have given you 1099-B (which is not the same as 1099-DIV, but may be consolidated by your broker into one large PDF and not provided separately). On 1099-B the sales proceeds are recorded, and if you purchased the stock after 2011 - the cost basis is also recorded. The difference between the proceeds and the cost basis is your gain (or loss, if it is negative). Fees are added to cost basis.", "title": "" }, { "docid": "54947", "text": "\"Buy the ETF with ticker \"\"SPY\"\". This will give you exposure to exactly the S&P 500 stocks, This is similar to the mutual fund suggestion by Ben Miller, except that the ETF has several advantages over mutual funds, especially as regards taxes. You can find information on the difference between ETF and mutual fund in other questions on this site or by searching the web.\"", "title": "" }, { "docid": "580802", "text": "You cannot do a 1031 exchange with stocks, bonds, mutual funds, or ETFs. There really isn't much difference between an ETF and its equivalent index mutual fund. Both will have minimal capital gains distributions. I would not recommend selling an index mutual fund and taking a short-term capital gain just to buy the equivalent ETF.", "title": "" }, { "docid": "183898", "text": "It is true that this is possible, however, it's very remote in the case of the large and reputable fund companies such as Vanguard. FDIC insurance protects against precisely this for bank accounts, but mutual funds and ETFs do not have an equivalent to FDIC insurance. One thing that does help you in the case of a mutual fund or ETF is that you indirectly (through the fund) own actual assets. In a cash account at a bank, you have a promise from the bank to pay, and then the bank can go off and use your money to make loans. You don't in any sense own the bank's loans. With a fund, the fund company cannot (legally) take your money out of the fund, except to pay the expense ratio. They have to use your money to buy stocks, bonds, or whatever the fund invests in. Those assets are then owned by the fund. Legally, a mutual fund is a special kind of company defined in the Investment Company Act of 1940, and is a separate company from the investment advisor (such as Vanguard): http://www.sec.gov/answers/mfinvco.htm Funds have their own boards, and in principle a fund board can even fire the company advising the fund, though this is not likely since boards aren't usually independent. (a quick google found this article for more, maybe someone can find a better one: http://www.marketwatch.com/story/mutual-fund-independent-board-rule-all-but-dead) If Vanguard goes under, the funds could continue to exist and get a new adviser, or could be liquidated with investors receiving whatever the assets are worth. Of course, all this legal stuff doesn't help you with outright fraud. If a fund's adviser says it bought the S&P 500, but really some guy bought himself a yacht, Madoff-style, then you have a problem. But a huge well-known ETF has auditors, tons of different employees, lots of brokerage and exchange traffic, etc. so to me at least it's tough to imagine a risk here. With a small fund company with just a few people - and there are lots of these! - then there's more risk, and you'd want to carefully look at what independent agent holds their assets, who their auditors are, and so forth. With regular mutual funds (not ETFs) there are more issues with diversifying across fund companies: With ETFs, there probably isn't much downside to diversifying since you could buy them all from one brokerage account. Maybe it even happens naturally if you pick the best ETFs you can find. Personally, I would just pick the best ETFs and not worry about advisor diversity. Update: maybe also deserving a mention are exchange-traded notes (ETNs). An ETN's legal structure is more like the bank account, minus the FDIC insurance of course. It's an IOU from the company that runs the ETN, where they promise to pay back the value of some index. There's no investment company as with a fund, and therefore you don't own a share of any actual assets. If the ETN's sponsor went bankrupt, you would indeed have a problem, much more so than if an ETF's sponsor went bankrupt.", "title": "" }, { "docid": "407602", "text": "Note that the rules around wash sales vary depending on where you live. For the U.S., the wash sale rules say that you cannot buy a substantially identical stock or security within 30 days (before or after) your sale. So, you could sell your stock today to lock in the capital losses. However, you would then have to wait at least 30 days before purchasing it back. If you bought it back within 30 days, you would disqualify the capital loss event. The risk, of course, is that the stock's price goes up substantially while you are waiting for the wash sale period. It's up to you to determine if the risk outweighs the benefit of locking in your capital losses. Note that this applies regardless of whether you sell SOME or ALL of the stock. Or indeed, if we are talking about securities other than stocks.", "title": "" }, { "docid": "472663", "text": "\"An Exchange-Traded Fund (ETF) is a special type of mutual fund that is traded on the stock exchange like a stock. To invest, you buy it through a stock broker, just as you would if you were buying an individual stock. When looking at a mutual fund based in the U.S., the easiest way to tell whether or not it is an ETF is by looking at the ticker symbol. Traditional mutual funds have ticker symbols that end in \"\"X\"\", and ETFs have ticker symbols that do not end in \"\"X\"\". The JPMorgan Emerging Markets Equity Fund, with ticker symbol JFAMX, is a traditional mutual fund, not an ETF. JPMorgan does have ETFs; the JPMorgan Diversified Return Emerging Markets Equity ETF, with ticker symbol JPEM, is an example. This ETF invests in similar stocks as JFAMX; however, because it is an index-based fund instead of an actively managed fund, it has lower fees. If you aren't sure about the ticker symbol, the advertising/prospectus of any ETF should clearly state that it is an ETF. (In the example of JPEM above, they put \"\"ETF\"\" right in the fund name.) If you don't see ETF mentioned, it is most likely a traditional mutual fund. Another way to tell is by looking at the \"\"investment minimums\"\" of the fund. JFAMX has a minimum initial investment of $1000. ETFs, however, do not have an investment minimum listed; because it is traded like a stock, you simply buy whole shares at whatever the current share price is. So if you look at the \"\"Fees and Investment Minimums\"\" section of the JPEM page, you'll see the fees listed, but not any investment minimums.\"", "title": "" }, { "docid": "220486", "text": "\"You cannot actually buy an index in the true sense of the word. An index is created and maintained by a company like Standard and Poor's who licenses the use of the index to firms like Vanguard. The S&P 500 is an example of an index. The S&P 500 \"\"index includes 500 leading companies\"\", many finical companies sell products which track to this index. The two most popular products which track to indexes are Mutual Funds (as called Index Funds and Index Mutual Funds) and Exchange Traded Funds (as called ETFs). Each Index Mutual Fund or ETF has an index which it tracks against, meaning they hold securities which make up a sample of the index (some indexes like bond indexes are very hard to hold everything that makes them up). Looking at the Vanguard S&P 500 Index Mutual Fund (ticker VFINX) we see that it tracks against the S&P 500 index. Looking at its holdings we see the 500-ish stocks that it holds along with a small amount of bonds and cash to handle cash flow for people buying and sell shares. If we look at the Vanguard S&P 500 ETF (ticker VOO) we see that it also tracks against the S&P 500 index. Looking at its holdings we see they are very similar to the similar Index Mutual Fund. Other companies like T. Rowe Price have similar offering. Look at the T. Rowe Price Equity Index 500 Fund (ticker PREIX) its holdings in stocks are the same as the similar Vanguard fund and like the Vanguard fund it also holds a small amount of bonds and cash to handle cash flow. The only real difference between different products which track against the same index is in the expense ratio (fees for managing the fund) and in the small differences in the execution of the funds. For the most part execution of the funds do not really matter to most people (it has a very small effect), what matters is the expense (the fees paid to own the fund). If we just compare the expense ratio of the Vanguard and T. Rowe Price funds we see (as of 27 Feb 2016) Vanguard has an expense ratio of 0.17% for it Index Mutual Fund and 0.05% for its ETF, while T. Rowe Price has an expense ratio of 0.27%. These are just the fees for the funds themselves, there are also account maintenance fees (which normally go down as the amount of money you have invested at a firm go up) and in the case of ETFs execution cost (cost to trade the shares along with the difference between the bid and ask on the shares). If you are just starting out I would say going with the Index Mutual Fund would easier and most likely would cost less over-all if you are buying a small amount of shares every month. When choosing a company look at the expense ratio on the funds and the account maintenance fees (along with the account minimals). Vanguard is well known for having low fees and they in fact were the first to offer Index Mutual Funds. For more info on the S&P 500 index see also this Investopedia entry on the S&P 500 index. Do not worry if this is all a bit confusing it is to most people (myself included) at first.\"", "title": "" }, { "docid": "281841", "text": "\"The amount, reliability and frequency of dividends paid by an ETF other than a stock, such as an index or mutual fund, is a function of the agreement under which the ETF was established by the managing or issuing company (or companies), and the \"\"basket\"\" of investments that a share in the fund represents. Let's say you invest in a DJIA-based index fund, for instance Dow Diamonds (DIA), which is traded on several exchanges including NASDAQ and AMEX. One share of this fund is currently worth $163.45 (Jan 22 2014 14:11 CDT) while the DJIA itself is $16,381.38 as of the same time, so one share of the ETF represents approximately 1% of the index it tracks. The ETF tracks the index by buying and selling shares of the blue chips proportional to total invested value of the fund, to maintain the same weighted percentages of the same stocks that make up the index. McDonald's, for instance, has an applied weight that makes the share price of MCD stock roughly 5% of the total DJIA value, and therefore roughly 5% of the price of 100 shares of DIA. Now, let's say MCD issued a dividend to shareholders of, say, $.20 per share. By buying 100 shares of DIA, you own, through the fund, approximately five MCD shares, and would theoretically be entitled to $1 in dividends. However, keep in mind that you do not own these shares directly, as you would if you spent $16k buying the correct percentage of all the shares directly off the exchange. You instead own shares in the DIA fund, basically giving you an interest in some investment bank that maintains a pool of blue-chips to back the fund shares. Whether the fund pays dividends or not depends on the rules under which that fund was set up. The investment bank may keep all the dividends itself, to cover the expenses inherent in managing the fund (paying fund management personnel and floor traders, covering losses versus the listed price based on bid-ask parity, etc), or it may pay some percentage of total dividends received from stock holdings. However, it will virtually never transparently cut you a check in the amount of your proportional holding of an indexed investment as if you held those stocks directly. In the case of the DIA, the fund pays dividends monthly, at a yield of 2.08%, virtually identical to the actual weighted DJIA yield (2.09%) but lower than the per-share mean yield of the \"\"DJI 30\"\" (2.78%). Differences between index yields and ETF yields can be reflected in the share price of the ETF versus the actual index; 100 shares of DIA would cost $16,345 versus the actual index price of 16,381.38, a delta of $(36.38) or -0.2% from the actual index price. That difference can be attributed to many things, but fundamentally it's because owning the DIA is not the exact same thing as owning the correct proportion of shares making up the DJIA. However, because of what index funds represent, this difference is very small because investors expect to get the price for the ETF that is inherent in the real-time index.\"", "title": "" } ]
8756
What is the principle of forming an arbitrage strategy?
[ { "docid": "553105", "text": "Well, arbitrage is a simple mean reversion strategy which states that any two similar commodity with some price difference (usually not much) will converge. So either you can bet on difference in prices in different exchanges or also you can bet on difference in futures value. For example if current price of stock is 14$ and if futures price is 10$. Then you can buy one futures contract and short one stock at the market price. This would lock in a profit of 4$ per share.", "title": "" }, { "docid": "355236", "text": "\"Arbitrage is basically taking advantage of a difference in price. Generally extending to \"\"in different places for the same thing\"\". A monetary version would be interlisted stocks, that is stocks in companies that are on both the NYSE/Nasdaq and Toronto stock exchanges. If somebody comes along and buys a large number of shares in Toronto, that will tend to make the price go up - standard supply and demand. But if someone else can buy shares instead in NY, and then sell them in Toronto where the first person is buying up shares, where the price is higher, they the the arbitrageur (second person) can make pretty easy money. By its very nature, this tends to bring the prices back in line, as NY will then go up and Toronto will then go down (ignoring FX rates and the like for ease of explanation). The same can work for physical goods, although it does tend to get more complex with taxes, duties, and the like.\"", "title": "" } ]
[ { "docid": "542608", "text": "The main risk I see to this plan is with a late payment to your credit card. For a variety of reasons, some outside your control, you could end up with a late payment on the CC and a +18% interest rate making your arbitrage attempts unprofitable. You sense that this is risky, and it derives from placing short-term risk on a long term asset. Your interest rate is high for the current market. What kind of things can you do reduce that rate? What kind of things can you do to reduce your principle? Those kind of things represent far less risk and accomplish the same goal.", "title": "" }, { "docid": "423513", "text": "If you are looking for a simple formula or buying order / strategy to guarantee a lower buying price, unfortunately this does not exist. Otherwise, all investors would employ this strategy and the financial markets would no longer have an validity (aka arbitrage). Buying any investment contains a certain level of risk (other than US treasuries of course). Having said that, there are many option buying strategies that can employed to help increase your ROR or hedge an existing position. Most of these strategies are based a predicted future direction of a stock on the investor's part. For example, you hold the Ford stock and feel they are releasing their earnings report next week. You feel that they will not meet investors' expectations. You don't want to sell your shares but what you can do is buy put options. If the stock does indeed go down then you make money on your put options. Here is a document on options. It is moderately technical but very good if you want a good introduction on the subject. The strategy that I described above is on pg 33. http://www.m-x.ca/f_publications_en/en.guide.options.pdf", "title": "" }, { "docid": "181924", "text": "Option prices are computed by determining the cost of obtaining the option returns using a strategy that trades the underlying asset continuously. It sounds like what you are describing is rapidly trading the option in order to obtain returns similar to those of the stock. The equality goes both ways. If the option is appropriately priced, then a strategy that replicates stock returns using the option will cost the same as buying the stock. Because you can't trade continuously, you won't actually be able to replicate the stock return, and it may seem like you are making arbitrage profit (puts may seem abnormally expensive), but you do so by bearing tail risk (i.e., selling puts loses more money than owning the associated stock if an unusually bad event occurs).", "title": "" }, { "docid": "124880", "text": "When you look at principles, whether you're a 'true' socialist, a watered-down SocialistLite or somwhere in between, the ideas are still anti-human. We can agree that he state of affairs between the US, in the throes of it's Socialist makeover and the Soviet Union, in the Communist heyday are wildly different in terms of results. To draw a comparison of the results would be a lot like comparing apples and deer, and not achieve very much. Let's look at the principles involved instead. Whether you call it Socialism, Communism, Post-Marxism or any other name, the core principle is the same: Man must look after his neighbour, but cannot be trusted to do so automatically. The state's role is to enforce this duty by using the gun and ensuring wealth is distributed according to doctrine, dogma and/or whim. No matter what that system calls itself or to what extent it actually materialises, the core principle is one of destruction, not creation. The state has no interest or agenda beyond using their gun to take from you in order to give to another. On the contrary, let's look at the principles that a true laissez-faire system would operate on. (I say 'would' because a truly free, laissez-faire system has never existed. The US came excruciatingly close, but ran before it was fully realised.) You have the right to your own life, liberty and pursuit of happiness. These form your individual rights. The role of the state is to use the gun, to ensure your individual rights are upheld. That's it. Notice how redistribution of wealth or any obligation to your brother is not mentioned. If you and your brothers wish to adopt those principles for yourself, please feel free. But the state will not use the gun to enforce your agenda against those who do not voluntarily agree with it.", "title": "" }, { "docid": "571016", "text": "Your strategy of longing company(a) and shorting company(b) is flawed as the prices of company(a) and company(b) can both increase and though you are right , you will lose money due to the shorting strategy. You should not engage in pair trading , which is normally used for arbitrage purposes You should just buy company(a) since you believed its a better company compared to company(b) , its as simple as that", "title": "" }, { "docid": "550992", "text": "\"I can address what it means to \"\"pick off\"\" all those trades... As quantycuenta & littleadv have said, it is absolutely true that professionals \"\"prey\"\" on less-sophisticated market participants. They aren't in the market for charity's sake. If you're not familiar with the definition of the word \"\"arbitrage\"\", look it up. One possible strategy that can be employed with HFT machinery in order to arbitrage successfully in the stock market is to 'intercept' orders that are placed on various exchanges. In order to do this, an HFT organization watches all the transactions at once to find opportunities to buy low and sell high. A good explanation of it is described here in this NY Times article; I'll paraphrase what that article lays out. Stocks are traded through multiple exchanges The first key point to understand is that stocks listed on one exchange (i.e. the NYSE) can be sold on multiple exchanges. That's where the actual \"\"I would like to sell 100 shares of Ford stock\"\" is matched with \"\"I would like to buy 100 shares of Ford stock.\"\" There are multiple clearinghouses on the various exchanges. Your order gets presented to one exchange at a Time An ideal market maker would like to look at the order books for a given stock, say Ford, and see that in exchange A there's a sell order for 100 shares of F at $15.85, and in exchange B there's a buy order for 100 shares of F at $15.90. Arbitrage Market maker buys from A, sells in B, and pockets $0.05 * 100... $5. It's not much, but it was relatively risk free. Also, scale this up to the scale of the US' multiple stock exchanges, and there are lots of opportunities to make $5 every second. Computers are (of course) faster than people To tie it in completely with your question about 'picking off trades', HFT rigs can be set up and programmed to go faster than an average retail investor's order. Let's say you execute the trade to buy 100 shares @ $15.85 as a retail investor. The HFT rigs see your order starting to make the rounds of the different exchanges that your brokerage works through, and go out in front in a matter of milliseconds, finding the orders that are less than $15.85 and less than or equal to 100 shares. They execute a transaction, buy them up, sell to you, and pocket the difference. You have been \"\"picked off\"\". It's admittedly not the only way to use HFT equipment to make money, but it's definitely one way to do it.\"", "title": "" }, { "docid": "572670", "text": "\"Okay - but that's about gold as an investment in today's world, and during an extremely unstable financial situation. Many other types of investments could be used similarly. Those who advocate gold as a hedge don't advocate buying it during a crisis, they advocate keeping some as part of an investment strategy... but again, that's gold as gold, not gold as currency. Leveraging your investments based on current financial situations is what investing is about. Gold as a medium for currency is a totally different thing. What you just described would be called \"\"arbitrage\"\" - in moving markets (or other situations I guess) looking for no-lose situations where you can trade things around and increase your net value doing it. it helps stabilize markets - as people take advantage of this situation it counters the effect and self-corrects... think about it ;)\"", "title": "" }, { "docid": "367391", "text": "\"Strategy would be my top factor. While this may be implied, I do think it helps to have an idea of what is causing the buy and sell signals in speculating as I'd rather follow a strategy than try to figure things out completely from scratch that doesn't quite make sense to me. There are generally a couple of different schools of analysis that may be worth passing along: Fundamental Analysis:Fundamental analysis of a business involves analyzing its financial statements and health, its management and competitive advantages, and its competitors and markets. When applied to futures and forex, it focuses on the overall state of the economy, interest rates, production, earnings, and management. When analyzing a stock, futures contract, or currency using fundamental analysis there are two basic approaches one can use; bottom up analysis and top down analysis. The term is used to distinguish such analysis from other types of investment analysis, such as quantitative analysis and technical analysis. Technical Analysis:In finance, technical analysis is a security analysis methodology for forecasting the direction of prices through the study of past market data, primarily price and volume. Behavioral economics and quantitative analysis use many of the same tools of technical analysis, which, being an aspect of active management, stands in contradiction to much of modern portfolio theory. The efficacy of both technical and fundamental analysis is disputed by the efficient-market hypothesis which states that stock market prices are essentially unpredictable. There are tools like \"\"Stock Screeners\"\" that will let you filter based on various criteria to use each analysis in a mix. There are various strategies one could use. Wikipedia under Stock Speculator lists: \"\"Several different types of stock trading strategies or approaches exist including day trading, trend following, market making, scalping (trading), momentum trading, trading the news, and arbitrage.\"\" Thus, I'd advise research what approach are you wanting to use as the \"\"Make it up as we go along losing real money all the way\"\" wouldn't be my suggested approach. There is something to be said for there being numerous columnists and newsletter peddlers if you want other ideas but I would suggest having a strategy before putting one's toe in the water.\"", "title": "" }, { "docid": "93836", "text": "\"Because ETFs, unlike most other pooled investments, can be easily shorted, it is possible for institutional investors to take an arbitrage position that is long the underlying securities and short the ETF. The result is that in a well functioning market (where ETF prices are what they should be) these institutional investors would earn a risk-free profit equal to the fee amount. How much is this amount, though? ETFs exist in a very competitive market. Not only do they compete with each other, but with index and mutual funds and with the possibility of constructing one's own portfolio of the underlying. ETF investors are very cost-conscious. As a result, ETF fees just barely cover their costs. Typically, ETF providers do not even do their own trading. They issue new shares only in exchange for a bundle of the underlying securities, so they have almost no costs. In order for an institutional investor to make money with the arbitrage you describe, they would need to be able to carry it out for less than the fees earned by the ETF. Unlike the ETF provider, these investors face borrowing and other shorting costs and limitations. As a result it is not profitable for them to attempt this. Note that even if they had no costs, their maximum upside would be a few basis points per year. Lots of low-risk investments do better than that. I'd also like to address your question about what would happen if there was an ETF with exorbitant fees. Two things about your suggested outcome are incorrect. If short sellers bid the price down significantly, then the shares would be cheap relative to their stream of future dividends and investors would again buy them. In a well-functioning market, you can't bid the price of something that clearly is backed by valuable underlying assets down to near zero, as you suggest in your question. Notice that there are limitations to short selling. The more shares are short-sold, the more difficult it is to locate share to borrow for this purpose. At first brokers start charging additional fees. As borrowable shares become harder to find, they require that you obtain a \"\"locate,\"\" which takes time and costs money. Finally they will not allow you to short at all. Unlimited short selling is not possible. If there was an ETF that charged exorbitant fees, it would fail, but not because of short sellers. There is an even easier arbitrage strategy: Investors would buy the shares of the ETF (which would be cheaper than the value of the underlying because of the fees) and trade them back to the ETF provider in exchange for shares of the underlying. This would drain down the underlying asset pool until it was empty. In fact, it is this mechanism (the ability to trade ETF shares for shares of the underlying and vice versa) that keeps ETF prices fair (within a small tolerance) relative to the underlying indices.\"", "title": "" }, { "docid": "594047", "text": "Yes, one such strategy is dividend arbitrage using stock and in the money options. You have to find out which option is the most mispriced before the ex-dividend date.", "title": "" }, { "docid": "534755", "text": "There is a strategy called merger-arbitrage where you buy the stock of the acquired company when it sells for less than the final acquisition price. Usually the price will rise to about the acquisition price fairly rapidly after the merge is announced, so you have to move fast. The danger is that the merger gets called off (regulatory reasons, the acquired company board votes no) and you get left holding shares bought at a price higher than the price after the merger collapses. This is kind of an advanced strategy and a tough one to back test since each M&A deal is unique.", "title": "" }, { "docid": "136520", "text": "you asked for strategies which use deep in the money options: dividend mispricing can use deep in the money options, basically its an arbitrage play on ex-dividend dates. and any kind of spread can use deep in the money options, depending on how wide you want your spread to be", "title": "" }, { "docid": "124038", "text": "Some liquidity Since you're using IB, and you seem to be an investor not a trader, so you won't notice especially if you walk your orders, but you will suffer the bid/ask spread as everyone else albeit wider. If buying, the best strategy unless if one is time constrained is to walk the entire bid from the best bid to the best ask. It is highly likely that someone will hit your order before you hit the best ask. If they don't, as a long term investor, the few pennies won't make or break you, especially if the price per share is 100 USD equivalent, but it is an excellent habit to form and fun. Since you're buying ETFs, even though your orders are small, you would be adding liquidity to your market, helping it become more efficient because your orders could be used to arbitrage against all of the ETF's holdings, in turn providing liquidity for those holdings. No liquidity This could only be done with an extremely low cost broker like IB because the trading commissions would make it prohibitively expensive. There are huge risks when trading an illiquid security such as VEUR. EWL would be much less risky thus less expensive. Securities with no liquidity can be traded, but they must be traded very carefully. In the case of a security that can only attract about 20 shares per day in volume, only single shares should be bid. The market makers, suffering from a dearth in volume may not even be willing to haggle; therefore, the only recourse is a statistical arbitrageur, who will attempt to profit from the spread between other more liquid versions of the security. Considering the available alternative, VEUR is not recommended to trade.", "title": "" }, { "docid": "9906", "text": "\"I'm loving this thread, by the way. The answer to your question is yes: the PDE method and the martingale method lead to the same result. I think this is intuitive, since they address the same things (drift, probability, etc). Heath &amp; Schweizer (2000) have a nice paper in the Journal of Applied Probability that shows the (fairly general) circumstances under which the two methods will always have the same result. It's titled \"\"Martingales versus PDEs in Finance: An Equivalence Result with Examples\"\". My argument is that Black-Scholes is really an equilibrium model, not an arbitrage-free model. Despite that, I'm claiming that it is possible to use BS (and any other equilibrium model) in a no-arbitrage manner by incorporating information from other securities, but that this doesn't make the underlying model and its assumptions a no-arbitrage model. I think, basically, what I'm trying to say is that I don't think market completeness is really the issue, but rather that the issue is the difference between the model and reality. Equilibrium models make a statement about what reality *should* be, given some parameters that you're supposed to know with certainty (all bets are off if you have to estimate them). Arbitrage-free models explicitly use external, observed prices, *but do not explain why we observe those prices*. In this context (and using these definitions), I'd say Black-Scholes is clearly an equilibrium model, albeit one built from some arguments that involve arbitrage.\"", "title": "" }, { "docid": "244442", "text": "\"You make several good points. I'll start with Black-Scholes; the arbitrage argument in Black-Scholes is between the option and a hypothetical and unobserved portfolio with identical cash flows (the replicating portfolio). We then value the replicating portfolio via an equilibrium model. When you use BS, there isn't necessarily *any* observed security whose is guaranteed not imply some arbitrage opportunity, because BS makes no reference to observed prices. A no-arbitrage modification might look like this: \"\"I observe the prices (and implied volatilities) of some options, and use the implied volatilities to price another option (maybe with a different strike). Doing so ensures that there is no arbitrage between my price and the market prices implied by my model.\"\" Realistically, the problem arbitrage-free models are addressing is that our models and assumptions are wrong, even though they're reasonable approximations a lot of the time. A no-arbitrage model removes some set of obvious deficiencies, but at the cost of not being able to explain why things are priced as they are. So, for instance, Vasicek won't reproduce the observed term structure, and Hull-White fixes this, but Hull-White doesn't explain where the term structure comes from (i.e., what the term structure *should* be).\"", "title": "" }, { "docid": "251300", "text": "The answer is to your question is somewhat complicated. You will be unable to compete with the firms traditionally associated with High Frequency Trading in any of their strategies. Most of these strategies which involve marketing making, latency arbitrage, and rebate collection. The amount of engineering required to build the infrastructure required to run this at scale makes it something which can only be undertaken by a team of highly skilled engineers. Indeed, the advantage of firms competing in this space such as TradeBot, TradeWorx, and Getco comes from this infrastructure as most of the strategies that are developed are necessarily simple due to the latency requirements. Now if you expand the definition of HFT to include all computerized automated trading you most certainly can build strategies that are profitable. It is not something that you probably want to tackle on your own but I know of a couple of people that did go it alone successfully for a couple of years before joining an established firm to run a book for them. In order to be successful you will most likely need to develop a unique strategies. The good news is because that you are trying to deploy a very tiny amount of capital you can engage in trades that larger firms would not because the strategies cannot hold enough capital relative to the firms capital base. I am the co-founder of a small trading firm that successfully trades the US Equities and Equity Derivatives markets. A couple of things to note is that if you want to do this you should consider building a real business. Having some more smart brains around you will help. You don't need exchange colocation for all strategies. Many firms, including ours, colocate in a data center that simply has proximity to the exchanges data centers. You will need to keep things simple to be effective. Don't except all the group think that this is impossible. It is possible although as a single individual it will be more difficult. It will require long, long hours as you climb the algorithmic trading learning curve. Good luck.", "title": "" }, { "docid": "294270", "text": "\"I'm not familiar with the Dupire model; I'll have to take a look at (it sounds cool though). I think that all arbitrage-free models are \"\"incomplete\"\" in the sense that they don't say, \"\"This is a price that doesn't imply any arbitrage opportunities *anywhere*,\"\" but instead say, \"\"This is a price that doesn't imply any arbitrage opportunities within a specific set of securities.\"\" What set you're using will vary from one model to another, and I'd say (although other people might reasonably disagree) that taking a volatility structure as given is as much no-arbitrage as taking a term structure as given. As a side note, I'd say that what (theoretically) distinguishes an equilibrium model is that you're supposed to *know* the parameters, not guess at them or observe them from the real world. By that definition, a really complete CAPM or Black-Scholes would explain how to derive the correct beta or volatility from fundamental analysis. Also, I've upvoted you elsewhere for some really good comments you made about intrinsic value.\"", "title": "" }, { "docid": "507117", "text": "with the semi-strong form of the Efficient Market Hypothesis expected dividends are priced into the options and security already. If you are able to locate such an arbitrage opportunity then you should take it, but I suspect it will be more more difficult than you think. Remember that many dividends require you to have been a shareholder by a certain date prior to the dividend occurring.", "title": "" }, { "docid": "284865", "text": "As your question is written now, it looks like you have a typo. Your stated APR is 5.542% = 0.05542, not 0.005542 as you've written. I ran the numbers that you gave (accounting for the typo) through the formula at Wikipedia and got $849.2528 / month, which will round to $849.25 for most payments. That doesn't match the number that you computed or the number on your TIL. (Maybe you also miskeyed the result of your calculation?) I agree that it's unlikely that this is just a calculation error by the mortgage company, although I wouldn't completely rule it out. Are you paying anything else like a property tax escrow? I didn't pull a blank TIL form to see what might go into the monthly payment line that you showed, but in many cases you do pay more than just principle and interest each month. (Not sure if that gets reflected at that point on the form though.)", "title": "" }, { "docid": "306961", "text": "SEC Form 3 and SEC Form 4 are filed when insiders make share/derivatives acquisitions, transfers, sells and buys There is a time limit AFTER the action where they can be filed, such as 12 business days, so this can be a substantial amount of time after the effect on the market, depending on your strategy. You can aggregate these forms from SEC sources or from third party websites and services. In some cases, types of insider trading are permissible at certain intervals, so if you learn about when certain shares become unlocked, you can try to predict what insider actions will be and share price movements around those times.", "title": "" }, { "docid": "513991", "text": "\"Forget the math's specifics for a moment: here's some principles. Additional housing for a renter gives you returns in the form of money. Additional housing for yourself pays its returns in the form of \"\"here is a nice house, live in it\"\". Which do you need more of? If you don't need the money, get a nicer house for yourself. If you need (or want) the money, get a modest house for yourself and either use the other house as a rental property, or invest the proceeds of its sale in the stock market. But under normal circumstances (++) don't expect that buying more house for yourself is a good way to increase how much money you have. It's not. (++ the exception being during situations where land/housing value rises quickly, and when that rise is not part of a housing bubble which later collapses. Generally long-term housing values tend to be relatively stable; the real returns are from the rent, or what economists call imputed rent when you're occupying it yourself.)\"", "title": "" }, { "docid": "49168", "text": "The creation mechanism for ETF's ensures that the value of the underlying stocks do not diverge significantly from the Fund's value. Authorized participants have a strong incentive to arbitrage any pricing differences and create/redeem blocks of stock/etf until the prices are back inline. Contrary to what was stated in a previous answer, this mechanism lowers the cost of management of ETF's when compared to mutual funds that must access the market on a regular basis when any investors enter/exit the fund. The ETF only needs to create/redeem in a wholesale basis, this allows them to operate with management fees that are much lower than those of a mutual fund. Expenses Due to the passive nature of indexed strategies, the internal expenses of most ETFs are considerably lower than those of many mutual funds. Of the more than 900 available ETFs listed on Morningstar in 2010, those with the lowest expense ratios charged about .10%, while those with the highest expenses ran about 1.25%. By comparison, the lowest fund fees range from .01% to more than 10% per year for other funds. (For more on mutual fund feeds, read Stop Paying High Fees.)", "title": "" }, { "docid": "349209", "text": "Technically, yes, you can do this. It's a form of arbitrage: you're taking advantage of a small price difference between two markets. But is it worth the hassle of keeping on top of the overdraft and making sure you don't incur any accidental penalties or fees? Interest rates are super low, and floating £1000 or £2000, you're only going to generate £10-20 per year in a basic savings account.", "title": "" }, { "docid": "174245", "text": "Academic research into ADRs seems to suggest that pairs-trading ADRs and their underlying shares reveals that there certainly are arbitrage opportunities, but that in most (but not all cases) such opportunities are quickly taken care of by the market. (See this article for the mexican case, the introduction has a list of other articles you could read on the subject). In some cases parity doesn't seem to be reached, which may have to do with transaction costs, the risk of transacting in a foreign market, as well as administrative & legal concerns that can affect the direct holder of a foreign share but don't impact the ADR holder (since those risks and costs are borne by the institution, which presumably has a better idea of how to manage such risks and costs). It's also worth pointing out that there are almost always arbitrage opportunities that get snapped up quickly: the law of one price doesn't apply for very short time-frames, just that if you're not an expert in that particular domain of the market, it might as well be a law since you won't see the arbitrage opportunities fast enough. That is to say, there are always opportunities for arbitrage with ADRs but chances are YOU won't be able to take advantage of it (In the Mexican case, the price divergence seems to have an average half-life of ~3 days). Some price divergence might be expected: ADR holders shouldn't be expected to know as much about the foreign market as the typical foreign share holder, and that uncertainty may also cause some divergence. There does seem to be some opportunity for arbitrage doing what you suggest in markets where it is not legally possible to short shares, but that likely is the value added from being able to short a share that belongs to a market where you can't do that.", "title": "" }, { "docid": "316993", "text": "Can't totally agree with that. Volatility trading is just one trading type of many. In my opinion it doesn't depend on whether you are a professional trader or not. As you might have heard, retail traders are said to create 'noise' on the market, mainly due to the fact that they aren't professional in their majority. So, I would assume, if an average retail trader decided to trade volatility he would create as much noise as if would have been betting on stock directions. Basically, most types of trading would require a considerable amount of effort spent on fundamental analysis of the underlying be it volatility or directional trading. Arbitrage trading would be an exception here, I guess. However, volatility trading relies more on trader's subjective expectations about future deviations, whereas trading stock directions requires deeper research of the underlying. Is it a drawback or an advantage? I.d.k. On the other hand-side volatility trading strategies cover both upward and downward movements, but you can set similar hedging strategies when going short or long on stocks, isn't it? To summarise, I think it is a matter of preference. Imagine yourself going long on S&P500 since 2009. Do you think there are many volatility traders who have outperformed that?", "title": "" }, { "docid": "221288", "text": "As the comments say it is still arbitrage. Arbitrage has nothing to do with the speed of execution or the type of order placed, it is commonly associated with automated trading but is not limited to it, which might be where the confusion comes in. The speed of execution is important for arbitrage trading because it lowers Execution risk Here is some reading you might find interesting: They are pretty extensive. Statistical Arbitrage in High Frequency Trading Based on Limit Order Book Dynamics A limit order book model for latency arbitrage. How riskless is “riskless” arbitrage?", "title": "" }, { "docid": "234002", "text": "\"By definition, there are no guaranteed profits. There are sometimes arbitrage opportunities, which are more accessible to some investors than others. In this case, I'm not referring to HFT as that is covered elsewhere on this site already. At certain times, in certain equity markets, candlestick charts were used for profitable trading, though more for trades set up for weeks or months, not day trading. I am referring specifically to Nikkei 225 equities, in the 1980's and 1990's. I don't know why it was effective, and it hasn't worked for me since then. I recommend reading and heeding this answer. Some people DO use technical analysis (see \"\"TA is not...\"\" section) as a primary trading strategy, but they are not going to divulge their methods, not here nor anywhere else.\"", "title": "" }, { "docid": "450716", "text": "\"You're mostly correct, although I think you're missing something essential about no-arbitrage versus an arbitrage argument. Black-Scholes makes an arbitrage argument, which is that the value of an option should be the same as any portfolio that has identical cash flows, and this is generally a sound argument. Notice, however, that BS is ultimately an equilibrium model: it tells you the \"\"correct\"\" price of an option if the assumptions of BS hold, and doesn't necessarily match observed market prices. A no-arbitrage condition or model deliberately incorporates observed prices (or yields, or whatever) into the model, so that there cannot be an arbitrage opportunity implied by the model. This comes up a lot in term structure of interest rate problems, where equilibrium models like Vasicek or Cox-Ingersoll-Ross won't perfectly reproduce the current, observed term structure, and so imply an arbitrage opportunity. No-arbitrage models like Hull-White specifically match the model's term structure to observed yields/prices, so that there is no arbitrage opportunity between the observed term structure and your model of it. It's important to note that this will still allow for arbitrage involving bonds that are *not* part of the observed term structure. As for equivalent martingale measures, you might think about it more generally. The process involves changing the probability distribution from the actual (which is hard to use for pricing) to a different one that's easier to use but will result in the same prices; this is nearly always a risk-neutral probability. You can think of equivalent martingale pricing as asking, \"\"how would this security behave, and be priced, in a world that is completely risk neutral\"\", and then making an argument that the prices are in fact equivalent. EDIT: grammar\"", "title": "" }, { "docid": "519801", "text": "\"Had they made a billion dollars it still wouldn't be arbitrage. The definition of arbitrage is \"\"the simultaneous purchase and sale of similar commodities in different markets to take advantage of price discrepancy\"\". What they did was take advantage of a loophole where they took free money to buy more free money. I believe the American government calls that Quantitative Easing. Bazinga.\"", "title": "" }, { "docid": "487377", "text": "\"Benninga's book(s) are pretty much the best crash course to financial modelling with Excel - be aware though, he has two distinct types of book. One is more of a walk-through of financial principles in Excel('Principles of Finance with Excel, 2nd Ed.'), and the other could better be described as a 'glossary' of financial applications in Excel(the oft-recommended 'Financial Modeling') . As far as I'm aware, both contain roughly the same volume of information about the same topics (could be some minor differences, as the walk-through-style book is newer), but are taught in somewhat different ways. It might be useful to obtain a copy of one or the other from a library and see if you enjoy the style of the book before purchasing it. I was fortunate enough to have a roommate where between us, we have both, but doing this individually is a 200+ dollar endeavor, and you will only be duplicating identical information. ;) If you're interested in reading other interesting material, that may help you develop different perspectives/insight into investing, I would suggest, aside from reading the usual stuff (Intelligent Investor, Random Walk, etc), also obtaining a copy of Seth Klarman's \"\"Margin of Safety\"\". You'll have to do so in .pdf form, as the book is entirely out of print (and from what I've heard, Klarman himself bought out many retailers of all of their copies and had them destroyed), but it's an interesting read, that has a lot of modern relevance - perhaps best evidenced by the fact that it's author, president of one of the largest hedge funds in the world, no longer wants it in print.\"", "title": "" } ]
208006
The action comedy film Baby Driver was written by Edgar Wright and directed by Mike Figgis.
[ { "docid": "Baby_Driver", "text": "Baby Driver is a 2017 British -- American action comedy film written and directed by Edgar Wright , and starring Ansel Elgort , Kevin Spacey , Lily James , Jon Bernthal , Eiza González , Jon Hamm and Jamie Foxx . The film follows a young getaway driver ( played by Elgort ) who is reluctantly coerced to work for a veteran kingpin ( played by Spacey ) at `` one last job '' in exchange to start a better life . The film had its world premiere at South by Southwest on March 11 , 2017 and is scheduled to be released theatrically on June 28 , 2017 , by TriStar Pictures .", "title": "" } ]
[ { "docid": "Nira_Park", "text": "Nira Park is a British television and film producer . Park founded award-winning UK film and television production company Big Talk in 1995 . She is best known for her collaborations with Edgar Wright , Simon Pegg and Nick Frost , having produced both series of the award-winning TV comedy Spaced and their celebrated Three Flavours Cornetto Trilogy . Following the success of Spaced , Park produced cult-comedy Shaun of the Dead , for which she received a Carl Foreman Award nomination at BAFTA . The film was the first instalment of Wright 's iconic Three Flavours Cornetto Trilogy , starring Simon Pegg and Nick Frost . Shaun was followed by 2007 hit Hot Fuzz and 2013 's The World 's End . Nira produced Wright 's Scott Pilgrim vs. The World in 2010 ; in 2011 Joe Cornish 's SXSW audience-award winning debut feature Attack the Block , and that same year Greg Mottola 's Paul , written by Pegg and Frost . In 2012 , she produced Ben Wheatley 's Cannes-premiered black-comedy Sightseers ; in 2013 Jeremy Lovering 's critically acclaimed psychological horror In Fear , which premiered at Sundance ; and in 2014 Cuban Fury , starring Nick Frost , Chris O'Dowd and Rashida Jones . Most recently Nira produced rom-com Man Up , starring Simon Pegg , Lake Bell and directed by Ben Palmer . The movie premiered at Tribeca Film Festival and won ` Best Comedy ' at the 2016 National Film Awards . She also produced Sacha Baron Cohen 's action-comedy Grimsby , which was released February 2016 . She is currently producing Edgar Wright 's latest movie Baby Driver , which is in shooting in Atlanta , GA and is scheduled for a spring 2017 release . For television , she has produced three series of the double BAFTA award-winning sitcom Black Books , Free Agents , and was an executive producer on Friday Night Dinner and the BAFTA award-winning Him and Her . Throughout 2016 and beyond Nira is developing a slate of projects with Joe Cornish and Edgar Wright attached to write and/or direct , as well as film and television projects with emerging and established UK talent .", "title": "" }, { "docid": "Hotel_(2001_film)", "text": "Hotel is a 2001 experimental British-Italian comedy thriller film directed by Mike Figgis .", "title": "" }, { "docid": "Baby_Driver_(disambiguation)", "text": "Baby Driver is a 2017 action-comedy-crime film . Baby Driver may also refer to : Baby Driver , a 1981 novel by Jan Kerouac `` Baby Driver '' , a song by Simon and Garfunkel on their album Bridge Over Troubled Water `` Baby Driver '' , a song by KISS on their album Rock and Roll Over", "title": "" }, { "docid": "Hot_Fuzz", "text": "Hot Fuzz is a 2007 British action comedy film directed by Edgar Wright , written by Wright and Simon Pegg , and starring Pegg and Nick Frost . The three and the film 's producer Nira Park had previously worked together on the television series Spaced and the 2004 film Shaun of the Dead . The film follows two police officers attempting to solve a series of mysterious deaths in an English village . Over a hundred action films were used as inspiration for developing the script . Filming took place over eleven weeks in early 2006 , and featured an extensive cast along with various uncredited cameos . Visual effects were developed by ten artists to expand on or add explosions , gore , and gunfire scenes . Debuting on 14 February 2007 in the United Kingdom and 20 April in the United States , Hot Fuzz received critical and commercial success . Shortly after the film 's release , two different soundtracks were released in the UK and US . The film is the second in Wright and Pegg 's Three Flavours Cornetto trilogy and was preceded by 2004 's Shaun of the Dead and followed by 2013 's The World 's End , each of them featuring a different flavour of Cornetto ice cream . It is also the most financially successful film in the trilogy .", "title": "" }, { "docid": "The_Loss_of_Sexual_Innocence", "text": "The Loss of Sexual Innocence is a 1999 film written and directed by Mike Figgis . It tells the story of the sexual development of a filmmaker through three stages of his life , in a non-linear and disjointed manner . The film stars British actress Saffron Burrows , whom Figgis dated for several years .", "title": "" }, { "docid": "Dead_Right_(film)", "text": "Dead Right is an early short film from Spaced and Shaun of the Dead director Edgar Wright . Filmed in 1992 and 1993 in his hometown of Wells , England when Wright was only 18 . He wrote , edited , produced and directed the film as well as shooting and recording the sound . It is a Zucker Brothers style comedy that parodies the action thriller genre , most notably the Dirty Harry series ( Dead Right was the working title for the original Dirty Harry ) . The film is shot on SVHS and contains an impressive cast of 70 actors ( mostly amateur ) , mainly made up of Wright 's school friends and colleagues . Clips from the film were first broadcast on Take Over TV -- the Channel 4 series consisting entirely of video clips sent in by viewers -- that also launched the careers of comedy duo Adam and Joe .", "title": "" }, { "docid": "Sightseers", "text": "Sightseers is a 2012 British horror comedy directed by Ben Wheatley and written by and starring Alice Lowe and Steve Oram , with additional material written by co-editor Amy Jump . It is produced by Edgar Wright and Nira Park , among others . The film was selected to be screened in the Directors ' Fortnight section at the 2012 Cannes Film Festival .", "title": "" }, { "docid": "Shaun_of_the_Dead", "text": "Shaun of the Dead is a 2004 British horror comedy film directed by Edgar Wright , written by Wright and Simon Pegg , and starring Pegg and Nick Frost . Pegg plays Shaun , a man attempting to get some kind of focus in his life as he deals with his girlfriend , his mother and stepfather . At the same time , he has to cope with an apocalyptic zombie uprising . The film was a critical and commercial success . Shaun of the Dead was also a BAFTA nominee . Pegg and Wright considered a sequel that would replace zombies with another monster , but decided against it as they were pleased with the first film as a stand-alone product , and thought too many characters died to continue the story . The film is the first in Wright and Pegg 's Three Flavours Cornetto trilogy , followed by 2007 's Hot Fuzz and 2013 's The World 's End .", "title": "" }, { "docid": "Liebestraum_(film)", "text": "Liebestraum ( German for `` dream of love '' ) is a 1991 American mystery film written and directed by Mike Figgis and starring Kevin Anderson , Pamela Gidley , Bill Pullman , Zach Grenier , Alicia Witt and Taina Elg , with Kim Novak in her last film role .", "title": "" }, { "docid": "Scott_Pilgrim_vs._the_World", "text": "Scott Pilgrim vs. the World is a 2010 comedy film co-written , produced and directed by Edgar Wright , based on the graphic novel series Scott Pilgrim by Bryan Lee O'Malley . It stars Michael Cera as Scott Pilgrim , a slacker musician who must battle his girlfriend Ramona 's seven evil exes . It was initially planned as a film after the first volume of the comic was released . Wright became attached to the project , and filming began in March 2009 in Toronto . The film premiered after a panel discussion at the San Diego Comic-Con International on July 22 , 2010 . It received a wide release in North America on August 13 , 2010 . The film grossed $ 47.7 million at the box office , against an estimated production budget of $ 85 -- 90 million .", "title": "" }, { "docid": "Figgis", "text": "Figgis is a surname . Notable people with the surname include : Anthony Figgis ( born 1940 ) , British politician Darrell Figgis ( 1882 -- 1925 ) , Irish writer and politician Jason Figgis , film director Jonathan Figgis , film director and producer Mike Figgis ( born 1948 ) , British film director , writer , and composer Neville Figgis ( 1866 -- 1919 ) , British historian , political philosopher and monk T. P. Figgis ( 1858 -- 1948 ) , British architect", "title": "" }, { "docid": "Timecode_(film)", "text": "Timecode is a 2000 American experimental film written and directed by Mike Figgis and featuring a large ensemble cast , including Salma Hayek , Stellan Skarsgård , Jeanne Tripplehorn , Suzy Nakamura , Kyle MacLachlan , Saffron Burrows , Holly Hunter , Julian Sands , Xander Berkeley , Leslie Mann and Mía Maestro . The film is constructed from four continuous 93-minute takes that were filmed simultaneously by four cameramen ; the screen is divided into quarters , and the four shots are shown simultaneously . The film depicts several groups of people in Los Angeles as they interact and conflict while preparing for the shooting of a movie in a production office . The dialogue was largely improvised , and the sound mix of the film is designed so that the most significant of the four sequences on screen dominates the soundtrack at any given moment . An allusion to this film can be heard during another of Mike Figgis 's films , Hotel . In the first moment the screen is split into four quadrants . The sound of milk being steamed in one quadrant combines with the sound of an actor tapping beats onto a paperback novel in another quadrant to create a very subtle imitation of the sounds and music heard during the first few minutes in Timecode .", "title": "" }, { "docid": "One_Night_Stand_(1997_film)", "text": "One Night Stand is a 1997 American drama film by British director Mike Figgis . The film starred Wesley Snipes , Nastassja Kinski , Kyle MacLachlan , Ming-Na and Robert Downey Jr. . The first draft of the screenplay was written by Joe Eszterhas , who had his name removed from the project following Figgis 's rewrite .", "title": "" }, { "docid": "The_Emoji_Movie", "text": "The Emoji Movie is an upcoming 2017 American 3D computer-animated buddy adventure comedy film written and directed by Tony Leondis and co-written by Eric Siegel and Mike White . It will star the voices of T.J. Miller , Anna Faris , James Corden , Patrick Stewart , Maya Rudolph , Steven Wright , Rob Riggle , Jennifer Coolidge , Jake T. Austin , Sofia Vergara , and Christina Aguilera . Produced by Sony Pictures Animation , the film is scheduled to be released on July 28 , 2017 , by Columbia Pictures .", "title": "" }, { "docid": "Run_Baby_Run_(2012_film)", "text": "Run Baby Run ( sometimes presented as Run Babby Run ) is a 2012 Malayalam action comedy thriller film directed by Joshiy , produced by Milan Jaleel and distributed by Galaxy Films . Written by Sachy of the Sachi-Sethu duo , it stars Mohanlal and Amala Paul in the lead roles . The cinematography was done by R. D. Rajasekhar . The film , which was set in the backdrop of news media , has Mohanlal playing the role of a channel cameraman Venu and Amala Paul that of a senior editor Renuka . The story traces their relationship and professional conflicts . It released worldwide on 29 August 2012 . The film was one of the highest grossed Malayalam film of 2012 .", "title": "" }, { "docid": "Joe_Cornish", "text": "Joseph Murray `` Joe '' Cornish ( born 20 December 1968 ) is an English comedian , television and radio presenter , film director , writer and actor , who together with his long-time comedy partner , Adam Buxton , forms the comedy duo Adam and Joe . In 2011 , Cornish released his directorial debut Attack the Block . He has also co-written The Adventures of Tintin : Secret of the Unicorn , with Steven Moffat and Edgar Wright , and Ant-Man , with Wright , Adam McKay and Paul Rudd .", "title": "" }, { "docid": "So_Undercover", "text": "So Undercover is a 2012 American action-comedy film directed by Tom Vaughan and written by Allan Loeb and Steven Pearl . Starring Miley Cyrus , Jeremy Piven , and Mike O'Malley , the film was released for the first time in the United Arab Emirates on December 6 , 2012 and released direct-to-video in the United States on February 5 , 2013 . The film has been released in theatres of only 13 countries worldwide .", "title": "" }, { "docid": "Stop_Look_and_Listen_(film)", "text": "Stop Look and Listen is a color , 10-minute 1967 comedy film written , directed by , and starring Len Janson and Chuck Menville . This movie was nominated for an Oscar in 1968 ( Best Short Subject , Live Action ) . The movie was mostly filmed in Griffith Park in pixilation ( stop-motion photography ) . This movie generates comedy by contrasting the safe and dangerous styles of two drivers who drive in the way made famous by Harold Lloyd : by sitting in the street and seeming to move their bodies as though they were automobiles .", "title": "" }, { "docid": "Three_Flavours_Cornetto_trilogy", "text": "The Three Flavours Cornetto trilogy ( also known as the Cornetto trilogy or the Blood and Ice Cream trilogy ) is a series of British comedic genre films directed by Edgar Wright , written by Wright and Simon Pegg , produced by Nira Park , and starring Pegg and Nick Frost . The trilogy consists of Shaun of the Dead ( 2004 ) , Hot Fuzz ( 2007 ) , and The World 's End ( 2013 ) . The name originates from a `` silly joke '' during the promotion of Hot Fuzz . Wright had written in Cornetto ice cream as a hangover cure for Frost 's character in Shaun of the Dead , based on his own experiences . In Hot Fuzz , Wright included a couple of brief throwaway scenes that referred to the Cornetto joke in Shaun . On the promotional tour of Hot Fuzz during production of The World 's End , one interviewer pointed out the use of Cornetto in the first two films , and Wright jokingly said that they represent a trilogy comparable to Krzysztof Kieślowski 's Three Colours film trilogy . Wright seriously considered the three films as a trilogy , and wrote The World 's End to complete themes set out in the earlier films , adding a Cornetto reference to the film . Each film in the trilogy is connected to a specific Cornetto flavour appearing in each film . Shaun of the Dead features a strawberry-flavoured Cornetto , which signifies the film 's bloody and gory elements , Hot Fuzz includes the blue original Cornetto , to signify the police element to the film , and The World 's End features the green mint chocolate chip flavour ( though only shown by a wrapper caught in the wind ) representing `` little green men '' and science fiction . According to Wright , Wall 's , manufacturer of the Cornetto , were `` very pleased with the namecheck '' . Wright considered each of the films a `` Trojan horse '' , `` genre films that have a relationship comedy smuggled inside a zombie movie , a cop movie and a sci-fi movie '' . Thematically , Wright saw each of the films containing common themes of `` the individuals in a collective -LSB- ... -RSB- about growing up and -LSB- ... -RSB- about the dangers of perpetual adolescence '' . Wright reworked the script of The World 's End to conclude on these themes . The films are further linked by a common set of actors . Wright , Park , Pegg , and Frost collaborated previously in the TV series Spaced from 1999 to 2001 . Martin Freeman , Bill Nighy , Rafe Spall , Julia Deakin , Patricia Franklin , and Garth Jennings appear in each of the films as well as other projects by Wright and Pegg . Clark Collis observes in Entertainment Weekly that the films also feature `` a running gag involving garden fences '' .", "title": "" }, { "docid": "The_Ringer", "text": "The Ringer ( s ) may refer to : The Ringer ( originally titled The Gaunt Stranger ) , a novel by Edgar Wallace , or the 1929 play adapted by Wallace from his novel The Ringer ( 1928 film ) , a British crime film directed by Arthur Maude based on the Edgar Wallace novel The Ringer ( 1931 film ) , a British crime film directed by Walter Forde based on the Edgar Wallace novel The Ringer ( 1938 film ) . a film made by the BBC The Ringer ( 1952 film ) , a British mystery directed by Guy Hamilton , based on Edgar Wallace 's play ( see next ) The Ringer ( 2005 film ) , a 2005 comedy starring Johnny Knoxville The Ringer ( 2013 film ) , a drama written and directed by Chris Shepherd for Canal + and CNC `` The Ringer '' , an episode of the TV series The Legend of Zelda The Ringers , an American rock band The Ringer ( Antarctica ) , a distinctive ring-shaped moraine at the mouth of Ringer Glacier The Ringer ( album ) The Ringer ( website )", "title": "" }, { "docid": "Timecode_(disambiguation)", "text": "Timecode may refer to : Timecode , a sequence of numeric codes generated at regular time intervals . Timecode ( film ) , directed by Mike Figgis . Timecode ( 2016 film ) , 2016 Spanish film", "title": "" }, { "docid": "List_of_Spaced_characters", "text": "Spaced is a British television situation comedy written by and starring Simon Pegg and Jessica Stevenson , and directed by Edgar Wright . Two series of seven episodes were broadcast in 1999 and 2001 on Channel 4 . Listed below are major and minor characters that appear in the two series .", "title": "" }, { "docid": "A_La_Cabaret", "text": "A La Cabaret is a 1916 silent comedy short directed and written by Walter Wright . The film premiered on August 19 , 1916 . This black and white film was directed by Walter Wright , produced by Mack Sennett and the cinematographer was L.B. Jenkins .", "title": "" }, { "docid": "Mike_Figgis", "text": "Michael `` Mike '' Figgis ( born 28 February 1948 ) is an English film director , screenwriter , and composer . He was nominated for two Academy Awards for his work in Leaving Las Vegas ( 1995 ) .", "title": "" }, { "docid": "The_World's_End_(film)", "text": "The World 's End is a 2013 British-American comic science fiction film directed by Edgar Wright , written by Wright and Simon Pegg , and starring Pegg , Nick Frost , Paddy Considine , Martin Freeman , Eddie Marsan and Rosamund Pike . The film follows a group of friends who discover an alien invasion during an epic pub crawl in their home town . Wright has described the film as `` social science fiction '' in the tradition of John Wyndham and Samuel Youd ( John Christopher ) . It is the third and final film in the Three Flavours Cornetto trilogy , following Shaun of the Dead ( 2004 ) and Hot Fuzz ( 2007 ) . The film was produced by Relativity Media , StudioCanal , Big Talk Productions , and Working Title Films .", "title": "" }, { "docid": "High_Heels_and_Low_Lifes", "text": "High Heels and Low Lifes is a 2001 action comedy-drama film starring Minnie Driver , Mary McCormack , Kevin McNally , Mark Williams , Danny Dyer and Michael Gambon . It was directed by Mel Smith and written by Kim Fuller and Georgia Pritchett . The film was remade in Bollywood as Paisa Vasool starring Manisha Koirala and Sushmita Sen.", "title": "" }, { "docid": "The_Browning_Version_(1994_film)", "text": "The Browning Version is a 1994 film directed by Mike Figgis and starring Albert Finney , Greta Scacchi and Matthew Modine . The film is based on the 1948 play by Terence Rattigan , which was previously adapted for film under the same name in 1951 .", "title": "" }, { "docid": "Mr._Jones_(1993_film)", "text": "Mr. Jones is a 1993 American romantic drama film starring Richard Gere , Lena Olin , Anne Bancroft , Tom Irwin and Delroy Lindo , and directed by Mike Figgis .", "title": "" }, { "docid": "Space_Cop", "text": "Space Cop is a 2016 American science fiction action comedy film directed , produced , and edited by Jay Bauman and Mike Stoklasa , and written by Stoklasa . The film stars Rich Evans , Stoklasa , Jocelyn Ridegly , and Bauman , with cameos including Patton Oswalt and others . Produced by RedLetterMedia , the film had been in production for at least seven years dating back to 2008 . The film was released on Blu-ray and digital download on January 12 , 2016 .", "title": "" }, { "docid": "Mrs._Mike_(film)", "text": "Mrs. Mike is a 1949 American drama film directed by Louis King and written by DeWitt Bodeen and Alfred Lewis Levitt . The film stars Dick Powell , Evelyn Keyes , J. M. Kerrigan , Angela Clarke , Will Wright and Nan Boardman . The film was released on December 23 , 1949 , by United Artists .", "title": "" } ]
PLAIN-41
Understanding Lifestyle Medicine From the Heart
[ { "docid": "MED-5327", "text": "OBJECTIVE: To investigate the associations between dietary patterns and mental health in early adolescence. METHOD: The Western Australian Pregnancy Cohort (Raine) Study is a prospective study of 2900 pregnancies recruited from 1989-1992. At 14 years of age (2003-2006; n=1324), the Child Behaviour Checklist (CBCL) was used to assess behaviour (characterising mental health status), with higher scores representing poorer behaviour. Two dietary patterns (Western and Healthy) were identified using factor analysis and food group intakes estimated by a 212-item food frequency questionnaire. Relationships between dietary patterns, food group intakes and behaviour were examined using general linear modelling following adjustment for potential confounding factors at age 14: total energy intake, body mass index, physical activity, screen use, family structure, income and functioning, gender and maternal education at pregnancy. RESULTS: Higher total (b=2.20, 95% CI=1.06, 3.35), internalizing (withdrawn/depressed) (b=1.25, 95% CI=0.15, 2.35) and externalizing (delinquent/aggressive) (b=2.60, 95% CI=1.51, 3.68) CBCL scores were significantly associated with the Western dietary pattern, with increased intakes of takeaway foods, confectionary and red meat. Improved behavioural scores were significantly associated with higher intakes of leafy green vegetables and fresh fruit (components of the Healthy pattern). CONCLUSION: These findings implicate a Western dietary pattern in poorer behavioural outcomes for adolescents. Better behavioural outcomes were associated with a higher intake of fresh fruit and leafy green vegetables.", "title": "The association between dietary patterns and mental health in early adolescence." }, { "docid": "MED-5341", "text": "The present study investigated the effects of a diet and exercise intervention on known breast cancer (BCa) risk factors, including estrogen, obesity, insulin, and insulin-like growth factor-I (IGF-I), in overweight/obese, postmenopausal women. In addition, using the subjects' pre- and postintervention serum in vitro, serum-stimulated growth and apoptosis of three estrogen receptor-positive BCa cell lines were studied. The women where placed on a low-fat (10-15% kcal), high-fiber (30-40 g per 1,000 kcal/day) diet and attended daily exercise classes for 2 wk. Serum estradiol was reduced in the women on hormone treatment (HT; n = 28) as well as those not on HT (n = 10). Serum insulin and IGF-I were significantly reduced in all women, whereas IGF binding protein-1 was increased significantly. In vitro growth of the BCa cell lines was reduced by 6.6% for the MCF-7 cells, 9.9% for the ZR-75-1 cells, and 18.5% for the T-47D cells. Apoptosis was increased by 20% in the ZR-75-1 cells, 23% in the MCF-7 cells, and 30% in the T-47D cells (n = 12). These results show that a very-low-fat, high-fiber diet combined with daily exercise results in major reductions in risk factors for BCa while subjects remained overweight/obese. These in vivo serum changes slowed the growth and induced apoptosis in serum-stimulated BCa cell lines in vitro.", "title": "Effects of a low-fat, high-fiber diet and exercise program on breast cancer risk factors in vivo and tumor cell growth and apoptosis in vitro." }, { "docid": "MED-4616", "text": "In a prospective, randomised, controlled trial to determine whether comprehensive lifestyle changes affect coronary atherosclerosis after 1 year, 28 patients were assigned to an experimental group (low-fat vegetarian diet, stopping smoking, stress management training, and moderate exercise) and 20 to a usual-care control group. 195 coronary artery lesions were analysed by quantitative coronary angiography. The average percentage diameter stenosis regressed from 40.0 (SD 16.9)% to 37.8 (16.5)% in the experimental group yet progressed from 42.7 (15.5)% to 46.1 (18.5)% in the control group. When only lesions greater than 50% stenosed were analysed, the average percentage diameter stenosis regressed from 61.1 (8.8)% to 55.8 (11.0)% in the experimental group and progressed from 61.7 (9.5)% to 64.4 (16.3)% in the control group. Overall, 82% of experimental-group patients had an average change towards regression. Comprehensive lifestyle changes may be able to bring about regression of even severe coronary atherosclerosis after only 1 year, without use of lipid-lowering drugs.", "title": "Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial." }, { "docid": "MED-5339", "text": "Recently, it has been suggested that the Escherichia coli causing urinary tract infection (UTI) may come from meat and animals. The purpose was to investigate if a clonal link existed between E. coli from animals, meat and UTI patients. Twenty-two geographically and temporally matched B2 E. coli from UTI patients, community-dwelling humans, broiler chicken meat, pork, and broiler chicken, previously identified to exhibit eight virulence genotypes by microarray-detection of approximately 300 genes, were investigated for clonal relatedness by PFGE. Nine isolates were selected and tested for in vivo virulence in the mouse model of ascending UTI. UTI and community-dwelling human strains were closely clonally related to meat strains. Several human derived strains were also clonally interrelated. All nine isolates regardless of origin were virulent in the UTI model with positive urine, bladder and kidney cultures. Further, isolates with the same gene profile also yielded similar bacterial counts in urine, bladder and kidneys. This study showed a clonal link between E. coli from meat and humans, providing solid evidence that UTI is zoonosis. The close relationship between community-dwelling human and UTI isolates may indicate a point source spread, e.g. through contaminated meat.", "title": "Is Escherichia coli urinary tract infection a zoonosis? Proof of direct link with production animals and meat." }, { "docid": "MED-4696", "text": "Several epidemiologic studies have shown that chronic inflammation predisposes individuals to various types of cancer. Many cancers arise from sites of infection, chronic irritation, and inflammation. Conversely, an oncogenic change induces an inflammatory microenvironment that promotes the development of tumors. Natural bioactive compounds in dietary plant products including fruits, vegetables, grains, legumes, tea, and wine are claimed to help prevent cancer, degenerative diseases, and chronic and acute inflammation. Modern methods in cell and molecular biology allow us to understand the interactions of different natural bioactive compounds with basic mechanisms of inflammatory response. The molecular pathways of this cancer-related inflammation are now unraveled. Natural bioactive compounds exert anti-inflammatory activity by modulating pro-inflammatory gene expressions have shown promising chemopreventive activity. This review summarizes current knowledge on natural bioactive compounds that act through the signaling pathways and modulate inflammatory gene expressions, thus providing evidence for these substances in cancer chemopreventive action.", "title": "Modulation of inflammatory genes by natural dietary bioactive compounds." }, { "docid": "MED-5335", "text": "Three recent case-control studies conclude that diets high in animal fat or cholesterol are associated with a substantial increase in risk for Parkinson's disease (PD); in contrast, fat of plant origin does not appear to increase risk. Whereas reported age-adjusted prevalence rates of PD tend to be relatively uniform throughout Europe and the Americas, sub-Saharan black Africans, rural Chinese, and Japanese, groups whose diets tend to be vegan or quasi-vegan, appear to enjoy substantially lower rates. Since current PD prevalence in African-Americans is little different from that in whites, environmental factors are likely to be responsible for the low PD risk in black Africans. In aggregate, these findings suggest that vegan diets may be notably protective with respect to PD. However, they offer no insight into whether saturated fat, compounds associated with animal fat, animal protein, or the integrated impact of the components of animal products mediates the risk associated with animal fat consumption. Caloric restriction has recently been shown to protect the central dopaminergic neurons of mice from neurotoxins, at least in part by induction of heat-shock proteins; conceivably, the protection afforded by vegan diets reflects a similar mechanism. The possibility that vegan diets could be therapeutically beneficial in PD, by slowing the loss of surviving dopaminergic neurons, thus retarding progression of the syndrome, may merit examination. Vegan diets could also be helpful to PD patients by promoting vascular health and aiding blood-brain barrier transport of L-dopa. Copyright 2001 Harcourt Publishers Ltd.", "title": "Does a vegan diet reduce risk for Parkinson's disease?" }, { "docid": "MED-5322", "text": "BACKGROUND/AIMS: This study aimed to investigate the quantitative and qualitative changes of bacteria, Bacteroides, Bifidobacterium and Clostridium cluster IV in faecal microbiota associated with a vegetarian diet. METHODS: Bacterial abundances were measured in faecal samples of 15 vegetarians and 14 omnivores using quantitative PCR. Diversity was assessed with PCR-DGGE fingerprinting, principal component analysis (PCA) and Shannon diversity index. RESULTS: Vegetarians had a 12% higher abundance of bacterial DNA than omnivores, a tendency for less Clostridium cluster IV (31.86 +/- 17.00%; 36.64 +/- 14.22%) and higher abundance of Bacteroides (23.93 +/- 10.35%; 21.26 +/- 8.05%), which were not significant due to high interindividual variations. PCA suggested a grouping of bacteria and members of Clostridium cluster IV. Two bands appeared significantly more frequently in omnivores than in vegetarians (p < 0.005 and p < 0.022). One was identified as Faecalibacterium sp. and the other was 97.9% similar to the uncultured gut bacteriumDQ793301. CONCLUSIONS: A vegetarian diet affects the intestinal microbiota, especially by decreasing the amount and changing the diversity of Clostridium cluster IV. It remains to be determined how these shifts might affect the host metabolism and disease risks. Copyright 2009 S. Karger AG, Basel.", "title": "Characterization of bacteria, clostridia and Bacteroides in faeces of vegetarians using qPCR and PCR-DGGE fingerprinting." }, { "docid": "MED-5324", "text": "Obesity has important health consequences, including elevating risk for heart disease, diabetes, and cancer. A high-fat diet is known to contribute to obesity. Little is known regarding the effect of a high-fat diet on pulmonary function, despite the dramatic increase in the prevalence of respiratory ailments (e.g., asthma). The purpose of our study was to determine whether a high-fat meal (HFM) would increase airway inflammation and decrease pulmonary function in healthy subjects. Pulmonary function tests (PFT) (forced expiratory volume in 1-s, forced vital capacity, forced expiratory flow at 25-75% of vital capacity) and exhaled nitric oxide (eNO; airway inflammation) were performed in 20 healthy (10 men, 10 women), inactive subjects (age 21.9 +/- 0.4 years) pre and 2 h post HFM (1 g fat/1 kg body weight; 74.2 +/- 4.1 g fat). Total cholesterol, triglycerides, and C-reactive protein (CRP; systemic inflammation) were determined via a venous blood sample pre and post HFM. Body composition was measured via dual energy X-ray absorptiometry. The HFM significantly increased total cholesterol by 4 +/- 1%, and triglycerides by 93 +/- 3%. ENO also increased (p < 0.05) due to the HFM by 19 +/- 1% (pre 17.2 +/- 1.6; post 20.6 +/- 1.7 ppb). ENO and triglycerides were significantly related at baseline and post-HFM (r = 0.82, 0.72 respectively). Despite the increased eNO, PFT or CRP did not change (p > 0.05) with the HFM. These results demonstrate that a HFM, which leads to significant increases in total cholesterol, and especially triglycerides, increases exhaled NO. This suggests that a high-fat diet may contribute to chronic inflammatory diseases of the airway and lung.", "title": "Effects of a high-fat meal on pulmonary function in healthy subjects." }, { "docid": "MED-5342", "text": "Background The physical health status of vegetarians has been extensively reported, but there is limited research regarding the mental health status of vegetarians, particularly with regard to mood. Vegetarian diets exclude fish, the major dietary source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), critical regulators of brain cell structure and function. Omnivorous diets low in EPA and DHA are linked to impaired mood states in observational and experimental studies. Methods We examined associations between mood state and polyunsaturated fatty acid intake as a result of adherence to a vegetarian or omnivorous diet in a cross-sectional study of 138 healthy Seventh Day Adventist men and women residing in the Southwest. Participants completed a quantitative food frequency questionnaire, Depression Anxiety Stress Scale (DASS), and Profile of Mood States (POMS) questionnaires. Results Vegetarians (VEG:n = 60) reported significantly less negative emotion than omnivores (OMN:n = 78) as measured by both mean total DASS and POMS scores (8.32 ± 0.88 vs 17.51 ± 1.88, p = .000 and 0.10 ± 1.99 vs 15.33 ± 3.10, p = .007, respectively). VEG reported significantly lower mean intakes of EPA (p < .001), DHA (p < .001), as well as the omega-6 fatty acid, arachidonic acid (AA; p < .001), and reported higher mean intakes of shorter-chain α-linolenic acid (p < .001) and linoleic acid (p < .001) than OMN. Mean total DASS and POMS scores were positively related to mean intakes of EPA (p < 0.05), DHA (p < 0.05), and AA (p < 0.05), and inversely related to intakes of ALA (p < 0.05), and LA (p < 0.05), indicating that participants with low intakes of EPA, DHA, and AA and high intakes of ALA and LA had better mood. Conclusions The vegetarian diet profile does not appear to adversely affect mood despite low intake of long-chain omega-3 fatty acids.", "title": "Vegetarian diets are associated with healthy mood states: a cross-sectional study in Seventh Day Adventist adults" }, { "docid": "MED-5337", "text": "PURPOSE: Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS AND METHODS: Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group. RESULTS: None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. CONCLUSIONS: Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.", "title": "Intensive lifestyle changes may affect the progression of prostate cancer." }, { "docid": "MED-5330", "text": "Although there is a well-established relation between serum cholesterol and coronary artery disease risk, individual and national variations in this association suggest that other factors are involved in atherogenesis. High-fat diet associated triglyceride-rich lipoproteins have also been suggested to be atherogenic. To assess the direct effect of postprandial triglyceride-rich lipoproteins on endothelial function, an early factor in atherogenesis--10 healthy, normocholesterolemic volunteers--were studied before and for 6 hours after single isocaloric high- and low-fat meals (900 calorie; 50 and 0 g fat, respectively). Endothelial function, in the form of flow-mediated vasoactivity, was assessed in the brachial artery using 7.5-MHz ultrasound as percent arterial diameter change 1 minute after 5 minutes of upper-arm arterial occlusion. Serum lipoproteins and glucose were determined before eating and 2 and 4 hours postprandially. Serum triglycerides increased from 94 +/- 55 mg/dl preprandially to 147 +/- 80 mg/dl 2 hours after the high-fat meal (p = 0.05). Flow-dependent vasoactivity decreased from 21 +/- 5% preprandially to 11 +/- 4%, 11 +/- 6%, and 10 +/- 3% at 2, 3, and 4 hours after the high-fat meal, respectively (all p <0.05 compared with low-fat meal data). No changes in lipoproteins or flow-mediated vasoactivity were observed after the low-fat meal. Fasting low-density lipoprotein cholesterol correlated inversely (r = -0.47, p = 0.04) with preprandial flow-mediated vasoactivity, but triglyceride level did not. Mean change in postprandial flow-mediated vasoactivity at 2, 3, and 4 hours correlated with change in 2-hour serum triglycerides (r = -0.51, p = 0.02). These results demonstrate that a single high-fat meal transiently impairs endothelial function. These findings identify a potential process by which a high-fat diet may be atherogenic independent of induced changes in cholesterol.", "title": "Effect of a single high-fat meal on endothelial function in healthy subjects." }, { "docid": "MED-5363", "text": "OBJECTIVE: Although several studies have reported associations of depressive state with specific nutrients and foods, few studies examined the association with dietary patterns in adults. We investigated the association between major dietary patterns and depressive symptoms in Japanese. METHODS: Subjects were 521 municipal employees (309 men and 212 women), aged 21-67 years, who participated in a health survey at the time of periodic checkup. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale. Dietary patterns were derived by using principal component analysis of the consumption of 52 food and beverage items, which was assessed by a validated brief diet history questionnaire. Logistic regression analysis was used to estimate odds ratios of depressive symptoms (CES-D >or=16) with adjustment for potential confounding variables. RESULTS: We identified three dietary patterns. A healthy Japanese dietary pattern characterized by high intakes of vegetables, fruit, mushrooms and soy products was associated with fewer depressive symptoms. The multivariate-adjusted odds ratios (95% confidence intervals) of having depressive symptoms for the lowest through highest tertiles of the healthy Japanese dietary pattern score were 1.00 (reference), 0.99 (0.62-1.59) and 0.44 (0.25-0.78), respectively (P for trend=0.006). Other dietary patterns were not appreciably associated with depressive symptoms. CONCLUSIONS: Our findings suggest that a healthy Japanese dietary pattern may be related to decreased prevalence of depressive status.", "title": "Dietary patterns and depressive symptoms among Japanese men and women." }, { "docid": "MED-5325", "text": "Objective Previous work studying vegetarians has often found that they have lower blood pressure (BP). Reasons may include their lower BMI and higher intake levels of fruit and vegetables. Here we seek to extend this evidence in a geographically diverse population containing vegans, lacto-ovo vegetarians and omnivores. Design Data are analysed from a calibration sub-study of the Adventist Health Study-2 (AHS-2) cohort who attended clinics and provided validated FFQ. Criteria were established for vegan, lacto-ovo vegetarian, partial vegetarian and omnivorous dietary patterns. Setting Clinics were conducted at churches across the USA and Canada. Dietary data were gathered by mailed questionnaire. Subjects Five hundred white subjects representing the AHS-2 cohort. Results Covariate-adjusted regression analyses demonstrated that the vegan vegetarians had lower systolic and diastolic BP (mmHg) than omnivorous Adventists (β =−6·8, P<0·05 and β = −6·9, P<0·001). Findings for lacto-ovo vegetarians (β = −9·1, P<0·001 and β = −5·8, P<0·001) were similar. The vegetarians (mainly the vegans) were also less likely to be using antihypertensive medications. Defining hypertension as systolic BP > 139 mmHg or diastolic BP > 89 mmHg or use of antihypertensive medications, the odds ratio of hypertension compared with omnivores was 0·37 (95 % CI 0·19, 0·74), 0·57 (95 % CI 0·36, 0·92) and 0·92 (95 % CI 0·50, 1·70), respectively, for vegans, lacto-ovo vegetarians and partial vegetarians. Effects were reduced after adjustment for BMI. Conclusions We conclude from this relatively large study that vegetarians, especially vegans, with otherwise diverse characteristics but stable diets, do have lower systolic and diastolic BP and less hypertension than omnivores. This is only partly due to their lower body mass.", "title": "Vegetarian diets and blood pressure among white subjects: results from the Adventist Health Study-2 (AHS-2)" }, { "docid": "MED-5328", "text": "Aim To evaluate the relationship of diet to incident diabetes among non-Black and Black participants in the Adventist Health Study-2. Methods and Results Participants were 15,200 men and 26,187 women (17.3% Blacks) across the U.S. and Canada who were free of diabetes and who provided demographic, anthropometric, lifestyle and dietary data. Participants were grouped as vegan, lacto ovo vegetarian, pesco vegetarian, semi-vegetarian or non-vegetarian (reference group). A follow-up questionnaire after two years elicited information on the development of diabetes. Cases of diabetes developed in 0.54% of vegans, 1.08% of lacto ovo vegetarians, 1.29% of pesco vegetarians, 0.92% of semi-vegetarians and 2.12% of non-vegetarians. Blacks had an increased risk compared to non-Blacks (odds ratio [OR] 1.364; 95% confidence interval [CI], 1.093–1.702). In multiple logistic regression analysis controlling for age, gender, education, income, television watching, physical activity, sleep, alcohol use, smoking and BMI, vegans (OR 0.381; 95% CI 0.236–0.617), lacto ovo vegetarians (OR 0.618; 95% CI 0.503–0.760) and semi-vegetarians (OR 0.486, 95% CI 0.312–0.755) had a lower risk of diabetes than non-vegetarians. In non-Blacks vegan, lacto ovo and semi-vegetarian diets were protective against diabetes (OR 0.429, 95% CI 0.249–0.740; OR 0.684, 95% CI 0.542–0.862; OR 0.501, 95% CI 0.303–0.827); among Blacks vegan and lacto ovo vegetarian diets were protective (OR 0.304, 95% CI 0.110–0.842; OR 0.472, 95% CI 0.270–0.825). These associations were strengthened when BMI was removed from the analyses. Conclusion Vegetarian diets (vegan, lacto ovo, semi-) were associated with a substantial and independent reduction in diabetes incidence. In Blacks the dimension of the protection associated with vegetarian diets was as great as the excess risk associated with Black ethnicity.", "title": "Vegetarian diets and incidence of diabetes in the Adventist Health Study-2" }, { "docid": "MED-5323", "text": "This study reviewed the literature on the relations between exposure to chemicals with endocrine-disrupting abilities and obesity in humans. The studies generally indicated that exposure to some of the endocrine-disrupting chemicals was associated with an increase in body size in humans. The results depended on the type of chemical, exposure level, timing of exposure and gender. Nearly all the studies investigating dichlorodiphenyldichloroethylene (DDE) found that exposure was associated with an increase in body size, whereas the results of the studies investigating polychlorinated biphenyl (PCB) exposure were depending on dose, timing and gender. Hexachlorobenzene, polybrominated biphenyls, beta-hexachlorocyclohexane, oxychlordane and phthalates were likewise generally associated with an increase in body size. Studies investigating polychlorinated dibenzodioxins and polychlorinated dibenzofurans found either associations with weight gain or an increase in waist circumference, or no association. The one study investigating relations with bisphenol A found no association. Studies investigating prenatal exposure indicated that exposure in utero may cause permanent physiological changes predisposing to later weight gain. The study findings suggest that some endocrine disruptors may play a role for the development of the obesity epidemic, in addition to the more commonly perceived putative contributors. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.", "title": "Endocrine-disrupting chemicals and obesity development in humans: a review." }, { "docid": "MED-5331", "text": "A global health transition is currently underway. The burden of non-communicable diseases (NCDs) is increasing rapidly in the developing world, very much as a result of changes in lifestyles. In addition to changes in tobacco use and physical activity, major changes are taking place in diets, contributing greatly to the growing epidemic of NCD. Thus, a huge global public health challenge is how to influence the trends in diet and nutrition for effective global NCD prevention. The health transition took place rapidly in Finland after World War II and mortality from cardiovascular disease (CVD) was exceptionally high. The North Karelia Project was launched in 1972 as a community-based, and later as a national, programme to influence diet and other lifestyles that are crucial in the prevention of CVD. The intervention had a strong theory base and it employed comprehensive strategies. Broad community organisation and the strong participation of people were the key elements. Evaluation has shown how the diet (particularly fat consumption) has changed and how these changes have led to a major reduction in population serum cholesterol and blood pressure levels. It has also shown how ischaemic heart disease mortality in a working-age population has declined by 73% in North Karelia and by 65% in the whole country from 1971 to 1995. Although Finland is an industrialised country, North Karelia was rural, of rather low socio-economic level and with many social problems in the 1970s and 1980s. The project was based on low-cost intervention activities, where people's participation and community organisations played a key role. Comprehensive interventions in the community were eventually supported by national activities--from expert guidelines and media activities to industry collaboration and policy. Similar principles for nutrition intervention programmes could be used in developing countries, obviously tailored to the local conditions. This paper discusses the experiences of the North Karelia Project in the light of needs from the less-industrialised countries and makes some general recommendations.", "title": "Influencing public nutrition for non-communicable disease prevention: from community intervention to national programme--experiences from Finland." }, { "docid": "MED-5340", "text": "In Asia, vegetarianism is a well-established eating behavior. It appears that the adoption of a vegan diet leads to a lessening of several health risk factors. Although vegetarianism has some notable effects on the hematological system, the effect on the nephrological system has not been well clarified. The pattern of renal function parameters was studied in 25 Thai vegans compared with 25 non-vegetarians. Of the studied parameters, it was found that urine protein was significantly different (p < 0.05) in vegans and controls. Vegans had significantly lower urine protein level.", "title": "Renal function parameters of Thai vegans compared with non-vegans." }, { "docid": "MED-5333", "text": "BACKGROUND/AIM: A vegetarian diet is known to prevent a series of diseases but may influence the balance of carbohydrate and fat metabolism as well as collagen synthesis. This study compares expression patterns of relevant genes in oral mucosa of omnivores and vegetarians. METHODS: Quantitative reverse transcriptase polymerase chain reaction was applied for analysis of mRNA levels from carnitine transporter OCTN2, hepatic CPT1A and nonhepatic CPT1B isoforms of carnitine palmitoyltransferase and collagen (CCOL2A1) in oral mucosa. RESULTS: Compared with volunteers with traditional eating habits, carbohydrate consumption was significantly higher (+22%) in vegetarians. This was associated with a significant stimulation of CPT1A (+50%) and OCTN2 (+10%) and a lowered collagen synthesis (-10%). CONCLUSION: These novel findings provide further insight into the association of a changed fat metabolism and reduced collagen synthesis in vegetarians, which could also play a role in the aging process. Copyright 2008 S. Karger AG, Basel.", "title": "Vegetarian diet affects genes of oxidative metabolism and collagen synthesis." }, { "docid": "MED-4617", "text": "The need for consistent and current data describing the true incidence of SCA and/or SCD was highlighted during the most recent Sudden Cardiac Arrest Thought Leadership Alliance’s (SCATLA) Think Tank meeting of national experts with broad representation of key stakeholders including thought leaders and representatives from the American College of Cardiology, American Heart Association, and the Heart Rhythm Society. As such, to evaluate the true magnitude of this public health problem, we performed a systematic literature search in MEDLINE using the MeSH headings, “death, sudden” OR the terms “sudden cardiac death” OR “sudden cardiac arrest” OR “cardiac arrest” OR “cardiac death” OR “sudden death” OR “arrhythmic death.” Study selection criteria included peer-reviewed publications of primary data used to estimate SCD incidence in the U.S. We used Web of Science®’s Cited Reference Search to evaluate the impact of each primary estimate on the medical literature by determining the number of times each “primary source” has been cited. The estimated U.S. annual incidence of SCD varied widely from 180,000 to > 450,000 among 6 included studies. These different estimates were in part due to different data sources (with data age ranging from 1980 to 2007), definitions of SCD, case ascertainment criteria, methods of estimation/extrapolation, and sources of case ascertainment. The true incidence of SCA and/or SCD in the U.S. remains unclear with a wide range in the available estimates, which are badly dated. As reliable estimates of SCD incidence are important for improving risk stratification and prevention, future efforts are clearly needed to establish uniform definitions of SCA and SCD and then to prospectively and precisely capture cases of SCA and SCD in the overall U.S. population.", "title": "Systematic Review of the Incidence of Sudden Cardiac Death in the United States" }, { "docid": "MED-5332", "text": "The gastrointestinal microbiota produces short-chain fatty acids, especially butyrate, which affect colonic health, immune function and epigenetic regulation. To assess the effects of nutrition and aging on the production of butyrate, the butyryl-CoA:acetate CoA-transferase gene and population shifts of Clostridium clusters lV and XlVa, the main butyrate producers, were analysed. Faecal samples of young healthy omnivores (24 ± 2.5 years), vegetarians (26 ± 5 years) and elderly (86 ± 8 years) omnivores were evaluated. Diet and lifestyle were assessed in questionnaire-based interviews. The elderly had significantly fewer copies of the butyryl-CoA:acetate CoA-transferase gene than young omnivores (P=0.014), while vegetarians showed the highest number of copies (P=0.048). The thermal denaturation of the butyryl-CoA:acetate CoA-transferase gene variant melting curve related to Roseburia/Eubacterium rectale spp. was significantly more variable in the vegetarians than in the elderly. The Clostridium cluster XIVa was more abundant in vegetarians (P=0.049) and in omnivores (P<0.01) than in the elderly group. Gastrointestinal microbiota of the elderly is characterized by decreased butyrate production capacity, reflecting increased risk of degenerative diseases. These results suggest that the butyryl-CoA:acetate CoA-transferase gene is a valuable marker for gastrointestinal microbiota function. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.", "title": "Quantification of butyryl CoA:acetate CoA-transferase genes reveals different butyrate production capacity in individuals according to diet and age." }, { "docid": "MED-5334", "text": "Until recently, intact protein that is rich in tryptophan was not seen as an alternative to pharmaceutical-grade tryptophan because protein also contains large neutral amino acids (LNAAs) that compete for transport sites across the blood-brain barrier. Recent evidence indicates that when deoiled gourd seed (a rich source of tryptophan with approximately 22 mg/g protein) is combined with glucose (a carbohydrate that reduces serum levels of competing LNAAs) a clinical effect similar to that of pharmaceutical-grade tryptophan is achieved. Objective and subjective measures of anxiety in those suffering from social phobia (also known as social anxiety disorder) were employed to measure changes in anxiety in response to a stimulus as part of a double-blind, placebo-controlled, crossover study with a wash-out period of 1 week between study sessions. Subjects were randomly assigned to start with either (i) protein-source tryptophan (deoiled gourd seed) in combination with carbohydrate or (ii) carbohydrate alone. One week after the initial session, subjects returned for a follow-up session and received the opposite treatment of that received at the first session. All 7 subjects who began the study completed the 2-week protocol. Protein-source tryptophan with carbohydrate, but not carbohydrate alone, resulted in significant improvement on an objective measure of anxiety. Protein-source tryptophan combined with a high glycemic carbohydrate is a potential anxiolytic to those suffering from social phobia.", "title": "Protein-source tryptophan as an efficacious treatment for social anxiety disorder: a pilot study." }, { "docid": "MED-2763", "text": "Despite compelling statistics that show we could eliminate 80%of all heart disease and strokes, 90% of all diabetes, and 60% of all cancers with basic lifestyle changes, we have failed to motivate the public to make these changes and failed to motivate policy makers to make healthy choices the easiest choice. Dr. Katz suggests we have failed because we have focused too much on statistics and too little on passion. He implores all of us to tap into people's passion by connecting each of these statistics with a human story.", "title": "Facing the facelessness of public health: what's the public got to do with it?" }, { "docid": "MED-5326", "text": "The effect of meat consumption on cancer risk is a controversial issue. However, recent meta-analyses show that high consumers of cured meats and red meat are at increased risk of colorectal cancer. This increase is significant but modest (20-30%). Current WCRF-AICR recommendations are to eat no more than 500 g per week of red meat, and to avoid processed meat. Moreover, our studies show that beef meat and cured pork meat promote colon carcinogenesis in rats. The major promoter in meat is heme iron, via N-nitrosation or fat peroxidation. Dietary additives can suppress the toxic effects of heme iron. For instance, promotion of colon carcinogenesis in rats by cooked, nitrite-treated and oxidized high-heme cured meat was suppressed by dietary calcium and by α-tocopherol, and a study in volunteers supported these protective effects in humans. These additives, and others still under study, could provide an acceptable way to prevent colorectal cancer. Copyright © 2011 Elsevier B.V. All rights reserved.", "title": "Red meat and colon cancer: should we become vegetarians, or can we make meat safer?" }, { "docid": "MED-5338", "text": "Summary Background and objectives Patients with advanced chronic kidney disease (CKD) are in positive phosphorus balance, but phosphorus levels are maintained in the normal range through phosphaturia induced by increases in fibroblast growth factor-23 (FGF23) and parathyroid hormone (PTH). This provides the rationale for recommendations to restrict dietary phosphate intake to 800 mg/d. However, the protein source of the phosphate may also be important. Design, setting, participants, & measurements We conducted a crossover trial in nine patients with a mean estimated GFR of 32 ml/min to directly compare vegetarian and meat diets with equivalent nutrients prepared by clinical research staff. During the last 24 hours of each 7-day diet period, subjects were hospitalized in a research center and urine and blood were frequently monitored. Results The results indicated that 1 week of a vegetarian diet led to lower serum phosphorus levels and decreased FGF23 levels. The inpatient stay demonstrated similar diurnal variation for blood phosphorus, calcium, PTH, and urine fractional excretion of phosphorus but significant differences between the vegetarian and meat diets. Finally, the 24-hour fractional excretion of phosphorus was highly correlated to a 2-hour fasting urine collection for the vegetarian diet but not the meat diet. Conclusions In summary, this study demonstrates that the source of protein has a significant effect on phosphorus homeostasis in patients with CKD. Therefore, dietary counseling of patients with CKD must include information on not only the amount of phosphate but also the source of protein from which the phosphate derives.", "title": "Original Articles: Vegetarian Compared with Meat Dietary Protein Source and Phosphorus Homeostasis in Chronic Kidney Disease" }, { "docid": "MED-5329", "text": "OBJECTIVE: This study was conducted to demonstrate the effectiveness of a strictly vegetarian, very low-fat diet on cardiac risk factor modification. METHODS: Five hundred men and women, participants in an intensive 12-day live-in program, were studied. The program focused on dietary modification, moderate exercise, and stress management at a hospital-based health-center. RESULTS: During this short time period, cardiac risk factors improved: there was an average reduction of total serum cholesterol of 11% (p < 0.001), of blood pressure of 6% (p < 0.001) and a weight loss of 2.5 kg for men and 1 kg for women. Serum triglycerides did not increase except for two subgroups: females age > or = 65 years with serum cholesterol < 6.5 mmol/L and for females 50 to 64 years with baseline serum cholesterol between 5.2-6.5 mmol/L. High-density lipoprotein cholesterol measured on 66 subjects decreased by 19%. CONCLUSION: A strict, very low-fat vegetarian diet free from all animal products combined with lifestyle changes that include exercise and weight loss is an effective way to lower serum cholesterol and blood pressure.", "title": "Rapid reduction of serum cholesterol and blood pressure by a twelve-day, very low fat, strictly vegetarian diet." } ]
[ { "docid": "MED-2924", "text": "Recent advances have been made in our scientific understanding of how berries promote human health and prevent chronic illnesses such as some cancers, heart disease, and neurodegenerative diseases. Cancer is rapidly overtaking heart disease as the number one killer disease in developed countries, and this phenomenon is coupled with a growing aging population and concomitant age-related diseases. Therefore, it is not surprising that consumers are turning toward foods with medicinal properties as promising dietary interventions for disease prevention and health maintenance. Among fruits, berries of all colors have emerged as champions with substantial research data supporting their abilities to positively affect multiple disease states. Apart from several essential dietary components found in berries, such as vitamins, minerals, and fiber, berries also contain numerous bioactives that provide health benefits that extend beyond basic nutrition. Berry bioactives encompass a wide diversity of phytochemicals (phytonutrients) ranging from fat-soluble/lipophilic to water-soluble/hydrophilic compounds. Recent research from laboratories across the globe has provided useful insights into the biological effects and underlying mechanisms of actions resulting from eating berries. The cluster of papers included here represents a cross section of topics discussed at the 2009 International Berry Health Benefits Symposium. Together, these papers provide valuable insight into recent research trends and advances made into evaluating the various health benefits that may result from the consumption of berries and their derived products.", "title": "Recent trends and advances in berry health benefits research." }, { "docid": "MED-1999", "text": "Diabetes is a major and growing public health challenge which threatens to overwhelm medical services in the future. Type 2 diabetes confers significant morbidity and mortality, most notably with target organ damage to the eyes, kidneys, nerves and heart. The magnitude of cardiovascular risk associated with diabetes is best illustrated by its position as a coronary heart disease risk equivalent. Complications related to neuropathy are also vast, often working in concert with vascular abnormalities and resulting in serious clinical consequences such as foot ulceration. Increased understanding of the natural history of this disorder has generated the potential to intervene and halt pathological progression before overt disease ensues, after which point management becomes increasingly challenging. The concept of prediabetes as a formal diagnosis has begun to be translated from the research setting to clinical practice, but with continually updated guidelines, varied nomenclature, emerging pharmacotherapies and an ever-changing evidence base, clinicians may be left uncertain of best practice in identifying and managing patients at the prediabetic stage. This review aims to summarize the epidemiological data, new concepts in disease pathogenesis and guideline recommendations in addition to lifestyle, pharmacological and surgical therapies targeted at stopping progression of prediabetes to diabetes. While antidiabetic medications, with newer anti-obesity medications and interventional bariatric procedures have shown some promising benefits, diet and therapeutic lifestyle change remains the mainstay of management to improve the metabolic profile of individuals with glucose dysregulation. New risk stratification tools to identify at-risk individuals, coupled with unselected population level intervention hold promise in future practice.", "title": "Strategies for preventing type 2 diabetes: an update for clinicians" }, { "docid": "MED-4243", "text": "CONTEXT: The Lifestyle Heart Trial demonstrated that intensive lifestyle changes may lead to regression of coronary atherosclerosis after 1 year. OBJECTIVES: To determine the feasibility of patients to sustain intensive lifestyle changes for a total of 5 years and the effects of these lifestyle changes (without lipid-lowering drugs) on coronary heart disease. DESIGN: Randomized controlled trial conducted from 1986 to 1992 using a randomized invitational design. PATIENTS: Forty-eight patients with moderate to severe coronary heart disease were randomized to an intensive lifestyle change group or to a usual-care control group, and 35 completed the 5-year follow-up quantitative coronary arteriography. SETTING: Two tertiary care university medical centers. INTERVENTION: Intensive lifestyle changes (10% fat whole foods vegetarian diet, aerobic exercise, stress management training, smoking cessation, group psychosocial support) for 5 years. MAIN OUTCOME MEASURES: Adherence to intensive lifestyle changes, changes in coronary artery percent diameter stenosis, and cardiac events. RESULTS: Experimental group patients (20 [71%] of 28 patients completed 5-year follow-up) made and maintained comprehensive lifestyle changes for 5 years, whereas control group patients (15 [75%] of 20 patients completed 5-year follow-up) made more moderate changes. In the experimental group, the average percent diameter stenosis at baseline decreased 1.75 absolute percentage points after 1 year (a 4.5% relative improvement) and by 3.1 absolute percentage points after 5 years (a 7.9% relative improvement). In contrast, the average percent diameter stenosis in the control group increased by 2.3 percentage points after 1 year (a 5.4% relative worsening) and by 11.8 percentage points after 5 years (a 27.7% relative worsening) (P=.001 between groups. Twenty-five cardiac events occurred in 28 experimental group patients vs 45 events in 20 control group patients during the 5-year follow-up (risk ratio for any event for the control group, 2.47 [95% confidence interval, 1.48-4.20]). CONCLUSIONS: More regression of coronary atherosclerosis occurred after 5 years than after 1 year in the experimental group. In contrast, in the control group, coronary atherosclerosis continued to progress and more than twice as many cardiac events occurred.", "title": "Intensive lifestyle changes for reversal of coronary heart disease." }, { "docid": "MED-3113", "text": "Chronic diseases with a lifestyle-based aetiology currently make up a significant proportion of primary care consultations, but management often falls between the demands of public and clinical health. A modified clinical approach, based around the concept of \"lifestyle medicine\", helps fill the gap by adding behavioural, motivational and environmental skills to conventional medical practice. When used in a multidisciplinary setting, lifestyle medicine offers potential cost and effectiveness benefits, which are beginning to be realised.", "title": "The emergence of \"lifestyle medicine\" as a structured approach for management of chronic disease." }, { "docid": "MED-4247", "text": "In a prospective, randomised, controlled trial to determine whether comprehensive lifestyle changes affect coronary atherosclerosis after 1 year, 28 patients were assigned to an experimental group (low-fat vegetarian diet, stopping smoking, stress management training, and moderate exercise) and 20 to a usual-care control group. 195 coronary artery lesions were analysed by quantitative coronary angiography. The average percentage diameter stenosis regressed from 40.0 (SD 16.9)% to 37.8 (16.5)% in the experimental group yet progressed from 42.7 (15.5)% to 46.1 (18.5)% in the control group. When only lesions greater than 50% stenosed were analysed, the average percentage diameter stenosis regressed from 61.1 (8.8)% to 55.8 (11.0)% in the experimental group and progressed from 61.7 (9.5)% to 64.4 (16.3)% in the control group. Overall, 82% of experimental-group patients had an average change towards regression. Comprehensive lifestyle changes may be able to bring about regression of even severe coronary atherosclerosis after only 1 year, without use of lipid-lowering drugs.", "title": "Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial." }, { "docid": "MED-3001", "text": "Over the last three decades, the concept of Western disease has become well established. Medicine has approached this group of diseases by searching for new cures but has achieved relatively little success. We argue that medicine should now accept the failure of this strategy and place a major emphasis on prevention. The key objective is to change the climate of opinion so that prevention is taken seriously by the general population. The chief activity should be a wide ranging public education campaign so as to persuade people to live a healthier lifestyle. Medicine will require restructuring in order to carry out this work. Medical education needs to be reformed so that medical students receive the necessary training. This must be done as part of an integrated approach in which government, industry and medical research all play a major role. Governments should use taxation and subsidies in areas such as food and tobacco so as to shift consumption patterns towards healthier products. Governments must also tighten laws on tobacco sales and advertising, support health education, and improve food labelling. Industry must be made far more responsive to the health needs of the population. This should be done both by public education, so as to alter demand, and by government action. Medical research should change its emphasis from studying the detailed mechanisms of disease (\"complex research\") to studying the role of lifestyle factors (\"simple research\").", "title": "Towards a new system of health: the challenge of Western disease." }, { "docid": "MED-2572", "text": "In traditional cultures, balancing health with a balanced lifestyle was a core belief. The diseases of modern civilization were rare. Indigenous people have patterns of illness very different from Western civilization; yet, they rapidly develop diseases once exposed to Western foods and lifestyles. Food and medicine were interwoven. All cultures used special or functional foods to prevent disease. Food could be used at different times either as food or medicine. Foods, cultivation, and cooking methods maximized community health and well-being. With methods passed down through generations, cooking processes were utilized that enhanced mineral and nutrient bioavailability. This article focuses on what researchers observed about the food traditions of indigenous people, their disease patterns, the use of specific foods, and the environmental factors that affect people who still eat traditional foods.", "title": "Traditional non-Western diets." }, { "docid": "MED-3704", "text": "The most relevant cause of morbidity and mortality in cystic fibrosis (CF) patients is the lung pathology characterized by chronic infection and inflammation sustained mainly by Pseudomonas aeruginosa (P. aeruginosa). Innovative pharmacological approaches to control the excessive inflammatory process in the lung of CF patients are thought to be beneficial to reduce the extensive airway tissue damage. Medicinal plants from the so-called traditional Asian medicine are attracting a growing interest because of their potential efficacy and safety. Due to the presence of different active compounds in each plant extract, understanding the effect of each component is important to pursue selective and reproducible applications. Extracts from Emblica officinalis (EO) were tested in IB3-1 CF bronchial epithelial cells exposed to the P. aeruginosa laboratory strain PAO1. EO strongly inhibited the PAO1-dependent expression of the neutrophil chemokines IL-8, GRO-alpha, GRO-gamma, of the adhesion molecule ICAM-1 and of the pro-inflammatory cytokine IL-6. Pyrogallol, one of the compounds extracted from EO, inhibited the P. aeruginosa-dependent expression of these pro-inflammatory genes similarly to the whole EO extract, whereas a second compound purified from EO, namely 5-hydroxy-isoquinoline, had no effect. These results identify Pyrogallol as an active compound responsible for the anti-inflammatory effect of EO and suggest to extend the investigation in pre-clinical studies in airway animal models in vivo, to test the efficacy and safety of this molecule in CF chronic lung inflammatory disease.", "title": "Pyrogallol, an active compound from the medicinal plant Emblica officinalis, regulates expression of pro-inflammatory genes in bronchial epithelial..." }, { "docid": "MED-4888", "text": "Epidemiological and prospective studies indicate that comprehensive lifestyle changes may modify the progression of prostate cancer. However, the molecular mechanisms by which improvements in diet and lifestyle might affect the prostate microenvironment are poorly understood. We conducted a pilot study to examine changes in prostate gene expression in a unique population of men with low-risk prostate cancer who declined immediate surgery, hormonal therapy, or radiation and participated in an intensive nutrition and lifestyle intervention while undergoing careful surveillance for tumor progression. Consistent with previous studies, significant improvements in weight, abdominal obesity, blood pressure, and lipid profile were observed (all P < 0.05), and surveillance of low-risk patients was safe. Gene expression profiles were obtained from 30 participants, pairing RNA samples from control prostate needle biopsy taken before intervention to RNA from the same patient's 3-month postintervention biopsy. Quantitative real-time PCR was used to validate array observations for selected transcripts. Two-class paired analysis of global gene expression using significance analysis of microarrays detected 48 up-regulated and 453 down-regulated transcripts after the intervention. Pathway analysis identified significant modulation of biological processes that have critical roles in tumorigenesis, including protein metabolism and modification, intracellular protein traffic, and protein phosphorylation (all P < 0.05). Intensive nutrition and lifestyle changes may modulate gene expression in the prostate. Understanding the prostate molecular response to comprehensive lifestyle changes may strengthen efforts to develop effective prevention and treatment. Larger clinical trials are warranted to confirm the results of this pilot study.", "title": "Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention" }, { "docid": "MED-1679", "text": "BACKGROUND: Healthy lifestyle choices such as eating a prudent diet, exercising regularly, managing weight, and not smoking may substantially reduce coronary heart disease (CHD) risk by improving lipids, blood pressure, and other risk factors. The burden of CHD that could be avoided through adherence to these modifiable lifestyle factors has not been assessed among middle-aged and older US men, specifically men taking medications for hypertension or hypercholesterolemia. METHODS AND RESULTS: We prospectively monitored 42 847 men in the Health Professionals Follow-up Study, 40 to 75 years of age and free of disease in 1986. Lifestyle factors were updated through self-reported questionnaires. Low risk was defined as (1) absence of smoking, (2) body mass index <25 kg/m2, (3) moderate-to-vigorous activity > or = 30 min/d, (4) moderate alcohol consumption (5 to 30 g/d), and (5) the top 40% of the distribution for a healthy diet score. Over 16 years, we documented 2183 incident cases of CHD (nonfatal myocardial infarction and fatal CHD). In multivariate-adjusted Cox proportional hazards models, men who were at low risk for 5 lifestyle factors had a lower risk of CHD (relative risk: 0.13; 95% confidence interval [CI]: 0.09, 0.19) compared with men who were at low risk for no lifestyle factors. Sixty-two percent (95% CI: 49%, 74%) of coronary events in this cohort may have been prevented with better adherence to these 5 healthy lifestyle practices. Among men taking medication for hypertension or hypercholesterolemia, 57% (95% CI: 32%, 79%) of all coronary events may have been prevented with a low-risk lifestyle. Compared with men who did not make lifestyle changes during follow-up, those who adopted > or = 2 additional low-risk lifestyle factors had a 27% (95% CI: 7%, 43%) lower risk of CHD. CONCLUSIONS: A majority of CHD events among US men may be preventable through adherence to healthy lifestyle practices, even among those taking medications for hypertension or hypercholesterolemia.", "title": "Healthy lifestyle factors in the primary prevention of coronary heart disease among men: benefits among users and nonusers of lipid-lowering and an..." }, { "docid": "MED-4452", "text": "Background: Evidence for the role of diet and physical activity in cancer incidence is well documented, but owing to increased cancer survivorship, an understanding of these lifestyle factors after a cancer diagnosis is of crucial importance. The purpose of this review was to update the literature in a review undertaken for the National Cancer Survivorship Initiative and to include observational studies that were not included in the WCRF survivorship systematic review. Methods: Evidence was initially gathered from pre-defined searches of the Cochrane Library Database and PubMed from March 2006 to February 2010. After a comprehensive review regarding lifestyle and cancer, for the purpose of this article, any studies not related to diet and physical activity, prognostic outcomes, and breast, colorectal or prostate cancers were excluded. Another search of 2011 literature was conducted to update the evidence. Results: A total of 43 records were included in this review. Evidence from observational studies suggests that a low-fat, high-fibre diet might be protective against cancer recurrence and progression. However, there is a paucity of RCTs substantiating this. There is more support for physical activity, with a dose response for better outcomes. When synthesized with findings from the World Cancer Research Fund review of RCTs investigating the effect of diet and physical activity interventions on cancer survival, evidence suggests that the mechanism of benefit from diet and physical activity pertains to body weight, with excess body weight being a risk factor, which is modifiable through lifestyle. Implications: Cancer survivors would like to have a more active role in their health care and to know how to look after themselves after diagnosis, including what diet and lifestyle changes they should make. The challenge is in integrating lifestyle support into standardised models of aftercare.", "title": "The role of diet and physical activity in breast, colorectal, and prostate cancer survivorship: a review of the literature" }, { "docid": "MED-839", "text": "Long-chain EPA/DHA omega-3 fatty acid supplementation can be co-preventative and co-therapeutic. Current research suggests increasing accumulated long chain omega-3s for health benefits and as natural medicine in several major diseases. But many believe plant omega-3 sources are nutritionally and therapeutically equivalent to the EPA/DHA omega-3 in fish oil. Although healthy, precursor ALA bio-conversion to EPA is inefficient and production of DHA is nearly absent, limiting the protective value of ALA supplementation from flax-oil, for example. Along with pollutants certain fish acquire high levels of EPA/DHA as predatory species. However, the origin of EPA/DHA in aquatic ecosystems is algae. Certain microalgae produce high levels of EPA or DHA. Now, organically produced DHA-rich microalgae oil is available. Clinical trials with DHA-rich oil indicate comparable efficacies to fish oil for protection from cardiovascular risk factors by lowering plasma triglycerides and oxidative stress. This review discusses 1) omega-3 fatty acids in nutrition and medicine; 2) omega-3s in physiology and gene regulation; 3) possible protective mechanisms of EPA/DHA in major diseases such as coronary heart disease, atherosclerosis, cancer and type 2 diabetes; 4) EPA and DHA requirements considering fish oil safety; and 5) microalgae EPA and DHA-rich oils and recent clinical results.", "title": "Omega-3 fatty acids for nutrition and medicine: considering microalgae oil as a vegetarian source of EPA and DHA." }, { "docid": "MED-1677", "text": "Background The combination of healthy lifestyle factors is associated with lower risk of coronary heart disease, diabetes and total cardiovascular disease. Little is known about the impact of multiple lifestyle factors on risk of stroke. Methods and results We conducted a prospective cohort study among 43,685 men from Health Professionals Follow-up Study and 71,243 women from the Nurses' Health Study. Diet and other lifestyle factors were updated from self-reported questionnaires. We defined a low-risk lifestyle as not smoking, a body mass index <25 kg/m 2, ≥30 minutes/day of moderate activity, consuming alcohol modestly (men:5–30g; women:5–15g alcohol/day), and scoring within the top 40% of a healthy diet score. We documented 1559 strokes (853 ischemic, 278 hemorrhagic) among women and 994 strokes (600 ischemic, 161 hemorrhagic) among men during follow-up. Women with all five low-risk factors had a relative risk of 0.21 (95%CI:0.12, 0.36) for total and 0.19 (95%CI:0.09, 0.40) for ischemic stroke, compared to women who had none of these factors. Among men, the relative risks were 0.31 (95%CI:0.19, 0.53) for total and 0.20 (95%CI: 0.10, 0.42) for ischemic stroke for the same comparison. Among the women, 47% (95%CI:18%, 69%) of total and 54% (95%CI:15%, 78%) of ischemic stroke cases were attributable to lack of adherence to a low-risk lifestyle; among the men, 35% (95%CI:7%, 58%) of total and 52% (95%CI:19%, 75%) of ischemic stroke may have been prevented. Conclusions A low-risk lifestyle that is associated with a reduced risk of multiple chronic diseases may also be beneficial in the prevention of stroke, especially ischemic stroke.", "title": "Primary prevention of stroke by healthy lifestyle" }, { "docid": "MED-5299", "text": "Background Knowledge of the number of deaths caused by risk factors is needed for health policy and priority setting. Our aim was to estimate the mortality effects of the following 12 modifiable dietary, lifestyle, and metabolic risk factors in the United States (US) using consistent and comparable methods: high blood glucose, low-density lipoprotein (LDL) cholesterol, and blood pressure; overweight–obesity; high dietary trans fatty acids and salt; low dietary polyunsaturated fatty acids, omega-3 fatty acids (seafood), and fruits and vegetables; physical inactivity; alcohol use; and tobacco smoking. Methods and Findings We used data on risk factor exposures in the US population from nationally representative health surveys and disease-specific mortality statistics from the National Center for Health Statistics. We obtained the etiological effects of risk factors on disease-specific mortality, by age, from systematic reviews and meta-analyses of epidemiological studies that had adjusted (i) for major potential confounders, and (ii) where possible for regression dilution bias. We estimated the number of disease-specific deaths attributable to all non-optimal levels of each risk factor exposure, by age and sex. In 2005, tobacco smoking and high blood pressure were responsible for an estimated 467,000 (95% confidence interval [CI] 436,000–500,000) and 395,000 (372,000–414,000) deaths, accounting for about one in five or six deaths in US adults. Overweight–obesity (216,000; 188,000–237,000) and physical inactivity (191,000; 164,000–222,000) were each responsible for nearly 1 in 10 deaths. High dietary salt (102,000; 97,000–107,000), low dietary omega-3 fatty acids (84,000; 72,000–96,000), and high dietary trans fatty acids (82,000; 63,000–97,000) were the dietary risks with the largest mortality effects. Although 26,000 (23,000–40,000) deaths from ischemic heart disease, ischemic stroke, and diabetes were averted by current alcohol use, they were outweighed by 90,000 (88,000–94,000) deaths from other cardiovascular diseases, cancers, liver cirrhosis, pancreatitis, alcohol use disorders, road traffic and other injuries, and violence. Conclusions Smoking and high blood pressure, which both have effective interventions, are responsible for the largest number of deaths in the US. Other dietary, lifestyle, and metabolic risk factors for chronic diseases also cause a substantial number of deaths in the US. Please see later in the article for Editors' Summary Editors' Summary A number of modifiable factors are responsible for many premature or preventable deaths. For example, being overweight or obese shortens life expectancy, while half of all long-term tobacco smokers in Western populations will die prematurely from a disease directly related to smoking. Modifiable risk factors fall into three main groups. First, there are lifestyle risk factors. These include tobacco smoking, physical inactivity, and excessive alcohol use (small amounts of alcohol may actually prevent diabetes and some types of heart disease and stroke). Second, there are dietary risk factors such as a high salt intake and a low intake of fruits and vegetables. Finally, there are “metabolic risk factors,” which shorten life expectancy by increasing a person's chances of developing cardiovascular disease (in particular, heart problems and strokes) and diabetes. Metabolic risk factors include having high blood pressure or blood cholesterol and being overweight or obese. Why Was This Study Done? It should be possible to reduce preventable deaths by changing modifiable risk factors through introducing public health policies, programs and regulations that reduce exposures to these risk factors. However, it is important to know how many deaths are caused by each risk factor before developing policies and programs that aim to improve a nation's health. Although previous studies have provided some information on the numbers of premature deaths caused by modifiable risk factors, there are two problems with these studies. First, they have not used consistent and comparable methods to estimate the number of deaths attributable to different risk factors. Second, they have rarely considered the effects of dietary and metabolic risk factors. In this new study, the researchers estimate the number of deaths due to 12 different modifiable dietary, lifestyle, and metabolic risk factors for the United States population. They use a method called “comparative risk assessment.” This approach estimates the number of deaths that would be prevented if current distributions of risk factor exposures were changed to hypothetical optimal distributions. What Did the Researchers Do and Find? The researchers extracted data on exposures to these 12 selected risk factors from US national health surveys, and they obtained information on deaths from difference diseases for 2005 from the US National Center for Health Statistics. They used previously published studies to estimate how much each risk factor increases the risk of death from each disease. The researchers then used a mathematical formula to estimate the numbers of deaths caused by each risk factor. Of the 2.5 million US deaths in 2005, they estimate that nearly half a million were associated with tobacco smoking and about 400,000 were associated with high blood pressure. These two risk factors therefore each accounted for about 1 in 5 deaths in US adults. Overweight–obesity and physical inactivity were each responsible for nearly 1 in 10 deaths. Among the dietary factors examined, high dietary salt intake had the largest effect, being responsible for 4% of deaths in adults. Finally, while alcohol use prevented 26,000 deaths from ischemic heart disease, ischemic stroke, and diabetes, the researchers estimate that it caused 90,000 deaths from other types of cardiovascular diseases, other medical conditions, and road traffic accidents and violence. What Do These Findings Mean? These findings indicate that smoking and high blood pressure are responsible for the largest number of preventable deaths in the US, but that several other modifiable risk factors also cause many deaths. Although the accuracy of some of the estimates obtained in this study will be affected by the quality of the data used, these findings suggest that targeting a handful of risk factors could greatly reduce premature mortality in the US. The findings might also apply to other countries, although the risk factors responsible for most preventable deaths may vary between countries. Importantly, effective individual-level and population-wide interventions are already available to reduce people's exposure to the two risk factors responsible for most preventable deaths in the US. The researchers also suggest that combinations of regulation, pricing, and education have the potential to reduce the exposure of US residents to other risk factors that are likely to shorten their lives. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000058.", "title": "The Preventable Causes of Death in the United States: Comparative Risk Assessment of Dietary, Lifestyle, and Metabolic Risk Factors" }, { "docid": "MED-3253", "text": "OBJECTIVES: Atherosclerosis begins in childhood and progresses during adolescence and young adulthood. The Pathobiological Determinants of Atherosclerosis in Youth Study previously reported risk scores to estimate the probability of advanced atherosclerotic lesions in young individuals aged 15 to 34 years using the coronary heart disease risk factors (gender, age, serum lipoprotein concentrations, smoking, hypertension, obesity, and hyperglycemia). In this study we investigated the relation of these risk scores to the early atherosclerotic lesions. METHODS: We measured atherosclerotic lesions in the left anterior descending coronary artery, right coronary artery, and abdominal aorta and the coronary heart disease risk factors in persons 15 to 34 years of age who died as a result of external causes and were autopsied in forensic laboratories. RESULTS: Risk scores computed from the modifiable risk factors were associated with prevalence of microscopically demonstrable lesions of atherosclerosis (American Heart Association grade 1) in the left anterior descending coronary artery and with the extent of the earliest detectable gross lesion (fatty streaks) in the right coronary artery and abdominal aorta. Risk scores computed from the modifiable risk factors also were associated with prevalence of lesions of higher degrees of microscopic severity (intermediate as well as advanced) in the left anterior descending coronary artery and with extent of lesions of higher degrees of severity (intermediate and raised lesions) in the right coronary artery and abdominal aorta. CONCLUSIONS: Risk scores calculated from traditional coronary heart disease risk factors to identify individual young persons with high probability of having advanced atherosclerotic lesions also are associated with earlier atherosclerotic lesions, including the earliest anatomically demonstrable atherosclerotic lesion. These results support lifestyle modification in youth to prevent development of the initial lesions and the subsequent progression to advanced lesions and, thereafter, to prevent or delay coronary heart disease.", "title": "Pathobiological determinants of atherosclerosis in youth risk scores are associated with early and advanced atherosclerosis." }, { "docid": "MED-2761", "text": "PURPOSE: The aim of this study was to examine the prevalence of self-reported multivitamin use in the Physicians' Health Study (PHS) cohort and its association with various lifestyle, clinical, and dietary factors to improve our understanding of who tends to use multivitamins. METHODS: Among 18,040 middle-aged and older men, information on lifestyle and clinical factors was collected from a baseline enrollment questionnaire, and supplement use and dietary factors were assessed through a food-frequency questionnaire. Four categories of multivitamin use were considered: (1) no supplement use, (2) use of multivitamins only, (3) use of multivitamins with other individual vitamin/mineral supplements, and (4) use of other supplements only. We used logistic regression to calculate multivariate odds ratios and 95% confidence intervals of taking multivitamin supplements for various lifestyle, clinical and dietary factors. RESULTS: Overall, 36% of men reported current multivitamin use. Men who were older, current smokers, and currently using aspirin were 143, 43, and 74% more likely to use multivitamins only. Men having a history of hypercholesterolemia were 16% more likely to use multivitamins only. A 14, 24, and 26% greater likelihood of using multivitamins was also observed among men consuming more fruits and vegetables, whole grains, and tea, respectively. Similar associations were observed for the likelihood of using multivitamins with other supplements; however, men with higher physical activity, history of cancer, hypertension, higher consumption of nuts, and lower consumption of red meat and coffee were also more likely to use multivitamins with other supplements (all P < 0.05). CONCLUSION: Self-reported multivitamin use associated with lifestyle, clinical and dietary factors may be an indicator of healthy behaviors. These results provide important information for the interpretation of the recent findings from the PHS II trial and consideration of results from observational studies of multivitamin use and chronic disease.", "title": "Who uses multivitamins? A cross-sectional study in the Physicians' Health Study." }, { "docid": "MED-2512", "text": "Ageing is a challenge for any living organism and human longevity is a complex phenotype. With increasing life expectancy, maintaining long-term health, functionality and well-being during ageing has become an essential goal. To increase our understanding of how ageing works, it may be advantageous to analyze the phenotype of centenarians, perhaps one of the best examples of successful ageing. Healthy ageing involves the interaction between genes, the environment, and lifestyle factors, particularly diet. Besides evaluating specific gene-environment interactions in relation to exceptional longevity, it is important to focus attention on modifiable lifestyle factors such as diet and nutrition to achieve extension of health span. Furthermore, a better understanding of human longevity may assist in the design of strategies to extend the duration of optimal human health. In this article we briefly discuss relevant topics on ageing and longevity with particular focus on dietary patterns of centenarians and nutrient-sensing pathways that have a pivotal role in the regulation of life span. Finally, we also discuss the potential role of Nrf2 system in the pro-ageing signaling emphasizing its phytohormetic activation.", "title": "Extending healthy ageing: nutrient sensitive pathway and centenarian population" }, { "docid": "MED-4609", "text": "Two pandemics of heart attack deaths have plagued the world's population during the past 130 years. The first pandemic, induced by beriberi, was caused by the industrial revolution altering the nutritional composition of rice. By 1892 a simple working knowledge, then at hand, could have terminated the beriberi plague; however, orthodox medicine being then enchanted with the false concept that all disease was caused by germs, permitted millions of Asians to die needlessly of beriberi by refusing to tell them to eat rice bran or to drink rice bran tea. A second pandemic of heart attack deaths, called myocardial infarction (MI), struck the developed nations of the Western World in full force after 1930. As a hypothesis, it is suggested that this MI pandemic, still raging today, was caused by a change in food processing that occurred after 1920, when the new oil seed industry introduced into our food three greatly harmful lipid substances. The unnatural trans-trans isomer of linoleic acid, which had never been in human food prior to 1920 and which entered our food in margarines and refined oils, blocked the conversion of natural cis-cis linoleic acid to prostaglandin E1, which tends to prevent MI, both by acting as a vasodilator and by minimizing platelet aggregation. Harmful lactones were also introduced into our food, increasing the risk of MI by decreasing the fibrinolytic activity of our blood. The oil seed industry also introduced into our diet free radical lipid peroxides that make the myocardium more vulnerable to infarction. It is suggested that except for the one in 500 of us who is afflicted by familial hypercholesterolemia, the cholesterol concept of MI is as false today as was the concept in 1900 that germs caused beriberi. It is further suggested that a working knowledge is at hand today that can make death from MI just as rare as death is now from a beriberi-induced heart attack.", "title": "The beriberi analogy to myocardial infarction." }, { "docid": "MED-1097", "text": "Moses Maimonides (1135-1204), physician and philosopher, was the greatest Jewish thinker of the Middle Ages. Faced with a life of persecution, exile, and tragedy, Maimonides overcame obstacles to become the leading physician in his era, a clinician whose skills were sought across continents. Despite long days caring for patients, Maimonides wrote extensively about both medicine and philosophy. His medical works span all topics of clinical medicine and reflect rational thinking and an understanding of the relationship between mind and body. Well known for his philosophical writings, such as The Guide for the Perplexed, Maimonides codified Jewish law and revolutionized Jewish thinking. This review of his life and achievements provides insight into the world of a remarkable 12th-century physician and may offer valuable lessons for physicians today.", "title": "Moses Maimonides: medieval physician and scholar." }, { "docid": "MED-1917", "text": "The telomere length is an indicator of biologic aging, and shorter telomeres have been associated with coronary artery calcium (CAC), a validated indicator of coronary atherosclerosis. It is unclear, however, whether healthy lifestyle behaviors affect the relation between telomere length and CAC. In a sample of subjects aged 40 to 64 years with no previous diagnosis of coronary heart disease, stroke, diabetes mellitus, or cancer (n = 318), healthy lifestyle behaviors of greater fruit and vegetable consumption, lower meat consumption, exercise, being at a healthy weight, and the presence of social support were examined to determine whether they attenuated the association between a shorter telomere length and the presence of CAC. Logistic regression analyses controlling for age, gender, race/ethnicity, and Framingham risk score revealed that the relation between having shorter telomeres and the presence of CAC was attenuated in the presence of high social support, low meat consumption, and high fruit and vegetable consumption. Those with shorter telomeres and these characteristics were not significantly different from those with longer telomeres. Conversely, the subjects with shorter telomeres and less healthy lifestyles had a significantly increased risk of the presence of CAC: low fruit and vegetable consumption (odds ratio 3.30, 95% confidence interval 1.61 to 6.75), high meat consumption (odds ratio 3.33, 95% confidence interval 1.54 to 7.20), and low social support (odds ratio 2.58, 95% confidence interval 1.24 to 5.37). Stratification by gender yielded similar results for men; however, among women, only fruit and vegetable consumption attenuated the shorter telomere length and CAC relation. In conclusion, the results of the present study suggest that being involved in healthy lifestyle behaviors might attenuate the association between shorter telomere length and coronary atherosclerosis, as identified using CAC. 2010 Elsevier Inc. All rights reserved.", "title": "Effect of healthy lifestyle behaviors on the association between leukocyte telomere length and coronary artery calcium." }, { "docid": "MED-2010", "text": "Legumes (including alfalfa, clover, lupins, green beans and peas, peanuts, soybeans, dry beans, broad beans, dry peas, chickpeas, and lentils) represent an important component of the human diet in several areas of the world, especially in the developing countries, where they complement the lack of proteins from cereals, roots, and tubers. In some regions of the world, legume seeds are the only protein supply in the diet. The health benefits of legume consumption have received rising interest from researchers, and their consumption and production extends worldwide. Among European countries, higher legume consumption is observed around the Mediterranean, with per capita daily consumption between 8 and 23 g, while in Northern Europe, the daily consumption is less than 5 g per capita. The physiological effects of different legumes vary significantly. These differences may result from the polysaccharides composition, in particular, the quantity and variety of dietary fibers and starch, protein make-up, and variability in phytochemical content. The majority of legumes contain phytochemicals: bioactive compounds, including enzyme inhibitors, phytohemagglutinins (lectins), phytoestrogens, oligosaccharides, saponins, and phenolic compounds, which play metabolic roles in humans who frequently consume these foods. Dietary intake of phytochemicals may provide health benefits, protecting against numerous diseases or disorders, such as coronary heart disease, diabetes, high blood pressure and inflammation. The synergistic or antagonistic effects of these phytochemical mixtures from food legumes, their interaction with other components of the diet, and the mechanism of their action have remained a challenge with regard to understanding the role of phytochemicals in health and diseases. Their mitigating effects and the mechanism of their action need to be further addressed if we are to understand the role of phytochemicals in health and diseases. This review provides an overview of the nutritional quality of legumes and their potential contribution in cardiometabolic risk prevention.", "title": "Nutritional quality of legumes, and their role in cardiometabolic risk prevention: a review." }, { "docid": "MED-4622", "text": "We developed a probabilistic model to characterize the plausible distribution of health and economic benefits that would accrue to the U.S. population following reduction of methyl mercury (MeHg) exposure. MeHg, a known human developmental neurotoxicant, may increase fatal heart attack risks. Model parameters reflect current understanding of the relationships between MeHg intake, health risks, and societal valuation of these risks. The expected monetary value of the annual health benefits generated by a 10% reduction in U.S. population exposure to MeHg for one year is $860 million; 80% of this is associated with reductions in fatal heart attacks and the remainder with IQ gains. The plausible distribution of the benefits is quite broad with 5th and 95th percentile estimates of approximately $50 million and $3.5 billion, respectively. The largest source of uncertainty is whether epidemiological associations between MeHg exposure and fatal heart attacks reflect causality. The next largest sources of uncertainty concern the slope of the relationship between maternal MeHg exposure and reduced intelligence among children and whether this relationship exhibits a threshold. Our analysis suggests that the possible causal relationship between MeHg exposure and fatal heart attacks should be better characterized, using additional epidemiological studies and formally elicited expert judgment.", "title": "A probabilistic characterization of the health benefits of reducing methyl mercury intake in the United States." }, { "docid": "MED-1376", "text": "Background. There are places around the world where people live longer and they are active past the age of 100 years, sharing common behavioral characteristics; these places (i.e., Sardinia in Italy, Okinawa in Japan, Loma Linda in California and Nicoya Peninsula in Costa Rica) have been named the “Blue Zones”. Recently it was reported that people in Ikaria Island, Greece, have also one of the highest life expectancies in the world, and joined the “Blue Zones”. The aim of this work work was to evaluate various demographic, lifestyle and psychological characteristics of very old (>80 years) people participated in Ikaria Study. Methods. During 2009, 1420 people (aged 30+) men and women from Ikaria Island, Greece, were voluntarily enrolled in the study. For this work, 89 males and 98 females over the age of 80 yrs were studied (13% of the sample). Socio-demographic, clinical, psychological and lifestyle characteristics were assessed using standard questionnaires and procedures. Results. A large proportion of the Ikaria Study's sample was over the age of 80; moreover, the percent of people over 90 were much higher than the European population average. The majority of the oldest old participants reported daily physical activities, healthy eating habits, avoidance of smoking, frequent socializing, mid-day naps and extremely low rates of depression. Conclusion. Modifiable risk factors, such as physical activity, diet, smoking cessation and mid-day naps, might depict the “secrets” of the long-livers; these findings suggest that the interaction of environmental, behavioral together with clinical characteristics may determine longevity. This concept must be further explored in order to understand how these factors relate and which are the most important in shaping prolonged life.", "title": "Sociodemographic and Lifestyle Statistics of Oldest Old People (>80 Years) Living in Ikaria Island: The Ikaria Study" }, { "docid": "MED-3425", "text": "OBJECTIVES: We examined whether common coronary heart disease (CHD) risk factors measured in mid-life predict erectile dysfunction (ED) 25 years later. BACKGROUND: Retrospective and cross-sectional studies have suggested that ED is associated with classic CHD risk factors, but few prospective studies have studied these associations. METHODS: In this prospective study of community-dwelling men age 30 to 69 years, seven classic CHD risk factors (age, smoking, hypertension, diabetes, hypercholesterolemia, hypertriglyceridemia, and obesity) were assessed from 1972 to 1974. In 1998, after an average follow-up of 25 years, surviving male participants were asked to complete the International Index of Erectile Function (IIEF-5), which allows stratification of ED into five groups. RESULTS: Sixty-eight percent of the surviving men returned, and 60% completed the IIEF-5 questionnaire. Respondents had more favorable levels of all heart disease risk factors at baseline than non-respondents. At baseline, the average age of the 570 ED study participants was 46 years; at follow-up, their average age was 72 years. Mean age, body mass index, cholesterol, and triglycerides were each significantly associated with an increased risk of ED. Cigarette smoking was marginally more common in those with severe/complete ED, as compared with those without ED. Blood pressure and fasting blood glucose were not significantly associated with ED, likely due to selective mortality. CONCLUSIONS: Improving CHD risk factors in mid-life may decrease the risk of ED as well as CHD. Erectile dysfunction should be included as an outcome in clinical trials of lipid-lowering agents and lifestyle modifications.", "title": "Heart disease risk factors predict erectile dysfunction 25 years later: the Rancho Bernardo Study." }, { "docid": "MED-2786", "text": "Alzheimer's disease (AD) is the most common form of dementia. There is limited choice in modern therapeutics, and drugs available have limited success with multiple side effects in addition to high cost. Hence, newer and alternate treatment options are being explored for effective and safer therapeutic targets to address AD. Turmeric possesses multiple medicinal uses including treatment for AD. Curcuminoids, a mixture of curcumin, demethoxycurcumin, and bisdemethoxycurcumin, are vital constituents of turmeric. It is generally believed that curcumin is the most important constituent of the curcuminoid mixture that contributes to the pharmacological profile of parent curcuminoid mixture or turmeric. A careful literature study reveals that the other two constituents of the curcuminoid mixture also contribute significantly to the effectiveness of curcuminoids in AD. Therefore, it is emphasized in this review that each component of the curcuminoid mixture plays a distinct role in making curcuminoid mixture useful in AD, and hence, the curcuminoid mixture represents turmeric in its medicinal value better than curcumin alone. The progress in understanding the disease etiology demands a multiple-site-targeted therapy, and the curcuminoid mixture of all components, each with different merits, makes this mixture more promising in combating the challenging disease. Copyright © 2013 John Wiley & Sons, Ltd.", "title": "Therapeutic potential of turmeric in Alzheimer's disease: curcumin or curcuminoids?" }, { "docid": "MED-4314", "text": "The prevalence of cardiovascular disease as the leading cause of morbidity and mortality is increasing worldwide. This fact is mainly attributed to the modern lifestyle with predominant characteristics the change of dietary habits and the reduced physical activity which lead to metabolic disorders such as obesity and diabetes. Therefore, drastic dietary interventions are considered necessary in order to reduce cardiovascular risk. Nuts, as a nutritional component have drawn particular attention, due to their beneficial cardiovascular properties derived from their nutrient composition. This is a comprehensive review concerning the potential general effects of nuts. It includes data from older large epidemiologic studies as well as recent significant information from clinical trials regarding this topic. All studies conclude that nuts can play an important role as part of a healthy diet in order to minimize cardiovascular risk and obtain multiple health benefits. Copyright © 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.", "title": "Nuts: anti-atherogenic food?" }, { "docid": "MED-2525", "text": "AIMS: Guidelines for cardiovascular disease (CVD) prevention cite high levels of low-density lipoprotein cholesterol (LDL-C) as a major risk factor and recommend LDL-C goals for various risk groups. Lifestyle changes are advised as first-line treatment for patients with high cholesterol, and statins are recommended in high-risk patients. The From The Heart study investigated current practice for the diagnosis and treatment of high cholesterol, and attitudes towards management of the condition. METHODS: Physicians were randomly selected from 10 countries, and completed a confidential, semi-structured questionnaire. RESULTS: Of 2790 physicians agreeing to participate, 750 (27%) responded. Physicians rated CVD as the leading cause of death, although physicians (80%) perceived that cancer was the most feared illness among patients. Physicians (71%) believed smoking to be the greatest CVD risk factor, while only 50% thought high cholesterol was the greatest risk. Most physicians (81%) used guidelines to set cholesterol goals, primarily their national guidelines (34%) or the National Cholesterol Education Program Adult Treatment Panel III guidelines (24%). Although only 47% of patients reached and maintained their cholesterol goals, 61% of physicians believed that a sufficient number of patients achieved goals, and 53% did not feel frustrated that they could not always effectively treat patients with CVD. CONCLUSION: Results indicate discrepancies between guideline recommendations and clinical practice. Although physicians appreciate the risk of CVD, the importance of achieving healthy cholesterol levels for CVD prevention does not seem to be widely endorsed. There is a need for improved communication regarding the importance of cholesterol lowering and investigation of initiatives to improve goal achievement among physicians.", "title": "A global survey of physicians' perceptions on cholesterol management: the From The Heart study." }, { "docid": "MED-5026", "text": "Background: Higher intakes of fruit, vegetables, and dark fish may prevent sudden cardiac death and arrhythmias, but the exact mechanisms are not fully understood. Objective: We examined whether high consumption of fruit, vegetables, and dark fish would be associated with beneficial changes in heart rate variability (HRV). Design: HRV variables were measured among 586 older men with 928 total observations from November 2000 to June 2007 in the Normative Aging Study, a community-based longitudinal study of aging. Dietary intake was evaluated with a self-administered semiquantitative food-frequency questionnaire and categorized into quartiles. Results: After controlling for potential confounders, intake of green leafy vegetables was positively associated with normalized high-frequency power and inversely associated with normalized low-frequency power (P for trend < 0.05). These significant associations were retained after further adjustment for healthy lifestyle factors, such as physical activity and use of multivitamins. No significant association was seen between HRV measures and intakes of other fruit and vegetables, vitamin C, carotenoids, tuna and dark-meat fish, or n–3 (omega-3) fatty acids. An effect modification of intake of noncitrus fruit by obesity and of total vegetables and cruciferous vegetables by cigarette smoking was seen, which warrants further investigation. Conclusion: These findings suggest that higher intake of green leafy vegetables may reduce the risk of cardiovascular disease through favorable changes in cardiac autonomic function.", "title": "Fruit, vegetable, and fish consumption and heart rate variability: the Veterans Administration Normative Aging Study" }, { "docid": "MED-3954", "text": "BACKGROUND: A male epidemic of ischaemic heart disease (IHD) emerges with economic development. It has previously been hypothesised that this epidemic is due to nutritionally driven levels of pubertal sex steroids, which lead to a more atherogenic body shape and lipid profile in boys but not girls, without any sex-specific effects on glucose metabolism. This study tests this hypothesis by examining the association of childhood meat eating with IHD risk in a developing Chinese population. METHODS: Multivariable linear and censored regression was used in a cross-sectional study of 19,418 Chinese older (≥ 50 years) men and women from the Guangzhou Biobank Cohort Study (phases 2 and 3) to assess the adjusted associations of childhood meat eating with waist to hip ratio (WHR), high-density lipoprotein cholesterol and fasting plasma glucose. RESULTS: Adjusted for age, childhood hunger, life-course socioeconomic position and current lifestyle childhood almost daily meat eating compared with less than weekly meat eating was associated with higher WHR (0.007, 95% CI 0.0003 to 0.01) in men but not women. No association with fasting glucose was observed. CONCLUSIONS: Given the potential limitations of this study, especially the crude nature of the exposure and modest findings, the results should be considered as preliminary. However, they do lend support to the hypothesis that the male epidemic of premature IHD and sexual divergence in IHD rates that occur with economic development may be nutritionally driven in childhood. In elucidating the developmental origins of non-communicable chronic diseases, more attention should be focused on the sociohistorical context and the role of puberty.", "title": "Does childhood meat eating contribute to sex differences in risk factors for ischaemic heart disease in a developing population?" }, { "docid": "MED-1398", "text": "The concept that the Mediterranean diet was associated with a lower incidence of cardiovascular disease (CVD) was first proposed in the 1950s. Since then, there have been randomized controlled trials and large epidemiological studies that reported associations with lower CVD: in 1994 and 1999, the reports of the intermediate and final analyses of the trial Lyon Diet Heart Study; in 2003, a major epidemiological study in Greece showing a strong inverse association between a Mediterranean score and the risk of cardiovascular complications; in 2011-2012, several reports showing that even non-Mediterranean populations can gain benefits from long-term adhesion to the Mediterranean diet; and in 2013, the PREDIMED trial showing a significant risk reduction in a low-risk population. Contrary to the pharmacological approach of cardiovascular prevention, the adoption of the Mediterranean diet has been associated with a significant reduction in new cancers and overall mortality. Thus, in terms of evidence-based medicine, the full adoption of a modern version of the Mediterranean diet pattern can be considered one of the most effective approaches for the prevention of fatal and nonfatal CVD complications.", "title": "Mediterranean diet and cardiovascular disease: historical perspective and latest evidence." } ]
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Phase information is useful for predicting donor-recipient matches in organ transplantation.
[ { "docid": "11527199", "text": "Background Current criteria for the selection of unrelated donors for hematopoietic cell transplantation (HCT) include matching for the alleles of each human leukocyte antigen (HLA) locus within the major histocompatibility complex (MHC). Graft-versus-host disease (GVHD), however, remains a significant and potentially life-threatening complication even after HLA-identical unrelated HCT. The MHC harbors more than 400 genes, but the total number of transplantation antigens is unknown. Genes that influence transplantation outcome could be identified by using linkage disequilibrium (LD)-mapping approaches, if the extended MHC haplotypes of the unrelated donor and recipient could be defined.", "title": "MHC Haplotype Matching for Unrelated Hematopoietic Cell Transplantation" } ]
[ { "docid": "16737210", "text": "CONTEXT Blood type and crossmatch incompatibility will exclude at least one third of patients in need from receiving a live donor kidney transplant. Kidney paired donation (KPD) offers incompatible donor/recipient pairs the opportunity to match for compatible transplants. Despite its increasing popularity, very few transplants have resulted from KPD. OBJECTIVE To determine the potential impact of improved matching schemes on the number and quality of transplants achievable with KPD. DESIGN, SETTING, AND POPULATION We developed a model that simulates pools of incompatible donor/recipient pairs. We designed a mathematically verifiable optimized matching algorithm and compared it with the scheme currently used in some centers and regions. Simulated patients from the general community with characteristics drawn from distributions describing end-stage renal disease patients eligible for renal transplantation and their willing and eligible live donors. MAIN OUTCOME MEASURES Number of kidneys matched, HLA mismatch of matched kidneys, and number of grafts surviving 5 years after transplantation. RESULTS A national optimized matching algorithm would result in more transplants (47.7% vs 42.0%, P<.001), better HLA concordance (3.0 vs 4.5 mismatched antigens; P<.001), more grafts surviving at 5 years (34.9% vs 28.7%; P<.001), and a reduction in the number of pairs required to travel (2.9% vs 18.4%; P<.001) when compared with an extension of the currently used first-accept scheme to a national level. Furthermore, highly sensitized patients would benefit 6-fold from a national optimized scheme (2.3% vs 14.1% successfully matched; P<.001). Even if only 7% of patients awaiting kidney transplantation participated in an optimized national KPD program, the health care system could save as much as $750 million. CONCLUSIONS The combination of a national KPD program and a mathematically optimized matching algorithm yields more matches with lower HLA disparity. Optimized matching affords patients the flexibility of customizing their matching priorities and the security of knowing that the greatest number of high-quality matches will be found and distributed equitably.", "title": "Kidney paired donation and optimizing the use of live donor organs." }, { "docid": "7034001", "text": "Donor kidney exchange is an established method to overcome incompatibility of donor-recipient pairs (DRP). A computerized algorithm was devised to exchange donor kidney and was tested in a multicenter setting. The algorithm was made according to the consensus of participating centers. It makes all possible exchange combinations not only between two incompatible DRP but also circularly among three DRP and selects an optimum set of exchange combinations, considering several factors that can affect the outcome of the exchanged transplant. The algorithm was implemented as a web-based program, and matching was performed five times. Fifty-three DRP were enrolled from five transplant centers. The numbers of DRP that were enrolled in each matching were 38 (25:13), 39 (34:5), 33 (31:2), 32 (28:4), and 34 (30:4) (carryover:newcomer). The numbers of generated exchange combinations were 4:11, 3:17, 2:12, 2:3, and 2:3 (two-pair exchange:three-pair exchange), and the numbers of DRP in selected exchange combinations were six, 12, six, five, and four in each matching. The numbers of DRP with blood type O recipient or AB donor were five and one, respectively, in selected exchange combinations. Six DRP of two-pair exchange combinations and six DRP of three-pair exchange combinations underwent transplantation successfully. Computerized algorithm of donor kidney exchange was tried not only between two incompatible DRP but also circularly among three DRP. It showed that the algorithm has potential to improve the outcome of donor kidney exchange, especially for disadvantaged DRP with blood type O recipients or AB donors.", "title": "Outcome of multipair donor kidney exchange by a web-based algorithm." }, { "docid": "21203899", "text": "Kidney donor exchanges enable recipients with immunologically incompatible donors to receive compatible living donor grafts; however, the financial management of these exchanges, especially when an organ is shipped, is complex and thus has the potential to impede the broader implementation of donor exchange programs. Representatives from transplant centers that utilize the National Kidney Registry database to facilitate donor exchange transplants developed a financial model applicable to paired donor exchanges and donor chain transplants. The first tenet of the model is to eliminate financial liability to the donor. Thereafter, it accounts for the donor evaluation, donor nephrectomy hospital costs, donor nephrectomy physician fees, organ transport, donor complications and recipient inpatient services. Billing between hospitals is based on Medicare cost report defined costs rather than charges. We believe that this model complies with current federal regulations and effectively captures costs of the donor and recipient services. It could be considered as a financial paradigm for the United Network for Organ Sharing managed donor exchange program.", "title": "Managing finances of shipping living donor kidneys for donor exchanges." }, { "docid": "41774099", "text": "We propose a Medicare Demonstration Project to develop a standard acquisition charge for kidney paired donation. A new payment strategy is required because Medicare and commercial insurance companies may not directly pay living donor costs intended to lead to transplantation of a beneficiary of a different insurance provider. Until the 1970s, when organ procurement organizations were empowered to serve as financial intermediaries to pay the upfront recovery expenses for deceased donor kidneys before knowing the identity of the recipient, there existed similar limitations in the recovery and placement of deceased donor organs. Analogous to the recovery of deceased donor kidneys, kidney paired donation requires the evaluation of living donors before identifying their recipient. Tissue typing, crossmatching and transportation of living donors or their kidneys represent additional financial barriers. Finally, the administrative expenses of the organizations that identify and coordinate kidney paired donation transplantation require reimbursement akin to that necessary for organ procurement organizations. To expand access to kidney paired donation for more patients, we propose a model to reimburse paired donation expenses analogous to the proven strategy used for over 30 years to pay for deceased donor solid organ transplantation in America.", "title": "Call to Develop a Standard Acquisition Charge Model for Kidney Paired Donation" }, { "docid": "33535222", "text": "CD4+CD25+ regulatory T cells (Treg's) play a pivotal role in preventing organ-specific autoimmune diseases and in inducing tolerance to allogeneic organ transplants. We and others recently demonstrated that high numbers of Treg's can also modulate graft-versus-host disease (GVHD) if administered in conjunction with allogeneic hematopoietic stem cell transplantation in mice. In a clinical setting, it would be impossible to obtain enough freshly purified Treg's from a single donor to have a therapeutic effect. Thus, we performed regulatory T cell expansion ex vivo by stimulation with allogeneic APCs, which has the additional effect of producing alloantigen-specific regulatory T cells. Here we show that regulatory T cells specific for recipient-type alloantigens control GVHD while favoring immune reconstitution. Irrelevant regulatory T cells only mediate a partial protection from GVHD. Preferential survival of specific regulatory T cells, but not of irrelevant regulatory T cells, was observed in grafted animals. Additionally, the use of specific regulatory T cells was compatible with some form of graft-versus-tumor activity. These data suggest that recipient-type specific Treg's could be preferentially used in the control of GVHD in future clinical trials.", "title": "Recipient-type specific CD4+CD25+ regulatory T cells favor immune reconstitution and control graft-versus-host disease while maintaining graft-versus-leukemia." }, { "docid": "24825841", "text": "The likelihood for immunological rejection of Human Leukocyte Antigens (HLA)-mismatched induced pluripotent stem cells (iPSCs) limits their therapeutic potential. Here we show how a tissue bank from 150 selected homozygous HLA-typed volunteers could match 93% of the UK population with a minimal requirement for immunosuppression. Our model provides a practical approach for using existing HLA-typed samples to generate an iPSC stem cell bank that circumvents prospective typing of a large number of individuals.", "title": "Generating an iPSC bank for HLA-matched tissue transplantation based on known donor and recipient HLA types." }, { "docid": "21859699", "text": "Providing transplantation opportunities for patients with incompatible live donors through kidney paired donation (KPD) is seen as one of the important strategies for easing the crisis in organ availability. It has been estimated that an additional 1000-2000 transplants per year could be accomplished if a national KPD program were implemented in the United States. While most of these transplants could be arranged within the participants' local or regional area, patients with hard-to-match blood types or broad HLA sensitization would benefit from matching across larger geographic areas. In this case, either patients or organs would need to travel in order to obtain maximum benefit from a national program. In this study, we describe how a triple KPD enabled a highly sensitized patient (PRA 96%) to receive a well-matched kidney from a live donor on the opposite coast. The kidney was removed in San Francisco and transported to Baltimore where it was reperfused 8 h later. The patient had prompt function and 1 year later has a serum creatinine of 1.1 mg/dl. This case provides a blueprint for solving some of the complexities that are inherent in the implementation of a national KPD program in a large country like the United States.", "title": "Successful three-way kidney paired donation with cross-country live donor allograft transport." }, { "docid": "27243019", "text": "Umbilical cord blood (UCB) is now widely used as an alternative hematopoietic stem cell source for patients lacking closely matched related or unrelated adult donors. UCB transplantation has traditionally been associated with delayed engraftment, poor immune reconstitution and consequent increased risk of infection. More recent clinical studies, however, suggest that conditioning regimens and in particular the omission of in vivo T-cell depletion may play a crucial role in post-transplant T-cell expansion, facilitating a uniquely rapid immune recovery after UCB transplantation. The peculiar characteristics of UCB cells, the importance of thymic function and the role of conditioning regimens and graft-versus-host disease influencing immune reconstitution are described. The last part of the review reports available data on UCB, as well as third-party peripheral blood derived anti-viral cell therapy, which provides a novel approach to rescue UCB recipients with viral complications in the post-transplant period.", "title": "Immune reconstitution after cord blood transplantation: peculiarities, clinical implications and management strategies." }, { "docid": "33684572", "text": "Recent studies indicate both clinical and mechanistic links between atherosclerotic heart disease and intestinal microbial metabolism of certain dietary nutrients producing trimethylamine N-oxide (TMAO). Here we test the hypothesis that gut microbial transplantation can transmit choline diet-induced TMAO production and atherosclerosis susceptibility. First, a strong association was noted between atherosclerotic plaque and plasma TMAO levels in a mouse diversity panel (n = 22 strains, r = 0.38; p = 0.0001). An atherosclerosis-prone and high TMAO-producing strain, C57BL/6J, and an atherosclerosis-resistant and low TMAO-producing strain, NZW/LacJ, were selected as donors for cecal microbial transplantation into apolipoprotein e null mice in which resident intestinal microbes were first suppressed with antibiotics. Trimethylamine (TMA) and TMAO levels were initially higher in recipients on choline diet that received cecal microbes from C57BL/6J inbred mice; however, durability of choline diet-dependent differences in TMA/TMAO levels was not maintained to the end of the study. Mice receiving C57BL/6J cecal microbes demonstrated choline diet-dependent enhancement in atherosclerotic plaque burden as compared with recipients of NZW/LacJ microbes. Microbial DNA analyses in feces and cecum revealed transplantation of donor microbial community features into recipients with differences in taxa proportions between donor strains that were transmissible to recipients and that tended to show coincident proportions with TMAO levels. Proportions of specific taxa were also identified that correlated with plasma TMAO levels in donors and recipients and with atherosclerotic lesion area in recipients. Atherosclerosis susceptibility may be transmitted via transplantation of gut microbiota. Gut microbes may thus represent a novel therapeutic target for modulating atherosclerosis susceptibility.", "title": "Transmission of atherosclerosis susceptibility with gut microbial transplantation." }, { "docid": "14647747", "text": "Strategies to prevent organ transplant rejection whilst minimizing long-term immunosuppression are currently under intense investigation with regulatory T cells (Tregs) nearing clinical application. The clinical trial, ThRIL, recently commenced at King's College London, proposes to use Treg cell therapy to induce tolerance in liver transplant recipients, the success of which has the potential to revolutionize the management of these patients and enable a future of drug-free transplants. This is the first report of the manufacture of clinical grade Tregs from prospective liver transplant recipients via a CliniMACS-based GMP isolation technique and expanded using anti-CD3/CD28 beads, IL-2 and rapamycin. We report the enrichment of a pure, stable population of Tregs (>95% CD4(+)CD25(+)FOXP3(+)), reaching adequate numbers for their clinical application. Our protocol proved successful in, influencing the expansion of superior functional Tregs, as compared to freshly isolated cells, whilst also preventing their conversion to Th17 cells under pro-inflammatory conditions. We conclude with the manufacture of the final Treg product in the clinical research facility (CRF), a prerequisite for the clinical application of these cells. The data presented in this manuscript together with the much-anticipated clinical results from ThRIL, will undoubtedly inform the improved management of the liver transplant recipient.", "title": "Successful expansion of functional and stable regulatory T cells for immunotherapy in liver transplantation" }, { "docid": "43587663", "text": "How the infection risks compare after umbilical cord blood (UCB) and bone marrow (BM) transplantation is not known. Therefore, we compared serious infections in the 2 years after pediatric myeloablative unrelated donor transplantation with unmanipulated BM (n = 52), T cell-depleted (TCD) BM (n = 24), or UCB (n = 60) for the treatment of hematologic malignancy. Overall, the cumulative incidence of 1 or more serious infections was comparable between groups (BM, 81%; TCD, 83%; UCB, 90%; P = .12). Furthermore, by taking all serious infections into account and using multivariate techniques with unmanipulated BM as the reference, there were also no significant differences between groups (TCD relative risk [RR], 1.6; P = .10; UCB RR, 1.0; P = .84). Within the time periods days 0 to 42, days 43 to 100, and days 101 to 180, the only difference was a greater risk of viral infections from days 0 to 42 in TCD recipients (RR, 3.5; P = .02). Notably, after day 180, TCD recipients had a significantly increased infection risk (RR, 3.1; P = .03), whereas the risk in UCB recipients (RR, 0.5; P = .23) was comparable to that in BM recipients. Other factors associated with an increased infection risk in the 2 years after transplantation were age > or = 8 years, graft failure, and severe acute graft-versus-host disease. These data suggest that the risk of serious infection after pediatric UCB transplantation is comparable to that with unmanipulated BM.", "title": "Serious infections after unrelated donor transplantation in 136 children: impact of stem cell source." }, { "docid": "11349166", "text": "BACKGROUND Since 2004, several reported transfusion transmissions of variant Creutzfeldt-Jakob disease (vCJD) in the United Kingdom have reawakened concerns about the possible risk of similar transmissions of nonvariant or classic forms of CJD. STUDY DESIGN AND METHODS Patients with a CJD diagnosis and a history of donating blood were reported to the study coordinator. Through review of blood distribution and hospital records, the recipients of blood components from these donors were identified. We then determined each recipient's vital status and, if deceased, the cause(s) of death identified by matching the recipient's personal identifiers with the Centers for Disease Control and Prevention's National Death Index database. We conducted such searches after recipients were enrolled in this study and annually thereafter for those who remained alive. RESULTS The study included a total of 36 blood donors who subsequently developed CJD and 436 recipients. Through 2006, 91 of these recipients were still alive, 329 were deceased, and 16 were lost to follow-up. After transfusion, these three groups had survived a total of 2096.0 person-years. A total of 144 recipients survived 5 years or longer after transfusion and 68 of them had received blood donated 60 or fewer months before the onset of CJD in the donor. We identified no recipient with CJD. CONCLUSIONS The current results of this large, ongoing lookback study show no evidence of transfusion transmission of CJD. They reinforce the conclusion that the risk, if any, of transfusion transmission of prion disease by CJD donors is significantly lower than the comparable risk of such transmission by vCJD donors.", "title": "Lack of evidence of transfusion transmission of Creutzfeldt-Jakob disease in a US surveillance study." }, { "docid": "7583161", "text": "In semisyngeneic heterotopic bone marrow transplants the donor or recipient origin of cells of osteogenic and hematopoietic tissues was identified by chromosome markers (T6) and by reverse transplantation into the initial donor line. In syngeneic and semisyngeneic grafts of bone marrow under the renal capsule bone and bone marrow are formed. In allogeneic grafts only bone is formed; this bone is subsequently resorbed. In 14-month semisyngeneic transplants the bone marrow consists of recipient cells. This is true for both the proliferating pool and the stem cells of hematopoietic tissue. At the same time, osteogenic precursor cells and bone tissue in these transplants are of donor origin. A discussion is presented of the interrelationship between determinated osteogenic precursor cells (preosteoblasts) and hematopoietic stem cells (or their descendants) in which osteogenesis is inducible.", "title": "Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues." }, { "docid": "26105746", "text": "Solid organ transplant recipients receiving chronic immunosuppressive agents are at increased risk to acquire influenza virus despite vaccination. Myocarditis is a known but rare complication of influenza infection. We present the first adult liver transplant recipient who received prophylactic vaccination but developed influenza A myocarditis. This may occur in solid organ transplant recipients, because they have reduced response to protein vaccines, which may leave them vulnerable to infections. Studies are needed to evaluate if antiviral chemoprophylaxis in solid organ transplant recipients during influenza season would be an effective preventive therapy against influenza in this high-risk population.", "title": "Influenza A myocarditis developing in an adult liver transplant recipient despite vaccination: a case report and review of the literature." }, { "docid": "21232018", "text": "We investigated the capacity of young ovaries, transplanted into old ovariectomized CBA mice, to improve remaining life expectancy of the hosts. Donor females were sexually mature 2-month-olds; recipients were prepubertally ovariectomized at 3 weeks and received transplants at 5, 8 or 11 months of age. Relative to ovariectomized control females, life expectancy at 11 months was increased by 60% in 11-month recipient females and by 40% relative to intact control females. Only 20% of the 11-month transplant females died in the 300-day period following ovarian transplantation, whereas nearly 65% of the ovariectomized control females died during this same period. The 11-month-old recipient females resumed oestrus and continued to cycle up to several months beyond the age of control female reproductive senescence. Across the three recipient age groups, transplantation of young ovaries increased life expectancy in proportion to the relative youth of the ovary. Our results relate to recent findings on the gonadal input upon aging in Caenorhabditis elegans and may suggest how the mammalian gonad, including that of humans, could regulate aging and determine longevity.", "title": "Age of ovary determines remaining life expectancy in old ovariectomized mice." }, { "docid": "9056874", "text": "Prolonged or intensive immunosuppressive therapy used after organ transplantation is complicated by an increased incidence of cancer. Striking differences in incidence are observed in heart and heart-lung transplant recipients when compared with renal transplant patients. The most significant increase was in the incidence of lymphomas in cardiac versus renal patients. Moreover, a two-fold greater increase of all neoplasms was found in cardiac recipients, with nearly a six-fold increase in visceral tumors. Several factors may account for these differences. In cardiac allograft recipients, intensive immunosuppression is frequently used to reverse acute rejection and the highest number of cardiac transplants was performed in the era of polypharmacy, usually consisting of triple therapy.", "title": "Incidence of cancer after immunosuppressive treatment for heart transplantation." }, { "docid": "24795767", "text": "The current study evaluates the role of quantitative measurement of peripheral lymphocyte subsets, especially CD4+ helper T-cell recovery, in predicting transplant outcomes including overall survival (OS) and non-relapse mortality (NRM) after allogeneic stem cell transplantation. A total of 69 allogeneic recipients were included with following diagnoses: acute myeloid leukemia 42, acute lymphoblastic leukemia 5, chronic myeloid leukemia 15, non-Hodgkin's lymphoma 5 and high-risk myelodysplastic syndrome 2. The peripheral lymphocyte subset counts (CD3+ T cells, CD3+4+ helper T cells, CD3+8+ cytotoxic T cells, CD19+ B cells, and CD56+ natural killer cells) were measured at 3, 6 and 12 months. The CD4+ helper T-cell reconstitution at 3 months was strongly correlated with OS (P<0.0001), NRM (P=0.0007), and opportunistic infections (P=0.0108) at the cutoff value of 200 × 106/l CD4+ helper T cells. Rapid CD4+ helper T-cell recovery was also associated with a higher CD4+ helper T-cell transplant dose (P=0.006) and donor type (P<0.001). An early CD4+ helper T-cell recovery at 3 months correlated with a subsequent faster helper T-cell recovery until 12 months, yet not with B-cell recovery. In a multivariate analysis, rapid recovery of CD4+ helper T cells at 3 months was a favorable prognostic factor together with higher CD34+ cell transplant dose in terms of OS (P=0.001) and NRM (P=0.005).", "title": "Rapid helper T-cell recovery above 200 × 106/l at 3 months correlates to successful transplant outcomes after allogeneic stem cell transplantation" }, { "docid": "8190282", "text": "CONTEXT Noninvasive ventilation (NIV) has been associated with lower rates of endotracheal intubation in populations of patients with acute respiratory failure. OBJECTIVE To compare NIV with standard treatment using supplemental oxygen administration to avoid endotracheal intubation in recipients of solid organ transplantation with acute hypoxemic respiratory failure. DESIGN AND SETTING Prospective randomized study conducted at a 14-bed, general intensive care unit of a university hospital. PATIENTS Of 238 patients who underwent solid organ transplantation from December 1995 to October 1997, 51 were treated for acute respiratory failure. Of these, 40 were eligible and 20 were randomized to each group. INTERVENTION Noninvasive ventilation vs standard treatment with supplemental oxygen administration. MAIN OUTCOME MEASURES The need for endotracheal intubation and mechanical ventilation at any time during the study, complications not present on admission, duration of ventilatory assistance, length of hospital stay, and intensive care unit mortality. RESULTS The 2 groups were similar at study entry. Within the first hour of treatment, 14 patients (70%) in the NIV group, and 5 patients (25%) in the standard treatment group improved their ratio of the PaO2 to the fraction of inspired oxygen (FIO2). Over time, a sustained improvement in PaO2 to FIO2 was noted in 12 patients (60%) in the NIV group, and in 5 patients (25%) randomized to standard treatment (P = .03). The use of NIV was associated with a significant reduction in the rate of endotracheal intubation (20% vs 70%; P = .002), rate of fatal complications (20% vs 50%; P = .05), length of stay in the intensive care unit by survivors (mean [SD] days, 5.5 [3] vs 9 [4]; P = .03), and intensive care unit mortality (20% vs 50%; P = .05). Hospital mortality did not differ. CONCLUSIONS These results indicate that transplantation programs should consider NIV in the treatment of selected recipients of transplantation with acute respiratory failure.", "title": "Noninvasive ventilation for treatment of acute respiratory failure in patients undergoing solid organ transplantation: a randomized trial." }, { "docid": "10582939", "text": "CONTEXT Antibody-based induction therapy plus calcineurin inhibitors (CNIs) reduce acute rejection rates in kidney recipients; however, opportunistic infections and toxic CNI effects remain challenging. Reportedly, mesenchymal stem cells (MSCs) have successfully treated graft-vs-host disease. OBJECTIVE To assess autologous MSCs as replacement of antibody induction for patients with end-stage renal disease who undergo ABO-compatible, cross-match-negative kidney transplants from a living-related donor. DESIGN, SETTING, AND PATIENTS One hundred fifty-nine patients were enrolled in this single-site, prospective, open-label, randomized study from February 2008-May 2009, when recruitment was completed. INTERVENTION Patients were inoculated with marrow-derived autologous MSC (1-2 x 10(6)/kg) at kidney reperfusion and two weeks later. Fifty-three patients received standard-dose and 52 patients received low-dose CNIs (80% of standard); 51 patients in the control group received anti-IL-2 receptor antibody plus standard-dose CNIs. MAIN OUTCOME MEASURES The primary measure was 1-year incidence of acute rejection and renal function (estimated glomerular filtration rate [eGFR]); the secondary measure was patient and graft survival and incidence of adverse events. RESULTS Patient and graft survival at 13 to 30 months was similar in all groups. After 6 months, 4 of 53 patients (7.5%) in the autologous MSC plus standard-dose CNI group (95% CI, 0.4%-14.7%; P = .04) and 4 of 52 patients (7.7%) in the low-dose group (95% CI, 0.5%-14.9%; P = .046) compared with 11 of 51 controls (21.6%; 95% CI, 10.5%-32.6%) had biopsy-confirmed acute rejection. None of the patients in either autologous MSC group had glucorticoid-resistant rejection, whereas 4 patients (7.8%) in the control group did (95% CI, 0.6%-15.1%; overall P = .02). Renal function recovered faster among both MSC groups showing increased eGFR levels during the first month after surgery than the control group. Patients receiving standard-dose CNI had a mean difference of 6.2 mL/min per 1.73 m(2) (95% CI, 0.4-11.9; P=.04) and those in the low-dose CNI of 10.0 mL/min per 1.73 m(2) (95% CI, 3.8-16.2; P=.002). Also, during the 1-year follow-up, combined analysis of MSC-treated groups revealed significantly decreased risk of opportunistic infections than the control group (hazard ratio, 0.42; 95% CI, 0.20-0.85, P=.02) CONCLUSION Among patients undergoing renal transplant, the use of autologous MSCs compared with anti-IL-2 receptor antibody induction therapy resulted in lower incidence of acute rejection, decreased risk of opportunistic infection, and better estimated renal function at 1 year. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00658073.", "title": "Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: a randomized controlled trial." }, { "docid": "3090454", "text": "In 93 allograft recipients, the numbers of marrow B-cell precursors on days 80 and 365 correlated with the counts of circulating B cells, suggesting that the posttransplantation B-cell deficiency is at least in part due to insufficient B lymphopoiesis. Factors that could affect B lymphopoiesis were evaluated. The number of marrow B-cell precursors on days 30 and 80 was at least 4-fold lower in patients with grade 2 to 4 acute graft-versus-host disease (GVHD) compared with patients with grade 0 to 1 acute GVHD. The number of B-cell precursors on day 365 was 18-fold lower in patients with extensive chronic GVHD compared with patients with no or limited chronic GVHD. The number of B-cell precursors was not related to CD34 cell dose, type of transplant (marrow versus blood stem cells), donor age, or patient age. It was concluded that posttransplantation B-cell deficiency results in part from inhibition of B lymphopoiesis by GVHD and/or its treatment.", "title": "Factors influencing B lymphopoiesis after allogeneic hematopoietic cell transplantation." }, { "docid": "24724242", "text": "BACKGROUND The absolute risk of fractures in renal transplant patients is 3 times that of matched controls. Most of the symptomatic fractures are peripheral, suggesting a greater compromise of cortical bone. Peripheral quantitative computed tomography (pQCT) is a new imaging technique that allows separate noninvasive evaluations of cortical and trabecular bones. We investigated cortical bone by pQCT in 12 renal transplant patients (seven men and five women) for comparison with 27 normal controls. METHODS pQCT (XCT 960, Stratec, Pforheim, Germany) was performed upon the distal radius of the nondominant forearm (15% the length of the ulna, proximal from the radius end plate). We evaluated total and cortical bone mineral density (TBMD, cBMD), total (cross-sectional) and cortical area (TA, cA), cortical thickness (cThk), endosteal and periosteal circumferences, and the buckling ratio (r/cThK). RESULTS Compared with normal controls transplant patients as a whole showed a significant increase in TA, in endosteal circumference (P < .001), and in the buckling ratio (P < .001) with a significant reduction in cThK (P < .001). Female patients had a marked decrease in cA (51.4 vs 69.3 [pixel n]; P < .0001) and cThK (2.08 vs 2.78 mm; P < .0001). Male patients also had a decrease in cThK (2.54 vs 3.30 mm; P = .0001) and an increase in endosteal perimeter (31.2 vs 26.4 mm; P < .0001). Total time on dialysis prior to renal graft correlated negatively with cortical thickness (r = .62; P < .01). CONCLUSIONS Our results suggest that a marked thinning of cortical bone may explain the increased incidence of peripheral fractures among renal transplant patients.", "title": "Evaluation of cortical bone by peripheral quantitative computed tomography in renal transplant recipients." }, { "docid": "5597586", "text": "OBJECTIVES Patients with AL amyloidosis can benefit from high-dose chemotherapy and autologous stem cell transplantation (ASCT). Transplantation can be challenging due to fluid shifts, sepsis, and cardiac dysrhythmias. Amyloidosis may present with autonomic neuropathy (AN) that renders peritransplant care problematic. The purpose of this study was to determine the outcome of patients with AN during and after ASCT. METHODS We performed a case-control study of patients with AL amyloidosis with associated AN and compared them to a large matched cohort without AN who also underwent ASCT. RESULTS We identified 13 patients with AN who underwent ASCT and a matched control group of 95 patients without AN. Patients with AN had more organs involved (median 2.5 vs 1, p < 0.001) and the conditioning dose of melphalan was often reduced by 30% compared to controls without AN (p = 0.0015). Median duration of hospitalization was similar for both cohorts, as were engraftment kinetics. Atrial fibrillation occurred in all patients with AN but in only 1 control patient (p < 0.0001). Median overall survival (OS) for patients with AN was 29 months but >60 months for controls (p < 0.0001). On univariate analysis, cardiac involvement (p = 0.0132), AN (p = 0.0011), glomerular filtration rate (p = 0.038), number of organs involved (p = 0.0064), and NT-pro-BNP (p = 0.039) all had an impact on OS. On multivariate analysis, AN retained an independent adverse impact on OS. CONCLUSIONS Patients with autonomic neuropathy secondary to AL amyloidosis can undergo autologous stem cell transplantation with relative safety. Autonomic neuropathy is an independent, adverse determinant of survival in these patients.", "title": "Stem cell transplantation in patients with autonomic neuropathy due to primary (AL) amyloidosis." }, { "docid": "13256155", "text": "BACKGROUND Molecularly targeted agents have been reported to have anti-tumour activity for patients whose tumours harbour the matching molecular alteration. These results have led to increased off-label use of molecularly targeted agents on the basis of identified molecular alterations. We assessed the efficacy of several molecularly targeted agents marketed in France, which were chosen on the basis of tumour molecular profiling but used outside their indications, in patients with advanced cancer for whom standard-of-care therapy had failed. METHODS The open-label, randomised, controlled phase 2 SHIVA trial was done at eight French academic centres. We included adult patients with any kind of metastatic solid tumour refractory to standard of care, provided they had an Eastern Cooperative Oncology Group performance status of 0 or 1, disease that was accessible for a biopsy or resection of a metastatic site, and at least one measurable lesion. The molecular profile of each patient's tumour was established with a mandatory biopsy of a metastatic tumour and large-scale genomic testing. We only included patients for whom a molecular alteration was identified within one of three molecular pathways (hormone receptor, PI3K/AKT/mTOR, RAF/MEK), which could be matched to one of ten regimens including 11 available molecularly targeted agents (erlotinib, lapatinib plus trastuzumab, sorafenib, imatinib, dasatinib, vemurafenib, everolimus, abiraterone, letrozole, tamoxifen). We randomly assigned these patients (1:1) to receive a matched molecularly targeted agent (experimental group) or treatment at physician's choice (control group) by central block randomisation (blocks of size six). Randomisation was done centrally with a web-based response system and was stratified according to the Royal Marsden Hospital prognostic score (0 or 1 vs 2 or 3) and the altered molecular pathway. Clinicians and patients were not masked to treatment allocation. Treatments in both groups were given in accordance with the approved product information and standard practice protocols at each institution and were continued until evidence of disease progression. The primary endpoint was progression-free survival in the intention-to-treat population, which was not assessed by independent central review. We assessed safety in any patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, number NCT01771458. FINDINGS Between Oct 4, 2012, and July 11, 2014, we screened 741 patients with any tumour type. 293 (40%) patients had at least one molecular alteration matching one of the 10 available regimens. At the time of data cutoff, Jan 20, 2015, 195 (26%) patients had been randomly assigned, with 99 in the experimental group and 96 in the control group. All patients in the experimental group started treatment, as did 92 in the control group. Two patients in the control group received a molecularly targeted agent: both were included in their assigned group for efficacy analyses, the patient who received an agent that was allowed in the experimental group was included in the experimental group for the purposes of safety analyses, while the other patient, who received a molecularly targeted agent and chemotherapy, was kept in the control group for safety analyses. Median follow-up was 11·3 months (IQR 5·8-11·6) in the experimental group and 11·3 months (8·1-11·6) in the control group at the time of the primary analysis of progression-free survival. Median progression-free survival was 2·3 months (95% CI 1·7-3·8) in the experimental group versus 2·0 months (1·8-2·1) in the control group (hazard ratio 0·88, 95% CI 0·65-1·19, p=0·41). In the safety population, 43 (43%) of 100 patients treated with a molecularly targeted agent and 32 (35%) of 91 patients treated with cytotoxic chemotherapy had grade 3-4 adverse events (p=0·30). INTERPRETATION The use of molecularly targeted agents outside their indications does not improve progression-free survival compared with treatment at physician's choice in heavily pretreated patients with cancer. Off-label use of molecularly targeted agents should be discouraged, but enrolment in clinical trials should be encouraged to assess predictive biomarkers of efficacy.", "title": "Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial." }, { "docid": "25817686", "text": "BACKGROUND Prolonged hypothermia, as occurs during solid organ transplantation, negatively influences transplantation outcome. Proteolysis is one of the deleterious events implicated in preservation injury of organ allografts. This strongly affects graft quality and hence immediate organ function. Since donor catecholamine treatment improves transplantation outcome after renal transplantation, the present study was conducted to examine the influence of dopamine (DA) pretreatment on hypothermia induced proteolysis in endothelial cells subjected to prolonged cold storage. MATERIALS AND METHODS Lactate dehydrogenase (LDH) assay, two-dimensional electrophoresis, ubiquitination analysis, intracellular calcium measurement, and Western blot analysis were performed on human umbilical vein endothelial cells (HUVEC) subjected to hypothermic preservation or not. RESULTS HUVEC were highly susceptible to cold storage, which was reflected by morphological changes, loss of viability, and by significant changes in cellular proteome. DA pretreatment prevented cell death during cold storage. Western blot analysis demonstrated a time dependent up-regulation of calpain 1 and 2 during cold storage, which could be prevented by addition of EDTA. DA pretreatment abolished autoproteolysis of calpain 1. Analysis of ubiquitination revealed a significant increase in ubiquitinated conjugates after cold storage. This was not prevented by DA pretreatment. Neither proteasome nor calpain inhibitors prevented cell death during cold storage. CONCLUSION In endothelial cells subjected to cold preservation, activation of the calpain pathway and the ubiquitin proteasome system occur. Although DA pretreatment inhibits the former, calpain inhibition did not protect endothelial cells during cold storage. DA pretreatment might influence proteolysis, but proteolysis is not the major cause of endothelial cell death.", "title": "Hypothermic preservation up-regulates calpain expression and increases ubiquitination in cultured vascular endothelial cells: influence of dopamine pretreatment." }, { "docid": "11344428", "text": "Leukemia in donor cells (donor cell leukemia; DCL) has been reported as a rare but severe complication of allogeneic stem cell transplantation (SCT). However, the incidence, potential pathogenetic factors, therapeutic options and outcome of patients suffering from DCL and the leukemia risk of their donors are not well defined. A questionnaire survey was carried out within European Blood and Marrow Transplantation Group (EBMT) centers. Ninety-one EBMT centers participated in this survey, covering 10489 allogeneic SCT between 12/1982 and 09/2003. Fourteen cases of DCL, most with a myeloid phenotype (7 cases of acute myeloid leukemia, 3 each of acute lymphocytic leukemia and 1 case of chronic myeloid leukemia) were identified. Demonstration of donor cell origin included molecular analysis of chimerism in most cases. DCL type and cytogenetic alterations were independent from the original disease. The median time between transplantation and diagnosis of DCL was 17 months (4-164). No type of conditioning, donor, graft manipulation, graft-versus-host disease prophylaxis or subsequent complications were identified as risk factors for DCL. Chemotherapy induced remissions in DCL and 2 of 5 patients remain alive in remission after a second transplant. None of the stem cell donors developed hematologic malignancies (median follow-up period of 9 years; range 6-30 years). DCL is an extremely rare complication of allogeneic SCT in which treatment attempts with chemotherapy and a second SCT are justified. Donors are not at an increased risk of developing hematologic malignancies.", "title": "Development of leukemia in donor cells after allogeneic stem cell transplantation--a survey of the European Group for Blood and Marrow Transplantation (EBMT)." }, { "docid": "27910499", "text": "Delayed T cell recovery and restricted T cell receptor (TCR) diversity after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are associated with increased risks of infection and cancer relapse. Technical challenges have limited faithful measurement of TCR diversity after allo-HSCT. Here we combined 5' rapid amplification of complementary DNA ends PCR with deep sequencing to quantify TCR diversity in 28 recipients of allo-HSCT using a single oligonucleotide pair. Analysis of duplicate blood samples confirmed that we accurately determined the frequency of individual TCRs. After 6 months, cord blood-graft recipients approximated the TCR diversity of healthy individuals, whereas recipients of T cell-depleted peripheral-blood stem cell grafts had 28-fold and 14-fold lower CD4(+) and CD8(+) T cell diversities, respectively. After 12 months, these deficiencies had improved for the CD4(+) but not the CD8(+) T cell compartment. Overall, this method provides unprecedented views of T cell repertoire recovery after allo-HSCT and may identify patients at high risk of infection or relapse.", "title": "Quantitative assessment of T-cell repertoire recovery after hematopoietic stem cell transplantation" }, { "docid": "24101431", "text": "Type 1 diabetes mellitus (T1DM) is a chronic metabolic disease that results from cell-mediated autoimmune destruction of insulin-producing cells. In T1DM animal models, it has been shown that the systemic administration of multipotent mesenchymal stromal cells, also referred as to mesenchymal stem cells (MSCs), results in the regeneration of pancreatic islets. Mechanisms underlying this effect are still poorly understood. Our aims were to assess whether donor MSCs (a) differentiate into pancreatic β-cells and (b) modify systemic and pancreatic pathophysiologic markers of T1DM. After the intravenous administration of 5 × 10(5) syngeneic MSCs, we observed that mice with T1DM reverted their hyperglycemia and presented no donor-derived insulin-producing cells. In contrast, 7 and 65 days post-transplantation, MSCs were engrafted into secondary lymphoid organs. This correlated with a systemic and local reduction in the abundance of autoaggressive T cells together with an increase in regulatory T cells. Additionally, in the pancreas of mice with T1DM treated with MSCs, we observed a cytokine profile shift from proinflammatory to antinflammatory. MSC transplantation did not reduce pancreatic cell apoptosis but recovered local expression and increased the circulating levels of epidermal growth factor, a pancreatic trophic factor. Therefore, the antidiabetic effect of MSCs intravenously administered is unrelated to their transdifferentiation potential but to their capability to restore the balance between Th1 and Th2 immunological responses along with the modification of the pancreatic microenvironment. Our data should be taken into account when designing clinical trials aimed to evaluate MSC transplantation in patients with T1DM since the presence of endogenous precursors seems to be critical in order to restore glycemic control.", "title": "The antidiabetic effect of mesenchymal stem cells is unrelated to their transdifferentiation potential but to their capability to restore Th1/Th2 balance and to modify the pancreatic microenvironment." }, { "docid": "44265107", "text": "ContextChronic hepatitis C is the leading cause for liver transplantation in the United States. Intravenous drug use, the major risk factor, accounts for approximately 60% of hepatitis C virus transmission. Information from the United Network of Organ Sharing (UNOS) does not address substance use among liver transplantation patients. ObjectiveTo identify addiction-related criteria for admission to the UNOS liver transplantation waiting list and posttransplantation problems experienced by patients who are prescribed maintenance methadone. Design, Setting, and ParticipantsMail survey of all 97 adult US liver transplantation programs (belonging to UNOS) in March 2000 with telephone follow-up conducted in May and June 2000.Main Outcome MeasuresPrograms' acceptance and management of patients with past or present substance use disorder. ResultsOf the 97 programs surveyed, 87 (90%) responded. All accept applicants with a history of alcoholism or other addictions, including heroin dependence. Eighty-eight percent of the responding programs require at least 6 months of abstinence from alcohol; 83% from illicit drugs. Ninety-four percent have addiction treatment requirements. Consultations from substance abuse specialists are obtained by 86%. Patients receiving methadone maintenance are accepted by 56% of the responding programs. Approximately 180 patients receiving methadone maintenance are reported to have undergone liver transplantation. ConclusionsMost liver transplantation programs have established policies for patients with substance use disorders. Opiate-dependent patients receiving opiate replacement therapy seem underrepresented in transplantation programs. Little anecdotal evidence for negative impact of opiate replacement therapy on liver transplantation outcome was found. Policies requiring discontinuation of methadone in 32% of all programs contradict the evidence base for efficacy of long-term replacement therapies and potentially result in relapse of previously stable patients.", "title": "Liver transplantation and opioid dependence." }, { "docid": "41380943", "text": "During embryonic development, gonadal steroid hormones (androgens and estrogens) are thought to organize the sexual differentiation of the brain in the heterogametic sexes of higher vertebrates (males in mammals, females in birds). Brain differentiation of the homogametic sexes is thought to proceed by default, not requiring sex hormones for sex-specific organization. In gallinaceous birds such as the Japanese quail, female brain organization is thought to develop via estrogen-dependent demasculinization of a default male brain phenotype. We performed male donor-to-female host (MF), female-to-male (FM), male-to-male (MM), and female-to-female (FF) isotopic, isochronic transplantation of the forebrain primordium in Japanese quail embryos before gonadal differentiation had occurred; brain chimeras had a forebrain (including the hypothalamus) originating exclusively from donor cells. MM, FF, and MF chimeras all showed sexual behavior governed by the genetic sex of the host. In contrast, FM chimeras (genetically female forebrain, all other tissues genetically male) showed no mounting and only rudimentary crowing behavior. Although MM, FF, MF, and FM chimeras all showed host-typical production of steroid hormones during embryonic life, only FM chimeras were hypogonadal, had atypical low levels of circulating testosterone in adulthood, and showed reduction (crowing) or absence (mounting) of reproductive behaviors. Morphological features of the medial preoptic nucleus (a sexually dimorphic brain area) also were not male-like in FM males. These data demonstrate a brain-intrinsic, genetically determined component that organizes the sex-typical production of gonadal hormones in adulthood and call for a reevaluation of the mechanisms underlying brain sexual differentiation in other higher-vertebrate species.", "title": "Male Japanese quails with female brains do not show male sexual behaviors." }, { "docid": "31634628", "text": "Cell-free tumor DNA (ctDNA) has the potential to enable non-invasive diagnostic tests for personalized medicine in providing similar molecular information as that derived from invasive tumor biopsies. The histology-independent phase II SHIVA trial matches patients with targeted therapeutics based on previous screening of multiple somatic mutations using metastatic biopsies. To evaluate the utility of ctDNA in this trial, as an ancillary study we performed de novo detection of somatic mutations using plasma DNA compared to metastasis biopsies in 34 patients covering 18 different tumor types, scanning 46 genes and more than 6800 COSMIC mutations with a multiplexed next-generation sequencing panel. In 27 patients, 28 of 29 mutations identified in metastasis biopsies (97%) were detected in matched ctDNA. Among these 27 patients, one additional mutation was found in ctDNA only. In the seven other patients, mutation detection from metastasis biopsy failed due to inadequate biopsy material, but was successful in all plasma DNA samples providing three more potential actionable mutations. These results suggest that ctDNA analysis is a potential alternative and/or replacement to analyses using costly, harmful and lengthy tissue biopsies of metastasis, irrespective of cancer type and metastatic site, for multiplexed mutation detection in selecting personalized therapies based on the patient's tumor genetic content.", "title": "Circulating tumor DNA as a non-invasive substitute to metastasis biopsy for tumor genotyping and personalized medicine in a prospective trial across all tumor types." } ]
218841
Thirteen is a drama film from the United States.
[ { "docid": "Thirteen_(2003_film)", "text": "Thirteen is a 2003 American semi-autobiographical drama film , directed by Catherine Hardwicke , and written by Hardwicke and Nikki Reed , based on events from Reed 's life at age 12 and 13 . It stars Evan Rachel Wood , with Wood 's character `` Tracy '' being loosely based upon Reed . Nikki Reed herself co-stars in the role of Evie Zamora . The script was written in six days . The film caused controversy upon its release , because it dealt with topics like drugs such as inhalants , marijuana , and alcohol , underage sexual behavior , and self-harm . The film earned Holly Hunter an Academy Award nomination for Best Actress in a Supporting Role and Golden Globe nominations for Hunter and Evan Rachel Wood for Best Supporting Actress and Best Actress in a Drama , respectively .", "title": "" } ]
[ { "docid": "Roger_Donaldson", "text": "Roger Donaldson ( born 15 November 1945 ) is an Australian-born New Zealand film director , producer and writer whose films include The World 's Fastest Indian ( 2005 ) , acclaimed 1981 relationship drama Smash Palace , and a run of titles shot in the United States , including the Kevin Costner films No Way Out ( 1987 ) and Thirteen Days ( 2000 ) , and the 1997 disaster film Dante 's Peak .", "title": "" }, { "docid": "Little_Thirteen", "text": "Little Thirteen is a 2012 German drama film directed by Christian Klandt . The film stars Muriel Wimmer as one of three troubled teenagers from different social backgrounds that face various challenges .", "title": "" }, { "docid": "Polisse", "text": "Polisse ( released at some film festivals as Poliss , -LSB- pɔˈlis -RSB- ) is a 2011 French drama film written , directed by and starring Maïwenn . It also stars Joeystarr , Karin Viard , Marina Foïs , Nicolas Duvauchelle , Emmanuelle Bercot and Riccardo Scamarcio . The film centres on the Child Protection Unit ( Brigade de Protection des Mineurs ) of the Paris Police , and a photographer who is assigned to cover the unit . The title is derived from Maïwenn 's son 's misspelling of the word `` police '' . The film won the Jury Prize at the 2011 Cannes Film Festival and in 2012 , was nominated for thirteen César Awards .", "title": "" }, { "docid": "Into_the_Fire_(Thirteen_Senses_song)", "text": "`` Into the Fire '' is a song by English alternative rock band Thirteen Senses , and is the opening track from their debut album , The Invitation . It was the second single released from the album in the United Kingdom on 13 September 2004 ( see 2004 in British music ) . It peaked on the UK Singles Chart at number 35 . The song has featured in many television programs . It was used in the Season 2 preview trailer for the American comedy-drama Rescue Me , as well as in the pilot episode of the medical drama Grey 's Anatomy , in the thirteenth episode of season eight , twelfth episode of season twelve , and again but a cover on episode twenty one of season eleven . Other TV appearances include the Season 3 premiere of The 4400 , Season 2 episode 4 of Pretty Little Liars and a Second Season episode of Tru Calling . It also featured in the French film Les Chevaliers du ciel and the BBC Drama Waterloo Road . It was also featured briefly in A Night Of Heroes , on 21 December 2009 . In February 2011 , a YouTube video montage of the anti-government uprising in Egypt used the song as its soundtrack . The video , edited by Tamaar Shabaan , attracted over one and a half million views in under a week . In 2012 , it was featured on the Burberry website , promoting the new Burberry The Britain watches .", "title": "" }, { "docid": "Mad_Men_(season_3)", "text": "The third season of the American television drama series Mad Men premiered on August 16 , 2009 and concluded on November 8 , 2009 . It consisted of thirteen episodes , each running approximately 47 minutes in length . AMC broadcast the third season on Sundays at 10:00 pm in the United States . Season three takes place six months after the conclusion of the second season ( roughly April/May 1963 ) and ends in December 1963 . It chronicles the end of the `` Camelot era '' as the characters go through immense change in their professional and personal lives . The third season was exalted by television critics and was a major winner in many television awards . Mad Men won the Primetime Emmy Award for Outstanding Drama Series , Golden Globe Award for Best Drama Series , and acknowledgement by the American Film Institute for the third year in a row .", "title": "" }, { "docid": "Dancer_in_the_Dark", "text": "Dancer in the Dark ( Danish : Danser i mørket ) is a 2000 Danish musical drama film directed by Lars von Trier . It stars Icelandic singer Björk as a daydreaming immigrant factory worker who suffers from a degenerative eye condition and is saving up to pay for an operation to prevent her young son from suffering the same fate . Catherine Deneuve , David Morse , Cara Seymour , Peter Stormare , Siobhan Fallon Hogan , and Joel Grey also star . The soundtrack for the film , released as the album Selmasongs , was written mainly by Björk , but a number of songs featured contributions from Mark Bell and the lyrics were by von Trier and Sjón . Three songs from Rodgers and Hammerstein 's The Sound of Music were also used in the film . This is the third film in von Trier 's `` Golden Heart Trilogy '' ; the other two films are Breaking the Waves ( 1996 ) and The Idiots ( 1998 ) . The film was an international co-production among companies based in thirteen countries and regions : Denmark , Argentina , Finland , France , Germany , Iceland , the Netherlands , Norway , Spain , Sweden , Taiwan , the United Kingdom , and the United States . It was shot with a handheld camera , and was somewhat inspired by a Dogme 95 look . Dancer in the Dark premiered at the 2000 Cannes Film Festival to standing ovations and controversy , but was nonetheless awarded the Palme d'Or , along with the Best Actress award for Björk . The song `` I 've Seen It All '' , with Thom Yorke , was nominated for an Academy Award for Best Song but lost to `` Things Have Changed '' by Bob Dylan from Wonder Boys . The film continues to polarize critics , being seen by some as melodramatic and by others as one of the most important films of the 2000s .", "title": "" }, { "docid": "Camp_Thirteen", "text": "Camp Thirteen ( French : Campement 13 ) is a 1940 French drama film directed by Jacques Constant and starring Alice Field , Gabriel Gabrio and Paul Azaïs . It is set amongst a group of workers who are housed in a barracks known as Camp Thirteen .", "title": "" }, { "docid": "Mad_Men_(season_2)", "text": "The second season of the American television drama series Mad Men premiered on July 27 , 2008 and concluded on October 26 , 2008 . It consisted of thirteen episodes , each running approximately 47 minutes in length . AMC broadcast the second season on Sundays at 10:00 pm in the United States ; it would occupy in this timeslot for the remainder of its run . Season two takes place between February and October 1962 , culminating with the Cuban Missile Crisis . It expands on Peggy 's rise in the workplace and the marital strife between Don and Betty Draper as Don 's infidelities further intrude on his family life . The second season also introduces an unknown acquaintance , with whom Don is corresponding by letter in secret . The second season of Mad Men was met with critical acclaim : it was honored with the Primetime Emmy Award for Outstanding Drama Series , the Golden Globe Award for Best Drama Series , and recognition by the American Film Institute , all for the second year in a row .", "title": "" }, { "docid": "Tessa_Ludwick", "text": "Tessa Ludwick ( born October 5 , 1988 ) is a Korean American actress from Apollo Beach , Florida . She began acting at age five , when she held a lead role in Allegra 's Window , a Nick Jr. children 's television program show taped at Universal Studios in Orlando , Florida . When filming on Allegra 's Window ended in May 1996 , seven-year-old Ludwick went from Allegra 's Window to a lead role in Big Bag , a live action television puppet program for preschoolers on the Cartoon Network . At 8 , she landed the role of Kate , an orphan girl in the touring Broadway musical Annie , the 20th Anniversary . For the next eight months , she toured the United States and Canada with the musical , during which time Ludwick gave eight performances per week . In 2003 , Ludwick appeared as the character Yumi in thirteen , an autobiographical drama film based on American film actress Nikki Reed 's experiences as a 12 and 13-year-old girl . In 2004 , Ludwick appeared on Movie Surfers , a Disney Channel mini-show where four teenagers go behind the scenes to report on Walt Disney-related films . Three years later in June 2007 , Ludwick began work on Teen Witch the Musical , a stage musical based on the 1989 fantasy-comedy film Teen Witch .", "title": "" }, { "docid": "The_Invisible_Woman_(2013_film)", "text": "The Invisible Woman is a 2013 British biographical drama film directed by Ralph Fiennes and starring Fiennes , Felicity Jones , Kristin Scott Thomas and Tom Hollander . Written by Abi Morgan , and based on the book The Invisible Woman by Claire Tomalin , the film is about the secret love affair between Charles Dickens and Nelly Ternan , which lasted for thirteen years until his death in 1870 . The film premiered at the Telluride Film Festival on 31 August 2013 , and was released in the United Kingdom on 7 February 2014 . The film received a Best Costume Design nomination ( Michael O'Connor ) at the 86th Academy Awards .", "title": "" }, { "docid": "Mad_Men_(season_4)", "text": "The fourth season of the American television drama series Mad Men premiered on July 25 , 2010 and concluded on October 17 , 2010 . It consisted of thirteen episodes , each running approximately 47 minutes in length . AMC broadcast the fourth season on Sundays at 10:00 pm in the United States . Season four takes place between November 1964 and October 1965 . It is set at the new and considerably more modern advertising agency , Sterling Cooper Draper Pryce . The main narrative of the fourth season is driven by Don Draper 's identity crisis . As Don falls deeper into existential despair , he begins regularly meeting with prostitutes and faces debilitating alcoholism . The fourth season of Mad Men was widely commended by television critics , who viewed it as continuing the show 's excellence in all areas of production while featuring strong character development in addition . Its seventh episode ( `` The Suitcase '' ) garnered especially strong praise . The season received the Primetime Emmy Award for Outstanding Drama Series and recognition from the American Film Institute for the show 's fourth year in a row .", "title": "" }, { "docid": "Ocean's_Thirteen", "text": "Ocean 's Thirteen is a 2007 American comedy heist film directed by Steven Soderbergh and starring an ensemble cast . It is the third and final film in the Soderbergh-directed Ocean 's Trilogy , following the 2004 sequel Ocean 's Twelve and the 2001 film Ocean 's Eleven , which itself was a remake of the 1960 Rat Pack film Ocean 's 11 . All the male cast members reprise their roles from the previous installments , but neither Julia Roberts nor Catherine Zeta-Jones returns . Al Pacino and Ellen Barkin joined the cast as their new targets . Filming began in July 2006 in Las Vegas and Los Angeles , based on a script by Brian Koppelman and David Levien . The film was screened for the Out of Competition presentation at the 2007 Cannes Film Festival . It was released on June 8 , 2007 , in the United States and in several countries in the Middle East on June 6 . It was the 16th highest-grossing film of 2007 .", "title": "" }, { "docid": "Happy_Lesson", "text": "Happy Lesson is a comedy manga , written by Mutsumi Sasaki and illustrated by Shinnosuke Mori , serialized in Dengeki G 's Magazine from April 1999 to September 2002 , featuring a high school student who is adopted by five of his teachers . It was adapted into a five-part OVA series in 2001 ; a thirteen-episode animated TV series in 2002 ; a sequel TV series , called Happy Lesson Advance , in 2003 ; and a second OVA series , Happy Lesson : The Final , in 2004 . The series has also been adapted into a series of drama CDs and a Dreamcast game . The first volume of the manga was licensed and released by A.D. Vision 's ADV Manga label in the United States ; the first three episodes of the OVA and the first TV series were licensed by the ADV Films label for Region 1 distribution .", "title": "" }, { "docid": "Who's_Afraid_of_Virginia_Woolf?_(film)", "text": "Who 's Afraid of Virginia Woolf ? is a 1966 American black comedy-drama film directed by Mike Nichols . The screenplay by Ernest Lehman is an adaptation of the play of the same title by Edward Albee . The film stars Elizabeth Taylor as Martha and Richard Burton as George , with George Segal as Nick and Sandy Dennis as Honey . The film was nominated for thirteen Academy Awards , including Best Picture and Best Director for Mike Nichols , and is one of only two films to be nominated in every eligible category at the Academy Awards ( the other being Cimarron ) . All of the film 's four main actors were nominated in their respective acting categories . The film won five awards , including a second Academy Award for Best Actress for Elizabeth Taylor and the Academy Award for Best Supporting Actress for Sandy Dennis . However , the film lost to A Man for All Seasons for the Best Picture , Best Director , Best Actor and Best Adapted Screenplay awards , and both Richard Burton and George Segal failed to win in their categories . In 2013 , the film was selected for preservation in the United States National Film Registry by the Library of Congress as being `` culturally , historically , or aesthetically significant '' .", "title": "" }, { "docid": "List_of_awards_and_nominations_received_by_Twin_Peaks", "text": "Twin Peaks is an American television serial drama , created by David Lynch and Mark Frost , that aired on the ABC network from April 8 , 1990 to June 10 , 1991 . The series centers on the investigation into the murder of schoolgirl Laura Palmer in the small rural town in Washington state after which the series is named . Since the broadcast of the pilot episode , Twin Peaks earned widespread critical acclaim . The first season earned thirteen Emmy Award nominations -- of which it won two awards -- a Directors Guild of America Award nomination , and won a Casting Society of America Award , two Golden Globe Awards and two Grammy Awards . Lead actor Kyle MacLachlan was twice nominated for an Emmy Award for Outstanding Lead Actor in a Drama Series and won the Golden Globe Award for Best Actor in a Television Series Drama . Piper Laurie , who was nominated for two Emmy Awards -- Outstanding Lead Actress in a Drama Series in 1990 and Outstanding Supporting Actress in a Drama Series in 1991 -- , won the Golden Globe Award for Best Supporting Actress in a Series , Miniseries or Television Film in 1990 .", "title": "" }, { "docid": "My_Place_(TV_series)", "text": "My Place is an Australian children 's television drama series based on the award-winning picture book of the same name by Nadia Wheatley and Donna Rawlins . The series first screened on ABC3 weeknights 8pm from 4 December 2009 and is currently being syndicated in the United States on Vibrant TV Network . My Place is produced by Penny Chapman and directed by Jessica Hobbs , Samantha Lang , Catriona McKenzie , Michael James Rowland and Shawn Seet . The series is accompanied by an interactive website for children that allows them to explore the house that is the series ' main setting . It won the 2010 Logie for Best Children 's Program . On 23 March 2010 Screen Australia announced they approved funding for a second series which will focus on the lives of children and their families from the time period of 1878 to before the White Settlement Filming began on 21 September 2010 and the first of thirteen episodes began airing on 26 June 2011 .", "title": "" }, { "docid": "Notarztwagen_7", "text": "Notarztwagen 7 is a 1976 -- 1977 German medical drama television series directed by Helmut Ashley . It is regarded as a cult television series in Germany . Thirteen 25 minute episodes were produced for ARD and it aired from 1 December 1976 . Notarztwagen means `` Mobile Intensive Care Unit '' . The series portrays the contemporary life of a rescue team , emergency physician and paramedics . It is filmed in and around Frankfurt as well as occasionally in Wiesbaden and set at BG Trauma Clinic Frankfurt am Main . The screenplay was written by Bruno Hampel . The theme tune was composed by Peter Thomas .", "title": "" }, { "docid": "Territorial_evolution_of_the_United_States", "text": "The United States of America was created on July 4 , 1776 , with the declaration of independence of thirteen British colonies . Since then , it has expanded across North America and the seas , growing from the thirteen original states to fifty states and many territories from the western Pacific Ocean to the Caribbean Sea .", "title": "" }, { "docid": "Salomé_(2013_film)", "text": "Salomé is a 2013 American drama film edited from the 2011 film Wilde Salomé , written and directed by Al Pacino , and starring Pacino and Jessica Chastain . It was released theatrically on August 10 , 2013 in the United States and on September 21 , 2014 in the United Kingdom and Ireland . The film is a companion piece to Pacino 's Wilde Salomé , an experimental film which featured a documentary ( mixed with dramatic performances ) based on Oscar Wilde 's play of the same name . Salomé presents instead the narrative and drama elements of the first film in its full form .", "title": "" }, { "docid": "SBS_independent", "text": "SBS independent ( SBSi ) operated as the commissioning house for Australia 's multicultural public broadcaster , the Special Broadcasting Service , between August 1994 and December 2007 . It was instituted via the landmark Creative Nation cultural policy initiative released in October 1994 by the Keating Government . The core purpose of the institution was to commission multicultural content from Australian independent film and television producers . At the end of December 2007 , SBSi ceased to function as an administratively independent institution , and was merged with the SBS Content and Online Division . For the thirteen years that it operated , SBSi commissioned more than 810 titles spanning feature film , animation , television drama , documentary , comedy , variety and reality programs , totalling over 1500 hours of content . This content was often commissioned from inexperienced and early career television and filmmakers , many of whom come from non-English speaking and Indigenous backgrounds . SBSi titles have attracted significant critical acclaim internationally , winning in excess of 450 awards , including a 2003 Academy Award for Adam Elliott 's animated short film , Harvie Krumpet . SBSi was a significant cultural institution that reshaped production and representational practices in the Australian film and television sectors . Most significantly , through collaborative partnerships with other federal and state film financing organisations , SBSi helped to nurture a new generation of Indigenous filmmakers including Ivan Sen , Warwick Thornton and Rachel Perkins . Its commissioned works have been widely recognised through film and television awards and acknowledged by broader community response throughout Australia and overseas . SBSi commissioned feature films , drama series , animation , single documentaries , and documentary series .", "title": "" }, { "docid": "Thirteen_Conversations_About_One_Thing", "text": "Thirteen Conversations About One Thing is a 2001 American drama film directed by Jill Sprecher . The screenplay by Sprecher and her sister Karen focuses on five seemingly disparate individuals in search of happiness whose paths intersect in ways that unexpectedly impact their lives .", "title": "" }, { "docid": "Head_of_State_(film)", "text": "Head of State is a 2003 comedy film directed , written by , and starring Chris Rock and co-starring Bernie Mac . It marked the directorial debut of Rock , who had previously worked as a writer , producer and actor . The film 's title refers to one of the key functions of the President of the United States , as the American head of state . This was the last film by cinematographer Donald E. Thorin , who died in 2016 , having not worked on a film in thirteen years .", "title": "" }, { "docid": "13_Assassins_(2010_film)", "text": "is a 2010 Japanese jidaigeki ( period drama ) film directed by Takashi Miike . The screenplay by Daisuke Tengan is based on the 1963 black-and-white Japanese film of the same name directed by Eiichi Kudo . A samurai epic with a loose historical basis , the film is set in 1844 toward the end of the medieval Edo period , where a group of thirteen assassins ( composed of twelve samurai and a hunter ) secretly plot to assassinate the ruthless leader of the Akashi clan , Lord Matsudaira Naritsugu , before his appointment to the powerful Shogunate Council . The film 's ensemble cast include Kōji Yakusho , Takayuki Yamada , Sōsuke Takaoka , Hiroki Matsukata , and Kazuki Namioka . It is the third film in which Yamada and Takaoka co-starred , the first two being Crows Zero and Crows Zero 2 , both directed by Miike . Filming took place in the course of two months in Tsuruoka , Yamagata , northern Japan , beginning in July 2009 and concluding in September 2009 . Toho released the film in Japan on 25 September 2010 , and Magnet Releasing in the United States on 29 April 2011 . 13 Assassins was met with widespread praise , with critics highlighting its production values , characters , and plot which takes after Akira Kurosawa 's Seven Samurai .", "title": "" }, { "docid": "List_of_Lebanese_submissions_for_the_Academy_Award_for_Best_Foreign_Language_Film", "text": "Lebanon has submitted films for the Academy Award for Best Foreign Language Film since 1978 . The award is handed out annually by the United States Academy of Motion Picture Arts and Sciences to a feature-length motion picture produced outside the United States that contains primarily non-English dialogue . As of 2016 Lebanon has submitted thirteen films for the award , but none has yet been nominated for an Oscar .", "title": "" }, { "docid": "Fourth_State", "text": "Fourth state or Fourth State may refer to : The Fourth State , 2012 German film The fourth state of matter Georgia ( U.S. state ) , one of the original Thirteen Colonies , and the fourth to ratify the Constitution of the United States of America in 1788 Puebla , admitted to the United Mexican States as its fourth state in 1823", "title": "" }, { "docid": "List_of_Luxembourgish_submissions_for_the_Academy_Award_for_Best_Foreign_Language_Film", "text": "The Grand Duchy of Luxembourg has submitted films for the Academy Award for Best Foreign Language Film since 1997 . The Foreign Language Film award is handed out annually by the United States Academy of Motion Picture Arts and Sciences to a feature-length motion picture produced outside the United States that contains primarily non-English dialogue . As of 2016 , thirteen Luxembourgian films have been submitted for the Academy Award for Best Foreign Language Film , but none have yet been nominated for an Academy Award .", "title": "" }, { "docid": "Vanessa_Hudgens", "text": "Vanessa Anne Hudgens ( born December 14 , 1988 ) is an American actress and singer . Hudgens rose to prominence playing Gabriella Montez in the High School Musical series . Hudgens has also appeared in various films and television series for the Disney Channel . She had her feature film debut in the 2003 film Thirteen , a teenage drama in which Hudgens had a supporting role . She had mainstream success following the release of the High School Musical trilogy , and her relationship with co-star Zac Efron was heavily publicized . Her appearance in the series helped make her a household name . Songs from the films also charted worldwide , with the song `` Breaking Free '' peaking inside the Top 10 of the Billboard Hot 100 . This led to Hudgens releasing her debut album , V , on September 26 , 2006 which entered the Billboard 200 at number 24 , and was later certified gold . Her second album , Identified , was released on July 1 , 2008 in the United States . Since the release of her albums and the High School Musical franchise , Hudgens has focused on her acting career . She has appeared in the films Bandslam ( 2009 ) , Beastly ( 2011 ) , Sucker Punch ( 2011 ) , Journey 2 : The Mysterious Island ( 2012 ) , Spring Breakers ( 2013 ) , and Machete Kills ( 2013 ) . She has also played the title role in the Broadway musical Gigi in 2015 , and the role of Rizzo in Grease : Live in 2016 .", "title": "" }, { "docid": "List_of_accolades_received_by_Atonement_(film)", "text": "Atonement is a 2007 British romantic World War II film directed by Joe Wright . Christopher Hampton adapted the screenplay from the eponymous novel by Ian McEwan . The film focuses on fictional lovers Cecilia ( Keira Knightley ) and Robbie ( James McAvoy ) , whose lives are ruined when Cecilia 's younger sister , Briony ( Saoirse Ronan ) , falsely accuses Robbie of a serious crime . The film opened the 64th Venice International Film Festival on 29 August 2007 and competed for the Golden Lion . The following month it screened at the Vancouver International Film Festival and the Toronto International Film Festival . Atonement was released in the United Kingdom by Universal Studios on 7 September 2007 . It was then released in the United States by Focus Features on 7 December 2007 . The film earned over # 84 million in its combined total gross at the box office . Atonement earned many awards and nominations in categories ranging from recognition of the film itself to Hampton 's screenplay and the cast 's acting performances , particularly those of Keira Knightley , James McAvoy and Saoirse Ronan . The film received seven Academy Award nominations and came away with one award for Best Original Score . The Alliance of Women Film Journalists awarded Atonement two accolades from six nominations , while the American Society of Cinematographers and the Art Directors Guild gave the film one nomination apiece . Atonement gathered fourteen nominations at the 61st British Academy Film Awards , the most of any film that year , but ultimately came away with two awards . Cinematographer Seamus McGarvey received a nomination for his work from the British Society of Cinematographers and costume designer , Jacqueline Durran , earned a nomination from the Costume Designers Guild . Atonement won three accolades out of five nominations at the 13th Empire Awards . The film also received five nominations from the Evening Standard British Film Awards , including Best Actress nominations for both Knightley and Romola Garai ( who played Briony aged 18 ) . McGarvey , Durran and Sarah Greenwood were awarded the Best Technical Achievement accolade . At the 65th Golden Globe Awards , Atonement was named Best Drama Motion Picture , while Dario Marianelli won the Golden Globe Award for Best Original Score . The composer would go on to win five more awards for the score , as well as the Film Music Composition of the Year accolade from the International Film Music Critics Association . Intralink Film garnered two nominations from the Golden Trailer Awards and won the Best Romance Trailer category . Ronan won five awards for her performance including Best Actress in a Supporting Role at the 5th Irish Film & Television Awards and Best Young Actress from the Women Film Critics Circle . Atonement earned eight nominations from the London Film Critics ' Circle ; McAvoy and Vanessa Redgrave ( who portrayed an elderly Briony ) won the British Actor of the Year and British Supporting Actress of the Year awards respectively . Knightley won Best International Actress at the 2007 Rembrandt Awards and was given the Choice Movie Drama Actress accolade from the Teen Choice Awards . Hampton earned a total of thirteen nominations for the screenplay .", "title": "" }, { "docid": "The_Song_of_Bernadette_(film)", "text": "The Song of Bernadette is a 1943 drama film that tells the story of Bernadette Soubirous ( later , Saint Bernadette ) , who , from February to July 1858 in Lourdes , France , reported eighteen visions of the Blessed Virgin Mary . It was directed by Henry King . The film was adapted by George Seaton from the 1941 novel The Song of Bernadette , written by Franz Werfel . The novel was extremely popular , spending more than a year on The New York Times Best Seller list and thirteen weeks heading the list . The story was also turned into a Broadway play , which opened at the Belasco Theatre in March 1943 .", "title": "" }, { "docid": "Charity_Case", "text": "`` Charity Case '' is the third episode of the eighth season of the American television medical drama series House and the 158th overall episode of the series . It aired on Fox in the United States on October 17 , 2011 . It is also the penultimate episode with Olivia Wilde as Dr. Remy Hadley ( Thirteen ) . This episode seems loosely based on the American investor Zell Kravinsky , even using his quote that `` to withhold a kidney from someone who would otherwise die means valuing one 's own life at 4,000 times that of a stranger '' .", "title": "" } ]
557
Immune complex triggered cell death leads to sequestration of oxidized mitochondrial DNA.
[ { "docid": "1049501", "text": "Neutrophil extracellular traps (NETs) are implicated in autoimmunity, but how they are generated and their roles in sterile inflammation remain unclear. Ribonucleoprotein immune complexes (RNP ICs), inducers of NETosis, require mitochondrial reactive oxygen species (ROS) for maximal NET stimulation. After RNP IC stimulation of neutrophils, mitochondria become hypopolarized and translocate to the cell surface. Extracellular release of oxidized mitochondrial DNA is proinflammatory in vitro, and when this DNA is injected into mice, it stimulates type I interferon (IFN) signaling through a pathway dependent on the DNA sensor STING. Mitochondrial ROS are also necessary for spontaneous NETosis of low-density granulocytes from individuals with systemic lupus erythematosus. This was also observed in individuals with chronic granulomatous disease, who lack NADPH oxidase activity but still develop autoimmunity and type I IFN signatures. Mitochondrial ROS inhibition in vivo reduces disease severity and type I IFN responses in a mouse model of lupus. Together, these findings highlight a role for mitochondria in the generation not only of NETs but also of pro-inflammatory oxidized mitochondrial DNA in autoimmune diseases.", "title": "Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease" } ]
[ { "docid": "42873134", "text": "Type 1 and type 2 diabetes are characterized by progressive beta-cell failure. Apoptosis is probably the main form of beta-cell death in both forms of the disease. It has been suggested that the mechanisms leading to nutrient- and cytokine-induced beta-cell death in type 2 and type 1 diabetes, respectively, share the activation of a final common pathway involving interleukin (IL)-1beta, nuclear factor (NF)-kappaB, and Fas. We review herein the similarities and differences between the mechanisms of beta-cell death in type 1 and type 2 diabetes. In the insulitis lesion in type 1 diabetes, invading immune cells produce cytokines, such as IL-1beta, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma. IL-1beta and/or TNF-alpha plus IFN-gamma induce beta-cell apoptosis via the activation of beta-cell gene networks under the control of the transcription factors NF-kappaB and STAT-1. NF-kappaB activation leads to production of nitric oxide (NO) and chemokines and depletion of endoplasmic reticulum (ER) calcium. The execution of beta-cell death occurs through activation of mitogen-activated protein kinases, via triggering of ER stress and by the release of mitochondrial death signals. Chronic exposure to elevated levels of glucose and free fatty acids (FFAs) causes beta-cell dysfunction and may induce beta-cell apoptosis in type 2 diabetes. Exposure to high glucose has dual effects, triggering initially \"glucose hypersensitization\" and later apoptosis, via different mechanisms. High glucose, however, does not induce or activate IL-1beta, NF-kappaB, or inducible nitric oxide synthase in rat or human beta-cells in vitro or in vivo in Psammomys obesus. FFAs may cause beta-cell apoptosis via ER stress, which is NF-kappaB and NO independent. Thus, cytokines and nutrients trigger beta-cell death by fundamentally different mechanisms, namely an NF-kappaB-dependent mechanism that culminates in caspase-3 activation for cytokines and an NF-kappaB-independent mechanism for nutrients. This argues against a unifying hypothesis for the mechanisms of beta-cell death in type 1 and type 2 diabetes and suggests that different approaches will be required to prevent beta-cell death in type 1 and type 2 diabetes.", "title": "Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities." }, { "docid": "20456030", "text": "Mitochondria play a pivotal role in energy metabolism, programmed cell death and oxidative stress. Mutated mitochondrial DNA in diseased cells compromises the structure of key enzyme complexes and, therefore, mitochondrial function, which leads to a myriad of health-related conditions such as cancer, neurodegenerative diseases, diabetes and aging. Early detection of mitochondrial and metabolic anomalies is an essential step towards effective diagnoses and therapeutic intervention. Reduced nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) play important roles in a wide range of cellular oxidation-reduction reactions. Importantly, NADH and FAD are naturally fluorescent, which allows noninvasive imaging of metabolic activities of living cells and tissues. Furthermore, NADH and FAD autofluorescence, which can be excited using distinct wavelengths for complementary imaging methods and is sensitive to protein binding and local environment. This article highlights recent developments concerning intracellular NADH and FAD as potential biomarkers for metabolic and mitochondrial activities.", "title": "Intracellular coenzymes as natural biomarkers for metabolic activities and mitochondrial anomalies." }, { "docid": "13380011", "text": "Partial inhibition of mitochondrial respiratory complex I by rotenone reproduces aspects of Parkinson's disease in rodents. The hypothesis that rotenone enhancement of neuronal cell death is attributable to oxidative stress was tested in an acute glutamate excitotoxicity model using primary cultures of rat cerebellar granule neurons. As little as 5 nM rotenone increased mitochondrial superoxide (O2*-) levels and potentiated glutamate-induced cytoplasmic Ca2+ deregulation, the first irreversible stage of necrotic cell death. However, the potent cell-permeant O2*- trap manganese tetrakis (N-ethylpyridinium-2yl) porphyrin failed to prevent the effects of the inhibitor. The bioenergetic consequences of rotenone addition were quantified by monitoring cell respiration. Glutamate activation of NMDA receptors used the full respiratory capacity of the in situ mitochondria, and >80% of the glutamate-stimulated respiration was attributable to increased cellular ATP demand. Rotenone at 20 nM inhibited basal and carbonyl cyanide p-trifluoromethoxyphenylhydrazone-stimulated cell respiration and caused respiratory failure in the presence of glutamate. ATP synthase inhibition by oligomycin was also toxic in the presence of glutamate. We conclude that the cell vulnerability in the rotenone model of partial complex I deficiency under these specific conditions is primarily determined by spare respiratory capacity rather than oxidative stress.", "title": "Spare respiratory capacity rather than oxidative stress regulates glutamate excitotoxicity after partial respiratory inhibition of mitochondrial complex I with rotenone." }, { "docid": "24349992", "text": "Loss of stromal fibroblast caveolin-1 (Cav-1) is a powerful single independent predictor of poor prognosis in human breast cancer patients, and is associated with early tumor recurrence, lymph node metastasis and tamoxifen-resistance. We developed a novel co-culture system to understand the mechanism(s) by which a loss of stromal fibroblast Cav-1 induces a \"lethal tumor micro-environment. \" Here, we propose a new paradigm to explain the powerful prognostic value of stromal Cav-1. In this model, cancer cells induce oxidative stress in cancer-associated fibroblasts, which then acts as a \"metabolic\" and \"mutagenic\" motor to drive tumor-stroma co-evolution, DNA damage and aneuploidy in cancer cells. More specifically, we show that an acute loss of Cav-1 expression leads to mitochondrial dysfunction, oxidative stress and aerobic glycolysis in cancer associated fibroblasts. Also, we propose that defective mitochondria are removed from cancer-associated fibroblasts by autophagy/mitophagy that is induced by oxidative stress. As a consequence, cancer associated fibroblasts provide nutrients (such as lactate) to stimulate mitochondrial biogenesis and oxidative metabolism in adjacent cancer cells (the \"Reverse Warburg Effect\"). We provide evidence that oxidative stress in cancer-associated fibroblasts is sufficient to induce genomic instability in adjacent cancer cells, via a bystander effect, potentially increasing their aggressive behavior. Finally, we directly demonstrate that nitric oxide (NO) over-production, secondary to Cav-1 loss, is the root cause for mitochondrial dysfunction in cancer associated fibroblasts. In support of this notion, treatment with anti-oxidants (such as N-acetyl-cysteine, metformin and quercetin) or NO inhibitors (L-NAME) was sufficient to reverse many of the cancer-associated fibroblast phenotypes that we describe. Thus, cancer cells use \"oxidative stress\" in adjacent fibroblasts (i) as an \"engine\" to fuel their own survival via the stromal production of nutrients and (ii) to drive their own mutagenic evolution towards a more aggressive phenotype, by promoting genomic instability. We also present evidence that the \"field effect\" in cancer biology could also be related to the stromal production of ROS and NO species. eNOS-expressing fibroblasts have the ability to downregulate Cav-1 and induce mitochondrial dysfunction in adjacent fibroblasts that do not express eNOS. As such, the effects of stromal oxidative stress can be laterally propagated, amplified and are effectively \"contagious\"--spread from cell-to-cell like a virus--creating an \"oncogenic/mutagenic\" field promoting widespread DNA damage.", "title": "Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution: A new paradigm for understanding tumor metabolism, the field effect and genomic instability in cancer cells." }, { "docid": "44693226", "text": "Many studies have shown that caloric restriction (40%) decreases mitochondrial reactive oxygen species (ROS) generation in rodents. Moreover, we have recently found that 7 weeks of 40% protein restriction without strong caloric restriction also decreases ROS production in rat liver. This is interesting since it has been reported that protein restriction can also extend longevity in rodents. In the present study we have investigated the possible role of dietary lipids in the effects of caloric restriction on mitochondrial oxidative stress. Using semipurified diets, the ingestion of lipids in male Wistar rats was decreased by 40% below controls, while the other dietary components were ingested at exactly the same level as in animals fed ad libitum. After 7 weeks of treatment the liver mitochondria of lipid-restricted animals showed significant increases in oxygen consumption with complex I-linked substrates (pyruvate/malate and glutamate/malate). Neither mitochondrial H(2)O(2) production nor oxidative damage to mitochondrial or nuclear DNA was modified in lipid-restricted animals. Oxidative damage to mitochondrial DNA was one order of magnitude higher than that of nuclear DNA in both dietary groups. These results deny a role for lipids and reinforce the possible role of dietary proteins as being responsible for the decrease in mitochondrial ROS production and DNA damage in caloric restriction.", "title": "Effect of lipid restriction on mitochondrial free radical production and oxidative DNA damage." }, { "docid": "43054703", "text": "Neutrophil extracellular traps (NETs) are webs of DNA covered with antimicrobial molecules that constitute a newly described killing mechanism in innate immune defense. Previous publications reported that NETs take up to 3-4 h to form via an oxidant-dependent event that requires lytic death of neutrophils. In this study, we describe neutrophils responding uniquely to Staphylococcus aureus via a novel process of NET formation that did not require neutrophil lysis or even breach of the plasma membrane. The multilobular nucleus rapidly became rounded and condensed. During this process, we observed the separation of the inner and outer nuclear membranes and budding of vesicles, and the separated membranes and vesicles were filled with nuclear DNA. The vesicles were extruded intact into the extracellular space where they ruptured, and the chromatin was released. This entire process occurred via a unique, very rapid (5-60 min), oxidant-independent mechanism. Mitochondrial DNA constituted very little if any of these NETs. They did have a limited amount of proteolytic activity and were able to kill S. aureus. With time, the nuclear envelope ruptured, and DNA filled the cytoplasm presumably for later lytic NET production, but this was distinct from the vesicular release mechanism. Panton-Valentine leukocidin, autolysin, and a lipase were identified in supernatants with NET-inducing activity, but Panton-Valentine leukocidin was the dominant NET inducer. We describe a new mechanism of NET release that is very rapid and contributes to trapping and killing of S. aureus.", "title": "A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus." }, { "docid": "13106686", "text": "Immune sensing of DNA is critical for antiviral immunity but can also trigger autoimmune diseases such as lupus erythematosus (LE). Here we have provided evidence for the involvement of a damage-associated DNA modification in the detection of cytosolic DNA. The oxidized base 8-hydroxyguanosine (8-OHG), a marker of oxidative damage in DNA, potentiated cytosolic immune recognition by decreasing its susceptibility to 3' repair exonuclease 1 (TREX1)-mediated degradation. Oxidizative modifications arose physiologically in pathogen DNA during lysosomal reactive oxygen species (ROS) exposure, as well as in neutrophil extracellular trap (NET) DNA during the oxidative burst. 8-OHG was also abundant in UV-exposed skin lesions of LE patients and colocalized with type I interferon (IFN). Injection of oxidized DNA in the skin of lupus-prone mice induced lesions that closely matched respective lesions in patients. Thus, oxidized DNA represents a prototypic damage-associated molecular pattern (DAMP) with important implications for infection, sterile inflammation, and autoimmunity.", "title": "Oxidative damage of DNA confers resistance to cytosolic nuclease TREX1 degradation and potentiates STING-dependent immune sensing." }, { "docid": "4306711", "text": "Human mitochondrial ribosomes are specialized in the synthesis of 13 proteins, which are fundamental components of the oxidative phosphorylation system. The pathway of mitoribosome biogenesis, the compartmentalization of the process, and factors involved remain largely unknown. Here, we have identified the DEAD-box protein DDX28 as an RNA granule component essential for the biogenesis of the mitoribosome large subunit (mt-LSU). DDX28 interacts with the 16S rRNA and the mt-LSU. RNAi-mediated DDX28 silencing in HEK293T cells does not affect mitochondrial mRNA stability or 16S rRNA processing or modification. However, it leads to reduced levels of 16S rRNA and mt-LSU proteins, impaired mt-LSU assembly, deeply attenuated mitochondrial protein synthesis, and consequent failure to assemble oxidative phosphorylation complexes. Our findings identify DDX28 as essential during the early stages of mitoribosome mt-LSU biogenesis, a process that takes place mainly near the mitochondrial nucleoids, in the compartment defined by the RNA granules.", "title": "The Human Mitochondrial DEAD-Box Protein DDX28 Resides in RNA Granules and Functions in Mitoribosome Assembly." }, { "docid": "24923605", "text": "Oxygen and its limitation are emerging as a crucial factor in plant fitness, growth and development. Recent studies revealed the mechanisms by which oxygen is perceived by plant cells. This sensory system partly relies on an oxygen-mediated branch of the N-end rule pathway for protein degradation acting on a specific clade of ethylene responsive transcription factors (ERF-VII). A complementary regulative step is provided by aerobic sequestration of an ERF-VII protein at the plasma membrane and its timely release when hypoxia occurs. Complete absence of oxygen triggers the transient accumulation of reactive hydrogen peroxide and induces an additional set of reactive oxygen species-related genes involved in both signaling and attenuation of oxidative stress. Moreover, temporary hypoxic environments that are built up as consequence of dense cell packing have been demonstrated to trigger cell-fate determination in maize anthers. Similarly, limited oxygen delivery in bulky fruit or tuber tissues growing in aerobic conditions were shown to stimulate anaerobic-like responses. These advances in low-oxygen signaling and its effect on cell development highlight the importance of taking hypoxia into account in agronomical practices as well as in breeding programs.", "title": "Molecular elements of low-oxygen signaling in plants." }, { "docid": "19957813", "text": "Oxidative phosphorylation (OXPHOS) is the major pathway for ATP production in humans. Deficiencies in OXPHOS can arise from mutations in either mitochondrial or nuclear genomes and comprise the largest collection of inborn errors of metabolism. At present we lack a complete catalog of human genes and pathways essential for OXPHOS. Here we introduce a genome-wide CRISPR \"death screen\" that actively selects dying cells to reveal human genes required for OXPHOS, inspired by the classic observation that human cells deficient in OXPHOS survive in glucose but die in galactose. We report 191 high-confidence hits essential for OXPHOS, including 72 underlying known OXPHOS diseases. Our screen reveals a functional module consisting of NGRN, WBSCR16, RPUSD3, RPUSD4, TRUB2, and FASTKD2 that regulates the mitochondrial 16S rRNA and intra-mitochondrial translation. Our work yields a rich catalog of genes required for OXPHOS and, more generally, demonstrates the power of death screening for functional genomic analysis.", "title": "A Genome-wide CRISPR Death Screen Identifies Genes Essential for Oxidative Phosphorylation." }, { "docid": "13651792", "text": "IRGM, a human immunity-related GTPase, confers autophagic defence against intracellular pathogens by an unknown mechanism. Here, we report an unexpected mode of IRGM action. IRGM demonstrated differential affinity for the mitochondrial lipid cardiolipin, translocated to mitochondria, affected mitochondrial fission and induced autophagy. Mitochondrial fission was necessary for autophagic control of intracellular mycobacteria by IRGM. IRGM influenced mitochondrial membrane polarization and cell death. Overexpression of IRGMd, but not IRGMb splice isoforms, caused mitochondrial depolarization and autophagy-independent, but Bax/Bak-dependent, cell death. By acting on mitochondria, IRGM confers autophagic protection or cell death, explaining IRGM action both in defence against tuberculosis and in the damaging inflammation caused by Crohn's disease.", "title": "Human IRGM Regulates Autophagy and Its Cell-Autonomous Immunity Functions Through Mitochondria" }, { "docid": "32665136", "text": "Traumatic spinal cord injury triggers a complex local inflammatory reaction capable of enhancing repair and exacerbating pathology. The composition and effector potential of the post-injury cellular and molecular immune cascade changes as a function of time and distance from the lesion. Production along this time-space continuum of cytokines, proteases, and growth factors establishes dynamic environments that lead to the death, damage, repair or growth of affected neurons and glia. Microenvironmental cues, therefore, generated by the cells therein, may determine these distinct fates of repair versus pathology. To harness repair, it is necessary to manipulate the assembly and phenotype of cells that comprise the neuroinflammatory response to injury. Here, the potential of the neuroinflammatory response to cause outcomes such as pain, regeneration, and functional recovery is reviewed.", "title": "Neuroinflammation in spinal cord injury: therapeutic targets for neuroprotection and regeneration." }, { "docid": "4319844", "text": "Alternative lengthening of telomeres (ALT) is a telomerase-independent telomere maintenance mechanism that occurs in a subset of cancers. By analyzing telomerase-positive cells and their human TERC knockout-derived ALT human cell lines, we show that ALT cells harbor more fragile telomeres representing telomere replication problems. ALT-associated replication defects trigger mitotic DNA synthesis (MiDAS) at telomeres in a RAD52-dependent, but RAD51-independent, manner. Telomeric MiDAS is a conservative DNA synthesis process, potentially mediated by break-induced replication, similar to type II ALT survivors in Saccharomyces cerevisiae Replication stresses induced by ectopic oncogenic expression of cyclin E, G-quadruplexes, or R-loop formation facilitate the ALT pathway and lead to telomere clustering, a hallmark of ALT cancers. The TIMELESS/TIPIN complex suppresses telomere clustering and telomeric MiDAS, whereas the SMC5/6 complex promotes them. In summary, ALT cells exhibit more telomere replication defects that result in persistent DNA damage responses at telomeres, leading to the engagement of telomeric MiDAS (spontaneous mitotic telomere synthesis) that is triggered by DNA replication stress, a potential driver of genomic duplications in cancer.", "title": "Alternative Lengthening of Telomeres Mediated by Mitotic DNA Synthesis Engages Break-Induced Replication Processes." }, { "docid": "39187170", "text": "Adipose tissue exerts important endocrine and metabolic functions in health and disease. Yet the bioenergetics of this tissue is not characterized in humans and possible regional differences are not elucidated. Using high resolution respirometry, mitochondrial respiration was quantified in human abdominal subcutaneous and intra-abdominal visceral (omentum majus) adipose tissue from biopsies obtained in 20 obese patients undergoing bariatric surgery. Mitochondrial DNA (mtDNA) and genomic DNA (gDNA) were determined by the PCR technique for estimation of mitochondrial density. Adipose tissue samples were permeabilized and respirometric measurements were performed in duplicate at 37 degrees C. Substrates (glutamate (G) + malate (M) + octanoyl carnitine (O) + succinate (S)) were added sequentially to provide electrons to complex I + II. ADP ((D)) for state 3 respiration was added after GM. Uncoupled respiration was measured after addition of FCCP. Visceral fat contained more mitochondria per milligram of tissue than subcutaneous fat, but the cells were smaller. Robust, stable oxygen fluxes were found in both tissues, and coupled state 3 (GMOS(D)) and uncoupled respiration were significantly (P < 0.05) higher in visceral (0.95 +/- 0.05 and 1.15 +/- 0.06 pmol O(2) s(1) mg(1), respectively) compared with subcutaneous (0.76 +/- 0.04 and 0.98 +/- 0.05 pmol O(2) s(1) mg(1), respectively) adipose tissue. Expressed per mtDNA, visceral adipose tissue had significantly (P < 0.05) lower mitochondrial respiration. Substrate control ratios were higher and uncoupling control ratio lower (P < 0.05) in visceral compared with subcutaneous adipose tissue. We conclude that visceral fat is bioenergetically more active and more sensitive to mitochondrial substrate supply than subcutaneous fat. Oxidative phosphorylation has a higher relative activity in visceral compared with subcutaneous adipose tissue.", "title": "Mitochondrial respiration in subcutaneous and visceral adipose tissue from patients with morbid obesity." }, { "docid": "935538", "text": "RNA-binding proteins are at the heart of posttranscriptional gene regulation, coordinating the processing, storage, and handling of cellular RNAs. We show here that GRSF1, previously implicated in the binding and selective translation of influenza mRNAs, is targeted to mitochondria where it forms granules that colocalize with foci of newly synthesized mtRNA next to mitochondrial nucleoids. GRSF1 preferentially binds RNAs transcribed from three contiguous genes on the light strand of mtDNA, the ND6 mRNA, and the long noncoding RNAs for cytb and ND5, each of which contains multiple consensus binding sequences. RNAi-mediated knockdown of GRSF1 leads to alterations in mitochondrial RNA stability, abnormal loading of mRNAs and lncRNAs on the mitochondrial ribosome, and impaired ribosome assembly. This results in a specific protein synthesis defect and a failure to assemble normal amounts of the oxidative phosphorylation complexes. These data implicate GRSF1 as a key regulator of posttranscriptional mitochondrial gene expression.", "title": "The mitochondrial RNA-binding protein GRSF1 localizes to RNA granules and is required for posttranscriptional mitochondrial gene expression." }, { "docid": "17368516", "text": "We describe a second primase in human cells, PrimPol, which has the ability to start DNA chains with deoxynucleotides unlike regular primases, which use exclusively ribonucleotides. Moreover, PrimPol is also a DNA polymerase tailored to bypass the most common oxidative lesions in DNA, such as abasic sites and 8-oxoguanine. Subcellular fractionation and immunodetection studies indicated that PrimPol is present in both nuclear and mitochondrial DNA compartments. PrimPol activity is detectable in mitochondrial lysates from human and mouse cells but is absent from mitochondria derived from PRIMPOL knockout mice. PRIMPOL gene silencing or ablation in human and mouse cells impaired mitochondrial DNA replication. On the basis of the synergy observed with replicative DNA polymerases Polγ and Polε, PrimPol is proposed to facilitate replication fork progression by acting as a translesion DNA polymerase or as a specific DNA primase reinitiating downstream of lesions that block synthesis during both mitochondrial and nuclear DNA replication.", "title": "PrimPol, an Archaic Primase/Polymerase Operating in Human Cells" }, { "docid": "28249680", "text": "Proteasome inhibitors induce rapid death of cancer cells. We show that in epithelial cancer cells, such death is associated with dramatic and simultaneous up-regulation of several BH3-only proteins, including BIK, BIM, MCL-1S, NOXA, and PUMA, as well as p53. Elevated levels of these proteins seem to be the result of direct inhibition of their proteasomal degradation, induction of transcription, and active translation. Subsequent cell death is independent of BAX, and probably BAK, and proceeds through the intrinsic mitochondrial apoptosis pathway. We identify the cascade of molecular events responsible for cell death induced by a prototypical proteasome inhibitor, MG132, starting with rapid accumulation of BH3-only proteins in the mitochondria, proceeding through mitochondrial membrane permeabilization and subsequent loss of DeltaPsi(m), and leading to irreversible changes of mitochondrial ultrastructure, degradation of mitochondrial network, and detrimental impairment of crucial mitochondrial functions. Our results also establish a rationale for the broader use of proteasome inhibitors to kill apoptosis-resistant tumor cells that lack functional BAX/BAK proteins.", "title": "BAX/BAK-independent mitoptosis during cell death induced by proteasome inhibition?" }, { "docid": "28107602", "text": "The oncogene MDMX is overexpressed in many cancers, leading to suppression of the tumor suppressor p53. Inhibitors of the oncogene product MDMX therefore might help reactivate p53 and enhance the efficacy of DNA-damaging drugs. However, we currently lack a quantitative understanding of how MDMX inhibition affects the p53 signaling pathway and cell sensitivity to DNA damage. Live cell imaging showed that MDMX depletion triggered two distinct phases of p53 accumulation in single cells: an initial postmitotic pulse, followed by low-amplitude oscillations. The response to DNA damage was sharply different in these two phases; in the first phase, MDMX depletion was synergistic with DNA damage in causing cell death, whereas in the second phase, depletion of MDMX inhibited cell death. Thus a quantitative understanding of signal dynamics and cellular states is important for designing an optimal schedule of dual-drug administration.", "title": "Schedule-dependent interaction between anticancer treatments" }, { "docid": "18473550", "text": "Bisphosphonates are widely used agents for the treatment of malignant bone disease. They inhibit osteoclast-mediated bone resorption and can have direct effects on cancer cells. In this study, we investigated whether the anticancer activity of the third-generation bisphosphonate zoledronic acid (ZOL) could be enhanced by combination with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA). We found that ZOL and SAHA cooperated to induce cell death in the prostate cancer cell lines LNCaP and PC-3. The effect was synergistic, as evidenced by combination index isobologram analysis. ZOL and SAHA synergized to induce dissipation of the mitochondrial transmembrane potential, to activate caspase-3, and to trigger DNA fragmentation, showing that the combination of ZOL and SAHA resulted in the initiation of apoptosis. Because ZOL acts by inhibiting the mevalonate pathway, thereby preventing protein prenylation, we explored whether the mevalonate pathway was also the target of the cooperative action of ZOL and SAHA. We found that geranylgeraniol, but not farnesol, significantly reduced ZOL/SAHA-induced cell death, indicating that the synergistic action of the agents was due to the inhibition of geranylgeranylation. Consistently, a direct inhibitor of geranylgeranylation, GGTI-298, synergized with SAHA to induce cell death, whereas an inhibitor of farnesylation, FTI-277, had no effect. In addition, SAHA synergized with mevastatin, an inhibitor of the proximal enzyme in the mevalonate pathway. These in vitro findings provide a rationale for an in vivo exploration into the potential of combining SAHA and ZOL, or other inhibitors of the mevalonate pathway, as an effective strategy for anticancer therapy.", "title": "Synergistic activity of the histone deacetylase inhibitor suberoylanilide hydroxamic acid and the bisphosphonate zoledronic acid against prostate cancer cells in vitro." }, { "docid": "1834762", "text": "Research on the human microbiome has established that commensal and pathogenic bacteria can influence obesity, cancer, and autoimmunity through mechanisms mostly unknown. We found that a component of bacterial biofilms, the amyloid protein curli, irreversibly formed fibers with bacterial DNA during biofilm formation. This interaction accelerated amyloid polymerization and created potent immunogenic complexes that activated immune cells, including dendritic cells, to produce cytokines such as type I interferons, which are pathogenic in systemic lupus erythematosus (SLE). When given systemically, curli-DNA composites triggered immune activation and production of autoantibodies in lupus-prone and wild-type mice. We also found that the infection of lupus-prone mice with curli-producing bacteria triggered higher autoantibody titers compared to curli-deficient bacteria. These data provide a mechanism by which the microbiome and biofilm-producing enteric infections may contribute to the progression of SLE and point to a potential molecular target for treatment of autoimmunity.", "title": "Amyloid-DNA Composites of Bacterial Biofilms Stimulate Autoimmunity." }, { "docid": "10607877", "text": "Cell surface receptors have been extensively studied because they initiate and regulate signal transduction cascades leading to a variety of functional cellular outcomes. An important class of immune receptors (e.g., T-cell antigen receptors) whose ligands are anchored to the surfaces of other cells remain poorly understood. The mechanism by which ligand binding initiates receptor phosphorylation, a process termed \"receptor triggering\", remains controversial. Recently, direct measurements of the (two-dimensional) receptor-ligand complex lifetimes at cell-cell interface were found to be smaller than (three-dimensional) lifetimes in solution but the underlying mechanism is unknown. At the cell-cell interface, the receptor-ligand complex spans a short intermembrane distance (15 nm) compared to long surface molecules (LSMs) whose ectodomains span >40 nm and these LSMs include phosphatases (e.g., CD45) that dephosphorylate the receptor. It has been proposed that size-based segregation of LSMs from a receptor-ligand complex is a mechanism of receptor triggering but it is unclear whether the mechanochemistry supports such small-scale segregation. Here we present a nanometer-scale mathematical model that couples membrane elasticity with the compressional stiffness and lateral mobility of LSMs. We find robust supradiffusive segregation of LSMs from a single receptor-ligand complex. The model predicts that LSM redistribution will result in a time-dependent tension on the complex leading to a decreased two-dimensional lifetime. Interestingly, the model predicts a nonlinear relationship between the three- and two-dimensional lifetimes, which can enhance the ability of receptors to discriminate between similar ligands.", "title": "Mechanical modulation of receptor-ligand interactions at cell-cell interfaces." }, { "docid": "25251625", "text": "The use of caspase inhibitors has revealed the existence of alternative backup cell death programs for apoptosis. The broad-spectrum caspase inhibitor zVAD-fmk modulates the three major types of cell death. Addition of zVAD-fmk blocks apoptotic cell death, sensitizes cells to necrotic cell death, and induces autophagic cell death. Several studies have shown a crucial role for the kinase RIP1 and the adenosine nucleotide translocator (ANT)-cyclophilin D (CypD) complex in necrotic cell death. The underlying mechanism of zVAD-fmk-mediated sensitization to necrotic cell death involves the inhibition of caspase-8-mediated proteolysis of RIP1 and disturbance of the ANT-CypD interaction. RIP1 is also involved in autophagic cell death. Caspase inhibitors and knockdown studies have revealed negative roles for catalase and caspase-8 in autophagic cell death. The positive role of RIP1 and the negative role of caspase-8 in both necrotic and autophagic cell death suggest that the pathways of these two types of cell death are interconnected. Necrotic cell death represents a rapid cellular response involving mitochondrial reactive oxygen species (ROS) production, decreased adenosine triphosphate concentration, and other cellular insults, whereas autophagic cell death first starts as a survival attempt by cleaning up ROS-damaged mitochondria. However, when this process occurs in excess, autophagy itself becomes cytotoxic and eventually leads to autophagic cell death. A better understanding of the molecular mechanisms of these alternative cell death pathways may provide therapeutic tools to combat cell death associated with neurodegenerative diseases, ischemia-reperfusion pathologies, and infectious diseases, and may also facilitate the development of alternative cytotoxic strategies in cancer treatment.", "title": "Caspase inhibitors promote alternative cell death pathways." }, { "docid": "38623601", "text": "Autophagy is the principal catabolic response to nutrient starvation and is necessary to clear dysfunctional or damaged organelles, but excessive autophagy can be cytotoxic or cytostatic and contributes to cell death. Depending on the abundance of enzymes involved in molecule biosynthesis, cells can be dependent on uptake of exogenous nutrients to provide these molecules. Argininosuccinate synthetase 1 (ASS1) is a key enzyme in arginine biosynthesis, and its abundance is reduced in many solid tumors, making them sensitive to external arginine depletion. We demonstrated that prolonged arginine starvation by exposure to ADI-PEG20 (pegylated arginine deiminase) induced autophagy-dependent death of ASS1-deficient breast cancer cells, because these cells are arginine auxotrophs (dependent on uptake of extracellular arginine). Indeed, these breast cancer cells died in culture when exposed to ADI-PEG20 or cultured in the absence of arginine. Arginine starvation induced mitochondrial oxidative stress, which impaired mitochondrial bioenergetics and integrity. Furthermore, arginine starvation killed breast cancer cells in vivo and in vitro only if they were autophagy-competent. Thus, a key mechanism underlying the lethality induced by prolonged arginine starvation was the cytotoxic autophagy that occurred in response to mitochondrial damage. Last, ASS1 was either low in abundance or absent in more than 60% of 149 random breast cancer biosamples, suggesting that patients with such tumors could be candidates for arginine starvation therapy.", "title": "Arginine Starvation Impairs Mitochondrial Respiratory Function in ASS1-Deficient Breast Cancer Cells" }, { "docid": "23403754", "text": "In this review I summarize interrelations between bioenergetic processes and such programmed death phenomena as cell suicide (apoptosis and necrosis) and mitochondrial suicide (mitoptosis). The following conclusions are made. (I) ATP and rather often mitochondrial hyperpolarization (i.e. an increase in membrane potential, ΔΨ) are required for certain steps of apoptosis and necrosis. (II) Apoptosis, even if it is accompanied by ΔΨ and [ATP] increases at its early stage, finally results in a ΔΨ collapse and ATP decrease. (III) Moderate (about three-fold) lowering of [ATP] for short and long periods of time induces apoptosis and necrosis, respectively. In some types of apoptosis and necrosis, the cell death is mediated by a ΔΨ-dependent overproduction of ROS by the initial (Complex I) and the middle (Complex III) spans of the respiratory chain. ROS initiate mitoptosis which is postulated to rid the intracellular population of mitochondria from those that are ROS overproducing. Massive mitoptosis can result in cell death due to release to cytosol of the cell death proteins normally hidden in the mitochondrial intermembrane space.", "title": "Bioenergetic aspects of apoptosis, necrosis and mitoptosis" }, { "docid": "37362689", "text": "The bulk of ATP consumed by various cellular processes in higher eukaryotes is normally produced by five multimeric protein complexes (I-V) embedded within the inner mitochondrial membrane, in a process known as oxidative phosphorylation (OXPHOS). Maintenance of energy homeostasis under most physiological conditions is therefore contingent upon the ability of OXPHOS to meet cellular changes in bioenergetic demand, with a chronic failure to do so being a frequent cause of human disease. With the exception of Complex II, the structural subunits of OXPHOS complexes are encoded by both the nuclear and the mitochondrial genomes. The physical separation of the two genomes necessitates that the expression of the 13 mitochondrially encoded polypeptides be co-ordinated with that of relevant nuclear-encoded partners in order to assemble functional holoenzyme complexes. Complex biogenesis is a highly ordered process, and several nuclear-encoded factors that function at distinct stages in the assembly of individual OXPHOS complexes have been identified.", "title": "Oxidative phosphorylation: synthesis of mitochondrially encoded proteins and assembly of individual structural subunits into functional holoenzyme complexes." }, { "docid": "1103795", "text": "Antibiotic mode-of-action classification is based upon drug-target interaction and whether the resultant inhibition of cellular function is lethal to bacteria. Here we show that the three major classes of bactericidal antibiotics, regardless of drug-target interaction, stimulate the production of highly deleterious hydroxyl radicals in Gram-negative and Gram-positive bacteria, which ultimately contribute to cell death. We also show, in contrast, that bacteriostatic drugs do not produce hydroxyl radicals. We demonstrate that the mechanism of hydroxyl radical formation induced by bactericidal antibiotics is the end product of an oxidative damage cellular death pathway involving the tricarboxylic acid cycle, a transient depletion of NADH, destabilization of iron-sulfur clusters, and stimulation of the Fenton reaction. Our results suggest that all three major classes of bactericidal drugs can be potentiated by targeting bacterial systems that remediate hydroxyl radical damage, including proteins involved in triggering the DNA damage response, e.g., RecA.", "title": "A Common Mechanism of Cellular Death Induced by Bactericidal Antibiotics" }, { "docid": "9878167", "text": "Neutrophil extracellular traps (NETs) represent extracellular structures able to bind and kill microorganisms. It is believed that they are generated by neutrophils undergoing cell death, allowing these dying or dead cells to kill microbes. We show that, following priming with granulocyte/macrophage colony-stimulating factor (GM-CSF) and subsequent short-term toll-like receptor 4 (TLR4) or complement factor 5a (C5a) receptor stimulation, viable neutrophils are able to generate NETs. Strikingly, NETs formed by living cells contain mitochondrial, but no nuclear, DNA. Pharmacological or genetic approaches to block reactive oxygen species (ROS) production suggested that NET formation is ROS dependent. Moreover, neutrophil populations stimulated with GM-CSF and C5a showed increased survival compared with resting neutrophils, which did not generate NETs. In conclusion, mitochondrial DNA release by neutrophils and NET formation do not require neutrophil death and do also not limit the lifespan of these cells.", "title": "Viable neutrophils release mitochondrial DNA to form neutrophil extracellular traps" }, { "docid": "19922508", "text": "Reactive oxygen species (ROS) are potentially harmful to cells because of their ability to oxidize cell constituents such as DNA, proteins, and lipids. However, at low levels, and under tight control, this feature makes them excellent modifiers in a variety of signal transduction pathways, including autophagy. Autophagy was traditionally associated with oxidative stress, acting in the degradation of oxidized proteins and organelles. Recently, a signaling role was suggested for ROS in the regulation of autophagy, leading, under different circumstances, either to survival or to death. To study the effects of ROS on this pathway, one must determine the localization, intensity, kinetics, and essentiality of the oxidative signal in autophagy. Moreover, once characterized, detection and manipulation of ROS formation could be used to monitor and control autophagic activity. In this chapter we discuss methods to examine ROS in the context of autophagy.", "title": "Monitoring starvation-induced reactive oxygen species formation." }, { "docid": "2543135", "text": "Autophagy plays a central role in regulating important cellular functions such as cell survival during starvation and control of infectious pathogens. Recently, it has been shown that autophagy can induce cells to die; however, the mechanism of the autophagic cell death program is unclear. We now show that caspase inhibition leading to cell death by means of autophagy involves reactive oxygen species (ROS) accumulation, membrane lipid oxidation, and loss of plasma membrane integrity. Inhibition of autophagy by chemical compounds or knocking down the expression of key autophagy proteins such as ATG7, ATG8, and receptor interacting protein (RIP) blocks ROS accumulation and cell death. The cause of abnormal ROS accumulation is the selective autophagic degradation of the major enzymatic ROS scavenger, catalase. Caspase inhibition directly induces catalase degradation and ROS accumulation, which can be blocked by autophagy inhibitors. These findings unveil a molecular mechanism for the role of autophagy in cell death and provide insight into the complex relationship between ROS and nonapoptotic programmed cell death.", "title": "Autophagic programmed cell death by selective catalase degradation." }, { "docid": "16242975", "text": "In mammalian mitochondria, 22 species of tRNAs encoded in mitochondrial DNA play crucial roles in the translation of 13 essential subunits of the respiratory chain complexes involved in oxidative phosphorylation. Following transcription, mitochondrial tRNAs are modified by nuclear-encoded tRNA-modifying enzymes. These modifications are required for the proper functioning of mitochondrial tRNAs (mt tRNAs), and the absence of these modifications can cause pathological consequences. To date, however, the information available about these modifications has been incomplete. To address this issue, we isolated all 22 species of mt tRNAs from bovine liver and comprehensively determined the post-transcriptional modifications in each tRNA by mass spectrometry. Here, we describe the primary structures with post-transcriptional modifications of seven species of mt tRNAs which were previously uncharacterized, and provide revised information regarding base modifications in five other mt tRNAs. In the complete set of bovine mt tRNAs, we found 15 species of modified nucleosides at 118 positions (7.48% of total bases). This result provides insight into the molecular mechanisms underlying the decoding system in mammalian mitochondria and enables prediction of candidate tRNA-modifying enzymes responsible for each modification of mt tRNAs.", "title": "A complete landscape of post-transcriptional modifications in mammalian mitochondrial tRNAs" } ]
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Diabetes remission occurs more in people treated with conventional therapy than in people treated with laparoscopic adjustable gastric banding surgery.
[ { "docid": "7098463", "text": "CONTEXT Observational studies suggest that surgically induced loss of weight may be effective therapy for type 2 diabetes. OBJECTIVE To determine if surgically induced weight loss results in better glycemic control and less need for diabetes medications than conventional approaches to weight loss and diabetes control. DESIGN, SETTING, AND PARTICIPANTS Unblinded randomized controlled trial conducted from December 2002 through December 2006 at the University Obesity Research Center in Australia, with general community recruitment to established treatment programs. Participants were 60 obese patients (BMI >30 and <40) with recently diagnosed (<2 years) type 2 diabetes. INTERVENTIONS Conventional diabetes therapy with a focus on weight loss by lifestyle change vs laparoscopic adjustable gastric banding with conventional diabetes care. MAIN OUTCOME MEASURES Remission of type 2 diabetes (fasting glucose level <126 mg/dL [7.0 mmol/L] and glycated hemoglobin [HbA1c] value <6.2% while taking no glycemic therapy). Secondary measures included weight and components of the metabolic syndrome. Analysis was by intention-to-treat. RESULTS Of the 60 patients enrolled, 55 (92%) completed the 2-year follow-up. Remission of type 2 diabetes was achieved by 22 (73%) in the surgical group and 4 (13%) in the conventional-therapy group. Relative risk of remission for the surgical group was 5.5 (95% confidence interval, 2.2-14.0). Surgical and conventional-therapy groups lost a mean (SD) of 20.7% (8.6%) and 1.7% (5.2%) of weight, respectively, at 2 years (P < .001). Remission of type 2 diabetes was related to weight loss (R2 = 0.46, P < .001) and lower baseline HbA1c levels (combined R2 = 0.52, P < .001). There were no serious complications in either group. CONCLUSIONS Participants randomized to surgical therapy were more likely to achieve remission of type 2 diabetes through greater weight loss. These results need to be confirmed in a larger, more diverse population and have long-term efficacy assessed. TRIAL REGISTRATION actr.org Identifier: ACTRN012605000159651.", "title": "Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial." } ]
[ { "docid": "5824985", "text": "BACKGROUND Bariatric surgery is becoming a more widespread treatment for obesity. Comprehensive evidence of the long-term effects of contemporary surgery on a broad range of clinical outcomes in large populations treated in routine clinical practice is lacking. The objective of this study was to measure the association between bariatric surgery, weight, body mass index, and obesity-related co-morbidities. METHODS AND FINDINGS This was an observational retrospective cohort study using data from the United Kingdom Clinical Practice Research Datalink. All 3,882 patients registered in the database and with bariatric surgery on or before 31 December 2014 were included and matched by propensity score to 3,882 obese patients without surgery. The main outcome measures were change in weight and body mass index over 4 y; incident diagnoses of type 2 diabetes mellitus (T2DM), hypertension, angina, myocardial infarction (MI), stroke, fractures, obstructive sleep apnoea, and cancer; mortality; and resolution of hypertension and T2DM. Weight measures were available for 3,847 patients between 1 and 4 mo, 2,884 patients between 5 and 12 mo, and 2,258 patients between 13 and 48 mo post-procedure. Bariatric surgery patients exhibited rapid weight loss for the first four postoperative months, at a rate of 4.98 kg/mo (95% CI 4.88-5.08). Slower weight loss was sustained to the end of 4 y. Gastric bypass (6.56 kg/mo) and sleeve gastrectomy (6.29 kg/mo) were associated with greater initial weight reduction than gastric banding (2.77 kg/mo). Protective hazard ratios (HRs) were detected for bariatric surgery for incident T2DM, 0.68 (95% CI 0.55-0.83); hypertension, 0.35 (95% CI 0.27-0.45); angina, 0.59 (95% CI 0.40-0.87);MI, 0.28 (95% CI 0.10-0.74); and obstructive sleep apnoea, 0.55 (95% CI 0.40-0.87). Strong associations were found between bariatric surgery and the resolution of T2DM, with a HR of 9.29 (95% CI 6.84-12.62), and between bariatric surgery and the resolution of hypertension, with a HR of 5.64 (95% CI 2.65-11.99). No association was detected between bariatric surgery and fractures, cancer, or stroke. Effect estimates for mortality found no protective association with bariatric surgery overall, with a HR of 0.97 (95% CI 0.66-1.43). The data used were recorded for the management of patients in primary care and may be subject to inaccuracy, which would tend to lead to underestimates of true relative effect sizes. CONCLUSIONS Bariatric surgery as delivered in the UK healthcare system is associated with dramatic weight loss, sustained at least 4 y after surgery. This weight loss is accompanied by substantial improvements in pre-existing T2DM and hypertension, as well as a reduced risk of incident T2DM, hypertension, angina, MI, and obstructive sleep apnoea. Widening the availability of bariatric surgery could lead to substantial health benefits for many people who are morbidly obese.", "title": "Bariatric Surgery in the United Kingdom: A Cohort Study of Weight Loss and Clinical Outcomes in Routine Clinical Care." }, { "docid": "32850528", "text": "OBJECTIVE To evaluate serum amylase and lipase levels and the rate of acute pancreatitis in patients with type 2 diabetes and high cardiovascular risk randomized to liraglutide or placebo and observed for 3.5-5.0 years. RESEARCH DESIGN AND METHODS A total of 9,340 patients with type 2 diabetes were randomized to either liraglutide or placebo (median observation time 3.84 years). Fasting serum lipase and amylase were monitored. Acute pancreatitis was adjudicated in a blinded manner. RESULTS Compared with the placebo group, liraglutide-treated patients had increases in serum lipase and amylase of 28.0% and 7.0%, respectively. Levels were increased at 6 months and then remained stable. During the study, 18 (0.4% [1.1 events/1,000 patient-years of observation] [PYO]) liraglutide-treated and 23 (0.5% [1.7 events/1,000 PYO]) placebo patients had acute pancreatitis confirmed by adjudication. Most acute pancreatitis cases occurred ≥12 months after randomization. Liraglutide-treated patients with prior history of pancreatitis (n = 147) were not more likely to develop acute pancreatitis than similar patients in the placebo group (n = 120). Elevations of amylase and lipase levels did not predict future risk of acute pancreatitis (positive predictive value <1.0%) in patients treated with liraglutide. CONCLUSIONS In a population with type 2 diabetes at high cardiovascular risk, there were numerically fewer events of acute pancreatitis among liraglutide-treated patients (regardless of previous history of pancreatitis) compared with the placebo group. Liraglutide was associated with increases in serum lipase and amylase, which were not predictive of an event of subsequent acute pancreatitis.", "title": "Amylase, Lipase, and Acute Pancreatitis in People With Type 2 Diabetes Treated With Liraglutide: Results From the LEADER Randomized Trial." }, { "docid": "25816994", "text": "BACKGROUND Angiotensin receptor blockers (ARB) and angiotensin converting enzyme (ACE) inhibitors are known to reduce proteinuria. Their combination might be more effective than either treatment alone, but long-term data for comparative changes in renal function are not available. We investigated the renal effects of ramipril (an ACE inhibitor), telmisartan (an ARB), and their combination in patients aged 55 years or older with established atherosclerotic vascular disease or with diabetes with end-organ damage. METHODS The trial ran from 2001 to 2007. After a 3-week run-in period, 25 620 participants were randomly assigned to ramipril 10 mg a day (n=8576), telmisartan 80 mg a day (n=8542), or to a combination of both drugs (n=8502; median follow-up was 56 months), and renal function and proteinuria were measured. The primary renal outcome was a composite of dialysis, doubling of serum creatinine, and death. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00153101. FINDINGS 784 patients permanently discontinued randomised therapy during the trial because of hypotensive symptoms (406 on combination therapy, 149 on ramipril, and 229 on telmisartan). The number of events for the composite primary outcome was similar for telmisartan (n=1147 [13.4%]) and ramipril (1150 [13.5%]; hazard ratio [HR] 1.00, 95% CI 0.92-1.09), but was increased with combination therapy (1233 [14.5%]; HR 1.09, 1.01-1.18, p=0.037). The secondary renal outcome, dialysis or doubling of serum creatinine, was similar with telmisartan (189 [2.21%]) and ramipril (174 [2.03%]; HR 1.09, 0.89-1.34) and more frequent with combination therapy (212 [2.49%]: HR 1.24, 1.01-1.51, p=0.038). Estimated glomerular filtration rate (eGFR) declined least with ramipril compared with telmisartan (-2.82 [SD 17.2] mL/min/1.73 m(2)vs -4.12 [17.4], p<0.0001) or combination therapy (-6.11 [17.9], p<0.0001). The increase in urinary albumin excretion was less with telmisartan (p=0.004) or with combination therapy (p=0.001) than with ramipril. INTERPRETATION In people at high vascular risk, telmisartan's effects on major renal outcomes are similar to ramipril. Although combination therapy reduces proteinuria to a greater extent than monotherapy, overall it worsens major renal outcomes.", "title": "Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial." }, { "docid": "750781", "text": "BACKGROUND Few studies have compared long-term status of bypass grafts between patients with and without diabetes, and uncertainty exists as to whether diabetes independently predicts poor clinical outcome after CABG. METHODS AND RESULTS Among 1526 patients in BARI who underwent CABG as initial revascularization, 99 of 292 (34%) with treated diabetes mellitus (TDM) (those on insulin or oral hypoglycemic agents) and 469 of 1234 (38%) without TDM had follow-up angiography. Angiograms with the longest interval from initial surgery and before any percutaneous graft intervention (mean 3.9 years) were reviewed. An average of 3.0 grafts were placed at initial CABG for patients with TDM (n=297; internal mammary artery [IMA], 33%) and 2.9 grafts for patients without TDM (n=1347; IMA, 34%). Patients with TDM were more likely than those without to have small (<1.5 mm) grafted distal vessels (29% versus 22%) and vessels of poor quality (9% versus 6%). On follow-up angiography, 89% of IMA grafts were free of stenoses > or =50% among patients with TDM versus 85% among patients without TDM (P=0.23). For vein grafts, the corresponding percentages were 71% versus 75% (P=0.40). After statistical adjustment, TDM was unrelated to having a graft stenosis > or =50% (adjusted odds ratio, 0.87; 95% CI, 0.58 to 1.32). CONCLUSIONS Despite diabetic patients' having smaller distal vessels and vessels judged to be of poorer quality, diabetes does not appear to adversely affect patency of IMA or vein grafts over an average of 4-year follow-up. Previously observed differences in survival between CABG-treated patients with and without diabetes may be largely a result of differential risk of mortality from noncardiac causes.", "title": "Coronary bypass graft patency in patients with diabetes in the Bypass Angioplasty Revascularization Investigation (BARI)." }, { "docid": "16390264", "text": "OBJECTIVES To determine the extent to which type of hospital admission (emergency compared with elective) and surgical procedure varied by socioeconomic circumstances, age, sex, and year of admission for colorectal, breast, and lung cancer. DESIGN Repeated cross sectional study with data from individual patients, 1 April 1999 to 31 March 2006. SETTING Hospital episode statistics (HES) dataset. PARTICIPANTS 564 821 patients aged 50 and over admitted with a diagnosis of colorectal, breast, or lung cancer. MAIN OUTCOME MEASURES Proportion of patients admitted as emergencies, and the proportion receiving the recommended surgical treatment. RESULTS Patients from deprived areas, older people, and women were more likely to be admitted as emergencies. For example, the adjusted odds ratio for patients with breast cancer in the least compared with most deprived fifth of deprivation was 0.63 (95% confidence interval 0.60 to 0.66) and the adjusted odds ratio for patients with lung cancer aged 80-89 compared with those aged 50-59 was 3.13 (2.93 to 3.34). There were some improvements in disparities between age groups but not for patients living in deprived areas over time. Patients from deprived areas were less likely to receive preferred procedures for rectal, breast, and lung cancer. These findings did not improve with time. For example, 67.4% (3529/5237) of patients in the most deprived fifth of deprivation had anterior resection for rectal cancer compared with 75.5% (4497/5959) of patients in the least deprived fifth (1.34, 1.22 to 1.47). Over half (54.0%, 11 256/20 849) of patients in the most deprived fifth of deprivation had breast conserving surgery compared with 63.7% (18 445/28 960) of patients in the least deprived fifth (1.21, 1.16 to 1.26). Men were less likely than women to undergo anterior resection and lung cancer resection and older people were less likely to receive breast conserving surgery and lung cancer resection. For example, the adjusted odds ratio for lung cancer patients aged 80-89 compared with those aged 50-59 was 0.52 (0.46 to 0.59). Conclusions Despite the implementation of the NHS Cancer Plan, social factors still strongly influence access to and the provision of care.", "title": "Social variations in access to hospital care for patients with colorectal, breast, and lung cancer between 1999 and 2006: retrospective analysis of hospital episode statistics" }, { "docid": "24921368", "text": "Impaired awareness of hypoglycaemia (IAH) is an acquired complication of insulin therapy, which affects people with type 1 and insulin-treated type 2 diabetes mellitus, whereby the ability to perceive the onset of hypoglycaemia becomes diminished or absent. Deficiencies of the counter-regulatory hormonal responses to hypoglycaemia usually co-exist. The development of IAH and counter-regulatory failure greatly increases the risk of severe hypoglycaemia. Scoring systems have been developed that can be used in the clinical setting and assist with identification of this group of individuals at risk of severe hypoglycaemia. The mainstay of treatment of IAH is the scrupulous avoidance of hypoglycaemia.", "title": "Impaired awareness of hypoglycaemia: a review." }, { "docid": "3190689", "text": "BACKGROUND Laparoscopic adhesiolysis for chronic abdominal pain is controversial and is not evidence based. We aimed to test our hypothesis that laparoscopic adhesiolysis leads to substantial pain relief and improvement in quality of life in patients with adhesions and chronic abdominal pain. METHODS Patients had diagnostic laparoscopy for chronic abdominal pain attributed to adhesions; other causes for their pain had been excluded. If adhesions were confirmed during diagnostic laparoscopy, patients were randomly assigned either to laparoscopic adhesiolysis or no treatment. Treatment allocation was concealed from patients, and assessors were unaware of patients' treatment and outcome. Pain was assessed for 1 year by visual analogue score (VAS) score (scale 0-100), pain change score, use of analgesics, and quality of life score. Analysis was by intention to treat. FINDINGS Of 116 patients enrolled for diagnostic laparoscopy, 100 were randomly allocated either laparoscopic adhesiolysis (52) or no treatment (48). Both groups reported substantial pain relief and a significantly improved quality of life, but there was no difference between the groups (mean change from baseline of VAS score at 12 months: difference 3 points, p=0.53; 95% CI -7 to 13). INTERPRETATION Although laparoscopic adhesiolysis relieves chronic abdominal pain, it is not more beneficial than diagnostic laparoscopy alone. Therefore, laparoscopic adhesiolysis cannot be recommended as a treatment for adhesions in patients with chronic abdominal pain.", "title": "Laparoscopic adhesiolysis in patients with chronic abdominal pain: a blinded randomised controlled multi-centre trial." }, { "docid": "58050905", "text": "The World Health Organisation has declared the period 2000 to 2010 the Bone and Joint Decade. This is indeed timely and appropriate. Hundreds of millions of people in the world today are beset with a host of disabilities caused by trauma, ageing and degeneration and other affections of the musculo-skeletal system. With the state of art of orthopaedic surgery and rheumatology, sufferers of bone and joint disabilities have benefited a great deal from advances in pharmacology, newer techniques of imaging, surgery and man-made materials to replace diseased or damaged bone and cartilage. However, man-made materials, being non-living, are subject to wear and tear and loosening in the host bone. As we advance into the Bone and Joint Decade, further improvement in the treatment of bone and joint diseases lies in more basic cartilage and bone research. The Human Genome Project has provided us with a better understanding of disease genes and the possibility of gene manipulation to prevent and treat specific diseases. Cartilage cells culture and transplant are already a reality. Tissue engineering, i.e. growing cells in three-dimensional substrates of collagen or synthetic biodegradable polymers, started in the 1980s, will in future be used to replace damaged bone and cartilage parts with living and bone and cartilaginous tissues, respectively. The first steps have been taken; more research needs to be done. And it is not unreasonable to expect a significant breakthrough in the treatment of bone and joint diseases at the end of this decade. Ann Acad Med Singapore 2002; 31:621-2", "title": "The Bone and Joint Decade 2000-2010." }, { "docid": "5687200", "text": "AIMS The aim of this study was to compare the effects of calorie-restricted vegetarian and conventional diabetic diets alone and in combination with exercise on insulin resistance, visceral fat and oxidative stress markers in subjects with Type 2 diabetes. METHODS A 24-week, randomized, open, parallel design was used. Seventy-four patients with Type 2 diabetes were randomly assigned to either the experimental group (n = 37), which received a vegetarian diet, or the control group (n = 37), which received a conventional diabetic diet. Both diets were isocaloric, calorie restricted (-500 kcal/day). All meals during the study were provided. The second 12 weeks of the diet were combined with aerobic exercise. Participants were examined at baseline, 12 weeks and 24 weeks. Primary outcomes were: insulin sensitivity measured by hyperinsulinaemic isoglycaemic clamp; volume of visceral and subcutaneous fat measured by magnetic resonance imaging; and oxidative stress measured by thiobarbituric acid reactive substances. Analyses were by intention to treat. RESULTS Forty-three per cent of participants in the experimental group and 5% of participants in the control group reduced diabetes medication (P < 0.001). Body weight decreased more in the experimental group than in the control group [-6.2 kg (95% CI -6.6 to -5.3) vs. -3.2 kg (95% CI -3.7 to -2.5); interaction group × time P = 0.001]. An increase in insulin sensitivity was significantly greater in the experimental group than in the control group [30% (95% CI 24.5-39) vs. 20% (95% CI 14-25), P = 0.04]. A reduction in both visceral and subcutaneous fat was greater in the experimental group than in the control group (P = 0.007 and P = 0.02, respectively). Plasma adiponectin increased (P = 0.02) and leptin decreased (P = 0.02) in the experimental group, with no change in the control group. Vitamin C, superoxide dismutase and reduced glutathione increased in the experimental group (P = 0.002, P < 0.001 and P = 0.02, respectively). Differences between groups were greater after the addition of exercise training. Changes in insulin sensitivity and enzymatic oxidative stress markers correlated with changes in visceral fat. CONCLUSIONS A calorie-restricted vegetarian diet had greater capacity to improve insulin sensitivity compared with a conventional diabetic diet over 24 weeks. The greater loss of visceral fat and improvements in plasma concentrations of adipokines and oxidative stress markers with this diet may be responsible for the reduction of insulin resistance. The addition of exercise training further augmented the improved outcomes with the vegetarian diet.", "title": "Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes" }, { "docid": "44384384", "text": "AIMS While randomized clinical trials have compared clopidogrel with higher potency adenosine diphosphate (ADP) receptor inhibitors among patients with acute myocardial infarction, little is known about the frequency, effectiveness and safety of switching between ADP receptor inhibitors in routine clinical practice. METHODS AND RESULTS We studied 11,999 myocardial infarction patients treated with percutaneous coronary intervention at 230 hospitals from April 2010 to October 2012 in the TRANSLATE-ACS study. Multivariable Cox regression was used to compare six-month post-discharge risks of major adverse cardiovascular events (MACE: death, myocardial infarction, stroke, or unplanned revascularization) and Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-defined bleeding between in-hospital ADP receptor inhibitor switching versus continuation of the initially selected therapy. Among 8715 patients treated initially with clopidogrel, 994 (11.4%) were switched to prasugrel or ticagrelor; switching occurred primarily after percutaneous coronary intervention (60.9%) and at the time of hospital discharge (26.7%). Among 3284 patients treated initially with prasugrel or ticagrelor, 448 (13.6%) were switched to clopidogrel; 48.2% of switches occurred after percutaneous coronary intervention and 48.0% at hospital discharge. Switching to prasugrel or ticagrelor was not associated with increased bleeding when compared with continuation on clopidogrel (2.7% vs. 3.3%, adjusted hazard ratio 0.96, 95% confidence interval 0.64-1.42, p=0.82). Switching from prasugrel or ticagrelor to clopidogrel was not associated with increased MACE (8.9% vs. 7.7%, adjusted hazard ratio 1.06, 95% confidence interval 0.75-1.49, p=0.76) when compared with continuation on the higher potency agent. CONCLUSIONS In-hospital ADP receptor inhibitor switching occurs in more than one in 10 myocardial infarction patients in contemporary practice. In this observational study, ADP receptor inhibitor switching does not appear to be significantly associated with increased hazard of MACE or bleeding.", "title": "In-hospital switching between adenosine diphosphate receptor inhibitors in patients with acute myocardial infarction treated with percutaneous coronary intervention: Insights into contemporary practice from the TRANSLATE-ACS study." }, { "docid": "8298120", "text": "PURPOSE Glaucoma is the leading cause of global irreversible blindness. Present estimates of global glaucoma prevalence are not up-to-date and focused mainly on European ancestry populations. We systematically examined the global prevalence of primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG), and projected the number of affected people in 2020 and 2040. DESIGN Systematic review and meta-analysis. PARTICIPANTS Data from 50 population-based studies (3770 POAG cases among 140,496 examined individuals and 786 PACG cases among 112 398 examined individuals). METHODS We searched PubMed, Medline, and Web of Science for population-based studies of glaucoma prevalence published up to March 25, 2013. Hierarchical Bayesian approach was used to estimate the pooled glaucoma prevalence of the population aged 40-80 years along with 95% credible intervals (CrIs). Projections of glaucoma were estimated based on the United Nations World Population Prospects. Bayesian meta-regression models were performed to assess the association between the prevalence of POAG and the relevant factors. MAIN OUTCOME MEASURES Prevalence and projection numbers of glaucoma cases. RESULTS The global prevalence of glaucoma for population aged 40-80 years is 3.54% (95% CrI, 2.09-5.82). The prevalence of POAG is highest in Africa (4.20%; 95% CrI, 2.08-7.35), and the prevalence of PACG is highest in Asia (1.09%; 95% CrI, 0.43-2.32). In 2013, the number of people (aged 40-80 years) with glaucoma worldwide was estimated to be 64.3 million, increasing to 76.0 million in 2020 and 111.8 million in 2040. In the Bayesian meta-regression model, men were more likely to have POAG than women (odds ratio [OR], 1.36; 95% CrI, 1.23-1.52), and after adjusting for age, gender, habitation type, response rate, and year of study, people of African ancestry were more likely to have POAG than people of European ancestry (OR, 2.80; 95% CrI, 1.83-4.06), and people living in urban areas were more likely to have POAG than those in rural areas (OR, 1.58; 95% CrI, 1.19-2.04). CONCLUSIONS The number of people with glaucoma worldwide will increase to 111.8 million in 2040, disproportionally affecting people residing in Asia and Africa. These estimates are important in guiding the designs of glaucoma screening, treatment, and related public health strategies.", "title": "Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis." }, { "docid": "154243324", "text": "Governments have shown an interest in early intervention strategies to reduce youth homelessness, but critics say that early intervention programs lack clear outcomes. This paper investigates what happens when early intervention programs are not in place and young people progress to adult homelessness. The paper assesses the 'social adaptation' hypothesis that the longer young people are homeless the more they adapt to homelessness as a way of life. The paper uses information on 1,677 individuals who first became homeless when they were 18 or younger. Three-quarters of the sample had progressed to adult homelessness (defined as 25 or older) and one-quarter were now young adults aged 19 to 24. The findings confirm that the longer people are homeless, the more difficult it becomes to get out of homelessness. However, the social adaptation account overstates the extent to which people accept homelessness as a 'way of life'. People can return to conventional accommodation if they are given long-term support. The paper concludes with three policy recommendations.", "title": "From youth to adult homelessness" }, { "docid": "1287809", "text": "IMPORTANCE The American College of Cardiology and the American Heart Association (ACC/AHA) cholesterol treatment guidelines have wide-scale implications for treating adults without history of atherosclerotic cardiovascular disease (ASCVD) with statins. OBJECTIVE To estimate the cost-effectiveness of various 10-year ASCVD risk thresholds that could be used in the ACC/AHA cholesterol treatment guidelines. DESIGN, SETTING, AND PARTICIPANTS Microsimulation model, including lifetime time horizon, US societal perspective, 3% discount rate for costs, and health outcomes. In the model, hypothetical individuals from a representative US population aged 40 to 75 years received statin treatment, experienced ASCVD events, and died from ASCVD-related or non-ASCVD-related causes based on ASCVD natural history and statin treatment parameters. Data sources for model parameters included National Health and Nutrition Examination Surveys, large clinical trials and meta-analyses for statin benefits and treatment, and other published sources. MAIN OUTCOMES AND MEASURES Estimated ASCVD events prevented and incremental costs per quality-adjusted life-year (QALY) gained. RESULTS In the base-case scenario, the current ASCVD threshold of 7.5% or higher, which was estimated to be associated with 48% of adults treated with statins, had an incremental cost-effectiveness ratio (ICER) of $37,000/QALY compared with a 10% or higher threshold. More lenient ASCVD thresholds of 4.0% or higher (61% of adults treated) and 3.0% or higher (67% of adults treated) had ICERs of $81,000/QALY and $140,000/QALY, respectively. Shifting from a 7.5% or higher ASCVD risk threshold to a 3.0% or higher ASCVD risk threshold was estimated to be associated with an additional 161,560 cardiovascular disease events averted. Cost-effectiveness results were sensitive to changes in the disutility associated with taking a pill daily, statin price, and the risk of statin-induced diabetes. In probabilistic sensitivity analysis, there was a higher than 93% chance that the optimal ASCVD threshold was 5.0% or lower using a cost-effectiveness threshold of $100,000/QALY. CONCLUSIONS AND RELEVANCE In this microsimulation model of US adults aged 45 to 75 years [corrected], the current 10-year ASCVD risk threshold (≥7.5% risk threshold) used in the ACC/AHA cholesterol treatment guidelines has an acceptable cost-effectiveness profile (ICER, $37,000/QALY), but more lenient ASCVD thresholds would be optimal using cost-effectiveness thresholds of $100,000/QALY (≥4.0% risk threshold) or $150,000/QALY (≥3.0% risk threshold). The optimal ASCVD threshold was sensitive to patient preferences for taking a pill daily, changes to statin price, and the risk of statin-induced diabetes.", "title": "Cost-effectiveness of 10-Year Risk Thresholds for Initiation of Statin Therapy for Primary Prevention of Cardiovascular Disease." }, { "docid": "23639838", "text": "Brain metastases occur in up to 40% of patients with cancer. Their management has been revolutionized in the last decade by three developments: improved imaging and detection of metastases, better treatment of systemic disease with the result that metastases occur more often; and improved surgical techniques including image-guided surgery to treat metastatic lesions. Class 1 data suggest that surgery is a better treatment for metastases than whole brain radiation. Other data suggest that metastases even in eloquent cortex can be removed safely. The complication rate is low and the recurrence rate is less than 10%. In general, indications for surgery include a mass with an unknown primary; a symptomatic mass including one in eloquent areas; a mass with considerable edema requiring high dose steroids; a mass greater than 3 cm; or patient preference when radiosurgery may also be an option. The question of radiosurgery or whole brain radiation as adjunct to surgical removal requires further evaluation.", "title": "Surgical Resection for Patients with Solid Brain Metastases: Current Status" }, { "docid": "5262240", "text": "AIMS To investigate the pattern of changes in HbA1c in people with Type 1 diabetes managed by long-term Continuous subcutaneous insulin infusion. METHODS We studied HbA1c changes using computerized clinic records in 35 adult people with Type 1 diabetes and an elevated HbA1c (≥ 64 mmol/mol, 8.0%) on multiple daily insulin injections, who were then switched to continuous subcutaneous insulin infusion for at least 5 years. RESULTS We identified three subgroups with similar baseline HbA1c but different long-term responses to pump therapy: group A--those with improvement followed by deterioration (57%); group B--those with improvement that was sustained throughout the 5 years (31%); and group C-those where HbA1c did not change significantly from baseline (12%). The patients in group C had a higher BMI: 31.0 ± 5.2 vs. 25.9 ± 3.3 vs. 25.2 ± 3.1 kg/m² (group C vs. group A and group B; P = 0.02). CONCLUSIONS Improved glycaemic control with continuous subcutaneous insulin infusion was maintained over 5 years by 88% of people with Type 1 diabetes in this study, but there were variations in the long-term efficacy, with some people improving and worsening, others maintaining strict control and a few subcutaneous insulin infusion 'non-responders'.", "title": "Variations in the quality and sustainability of long-term glycaemic control with continuous subcutaneous insulin infusion." }, { "docid": "5402581", "text": "CONTEXT Atypical antipsychotic medications are widely used to treat delusions, aggression, and agitation in people with Alzheimer disease and other dementia; however, concerns have arisen about the increased risk for cerebrovascular adverse events, rapid cognitive decline, and mortality with their use. OBJECTIVE To assess the evidence for increased mortality from atypical antipsychotic drug treatment for people with dementia. DATA SOURCES MEDLINE (1966 to April 2005), the Cochrane Controlled Trials Register (2005, Issue 1), meetings presentations (1997-2004), and information from the sponsors were searched using the terms for atypical antipsychotic drugs (aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone), dementia, Alzheimer disease, and clinical trial. STUDY SELECTION Published and unpublished randomized placebo-controlled, parallel-group clinical trials of atypical antipsychotic drugs marketed in the United States to treat patients with Alzheimer disease or dementia were selected by consensus of the authors. DATA EXTRACTION Trials, baseline characteristics, outcomes, all-cause dropouts, and deaths were extracted by one reviewer; treatment exposure was obtained or estimated. Data were checked by a second reviewer. DATA SYNTHESIS Fifteen trials (9 unpublished), generally 10 to 12 weeks in duration, including 16 contrasts of atypical antipsychotic drugs with placebo met criteria (aripiprazole [n = 3], olanzapine [n = 5], quetiapine [n = 3], risperidone [n = 5]). A total of 3353 patients were randomized to study drug and 1757 were randomized to placebo. Outcomes were assessed using standard methods (with random- or fixed-effects models) to calculate odds ratios (ORs) and risk differences based on patients randomized and relative risks based on total exposure to treatment. There were no differences in dropouts. Death occurred more often among patients randomized to drugs (118 [3.5%] vs 40 [2.3%]. The OR by meta-analysis was 1.54; 95% confidence interval [CI], 1.06-2.23; P = .02; and risk difference was 0.01; 95% CI, 0.004-0.02; P = .01). Sensitivity analyses did not show evidence for differential risks for individual drugs, severity, sample selection, or diagnosis. CONCLUSIONS Atypical antipsychotic drugs may be associated with a small increased risk for death compared with placebo. This risk should be considered within the context of medical need for the drugs, efficacy evidence, medical comorbidity, and the efficacy and safety of alternatives. Individual patient analyses modeling survival and causes of death are needed.", "title": "Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials." }, { "docid": "12584053", "text": "OBJECTIVE To measure whether the benefits of a single education and self management structured programme for people with newly diagnosed type 2 diabetes mellitus are sustained at three years. DESIGN Three year follow-up of a multicentre cluster randomised controlled trial in primary care, with randomisation at practice level. SETTING 207 general practices in 13 primary care sites in the United Kingdom. PARTICIPANTS 731 of the 824 participants included in the original trial were eligible for follow-up. Biomedical data were collected on 604 (82.6%) and questionnaire data on 513 (70.1%) participants. INTERVENTION A structured group education programme for six hours delivered in the community by two trained healthcare professional educators compared with usual care. MAIN OUTCOME MEASURES The primary outcome was glycated haemoglobin (HbA(1c)) levels. The secondary outcomes were blood pressure, weight, blood lipid levels, smoking status, physical activity, quality of life, beliefs about illness, depression, emotional impact of diabetes, and drug use at three years. RESULTS HbA(1c) levels at three years had decreased in both groups. After adjusting for baseline and cluster the difference was not significant (difference -0.02, 95% confidence interval -0.22 to 0.17). The groups did not differ for the other biomedical and lifestyle outcomes and drug use. The significant benefits in the intervention group across four out of five health beliefs seen at 12 months were sustained at three years (P<0.01). Depression scores and quality of life did not differ at three years. CONCLUSION A single programme for people with newly diagnosed type 2 diabetes mellitus showed no difference in biomedical or lifestyle outcomes at three years although there were sustained improvements in some illness beliefs. TRIAL REGISTRATION Current Controlled Trials ISRCTN17844016.", "title": "Effectiveness of a diabetes education and self management programme (DESMOND) for people with newly diagnosed type 2 diabetes mellitus: three year follow-up of a cluster randomised controlled trial in primary care" }, { "docid": "6751418", "text": "UNLABELLED In patients with a large, multinodular goiter (> 100 g), radiation absorbed doses in the thyroid, surrounding tissues and remainder of the body were estimated after therapeutic administration of 131I(3.7 MBq or 100 microCi/g of thyroid tissue retained at 24 hr). METHODS Thermoluminescent dosimeter (TLD) measurements were performed on 23 patients (12 euthyroid and 1I hyperthyroid; thyroid weight 222 +/- 72 g; 2.1 +/- 0.9 GBq 131I) on the skin over the thyroid, over the submandibular gland and over the parotid gland. Thyroid radioactivity measurements were done daily in 6 euthyroid and 6 hyperthyroid patients (thyroid weight 204 +/- 69 g; 1.9 +/- 0.9 GBq 131I). An iodine biokinetic model and the MIRD methodology were used to estimate absorbed doses in organs. Cancer risks were calculated using ICRP Publication 60. RESULTS Cumulated absorbed doses on the skin (TLD measurements) were 4.2 +/- 1.4 Gy (thyroid), 1.2 +/- 0.6 Gy (submandibular) and 0.4 +/- 0.2 Gy (parotid). All these values were significantly correlated with the amount of radioiodine retained in the thyroid at 24 hr (euthyroid versus hyperthyroid not significant). Absorbed doses in the thyroid of 94 +/- 25 Gy for euthyroid and 93 +/- 17 Gy for hyperthyroid patients were calculated (thyroid radioactivity measurements). Extrathyroidal absorbed doses (means of 12 patients) were 0.88 Gy in the urinary bladder, 0.57 Gy in the small intestine, 0.38 Gy in the stomach, and ranged from 0.05 to 0.30 Gy in other organs (euthyroid versus hyperthyroid not significant). A 1.6% life-time risk of development of cancer outside the thyroid gland was calculated. When applied to people of 65 yr and older the estimated risk is approximately 0.5%. CONCLUSION These data may help in choosing the treatment regimen for individual patients with a large, multinodular goiter, who have to be treated for hyperthyroidism or compressive problems. In younger patients, surgery may be preferred. However, for elderly patients and patients with cardiopulmonary disease, the advantages of noninvasive radioiodine treatment will outweight the life-time risk of this mode of therapy.", "title": "Dosimetry and risk estimates of radioiodine therapy for large, multinodular goiters." }, { "docid": "43122426", "text": "We studied 201 consecutive patients who received a relatively fixed dose of radioiodine for the treatment of hyperthyroidism between the years 1981-6. Patients with Graves' disease (170) were initially treated with a mean (SE) dose of 369 (10) MBq 131-I with a remission rate of 94% at 6 months and a cumulative relapse rate of 12% at one year and 21% at 5 years. The cumulative incidence of hypothyroidism was 26% at 3 months, 55% at 6 months, 61% at 1 year and 66% at 5 years. Patients with a uninodular goitre (10) were initially treated with a mean (SE) dose of 438 (85) MBq 131-I with a remission rate of 100% at 6 months, without relapse at 1 year but relapsing in 17% at 5 years. The cumulative incidence of hypothyroidism was 26% at 3 months, 30% at 6 months, 40% at 1 year and 40% at 5 years. Patients with a multinodular goitre (21) were initially treated with a mean (SE) dose of 613 (77) MBq 131-I with a remission rate of 79% at 6 months and a cumulative relapse rate of 26% at 1 year and 39% at 5 years. The cumulative incidence of hypothyroidism was 5% at 3 months, 14% at 6 months, 24% at 1 year and 24% at 5 years.", "title": "131-I radioiodine therapy for hyperthyroidism in patients with Graves' disease, uninodular goitre and multinodular goitre." }, { "docid": "13900610", "text": "BACKGROUND Self-harm and suicide are common in prisoners, yet robust information on the full extent and characteristics of people at risk of self-harm is scant. Furthermore, understanding how frequently self-harm is followed by suicide, and in which prisoners this progression is most likely to happen, is important. We did a case-control study of all prisoners in England and Wales to ascertain the prevalence of self-harm in this population, associated risk factors, clustering effects, and risk of subsequent suicide after self-harm. METHODS Records of self-harm incidents in all prisons in England and Wales were gathered routinely between January, 2004, and December, 2009. We did a case-control comparison of prisoners who self-harmed and those who did not between January, 2006, and December, 2009. We also used a Bayesian approach to look at clustering of people who self-harmed. Prisoners who self-harmed and subsequently died by suicide in prison were compared with other inmates who self-harmed. FINDINGS 139,195 self-harm incidents were recorded in 26,510 individual prisoners between 2004 and 2009; 5-6% of male prisoners and 20-24% of female inmates self-harmed every year. Self-harm rates were more than ten times higher in female prisoners than in male inmates. Repetition of self-harm was common, particularly in women and teenage girls, in whom a subgroup of 102 prisoners accounted for 17,307 episodes. In both sexes, self-harm was associated with younger age, white ethnic origin, prison type, and a life sentence or being unsentenced; in female inmates, committing a violent offence against an individual was also a factor. Substantial evidence was noted of clustering in time and location of prisoners who self-harmed (adjusted intra-class correlation 0·15, 95% CI 0·11-0·18). 109 subsequent suicides in prison were reported in individuals who self-harmed; the risk was higher in those who self-harmed than in the general prison population, and more than half the deaths occurred within a month of self-harm. Risk factors for suicide after self-harm in male prisoners were older age and a previous self-harm incident of high or moderate lethality; in female inmates, a history of more than five self-harm incidents within a year was associated with subsequent suicide. INTERPRETATION The burden of self-harm in prisoners is substantial, particularly in women. Self-harm in prison is associated with subsequent suicide in this setting. Prevention and treatment of self-harm in prisoners is an essential component of suicide prevention in prisons. FUNDING Wellcome Trust, National Institute for Health Research, National Offender Management Service, and Department of Health.", "title": "Self-harm in prisons in England and Wales: an epidemiological study of prevalence, risk factors, clustering, and subsequent suicide" }, { "docid": "21590125", "text": "Data of prescribing practices for antipsychotics are of great interest with respect to quality of care. Consequently, we analysed all prescriptions under the statutory health insurance redeemed at pharmacies in Southern Germany between July 1999 and December 2001. The database covers prescriptions for approximately 25 million people. Up to 6% of the population were prescribed an antipsychotic at least once during the study period. Most prescriptions were for conventional antipsychotics and written by non-specialists. Patients receiving second generation antipsychotics were more likely to receive continuous antipsychotic therapy. For a large proportion of patients, antipsychotic polypharmacy, as well as comedication for somatic illnesses, were observed. In particular, drugs for the treatment of cardiovascular and metabolic disorders were frequently co-prescribed. Physicians should consider patients' cardiovascular and metabolic risk profile when making treatment choices. The data suggest that the majority of antipsychotics are used for the treatment of disorders other than schizophrenia. It is important to raise awareness among non-specialists about the indications, efficacy and side-effects of the antipsychotics because these physicians account for the majority of antipsychotic prescriptions.", "title": "Antipsychotic prescribing patterns in Germany: a retrospective analysis using a large outpatient prescription database." }, { "docid": "5698494", "text": "OBJECTIVES To investigate whether statins reduce all cause mortality and major coronary and cerebrovascular events in people without established cardiovascular disease but with cardiovascular risk factors, and whether these effects are similar in men and women, in young and older (>65 years) people, and in people with diabetes mellitus. DESIGN Meta-analysis of randomised trials. DATA SOURCES Cochrane controlled trials register, Embase, and Medline. Data abstraction Two independent investigators identified studies on the clinical effects of statins compared with a placebo or control group and with follow-up of at least one year, at least 80% or more participants without established cardiovascular disease, and outcome data on mortality and major cardiovascular disease events. Heterogeneity was assessed using the Q and I(2) statistics. Publication bias was assessed by visual examination of funnel plots and the Egger regression test. RESULTS 10 trials enrolled a total of 70 388 people, of whom 23 681 (34%) were women and 16 078 (23%) had diabetes mellitus. Mean follow-up was 4.1 years. Treatment with statins significantly reduced the risk of all cause mortality (odds ratio 0.88, 95% confidence interval 0.81 to 0.96), major coronary events (0.70, 0.61 to 0.81), and major cerebrovascular events (0.81, 0.71 to 0.93). No evidence of an increased risk of cancer was observed. There was no significant heterogeneity of the treatment effect in clinical subgroups. CONCLUSION In patients without established cardiovascular disease but with cardiovascular risk factors, statin use was associated with significantly improved survival and large reductions in the risk of major cardiovascular events.", "title": "The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials" }, { "docid": "23670644", "text": "BACKGROUND The ketogenic diet has been widely and successfully used to treat children with drug-resistant epilepsy since the 1920s. The aim of this study was to test the efficacy of the ketogenic diet in a randomised controlled trial. METHODS 145 children aged between 2 and 16 years who had at least daily seizures (or more than seven seizures per week), had failed to respond to at least two antiepileptic drugs, and had not been treated previously with the ketogenic diet participated in a randomised controlled trial of its efficacy to control seizures. Enrolment for the trial ran between December, 2001, and July, 2006. Children were seen at one of two hospital centres or a residential centre for young people with epilepsy. Children were randomly assigned to receive a ketogenic diet, either immediately or after a 3-month delay, with no other changes to treatment (control group). Neither the family nor investigators were blinded to the group assignment. Early withdrawals were recorded, and seizure frequency on the diet was assessed after 3 months and compared with that of the controls. The primary endpoint was a reduction in seizures; analysis was intention to treat. Tolerability of the diet was assessed by questionnaire at 3 months. The trial is registered with ClinicalTrials.gov, number NCT00564915. FINDINGS 73 children were assigned to the ketogenic diet and 72 children to the control group. Data from 103 children were available for analysis: 54 on the ketogenic diet and 49 controls. Of those who did not complete the trial, 16 children did not receive their intervention, 16 did not provide adequate data, and ten withdrew from the treatment before the 3-month review, six because of intolerance. After 3 months, the mean percentage of baseline seizures was significantly lower in the diet group than in the controls (62.0%vs 136.9%, 75% decrease, 95% CI 42.4-107.4%; p<0.0001). 28 children (38%) in the diet group had greater than 50% seizure reduction compared with four (6%) controls (p<0.0001), and five children (7%) in the diet group had greater than 90% seizure reduction compared with no controls (p=0.0582). There was no significant difference in the efficacy of the treatment between symptomatic generalised or symptomatic focal syndromes. The most frequent side-effects reported at 3-month review were constipation, vomiting, lack of energy, and hunger. INTERPRETATION The results from this trial of the ketogenic diet support its use in children with treatment-intractable epilepsy. FUNDING HSA Charitable Trust; Smiths Charity; Scientific Hospital Supplies; Milk Development Council.", "title": "The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial." }, { "docid": "17482507", "text": "OBJECTIVE To review the evidence for the use of bisphosphonates to reduce skeletal morbidity in cancer patients with bone metastases. DATA SOURCES Electronic databases, scanning reference lists, and consultation with experts and pharmaceutical companies. Foreign language papers were included. STUDY SELECTION Included trials were randomised controlled trials of patients with malignant disease and bone metastases who were treated with oral or intravenous bisphosphonate compared with another bisphosphonate, placebo, or standard care. All trials measured at least one outcome of skeletal morbidity. RESULTS 95 articles were identified; 30 studies fulfilled inclusion criteria. In studies that lasted > or = 6 months, compared with placebo bisphosphonates significantly reduced the odds ratio for fractures (vertebral 0.69, 95% confidence interval 0.57 to 0.84, P < 0.0001; non-vertebral 0.65, 0.54 to 0.79, P < 0.0001; combined 0.65, 0.55 to 0.78, P < 0.0001), radiotherapy (0.67, 0.57 to 0.79, P < 0.0001), and hypercalcaemia (0.54, 0.36 to 0.81, P = 0.003) but not for orthopaedic surgery (0.70, 0.46 to 1.05, P = 0.086) or spinal cord compression (0.71, 0.47 to 1.08, P = 0.113). The reduction in orthopaedic surgery was significant in studies that lasted over a year (0.59, 0.39 to 0.88, P = 0.009). Use of bisphosphonates significantly increased time to first skeletal related event but did not increase survival. Subanalyses showed that most evidence supports use of intravenous aminobisphosphonates. CONCLUSIONS In people with metastatic bone disease bisphosphonates significantly decrease skeletal morbidity, except for spinal cord compression and increased time to first skeletal related event. Treatment should start when bone metastases are diagnosed and continue until it is no longer clinically relevant.", "title": "Systematic review of role of bisphosphonates on skeletal morbidity in metastatic cancer." }, { "docid": "20130904", "text": "BACKGROUND Gastric bypass patients with a range of disturbed eating patterns before surgery may be at risk of returning to old patterns postoperatively. Recent research has shown that binge eating is common among the obese before surgery as well as in the postoperative maintenance phase and appears to be linked to poorer outcome. Although \"grazing\" behavior has not been specifically studied, it is also a high-risk pattern. This paper is a descriptive investigation summarizing postoperative eating patterns in a group of patients. METHODS Patients completed self-report questionnaires before surgery and were seen for a preoperative mental health evaluation with particular focus on assessing eating patterns. Patients with high-risk eating patterns, both binge eating and \"grazing\", were identified, invited to attend a post-surgery therapy group, and were given additional follow-up questionnaires regarding postoperative eating patterns. RESULTS Consistent with recent studies, many high-risk patients reported recurrent loss of control over eating and, in some cases, subsequent weight gain. Although no longer able to eat large amounts, \"grazing\" became a more common pattern, appearing >or=6 months following surgery. CONCLUSION Different forms of overeating need to be assessed in this population, focusing on the subjective loss of control rather than on the quantity consumed. Although many patients do not meet strict criteria for binge eating disorder before surgery, these \"grazers\" are also high-risk. Former binge eaters often turn into \"grazers\" following surgery. Interventions are needed for at-risk patients.", "title": "\"Grazing\": a high-risk behavior." }, { "docid": "36003142", "text": "OBJECTIVE Mortality rates in the year following new antipsychotic medication starts for neuropsychiatric symptoms of dementia were compared with rates after starts of other psychiatric medications. METHOD The retrospective, cohort study used national data from the Department of Veterans Affairs (fiscal years 2001-2005) on patients older than 65 years who began outpatient treatment with psychiatric medication following a dementia diagnosis (N=10,615). Twelve-month mortality rates were compared in patients taking antipsychotics and those taking other psychiatric medications. The authors controlled for confounding by using multivariate models and propensity-scoring methods. Secondary analyses included a no-medication group and examination of mortality causes. RESULTS All groups taking antipsychotics had significantly higher mortality rates (22.6%-29.1%) than patients taking nonantipsychotic medications (14.6%). Adjusted mortality risks for atypicals and for combined atypical and conventional antipsychotics were similar to those for conventional antipsychotics. The mortality risk was significantly lower for nonantipsychotic medications than conventional antipsychotics. Except for anticonvulsants, the adjusted risks for all individual classes of nonantipsychotics were significantly lower than the risk for antipsychotics. Mortality risks did not change over 12 months. The proportions of patients taking antipsychotics who died from cerebrovascular, cardiovascular, or infectious causes were not higher than rates for those taking nonantipsychotic psychiatric medications. CONCLUSIONS Antipsychotic medications taken by patients with dementia were associated with higher mortality rates than were most other medications used for neuropsychiatric symptoms. The association between mortality and antipsychotics is not well understood and may be due to a direct medication effect or the pathophysiology underlying neuropsychiatric symptoms that prompt antipsychotic use.", "title": "Mortality risk in patients with dementia treated with antipsychotics versus other psychiatric medications." }, { "docid": "70516463", "text": "Human beings, make errors Healthcare Services is a complex industry prone to accidents. The IOM Report [1] points out that some systems are more prone to accidents than others. When a system fails there are often multiple faults. In healthcare,human errors are the greatest contributors to accidents,however when human error is to blame it often depends upon failures within the system. These failures exists in the system before the error occurs, the same as with latent errors which are difficult to identify since they may be hidden in computers or within the various managerial layers. Most of the errors can be prevented by designing systems that make it hard for people to do the wrong thing and easy for people to do the right thing. In healthcare, this means designing processes that are able to ensure that patients are safe from accidental injury. As healthcare and the system that delivers it become more complex, the opportunities for errors abound. The IOM report “To Err is Human” proposes an approach for reducing medical errors and improving patient safety. The environment within which this occurs has a critical influence on quality. This influence may contain two dimensions; the first consists of the domain of quality which includes the practice that is consistent with current medical knowledge. The second dimension consists of forces in the external environment that can drive quality improvement in the delivery system. Although the risk of dying as a result of a medical error, far surpasses the risk of dying in an airline accident, public attention has been more focused on improving safety in the airline industry than in healthcare systems. Because of the absence of standardized nomenclature, it is important to define what an error is and what is an adverse event, the IOM Report defines them in the following way: “An error is the failure of a planned action to be completed as intended or the use of a wrong plan to achieve an aim. ” An adverse event is an injury caused by medical management rather than the underlying condition of the patient. An adverse event attributable to error is a “preventable adverse event”.", "title": "To err is human. Building a safer health system" }, { "docid": "33127778", "text": "Since the concept of early gastric cancer was first described in Japan in 1962, its treatment has evolved from curative surgical resection to endoscopic resection, initially with polypectomy to more recently with endoscopic submucosal dissection. As worldwide experience with these endoscopic techniques evolve and gain acceptance, studies have confirmed its comparable effectiveness with historical surgical outcomes in carefully selected patients. The criteria for endoscopic resection have expanded to offer more patients improved quality of life, avoiding the morbidity and mortality associated with surgery. This article summarizes the evolutional role of endoscopic and surgical therapy in early gastric cancer.", "title": "Early gastric cancer and dysplasia." }, { "docid": "2391552", "text": "INTRODUCTION Induction of an inflammatory response is thought to have a significant role in the complications that follow cardiopulmonary bypass (CPB). The statin drugs are increasingly being recognized as having potent anti-inflammatory effects and hence have potential to influence an important mechanism of injury in CPB, although there is no current confirmation that this is indeed the case. Our objective was to systematically review if pre-operative prophylactic statin therapy, compared with placebo or standard of care, can decrease the inflammatory response in people undergoing heart surgery with CPB. METHODS We performed a systematic and comprehensive literature search for all randomized controlled trials (RCTs) of open heart surgery with CPB in adults or children who received prophylactic statin treatment prior to CPB, with reported outcomes which included markers of inflammation. Two authors independently identified eligible studies, extracted data, and assessed study quality using standardized instruments. Weighted mean difference (WMD) was the primary summary statistic with data pooled using a random effects model. Descriptive analysis was used when data could not be pooled. RESULTS Eight RCTs were included in the review, with the number of trials for each inflammatory outcome being even more limited. Pooled data demonstrated benefit with the use of statin to attenuate the post-CPB increase in interleukins 6 and 8 (IL-6, IL-8), peak high sensitivity C-reactive protein (hsCRP), and tumor necrosis factor-alpha (TNF-alpha) post-CPB (WMD [95% confidence interval (CI)] -23.5 pg/ml [-36.6 to -10.5]; -23.4 pg/ml [-35.8 to -11.0]; -15.3 mg/L [CI -26.9 to -3.7]; -2.10 pg/ml [-3.83 to -0.37] respectively). Very limited RCT evidence suggests that prophylactic statin therapy may also decrease adhesion molecules following CPB including neutrophil CD11b and soluble P (sP)-selectin. CONCLUSIONS Although the RCT evidence may suggest a reduction in post-CPB inflammation by statin therapy, the evidence is not definitive due to significant limitations. Several of the trials were not methodologically rigorous and statin intervention was highly variable in this small number of studies. This systematic review demonstrates that there is a significant gap that exists in the current literature in regards to the potential anti-inflammatory effect of statin therapy prior to CPB.", "title": "Statin prophylaxis and inflammatory mediators following cardiopulmonary bypass: a systematic review" }, { "docid": "34121231", "text": "INTRODUCTION Cold-related respiratory symptoms are common among northern populations, especially among people suffering from respiratory diseases. However, the prevalence of such symptoms in the general population and the threshold temperatures at which the symptoms start to emerge are poorly known. OBJECTIVES The present study determined the prevalence and threshold temperatures of self-reported respiratory symptoms related to cold, separately for healthy people and those with respiratory disease. MATERIALS AND METHODS Six thousand five hundred ninety-one men and women aged 25 years-74 years from the national FINRISK study were queried about cold-related respiratory symptoms. The results were expressed as age-adjusted prevalence figures and coefficients from multivariate regressions. RESULTS Cold-related respiratory symptoms were more often reported by people with asthma (men 69%/women 78%) and by subjects with chronic bronchitis (65%/76%) than the healthy subjects (18%/21%). A binomial regression showed an increase of symptom prevalence by age and excesses of 4%, 50% and 21% units because of female sex, asthma and chronic bronchitis, respectively. The reported threshold temperature for cold-related symptoms was -14 degrees C for males and -15 degrees C for females, and it showed some increase by age (0 degrees C-5 degrees C), asthma (2 degrees C) and chronic bronchitis (3 degrees C). The threshold temperature for mucus production was exceptional as it decreased by age (2 degrees C-5 degrees C) and asthma (2 degrees C). The effects of smoking and education were marginal. CONCLUSION Cold-related respiratory symptoms are common in patients with chronic respiratory diseases, but they start to emerge at relatively low temperatures. In a cold climate, the cold-related symptoms may have an impact on the health-related quality of life.", "title": "Cold-related respiratory symptoms in the general population." } ]
PLAIN-1149
eye health
[ { "docid": "MED-2003", "text": "Background Type 2 diabetes affects approximately 8 percent of adults in the United States. Some risk factors — elevated plasma glucose concentrations in the fasting state and after an oral glucose load, over-weight, and a sedentary lifestyle — are potentially reversible. We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes. Methods We randomly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo, metformin (850 mg twice daily), or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week. The mean age of the participants was 51 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 34.0; 68 percent were women, and 45 percent were members of minority groups. Results The average follow-up was 2.8 years. The incidence of diabetes was 11.0, 7.8, and 4.8 cases per 100 person-years in the placebo, metformin, and lifestyle groups, respectively. The lifestyle intervention reduced the incidence by 58 percent (95 percent confidence interval, 48 to 66 percent) and metformin by 31 percent (95 percent confidence interval, 17 to 43 percent), as compared with placebo; the lifestyle intervention was significantly more effective than metformin. To prevent one case of diabetes during a period of three years, 6.9 persons would have to participate in the lifestyle-intervention program, and 13.9 would have to receive metformin. Conclusions Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk. The lifestyle intervention was more effective than metformin.", "title": "REDUCTION IN THE INCIDENCE OF TYPE 2 DIABETES WITH LIFESTYLE INTERVENTION OR METFORMIN" }, { "docid": "MED-3169", "text": "BACKGROUND: Anecdotal reports and a single case-control epidemiological survey have suggested an association between the helminthic disease neurocysticercosis and primary headache. The present study was undertaken to determine whether neurocysticercosis is more common among patients with primary headaches than in other neurological disorders. METHODS: We determined the prevalence of neurocysticercosis in a cohort of patients with primary headache who were seen at our institution over a 20-year period. We used as controls all people from the same cohort with four major different categories of neurological disorders, including cerebrovascular disease, degenerative disorders of the CNS, head trauma, and primary brain tumors. We evaluated differences in the prevalence of neurocysticercosis between patients and controls. RESULTS: Forty-eight of 1017 patients with primary headache and 31 of 1687 controls had neurocysticercosis (4.7% vs 1.8%, p < 0.0001). Calcified parenchymal brain cysticerci were more frequent among patients with primary headache than in those with cerebrovascular disease (4.7% vs 1%, p < 0.001), degenerative disorders of the CNS (4.7% vs 2.4%, p < 0.05), and head trauma (4.7% vs 2.3%, p < 0.05). There were no significant differences, however, for the subset of controls with primary brain tumors (4.7% vs 3.5%), a condition that has also been associated with neurocysticercosis. CONCLUSIONS: There is a relationship between calcified neurocysticercosis and primary headache disorders. It is possible that periodic remodeling of cysticercotic calcifications, with liberation of antigens to the brain parenchyma, contributes to the occurrence of headache in these patients.", "title": "Calcified neurocysticercosis among patients with primary headache." }, { "docid": "MED-2884", "text": "Two carotenoids found in egg yolk, lutein and zeaxanthin, accumulate in the macular retina where they may reduce photostress. Increases in serum lutein and zeaxanthin were observed in previous egg interventions, but no study measured macular carotenoids. The objective of this project was to determine whether increased consumption of eggs would increase retinal lutein and zeaxanthin, or macular pigment. Twenty-four females, between 24 and 59 y, were assigned to a pill treatment (PILL) or 1 of 2 egg treatments for 12 wk. Individuals in the PILL treatment consumed 1 sugar-filled capsule/d. Individuals in the egg treatments consumed 6 eggs/wk, containing either 331 microg (EGG 1) or 964 microg (EGG 2) of lutein and zeaxanthin/yolk. Serum cholesterol, serum carotenoids, and macular pigment OD (MPOD) were measured at baseline and after 4, 8, and 12 wk of intervention. Serum cholesterol concentrations did not change in either egg treatment group, but total cholesterol (P = 0.04) and triglycerides (P = 0.02) increased in the PILL group. Serum zeaxanthin, but not serum lutein, increased in both the EGG 1 (P = 0.04) and EGG 2 (P = 0.01) groups. Likewise, MPOD increased in both the EGG 1 (P = 0.001) and EGG 2 (P = 0.049) groups. Although the aggregate concentration of carotenoid in 1 egg yolk may be modest relative to other sources, such as spinach, their bioavailability to the retina appears to be high. Increasing egg consumption to 6 eggs/wk may be an effective method to increase MPOD.", "title": "A 12-wk egg intervention increases serum zeaxanthin and macular pigment optical density in women." }, { "docid": "MED-2819", "text": "OBJECTIVES: Curcumin (diferuloylmethane) is the principal biochemical component of the spice turmeric and has been shown to possess potent anti-catabolic, anti-inflammatory and antioxidant, properties. This article aims to provide a summary of the actions of curcumin on articular chondrocytes from the available literature with the use of a text-mining tool. We highlight both the potential benefits and drawbacks of using this chemopreventive agent for treating osteoarthritis (OA). We also explore the recent literature on the molecular mechanisms of curcumin mediated alterations in gene expression mediated via activator protein 1 (AP-1)/nuclear factor-kappa B (NF-kappaB) signalling in chondrocytes, osteoblasts and synovial fibroblasts. METHODS: A computer-aided search of the PubMed/Medline database aided by a text-mining tool to interrogate the ResNet Mammalian database 6.0. RESULTS: Recent work has shown that curcumin protects human chondrocytes from the catabolic actions of interleukin-1 beta (IL-1beta) including matrix metalloproteinase (MMP)-3 up-regulation, inhibition of collagen type II and down-regulation of beta1-integrin expression. Curcumin blocks IL-1beta-induced proteoglycan degradation, AP-1/NF-kappaB signalling, chondrocyte apoptosis and activation of caspase-3. CONCLUSIONS: The available data from published in vitro and in vivo studies suggest that curcumin may be a beneficial complementary treatment for OA in humans and companion animals. Nevertheless, before initiating extensive clinical trials, more basic research is required to improve its solubility, absorption and bioavailability and gain additional information about its safety and efficacy in different species. Once these obstacles have been overcome, curcumin and structurally related biochemicals may become safer and more suitable nutraceutical alternatives to the non-steroidal anti-inflammatory drugs that are currently used for the treatment of OA. Copyright 2009 Osteoarthritis Research Society International. All rights reserved.", "title": "Biological actions of curcumin on articular chondrocytes." }, { "docid": "MED-2825", "text": "Turmeric, a dried powder derived from the rhizome of Curcuma longa, has been used for centuries in certain parts of the world and has been linked to numerous biological activities including antioxidant, anti-inflammatory, anticancer, antigrowth, anti-arthritic, anti-atherosclerotic, antidepressant, anti-aging, antidiabetic, antimicrobial, wound healing, and memory-enhancing activities. One component of turmeric is curcumin, which has been extensively studied, as indicated by more than 5600 citations, most of which have appeared within the past decade. Recent research has identified numerous chemical entities from turmeric other than curcumin. It is unclear whether all of the activities ascribed to turmeric are due to curcumin or whether other compounds in turmeric can manifest these activities uniquely, additively, or synergistically with curcumin. However, studies have indicated that turmeric oil, present in turmeric, can enhance the bioavailability of curcumin. Studies over the past decade have indicated that curcumin-free turmeric (CFT) components possess numerous biological activities including anti-inflammatory, anticancer, and antidiabetic activities. Elemene derived from turmeric is approved in China for the treatment of cancer. The current review focuses on the anticancer and anti-inflammatory activities exhibited by CFT and by some individual components of turmeric, including turmerin, turmerone, elemene, furanodiene, curdione, bisacurone, cyclocurcumin, calebin A, and germacrone. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.", "title": "Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric." }, { "docid": "MED-2812", "text": "Curcumin derived from the tropical plant Curcuma longa has a long history of use as a dietary agent, food preservative, and in traditional Asian medicine. It has been used for centuries to treat biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. The preventive and therapeutic properties of curcumin are associated with its antioxidant, anti-inflammatory, and anticancer properties. Extensive research over several decades has attempted to identify the molecular mechanisms of curcumin action. Curcumin modulates numerous molecular targets by altering their gene expression, signaling pathways, or through direct interaction. Curcumin regulates the expression of inflammatory cytokines (e.g., TNF, IL-1), growth factors (e.g., VEGF, EGF, FGF), growth factor receptors (e.g., EGFR, HER-2, AR), enzymes (e.g., COX-2, LOX, MMP9, MAPK, mTOR, Akt), adhesion molecules (e.g., ELAM-1, ICAM-1, VCAM-1), apoptosis related proteins (e.g., Bcl-2, caspases, DR, Fas), and cell cycle proteins (e.g., cyclin D1). Curcumin modulates the activity of several transcription factors (e.g., NF-κB, AP-1, STAT) and their signaling pathways. Based on its ability to affect multiple targets, curcumin has the potential for the prevention and treatment of various diseases including cancers, arthritis, allergies, atherosclerosis, aging, neurodegenerative disease, hepatic disorders, obesity, diabetes, psoriasis, and autoimmune diseases. This review summarizes the molecular mechanisms of modulation of gene expression by curcumin. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.", "title": "Molecular mechanisms of curcumin action: gene expression." }, { "docid": "MED-3391", "text": "Aim: To review special safety topics associated with sildenafil and to document the tolerability of 50- and 100-mg doses, overall and by age, in men with erectile dysfunction (ED). Methods: Data were collated from 67 double-blind placebo-controlled (DBPC) trials (> 14,000 men) conducted by the manufacturer and from the manufacturer’s postmarketing safety database (39,277 patients). The DBPC data were stratified by dose, starting dose and age (≥ 65 and ≥ 75 years). Special safety topics included cardiovascular risk, priapism, non-arteritic anterior ischaemic optic neuropathy (NAION), impaired renal and hepatic function, drug interactions (i.e. nitrates, cytochrome P3A4 inhibitors, other ED therapies and α-blockers) and incorrect use. Results: Sildenafil was well tolerated at a dose of 50 or 100 mg in men with ED, overall, in those aged ≥ 65 years, and in those aged ≥ 75 years. Analyses of the databases did not reveal any causal link between sildenafil and cardiovascular events, or any new safety risks relating to cardiovascular events, priapism, NAION, hearing loss or drug interactions. In the small number of men with moderate impairment of renal function or hepatic function who were treated with sildenafil in DBPC trials, the safety profile was similar to that in men with no impairment of renal or hepatic function. Overdose with sildenafil was rare in the ED population. No new safety issues, emerging trends or adverse reactions were identified in conjunction with overdose, dependence, abuse or misuse. Conclusion: This collated review confirms generally the good tolerability and established safety profile of sildenafil 50 and 100 mg in men with ED and reveals no new safety issues.", "title": "Safety of sildenafil citrate: review of 67 double-blind placebo-controlled trials and the postmarketing safety database" }, { "docid": "MED-1990", "text": "BACKGROUND: The optimal target range for blood glucose in critically ill patients remains unclear. METHODS: Within 24 hours after admission to an intensive care unit (ICU), adults who were expected to require treatment in the ICU on 3 or more consecutive days were randomly assigned to undergo either intensive glucose control, with a target blood glucose range of 81 to 108 mg per deciliter (4.5 to 6.0 mmol per liter), or conventional glucose control, with a target of 180 mg or less per deciliter (10.0 mmol or less per liter). We defined the primary end point as death from any cause within 90 days after randomization. RESULTS: Of the 6104 patients who underwent randomization, 3054 were assigned to undergo intensive control and 3050 to undergo conventional control; data with regard to the primary outcome at day 90 were available for 3010 and 3012 patients, respectively. The two groups had similar characteristics at baseline. A total of 829 patients (27.5%) in the intensive-control group and 751 (24.9%) in the conventional-control group died (odds ratio for intensive control, 1.14; 95% confidence interval, 1.02 to 1.28; P=0.02). The treatment effect did not differ significantly between operative (surgical) patients and nonoperative (medical) patients (odds ratio for death in the intensive-control group, 1.31 and 1.07, respectively; P=0.10). Severe hypoglycemia (blood glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was reported in 206 of 3016 patients (6.8%) in the intensive-control group and 15 of 3014 (0.5%) in the conventional-control group (P<0.001). There was no significant difference between the two treatment groups in the median number of days in the ICU (P=0.84) or hospital (P=0.86) or the median number of days of mechanical ventilation (P=0.56) or renal-replacement therapy (P=0.39). CONCLUSIONS: In this large, international, randomized trial, we found that intensive glucose control increased mortality among adults in the ICU: a blood glucose target of 180 mg or less per deciliter resulted in lower mortality than did a target of 81 to 108 mg per deciliter. (ClinicalTrials.gov number, NCT00220987.) 2009 Massachusetts Medical Society", "title": "Intensive versus conventional glucose control in critically ill patients." }, { "docid": "MED-3432", "text": "Men with the metabolic syndrome demonstrate an increased prevalence of erectile dysfunction (ED). In the present study, we tested the effect of a Mediterranean-style diet on ED in men with the metabolic syndrome. Men were identified in our database of subjects participating in controlled trials evaluating the effect of lifestyle changes and were included if they had a diagnosis of ED associated with a diagnosis of metabolic syndrome, complete follow-up in the study trial, and intervention focused mainly on dietary changes. Sixty-five men with the metabolic syndrome met the inclusion/exclusion criteria; 35 out of them were assigned to the Mediterranean-style diet and 30 to the control diet. After 2 years, men on the Mediterranean diet consumed more fruits, vegetables, nuts, whole grain, and olive oil as compared with men on the control diet. Endothelial function score and inflammatory markers (C-reactive protein) improved in the intervention group, but remained stable in the control group. There were 13 men in the intervention group and two in the control group (P=0.015) that reported an IIEF score of 22 or higher. Mediterranean-style diet rich in whole grain, fruits, vegetables, legumes, walnut, and olive oil might be effective per se in reducing the prevalence of ED in men with the metabolic syndrome.", "title": "Mediterranean diet improves erectile function in subjects with the metabolic syndrome." }, { "docid": "MED-3784", "text": "Dietary choline and betaine have been hypothesized to decrease the risk of cancer because of their role as methyl donors in the one-carbon metabolism. However, it remains unknown whether dietary intake of choline and betaine is associated with colorectal cancer risk. We prospectively examined the associations between dietary choline and betaine intake and risk of colorectal cancer in men in the Health Professionals Follow-up Study. We followed 47,302 men and identified a total of 987 incident colorectal cancer cases from 1986 to 2004. We assessed dietary and supplemental choline and betaine intake every four years using a validated semi-quantitative food frequency questionnaire. The Cox proportional hazards model was used to estimate multivariate relative risks (RRs) and 95% confidence intervals (95% CIs). All statistical tests were two-sided. We did not find any statistically significant associations between choline intake or betaine intake and risk of colorectal cancer. Comparing the top quintile with bottom quintile, multivariate RRs (95% CI) were 0.97 (0.79-1.20; Ptrend = 0.87) for choline intake and 0.94 (0.77-1.16; Ptrend = 0.79) for betaine intake. Similarly, we observed no associations between colorectal cancer risk and choline from free choline, glycerophosphocholine, phosphocholine, phosphatidylcholine, or sphingomyelin. Our data do not support that choline and betaine intake is inversely associated with colorectal cancer risk.", "title": "Choline and betaine intake and the risk of colorectal cancer in men" }, { "docid": "MED-3248", "text": "OBJECTIVE: To examine the relation between retinal artery disease and cerebral small-vessel disease (SVD). METHODS: In a prospective cohort of patients with symptomatic atherosclerotic disease, the authors performed retinal photographs and brain MRI. Two ophthalmologists, not aware of the MR results, independently assessed retinal arterial narrowing, crossings, sclerosis, and tortuosity according to standard scoring lists. Two observers independently assessed white matter lesions (WML) and lacunar infarcts on the MR images. Lesions were considered abnormal only when both ophthalmologists or MR raters agreed. Cerebral SVD was defined as the presence of WML or lacunar infarcts. RESULTS: In 179 patients, retinal photographs and brain MRI were performed. Of the 108 patients with MR signs of SVD, 92% had at least one retinal vascular abnormality; of the 71 patients without SVD, 77% had retinal pathology (p < 0.01). All types of retinal vascular pathology occurred more frequently in patients with SVD, but only retinal arterial narrowing and sclerosis differed significantly. In the 109 normotensive patients, the presence of any retinal vascular change correlated with signs of SVD (p = 0.01). CONCLUSION: Pathologic changes in the retinal arteries parallel changes in the small cerebral arteries that cause WML and lacunes, both in hypertensive and in normotensive patients.", "title": "Retinal arterial changes correlate with cerebral small-vessel disease." }, { "docid": "MED-3394", "text": "Few studies have examined multiple risk factors for mortality or formally compared their associations across specific causes of death. The authors used competing risks survival analysis to evaluate associations of lifestyle and dietary factors with all-cause and cause-specific mortality among 50,112 participants in the Nurses’ Health Study. There were 4,893 deaths between 1986 and 2004: 1,026 from cardiovascular disease, 931 from smoking-related cancers, 1,430 from cancers not related to smoking, and 1,506 from all other causes. Age, body mass index at age 18 years, weight change, height, current smoking and pack-years of smoking, glycemic load, cholesterol intake, systolic blood pressure and use of blood pressure medications, diabetes, parental myocardial infarction before age 60 years, and time since menopause were directly related to all-cause mortality, whereas there were inverse associations for physical activity and intakes of nuts, polyunsaturated fat, and cereal fiber. Moderate alcohol consumption was associated with decreased mortality. A model that incorporated differences in the associations of some risk factors with specific causes of death had a significantly better fit compared with a model in which all risk factors had common associations across all causes. In the future, this new model may be used to identify individuals at increased risk of mortality.", "title": "Risk Factors for Mortality in the Nurses’ Health Study: A Competing Risks Analysis" }, { "docid": "MED-2814", "text": "Curcumin (diferuloylmethane), an active constituent of turmeric, is a well-described phytochemical, which has been used since ancient times for the treatment of various diseases. The dysregulation of cell signaling pathways by the gradual alteration of regulatory proteins is the root cause of cancers. Curcumin modulates regulatory proteins through various molecular mechanisms. Several research studies have provided in-depth analysis of multiple targets through which curcumin induces protective effects against cancers including gastrointestinal, genitourinary, gynecological, hematological, pulmonary, thymic, brain, breast, and bone. The molecular mechanisms of action of curcumin in treating different types of cancers remain under investigation. The multifaceted role of this dietary agent is mediated through its inhibition of several cell signaling pathways at multiple levels. Curcumin has the ability to inhibit carcinogenicity through the modulation of the cell cycle by binding directly and indirectly to molecular targets including transcription factors (NF-kB, STAT3, β-catenin, and AP-1), growth factors (EGF, PDGF, and VEGF), enzymes (COX-2, iNOS, and MMPs), kinases (cyclin D1, CDKs, Akt, PKC, and AMPK), inflammatory cytokines (TNF, MCP, IL-1, and IL-6), upregulation of proapoptotic (Bax, Bad, and Bak) and downregulation of antiapoptotic proteins (Bcl(2) and Bcl-xL). A variety of animal models and human studies have proven that curcumin is safe and well tolerated even at very high doses. This study elaborates the current understanding of the chemopreventive effects of curcumin through its multiple molecular pathways and highlights its therapeutic value in the treatment and prevention of a wide range of cancers. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.", "title": "Curcumin in various cancers." }, { "docid": "MED-2901", "text": "Purpose. To investigate the relationship between supplementary consumption of the oxidants calcium and iron and the prevalence of glaucoma. Methods. This cross-sectional study included 3833 participants in the National Health and Nutrition Examination Survey (NHANES) for 2007 and 2008, ≥40 years of age, who reported a presence or absence of glaucoma. Participants were interviewed regarding the use of dietary supplements and antacids during the preceding 30-day period. Data pertaining to the supplementary intake of calcium and iron was aggregated and divided into quintiles. Information regarding the presence or absence of glaucoma and demographics, comorbidities, and health-related behavior was obtained via interview. Results. Participants who consumed ≥800 mg/d of supplementary calcium or ≥18 mg/d of supplementary iron had significantly higher odds of having been diagnosed with glaucoma than did those who had not consumed supplementary calcium or iron, after adjustment for potential confounders (odds ratio [OR] 2.44, 95% confidence interval [CI] 1.25–4.76 for calcium; OR 3.80, 95% CI 1.79–8.06 for iron). Concurrent consumption of both calcium and iron above these levels was associated with still greater odds of having been diagnosed with glaucoma (OR 7.24, 95% CI 2.42–21.62). A clear dose–response relationship between quintiles of supplementary calcium or iron intake and glaucoma prevalence was not found. Conclusions. These results suggest that there may be a threshold intake of iron and calcium above which there is an increased risk of development of glaucoma. Prospective longitudinal studies are needed, to assess whether oxidant intake is a risk factor for development and progression of glaucoma.", "title": "The Association between Glaucoma Prevalence and Supplementation with the Oxidants Calcium and Iron" }, { "docid": "MED-3781", "text": "In this study, a panel of normal human prostate cells (HPCs) and tumor cells derived from metastases were studied by (1)H NMR spectroscopy to determine whether the malignant transformation of HPCs results in the elevation of choline compounds. Although an elevated choline signal has been observed previously in clinical studies, the contribution of the different Cho compounds to this elevation, as well as their quantification, has not been established until now. Here we have shown that HPCs derived from metastases exhibit significantly higher phosphocholine as well as glycerophosphocholine levels compared with normal prostate epithelial and stromal cells. Thus the elevation of the choline peak observed clinically in prostate cancer is attributable to an alteration of phospholipid metabolism and not simply to increased cell density, doubling time, or other nonspecific effects. Androgen deprivation of the androgen receptor-positive cell lines resulted in a significant increase of choline compounds after chronic androgen deprivation of the LNCaP cell line and in a decrease of choline compounds after a more acute androgen deprivation of the LAPC-4 cell line. These data strongly support the use of proton magnetic resonance spectroscopic imaging to detect the presence of prostate cancer for diagnosis, to detect response subsequent to androgen ablation therapy, and to detect recurrence.", "title": "Detection of increased choline compounds with proton nuclear magnetic resonance spectroscopy subsequent to malignant transformation of human prosta..." }, { "docid": "MED-4968", "text": "Vibrios are ubiquitous in the aquatic environment and are commonly present in or on shellfish and other seafood. A small subset of strains/species are able to cause human disease, including the cholera toxin-producing strains of Vibrio cholerae that are responsible for epidemic/pandemic cholera; thermostable direct hemolysin-producing strains of Vibrio parahaemolyticus; and Vibrio vulnificus, which can cause fulminant sepsis. Cholera outbreaks can be initiated by transmission of \"epidemic\" V. cholerae strains from their environmental reservoir to humans through seafood or other environmentally related food or water sources. \"Nonepidemic\" strains of V. cholerae and strains of other Vibrio species, including V. parahaemolyticus and V. vulnificus, are generally acquired by eating seafood (particularly raw oysters/oysters on the half shell). Although the primary clinical manifestation of infection with these strains is gastroenteritis, they can also cause wound infections and (particularly for V. vulnificus) septicemia in persons who have liver disease or are immunocompromised.", "title": "Cholera and other types of vibriosis: a story of human pandemics and oysters on the half shell." }, { "docid": "MED-3170", "text": "Background Few studies have focused on the cognitive morbidity of neurocysticercosis (NCC), one of the most common parasitic infections of the central nervous system. We longitudinally assessed the cognitive status and quality of life (QoL) of patients with incident symptomatic NCC cases and matched controls. Methodology/Principal Findings The setting of the study was the Sabogal Hospital and Cysticercosis Unit, Department of Transmissible Diseases, National Institute of Neurological Sciences, Lima, Peru. The design was a longitudinal study of new onset NCC cases and controls. Participants included a total of 14 patients with recently diagnosed NCC along with 14 healthy neighborhood controls and 7 recently diagnosed epilepsy controls. A standardized neuropsychological battery was performed at baseline and at 6 months on NCC cases and controls. A brain MRI was performed in patients with NCC at baseline and 6 months. Neuropsychological results were compared between NCC cases and controls at both time points. At baseline, patients with NCC had lower scores on attention tasks (p<0.04) compared with epilepsy controls but no significant differences compared to healthy controls. Six months after receiving anti-parasitic treatment, the NCC group significantly improved on tasks involving psychomotor speed (p<0.02). QoL at baseline suggested impaired mental function and social function in both the NCC and epilepsy group compared with healthy controls. QoL gains in social function (p = 0.006) were noted at 6 months in patients with NCC. Conclusions/Significance Newly diagnosed patients with NCC in this sample had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment. Author Summary Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system. Cognitive changes have been frequently reported with this disease but have not been well studied. Our study team recruited a group of new onset NCC cases and a matched set of healthy neighborhood controls and new onset epilepsy controls in Lima, Peru for this study. A neuropsychological battery was administered at baseline and at 6 months to all groups. Brain MRI studies were also obtained on NCC cases at baseline and at 6 months. Newly diagnosed patients with NCC had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment. This study is the first to assess cognitive status and quality of life longitudinally in patients with NCC and provides new data on an important clinical morbidity outcome.", "title": "Cognitive Changes and Quality of Life in Neurocysticercosis: A Longitudinal Study" }, { "docid": "MED-2977", "text": "OBJECTIVE—Whereas limited and inconsistent findings have been reported on the relation between dietary cholesterol or egg consumption and fasting glucose, no previous study has examined the association between egg consumption and type 2 diabetes. This project sought to examine the relation between egg intake and the risk of type 2 diabetes in two large prospective cohorts. RESEARCH DESIGN AND METHODS—In this prospective study, we used data from two completed randomized trials: 20,703 men from the Physicians' Health Study I (1982–2007) and 36,295 women from the Women's Health Study (1992–2007). Egg consumption was ascertained using questionnaires, and we used the Cox proportional hazard model to estimate relative risks of type 2 diabetes. RESULTS—During mean follow-up of 20.0 years in men and 11.7 years in women, 1,921 men and 2,112 women developed type 2 diabetes. Compared with no egg consumption, multivariable adjusted hazard ratios for type 2 diabetes were 1.09 (95% CI 0.87–1.37), 1.09 (0.88–1.34), 1.18 (0.95–1.45), 1.46 (1.14–1.86), and 1.58 (1.25–2.01) for consumption of <1, 1, 2–4, 5–6, and ≥7 eggs/week, respectively, in men (P for trend <0.0001). Corresponding multivariable hazard ratios for women were 1.06 (0.92–1.22), 0.97 (0.83–1.12), 1.19 (1.03–1.38), 1.18 (0.88–1.58), and 1.77 (1.28–2.43), respectively (P for trend <0.0001). CONCLUSIONS—These data suggest that high levels of egg consumption (daily) are associated with an increased risk of type 2 diabetes in men and women. Confirmation of these findings in other populations is warranted.", "title": "Egg Consumption and Risk of Type 2 Diabetes in Men and Women" }, { "docid": "MED-4388", "text": "Objective To examine overall diet quality in relation to advanced age-related macular degeneration (AMD). Methods This case-control study identified 437 advanced AMD patients and 259 unrelated controls using stereoscopic color fundus photographs. Participants were predominantly non-Hispanic white men and women from North Carolina and Tennessee. A 97-item Block food frequency questionnaire was used to gather diet information, and overall diet quality was measured using the Healthy Eating Index (HEI) and Alternate Healthy Eating Index (AHEI). Results Participants in the highest quartile of diet quality had significantly reduced odds of AMD according to the AHEI score (0.54, 95% confidence interval 0.30 – 0.99) and non-significantly reduced odds of AMD according to the HEI (0.75, 0.41 – 1.38). Odds of AMD were also 51% lower in the highest quartile of fish intake compared to the lowest quartile (odds ratio = 0.49, 0.26 – 0.90). Conclusions We found that advanced AMD was significantly related to overall diet quality. The AHEI score may be a useful instrument for assessing AMD risk due to diet, and it could potentially be improved by incorporating more specific information regarding micronutrient intake.", "title": "Overall diet quality and age-related macular degeneration" }, { "docid": "MED-2810", "text": "Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be \"Curecumin\".", "title": "Curcumin as \"Curecumin\": from kitchen to clinic." }, { "docid": "MED-2894", "text": "AIM: To examine the influence of the black currant anthocyanins (BCACs) on the disease progression of open-angle glaucoma (OAG), a randomized, placebo-controlled, double-masked trial was made in 38 patients with OAG treated by antiglaucoma drops. METHODS: BCACs (50 mg/day, n = 19) or their placebos (n = 19) were orally administered once daily for a 24-month period. Systemic blood pressure, pulse rates, intraocular pressure (IOP), ocular blood circulation by laser-speckle flowgraphy, and Humphrey visual field mean deviation (MD) were measured during the 24-month period. RESULTS: As a main outcome measurement, we evaluated the difference between the groups in MD deterioration in the eye with a better MD from the trial's baseline through 24 months. A statistically significant difference was observed between the treatment groups in mean change from baseline in MD 24 months after therapy (p = 0.039, unpaired t test). Upon administration of BCACs, the ocular blood flows during the 24-month observational period increased in comparison with placebo-treated patients. However, no significant changes were observed in systemic and ocular conditions including IOP during the 24-month period. CONCLUSIONS: Our results suggest that oral administration of BCACs may be a safe and promising supplement for patients with OAG in addition to antiglaucoma medication. Copyright © 2012 S. Karger AG, Basel.", "title": "Two-year randomized, placebo-controlled study of black currant anthocyanins on visual field in glaucoma." }, { "docid": "MED-2978", "text": "Diets high in protein have shown positive effects on short-term weight reduction and glycaemic control. However, the understanding of how dietary macronutrient composition relates to long-term risk of type 2 diabetes is limited. The aim of the present study was to examine intakes of macronutrients, fibre and protein sources in relation to incident type 2 diabetes. In total, 27 140 individuals, aged 45-74 years, from the population-based Malmö Diet and Cancer cohort, were included. Dietary data were collected with a modified diet history method, including registration of cooked meals. During 12 years of follow-up, 1709 incident type 2 diabetes cases were identified. High protein intake was associated with increased risk of type 2 diabetes (hazard ratio (HR) 1.27 for highest compared with lowest quintile; 95 % CI 1.08, 1.49; P for trend = 0.01). When protein consumption increased by 5 % of energy at the expense of carbohydrates (HR 1.20; 95 % CI 1.09, 1.33) or fat (HR 1.21; 95 % CI 1.09, 1.33), increased diabetes risk was observed. Intakes in the highest quintiles of processed meat (HR 1.16; 95 % CI 1.00, 1.36; P for trend = 0.01) and eggs (HR 1.21; 95 % CI 1.04, 1.41; P for trend = 0.02) were associated with increased risk. Intake of fibre-rich bread and cereals was inversely associated with type 2 diabetes (HR 0.84; 95 % CI 0.73, 0.98; P for trend = 0.004). In conclusion, results from the present large population-based prospective study indicate that high protein intake is associated with increased risk of type 2 diabetes. Replacing protein with carbohydrates may be favourable, especially if fibre-rich breads and cereals are chosen as carbohydrate sources.", "title": "High intakes of protein and processed meat associate with increased incidence of type 2 diabetes." }, { "docid": "MED-3181", "text": "OBJECTIVE: To determine the frequency and features of psychiatric morbidity in a cross section of 38 outpatients with neurocysticercosis. METHODS: Diagnosis of neurocysticercosis was established by CT, MRI, and CSF analysis. Psychiatric diagnoses were made by using the present state examination and the schedule for affective disorders and schizophrenia-lifetime version; cognitive state was assessed by mini mental state examination and Strub and Black's mental status examination. RESULTS: Signs of psychiatric disease and cognitive decline were found in 65.8 and 87.5% of the cases respectively. Depression was the most frequent psychiatric diagnosis (52.6%) and 14.2% of the patients were psychotic. Active disease and intracranial hypertension were associated with higher psychiatric morbidity, and previous history of mood disorders was strongly related to current depression. Other variables, such as number and type of brain lesions, severity of neuropsychological deficits, epilepsy, and use of steroids did not correlate with mental disturbances in this sample. CONCLUSIONS: Psychiatric abnormalities, particularly depression syndromes, are frequent in patients with neurocysticercosis. Although regarded as a rare cause of dementia, mild cognitive impairment may be a much more prevalent neuropsychological feature of patients with neurocysticercosis. The extent to which organic mechanisms related to brain lesions may underlie the mental changes is yet unclear, although the similar sex distribution of patients with and without depression, as well as the above mentioned correlations, provide further evidence of the part played by organic factors in the cause of these syndromes.", "title": "Psychiatric manifestations of neurocysticercosis: a study of 38 patients from a neurology clinic in Brazil." }, { "docid": "MED-4984", "text": "Vegetarian and vegan diets offer significant benefits for diabetes management. In observational studies, individuals following vegetarian diets are about half as likely to develop diabetes, compared with non-vegetarians. In clinical trials in individuals with type 2 diabetes, low-fat vegan diets improve glycemic control to a greater extent than conventional diabetes diets. Although this effect is primarily attributable to greater weight loss, evidence also suggests that reduced intake of saturated fats and high-glycemic-index foods, increased intake of dietary fiber and vegetable protein, reduced intramyocellular lipid concentrations, and decreased iron stores mediate the influence of plant-based diets on glycemia. Vegetarian and vegan diets also improve plasma lipid concentrations and have been shown to reverse atherosclerosis progression. In clinical studies, the reported acceptability of vegetarian and vegan diets is comparable to other therapeutic regimens. The presently available literature indicates that vegetarian and vegan diets present potential advantages for the management of type 2 diabetes.", "title": "Vegetarian and vegan diets in type 2 diabetes management." }, { "docid": "MED-2815", "text": "Curcumin, an active polyphenol of the golden spice turmeric, is a highly pleiotropic molecule with the potential to modulate the biological activity of a number of signaling molecules. Traditionally, this polyphenol has been used in Asian countries to treat such human ailments as acne, psoriasis, dermatitis, and rash. Recent studies have indicated that curcumin can target newly identified signaling pathways including those associated with microRNA, cancer stem cells, and autophagy. Extensive research from preclinical and clinical studies has delineated the molecular basis for the pharmaceutical uses of this polyphenol against cancer, pulmonary diseases, neurological diseases, liver diseases, metabolic diseases, autoimmune diseases, cardiovascular diseases, and numerous other chronic diseases. Multiple studies have indicated the safety and efficacy of curcumin in numerous animals including rodents, monkeys, horses, rabbits, and cats and have provided a solid basis for evaluating its safety and efficacy in humans. To date, more than 65 human clinical trials of curcumin, which included more than 1000 patients, have been completed, and as many as 35 clinical trials are underway. Curcumin is now used as a supplement in several countries including the United States, India, Japan, Korea, Thailand, China, Turkey, South Africa, Nepal, and Pakistan. In this review, we provide evidence for the pharmaceutical uses of curcumin for various diseases. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.", "title": "Curcumin, a component of turmeric: from farm to pharmacy." }, { "docid": "MED-2888", "text": "Age-related macular degeneration (AMD) is a common disorder that causes irreversible loss of central vision. Increased intake of foods containing zeaxanthin may be effective in preventing AMD because the macula accumulates zeaxanthin and lutein, oxygenated carotenoids with antioxidant and blue light-absorbing properties. Lycium barbarum L. is a small red berry known as Fructus lycii and wolfberry in the West, and Kei Tze and Gou Qi Zi in Asia. Wolfberry is rich in zeaxanthin dipalmitate, and is valued in Chinese culture for being good for vision. The aim of this study, which was a single-blinded, placebo-controlled, human intervention trial of parallel design, was to provide data on how fasting plasma zeaxanthin concentration changes as a result of dietary supplementation with whole wolfberries. Fasting blood was collected from healthy, consenting subjects; fourteen subjects took 15 g/d wolfberry (estimated to contain almost 3 mg zeaxanthin) for 28 d. Repeat fasting blood was collected on day 29. Age- and sex-matched controls (n 13) took no wolfberry. Responses in the two groups were compared using the Mann-Whitney test. After supplementation, plasma zeaxanthin increased 2.5-fold: mean values on day 1 and 29 were 0.038 (sem 0.003) and 0.096 (sem 0.009) micromol/l (P<0.01), respectively, for the supplementation group; and 0.038 (sem 0.003) and 0.043 (sem 0.003) micromol/l (P>0.05), respectively, for the control group. This human supplementation trial shows that zeaxanthin in whole wolfberries is bioavailable and that intake of a modest daily amount markedly increases fasting plasma zeaxanthin levels. These new data will support further study of dietary strategies to maintain macular pigment density.", "title": "Fasting plasma zeaxanthin response to Fructus barbarum L. (wolfberry; Kei Tze) in a food-based human supplementation trial." }, { "docid": "MED-4962", "text": "BACKGROUND: Vibrio species are a rare cause of necrotizing soft-tissue infections and primary septicemia, which are likely to occur in patients with hepatic disease, diabetes, adrenal insufficiency, and immunocompromised conditions. These organisms thrive in warm seawater and are often present in raw oysters, shellfish, and other seafood. This study examined fulminating clinical characteristics of Vibrio vulnificus and Vibrio cholerae non-O1 soft-tissue infections and identified outcome predictors. MATERIALS: Thirty patients with necrotizing fasciitis and sepsis caused by Vibrio species were retrospectively reviewed. Twenty-eight patients had a history of contact with seawater or raw seafood. Eight patients had hepatic disease such as hepatitis or liver cirrhosis, and seven patients had diabetes mellitus. Nine patients had hepatic dysfunction combined with diabetes mellitus. Microbiology laboratory culture studies confirmed V. vulnificus in 23 patients and V. cholerae non-O1 in seven patients. RESULTS: Surgical debridement or immediate limb amputation was initially performed in all patients with necrotizing soft-tissue infections. Eleven patients (37%) died within several days of admission and 19 survived. The mortality of V. cholerae non-O1 group (57%) is higher than that of the V. vulnificus group (30%). A significantly higher mortality rate was noted in patients with initial presentations of a systolic blood pressure of < or =90 mm Hg, leukopenia, decreased platelet counts, and a combination of hepatic dysfunction and diabetes mellitus. CONCLUSIONS: Vibrio necrotizing soft-tissue infections should be suspected in patients with appropriate clinical findings and history of contact with seawater or seafood. V. cholerae non-O1 may cause bacteremia more often than V. vulnificus in patients with liver cirrhosis. Early fasciotomy and culture-directed antimicrobial therapy are aggressively recommended in patients with hypotensive shock, leukopenia, high band forms of white blood cells, decreased platelet counts, severe hypoalbuminemia, and underlying chronic illness, such as hepatic dysfunction and diabetes mellitus.", "title": "Necrotizing soft-tissue infections and primary sepsis caused by Vibrio vulnificus and Vibrio cholerae non-O1." }, { "docid": "MED-2813", "text": "The use of turmeric, derived from the root of the plant Curcuma longa, for treatment of different inflammatory diseases has been described in Ayurveda and in traditional Chinese medicine for thousands of years. The active component of turmeric responsible for this activity, curcumin, was identified almost two centuries ago. Modern science has revealed that curcumin mediates its effects by modulation of several important molecular targets, including transcription factors (e.g., NF-kappaB, AP-1, Egr-1, beta-catenin, and PPAR-gamma), enzymes (e.g., COX2, 5-LOX, iNOS, and hemeoxygenase-1), cell cycle proteins (e.g., cyclin D1 and p21), cytokines (e.g., TNF, IL-1, IL-6, and chemokines), receptors (e.g., EGFR and HER2), and cell surface adhesion molecules. Because it can modulate the expression of these targets, curcumin is now being used to treat cancer, arthritis, diabetes, Crohn's disease, cardiovascular diseases, osteoporosis, Alzheimer's disease, psoriasis, and other pathologies. Interestingly, 6-gingerol, a natural analog of curcumin derived from the root of ginger (Zingiber officinalis), exhibits a biologic activity profile similar to that of curcumin. The efficacy, pharmacologic safety, and cost effectiveness of curcuminoids prompt us to \"get back to our roots.\"", "title": "Curcumin: getting back to the roots." }, { "docid": "MED-4384", "text": "PURPOSE: To explore the association between the consumption of fruits and vegetables and the presence of glaucoma. DESIGN: Cross-sectional cohort study. METHODS: In a sample of 1,155 women located in multiple centers in the United States, glaucoma specialists diagnosed glaucoma in at least one eye by assessing optic nerve head photographs and 76-point suprathreshold screening visual fields. Consumption of fruits and vegetables was assessed using the Block Food Frequency Questionnaire. The relationship between selected fruit and vegetable consumption and glaucoma was investigated using adjusted logistic regression models. RESULTS: Among 1,155 women, 95 (8.2%) were diagnosed with glaucoma. In adjusted analysis, the odds of glaucoma risk were decreased by 69% (odds ratio [OR], 0.31; 95% confidence interval [CI], 0.11 to 0.91) in women who consumed at least one serving per month of green collards and kale compared with those who consumed fewer than one serving per month, by 64% (OR, 0.36; 95% CI, 0.17 to 0.77) in women who consumed more than two servings per week of carrots compared with those who consumed fewer than one serving per week, and by 47% (OR, 0.53; 95% CI, 0.29 to 0.97) in women who consumed at least one serving per week of canned or dried peaches compared with those who consumed fewer than one serving per month. CONCLUSIONS: A higher intake of certain fruits and vegetables may be associated with a decreased risk of glaucoma. More studies are needed to investigate this relationship.", "title": "Glaucoma risk and the consumption of fruits and vegetables among older women in the study of osteoporotic fractures." }, { "docid": "MED-1996", "text": "Until recently, the majority of cases of diabetes mellitus among children and adolescents were immune-mediated type 1a diabetes. Obesity has led to a dramatic increase in the incidence of type 2 diabetes (T2DM) among children and adolescents over the past 2 decades. Obesity is strongly associated with insulin resistance, which, when coupled with relative insulin deficiency, leads to the development of overt T2DM. Children and adolescents with T2DM may experience the microvascular and macrovascular complications of this disease at younger ages than individuals who develop diabetes in adulthood, including atherosclerotic cardiovascular disease, stroke, myocardial infarction, and sudden death; renal insufficiency and chronic renal failure; limb-threatening neuropathy and vasculopathy; and retinopathy leading to blindness. Health care professionals are advised to perform the appropriate screening in children at risk for T2DM, diagnose the condition as early as possible, and provide rigorous management of the disease.", "title": "Childhood obesity and type 2 diabetes mellitus." }, { "docid": "MED-3786", "text": "This article describes the development of a series of choline- and betaine-controlled diets that were served to research subjects as part of an ongoing study of diet requirements in humans. These diets were developed based on the analysis of choline and betaine in individual foods. The calculated diets were compared with analyses of all foods combined into a single sample for each day. The laboratory analyses of choline and betaine in the whole-diet aliquots matched the estimated amounts in the diets that were calculated from the analyses of individual foods. These diets were adjusted for several levels of choline and betaine and were well accepted by research subjects who consumed them for a time period of up to 2 months. This article describes applications of this diet for use in clinical research on methyl-group requirements in humans and for use in clinical practice for counseling the client who requires a choline-controlled diet.", "title": "Choline- and betaine-defined diets for use in clinical research and for the management of trimethylaminuria." }, { "docid": "MED-2001", "text": "In 2010, approximately one in three U.S. adults aged≥20 years (an estimated 79 million persons) had prediabetes, a condition in which blood glucose or hemoglobin A1c (A1c) levels are higher than normal but not high enough to be classified as diabetes. Persons with prediabetes are at high risk for developing type 2 diabetes, which accounts for 90%-95% of all cases of diabetes. Each year, 11% of persons with prediabetes who do not lose weight and do not engage in moderate physical activity will progress to type 2 diabetes during the average 3 years of follow-up. Evidence-based lifestyle programs that encourage dietary changes, moderate-intensity physical activity, and modest weight loss can delay or prevent type 2 diabetes in persons with prediabetes. Identifying persons with prediabetes and informing them about their increased risk for type 2 diabetes are first steps in encouraging persons with prediabetes to make healthy lifestyle changes. However, during 2005-2006, only approximately 7% of persons with prediabetes were aware that they had prediabetes. To examine recent changes in awareness of prediabetes and factors associated with awareness among adults aged≥20 years, CDC analyzed data from the National Health and Nutrition Examination Survey (NHANES). This report describes the results of that analysis, which indicated that, during 2009-2010, approximately 11% of those with prediabetes were aware of their condition. Furthermore, during 2005-2010, estimated awareness of prediabetes was <14% across all population subgroups, different levels of health-care access or use, and other factors. In the United States, persons with prediabetes, including those with regular access to health care, might benefit from efforts aimed at making them aware that they are at risk for developing type 2 diabetes and that they can reduce that risk by making modest lifestyle changes. Efforts are needed to increase awareness.", "title": "Awareness of prediabetes--United States, 2005-2010." }, { "docid": "MED-2809", "text": "Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn’s disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin’s pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF–κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E2, prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the effect of curcumin has been investigated.", "title": "Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials" }, { "docid": "MED-4955", "text": "Research on infectious agents as a possible cause of schizophrenia has become prominent in the past decade. Toxoplasma gondii has emerged as a prime candidate for a variety of reasons; (i) many studies have reported that individuals with schizophrenia, compared to controls, have a higher prevalence of antibodies to T. gondii, (ii) some individuals with adult toxoplasmosis develop psychotic symptoms similar to those of schizophrenia, (iii) epidemiologically, there are many similarities between toxoplasmosis and schizophrenia, (iv) antipsychotic drugs known to be effective in schizophrenia also inhibit some parasites, including T. gondii, (v) Toxoplasma has been shown to induce elevated levels of dopamine in experimentally infected animals (elevated dopamine is commonly seen in individuals with schizophrenia) and (vi) studies have shown that individuals with schizophrenia, compared to controls, have had greater exposure to cats in childhood. A number of questions remain concerning a role for Toxoplasma in the aetiology of schizophrenia, including the roles of strain variation, the timing and source of infection, and the role of host genes in determining disease susceptibility. The establishment of a firm association between Toxoplasma and the aetiology of schizophrenia and related disorders would represent a major breakthrough in the understanding of these disorders and would lead to novel methods for their treatment and prevention.", "title": "Toxoplasma and schizophrenia." }, { "docid": "MED-2822", "text": "Curcumin is known to possess potent antiinflammatory and antiarthritic properties. This pilot clinical study evaluated the safety and effectiveness of curcumin alone, and in combination with diclofenac sodium in patients with active rheumatoid arthritis (RA). Forty-five patients diagnosed with RA were randomized into three groups with patients receiving curcumin (500 mg) and diclofenac sodium (50 mg) alone or their combination. The primary endpoints were reduction in Disease Activity Score (DAS) 28. The secondary endpoints included American College of Rheumatology (ACR) criteria for reduction in tenderness and swelling of joint scores. Patients in all three treatment groups showed statistically significant changes in their DAS scores. Interestingly, the curcumin group showed the highest percentage of improvement in overall DAS and ACR scores (ACR 20, 50 and 70) and these scores were significantly better than the patients in the diclofenac sodium group. More importantly, curcumin treatment was found to be safe and did not relate with any adverse events. Our study provides the first evidence for the safety and superiority of curcumin treatment in patients with active RA, and highlights the need for future large-scale trials to validate these findings in patients with RA and other arthritic conditions. Copyright © 2012 John Wiley & Sons, Ltd.", "title": "A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis." }, { "docid": "MED-3180", "text": "Four cases of suggestive inflammatory aneurysms in patients with neurocysticercosis have been described. We report a case of a 49-year-old woman who presented with subarachnoid haemorrhage from a right middle cerebral artery bifurcation aneurysm and had a casual relationship with neurocysticercosis. At surgery, a viable cysticercus without signs of inflammation or thickened leptomeninges was found in the distal position of the aneurysm. Postoperatively, the patient received albendazole and dextrochlorpheniramine. In the subsequent three years, the patient was asymptomatic and took drugs to prevent convulsion and arterial hypertension. The relationship between NCC and the presence of cerebral aneurysm is discussed.", "title": "Aneurysm and Neurocysticercosis: Casual or Causal Relationship? Case Report and Review of the Literature" }, { "docid": "MED-2221", "text": "Context: In 1954 the tobacco industry paid to publish the “Frank Statement to Cigarette Smokers” in hundreds of U.S. newspapers. It stated that the public's health was the industry's concern above all others and promised a variety of good-faith changes. What followed were decades of deceit and actions that cost millions of lives. In the hope that the food history will be written differently, this article both highlights important lessons that can be learned from the tobacco experience and recommends actions for the food industry. Methods: A review and analysis of empirical and historical evidence pertaining to tobacco and food industry practices, messages, and strategies to influence public opinion, legislation and regulation, litigation, and the conduct of science. Findings: The tobacco industry had a playbook, a script, that emphasized personal responsibility, paying scientists who delivered research that instilled doubt, criticizing the “junk” science that found harms associated with smoking, making self-regulatory pledges, lobbying with massive resources to stifle government action, introducing “safer” products, and simultaneously manipulating and denying both the addictive nature of their products and their marketing to children. The script of the food industry is both similar to and different from the tobacco industry script. Conclusions: Food is obviously different from tobacco, and the food industry differs from tobacco companies in important ways, but there also are significant similarities in the actions that these industries have taken in response to concern that their products cause harm. Because obesity is now a major global problem, the world cannot afford a repeat of the tobacco history, in which industry talks about the moral high ground but does not occupy it.", "title": "The Perils of Ignoring History: Big Tobacco Played Dirty and Millions Died. How Similar Is Big Food?" }, { "docid": "MED-2882", "text": "Retinal pigment epithelium (RPE) cells are vital for retinal health. However, they are susceptible to injury with ageing and exposure to excessive light, including UV (100-380 nm) and visible (380-760 nm) radiation. To evaluate the protective effect of blueberry anthocyanins on RPE cells, in vitro cell models of replicative senescent and light-induced damage were established in the present study. After purification and fractionation, blueberry anthocyanin extracts (BAE) were yielded with total anthocyanin contents of 31·0 (SD 0·5) % and were used in this study. Replicative senescence of RPE cells was induced by repeatedly passaging cells from the fourth passage to the tenth. From the fifth passage, cultured RPE cells began to enter a replicative senescence, exhibiting reduced cell proliferation along with an increase in the number of β-galactosidase-positive cells. RPE cells maintained high cell viability (P < 0·01) and a low (P < 0·01) percentage of β-galactosidase-positive cells when treated with 0·1 μg/ml BAE. In contrast, after exposure to 2500 (SD 500) lx light (420-800 nm) for 12 h, RPE cells in the positive control (light exposure, no BAE treatment) exhibited premature senescence, low (P < 0·01) cell viability and increased (P < 0·01) vascular endothelial growth factor (VEGF) release compared with negative control cells, which were not subjected to light irradiation and BAE exposure. Correspondingly, BAE is beneficial to RPE cells by protecting these cells against light-induced damage through the suppression of ageing and apoptosis as well as the down-regulation of the over-expressed VEGF to normal level. These results demonstrate that BAE is efficacious against senescence and light-induced damage of RPE cells.", "title": "Blueberry anthocyanins: protection against ageing and light-induced damage in retinal pigment epithelial cells." }, { "docid": "MED-1993", "text": "Type 2 diabetes mellitus is emerging as a new clinical problem within pediatric practice. Recent reports indicate an increasing prevalence of type 2 diabetes mellitus in children and adolescents around the world in all ethnicities, even if the prevalence of obesity is not increasing any more. The majority of young people diagnosed with type 2 diabetes mellitus was found in specific ethnic subgroups such as African-American, Hispanic, Asian/Pacific Islanders and American Indians. Clinicians should be aware of the frequent mild or asymptomatic manifestation of type 2 diabetes mellitus in childhood. Therefore, a screening seems meaningful especially in high risk groups such as children and adolescents with obesity, relatives with type 2 diabetes mellitus, and clinical features of insulin resistance (hypertension, dyslipidemia, polycystic ovarian syndrome, or acanthosis nigricans). Treatment of choice is lifestyle intervention followed by pharmacological treatment (e.g., metformin). New drugs such as dipeptidyl peptidase inhibitors or glucagon like peptide 1 mimetics are in the pipeline for treatment of youth with type 2 diabetes mellitus. However, recent reports indicate a high dropout of the medical care system of adolescents with type 2 diabetes mellitus suggesting that management of children and adolescents with type 2 diabetes mellitus requires some remodeling of current healthcare practices.", "title": "Type 2 diabetes mellitus in children and adolescents" }, { "docid": "MED-4969", "text": "Transmission of viruses, bacteria, and parasites to food by way of improperly washed hands is a major contributing factor in the spread of foodborne illnesses. Field observers have assessed compliance with hand washing regulations, yet few studies have included consideration of frequency and methods used by sectors of the food service industry or have included benchmarks for hand washing. Five 3-h observation periods of employee (n = 80) hand washing behaviors during menu production, service, and cleaning were conducted in 16 food service operations for a total of 240 h of direct observation. Four operations from each of four sectors of the retail food service industry participated in the study: assisted living for the elderly, childcare, restaurants, and schools. A validated observation form, based on 2005 Food Code guidelines, was used by two trained researchers. Researchers noted when hands should have been washed, when hands were washed, and how hands were washed. Overall compliance with Food Code recommendations for frequency during production, service, and cleaning phases ranged from 5% in restaurants to 33% in assisted living facilities. Procedural compliance rates also were low. Proposed benchmarks for the number of times hand washing should occur by each employee for each sector of food service during each phase of operation are seven times per hour for assisted living, nine times per hour for childcare, 29 times per hour for restaurants, and 11 times per hour for schools. These benchmarks are high, especially for restaurant employees. Implementation would mean lost productivity and potential for dermatitis; thus, active managerial control over work assignments is needed. These benchmarks can be used for training and to guide employee hand washing behaviors.", "title": "Hand washing frequencies and procedures used in retail food services." }, { "docid": "MED-2820", "text": "Scope The incidence of cancer is significantly lower in regions where turmeric is heavily consumed. Whether lower cancer incidence is due to turmeric was investigated by examining its effects on tumor cell proliferation, on pro-inflammatory transcription factors NF-κB and STAT3, and on associated gene products. Methods and results Cell proliferation and cell cytotoxicity were measured by the MTT method, NF-κB activity by EMSA, protein expression by Western blot analysis, ROS generation by FACS analysis, and osteoclastogenesis by TRAP assay. Turmeric inhibited NF-κB activation and down-regulated NF-κB-regulated gene products linked to survival (Bcl-2, cFLIP, XIAP, and cIAP1), proliferation (cyclin D1 and c-Myc), and metastasis (CXCR4) of cancer cells. The spice suppressed the activation of STAT3, and induced the death receptors (DR)4 and DR5. Turmeric enhanced the production of ROS, and suppressed the growth of tumor cell lines. Furthermore, turmeric sensitized the tumor cells to chemotherapeutic agents capecitabine and taxol. Turmeric was found to be more potent than pure curcumin for cell growth inhibition. Turmeric also inhibited NF-κB activation induced by RANKL that correlated with the suppression of osteoclastogenesis. Conclusion Our results indicate that turmeric can effectively block the proliferation of tumor cells through the suppression of NF-κB and STAT3 pathways.", "title": "Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis" }, { "docid": "MED-2891", "text": "BACKGROUND: Patients who report use of herbs to their physicians may not be able to accurately describe the ingredients or recommended dosage because the products for the same herb may differ. The purpose of this study was to describe variations in label information of products for each of the 10 most commonly purchased herbs. METHODS: Products for each of 10 herbs were surveyed in a convenience sample of 20 retail stores in a large metropolitan area. Herbs were those with the greatest sales dollars in 1998: echinacea, St John's wort, Ginkgo biloba, garlic, saw palmetto, ginseng, goldenseal, aloe, Siberian ginseng, and valerian. RESULTS: Each herb had a large range in label ingredients and recommended daily dose (RDD) across available products. Strengths were not directly comparable because of ingredient variability. Among 880 products, 43% were consistent with a benchmark in ingredients and RDD, 20% in ingredients only, and 37% were either not consistent or label information was insufficient. Price per RDD was a significant predictor of consistency with the benchmark, but store type was not. CONCLUSIONS: Persons self-medicating with an herb may be ingesting ingredients substantially different from that recommended by a benchmark, both in quantity and content. Higher price per label RDD was the best predictor of consistency with a benchmark. This study demonstrates that health providers and consumers need to closely examine label ingredients of presumably the same or similar herbal products.", "title": "Variations in product choices of frequently purchased herbs: caveat emptor." }, { "docid": "MED-2890", "text": "Myopia is a worldwide public health problem. However, its understanding is incomplete, and many of its preventative and therapeutic aspects remain controversial. Nearwork is a primary, environmentally based factor in the aetiology of permanent myopia (PM), with nearwork-induced transient myopia (NITM) being a possible contributory component. A relationship between PM and NITM has been suggested, but that connection has remained somewhat indirect and elusive. However, based on recent converging evidence from clinical, laboratory and modelling studies, a five-fold argument will be advanced for a possible link between PM and NITM.", "title": "Nearwork-induced transient myopia (NITM) and permanent myopia--is there a link?" }, { "docid": "MED-5092", "text": "BACKGROUND: While there is a large body of data on the effects of long-chain polyunsaturated fatty acid supplementation of infant formula on visual and cognitive maturation during infancy, longterm visual and cognitive outcome data from randomized trials are scarce. AIM: To evaluate docosahexaenoic acid (DHA) and arachidonic acid (ARA)-supplementation of infant formula on visual and cognitive outcomes at 4 years of age. METHODS: Fifty-two of 79 healthy term infants who were enrolled in a single-center, double-blind, randomized clinical trial of DHA and ARA supplementation of infant formula were available for follow-up at 4 years of age. In addition, 32 breast-fed infants served as a \"gold standard\". Outcome measures were visual acuity and the Wechsler Preschool and Primary Scale of Intelligence--Revised. RESULTS: At 4 years, the control formula group had poorer visual acuity than the breast-fed group; the DHA- and DHA+ARA-supplemented groups did not differ significantly from the breast-fed group. The control formula and DHA-supplemented groups had Verbal IQ scores poorer than the breast-fed group. CONCLUSION: DHA and ARA-supplementation of infant formula supports visual acuity and IQ maturation similar to that of breast-fed infants.", "title": "Visual acuity and cognitive outcomes at 4 years of age in a double-blind, randomized trial of long-chain polyunsaturated fatty acid-supplemented in..." }, { "docid": "MED-3250", "text": "The purpose of this study was to determine whether a single LDL apheresis would improve impaired endothelium-dependent dilation of the coronary artery in patients with hypercholesterolemia. Hypercholesterolemia is associated with impaired endothelial function, and human studies using cholesterol-lowering drugs indicate that endothelial function in the coronary arteries improves with reduction of serum LDL cholesterol over 6 to 12 months. The internal diameter of the left coronary artery and the coronary blood flow were measured by intracoronary Doppler-wire measurement and quantitative angiography before and immediately after a single LDL apheresis in a population of 15 patients with familial hypercholesterolemia. Endothelium-dependent vasodilation was assessed by intracoronary infusion of acetylcholine (1, 10, and 50 microg/min), and endothelium-independent vasodilation was assessed by intracoronary bolus infusion of isosorbide dinitrate (2.5 mg) or papaverine (10 mg). A single 3-hour LDL apheresis reduced serum LDL cholesterol by an average of 86.6 +/- 1.7%. After the LDL apheresis, the changes in the coronary artery diameter and coronary blood flow in response to an infusion of 50 microg/min of acetylcholine increased significantly compared to the pre-apheresis values (from -19.7 +/- 4.8 to -2.9 +/- 3.0% [P < 0.01] and from 80.7 +/- 27.6 to 155.3 +/- 23.5% [P < 0.01], respectively). The LDL apheresis did not significantly change the response of either parameter to infusion with isosorbide dinitrate or papaverine. The endothelial function of the epicardial coronary artery and the coronary microvasculature improved in hypercholesterolemic patients after only a single LDL apheresis, a procedure that markedly reduces the serum level of LDL cholesterol. Copyright 2004 Wiley-Liss, Inc.", "title": "Improvement of endothelium-dependent coronary vasodilation after a single LDL apheresis in patients with hypercholesterolemia." }, { "docid": "MED-2000", "text": "Background People with diabetes can suffer from diverse complications that seriously erode quality of life. Diabetes, costing the United States more than $174 billion per year in 2007, is expected to take an increasingly large financial toll in subsequent years. Accurate projections of diabetes burden are essential to policymakers planning for future health care needs and costs. Methods Using data on prediabetes and diabetes prevalence in the United States, forecasted incidence, and current US Census projections of mortality and migration, the authors constructed a series of dynamic models employing systems of difference equations to project the future burden of diabetes among US adults. A three-state model partitions the US population into no diabetes, undiagnosed diabetes, and diagnosed diabetes. A four-state model divides the state of \"no diabetes\" into high-risk (prediabetes) and low-risk (normal glucose) states. A five-state model incorporates an intervention designed to prevent or delay diabetes in adults at high risk. Results The authors project that annual diagnosed diabetes incidence (new cases) will increase from about 8 cases per 1,000 in 2008 to about 15 in 2050. Assuming low incidence and relatively high diabetes mortality, total diabetes prevalence (diagnosed and undiagnosed cases) is projected to increase from 14% in 2010 to 21% of the US adult population by 2050. However, if recent increases in diabetes incidence continue and diabetes mortality is relatively low, prevalence will increase to 33% by 2050. A middle-ground scenario projects a prevalence of 25% to 28% by 2050. Intervention can reduce, but not eliminate, increases in diabetes prevalence. Conclusions These projected increases are largely attributable to the aging of the US population, increasing numbers of members of higher-risk minority groups in the population, and people with diabetes living longer. Effective strategies will need to be undertaken to moderate the impact of these factors on national diabetes burden. Our analysis suggests that widespread implementation of reasonably effective preventive interventions focused on high-risk subgroups of the population can considerably reduce, but not eliminate, future increases in diabetes prevalence.", "title": "Projection of the year 2050 burden of diabetes in the US adult population: dynamic modeling of incidence, mortality, and prediabetes prevalence" }, { "docid": "MED-2004", "text": "The incidence and prevalence of diabetes (primarily type 2 diabetes) has risen sharply since 1990. It is projected to increase another 64% between 2010 and 2025, affecting 53.1 million people and resulting in medical and societal costs of a half trillion dollars a year. We know how to prevent many cases of diabetes and how to treat it effectively. Early appropriate treatment makes a significant difference in preventing major complications and reducing premature death, but it does not cure the disease. Early detection of prediabetes, in conjunction with lifestyle changes, can reduce the number of people with diabetes. A dramatic reduction in diabetes prevalence over time will require significant lifestyle changes on the part of society as a whole. The purpose of this study is to increase public awareness of the severity of regional diabetes trends by providing detailed forecasts for all states and several metropolitan areas for 2010, 2015, and 2025. A model was created to utilize the latest national diabetes and population data and projections, and to transform these into state and metropolitan area forecasts for the whole population and major subgroups. These forecasts were then summarized in easy-to-understand briefing papers for each state and selected metro areas, which are provided online for easy public access. This research is important because little data exist that project the future prevalence and potential costs of diabetes at the state and metro area level. With this data, key stakeholders can make informed decisions concerning diabetes, its impact on their communities, and resource allocation.", "title": "Creating public awareness: state 2025 diabetes forecasts." }, { "docid": "MED-3422", "text": "In the present study, we tested the effect of a Mediterranean-style diet on sexual function in women with the metabolic syndrome. Women were identified in our database of subjects participating in controlled trials evaluating the effect of lifestyle changes and were included if they had a diagnosis of female sexual dysfunction (FSD) associated with a diagnosis of metabolic syndrome, a complete follow-up in the study trial and an intervention focused mainly on dietary changes. Fifty-nine women met the inclusion/exclusion criteria; 31 out of them were assigned to the Mediterranean-style diet and 28 to the control diet. After 2 years, women on the Mediterranean diet consumed more fruits, vegetables, nuts, whole grain and olive oil as compared with the women on the control diet. Female sexual function index (FSFI) improved in the intervention group, from a mean basal value of 19.7+/-3.1 to a mean post-treatment value of 26.1+/-4.1 (P=0.01), and remained stable in the control group. C-reactive protein (CRP) levels were significantly reduced in the intervention group (P<0.02). No single sexual domain (desire, arousal, lubrication, orgasm, satisfaction, pain) was significantly ameliorated by the dietary treatment, suggesting that the whole female sexuality may find benefit from lifestyle changes. A Mediterranean-style diet might be effective in ameliorating sexual function in women with metabolic syndrome.", "title": "Mediterranean diet improves sexual function in women with the metabolic syndrome." }, { "docid": "MED-5124", "text": "Background Reduction in dietary cholesterol is recommended to prevent cardiovascular disease (CVD). Although eggs are important sources of cholesterol and other nutrients, limited and inconsistent data are available on the effects of egg consumption on the risk of CVD and mortality. Objectives To examine the association between egg consumption and the risk of CVD and mortality. Design Prospective cohort study of 21,327 participants from the Physicians' Health Study I. Egg consumption was assessed using a simple abbreviated food questionnaire. We used Cox regression to estimate relative risks. Results After an average follow up of 20 years, a total of 1,550 new myocardial infarction (MI), 1,342 incident strokes, and 5,169 deaths occurred in this cohort. Egg consumption was not associated with incident MI or stroke in a multivariable Cox regression. In contrast, adjusted hazard ratios (95% CI) for mortality were 1.0 (reference), 0.94 (0.87-1.02), 1.03 (0.95-1.11), 1.05 (0.93-1.19), and 1.23 (1.11-1.36) for egg consumption of <1, 1, 2-4, 5-6, and 7+ per week, respectively, (p for trend <0.0001). This association was stronger among diabetic subjects with a 2-fold increased risk of death comparing the highest to the lowest category of egg consumption than non-diabetic subjects (HR: 1.22 (1.09-1.35) (p for interaction 0.09). Conclusions Our data suggest that infrequent egg consumption does not influence the risk of CVD and only confers a modest increased risk for total mortality in male physicians. In addition, egg consumption was positively related to mortality and such relation was stronger among diabetic subjects in this selective population.", "title": "Egg Consumption and Cardiovascular Disease and Mortality The Physicians' Health Study" }, { "docid": "MED-2005", "text": "Diabetic retinopathy and diabetic nephropathy extract an enormous toll on patients with diabetes and an enormous burden on the health care system. With aggressive control of glycemia and blood pressure, coupled with aggressive use of laser photocoagulation and treatment of microalbuminuria, these problems can largely be eliminated. In the future, specific interventions may emerge that will allow interdiction of the pathophysiologic processes that lead to initiation and progression of these microvascular complications. The challenge for the primary care physician and diabetologist is to attain excellent glycemic control and aggressive control of blood pressure, while assuring that every patient has appropriate dilated fundus examinations at least annually, preferably by an ophthalmologist or retinal specialist, and regular screening for microalbuminuria. With such medical management, appropriate intervention can occur to reduce the risk of blindness and renal failure and to lessen the burden from diabetic retinopathy and nephropathy.", "title": "Microvascular complications. Retinopathy and nephropathy." }, { "docid": "MED-1655", "text": "In 1940, a young German refugee physician scientist at Duke University in Durham, North Carolina began to treat patients with accelerated or \"malignant\" hypertension with a radical diet consisting of only white rice and fruit, with strikingly favorable results. He reported rapid reduction in blood pressure, rapid improvement in renal failure, papilledema, congestive heart failure and other manifestations of this previously fatal illness. This treatment was based on his theory that the kidney had both an excretory and a metabolic function, and that removing most of the sodium and protein burden from this organ enabled it to regain its normal ability to perform its more important metabolic functions. It was also effective in \"ordinary\" hypertension, in the absence of the dramatic vasculopathy of the accelerated form. The results were so dramatic that many experienced physicians suspected him of falsifying data. Among these results was the normalization of the ECG changes seen with hypertension. This paper reviews his published experience with this radical therapy, its controversial rise to fame, and its decline in popularity with the advent of effective antihypertensive drugs. It features the ECG changes seen in this then fatal disease, and the reversal of these changes by the rice diet. This treatment, though very difficult for the patient, produced effects which make it equal or superior to current multi-drug treatment of hypertension. A poorly known but important observation was that patients who were able to follow the regime, and who were slowly guided through a gradual modification of the diet over many months, were able to transition into a very tolerable low fat, largely vegetarian diet, while leading a normal, active life, without medications, indicating that the disease state had been permanently modified. Copyright © 2014 Elsevier Inc. All rights reserved.", "title": "An archaeologic dig: a rice-fruit diet reverses ECG changes in hypertension." }, { "docid": "MED-3396", "text": "OBJECTIVES: To summarize and compare evidence on harms in sildenafil- and placebo-treated men with erectile dysfunction (ED) in a systematic review and meta-analysis. METHODS: Randomized placebo-controlled trials (RCTs) were identified using an electronic search in MEDLINE, EMBASE, PsycINFO, SCOPUS, and Cochrane CENTRAL. The rates of any adverse events (AEs), most commonly reported AEs, withdrawals because of adverse events, and serious adverse events were ascertained and compared between sildenafil and placebo groups. The results of men with ED were stratified by clinical condition(s). Statistical heterogeneity was explored. Meta-analyses based on random-effects model were also performed. RESULTS: A total of 49 RCTs were included. Sildenafil-treated men had a higher risk for all-cause AEs (RR = 1.56, 95% CI: 1.38, 1.76), headache, flushing, dyspepsia, and visual disturbances compared with placebo-treated men. The magnitude of excess risk was greater in fixed- than in flexible-dose trials. The rates of serious adverse events and withdrawals because of adverse events did not differ in sildenafil vs placebo groups. A higher dose of sildenafil corresponded to a greater risk of AEs. The increased risk of harms was observed within and across clinically defined specific groups of patients. CONCLUSIONS: There was a lack of RCTs reporting long-term (>6 months) harms data. In short-term trials, men with ED randomized to sildenafil had an increased risk of all-cause any AEs, headache, flushing, dyspepsia, and visual disturbances. The exploration of different modes of dose optimization of sildenafil may be warranted.", "title": "Oral sildenafil citrate (viagra) for erectile dysfunction: a systematic review and meta-analysis of harms." }, { "docid": "MED-2006", "text": "Eisenberg's helical hydrophobic moment (less than mu H greater than) algorithm was applied to the analysis of the primary structure of amphipathic alpha-helical peptide hormones and an optimal method for identifying other peptides of this class determined. We quantitate and compare known amphipathic helical peptide hormones with a second group of peptides with proven nonamphipathic properties and determine the best method of distinguishing between them. The respective means of the maximum 11 residue less than mu H greater than for the amphipathic helical and control peptides were 0.46 (+/-/-0.07) and 0.33 (0.07) (P + 0.004). To better reflect the amphipathic potential of the entire peptide, the percent of 11 residue segments in each peptide above a particular less than mu H greater than was plotted vs less than mu H greater than. The resulting curves are referred to as HM-C. The mean HM-C (of the two groups) was highly significantly different such that the HM-C method was superior to others in its ability to distinguish amphipathic from nonamphipathic peptides. Several potential new members of this structural class were identified using this approach. Molecular modeling of a portion of one of these, prolactin inhibitory factor, reveals a strongly amphipathic alpha helix at residues 4-21. This computer-based method may enable rapid identification of peptides of the amphipathic alpha-helix class.", "title": "Identification of peptide hormones of the amphipathic helix class using the helical hydrophobic moment algorithm." }, { "docid": "MED-2895", "text": "PURPOSE: The retinal carotenoids lutein (L) and zeaxanthin (Z) that form the macular pigment (MP) may help to prevent neovascular age-related macular degeneration. The purpose of this study was to determine whether MP density in the retina could be raised by increasing dietary intake of L and Z from foods. METHODS: Macular pigment was measured psychophysically for 13 subjects. Serum concentrations of L, Z, and beta-carotene were measured by high-performance liquid chromatography. Eleven subjects modified their usual daily diets by adding 60 g of spinach (10.8 mg L, 0.3 mg Z, 5 mg beta-carotene) and ten also added 150 g of corn (0.3 mg Z, 0.4 mg L); two other subjects were given only corn. Dietary modification lasted up to 15 weeks. RESULTS: For the subjects fed spinach or spinach and corn, three types of responses to dietary modification were identified: Eight \"retinal responders\" had increases in serum L (mean, 33%; SD, 22%) and in MP density (mean, 19%; SD, 11%); two \"retinal nonresponders\" showed substantial increases in serum L (mean, 31%) but not in MP density (mean, -11%); one \"serum and retinal nonresponder\" showed no changes in serum L, Z, or beta-carotene and no change in MP density. For the two subjects given only corn, serum L changed little (+11%, -6%), but in one subject serum Z increased (70%) and MP density increased (25%). CONCLUSIONS: Increases in MP density were obtained within 4 weeks of dietary modification for most, but not all, subjects. When MP density increased with dietary modification, it remained elevated for at least several months after resuming an unmodified diet. Augmentation of MP for both experimental and clinical investigation appears to be feasible for many persons.", "title": "Dietary modification of human macular pigment density." }, { "docid": "MED-2007", "text": "BACKGROUND: Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are pre-diabetic states, treatment of which may prevent or delay the onset of overt diabetes and thus potentially reduce major cardiovascular (CV) events. We therefore sought to determine whether interventions (including diet, exercise and pharmacological therapy), altered all-cause and cardiovascular related mortality in such subjects. METHODS: We performed a meta-analysis of prospective, randomised controlled trials (RCTs) that were identified in the medical literature and databases. Trials were eligible for inclusion if they reported all-cause mortality rates (at a minimum), recruited approximately 100 patients and had a minimum follow-up of one year. Interventions were divided into pharmacological and non-pharmacological. RESULTS: Ten RCTs that enrolled 23,152 patients met the above entry criteria. Trials ran for an average of 3.75 years. Diabetes was delayed or prevented by these interventions vs control (risk ratio 0.83, 95%CI 0.80-0.86). Non-drug approaches (n = 3495) were superior to drug-based approaches (n = 20,872) in diabetes prevention (0.52, 0.46-0.58 vs 0.70, 0.58-0.85, P < 0.05). There was no difference in risk of all-cause mortality in the intervention versus control group (0.96, 0.84-1.10) and no difference in CV death (1.04, 0.61-1.78). There was a non-significant trend towards reduction in fatal and non-fatal myocardial infarction (0.59, 0.23-1.50). Fatal and non-fatal stroke was borderline reduced (0.76, 0.58-0.99) with intervention versus control. CONCLUSIONS: Despite interventions being mostly successful in retarding progression to overt diabetes, this did not result in reductions in all-cause or cardiovascular mortality, or myocardial infarction, with the possible exception of stroke.", "title": "Prevention of diabetes and reduction in major cardiovascular events in studies of subjects with prediabetes: meta-analysis of randomised controlled..." }, { "docid": "MED-3252", "text": "It is commonly accepted that nutrition is one of the possible environmental factors involved in the pathogenesis of multiple sclerosis (MS), but its role as complementary MS treatment is unclear and largely disregarded. At present, MS therapy is not associated to a particular diet, probably due to lack of information on the effects of nutrition on the disease. To overcome the distrust of the usefulness of dietary control in MS and to encourage nutritional interventions in the course of the disease, it is necessary to assess the nature and the role of bioactive dietary molecules and their targets, and establish how a dietary control can influence cell metabolism and improve the wellness of MS patients. The aim of this review is to provide a rationale for a nutritional intervention in MS by evaluating at the molecular level the effects of dietary molecules on the inflammatory and autoimmune processes involved in the disease. Present data reveal that healthy dietary molecules have a pleiotropic role and are able to change cell metabolism from anabolism to catabolism and down-regulate inflammation by interacting with enzymes, nuclear receptors and transcriptional factors. The control of gut dysbiosis and the combination of hypo-caloric, low-fat diets with specific vitamins, oligoelements and dietary integrators, including fish oil and polyphenols, may slow-down the progression of the disease and ameliorate the wellness of MS patients. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "The molecular basis of nutritional intervention in multiple sclerosis: a narrative review." }, { "docid": "MED-3182", "text": "OBJECTIVE: Review of human cysticercosis in Canada, to estimate the magnitude of the disease and to describe the pattern of disease expression in this country. METHODS: MEDLINE and manual search of case reports and case series of patients with cysticercosis diagnosed in Canada. ed data included year of diagnosis, citizenship status, clinical manifestations, and form of cysticercosis. FINDINGS: A total of 21 articles reporting 60 patients were found. Forty (67%) of these patients were diagnosed in the past two decades. Most cases came from Ontario (n=43) and Quebec (n=14). Immigrants accounted for 96% of the 28 cases in whom citizenship information was available. Neurocysticercosis was observed in 55 patients, and isolated compromise of striated muscles in the remaining five. Seizures was the primary or sole manifestation of the disease in 72% of patients, and most of them had parenchymal brain cysticerci (either viable cysts or calcifications). Two of seven patients were positive for Taenia eggs. In no case were household contacts of the patients investigated for taeniasis. CONCLUSIONS: An increasing number of patients with cysticercosis have been reported from Canada in the past two decades, suggesting that the prevalence of this parasitic disease may be on the rise. While most cases occur in immigrants, it is possible that at least some of these patients had acquired the disease in Canada.", "title": "A review of cases of human cysticercosis in Canada." }, { "docid": "MED-3179", "text": "OBJECTIVES: Neurocysticercosis (NCYST) is the most frequent CNS parasitic disease worldwide, affecting more than 50 million people. However, some of its clinical findings, such as cognitive impairment and dementia, remain poorly characterized, with no controlled studies conducted so far. We investigated the frequency and the clinical profile of cognitive impairment and dementia in a sample of patients with NCYST in comparison with cognitively healthy controls (HC) and patients with cryptogenic epilepsy (CE). METHODS: Forty treatment-naive patients with NCYST, aged 39.25 +/- 10.50 years and fulfilling absolute criteria for definitive active NCYST on MRI, were submitted to a comprehensive cognitive and functional evaluation and were compared with 49 HC and 28 patients with CE of similar age, educational level, and seizure frequency. RESULTS: Patients with NCYST displayed significant impairment in executive functions, verbal and nonverbal memory, constructive praxis, and verbal fluency when compared with HC (p < 0.05). Dementia was diagnosed in 12.5% patients with NCYST according to DSM-IV criteria. When compared with patients with CE, patients with NCYST presented altered working and episodic verbal memory, executive functions, naming, verbal fluency, constructive praxis, and visual-spatial orientation. No correlation emerged between cognitive scores and number, localization, or type of NCYST lesions on MRI. CONCLUSIONS: Cognitive impairment was ubiquitous in this sample of patients with active neurocysticercosis (NCYST). Antiepileptic drug use and seizure frequency could not account for these features. Dementia was present in a significant proportion of patients. These data broaden our knowledge on the clinical presentations of NCYST and its impact in world public health.", "title": "Cognitive impairment and dementia in neurocysticercosis: a cross-sectional controlled study." }, { "docid": "MED-4963", "text": "Because of the worldwide popularization of Japanese cuisine, the traditional Japanese fish dishes sushi and sashimi that are served in Japanese restaurants and sushi bars have been suspected of causing fishborne parasitic zoonoses, especially anisakiasis. In addition, an array of freshwater and brackish-water fish and wild animal meats, which are important sources of infection with zoonotic parasites, are served as sushi and sashimi in rural areas of Japan. Such fishborne and foodborne parasitic zoonoses are also endemic in many Asian countries that have related traditional cooking styles. Despite the recent increase in the number of travelers to areas where these zoonoses are endemic, travelers and even infectious disease specialists are unaware of the risk of infection associated with eating exotic ethnic dishes. The aim of this review is to provide practical background information regarding representative fishborne and foodborne parasitic zoonoses endemic in Asian countries.", "title": "Sushi delights and parasites: the risk of fishborne and foodborne parasitic zoonoses in Asia." }, { "docid": "MED-2816", "text": "Plants contain numerous polyphenols, which have been shown to reduce inflammation and hereby to increase resistance to disease. Examples of such polyphenols are isothiocyanates in cabbage and broccoli, epigallocatechin in green tee, capsaicin in chili peppers, chalones, rutin and naringenin in apples, resveratrol in red wine and fresh peanuts and curcumin/curcuminoids in turmeric. Most diseases are maintained by a sustained discreet but obvious increased systemic inflammation. Many studies suggest that the effect of treatment can be improved by a combination of restriction in intake of proinflammatory molecules such as advanced glycation end products (AGE), advanced lipoperoxidation end products (ALE), and rich supply of antiinflammatory molecules such as plant polyphenols. To the polyphenols with a bulk of experimental documentation belong the curcuminoid family and especially its main ingredient, curcumin. This review summarizes the present knowledge about these turmericderived ingredients, which have proven to be strong antioxidants and inhibitors of cyclooxigenase-2 (COX-2), lipoxygenase (LOX) and nuclear factor kappa B (NF-kappaB) but also AGE. A plethora of clinical effects are reported in various experimental diseases, but clinical studies in humans are few. It is suggested that supply of polyphenols and particularly curcuminoids might be value as complement to pharmaceutical treatment, but also prebiotic treatment, in conditions proven to be rather therapy-resistant such as Crohn's, long-stayed patients in intensive care units, but also in conditions such as cancer, liver cirrhosis, chronic renal disease, chronic obstructive lung disease, diabetes and Alzheimer's disease.", "title": "Plant-derived health: the effects of turmeric and curcuminoids." }, { "docid": "MED-2002", "text": "BACKGROUND: Type 2 diabetes mellitus is increasingly common, primarily because of increases in the prevalence of a sedentary lifestyle and obesity. Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known. METHODS: We randomly assigned 522 middle-aged, overweight subjects (172 men and 350 women; mean age, 55 years; mean body-mass index [weight in kilograms divided by the square of the height in meters], 31) with impaired glucose tolerance to either the intervention group or the control group. Each subject in the intervention group received individualized counseling aimed at reducing weight, total intake of fat, and intake of saturated fat and increasing intake of fiber and physical activity. An oral glucose-tolerance test was performed annually; the diagnosis of diabetes was confirmed by a second test. The mean duration of follow-up was 3.2 years. RESULTS: The mean (+/-SD) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group (P<0.001 for both comparisons between the groups). The cumulative incidence of diabetes after four years was 11 percent (95 percent confidence interval, 6 to 15 percent) in the intervention group and 23 percent (95 percent confidence interval, 17 to 29 percent) in the control group. During the trial, the risk of diabetes was reduced by 58 percent (P<0.001) in the intervention group. The reduction in the incidence of diabetes was directly associated with changes in lifestyle. CONCLUSIONS: Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects.", "title": "Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance." }, { "docid": "MED-4359", "text": "Unintentional ingestion of a fishbone (FB) is common, especially in populations with a high consumption of seafood. In most instances, the ingested FB passes uneventfully through the gastrointestinal (GI) tract, usually within a week. However, in certain cases, the FB may become impacted and lead to complications. Awareness of these complications is important as patients usually present with nonspecific symptoms and could be unaware of having ingested an FB.", "title": "Pictorial essay: Complications of a swallowed fish bone" }, { "docid": "MED-3249", "text": "144 multiple sclerosis patients took a low-fat diet for 34 years. For each of three categories of neurological disability (minimum, moderate, severe) patients who adhered to the prescribed diet (less than or equal to 20 g fat/day) showed significantly less deterioration and much lower death rates than did those who consumed more fat than prescribed (greater than 20 g fat/day). The greatest benefit was seen in those with minimum disability at the start of the trial; in this group, when those who died from non-MS diseases were excluded from the analysis, 95% survived and remained physically active.", "title": "Effect of low saturated fat diet in early and late cases of multiple sclerosis." }, { "docid": "MED-3177", "text": "Neurocysticercosis (NCC) is an infection of the central nervous system (CNS) caused by the metacestode larval form of the parasite Taenia sp. Many factors can contribute to the endemic nature of cysticercosis. The inflammatory process that occurs in the tissue surrounding the parasite and/or distal from it can result from several associated mechanisms and may be disproportionate with the number of cysts. This discrepancy may lead to difficulty with the proper diagnosis in people from low endemic regions or regions that lack laboratory resources. In the CNS, the cysticerci have two basic forms, isolated cysts (Cysticercus cellulosae=CC) and racemose cysts (Cysticercus racemosus=CR), and may be meningeal, parenchymal, or ventricular or have a mixed location. The clinical manifestations are based on two fundamental syndromes that may occur in isolation or be associated: epilepsy and intracranial hypertension. They may be asymptomatic, symptomatic or fatal; have an acute, sub-acute or chronic picture; or may be in remission or exacerbated. The cerebrospinal fluid (CSF) may be normal, even in patients with viable cysticerci, until the patients begin to exhibit the classical syndrome of NCC in the CSF, or show changes in one or more routine analysed parameters. Computed tomography (CT) and magnetic resonance imaging (MRI) have allowed non-invasive diagnoses, but can lead to false negatives. Treatment is a highly controversial issue and is characterised by individualised therapy sessions. Two drugs are commonly used, praziquantel (PZQ) and albendazole (ABZ). The choice of anti-inflammatory drugs includes steroids and dextrochlorpheniramine (DCP). Hydrocephalus is a common secondary effect of NCC. Surgical cases of hydrocephalus must be submitted to ventricle-peritoneal shunt (VPS) immediately before cysticidal treatment, and surgical extirpation of the cyst may lead to an absence of the surrounding inflammatory process. The progression of NCC may be simple or complicated, have remission with or without treatment and may exhibit symptoms that can disappear for long periods of time or persist until death. Unknown, neglected and controversial aspects of NCC, such as the impaired fourth ventricle syndrome, the presence of chronic brain oedema and psychic complaints, in addition to the lack of detectable glucose in the CSF and re-infection are discussed.", "title": "Neurocysticercosis: the enigmatic disease." }, { "docid": "MED-3178", "text": "Neurocysticercosis (NCC) is the most frequent parasitic disease of the human brain. Modern imaging studies, CT and MRI, have defined the diagnosis and characterization of the disease. Through these studies the therapeutic approach for each case may be individualized with the aid of antihelmintics, steroids, symptomatic medicines, or surgery. The use of one or various therapeutic measures largely depends on the peculiar combination of number, location, and biological stage of lesions as well as the degree of inflammatory response to the parasites. Although there is not a typical clinical picture of NCC, epilepsy is the most frequent manifestation of parenchymal NCC, whereas hydrocephalus is the most frequent manifestation of meningeal NCC. Eradication of cysticercosis is an attainable goal by public education and sanitary improvement in endemic areas.", "title": "Clinical manifestations, diagnosis, and treatment of neurocysticercosis." }, { "docid": "MED-4385", "text": "The idea that normal constituents of the diet can influence visual function is not new. As early as 1782, Buzzi identified the yellow of the macula and Schulze (1866) specifically postulated that the yellow pigments led to improvements in human vision. These pigments were later found to be derived from dietary lutein and zeaxanthin that are known to be oxygenated carotenoids (xanthophylls). Walls and Judd (1933) postulated that these yellow intraocular pigments could improve visual performance by absorbing light scattered both within (for example, glare) and outside of the eye (increasing visual range by absorbing blue light scattered in the atmosphere), and by improving spatial vision through enhancing contrast and reducing chromatic blur. In this article, evidence for these ideas is reviewed with particular emphasis towards more recent data on glare effects.", "title": "The influence of dietary lutein and zeaxanthin on visual performance." }, { "docid": "MED-1986", "text": "BACKGROUND: Overweight in adults is associated with increased morbidity and mortality. In contrast, the long-term effect of overweight in adolescence on morbidity and mortality is not known. METHODS: We studied the relation between overweight and morbidity and mortality in 508 lean or overweight adolescents 13 to 18 years old who participated in the Harvard Growth Study of 1922 to 1935. Overweight adolescents were defined as those with a body-mass index that on two occasions was greater than the 75th percentile in subjects of the same age and sex in a large national survey. Lean adolescents were defined as those with a body-mass index between the 25th and 50th percentiles. Subjects who were still alive were interviewed in 1988 to obtain information about their medical history, weight, functional capacity, and other risk factors. For those who had died, information on the cause of death was obtained from death certificates. RESULTS: Overweight in adolescent subjects was associated with an increased risk of mortality from all causes and disease-specific mortality among men, but not among women. The relative risks among men were 1.8 (95 percent confidence interval, 1.2 to 2.7; P = 0.004) for mortality from all causes and 2.3 (95 percent confidence interval, 1.4 to 4.1; P = 0.002) for mortality from coronary heart disease. The risk of morbidity from coronary heart disease and atherosclerosis was increased among men and women who had been overweight in adolescence. The risk of colorectal cancer and gout was increased among men and the risk of arthritis was increased among women who had been overweight in adolescence. Overweight in adolescence was a more powerful predictor of these risks than overweight in adulthood. CONCLUSIONS: Overweight in adolescence predicted a broad range of adverse health effects that were independent of adult weight after 55 years of follow-up.", "title": "Long-term morbidity and mortality of overweight adolescents. A follow-up of the Harvard Growth Study of 1922 to 1935." }, { "docid": "MED-4539", "text": "This review is an updated and expanded version of two prior reviews that were published in this journal in 1997 and 2003. In the case of all approved agents the time frame has been extended to include the 251/2 years from 01/1981 to 06/2006 for all diseases worldwide and from 1950 (earliest so far identified) to 06/2006 for all approved antitumor drugs worldwide. We have continued to utilize our secondary subdivision of a \"natural product mimic\" or \"NM\" to join the original primary divisions. From the data presented, the utility of natural products as sources of novel structures, but not necessarily the final drug entity, is still alive and well. Thus, in the area of cancer, over the time frame from around the 1940s to date, of the 155 small molecules, 73% are other than \"S\" (synthetic), with 47% actually being either natural products or directly derived therefrom. In other areas, the influence of natural product structures is quite marked, with, as expected from prior information, the antiinfective area being dependent on natural products and their structures. Although combinatorial chemistry techniques have succeeded as methods of optimizing structures and have, in fact, been used in the optimization of many recently approved agents, we are able to identify only one de novo combinatorial compound approved as a drug in this 25 plus year time frame. We wish to draw the attention of readers to the rapidly evolving recognition that a significant number of natural product drugs/leads are actually produced by microbes and/or microbial interactions with the \"host from whence it was isolated\", and therefore we consider that this area of natural product research should be expanded significantly.", "title": "Natural products as sources of new drugs over the last 25 years." }, { "docid": "MED-4956", "text": "Little information is available on the presence of viable Toxoplasma gondii in tissues of lambs worldwide. The prevalence of T. gondii was determined in 383 lambs (<1 year old) from Maryland, Virginia and West Virginia, USA. Hearts of 383 lambs were obtained from a slaughter house on the day of killing. Blood removed from each heart was tested for antibodies to T. gondii by using the modified agglutination test (MAT). Sera were first screened using 1:25, 1:50, 1: 100 and 1:200 dilutions, and hearts were selected for bioassay for T. gondii. Antibodies (MAT, 1:25 or higher) to T. gondii were found in 104 (27.1%) of 383 lambs. Hearts of 68 seropositive lambs were used for isolation of viable T. gondii by bioassay in cats, mice or both. For bioassays in cats, the entire myocardium or 500g was chopped and fed to cats, one cat per heart and faeces of the recipient cats were examined for shedding of T. gondii oocysts. For bioassays in mice, 50g of the myocardium was digested in an acid pepsin solution and the digest inoculated into mice; the recipient mice were examined for T. gondii infection. In total, 53 isolates of T. gondii were obtained from 68 seropositive lambs. Genotyping of the 53 T. gondii isolates using 10 PCR-restriction fragment length polymorphism markers (SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico) revealed 57 strains with 15 genotypes. Four lambs had infections with two T. gondii genotypes. Twenty-six (45.6%) strains belong to the clonal Type II lineage (these strains can be further divided into two groups based on alleles at locus Apico). Eight (15.7%) strains belong to the Type III lineage. The remaining 22 strains were divided into 11 atypical genotypes. These results indicate high parasite prevalence and high genetic diversity of T. gondii in lambs, which has important implications in public health. We believe this is the first in-depth genetic analysis of T. gondii isolates from sheep in the USA.", "title": "High prevalence and abundant atypical genotypes of Toxoplasma gondii isolated from lambs destined for human consumption in the USA." }, { "docid": "MED-2763", "text": "Despite compelling statistics that show we could eliminate 80%of all heart disease and strokes, 90% of all diabetes, and 60% of all cancers with basic lifestyle changes, we have failed to motivate the public to make these changes and failed to motivate policy makers to make healthy choices the easiest choice. Dr. Katz suggests we have failed because we have focused too much on statistics and too little on passion. He implores all of us to tap into people's passion by connecting each of these statistics with a human story.", "title": "Facing the facelessness of public health: what's the public got to do with it?" }, { "docid": "MED-3172", "text": "Recent studies suggest that neurocysticercosis may be a risk factor for human cancer. Pathogenetic mechanisms explaining possible oncogenic effects of cysticerci include the following: (a) parasite-induced modulation of the host immune response that may be associated with loss of regulatory mechanisms implicated in the immunological surveillance against cancer; (b) transfer of genetic material from the parasite to the host, causing DNA damage and malignant transformation of host cells, and (c) chronic inflammation with liberation of nitric oxide and inhibition of tumor suppressor genes. Further research is needed to confirm the potential role of cysticercosis in the development of cancer. These studies should determine the presence of cysticercotic factors responsible for the transfer of genetic material and potential mutations in the tumor suppressor genes in proliferating astrocytes surrounding cysticercotic lesions. Additionally, the complex interaction between the immune state of the host with variable cytokine release and the presence of inflammatory cells releasing nitric oxide that cause DNA damage and impair tumor suppressive mechanisms needs to be investigated.", "title": "Neurocysticercosis and oncogenesis." }, { "docid": "MED-4382", "text": "BACKGROUND: Age-related cataract is a major cause of morbidity. Previous studies of diet and cataract risk have focused on specific nutrients or healthy eating indexes but not on identifiable dietary groups such as vegetarians. OBJECTIVE: We investigated the association between diet and cataract risk in a population that has a wide range of diets and includes a high proportion of vegetarians. DESIGN: We used Cox proportional hazards regression to study cataract risk in relation to baseline dietary and lifestyle characteristics of 27,670 self-reported nondiabetic participants aged ≥40 y at recruitment in the Oxford (United Kingdom) arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Oxford) by using data from the Hospital Episode Statistics in England and Scottish Morbidity Records. RESULTS: There was a strong relation between cataract risk and diet group, with a progressive decrease in risk of cataract in high meat eaters to low meat eaters, fish eaters (participants who ate fish but not meat), vegetarians, and vegans. After multivariable adjustment, incidence rate ratios (95% CIs) for moderate meat eaters (50-99 g meat/d), low meat eaters (<50 g meat/d), fish eaters, vegetarians, and vegans compared with high-meat eaters (≥100 g meat/d) were 0.96 (0.84, 1.11), 0.85 (0.72, 0.99), 0.79 (0.65, 0.97), 0.70 (0.58, 0.84), and 0.60 (0.38, 0.96), respectively (P < 0.001 for heterogeneity). Associations between cataract risk and intakes of selected nutrients and foods generally reflected the strong association with diet group. CONCLUSION: Vegetarians were at lower risk of cataract than were meat eaters in this cohort of health-conscious British residents.", "title": "Diet, vegetarianism, and cataract risk." }, { "docid": "MED-1987", "text": "OBJECTIVE: Over the last 3 decades, the prevalence of childhood obesity has increased dramatically in North America, ushering in a variety of health problems, including type 2 diabetes mellitus (T2DM), which previously was not typically seen until much later in life. This technical report describes, in detail, the procedures undertaken to develop the recommendations given in the accompanying clinical practice guideline, \"Management of Type 2 Diabetes Mellitus in Children and Adolescents,\" and provides in-depth information about the rationale for the recommendations and the studies used to make the clinical practice guideline's recommendations. METHODS: A primary literature search was conducted relating to the treatment of T2DM in children and adolescents, and a secondary literature search was conducted relating to the screening and treatment of T2DM's comorbidities in children and adolescents. Inclusion criteria were prospectively and unanimously agreed on by members of the committee. An article was eligible for inclusion if it addressed treatment (primary search) or 1 of 4 comorbidities (secondary search) of T2DM, was published in 1990 or later, was written in English, and included an abstract. Only primary research inquiries were considered; review articles were considered if they included primary data or opinion. The research population had to constitute children and/or adolescents with an existing diagnosis of T2DM; studies of adult patients were considered if at least 10% of the study population was younger than 35 years. All retrieved titles, abstracts, and articles were reviewed by the consulting epidemiologist. RESULTS: Thousands of articles were retrieved and considered in both searches on the basis of the aforementioned criteria. From those, in the primary search, 199 abstracts were identified for possible inclusion, 58 of which were retained for systematic review. Five of these studies were classified as grade A studies, 1 as grade B, 20 as grade C, and 32 as grade D. Articles regarding treatment of T2DM selected for inclusion were divided into 4 major subcategories on the basis of type of treatment being discussed: (1) medical treatments (32 studies); (2) nonmedical treatments (9 studies); (3) provider behaviors (8 studies); and (4) social issues (9 studies). From the secondary search, an additional 336 abstracts relating to comorbidities were identified for possible inclusion, of which 26 were retained for systematic review. These articles included the following: 1 systematic review of literature regarding comorbidities of T2DM in adolescents; 5 expert opinions presenting global recommendations not based on evidence; 5 cohort studies reporting natural history of disease and comorbidities; 3 with specific attention to comorbidity patterns in specific ethnic groups (case-control, cohort, and clinical report using adult literature); 3 reporting an association between microalbuminuria and retinopathy (2 case-control, 1 cohort); 3 reporting the prevalence of nephropathy (cohort); 1 reporting peripheral vascular disease (case series); 2 discussing retinopathy (1 case-control, 1 position statement); and 3 addressing hyperlipidemia (American Heart Association position statement on cardiovascular risks; American Diabetes Association consensus statement; case series). A breakdown of grade of recommendation shows no grade A studies, 10 grade B studies, 6 grade C studies, and 10 grade D studies. With regard to screening and treatment recommendations for comorbidities, data in children are scarce, and the available literature is conflicting. Therapeutic recommendations for hypertension, dyslipidemia, retinopathy, microalbuminuria, and depression were summarized from expert guideline documents and are presented in detail in the guideline. The references are provided, but the committee did not independently assess the supporting evidence. Screening tools are provided in the Supplemental Information.", "title": "Management of type 2 diabetes mellitus in children and adolescents." }, { "docid": "MED-3785", "text": "PURPOSE: Components of one-carbon metabolism are believed to influence cancer development with suggested mechanisms, including DNA methylation and DNA repair mechanisms. However, few prospective studies have investigated one-carbon metabolism in relation to prostate cancer risk, and the results have been conflicting. The aim of this study was to do a comprehensive investigation of the components of one-carbon metabolism in relation to prostate cancer risk. A panel of seven circulating B vitamins and related metabolites was selected, most of which have not been studied before. MATERIALS AND METHODS: We analyzed plasma concentrations of betaine, choline, cysteine, methionine, methylmalonic acid (MMA), vitamin B2, and vitamin B6 in 561 cases and 1,034 controls matched for age and recruitment date, nested within the population-based Northern Sweden Health and Disease Cohort. Relative risks of prostate cancer were estimated by conditional logistic regression. RESULTS: Positive associations with prostate cancer risk were observed for choline and vitamin B2, and an inverse association was observed for MMA. The relative risks for a doubling in concentrations were 1.46 [95% confidence interval (95% CI), 1.04-2.05; P(trend) = 0.03] for choline, 1.11 (95% CI, 1.00-1.23; P(trend) = 0.04) for vitamin B2, and 0.78 (95% CI, 0.63-0.97; P(trend) = 0.03) for MMA. Concentrations of betaine, cysteine, methionine, and vitamin B6 were not associated with prostate cancer risk. CONCLUSION: The results of this large prospective study suggest that elevated plasma concentrations of choline and vitamin B2 may be associated with an increased risk of prostate cancer. These novel findings support a role of one-carbon metabolism in prostate cancer etiology and warrant further investigation.", "title": "One-carbon metabolism and prostate cancer risk: prospective investigation of seven circulating B vitamins and metabolites." }, { "docid": "MED-5091", "text": "BACKGROUND: Docosahexaenoic acid (DHA) is important to neural development. Whether DHA intakes are low enough in some pregnant women to impair infant development is uncertain. OBJECTIVE: We sought to determine whether DHA deficiency occurs in pregnant women and contributes to poor infant development. DESIGN: Biochemical cutoffs, dietary intakes, or developmental scores indicative of DHA deficiency are not defined. Infant development has a distribution in which an individual's potential development is unknown. This was a randomized intervention to establish a distribution of developmental scores for infants of women with DHA intakes considered to be above requirements against which to compare the development of infants of mothers consuming their usual diet. DHA (400 mg/d; n = 67) or a placebo (n = 68) was consumed by the women from 16 wk gestation until delivery. We determined maternal red blood cell ethanolamine phosphoglyceride fatty acids, dietary intakes at 16 and 36 wk gestation, and infant visual acuity at 60 d of age. RESULTS: We described an approach to identify DHA deficiency when biochemical and functional markers of deficiency are unknown. In multivariate analyses, infant visual acuity was related to sex (beta = 0.660, SE = 0.93, and odds ratio = 1.93) and maternal DHA intervention (beta = 1.215, SE = 1.64, and odds ratio = 3.37). More infant girls in the placebo than in the DHA intervention group had a visual acuity below average (P = 0.048). Maternal red blood cell ethanolamine phosphoglyceride docosatetraenoic acid was inversely related to visual acuity in boys (rho = -0.37, P < 0.05) and girls (rho = -0.48, P < 0.01). CONCLUSIONS: These studies suggest that some pregnant women in our study population were DHA-deficient.", "title": "Essential n-3 fatty acids in pregnant women and early visual acuity maturation in term infants." }, { "docid": "MED-4389", "text": "Significant benefits for diabetes prevention and management have been observed with vegetarian and especially vegan diets. This article reviews observational studies and intervention trials on such diets, and discusses their efficacy, nutritional adequacy, acceptability, and sustainability. Research to date has demonstrated that a low-fat, plant-based nutritional approach improves control of weight, glycemia, and cardiovascular risk. These studies have also shown that carefully planned vegan diets can be more nutritious than diets based on more conventional diet guidelines, with an acceptability that is comparable with that of other therapeutic regimens. Current intervention guidelines from professional organizations offer support for this approach. Vegetarian and vegan diets present potential advantages in managing type 2 diabetes that merit the attention of individuals with diabetes and their caregivers.", "title": "Usefulness of vegetarian and vegan diets for treating type 2 diabetes." }, { "docid": "MED-4541", "text": "Objective To determine the comparative effects of the thiazolidinediones (rosiglitazone and pioglitazone) on myocardial infarction, congestive heart failure, and mortality in patients with type 2 diabetes. Design Systematic review and meta-analysis of observational studies. Data sources Searches of Medline and Embase in September 2010. Study selection Observational studies that directly compared the risk of cardiovascular outcomes for rosiglitazone and pioglitazone among patients with type 2 diabetes mellitus were included. Data extraction Random effects meta-analysis (inverse variance method) was used to calculate the odds ratios for cardiovascular outcomes with thiazolidinedione use. The I2 statistic was used to assess statistical heterogeneity. Results Cardiovascular outcomes from 16 observational studies (4 case-control studies and 12 retrospective cohort studies), including 810 000 thiazolidinedione users, were evaluated after a detailed review of 189 citations. Compared with pioglitazone, use of rosiglitazone was associated with a statistically significant increase in the odds of myocardial infarction (n=15 studies; odds ratio 1.16, 95% confidence interval 1.07 to 1.24; P<0.001; I2=46%), congestive heart failure (n=8; 1.22, 1.14 to 1.31; P<0.001; I2=37%), and death (n=8; 1.14, 1.09 to 1.20; P<0.001; I2=0%). Numbers needed to treat to harm (NNH), depending on the population at risk, suggest 170 excess myocardial infarctions, 649 excess cases of heart failure, and 431 excess deaths for every 100 000 patients who receive rosiglitazone rather than pioglitazone. Conclusion Among patients with type 2 diabetes, use of rosiglitazone is associated with significantly higher odds of congestive heart failure, myocardial infarction, and death relative to pioglitazone in real world settings.", "title": "Comparative cardiovascular effects of thiazolidinediones: systematic review and meta-analysis of observational studies" }, { "docid": "MED-3429", "text": "Sexual problems are diffuse in both genders. Although epidemiologic evidence seems to support a role for lifestyle factors in erectile dysfunction, limited data are available suggesting the treatment of underlying risk factors may improve erectile dysfunction. The results are sparse regarding associations between lifestyle factors and female sexual dysfunction, and conclusions regarding influence of healthy behaviors on female sexual dysfunction cannot be made before more studies have been performed. Beyond the specific effects on sexual dysfunctions in men and women, adoption of these measures promotes a healthier life and increased well-being, which may help reduce the burden of sexual dysfunction. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Lifestyle/dietary recommendations for erectile dysfunction and female sexual dysfunction." }, { "docid": "MED-4383", "text": "OBJECTIVE: We investigated the relation between plasma carotenoids, retinol and tocopherol levels and ovarian cancer risk in Korean women. DESIGN: Hospital-based case-control study. SETTING: Six tertiary medical institutes in Korea. POPULATION: Forty-five epithelial ovarian cancers and 135 age-matched controls. METHODS: Preoperative plasma concentrations of beta-carotene, lycopene, zeaxanthin plus lutein, retinol, alpha-tocopherol, and gamma-tocopherol were measured by reverse-phase, gradient high-pressure liquid chromatography. MAIN OUTCOME MEASURES: Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated by tertiles to evaluate the effect of micronutrients on endometrial cancer risk after adjustment for body mass (BMI) index, menopause, parity, oral contraceptive use, smoking status, and alcohol consumption status. RESULTS: Women in the highest tertile for beta-carotene had 0.12-times the risk of ovarian cancer of in the lowest tertile (OR 0.12; 95%CI 0.04-0.36). Women with the highest tertiles of lycopene (OR 0.09; 95%CI 0.03-0.32), zeaxanthin/lutein (OR 0.21; 95%CI 0.09-0.52), retinol (OR 0.45; 95%CI 0.21-0.98), alpha-tocopherol (OR 0.23; 95%CI 0.10-0.53) and gamma-tocopherol (OR 0.28; 95%CI 0.11-0.70) had lower risk of ovarian cancer than women in the lowest tertiles. Results were consistent across strata of socio-epidemiologic factors. CONCLUSIONS: Micronutrients, specifically ss-carotene, lycopene, zeaxanthin, lutein, retinol, alpha-tocopherol, and gamma-tocopherol, may play a role in reducing the risk of ovarian cancer.", "title": "Plasma carotenoids, retinol and tocopherol levels and the risk of ovarian cancer." }, { "docid": "MED-4932", "text": "Annual global aquaculture production has more than tripled within the past 15 years, and by 2015, aquaculture is predicted to account for 39% of total global seafood production by weight. Given that lack of adequate nutrition is a leading contributor to the global burden of disease, increased food production through aquaculture is a seemingly welcome sign. However, as production surges, aquaculture facilities increasingly rely on the heavy input of formulated feeds, antibiotics, antifungals, and agrochemicals. This review summarizes our current knowledge concerning major chemical, biological and emerging agents that are employed in modern aquaculture facilities and their potential impacts on public health. Findings from this review indicate that current aquaculture practices can lead to elevated levels of antibiotic residues, antibiotic-resistant bacteria, persistent organic pollutants, metals, parasites, and viruses in aquacultured finfish and shellfish. Specific populations at risk of exposure to these contaminants include individuals working in aquaculture facilities, populations living around these facilities, and consumers of aquacultured food products. Additional research is necessary not only to fully understand the human health risks associated with aquacultured fish versus wild-caught fish but also to develop appropriate interventions that could reduce or prevent these risks. In order to adequately understand, address and prevent these impacts at local, national and global scales, researchers, policy makers, governments, and aquaculture industries must collaborate and cooperate in exchanging critical information and developing targeted policies that are practical, effective and enforceable.", "title": "Aquaculture practices and potential human health risks: current knowledge and future priorities." }, { "docid": "MED-4966", "text": "Ciguatera fish poisoning (CFP) is a distinctive type of foodborne disease that results from eating predatory ocean fish contaminated with ciguatoxins. As many as 50,000 cases are reported worldwide annually, and the condition is endemic in tropical and subtropical regions of the Pacific basin, Indian Ocean, and Caribbean. In the United States, 5--70 cases per 10,000 persons are estimated to occur yearly in ciguatera-endemic states and territories. CFP can cause gastrointestinal symptoms (nausea, vomiting, abdominal cramps, or diarrhea) within a few hours of eating contaminated fish. Neurologic symptoms, with or without gastrointestinal disturbance, can include fatigue, muscle pain, itching, tingling, and (most characteristically) reversal of hot and cold sensation. This report describes a cluster of nine cases of CFP that occurred in North Carolina in June 2007. Among the nine patients, six experienced reversal of hot and cold sensations, five had neurologic symptoms only, and overall symptoms persisted for more than 6 months in three patients. Among seven patients who were sexually active, six patients also complained of painful intercourse. This report highlights the potential risks of eating contaminated ocean fish. Local and state health departments can train emergency and urgent care physicians in the recognition of CFP and make them aware that symptoms can persist for months to years.", "title": "Cluster of ciguatera fish poisoning--North Carolina, 2007." }, { "docid": "MED-1988", "text": "PURPOSE OF REVIEW: To review recent literature on important topics in pediatric office practice: bullying, screening for the prediabetic state, and pediatric oral health. RECENT FINDINGS: Recent literature shows that bullying behaviors are common in children as young as kindergarten age, that there is a strong association between being a bully or victim and a range of psychosomatic and depressive symptoms in children, and that interventions including family therapy and school-based programs are effective for bullies and victims. Recent studies have further delineated glucose and insulin metabolism. Recent work has provided new models to help practitioners screen for the prediabetic state in hope of providing earlier opportunities to intervene and avoid the morbidities associated with type 2 diabetes mellitus. Recent literature emphasizes continued gaps in dental healthcare for patients who are most at risk. Recent studies emphasize the important role that diet and sealants have in preventing dental caries. SUMMARY: Recent literature emphasizes the important role that office-based pediatricians have in identifying patients who are involved in bullying, at risk of developing type 2 diabetes mellitus, or have poor dental health. Future research will help delineate these problems and provide us with refined primary prevention and treatment guidelines.", "title": "Pediatrician's role in screening and treatment: bullying, prediabetes, oral health." }, { "docid": "MED-2817", "text": "Curcumin (diferuloylmethane), a yellow coloring agent extracted from turmeric is also used as a remedy for the treatment and prevention of inflammatory diseases. Acute and chronic inflammation is a major factor in the progression of obesity, type II diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Turmeric has a long history of use in Ayurvedic medicine for the treatment of inflammatory disorders. Recent studies on the efficacy and therapeutic applicability of turmeric have suggested that the active ingredient of tumeric is curcumin. Further, compelling evidence has shown that curcumin has the ability to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the current study, the anti-inflammatory effects of curcumin were evaluated relative to various chronic inflammatory diseases. Based on the available pharmacological data obtained from in vitro and in vivo research, as well as clinical trials, an opportunity exists to translate curcumin into clinics for the prevention of inflammatory diseases in the near future. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.", "title": "Curcumin in inflammatory diseases." }, { "docid": "MED-4967", "text": "BACKGROUND: From 2003 through 2007, Vibrio cholerae serogroup O75 strains possessing the cholera toxin gene were isolated from 6 patients with severe diarrhea, including 3 in Georgia, 2 in Alabama, and 1 in South Carolina. These reports represent the first identification of V. cholerae O75 as a cause of illness in the United States. V. cholerae O75 was isolated from a water sample collected from a pond in Louisiana in 2004. Subsequently, 3 V. cholerae isolates from Louisiana (2 from patients with diarrhea in 2000 and 1 from a water sample collected in 1978) that had been previously reported as serogroup O141 were also discovered to be serogroup O75. RESULTS: All 8 patients who were infected with V. cholerae O75 were adults who became ill after consuming seafood; 2 had eaten raw oysters traced back to the Gulf Coast of the United States. All 10 isolates possessed the cholera toxin gene and were susceptible to 10 antimicrobials. One clinical isolate and 1 environmental (water) isolate had the same pulsed-field gel electrophoresis pattern; 4 clinical isolates shared a common pulsed-field gel electrophoresis pattern. CONCLUSIONS: The occurrence of these cases over many years and the concurrent identification of V. cholerae O75 in water from a Gulf Coast state suggest that these strains may survive for long periods in this environment. The patients' exposure histories suggest that infection can be acquired from consumption of raw oysters from the Gulf Coast. Clinicians and public health authorities should be vigilant for the occurrence of new toxigenic serogroups of V. cholerae that are capable of causing severe diarrhea.", "title": "Severe diarrhea caused by cholera toxin-producing vibrio cholerae serogroup O75 infections acquired in the southeastern United States." }, { "docid": "MED-3398", "text": "Although erectile dysfunction is frequently seen in patients with manifestations of arteriosclerotic disease, the independent contribution of serum cholesterol in predicting erectile dysfunction is unclear. The aim of this study was to examine the relation between serum cholesterol and erectile dysfunction. Medical histories, physical examinations, and blood tests were obtained at Cooper Clinic, Dallas, Texas, from 3,250 men aged 26-83 years (mean, 51 years) without erectile dysfunction at their first visit, who had one more clinic visit, all between 1987 and 1991. These men were followed 6-48 months after the first clinic visit (mean, 22 months). Erectile dysfunction was reported in 71 men (2.2%) during follow-up. Every mmol/liter of increase in total cholesterol was associated with 1.32 times the risk of erectile dysfunction (95% confidence interval 1.04-1.68), while every mmol/liter of increase in high density lipoprotein cholesterol was associated with 0.38 times the risk (95% confidence interval 0.18-0.80). Men with a high density lipoprotein cholesterol measurement over 1.55 mmol/liter (60 mg/dl) had 0.30 times the risk (95% confidence interval 0.09-1.03) as did men with less than 0.78 mmol/liter (30 mg/dl). Men with total cholesterol over 6.21 mmol/liter (240 mg/dl) had 1.83 times the risk (95% confidence interval 1.00-3.37) as did men with less than 4.65 mmol/liter (180 mg/dl). Those differences remained essentially unchanged after adjustment for other potential confounders. The authors conclude that a high level of total cholesterol and a low level of high density lipoprotein cholesterol are important risk factors for erectile dysfunction.", "title": "Total cholesterol and high density lipoprotein cholesterol as important predictors of erectile dysfunction." }, { "docid": "MED-3174", "text": "To assess the burden of neurocysticercosis (NCC) in California we examined statewide hospital discharge data for 2009. There were 304 cases hospitalized with NCC identified (incidence = 0.8 per 100,000). Cases were mostly Latino (84.9%), slightly more likely to be male than female (men 57.6%, women 42.4%) with an average age of 43.5 years. A majority of cases were hospitalized in Southern California (72.1%) and many were hospitalized in Los Angeles County (44.7%). Men were more likely than women to have severe disease including hydrocephalus (29.7% vs. 18.6%, p = 0.027), resulting in longer hospitalizations (>4 days, 48.0% vs. 32.6%, p = 0.007) that were more costly (charge>$40 thousand men = 46.9% vs. woman = 4.1%, p = 0.026). Six deaths were recorded (2.0%). The total of NCC-related hospital charges exceeded $17 million; estimated hospital costs exceeded $5 million. Neurocysticercosis causes appreciable disease and exacts a considerable economic burden in California. Author Summary Neurocysticercosis (NCC) is considered one of the major neglected infections of poverty in the United States, with mortality studies indicating that California bears the highest burden of this disease. Although NCC is a reportable disease in California, studies indicate that this disease goes largely under-reported, contributing to the lack of information about the disease distribution and burden. In this manuscript, we reviewed the distribution of NCC hospitalizations in California, demographics of those hospitalized and total hospital-related charges for 2009. This study revealed that a majority of persons hospitalized with NCC in California receive their medical service in Southern California hospitals, primarily in the County of Los Angeles. As compared to women hospitalized for this disease, men had a longer and more costly hospitalization with more severe symptoms such as hydrocephalus, a diagnosis suggestive of extraparenchymal infection. The reasons for this difference in NCC severity by gender are not clear, but do not appear to be due to delay in seeking medical care or a language barrier. The intensity of hospital care needed to manage these cases and the sizable NCC hospitalization charge underscores the considerable economic burden this disease presents in California.", "title": "The Impact of Neurocysticercosis in California: A Review of Hospitalized Cases" }, { "docid": "MED-3433", "text": "OBJECTIVES: Our goal was to evaluate the association between erectile dysfunction (ED) and risk of cardiovascular disease (CVD) and all-cause mortality by conducting a meta-analysis of prospective cohort studies. BACKGROUND: Observational studies suggest an association between ED and the incidence of CVD. However, whether ED is an independent risk factor of CVD remains controversial. METHODS: The PubMed database was searched through January 2011 to identify studies that met pre-stated inclusion criteria. Reference lists of retrieved articles were also reviewed. Two authors independently extracted information on the designs of the studies, the characteristics of the study participants, exposure and outcome assessments, and control for potential confounding factors. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. RESULTS: Twelve prospective cohort studies involving 36,744 participants were included in the meta-analysis. The overall combined relative risks for men with ED compared with the reference group were 1.48 (95% confidence interval [CI]: 1.25 to 1.74) for CVD, 1.46 (95% CI: 1.31 to 1.63) for coronary heart disease, 1.35 (95% CI: 1.19 to 1.54) for stroke, and 1.19 (95% CI: 1.05 to 1.34) for all-cause mortality. Sensitivity analysis restricted to studies with control for conventional cardiovascular risk factors yielded similar results. No evidence of publication bias was observed. CONCLUSIONS: This meta-analysis of prospective cohort studies suggests that ED significantly increases the risk of CVD, coronary heart disease, stroke, and all-cause mortality, and the increase is probably independent of conventional cardiovascular risk factors. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.", "title": "Erectile dysfunction and risk of cardiovascular disease: meta-analysis of prospective cohort studies." }, { "docid": "MED-1991", "text": "The objective of this article is to review the epidemiologic literature examining the role of plant foods and plant-based diets in the prevention of childhood obesity. Available data suggest a protective effect of ready-to-eat cereal on risk of obesity, although prospective studies are still needed. Studies on fruit and vegetables; grains other than cereal; high-protein foods, including beans, legumes, and soy; fiber; and plant-based dietary patterns are inconsistent or generally null. The evidence base is limited, and most studies are fraught with methodologic limitations, including cross-sectional design, inadequate adjustment for potential confounders, and lack of consideration of reporting errors, stage of growth, and genetic influences. Well-designed prospective studies are needed. The lack of evidence showing an association between plant-based diets and childhood obesity does not mean that such diets should not be encouraged. Plant foods are highlighted in the Dietary Guidelines for Americans, and children do not meet the current recommendations for most plant foods. Although the advice to consume a plant-based, low-energy-dense diet is sound, ethical questions arise concerning the relatively high price of these diets in the United States and the way in which such diets are perceived in other parts of the world. Reducing the burden of childhood obesity, eliminating health disparities, and preventing the further spread of the disease around the globe will require not only policy interventions to ensure that plant foods are affordable and accessible to children of all income levels but also awareness of sociocultural norms that affect consumption.", "title": "Plant foods and plant-based diets: protective against childhood obesity?" }, { "docid": "MED-2821", "text": "The purpose of this review is to summarize the pertinent literature published in the present era regarding the antiulcerogenic property of curcumin against the pathological changes in response to ulcer effectors (Helicobacter pylori infection, chronic ingestion of non-steroidal anti-inflammatory drugs, and exogenous substances). The gastrointestinal problems caused by different etiologies was observed to be associated with the alterations of various physiologic parameters such as reactive oxygen species, nitric oxide synthase, lipid peroxidation, and secretion of excessive gastric acid. Gastrointestinal ulcer results probably due to imbalance between the aggressive and the defensive factors. In 80% of the cases, gastric ulcer is caused primarily due to the use of non-steroidal anti-inflammatory category of drug, 10% by H. pylori, and about 8-10% by the intake of very spicy and fast food. Although a number of antiulcer drugs and cytoprotectants are available, all these drugs have side effects and limitations. In the recent years a widespread search has been launched to identify new antiulcer drugs from synthetic and natural resources. An Indian dietary derivative (curcumin), a yellow pigment found in the rhizome of Curcuma longa, has been widely used for the treatment of several diseases. Epidemiologically, it was suggested that curcumin might reduce the risk of inflammatory disorders, such as cancer and ulcer. These biological effects are attributed to its anti-inflammatory and antioxidant activities. It can, therefore, be reported from the literature that curcumin PRevents gastrointestinal-induced ulcer and can be recommended as a novel drug for ulcer treatment.", "title": "Turmeric (curcumin) remedies gastroprotective action" }, { "docid": "MED-2899", "text": "The present study was designed to assess the relationship between iris color and macular pigment optical density. Both melanin and carotenoids (responsible for iris color and macular pigment composition, respectively) appear to protect the retina through similar mechanisms and higher concentrations may reduce the incidence of retinal degenerations. To evaluate this relationship, 95 subjects were examined and the following variables were measured: iris color; macular pigment optical density (MP); plasma concentrations of lutein and zeaxanthin and beta-carotene; dietary intake of lutein and zeaxanthin and beta-carotene; and total fat intake. Iris color was determined by self assessment and classified as blue or gray (group I), green or hazel (group II) or brown or black (group III). MP density was measured psychophysically by measuring foveal and parafoveal sensitivities to lights of 460 and 550 nm, using the method of heterochromatic flicker photometry. Plasma carotenoid concentrations were measured using reverse-phase high-performance liquid chromatography. Dietary intake was determined by a detailed food-frequency questionnaire. Despite similarities in diet and in blood concentrations of carotenoids, significant differences in macular pigment density (P < 0.02) were found for different colored irises (group I, n = 38, MP = 0.25; group II, n = 26, MP = 0.32; group III, n = 31, MP = 0.38). The covariation of iris color and MP indicates that past epidemiologic studies have not adequately determined the independent effects of either factor. The relationship of MP and iris color may be the result of one or two factors: the evolution of a shared tendency to accumulate melanin and carotenoids due to similar environmental pressures (e.g. light and oxygen); and/or MP might be depleted due to the tendency for eyes with light irises to transmit more light than eyes with dark irises, thus causing increased oxidative stress.", "title": "Iris color and macular pigment optical density." }, { "docid": "MED-2896", "text": "The relation between dietary antioxidant intake and primary open-angle glaucoma risk was examined in participants aged over 40 years in the Nurses' Health Study (n = 76,200) and the Health Professionals Follow-up Study (n = 40,284). They were followed biennially from 1980 and 1986, respectively, to 1996, during periods when they received an eye examination. Dietary intakes were measured repeatedly from 1980 in the Nurses' Health Study and from 1986 in the Health Professionals Follow-up Study using validated food frequency questionnaires. The authors analyzed 474 self-reported glaucoma cases confirmed by medical chart review to have primary open-angle glaucoma with visual field loss. The authors used Cox proportional hazards models for cohort-specific multivariate analyses, and results were pooled using random effects models. The pooled multivariate rate ratios for primary open-angle glaucoma comparing the highest versus lowest quintile of cumulative updated intake were 1.17 (95% confidence interval (CI): 0.87, 1.58) for alpha-carotene, 1.10 (95% CI: 0.82, 1.48) for beta-carotene, 0.95 (95% CI: 0.70, 1.29) for beta-cryptoxanthin, 0.82 (95% CI: 0.60, 1.12) for lycopene, 0.92 (95% CI: 0.69, 1.24) for lutein/zeaxanthin, 1.05 (95% CI: 0.59, 1.89) for vitamin C, 0.97 (95% CI: 0.62, 1.52) for vitamin E, and 1.11 (95% CI: 0.82, 1.51) for vitamin A. In conclusion, the authors did not observe any strong associations between antioxidant consumption and the risk of primary open-angle glaucoma.", "title": "Antioxidant intake and primary open-angle glaucoma: a prospective study." }, { "docid": "MED-3783", "text": "Fish odour syndrome (trimethylaminuria) is a metabolic syndrome caused by abnormal excretion of trimethylamine in the breath, urine, sweat, saliva and vaginal secretions. Trimethylamine is derived from the intestinal bacterial degradation of foods rich in choline and carnitine and is normally oxidised by the liver to odourless trimethylamine N-oxide which is then excreted in the urine. Impaired oxidation of trimethylamine is thought to be the cause of the fish odour syndrome and is responsible for the smell of rotting fish. Certain foods rich in choline exacerbate the condition and the patients have a variety of psychological problems. Recognition of the condition is important as dietary adjustments reduce the excretion of trimethylamine and may reduce the odour. Occasionally, a short course of metronidazole, neomycin and lactulose may suppress production of trimethylamine by reducing the activity of gut microflora. Keywords: fish odour syndrome; trimethylaminuria", "title": "Fish odour syndrome" }, { "docid": "MED-4360", "text": "Ciguatera is a type of food poisoning associated with the consumption of contaminated marine fish. We report two cases in which painful ejaculation in an affected male and dyspareunia in an unaffected female following her partner's ejaculation suggest the sexual transfer of the responsible agent, ciguatoxin (CTX). Immunoassay of semen samples for CTX were not diagnostic, but the sensitivity and timing of the test employed may have precluded detection of small quantities of the toxin. We conclude that CTX may be present in the semen of men affected with ciguatera toxicity and be capable of producing symptomatology in both males and females during sexual intercourse.", "title": "Can ciguatera be a sexually transmitted disease?" }, { "docid": "MED-2808", "text": "Chemotherapy remains the core of anticancer treatment. However, despite the tremendous strides made in the development of targeted anticancer therapies, emergence of resistance to chemotherapeutic drugs is still a major obstacle in the successful management of resistant tumours. Therefore, profound investigation into the in-depth molecular mechanisms of drug resistance is essential and may hopefully translate into effective therapies that can flip the switch from drug resistance to susceptibility. Mechanistically, resistance phenomena may be explained by (i) overexpression of drug efflux pumps, (ii) enhanced drug detoxification, (iii) rapid DNA repair efficiency, (iv) defects in apoptosis regulation, and (v) active cell survival signals. Several adverse effects associated with multidrug resistance and the need for safe multi-targeted anticancer drugs instigated the use of the phytochemical, curcumin, the yellow pigment of the spice turmeric, which has pleotropic activities. We performed a structured literature review using PubMed and Medline searches with secondary review of cited publications, identifying studies on the role of curcumin in conquering drug resistance in cancer. This review describes how curcumin sensitizes cancer cells through regulation of multiple multidrug resistance pathways, thus employing one drug for multiple targets. Curcumin helps the cancer cells to regain their 'forgotten' apoptosis, modulates drug-target interaction at different levels, restrains survival pathways when their proteins are overexpressed, and finds an alternate way to carry forward the process of sensitization of different resistant tumours. Additionally, the review dissects the role of curcumin, if any, in targeting the major culprit of drug resistance, cancer stem cells (CSC), thereby circumventing resistance. Taken together, this review strongly suggests that curcumin is a promising chemosensitizing agent and that the unique properties of curcumin may be exploited for successful management of resistant tumours.", "title": "Death by design: where curcumin sensitizes drug-resistant tumours." }, { "docid": "MED-4964", "text": "The microbial quality of raw fillets of aquacultured catfish, salmon, tilapia, and trout was evaluated. A total of 272 fillets from nine local and nine Internet retail markets were tested. Mean values were 5.7 log CFU/g for total aerobic mesophiles, 6.3 log CFU/g for psychrotrophs, and 1.9 log most probable number (MPN) per gram for coliforms. Differences in these microbial levels between the two kinds of markets and among the four types of fish were not significant (P > 0.05), except that Internet trout fillets had about 0.8-log higher aerobic mesophiles than did trout fillets purchased locally. Although Escherichia coli was detected in 1.4, 1.5, and 5.9% of trout, salmon, and tilapia, respectively, no sample had > or = 1.0 log MPN/g. However, E. coli was found in 13.2% of catfish, with an average of 1.7 log MPN/g. About 27% of all fillets had Listeria spp., and a positive correlation between the prevalence of Listeria spp. and Listeria monocytogenes was observed. Internet fillets had a higher prevalence of both Listeria spp. and L. monocytogenes than did those fillets purchased locally. L. monocytogenes was present in 23.5% of catfish but in only 5.7, 10.3, and 10.6% of trout, tilapia, and salmon, respectively. Salmonella and E. coli O157 were not found in any sample. A follow-up investigation using catfish operation as a model revealed that gut waste exposed during evisceration is a potential source of coliforms and Listeria spp.", "title": "Microbial quality of raw aquacultured fish fillets procured from Internet and local retail markets." }, { "docid": "MED-1994", "text": "PURPOSE OF REVIEW: The prevalence of obesity in youth is increasing alarmingly among children and adolescents in the United States. The problem falls disproportionately on African-American and Hispanic children. Many of the metabolic and cardiovascular complications associated with obesity are already present during childhood and are closely linked to the concomitant insulin resistance/hyperinsulinemia and degree of obesity. Moreover, these co-morbidities persist into adulthood. RECENT FINDINGS: The progression from normal glucose tolerance to type 2 diabetes mellitus involves an intermediate stage known as prediabetes or impaired glucose regulation. Prediabetes is characterized by peripheral insulin-resistance and impaired glucose sensitivity of first-phase insulin secretion. On the other hand, in overt type 2 diabetes mellitus beta-cell failure becomes fully manifested. Progression from prediabetes to type 2 diabetes mellitus in youth is characterized by marked weight gain and further reduction in insulin secretion and insulin resistance. SUMMARY: Reverting obesity through lifestyle modification, that involves nutrition education, behavior modification and exercise, is an important step to prevent the progression to diabetes.", "title": "Prediabetes and type 2 diabetes in youth: an emerging epidemic disease?" }, { "docid": "MED-1998", "text": "The growing epidemic of type 2 diabetes is one of the leading causes of premature morbidity and mortality worldwide, mainly due to the micro- and macrovascular complications associated with the disease. A growing body of evidence suggests that although the risk of developing complications is greater with glucose levels beyond the established threshold for diagnosis--increasing in parallel with rising hyperglycemia-individuals with glucose levels in the prediabetic range are already at increased risk. Early intervention, ideally as soon as abnormalities in glucose homeostasis are detected, is of great importance to minimize the burden of the disease. However, as the early stages of the disease are asymptomatic, diagnosing prediabetes and early overt type 2 diabetes is challenging. The aim of this article is to discuss these challenges, the benefits of early intervention--with emphasis on the prevention trials showing that progression to type 2 diabetes can be delayed by addressing prediabetes--and the existing evidence-based guidelines that have been drawn to optimize the standards of care at the prediabetes and overt type 2 diabetes stages. Copyright © 2013. Published by Elsevier Inc.", "title": "The early treatment of type 2 diabetes." }, { "docid": "MED-3173", "text": "Objectives Polyphenols, natural compounds found in plant-based foods, possess special properties that can battle oxidative stress and stimulate the activation of molecules that aid in synaptic plasticity, a process that underlies cognitive function. Unlike many traditional treatments, polyphenols affect a broad range of mechanisms in the brain that can assist in the maintenance of cognitive and mental health, as well as the recovery from neurodegenerative diseases. Examining the molecular basis underlying the link between food intake and brain function has presented the exciting possibility of using diet as a viable method to battle cognitive and psychiatric disorders. Methods We will discuss the molecular systems that link polyphenols, the gut, and the brain, as well as introduce published human and animal studies demonstrating the effects of polyphenol consumption on brain plasticity and cognition. Results By influencing cellular energy metabolism and modulating the signaling pathways of molecules involved with brain plasticity, dietary factors – formerly recognized for just their effects on bodily systems – have emerged as affecters of the brain. Conclusion Thus, the consumption of diets enriched with polyphenols may present the potential of dietary manipulation as a non-invasive, natural, and inexpensive therapeutic means to support a healthy brain.", "title": "Natural mood foods: The actions of polyphenols against psychiatric and cognitive disorders" }, { "docid": "MED-3193", "text": "Background Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8). Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.", "title": "11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma" }, { "docid": "MED-2886", "text": "PURPOSE: Goji berry (Lycium barbarum L.) is purported to benefit vision because of its high antioxidant (especially zeaxanthin) content, although this effect has not been demonstrated in high-quality human studies. The purpose of this study was to evaluate the effects of daily supplementation with a proprietary milk-based formulation of goji berry, Lacto-Wolfberry (LWB), on macular characteristics and plasma zeaxanthin and antioxidant capacity levels in elderly subjects. METHODS: This was a double-masked, randomized, placebo-controlled trial in healthy elderly subjects (range, 65 to 70 years) receiving 13.7 g/d of LWB (n = 75) or placebo (n = 75) for 90 days. Subjects underwent direct ophthalmic examination to assess pigmentation and soft drusen count in the macula and a blood draw to measure plasma zeaxanthin level and total antioxidant capacity. RESULTS: The placebo group demonstrated hypopigmentation and soft drusen accumulation in the macula, whereas the LWB group remained stable. Both plasma zeaxanthin level and antioxidant capacity increased significantly in the LWB group, by 26% and 57%, respectively, but did not change in the placebo group. No product-related adverse events were reported in either group. CONCLUSIONS: Overall, daily dietary supplementation with goji berry for 90 days increases plasma zeaxanthin and antioxidant levels as well as protects from hypopigmentation and soft drusen accumulation in the macula of elderly subjects. However, the mechanism of action is unclear, given the lack of relationship between change in plasma zeaxanthin and change in macular characteristics.", "title": "Goji berry effects on macular characteristics and plasma antioxidant levels." }, { "docid": "MED-3427", "text": "Lifestyle and nutrition have been increasingly recognized as central factors influencing vascular nitric oxide (NO) production and erectile function. This review underscores the importance of NO as the principal mediator influencing cardiovascular health and erectile function. Erectile dysfunction (ED) is associated with smoking, excessive alcohol intake, physical inactivity, abdominal obesity, diabetes, hypertension, and decreased antioxidant defenses, all of which reduce NO production. Better lifestyle choices; physical exercise; improved nutrition and weight control; adequate intake of or supplementation with omega-3 fatty acids, antioxidants, calcium, and folic acid; and replacement of any testosterone deficiency will all improve vascular and erectile function and the response to phosphodiesterase-5 inhibitors, which also increase vascular NO production. More frequent penile-specific exercise improves local endothelial NO production. Excessive intake of vitamin E, calcium, l-arginine, or l-citrulline may impart significant cardiovascular risks. Interventions discussed also lower blood pressure or prevent hypertension. Certain angiotensin II receptor blockers improve erectile function and reduce oxidative stress. In men aged <60 years and in men with diabetes or hypertension, erectile dysfunction can be a critical warning sign for existing or impending cardiovascular disease and risk for death. The antiarrhythmic effect of omega-3 fatty acids may be particularly crucial for these men at greatest risk for sudden death. In conclusion, by better understanding the complex factors influencing erectile and overall vascular health, physicians can help their patients prevent vascular disease and improve erectile function, which provides more immediate motivation for men to improve their lifestyle habits and cardiovascular health. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "The link between erectile and cardiovascular health: the canary in the coal mine." }, { "docid": "MED-2823", "text": "Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical which has a variety of biological activities: anti-inflammatory and anti-oxidative. In this review we discuss the biological mechanisms and possible clinical effects of curcumin treatment on cancer therapy, and neurodegenerative diseases such as Alzheimer's Disease, with particular attention to the cell death processes induced by curcumin. Since oxidative stress and inflammation are major determinants of the aging process, we also argue that curcumin can have a more general effect that slows down the rate of aging. Finally, the effects of curcumin can be described as xenohormetic, since it activates a sort of stress response in mammalian cells.", "title": "Curcumin in Cell Death Processes: A Challenge for CAM of Age-Related Pathologies" }, { "docid": "MED-2889", "text": "Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. Cataract extraction is the most common surgical procedure in developed countries. Lutein (L) and zeaxanthin (Z), retinal carotenoids, are the most powerful retinal anti-oxidants and absorb the harmful blue light. The depletion of L+Z induces the development of the lens opacification-cataract. Cataract reduces the retinal oxidative stress (OS), which causes a reduction of the probability to develop AMD. Oxidative Stress at the retinal level is the common pathway in the development of AMD and cataract. AMD and cataract are not two independent processes. Cataract is a self-defense reaction of the retina to reduce OS and retinal damage. Restoring the anti-oxidative capabilities of the retina by increasing intake of L+Z reduces the likelihood of AMD and cataract. Extracting the opaque lens elevates the retinal OS and increases the rate of AMD. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Cataract is a self-defence reaction to protect the retina from oxidative damage." }, { "docid": "MED-4165", "text": "Ergothioneine is a native membrane-impermeable thiol compound that is specifically accumulated in cells via the organic cation transporter OCTN1. In humans, OCTN1 and ergothioneine have been implicated in the etiopathogenesis of autoimmune disorders. However, available evidence about dietary sources and the functional role of ergothioneine in human physiology is scarce. Here, we analyzed the ergothioneine content in common foods using liquid chromatography tandem-mass spectrometry. Additionally, we assessed the protective potency of ergothioneine against various oxidative stressors in OCTN1-expressing cells in comparison with the main intracellular thiol antioxidant glutathione by evaluating cell viability with the MTT reduction assay. Only some food contained ergothioneine with highest concentrations detected in specialty mushrooms, kidney, liver, black and red beans, and oat bran. Ergothioneine exhibited cell protection only against copper(II)-induced toxicity but was far less potent than glutathione, indicting that ergothioneine is not involved in the intracellular antioxidant thiol defense system.", "title": "Dietary sources and antioxidant effects of ergothioneine." }, { "docid": "MED-2885", "text": "OBJECTIVE: This overview of ultraviolet (UV) phototoxicity considers the interaction of UVA and short-wavelength VIS light with the retina and retinal pigment epithelium. METHODS: The damage mechanisms underlying UV retinal phototoxicity are illustrated with a literature survey and presentation of experimental results. RESULTS: Depending on the wavelength and exposure duration, light interacts with tissue by three general mechanisms: thermal, mechanical, or photochemical. Although the anterior structures of the eye absorb much of the UV component of the optical radiation spectrum, a portion of the UVA band (315-400 nm) penetrates into the retina. Natural sources, such as the sun, emit energetic UV photons in relatively long durations, which typically do not result in energy confinement in the retina, and thus do not produce thermal or mechanical damage but are capable of inducing photochemical damage. Photochemical damage in the retina proceeds through Type 1 (direct reactions involving proton or electron transfers) and Type 2 (reactions involving reactive oxygen species) mechanisms. Commonly used drugs, such as certain antibiotics, nonsteroidal anti-inflammatory drugs, psychotherapeutic agents, and even herbal medicines, may act as photosensitizers that promote retinal UV damage, if they are excited by UVA or visible light and have sufficient retinal penetration. CONCLUSIONS: Although the anterior portion of the eye is the most susceptible to UV damage, the retina is at risk to the longer UV wavelengths that propagate through the ocular media. Some phototoxicity may be counteracted or reduced by dietary intake of antioxidants and protective phytonutrients.", "title": "Ultraviolet phototoxicity to the retina." }, { "docid": "MED-1997", "text": "The increased prevalence of childhood overweight and obesity is not unique to industrialized societies; dramatic increases are occurring in urbanized areas of developing countries. In light of the consensus that obesity is a significant public health concern and that many weight-loss interventions have been unsuccessful in the long term, an exploration of food patterns that are beneficial in the primary prevention of obesity is warranted. The focus of this article is to review the relation between vegetarian diets and obesity, particularly as they relate to childhood obesity. Epidemiologic studies indicate that vegetarian diets are associated with a lower body mass index (BMI) and a lower prevalence of obesity in adults and children. A meta-analysis of adult vegetarian diet studies estimated a reduced weight difference of 7.6 kg for men and 3.3 kg for women, which resulted in a 2-point lower BMI (in kg/m(2)). Similarly, compared with nonvegetarians, vegetarian children are leaner, and their BMI difference becomes greater during adolescence. Studies exploring the risk of overweight and food groups and dietary patterns indicate that a plant-based diet seems to be a sensible approach for the prevention of obesity in children. Plant-based diets are low in energy density and high in complex carbohydrate, fiber, and water, which may increase satiety and resting energy expenditure. Plant-based dietary patterns should be encouraged for optimal health and environmental benefits. Food policies are warranted to support social marketing messages and to reduce the cultural and economic forces that make it difficult to promote plant-based dietary patterns.", "title": "Vegetarian diets and childhood obesity prevention." }, { "docid": "MED-2900", "text": "Purpose To explore the association between consumption of fruits and vegetables and the presence of glaucoma in older African American women. Design Cross-sectional study. Methods Disc photographs and suprathreshold visual fields were obtained from the 662 African American participants in the Study of Osteoporotic Fractures. Masked, trained readers graded all discs, and two glaucoma specialists reviewed photos and visual fields. The Block Food Frequency Questionnaire assessed food consumption. Relationships between selected fruit/vegetable/nutrient consumption and glaucoma were evaluated using logistic regression models after adjusting for potential confounders. Results After excluding women missing Food Frequency Questionnaire and disc data, 584 African American women (88.2% of total African American cohort) were included. Glaucoma was diagnosed in at least one eye in 77 subjects (13%). Women who ate 3 or more servings/day of fruits/fruit juices were 79% (odds ratio [OR]=0.21; 95% confidence interval [CI]: 0.08–0.60) less likely to have glaucoma than women who ate less than one serving/day. Women who consumed more than 2 servings/week of fresh oranges (OR=0.18; 95%CI: 0.06–0.51) and peaches (OR=0.30; 95%CI: 0.13–0.67) had a decreased odds of glaucoma compared to those consuming less than one serving/week. For vegetables, >1 serving/week compared to ≤1 serving/month of collard-greens/kale decreased the odds of glaucoma by 57% (OR=0.43; 95%CI: 0.21–0.85). There was a protective trend against glaucoma in those consuming more fruit/fruit juices (p=0.023), fresh oranges (p=0.002), fresh peaches (p=0.002), and collard greens/kale (p=0.014). Higher consumption of carrots (p=0.061) and spinach (p=0.094) also showed some associations. Individual nutrient intake from food sources found protective trends with higher intakes of vitamin A (p=0.011), vitamin C (p=0.018), and α-carotene (p=0.021), and close to statistically significant trends with β-carotene (p=0.052), folate (p=0.056), and lutein/zeaxanthin (p=0.077). Conclusion Higher intake of certain fruits and vegetables high in Vitamins A and C and carotenoids may be associated with a decreased likelihood of glaucoma in older African American women. Randomized controlled trials are needed to determine whether the intake of specific nutrients changes the risk of glaucoma.", "title": "The Association of Consumption of Fruits/Vegetables with Decreased Risk of Glaucoma among Older African American Women in the Study of Osteoporotic Fractures" }, { "docid": "MED-1999", "text": "Diabetes is a major and growing public health challenge which threatens to overwhelm medical services in the future. Type 2 diabetes confers significant morbidity and mortality, most notably with target organ damage to the eyes, kidneys, nerves and heart. The magnitude of cardiovascular risk associated with diabetes is best illustrated by its position as a coronary heart disease risk equivalent. Complications related to neuropathy are also vast, often working in concert with vascular abnormalities and resulting in serious clinical consequences such as foot ulceration. Increased understanding of the natural history of this disorder has generated the potential to intervene and halt pathological progression before overt disease ensues, after which point management becomes increasingly challenging. The concept of prediabetes as a formal diagnosis has begun to be translated from the research setting to clinical practice, but with continually updated guidelines, varied nomenclature, emerging pharmacotherapies and an ever-changing evidence base, clinicians may be left uncertain of best practice in identifying and managing patients at the prediabetic stage. This review aims to summarize the epidemiological data, new concepts in disease pathogenesis and guideline recommendations in addition to lifestyle, pharmacological and surgical therapies targeted at stopping progression of prediabetes to diabetes. While antidiabetic medications, with newer anti-obesity medications and interventional bariatric procedures have shown some promising benefits, diet and therapeutic lifestyle change remains the mainstay of management to improve the metabolic profile of individuals with glucose dysregulation. New risk stratification tools to identify at-risk individuals, coupled with unselected population level intervention hold promise in future practice.", "title": "Strategies for preventing type 2 diabetes: an update for clinicians" }, { "docid": "MED-2811", "text": "Inflammatory bowel disease (IBD) comprising of ulcerative colitis (UC) and Crohn's disease (CD) is a major ailment affecting the small and large bowel. In clinics, IBD is treated using 5-amninosalicylates, antibiotics, the steroids and immunomodulators. Unfortunately, the long term usages of these agents are associated with undue side effects and compromise the therapeutic advantage. Accordingly, there is a need for novel agents that are effective, acceptable and non toxic to humans. Preclinical studies in experimental animals have shown that curcumin, an active principle of the Indian spice turmeric (Curcuma longa Linn) is effective in preventing or ameliorating UC and inflammation. Over the last few decades there has been increasing interest in the possible role of curcumin in IBD and several studies with various experimental models of IBD have shown it to be effective in mediating the inhibitory effects by scavenging free radicals, increasing antioxidants, influencing multiple signaling pathways, especially the kinases (MAPK, ERK), inhibiting myeloperoxidase, COX-1, COX-2, LOX, TNF-α, IFN-γ, iNOS; inhibiting the transcription factor NF-κB. Clinical studies have also shown that co-administration of curcumin with conventional drugs was effective, to be well-tolerated and treated as a safe medication for maintaining remission, to prevent relapse and improve clinical activity index. Large randomized controlled clinical investigations are required to fully understand the potential of oral curcumin for treating IBD.", "title": "Curcumin, an active component of turmeric in the prevention and treatment of ulcerative colitis: preclinical and clinical observations." }, { "docid": "MED-4553", "text": "Alzheimer's disease (AD) is the most common dementing disorder of late life. Although there might be various different triggering events in the early stages of the disease, they seem to converge on a few characteristic final pathways in the late stages, characterized by inflammation and neurodegeneration. In this review, we put forward the hypothesis that advanced glycation end products (AGEs) and their precursors, including methylglyoxal, are both biomarkers and causative agents (\"gerontotoxins\") characteristic for this disorder. Accumulation of AGEs is a normal feature of aging, but is accelerated in AD, where AGEs can be detected in amyloid plaques and neurofibrillary tangles. AGE modification may explain many of the neuropathological and biochemical features of AD such as extensive protein cross-linking, inflammation, oxidative stress and neuronal cell death. We suggest that methylglyoxal is one of the major carbonyl species responsible for the formation of AGEs. We propose that one promising pharmacological approach to prevent the formation of AGEs would be to lower the methylglyoxal concentration. This can be achieved, for example, by decreasing the concentration of methylglyoxal precursors such as d-glyceraldehyde-3-phosphate by allowing a higher flux through the pentose phosphate pathway or by increasing methylglyoxal detoxification through the glyoxalase system. Alternatively, methylglyoxal could be scavenged by various types of carbonyl scavengers. Copyright © 2010 Elsevier Inc. All rights reserved.", "title": "Advanced glycation end products as biomarkers and gerontotoxins - A basis to explore methylglyoxal-lowering agents for Alzheimer's disease?" }, { "docid": "MED-5093", "text": "BACKGROUND: There are few studies reporting on docosahexaenoic acid (DHA, 22:6n-3) supplementation during pregnancy and infant cognitive function. DHA supplementation in pregnancy and infant problem solving in the first year have not been investigated. OBJECTIVE: We tested the hypothesis that infants born to women who consumed a DHA-containing functional food during pregnancy would demonstrate better problem-solving abilities and recognition memory than would infants born to women who consumed the placebo during pregnancy. DESIGN: In a double-blind, placebo-controlled, randomized trial, pregnant women consumed a DHA-containing functional food or a placebo from gestation week 24 until delivery. Study groups received DHA-containing cereal-based bars (300 mg DHA/92-kcal bar; average consumption: 5 bars/wk; n = 14) or cereal-based placebo bars (n = 15). The Infant Planning Test and Fagan Test of Infant Intelligence were administered to infants at age 9 mo. The problem-solving trial included a support step and a search step. The procedure was scored on the basis of the infant's performance on each step and on the entire problem (intention score and total intentional solutions). Scores were generated on the basis of the cumulative performance of the infant on 5 trials. RESULTS: Treatment had significant effects on the performance of problem-solving tasks: total intention score (P = 0.017), total intentional solutions (P = 0.011), and number of intentional solutions on both cloth (P = 0.008) and cover (P = 0.004) steps. There were no significant differences between groups in any measure of Fagan Test of Infant Intelligence. CONCLUSION: These data point to a benefit for problem solving but not for recognition memory at age 9 mo in infants of mothers who consumed a DHA-containing functional food during pregnancy.", "title": "Maternal consumption of a docosahexaenoic acid-containing functional food during pregnancy: benefit for infant performance on problem-solving but n..." }, { "docid": "MED-1985", "text": "The relationship between diet and attained height was studied in children and adolescents in Southern California. Diet pattern was determined from an extensive food frequency questionnaire in 1765 Caucasian children of 7-18 years, attending state schools (452 m and 443 f) and Seventh-day Adventist schools (427 m and 443 f). The major difference in diet pattern between state and Adventist school children was in meat consumption. The Adventist children were split evenly between three categories of frequency in meat consumption (less than 1/week, 1/week-less than 1/d, and greater than or equal to 1/d), while 92 percent of state school children consumed meat daily. Vegetarians (those consuming meat less than 1/week) differed significantly in the consumption of other major food groups, such as fruit and vegetables. All school and diet subgroups were at or above the 50th percentile of the National Center for Health Statistics. Age-adjusted regression analysis showed that on average Adventist vegetarian children were taller than their meat-consuming classmates (2.5 and 2.0 cm for boys and girls, respectively). These results did not change materially when adjusting for other food groups. Nor did adjustment for parental height and socioeconomic factors in a sub-sample of 518 children. The results indicate that vegetarian children and adolescents on a balanced diet grow at least as tall as children who consume meat.", "title": "Attained height of lacto-ovo vegetarian children and adolescents." }, { "docid": "MED-4936", "text": "Food and nutrition professionals question whether supplement-sourced nutrients appear to be equivalent to those derived from natural food sources. We compared the nutritional availability of docosahexaenoic acid (DHA) from algal-oil capsules to that from assayed cooked salmon in 32 healthy men and women, ages 20 to 65 years, in a randomized, open-label, parallel-group study. In this 2-week study comparing 600 mg DHA/day from algal-oil capsules to that from assayed portions of cooked salmon, mean change from baseline in plasma phospholipids and erythrocyte DHA levels was analyzed and DHA levels were compared by Student's t tests. In post-hoc analyses to determine bioequivalence, least-squares mean ratios of percent change from baseline in plasma phospholipid and erythrocyte DHA levels were compared. DHA levels increased by approximately 80% in plasma phospholipids and by approximately 25% in erythrocytes in both groups. Changes in DHA levels in plasma phospholipids and erythrocytes were similar between groups. As measured by delivery of DHA to both plasma and erythrocytes, fish and algal-oil capsules were equivalent. Both regimens were generally well-tolerated. These results indicate that algal-oil DHA capsules and cooked salmon appear to be bioequivalent in providing DHA to plasma and red blood cells and, accordingly, that algal-oil DHA capsules represent a safe and convenient source of non-fish-derived DHA.", "title": "Algal-oil capsules and cooked salmon: nutritionally equivalent sources of docosahexaenoic acid." }, { "docid": "MED-2818", "text": "Curcumin is a polyphenol derived from the herbal remedy and dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties following oral or topical administration. Apart from curcumin's potent antioxidant capacity at neutral and acidic pH, its mechanisms of action include inhibition of several cell signalling pathways at multiple levels, effects on cellular enzymes such as cyclooxygenase and glutathione S-transferases, immuno-modulation and effects on angiogenesis and cell-cell adhesion. Curcumin's ability to affect gene transcription and to induce apoptosis in preclinical models is likely to be of particular relevance to cancer chemoprevention and chemotherapy in patients. Although curcumin's low systemic bioavailability following oral dosing may limit access of sufficient concentrations for pharmacological effect in certain tissues, the attainment of biologically active levels in the gastrointestinal tract has been demonstrated in animals and humans. Sufficient data currently exist to advocate phase II clinical evaluation of oral curcumin in patients with invasive malignancy or pre-invasive lesions of the gastrointestinal tract, particularly the colon and rectum.", "title": "Curcumin: the story so far." }, { "docid": "MED-3780", "text": "Metabolomics studies hold promise for discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. A metabolomics approach was used to generate unbiased small molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine, namely choline, trimethylamine N-oxide (TMAO), and betaine, were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted up-regulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases (FMOs), an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidemic mice. Discovery of a relationship between gut flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for development of both novel diagnostic tests and therapeutic approaches for atherosclerotic heart disease.", "title": "Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease" }, { "docid": "MED-2973", "text": "OBJECTIVE: Type 2 diabetes mellitus appears to involve an interaction between susceptible genetic backgrounds and environmental factors including highly calorific diets. As it is important to identify modifiable risk factors that may help reduce the risk of type 2 diabetes mellitus, the aim of the present study was to determine the association between egg consumption and the risk of type 2 diabetes mellitus. DESIGN: A specifically designed questionnaire was used to collect information on possible risk factors of type 2 diabetes mellitus. The odds ratios and 95 % confidence intervals for type 2 diabetes mellitus were calculated by conditional logistic regression. SETTING: A case-control study in a Lithuanian out-patient clinic was performed in 2001. SUBJECTS: A total of 234 cases with a newly confirmed diagnosis of type 2 diabetes mellitus and 468 controls free of the disease. RESULTS: Variables such as BMI, family history of diabetes, cigarette smoking, education, morning exercise and plasma TAG level were retained in multivariate logistic regression models as confounders because their inclusion changed the value of the odds ratio by more than 10 % in any exposure category. After adjustment for possible confounders more than twofold increased risk of type 2 diabetes mellitus was determined for individuals consuming 3-4·9 eggs/week (OR = 2·60; 95 % CI 1·34, 5·08) and threefold increased risk of the disease was determined for individuals consuming ≥5 eggs/week (OR = 3·02; 95 % CI 1·14, 7·98) compared with those eating <1 egg/week. CONCLUSIONS: Our data support a possible relationship of egg consumption and increased risk of type 2 diabetes mellitus.", "title": "Egg consumption and the risk of type 2 diabetes mellitus: a case-control study." }, { "docid": "MED-2975", "text": "BACKGROUND: Although egg consumption has been associated with elevated plasma levels of cholesterol and triglyceride and with risk of cardiovascular disease in some populations, epidemiologic studies on egg consumption and the risk of diabetes are extremely sparse, particularly in the Chinese population. METHOD: Data from a household survey in the year 2002 among 2849 adults aged ≥20 y from a nationally representative sample in Jiangsu Province, China, were used. Dietary information was assessed by a validated food frequency questionnaire and 3 d weighed food records. Fasting blood specimens were collected. RESULTS: After the adjustment for age, total calorie intake, education, smoking, family history of diabetes, and sedentary activity, egg consumption was significantly and positively associated with diabetes risk, particularly in women. The odds ratios (OR) (95% CI) of diabetes associated with egg consumption <2/wk, 2-6/wk, and ≥1/d in the total sample were 1.00, 1.75, 2.28 (1.14-4.54), respectively (P for trend 0.029). Corresponding ORs (95% CI) in women were 1.00, 1.66, and 3.01 (1.12, 8.12), respectively (P for trend 0.022). Additional adjustment of body mass index attenuated the association, but it remained significant. There was a similar, however, not statistically significant association in men. In addition, plasma triglyceride and total cholesterol levels were significantly higher in women who consumed ≥2 eggs/wk than those who consumed eggs less often. CONCLUSION: Egg consumption was positively associated with the risk of diabetes among the Chinese, particularly in women. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Egg consumption and the risk of diabetes in adults, Jiangsu, China." }, { "docid": "MED-1992", "text": "Summary Prediabetes (or “intermediate hyperglycaemia”), based on glycaemic parameters above normal but below diabetes thresholds is a high risk state for diabetes with an annualized conversion rate of 5%–10%; with similar proportion converting back to normoglycaemia. The prevalence of prediabetes is increasing worldwide and it is projected that >470 million people will have prediabetes in 2030. Prediabetes is associated with the simultaneous presence of insulin resistance and β-cell dysfunction, abnormalities that start before glucose changes are detectable. Observational evidence shows associations of prediabetes with early forms of nephropathy, chronic kidney disease, small fibre neuropathy, diabetic retinopathy, and increased risk of macrovascular disease. Multifactorial risk scores could optimize the estimation of diabetes risk using non-invasive parameters and blood-based metabolic traits in addition to glycaemic values. For prediabetic individuals, lifestyle modification is the cornerstone of diabetes prevention with evidence of a 40%–70% relative risk reduction. Accumulating data also suggests potential benefits from pharmacotherapy.", "title": "Prediabetes: A high-risk state for developing diabetes" }, { "docid": "MED-3395", "text": "The available large prospective studies supporting an inverse association between better adherence to the Mediterranean diet and lower mortality have mainly included older adults. It is not clear whether this inverse association is also present among younger individuals at lower mortality risk. Our aim was to assess the association between adherence to the Mediterranean diet and total mortality in middle-aged adults from the Seguimiento Universidad de Navarra (SUN) Project. We followed 15,535 Spanish university graduates for a mean of 6.8 y. Their mean age was 38 ± 12 y, 59.6% were females, and all were initially free of cardiovascular disease, cancer, and diabetes. A validated FFQ was used to assess dietary habits. Adherence to the Mediterranean diet was categorized into 3 groups according to the Mediterranean Diet Score (low, 0-2 points; moderate, 3-5 points; and high, 6-9 points). The outcome variable was total mortality. Cox proportional hazards models were used to estimate HR and 95% CI. We adjusted the estimates for sex, age, years of university education, BMI, smoking, physical activity, television watching, history of depression and baseline hypertension, and hypercholesterolemia. We observed 125 deaths during 105,980 person-years of follow-up. The fully adjusted HR for moderate and high adherence were 0.58 (95% CI: 0.34, 0.99; P = 0.05) and 0.38 (95% CI: 0.21, 0.70; P = 0.002), respectively. For each 2-point increment in the Mediterranean Diet Score, the HR of death was 0.72 (95% CI: 0.58, 0.91; P = 0.006). Among highly educated, middle-aged adults, adherence to the traditional Mediterranean diet was associated with reduced risk of death.", "title": "The Mediterranean diet is associated with a reduction in premature mortality among middle-aged adults." }, { "docid": "MED-2898", "text": "PURPOSE: Age and advanced disease in the fellow eye are the two most important risk factors for age-related macular degeneration (AMD). In this study, the authors investigated the relationship between these variables and the optical density of macular pigment (MP) in a group of subjects from a northern European population. METHODS: The optical density of MP was measured psychophysically in 46 subjects ranging in age from 21 to 81 years with healthy maculae and in 9 healthy eyes known to be at high-risk of AMD because of advanced disease in the fellow eye. Each eye in the latter group was matched with a control eye on the basis of variables believed to be associated with the optical density of MP (iris color, gender, smoking habits, age, and lens density). RESULTS: There was an age-related decline in the optical density of macular pigment among volunteers with no ocular disease (right eye: r(2) = 0.29, P = 0.0006; left eye: r(2) = 0.29, P < 0.0001). Healthy eyes predisposed to AMD had significantly less MP than healthy eyes at no such risk (Wilcoxon's signed rank test: P = 0.015). CONCLUSIONS: The two most important risk factors for AMD are associated with a relative absence of MP. These findings are consistent with the hypothesis that supplemental lutein and zeaxanthin may delay, avert, or modify the course of this disease.", "title": "Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population." }, { "docid": "MED-2824", "text": "Cancer is primarily a disease of old age, and that life style plays a major role in the development of most cancers is now well recognized. While plant-based formulations have been used to treat cancer for centuries, current treatments usually involve poisonous mustard gas, chemotherapy, radiation, and targeted therapies. While traditional plant-derived medicines are safe, what are the active principles in them and how do they mediate their effects against cancer is perhaps best illustrated by curcumin, a derivative of turmeric used for centuries to treat a wide variety of inflammatory conditions. Curcumin is a diferuloylmethane derived from the Indian spice, turmeric (popularly called \"curry powder\") that has been shown to interfere with multiple cell signaling pathways, including cell cycle (cyclin D1 and cyclin E), apoptosis (activation of caspases and down-regulation of antiapoptotic gene products), proliferation (HER-2, EGFR, and AP-1), survival (PI3K/AKT pathway), invasion (MMP-9 and adhesion molecules), angiogenesis (VEGF), metastasis (CXCR-4) and inflammation (NF-kappaB, TNF, IL-6, IL-1, COX-2, and 5-LOX). The activity of curcumin reported against leukemia and lymphoma, gastrointestinal cancers, genitourinary cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers, and sarcoma reflects its ability to affect multiple targets. Thus an \"old-age\" disease such as cancer requires an \"age-old\" treatment.", "title": "Curcumin and cancer: an \"old-age\" disease with an \"age-old\" solution." }, { "docid": "MED-3251", "text": "CONTEXT: Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established. OBJECTIVE: To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n = 868) were compared with untreated contemporary (n = 829) and historical (n = 959) cohorts. MAIN OUTCOME MEASURES: The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication. RESULTS: The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta-treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P = .14) or the historical control cohort (hazard ratio, 0.77; 95% CI, 0.58-1.02; P = .07) were considered. Further adjustment for comorbidities and socioeconomic status, where possible, did not change interpretations, and propensity score adjustment did not substantially change the results. CONCLUSION: Among patients with relapsing-remitting MS, administration of interferon beta was not associated with a reduction in progression of disability.", "title": "Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis." }, { "docid": "MED-4554", "text": "Modern diets are largely heat-processed and as a result contain high levels of advanced glycation end products (AGEs). Dietary advanced glycation end products (dAGEs) are known to contribute to increased oxidant stress and inflammation, which are linked to the recent epidemics of diabetes and cardiovascular disease. This report significantly expands the available dAGE database, validates the dAGE testing methodology, compares cooking procedures and inhibitory agents on new dAGE formation, and introduces practical approaches for reducing dAGE consumption in daily life. Based on the findings, dry heat promotes new dAGE formation by >10- to 100-fold above the uncooked state across food categories. Animal-derived foods that are high in fat and protein are generally AGE-rich and prone to new AGE formation during cooking. In contrast, carbohydrate-rich foods such as vegetables, fruits, whole grains, and milk contain relatively few AGEs, even after cooking. The formation of new dAGEs during cooking was prevented by the AGE inhibitory compound aminoguanidine and significantly reduced by cooking with moist heat, using shorter cooking times, cooking at lower temperatures, and by use of acidic ingredients such as lemon juice or vinegar. The new dAGE database provides a valuable instrument for estimating dAGE intake and for guiding food choices to reduce dAGE intake.", "title": "Advanced Glycation End Products in Foods and a Practical Guide to Their Reduction in the Diet" }, { "docid": "MED-3175", "text": "Infection with pork tapeworm, or Taenia solium, affects approximately 50 million people worldwide. The most important and potentially devastating form of the infestation, neurocysticercosis, occurs when the parasite invades the central nervous system. There has been a significant increase in the number of cases in the United States due to immigration from endemic areas. This case study of a pregnant woman in the 35th week of gestation exemplifies the serious consequences of this infection in pregnancy, and discusses an evidence-based approach to the diagnosis, treatment and eradication of this preventable disease. © 2012 AWHONN.", "title": "Neurocysticercosis in pregnancy: not just another headache." }, { "docid": "MED-3397", "text": "INTRODUCTION: Phosphodiesterase type 5 (PDE5) inhibitors are the first line drugs for treatment of erectile dysfunction. Sildenafil (Viagra(R)), tadalafil (Cialis(R)), and vardenafil (Levitra(R)) are from the same class of drugs that inhibit PDE5. Transient visual symptoms such as change in color perception and increased light sensitivity are well-known adverse effects of these drugs and occur in 3-11% of sildenafil users. Vision-threatening (serious) ocular complications, such as nonarteritic ischemic optic neuropathy and cilio-retinal artery occlusion have rarely been reported in PDE5 inhibitor users. AIMS: To highlight and analyze the most recently published case literature on serious ocular complications of PDE5 inhibitors. METHODS: Search of the peer-reviewed English literature was conducted using Medline. The following databases also were searched: Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Global Health, and MD Consult. The causality assessment of the reported adverse drug reactions was analyzed by applying both the World Health Organization (WHO) Probability Scale and the criteria utilized by the National Registry of Drug-Induced Ocular Side Effects. MAIN OUTCOME MEASURES: To scientifically and objectively find out if PDE5 inhibitors are associated with vision-threatening ocular complications. RESULTS: Eight case reports of serious PDE5 inhibitor-associated ocular complications were identified since January 2006 until February 2011. Case reports included cases of anterior and posterior nonarteritic ischemic optic neuropathy, central retinal vein occlusion, cilio-retinal artery occlusion, acute angle closure glaucoma and optic atrophy after sildenafil use. CONCLUSION: There is lack of conclusive evidence to indicate a direct cause-effect relationship between PDE5 inhibitor use and vision-threatening ocular events. Men who use PDE5 inhibitors appear to suffer vision-threatening complications at the same frequency as the general population. However, minor visual adverse effects occur in 3-11% of users and they are transient and reversible. © 2011 International Society for Sexual Medicine.", "title": "Are phosphodiesterase type 5 inhibitors associated with vision-threatening adverse events? A critical analysis and review of the literature." }, { "docid": "MED-2976", "text": "Background: Type 2 diabetes (T2D) remains an important public health issue in the United States. There are limited and inconsistent data on the association between egg consumption and fasting glucose or incident diabetes. Objectives: We assessed the association between egg intake and incident diabetes in older adults. Design: In this prospective study of 3898 men and women from the Cardiovascular Health Study (1989–2007), we assessed egg consumption by using a picture-sorted food questionnaire and ascertained incident T2D annually by using information on hypoglycemic agents and plasma glucose. We used Cox proportional hazards models to estimate adjusted relative risks. Results: During a mean follow-up of 11.3 y, 313 new cases of T2D occurred. Crude incidence rates of T2D were 7.39, 6.83, 7.00, 6.72, and 12.20 per 1000 person-years in people who reported egg consumption of never, <1 egg/mo, 1–3 eggs/mo, 1–4 eggs/wk, and almost daily, respectively. In multivariable-adjusted models, there was no association between egg consumption and increased risk of T2D in either sex and overall. In a secondary analysis, dietary cholesterol was not associated with incident diabetes (P for trend = 0.47). In addition, egg consumption was not associated with clinically meaningful differences in fasting glucose, fasting insulin, or measures of insulin resistance despite small absolute analytic differences that were significant. Conclusion: In this cohort of older adults with limited egg intake, there was no association between egg consumption or dietary cholesterol and increased risk of incident T2D.", "title": "Egg consumption and risk of type 2 diabetes in older adults" }, { "docid": "MED-3171", "text": "A method for culturing cysticerci that allows successful evagination and growth of scolexes from metacestodes of Taenia solium was used to study the survival of cysticerci subjected to low temperatures. Refrigeration of pork muscle infested with cysticerci at temperatures above 0 degrees C did not affect the parasites' survival in culture. Conversely, freezing of meat prevented survival of cysts. A practical procedure to kill cysticerci is the storage of pork muscle for four days at -5 degrees C, three days at -15 degrees C, or one day at -24 degrees C. These simple measures would help prevent the most frequent parasitosis of man's central nervous system.", "title": "Freezing of infested pork muscle kills cysticerci." }, { "docid": "MED-3399", "text": "We investigated the effects of Antep pistachio on International Index of Erectile Function (IIEF) scores, penile color Doppler ultrasound (PCDU) parameters and serum lipid levels in patients with ED. A total of 17 married male patients with ED for at least 12 months were included in this prospective study. Patients were put on a 100 g pistachio nuts diet for 3 weeks. IIEF and PCDU were evaluated before and after the pistachio diet. In addition, plasma total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride were measured before and after dietary modifications from all subjects. Mean IIEF-15 score was 36 ± 7.5 before the diet and 54.2 ± 4.9 after the diet (P=0.001). Similarly, an increase in all five domains of IIEF was observed after the diet (P<0.05). Mean peak systolic velocity values before and after the pistachio diet were 35.5 ± 15.2 and 43.3 ± 12.4 cm s(-1), respectively (P=0.018). After the pistachio diet, TC and LDL levels decreased significantly, whereas HDL level increased (P=0.008, 0.007 and 0.001, respectively). We demonstrated that a pistachio diet improved IIEF scores and PCDU parameters without any associated side effects in patients with ED. Furthermore, the lipid parameters showed statistically significant improvements after this diet.", "title": "Pistachio diet improves erectile function parameters and serum lipid profiles in patients with erectile dysfunction." }, { "docid": "MED-2893", "text": "Lutein and zeaxanthin are thought to decrease the incidence of age-related macular degeneration (AMD); however, findings have been inconsistent. We conducted a systematic literature review and meta-analysis to evaluate the relationship between dietary intake of lutein and zeaxanthin and AMD risk. Relevant studies were identified by searching five databases up to April 2010. Reference lists of articles were retrieved, and experts were contacted. Literature search, data extraction and study quality assessment were performed independently by two reviewers and results were pooled quantitatively using meta-analysis methods. The potential sources of heterogeneity and publication bias were also estimated. The search yielded six longitudinal cohort studies. The pooled relative risk (RR) for early AMD, comparing the highest with the lowest category of lutein and zeaxanthin intake, was 0·96 (95 % CI 0·78, 1·17). Dietary intake of these carotenoids was significantly related with a reduction in risk of late AMD (RR 0·74; 95 % CI 0·57, 0·97); and a statistically significant inverse association was observed between lutein and zeaxanthin intake and neovascular AMD risk (RR 0·68; 95 % CI 0·51, 0·92). The results were essentially consistent among subgroups stratified by participant characteristics. The findings of the present meta-analysis indicate that dietary lutein and zeaxanthin is not significantly associated with a reduced risk of early AMD, whereas an increase in the intake of these carotenoids may be protective against late AMD. However, additional studies are needed to confirm these relationships.", "title": "Lutein and zeaxanthin intake and the risk of age-related macular degeneration: a systematic review and meta-analysis." }, { "docid": "MED-4540", "text": "BACKGROUND: Red yeast rice (RYR) is a widely available dietary supplement used by millions of patients as an alternative therapy for hyperlipidemia. It contains 14 active compounds called monacolins that inhibit hepatic cholesterol synthesis. Although studies have suggested that some formulations of RYR may be effective and safe for lipid lowering, monacolin levels are not standardized among marketed products and are generally not published on labels. We evaluated monacolin levels in 12 commercial RYR formulations and tested for citrinin, a mycotoxin that is nephrotoxic in animals. METHODS: Each formulation of RYR was labeled \"600 mg/capsule\" of active product. Analyses for monacolins and citrinin were performed between August 2006 and June 2008 using high-performance liquid chromatography with mass spectroscopy-mass spectroscopy detection. Laboratory analyses of RYR products were conducted by ConsumerLab.com, White Plains, New York. RESULTS: There was marked variability in the 12 RYR products in total monacolins (0.31-11.15 mg/capsule), monacolin K (lovastatin) (0.10-10.09 mg/capsule), and monacolin KA (0.00-2.30 mg/capsule). Four products had elevated levels of citrinin. CONCLUSIONS: We found striking variability in monacolin content in 12 proprietary RYR products and the presence of citrinin in one-third of the formulations tested. Although RYR may have potential as an alternative lipid-lowering agent, our findings suggest the need for improved standardization of RYR products and product labeling. Until this occurs, physicians should be cautious in recommending RYR to their patients for the treatment of hyperlipidemia and primary and secondary prevention of cardiovascular disease.", "title": "Marked variability of monacolin levels in commercial red yeast rice products: buyer beware!" }, { "docid": "MED-3247", "text": "Objective: The chemotherapeutic agent mitoxantrone was approved for use in multiple sclerosis (MS) in 2000. After a review of all the available evidence, the original report of the Therapeutics and Technology Assessment Subcommittee in 2003 concluded that mitoxantrone probably reduced clinical attack rates, MRI activity, and disease progression. Subsequent reports of decreased systolic function, heart failure, and leukemia prompted the US Food and Drug Administration to institute a “black box” warning in 2005. This review was undertaken to examine the available literature on the efficacy and safety of mitoxantrone use in patients with MS since the initial report. Methods: Relevant articles were obtained through a review of the medical literature and the strength of the available evidence was graded according to the American Academy of Neurology evidence classification scheme. Results: The accumulated Class III and IV evidence suggests an increased incidence of systolic dysfunction and therapy-related acute leukemia (TRAL) with mitoxantrone therapy. Systolic dysfunction occurs in ∼12% of patients with MS treated with mitoxantrone, congestive heart failure occurs in ∼0.4%, and leukemia occurs in ∼0.8%. The number needed to harm is 8 for systolic dysfunction and 123 for TRAL. There is no new efficacy evidence that would change the recommendation from the previous report. Conclusions: The risk of systolic dysfunction and leukemia in patients treated with mitoxantrone is higher than suggested at the time of the previous report, although comprehensive postmarketing surveillance data are lacking. GLOSSARY", "title": "Evidence Report: The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis" }, { "docid": "MED-2892", "text": "PURPOSE: The purpose of this study was to investigate the effect of bilberry on night visual acuity (VA) and night contrast sensitivity (CS). METHODS: This study utilized a double-blind, placebo-controlled, crossover design. The subjects were young males with good vision; eight received placebo and seven received active capsules for three weeks. Active capsules contained 160 mg of bilberry extract (25-percent anthocyanosides), and the placebo capsules contained only inactive ingredients. Subjects ingested one active or placebo capsule three times daily for 21 days. After the three-week treatment period, a one-month washout period was employed to allow any effect of bilberry on night vision to dissipate. In the second three-week treatment period, the eight subjects who first received placebo were given active capsules, and the seven who first received active capsules were given placebo. Night VA and night CS was tested throughout the three-month experiment. RESULTS: There was no difference in night VA during any of the measurement periods when examining the average night VA or the last night VA measurement during active and placebo treatments. In addition, there was no difference in night CS during any of the measurement periods when examining the average night CS or the last night CS measurement during active and placebo treatments. CONCLUSION: The current study failed to find an effect of bilberry on night VA or night CS for a high dose of bilberry taken for a significant duration. Hence, the current study casts doubt on the proposition that bilberry supplementation, in the forms currently available and in the doses recommended, is an effective treatment for the improvement of night vision in this population.", "title": "The effect of bilberry nutritional supplementation on night visual acuity and contrast sensitivity." }, { "docid": "MED-3176", "text": "Methods: Ninety consecutive patients with untreated NCC underwent a cognitive assessment (Mini-mental State Examination, Neurobehavioral Cognitive Status Examination, and IQCODE) and were classified as having or not having dementia according to DSM-IV criteria. Imaging and cerebrospinal fluid examination data were recorded. The cognitive measures were repeated six months after treatment with albendazole and steroids. Results: At the initial evaluation 15.5% (n = 14) of the patients were classified as having dementia. Dementia was associated with older age, lower education level, increased number of parasitic lesions in the brain (mostly in the frontal, temporal, and parietal lobes). After six months, 21.5% of the patients from the dementia group continued to have a full dementia disorder and 78.5% no longer fulfilled the DSM-IV criteria for dementia, although some of these patients still showed mild cognitive decline. Conclusions: The results of this study suggest that dementia occurs frequently in patients with untreated NCC, and it is reversible in most cases.", "title": "Is dementia reversible in patients with neurocysticercosis?" }, { "docid": "MED-3789", "text": "Background: Meat, milk, and eggs have been inconsistently associated with the risk of advanced prostate cancer. These foods are sources of choline—a nutrient that may affect prostate cancer progression through cell membrane function and one-carbon metabolism. No study has examined dietary choline and the risk of lethal prostate cancer. Objective: Our objective was to examine whether dietary choline, choline-containing compounds, and betaine (a choline metabolite) increase the risk of lethal prostate cancer. Design: We prospectively examined the intake of these nutrients and the risk of lethal prostate cancer among 47,896 men in the Health Professionals Follow-Up Study. In a case-only survival analysis, we examined the postdiagnostic intake of these nutrients and the risk of lethal prostate cancer among 4282 men with an initial diagnosis of nonmetastatic disease during follow-up. Diet was assessed with a validated questionnaire 6 times during 22 y of follow-up. Results: In the incidence analysis, we observed 695 lethal prostate cancers during 879,627 person-years. Men in the highest quintile of choline intake had a 70% increased risk of lethal prostate cancer (HR: 1.70; 95% CI: 1.18, 2.45; P-trend = 0.005). In the case-only survival analysis, we observed 271 lethal cases during 33,679 person-years. Postdiagnostic choline intake was not statistically significantly associated with the risk of lethal prostate cancer (HR for quintile 5 compared with quintile 1: 1.69; 95% CI: 0.93, 3.09; P-trend = 0.20). Conclusion: Of the 47,896 men in our study population, choline intake was associated with an increased risk of lethal prostate cancer.", "title": "Choline intake and risk of lethal prostate cancer: incidence and survival" } ]
[ { "docid": "MED-5214", "text": "The report of the Epidemiology Subcommittee of the 2007 Dry Eye WorkShop summarizes current knowledge on the epidemiology of dry eye disease, providing prevalence and incidence data from various populations. It stresses the need to expand epidemiological studies to additional geographic regions, to incorporate multiple races and ethnicities in future studies, and to build a consensus on dry eye diagnostic criteria for epidemiological studies. Recommendations are made regarding several characteristics of dry eye questionnaires that might be suitable for use in epidemiological studies and randomized controlled clinical trials. Risk factors for dry eye and morbidity of the disease are identified, and the impact of dry eye disease on quality of life and visual function are outlined. Suggestions are made for further prospective research that would lead to improvement of both eye and general public health.", "title": "The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye WorkShop (2007)." }, { "docid": "MED-5220", "text": "PURPOSE: The aim of this study was to estimate both the direct and indirect annual cost of managing dry eye disease (DED) in the United States from a societal and a payer's perspective. METHODS: A decision analytic model was developed to estimate the annual cost for managing a cohort of patients with dry eye with differing severity of symptoms and treatment. The direct costs included ocular lubricants, cyclosporine, punctal plugs, physician visits, and nutritional supplements. The indirect costs were measured as the productivity loss because of absenteeism and presenteeism. The model was populated with data that were obtained from surveys that were completed by dry eye sufferers who were recruited from online databases. Sensitivity analyses were employed to evaluate the impact of changes in parameters on the estimation of costs. All costs were converted to 2008 US dollars. RESULTS: Survey data were collected from 2171 respondents with DED. Our analysis indicated that the average annual cost of managing a patient with dry eye at $783 (variation, $757-$809) from the payers' perspective. When adjusted to the prevalence of DED nationwide, the overall burden of DED for the US healthcare system would be $3.84 billion. From a societal perspective, the average cost of managing DED was estimated to be $11,302 per patient and $55.4 billion to the US society overall. CONCLUSIONS: DED poses a substantial economic burden on the payer and on the society. These findings may provide valuable information for health plans or employers regarding budget estimation.", "title": "The economic burden of dry eye disease in the United States: a decision tree analysis." }, { "docid": "MED-5223", "text": "Symptoms of tear dysfunction after laser in situ keratomileusis (LASIK) occur in nearly all patients and resolve in the vast majority. Although dry eye complaints are a leading cause of patient discomfort and dissatisfaction after LASIK, the symptoms are not uniform, and the disease is not a single entity. Post-LASIK tear dysfunction syndrome or dry eye is a term used to describe a spectrum of disease encompassing transient or persistent post-operative neurotrophic disease, tear instability, true aqueous tear deficiency, and neuropathic pain states. Neural changes in the cornea and neuropathic causes of ocular surface discomfort may play a separate or synergistic role in the development of symptoms in some patients. Most cases of early post-operative dry eye symptoms resolve with appropriate management, which includes optimizing ocular surface health before and after surgery. Severe symptoms or symptoms persisting after 9 months rarely respond satisfactorily to traditional treatment modalities and require aggressive management. This review covers current theories of post-LASIK dry eye disease, pathophysiology, risk factors, and management options for this disease spectrum of post-LASIK tear dysfunction and neuropathic pain.", "title": "Post-LASIK Tear Dysfunction and Dysesthesia" }, { "docid": "MED-5222", "text": "BACKGROUND: Symptomatic dryness of the eyes is a most common blepharoplasty complication. The authors reviewed the medications and herbal products that may potentiate this complication. METHODS: The MEDLINE and PubMed databases were searched for the years 1991 to 2011. Search terms included \"dry eye syndrome,\" \"keratitis sicca,\" \"keratoconjunctivitis sicca,\" \"ocular side effects,\" \"herbal supplements,\" \"herbals and dry eye,\" \"dry eye risk factors,\" \"etiology of dry eye,\" \"drugs side effects,\" \"drugs and dry eye,\" \"dietary supplements,\" \"ocular toxicity,\" and \"tear film.\" References from herbal product reviews and eligible medication reports were searched for additional articles. A manual search was also conducted based on citations in the published literature. RESULTS: Of 232 articles found to be related to dry eye syndrome and possible risk factors, 196 were excluded because they did not discuss medications or herbal products as risk factors in dry eye syndrome. Thirty-six articles that examined the pathophysiology and risk factors of dry eye were included. Nine books were reviewed that contained some information regarding the association of medications and herbal products with dry eye. These agents were then categorized based on mechanism of action and usage. Medications listed include antihistamines, decongestants, antidepressants, anticonvulsants, antipsychotics, antiparkinson drugs, beta-blockers, and hormone replacement therapy. The three main herbal products that contribute to dry eye are niacin, echinacea, and kava. There was a strong association between anticholinergic alkaloids and dry eye. CONCLUSION: This study identifies the medications and herbal products that should be considered when a patient undergoes blepharoplasty and complains of symptoms associated with dryness of the eyes.", "title": "Pharmaceutical and herbal products that may contribute to dry eyes." }, { "docid": "MED-5210", "text": "To assess the prevalence of eye disease among malnourished children in a rural Ethiopian health center and evaluate correlations between xerophthalmia and grades of malnutrition. A retrospective, cross-sectional survey. An institution-based cross-sectional prospective study was performed at Bushulo Health Center in rural south Ethiopia and included all children age 6 months to 14 years receiving care for malnourishment from June 1st to July 30th, 2008. Data collection involved a combination of interviews with caretakers, ocular examination by a pediatric ophthalmologist and anthropometric measurements. One hundred and seventy-three children (average age at examination 2.9 ± 0.2 years) were treated for malnutrition (97 female, 76 male). One hundred and forty-nine patients had moderate malnutrition (86.03 %) and 24 had severe malnutrition (13.9 %). The following eye diseases were diagnosed--trachoma (12.1 %), blepharitis (13.3 %) and xerophthalmia (20.8 %). Severely malnourished children were more likely to suffer from xerophthalmia than moderately malnourished children (p < 0.0001). When comparing anthropometric measurements to the diagnosis of xerophthalmia, only weight percentile showed significance (p = 0.008). Xerophthalmia is a common global cause of pediatric blindness and is highly correlated with severe malnutrition. Continued efforts are necessary to improve nutrition and outcomes in these patients.", "title": "Prevalence of xerophthalmia among malnourished children in rural Ethiopia." }, { "docid": "MED-5219", "text": "Dry eye is one of the most common eye disorders affecting millions of people. It causes ocular irritation or discomfort, and decreases functional vision, causing a dramatic deterioration in the quality of life. Although new treatments such as the P2Y2 agonist or cyclosporine eye drops have been developed and a certain level of patient satisfaction can now be obtained, no fundamental treatment has been developed. Currently, there is no therapy available to recover lacrimal function to its normal status. Recent progress in the understanding of aging has laid the foundations for a new way of thinking about intervention of the aging process. Because dry eye is accelerated by aging, a useful approach for the prevention or treatment of dry eye may be to interfere with the aging process. In the scientific community, there is a global consensus that calorie restriction can extend the life span of various kinds of animals, establishing an intervention to aging. Another important hypothesis believed to be involved in aging is the free radical theory. According to these theories, the aging process may be managed by controlling levels of calories or reactive oxygen species. In this review, these 2 important aging theories, calorie restriction and free radical aging, are examined, and we discuss how to apply these theories to the prevention and treatment of dry eye.", "title": "The antiaging approach for the treatment of dry eye." }, { "docid": "MED-1021", "text": "CONTEXT: Diabetic retinopathy (DR) is the leading cause of blindness in the working-aged population in the United States. There are many new interventions for DR, but evidence to support their use is uncertain. OBJECTIVE: To review the best evidence for primary and secondary intervention in the management of DR, including diabetic macular edema. EVIDENCE ACQUISITION: Systematic review of all English-language articles, retrieved using a keyword search of MEDLINE (1966 through May 2007), EMBASE, Cochrane Collaboration, the Association for Research in Vision and Ophthalmology database, and the National Institutes of Health Clinical Trials Database, and followed by manual searches of reference lists of selected major review articles. All English-language randomized controlled trials (RCTs) with more than 12 months of follow-up and meta-analyses were included. Delphi consensus criteria were used to identify well-conducted studies. EVIDENCE SYNTHESIS: Forty-four studies (including 3 meta-analyses) met the inclusion criteria. Tight glycemic and blood pressure control reduces the incidence and progression of DR. Pan-retinal laser photocoagulation reduces the risk of moderate and severe visual loss by 50% in patients with severe nonproliferative and proliferative retinopathy. Focal laser photocoagulation reduces the risk of moderate visual loss by 50% to 70% in eyes with macular edema. Early vitrectomy improves visual recovery in patients with proliferative retinopathy and severe vitreous hemorrhage. Intravitreal injections of steroids may be considered in eyes with persistent loss of vision when conventional treatment has failed. There is insufficient evidence for the efficacy or safety of lipid-lowering therapy, medical interventions, or antivascular endothelial growth factors on the incidence or progression of DR. CONCLUSIONS: Tight glycemic and blood pressure control remains the cornerstone in the primary prevention of DR. Pan-retinal and focal retinal laser photocoagulation reduces the risk of visual loss in patients with severe DR and macular edema, respectively. There is currently insufficient evidence to recommend routine use of other treatments.", "title": "Management of diabetic retinopathy: a systematic review." }, { "docid": "MED-5211", "text": "PURPOSE: To identify if whole-body hydration plays an important role in dry eye (DE). We hypothesized that individuals classified as DE have higher plasma osmolality (Posm), indicating suboptimal hydration, compared with those classified as non-DE. METHODS: Using a hospital-based observational cross-sectional design, assessment of DE and hydration was performed upon admission in 111 participants (N = 56 males and 55 females; mean ± SD age 77 ± 8 years). Assessments of DE included tear osmolarity (Tosm), the 5-item dry eye questionnaire (DEQ-5), rating of eye dryness using a visual analogue scale (VAS), and noninvasive tear film breakup time (NITBUT). Hydration assessment was performed by measuring Posm using freezing-point depression osmometry. RESULTS: Posm was higher in DE than control (CON), indicating suboptimal hydration when using the 316 mOsm/L Tosm cutoff for DE (mean Posm + 11 mOsm/kg versus CON, P = 0.004, Cohen's effect size [d]) = 0.83) and the more conservative Tosm classification for DE where Tosm >324 and CON <308 mOsm/L (mean Posm + 12 mOsm/kg versus CON, P = 0.006, d = 0.94). Posm was also higher in DE than CON when using composite DE assessments, including Tosm and DEQ-5 (P = 0.021, d = 1.07); Tosm and NITBUT (P = 0.013, d = 1.08); and the VAS and DEQ-5 (P = 0.034, d = 0.58). CONCLUSIONS: These are the first published data to show that individuals classified as DE have higher Posm, indicating suboptimal hydration, compared with non-DE. These findings indicate that whole-body hydration is an important consideration in DE.", "title": "Is whole-body hydration an important consideration in dry eye?" }, { "docid": "MED-5212", "text": "PURPOSE: To report the rate of recanalization and the efficacy of punctal occlusion surgery with a high heat-energy-releasing cautery device in patients with severe dry eye disease and recurrent punctal plug extrusion. DESIGN: Prospective, interventional case series. METHODS: Seventy puncta from 44 eyes of 28 dry eye patients underwent punctal occlusion with thermal cautery. All patients had a history of recurrent punctal plug extrusion. A high heat-energy-releasing thermal cautery device (Optemp II V; Alcon Japan) was used for punctal occlusion surgery. Symptom scores, best-corrected visual acuity, fluorescein staining score, rose bengal staining score, tear film break-up time, and Schirmer test values were compared before and 3 months after the surgery. Rate of punctal recanalization also was examined. RESULTS: Three months after surgical cauterization, symptom score decreased from 3.9 ± 0.23 to 0.56 ± 0.84 (P < .0001). Logarithm of the minimal angle of resolution best-corrected visual acuity improved from 0.11 ± 0.30 to 0.013 ± 0.22 (P = .003). Fluorescein staining score, rose bengal staining score, tear film break-up time, and the Schirmer test value also improved significantly after the surgery. Only 1 of 70 puncta recanalized after thermal cauterization (1.4%). CONCLUSIONS: Punctal occlusion with the high heat-energy-releasing cautery device not only was associated with a low recanalization rate, but also with improvements in ocular surface wetness and better visual acuity. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Surgical punctal occlusion with a high heat-energy releasing cautery device for severe dry eye with recurrent punctal plug extrusion." }, { "docid": "MED-5224", "text": "Dry-eye syndrome (DES) is a multifactorial disease affecting millions of individuals worldwide. Various factors, including age, hormonal status, genetics, sex, immune status, innervation status, nutrition, pathogens, and environmental stress, can alter the cellular and molecular structure or function of components of the ocular surface system. The resulting imbalance increases susceptibility to desiccation and epithelial damage, leading to a vicious circle in which inflammation amplifies and sustains further damage by chronic deregulation of the system. Lubricating agents and steroids have been used as treatment options. However, as the causes of the disease become better elucidated, the more chemically complex cyclosporine A has become an increasingly useful treatment option and in the United States is currently the only Food and Drug Administration (FDA)-approved prescription drug for the treatment of dry eye. The safety and efficacy of cyclosporine have been shown in numerous studies.", "title": "Safety and Efficacy of Cyclosporine in the Treatment of Chronic Dry Eye" }, { "docid": "MED-5071", "text": "Dietary intervention with anthocyanins may confer benefits in brain function, including vision. Research to date indicates that animals have only a limited capacity to absorb anthocyanins, compared to other types of flavonoids. Pigs, which are a suitable model for human digestive absorption, were used to examine the deposition of anthocyanins in tissues including the liver, eye, and brain tissue. Pigs were fed diets supplemented with 0, 1, 2, or 4% w/w blueberries ( Vaccinium corymbosum L. 'Jersey') for 4 weeks. Prior to euthanasia, pigs were fasted for 18-21 h. Although no anthocyanins were detected in the plasma or urine of the fasted animals, intact anthocyanins were detected in all tissues where they were sought. LC-MS/MS results are presented for the relative concentration of 11 intact anthocyanins in the liver, eye, cortex, and cerebellum. The results suggest that anthocyanins can accumulate in tissues, including tissues beyond the blood-brain barrier.", "title": "Identification of anthocyanins in the liver, eye, and brain of blueberry-fed pigs." }, { "docid": "MED-863", "text": "Durian may inflict severe body injury when it drops from the tree. This case report describes a patient who presented with facial and penetrating eye injury when a ripe durian fruit dropped onto her face while harvesting the fruits under the tree. The authors emphasized the importance of facial and eye protective devices during durian fruit harvesting season.", "title": "Penetrating ocular injury by durian fruit." }, { "docid": "MED-5215", "text": "Punctal and canalicular plugs are widely used for both temporary and permanent occlusion of the lacrimal puncta in dry eyes. There are many designs and materials available on the market. While their efficacy in improving dry eye symptoms is widely proven, the gamut of complications associated with these devices have never been subject to a general review, although there are numerous case series in the literature associated with one particular device. This review aims to examine the track record of a variety of plugs currently in use, to review the management of complications, and propose strategies for both the prevention of these complications and their treatment.", "title": "A review of the complications of lacrimal occlusion with punctal and canalicular plugs." }, { "docid": "MED-5213", "text": "Dry eye disease (DED) treatment is an area of increasing complexity, with the emergence of several new treatment agents in recent years. Evaluation of the efficacy of these agents is limited by heterogeneity in outcomes definition and the small number of comparative studies. We provide a systematic review of clinical trials (CTs) related to DED treatment and a critical appraisal of CT public databases. CT reports obtained from eight databases were reviewed, as well as public free-access electronic databases for CT registration. Data evaluation was based on endpoints such as symptoms, Schirmer test, ocular surface staining scores, recruitment of patients, type and efficacy of the drug, and the design and site of performance of the study. Forty-nine CTs were evaluated involving 5,189 patients receiving DED treatment. Heterogeneity in study design prevented meta-analysis from yielding meaningful results, and a descriptive analysis of these studies was conducted. The most frequent categories of drugs for DED in these studies were artificial tears, followed by anti-inflammatory drugs and secretagogues. Although 116 studies have been completed, according to the registration database for clinical trials, only 17 of them (15.5%) were published. Out of 185 registered CTs related to DED, 72% were performed in the USA. The pharmaceutical industry sponsored 78% of them. The identification of effective DED treatment strategies is hindered by the lack of an accepted set of definitive criteria for evaluating disease severity. Copyright © 2013 Elsevier Inc. All rights reserved.", "title": "Dry eye disease treatment: a systematic review of published trials and a critical appraisal of therapeutic strategies." }, { "docid": "MED-855", "text": "Hydrogen peroxide is an oxidising agent that is used in a number of household products, including general-purpose disinfectants, chlorine-free bleaches, fabric stain removers, contact lens disinfectants and hair dyes, and it is a component of some tooth whitening products. In industry, the principal use of hydrogen peroxide is as a bleaching agent in the manufacture of paper and pulp. Hydrogen peroxide has been employed medicinally for wound irrigation and for the sterilisation of ophthalmic and endoscopic instruments. Hydrogen peroxide causes toxicity via three main mechanisms: corrosive damage, oxygen gas formation and lipid peroxidation. Concentrated hydrogen peroxide is caustic and exposure may result in local tissue damage. Ingestion of concentrated (>35%) hydrogen peroxide can also result in the generation of substantial volumes of oxygen. Where the amount of oxygen evolved exceeds its maximum solubility in blood, venous or arterial gas embolism may occur. The mechanism of CNS damage is thought to be arterial gas embolisation with subsequent brain infarction. Rapid generation of oxygen in closed body cavities can also cause mechanical distension and there is potential for the rupture of the hollow viscus secondary to oxygen liberation. In addition, intravascular foaming following absorption can seriously impede right ventricular output and produce complete loss of cardiac output. Hydrogen peroxide can also exert a direct cytotoxic effect via lipid peroxidation. Ingestion of hydrogen peroxide may cause irritation of the gastrointestinal tract with nausea, vomiting, haematemesis and foaming at the mouth; the foam may obstruct the respiratory tract or result in pulmonary aspiration. Painful gastric distension and belching may be caused by the liberation of large volumes of oxygen in the stomach. Blistering of the mucosae and oropharyngeal burns are common following ingestion of concentrated solutions, and laryngospasm and haemorrhagic gastritis have been reported. Sinus tachycardia, lethargy, confusion, coma, convulsions, stridor, sub-epiglottic narrowing, apnoea, cyanosis and cardiorespiratory arrest may ensue within minutes of ingestion. Oxygen gas embolism may produce multiple cerebral infarctions. Although most inhalational exposures cause little more than coughing and transient dyspnoea, inhalation of highly concentrated solutions of hydrogen peroxide can cause severe irritation and inflammation of mucous membranes, with coughing and dyspnoea. Shock, coma and convulsions may ensue and pulmonary oedema may occur up to 24-72 hours post exposure. Severe toxicity has resulted from the use of hydrogen peroxide solutions to irrigate wounds within closed body cavities or under pressure as oxygen gas embolism has resulted. Inflammation, blistering and severe skin damage may follow dermal contact. Ocular exposure to 3% solutions may cause immediate stinging, irritation, lacrimation and blurred vision, but severe injury is unlikely. Exposure to more concentrated hydrogen peroxide solutions (>10%) may result in ulceration or perforation of the cornea. Gut decontamination is not indicated following ingestion, due to the rapid decomposition of hydrogen peroxide by catalase to oxygen and water. If gastric distension is painful, a gastric tube should be passed to release gas. Early aggressive airway management is critical in patients who have ingested concentrated hydrogen peroxide, as respiratory failure and arrest appear to be the proximate cause of death. Endoscopy should be considered if there is persistent vomiting, haematemesis, significant oral burns, severe abdominal pain, dysphagia or stridor. Corticosteroids in high dosage have been recommended if laryngeal and pulmonary oedema supervene, but their value is unproven. Endotracheal intubation, or rarely, tracheostomy may be required for life-threatening laryngeal oedema. Contaminated skin should be washed with copious amounts of water. Skin lesions should be treated as thermal burns; surgery may be required for deep burns. In the case of eye exposure, the affected eye(s) shod eye(s) should be irrigated immediately and thoroughly with water or 0.9% saline for at least 10-15 minutes. Instillation of a local anaesthetic may reduce discomfort and assist more thorough decontamination.", "title": "Hydrogen peroxide poisoning." }, { "docid": "MED-1503", "text": "Epidemiologic studies suggest that dietary lutein and zeaxanthin may be of benefit in maintaining cognitive health. Among the carotenoids, lutein and zeaxanthin are the only two that cross the blood-retina barrier to form macular pigment (MP) in the eye. They also preferentially accumulate in the human brain. Lutein and zeaxanthin in macula from nonhuman primates were found to be significantly correlated with their concentrations in matched brain tissue. Therefore, MP can be used as a biomarker of lutein and zeaxanthin in primate brain tissue. This is of interest given that a significant correlation was found between MP density and global cognitive function in healthy older adults. An examination of a relation between cognition and lutein and zeaxanthin concentrations in the brain tissue of decedents from a population-based study in centenarians found that zeaxanthin concentrations in brain tissue were significantly related to antemortem measures of global cognitive function, memory retention, verbal fluency, and dementia severity after adjustment for age, sex, education, hypertension, and diabetes. In univariate analyses, lutein was related to recall and verbal fluency, but the strength of the associations was attenuated with adjustment for covariates. However, lutein concentrations in the brain were significantly lower in individuals with mild cognitive impairment than in those with normal cognitive function. Last, in a 4-mo, double-blinded, placebo-controlled trial in older women that involved lutein supplementation (12 mg/d), alone or in combination with DHA (800 mg/d), verbal fluency scores improved significantly in the DHA, lutein, and combined-treatment groups. Memory scores and rate of learning improved significantly in the combined-treatment group, who also showed a trend toward more efficient learning. When all of these observations are taken into consideration, the idea that lutein and zeaxanthin can influence cognitive function in older adults warrants further study.", "title": "A possible role for lutein and zeaxanthin in cognitive function in the elderly." }, { "docid": "MED-5095", "text": "Docosahexaenoic acid (DHA), a long-chain omega-3 fatty acid, is important for eye and brain development and ongoing visual, cognitive, and cardiovascular health. Unlike fish-sourced oils, the bioavailability of DHA from vegetarian-sourced (algal) oils has not been formally assessed. We assessed bioequivalence of DHA oils in capsules from two different algal strains versus bioavailability from an algal-DHA-fortified food. Our 28-day randomized, placebo-controlled, parallel group study compared bioavailability of (a) two different algal DHA oils in capsules (\"DHASCO-T\" and \"DHASCO-S\") at doses of 200, 600, and 1,000 mg DHA per day (n = 12 per group) and of (b) an algal-DHA-fortified food (n = 12). Bioequivalence was based on changes in plasma phospholipid and erythrocyte DHA levels. Effects on arachidonic acid (ARA), docosapentaenoic acid-n-6 (DPAn-6), and eicosapentaenoic acid (EPA) were also determined. Both DHASCO-T and DHASCO-S capsules produced equivalent DHA levels in plasma phospholipids and erythrocytes. DHA response was dose-dependent and linear over the dose range, plasma phospholipid DHA increased by 1.17, 2.28 and 3.03 g per 100 g fatty acid at 200, 600, and 1,000 mg dose, respectively. Snack bars fortified with DHASCO-S oil also delivered equivalent amounts of DHA on a DHA dose basis. Adverse event monitoring revealed an excellent safety and tolerability profile. Two different algal oil capsule supplements and an algal oil-fortified food represent bioequivalent and safe sources of DHA.", "title": "Bioequivalence of Docosahexaenoic acid from different algal oils in capsules and in a DHA-fortified food." }, { "docid": "MED-5209", "text": "A 5-year-old boy with autism developed dry eye and xerophthalmia. Serum vitamin A was undetectable. Dietary history revealed a markedly altered intake consisting of only fried potatoes and rice balls for 2 years. Fried potatoes contain no vitamin A. Autism is a multifaceted developmental disorder infrequently accompanied by abnormal eating practices. To the authors' knowledge, most children with autism who develop dietary vitamin A deficiency have consumed an excess of fried potatoes. Attention to possible vitamin A deficiency is essential when fried potatoes are consumed exclusively.", "title": "Fried-potato diet causes vitamin A deficiency in an autistic child." }, { "docid": "MED-5218", "text": "The effect of diet on tear function is illustrated clearly by malnutrition-induced xerophthalmia. Dietary habits in well nourished North American society have been implicated as a cause of some tear dysfunction. A review of the ocular literature suggests that sufficient dietary protein, vitamins A, B6 and C, potassium, and zinc may be necessary for normal tear function. Excesses of dietary fats, salt, cholesterol, alcohol, protein, and sucrose have been associated with or suggested as causes of tear dysfunction. No unequivocal link has been established between diet and remission of dry eye states in a well nourished population.", "title": "Influence of diet on tear function." }, { "docid": "MED-5050", "text": "Tea is the most widely consumed beverage in the world after water. Tea is known to be a rich source of flavonoid antioxidants. However tea also contains a unique amino acid, L-theanine that may modulate aspects of brain function in humans. Evidence from human electroencephalograph (EEG) studies show that it has a direct effect on the brain (Juneja et al. Trends in Food Science & Tech 1999;10;199-204). L-theanine significantly increases activity in the alpha frequency band which indicates that it relaxes the mind without inducing drowsiness. However, this effect has only been established at higher doses than that typically found in a cup of black tea (approximately 20mg). The aim of the current research was to establish this effect at more realistic dietary levels. EEG was measured in healthy, young participants at baseline and 45, 60, 75, 90 and 105 minutes after ingestion of 50mg L-theanine (n=16) or placebo (n=19). Participants were resting with their eyes closed during EEG recording. There was a greater increase in alpha activity across time in the L-theanine condition (relative to placebo (p+0.05). A second study replicated this effect in participants engaged in passive activity. These data indicate that L-theanine, at realistic dietary levels, has a significant effect on the general state of mental alertness or arousal. Furthermore, alpha activity is known to play an important role in critical aspects of attention, and further research is therefore focussed on understanding the effect of L-theanine on attentional processes.", "title": "L-theanine, a natural constituent in tea, and its effect on mental state." }, { "docid": "MED-1832", "text": "The need for a dietary supply of docosahexaenoic acid (DHA) and arachidonic aid (AA) in term infants was evaluated in a double-masked randomized clinical trial of the effects of supplementation of term infant formula with DHA (0.35% of total fatty acids) or with DHA (0.36%) and AA (0.72%) on visual acuity development. One hundred and eight healthy term infants were enrolled in the study; 79 were exclusively formula-fed from birth (randomized group) and 29 were exclusively breast-fed (gold standard group). Infants were evaluated at four time points during the first 12 mo of life for blood fatty acid composition, growth, sweep visual evoked potential (VEP) acuity, and forced choice preferential looking acuity. Supplementation of term infant formula with DHA or with DHA and AA during the first 4 mo of life yields clear differences in total red blood cell (RBC) lipid composition. Supplementation of term infant formula with DHA or with DHA and AA also yields better sweep VEP acuity at 6, 17, and 52 wk of age but not at 26 wk of age, when acuity development reaches a plateau. The RBC lipid composition and sweep VEP acuity of supplemented infants was similar to that of human milk-fed infants, whereas the RBC lipid composition and sweep VEP acuity of unsupplemented infants was significantly different from human milk-fed infants. Differences in acuity among diet groups were too subtle to be detected by the forced choice preferential looking protocol. Infants in all diet groups had similar rates of growth and tolerated all diets well. Thus, early dietary intake of preformed DHA and AA appears necessary for optimal development of the brain and eye of the human infant.", "title": "Visual acuity and the essentiality of docosahexaenoic acid and arachidonic acid in the diet of term infants." }, { "docid": "MED-5247", "text": "Purpose We investigated whether caffeine, which transiently increases intraocular pressure (IOP) is associated with risk of primary open-angle glaucoma (POAG). Methods We followed 79,120 women from 1980 and 42,052 men from 1986 to 2004 who were 40+ years old, did not have POAG, and reported receiving eye examinations. Information on caffeine consumption, potential confounders and POAG diagnoses were repeatedly updated in validated follow-up questionnaires. We confirmed 1,011 incident POAG cases with medical record review. Cohort-specific and pooled analyses across cohorts were conducted to calculate multivariable rate ratios (RR). Results Compared with daily intake of < 150 mg, the pooled multivariable RRs were 1.05 [95% Confidence Interval (CI), 0.89–1.25] for consuming 150–299 mg, 1.19 [95% CI, 0.99–1.43] for 300 – 449 mg/day, 1.13 [95% CI, 0.89–1.43] for 450–559 mg and 1.17 [95% CI, 0.90, 1.53] for 600+ mg+ [p for trend = 0.11]. However, for consuming 5+ cups of caffeinated coffee daily, RR was 1.61 [95% CI, 1.00, 2.59; p for trend=0.02]; tea or caffeinated cola intake were not associated with risk. Greater caffeine intake was more adversely associated with POAG among those reporting family history of glaucoma, particularly in relation to POAG with elevated IOP (p for trend =0.0009; p-interaction=0.04). Conclusion Overall caffeine intake was not associated with increased risk of POAG. However, in secondary analyses, caffeine appeared to elevate risk of high-tension POAG among those with a family history of glaucoma; this may be due to chance, but warrants further study.", "title": "Caffeine Consumption and the Risk of Primary Open - Angle Glaucoma: A Prospective Cohort Study" }, { "docid": "MED-4747", "text": "In contrast to the use of hormonal doping agents in sports to enhance the performance of athletes, in the livestock industry hormonal growth promoters (\"anabolics\") are used to increase the production of muscle meat. This leads to international disputes about the safety of meat originating from animals treated with such anabolics.As a consequence of the total ban in the EU of all hormonal active growth promoters (\"hormones\") in livestock production, in contrast to their legal use [e.g. of five such hormones (17beta-estradiol, testosterone, progesterone, trenbolone and zeranol) as small solid ear implants and two hormones as feed additives for feedlot heifers (melengestrol acetate) and for swine (ractopamine) in the USA], the regulatory controls also differ sharply between the EU and the USA.In the EU the treatment of slaughter animals is the regulatory offence that has to be controlled in inspection programs. In the USA testing for compliance of a regulatory maximum residue level in the edible product (muscle, fat, liver or kidney) is the purpose of the inspection program (if any).The EU inspection programs focus on sample materials that are more suitable for testing for banned substances, especially if the animals are still on the farm, such as urine and feces or hair. In the case of slaughtered animals, the more favored sample materials are bile, blood, eyes and sometimes liver. Only in rare occasions is muscle meat sampled. This happens only in the case of import controls or in monitoring programs of meat sampled in butcher shops or supermarkets.As a result, data on hormone concentrations in muscle meat samples from the EU market are very rare and are obtained in most cases from small programs on an ad hoc basis. EU data for natural hormones in meat are even rarer because of the absence of \"legal natural levels\" for these hormones in compliance testing. With the exception of samples from the application sites - in the EU the site of injection of liquid hormone preparations or the site of application of \"pour on\" preparations - the hormone concentrations observed in meat samples of illegally treated animals are typically in the range of a few micrograms per kilogram (ppb) down to a few tenths of a microgram per kilogram. In the EU dozens of illegal hormones are used and the number of active compounds is still expanding. Besides estrogenic, androgenic and progestagenic compounds also thyreostatic, corticosteroidal and beta-adrenergic compounds are used alone or in \"smart\" combinations.An overview is given of the compounds identified on the EU black market. An estimate is also given of the probability of consumption in the EU of \"highly\" contaminated meat from the application sites in cattle. Finally some data are presented on the concentration of estradiol in bovine meat from animals treated and not treated with hormone implants. These data are compared with the recent findings for estradiol concentrations in hen's eggs. From this comparison, the preliminary conclusion is that hen's eggs are the major source of 17alpha- and 17beta-estradiol in the consumer's daily \"normal\" diet.", "title": "Hormonal growth promoting agents in food producing animals." }, { "docid": "MED-2304", "text": "Background There is overwhelming evidence that behavioural factors influence health, but their combined impact on the general population is less well documented. We aimed to quantify the potential combined impact of four health behaviours on mortality in men and women living in the general community. Methods and Findings We examined the prospective relationship between lifestyle and mortality in a prospective population study of 20,244 men and women aged 45–79 y with no known cardiovascular disease or cancer at baseline survey in 1993–1997, living in the general community in the United Kingdom, and followed up to 2006. Participants scored one point for each health behaviour: current non-smoking, not physically inactive, moderate alcohol intake (1–14 units a week) and plasma vitamin C >50 mmol/l indicating fruit and vegetable intake of at least five servings a day, for a total score ranging from zero to four. After an average 11 y follow-up, the age-, sex-, body mass–, and social class–adjusted relative risks (95% confidence intervals) for all-cause mortality(1,987 deaths) for men and women who had three, two, one, and zero compared to four health behaviours were respectively, 1.39 (1.21–1.60), 1.95 (1.70–-2.25), 2.52 (2.13–3.00), and 4.04 (2.95–5.54) p < 0.001 trend. The relationships were consistent in subgroups stratified by sex, age, body mass index, and social class, and after excluding deaths within 2 y. The trends were strongest for cardiovascular causes. The mortality risk for those with four compared to zero health behaviours was equivalent to being 14 y younger in chronological age. Conclusions Four health behaviours combined predict a 4-fold difference in total mortality in men and women, with an estimated impact equivalent to 14 y in chronological age. Editors' Summary Background. Every day, or so it seems, new research shows that some aspect of lifestyle—physical activity, diet, alcohol consumption, and so on—affects health and longevity. For the person in the street, all this information is confusing. What is a healthy diet, for example? Although there are some common themes such as the benefit of eating plenty of fruit and vegetables, the details often differ between studies. And exactly how much physical activity is needed to improve health? Is a gentle daily walk sufficient or simply a stepping stone to doing enough exercise to make a real difference? The situation with alcohol consumption is equally confusing. Small amounts of alcohol apparently improve health but large amounts are harmful. As a result, it can be hard for public-health officials to find effective ways to encourage the behavioral changes that the scientific evidence suggests might influence the health of populations. Why Was This Study Done? There is another factor that is hindering official attempts to provide healthy lifestyle advice to the public. Although there is overwhelming evidence that individual behavioral factors influence health, there is very little information about their combined impact. If the combination of several small differences in lifestyle could be shown to have a marked effect on the health of populations, it might be easier to persuade people to make behavioral changes to improve their health, particularly if those changes were simple and relatively easy to achieve. In this study, which forms part of the European Prospective Investigation into Cancer and Nutrition (EPIC), the researchers have examined the relationship between lifestyle and the risk of dying using a health behavior score based on four simply defined behaviors—smoking, physical activity, alcohol drinking, and fruit and vegetable intake. What Did the Researchers Do and Find? Between 1993 and 1997, about 20,000 men and women aged 45–79 living in Norfolk UK, none of whom had cancer or cardiovascular disease (heart or circulation problems), completed a health and lifestyle questionnaire, had a health examination, and had their blood vitamin C level measured as part of the EPIC-Norfolk study. A health behavior score of between 0 and 4 was calculated for each participant by giving one point for each of the following healthy behaviors: current non-smoking, not physically inactive (physical inactivity was defined as having a sedentary job and doing no recreational exercise), moderate alcohol intake (1–14 units a week; a unit of alcohol is half a pint of beer, a glass of wine, or a shot of spirit), and a blood vitamin C level consistent with a fruit and vegetable intake of at least five servings a day. Deaths among the participants were then recorded until 2006. After allowing for other factors that might have affected their likelihood of dying (for example, age), people with a health behavior score of 0 were four times as likely to have died (in particular, from cardiovascular disease) than those with a score of 4. People with a score of 2 were twice as likely to have died. What Do These Findings Mean? These findings indicate that the combination of four simply defined health behaviors predicts a 4-fold difference in the risk of dying over an average period of 11 years for middle-aged and older people. They also show that the risk of death (particularly from cardiovascular disease) decreases as the number of positive health behaviors increase. Finally, they can be used to calculate that a person with a health score of 0 has the same risk of dying as a person with a health score of 4 who is 14 years older. These findings need to be confirmed in other populations and extended to an analysis of how these combined health behaviors affect the quality of life as well as the risk of death. Nevertheless, they strongly suggest that modest and achievable lifestyle changes could have a marked effect on the health of populations. Armed with this information, public-health officials should now be in a better position to encourage behavior changes likely to improve the health of middle-aged and older people. Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050012.", "title": "Combined Impact of Health Behaviours and Mortality in Men and Women: The EPIC-Norfolk Prospective Population Study" }, { "docid": "MED-1546", "text": "Background “Cardiovascular health” is a new construct defined by the American Heart Association (AHA) as part of its 2020 Impact Goals definition. The applicability of this construct to community-based populations and the distributions of its components by race and sex have not been reported. Methods and Results The AHA construct of “cardiovascular health” and the AHA “ideal health behaviors index” and “ideal health factors index” were evaluated among 1933 participants (mean age 59 years; 44% blacks; 66% female) in the community-based Heart Strategies Concentrating on Risk Evaluation study. One of 1933 participants (0.1%) met all 7 components of the AHA's definition of ideal cardiovascular health. Less than 10% of participants met ≥5 components of ideal cardiovascular health in all subgroups (by race, sex, age and income level). Thirty-nine subjects (2.0%) had all four components of the ideal health behaviors index and 27 (1.4%) had all three components of the ideal health factors index. Blacks had significantly fewer ideal cardiovascular health components than whites (2.0±1.2 vs. 2.6±1.4, p<0.001). After adjustment by sex, age and income level, blacks had 82% lower odds of having ≥5 components of ideal cardiovascular health (Odds Ratio 0.18, 95% Confidence Interval (CI)=0.10-0.34, p<0.001). No interaction was found between race and sex. Conclusion The prevalence of ideal cardiovascular health is extremely low in a middle-age community-based study population. Comprehensive individual and population-based interventions must be developed to support the attainment of the AHA's 2020 Impact Goals for cardiovascular health.", "title": "Low Prevalence of “Ideal Cardiovascular Health” in a Community-Based Population: The Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) Study" }, { "docid": "MED-762", "text": "The Ethiopian Field Epidemiology and Laboratory Training Program (EFELTP) is a comprehensive two-year competency-based training and service program designed to build sustainable public health expertise and capacity. Established in 2009, the program is a partnership between the Ethiopian Federal Ministry of Health, the Ethiopian Health and Nutrition Research Institute, Addis Ababa University School of Public Health, the Ethiopian Public Health Association and the US Centers of Disease Control and Prevention. Residents of the program spend about 25% of their time undergoing didactic training and the 75% in the field working at program field bases established with the MOH and Regional Health Bureaus investigating disease outbreaks, improving disease surveillance, responding to public health emergencies, using health data to make recommendations and undertaking other field Epidemiology related activities on setting health policy. Residents from the first 2 cohorts of the program have conducted more than 42 outbreaks investigations, 27analyses of surveillance data, evaluations of 11 surveillance systems, had28oral and poster presentation abstracts accepted at 10 scientific conferences and submitted 8 manuscripts of which 2are already published. The EFELTP has provided valuable opportunities to improve epidemiology and laboratory capacity building in Ethiopia. While the program is relatively young, positive and significant impacts are assisting the country better detect and respond to epidemics and address diseases of major public health significance.", "title": "The Ethiopian Field Epidemiology and Laboratory Training Program: strengthening public health systems and building human resource capacity." }, { "docid": "MED-1213", "text": "Background The American Heart Association’s 2020 Strategic Impact Goals target a 20% relative improvement in overall cardiovascular health with the use of 4 health behavior (smoking, diet, physical activity, body mass) and 3 health factor (plasma glucose, cholesterol, blood pressure) metrics. We sought to define current trends and forward projections to 2020 in cardiovascular health. Methods and Results We included 35 059 cardiovascular disease–free adults (aged ≥20 years) from the National Health and Nutrition Examination Survey 1988–1994 and subsequent 2-year cycles during 1999–2008. We calculated population prevalence of poor, intermediate, and ideal health behaviors and factors and also computed a composite, individual-level Cardiovascular Health Score for all 7 metrics (poor=0 points; intermediate=1 point; ideal=2 points; total range, 0–14 points). Prevalence of current and former smoking, hypercholesterolemia, and hypertension declined, whereas prevalence of obesity and dysglycemia increased through 2008. Physical activity levels and low diet quality scores changed minimally. Projections to 2020 suggest that obesity and impaired fasting glucose/diabetes mellitus could increase to affect 43% and 77% of US men and 42% and 53% of US women, respectively. Overall, population-level cardiovascular health is projected to improve by 6% overall by 2020 if current trends continue. Individual-level Cardiovascular Health Score projections to 2020 (men=7.4 [95% confidence interval, 5.7–9.1]; women=8.8 [95% confidence interval, 7.6–9.9]) fall well below the level needed to achieve a 20% improvement (men=9.4; women=10.1). Conclusions The American Heart Association 2020 target of improving cardiovascular health by 20% by 2020 will not be reached if current trends continue.", "title": "Cardiovascular Health Behavior and Health Factor Changes (1988 –2008) and Projections to 2020" }, { "docid": "MED-1542", "text": "Background The American Heart Association's 2020 Strategic Impact Goals define a new concept, “cardiovascular (CV) health”; however, current prevalence estimates of the status of CV health in U.S. adults according to age, sex and race/ethnicity have not been published. Methods and Results We included 14,515 adults (≥20 years) from the 2003-2008 National Health and Nutrition Examination Surveys. Participants were stratified by young (20-39 years), middle (40-64 years), and older ages (65+ years). CV health behaviors (diet, physical activity, body mass index, smoking) and CV health factors (blood pressure, total cholesterol, fasting blood glucose, smoking) were defined as poor, intermediate, or ideal. Less than 1% of adults exhibited ideal CV health for all 7 metrics. For CV health behaviors, non-smoking was most prevalent (range:60.2-90.4%) while ideal Healthy Diet Score was least prevalent (range:0.2-2.6%) across groups. Prevalence of ideal BMI (range:36.5-45.3%) and ideal physical activity levels (range:50.2-58.8%) were higher in young adults compared to middle or older ages. Ideal total cholesterol (range:23.7-36.2%), blood pressure (range:11.9-16.3%) and fasting blood glucose (range:31.2-42.9%) were lower in older adults compared with young and middle age adults.Prevalence of poor CV health factors was lowest in young age but higher at middle and older ages. Prevalence estimates by age and sex were consistent across race/ethnic groups. Conclusions These prevalence estimates of CV health represent a starting point from which effectiveness of efforts to promote CV health and prevent CV disease can be monitored and compared in U.S. adult populations.", "title": "Status of Cardiovascular Health in US Adults: Prevalence Estimates from the National Health and Nutrition Examination Surveys (NHANES) 2003-2008" }, { "docid": "MED-4598", "text": "OBJECTIVE: The present study aimed to evaluate the knowledge and practices of public-sector primary-care health professionals and final-year students regarding the role of nutrition, physical activity and smoking cessation (lifestyle modification) in the management of chronic diseases of lifestyle within the public health-care sector. DESIGN: A comparative cross-sectional descriptive quantitative study was conducted in thirty primary health-care facilities and four tertiary institutions offering medical and/or nursing programmes in Cape Town in the Western Cape Metropole. Stratified random sampling, based on geographical location, was used to select the health facilities while convenience sampling was used to select students at the tertiary institutions. A validated self-administered knowledge test was used to obtain data from the health professionals. RESULTS: Differential lifestyle modification knowledge exists among both health professionals and students, with less than 10 % achieving the desired scores of 80 % or higher. The majority of health professionals seem to be promoting the theoretical concepts of lifestyle modification but experience difficulty in providing practical advice to patients. Of the health professionals evaluated, doctors appeared to have the best knowledge of lifestyle modification. Lack of time, lack of patient adherence and language barriers were given as the main barriers to providing lifestyle counselling. CONCLUSIONS: The undergraduate curricula of medical and nursing students should include sufficient training on lifestyle modification, particularly practical advice on diet, physical activity and smoking cessation. Health professionals working at primary health-care facilities should be updated by providing lifestyle modification education as part of continuing medical education.", "title": "They think they know but do they? Misalignment of perceptions of lifestyle modification knowledge among health professionals." }, { "docid": "MED-4673", "text": "OBJECTIVE: The present study aimed to evaluate the knowledge and practices of public-sector primary-care health professionals and final-year students regarding the role of nutrition, physical activity and smoking cessation (lifestyle modification) in the management of chronic diseases of lifestyle within the public health-care sector. DESIGN: A comparative cross-sectional descriptive quantitative study was conducted in thirty primary health-care facilities and four tertiary institutions offering medical and/or nursing programmes in Cape Town in the Western Cape Metropole. Stratified random sampling, based on geographical location, was used to select the health facilities while convenience sampling was used to select students at the tertiary institutions. A validated self-administered knowledge test was used to obtain data from the health professionals. RESULTS: Differential lifestyle modification knowledge exists among both health professionals and students, with less than 10 % achieving the desired scores of 80 % or higher. The majority of health professionals seem to be promoting the theoretical concepts of lifestyle modification but experience difficulty in providing practical advice to patients. Of the health professionals evaluated, doctors appeared to have the best knowledge of lifestyle modification. Lack of time, lack of patient adherence and language barriers were given as the main barriers to providing lifestyle counselling. CONCLUSIONS: The undergraduate curricula of medical and nursing students should include sufficient training on lifestyle modification, particularly practical advice on diet, physical activity and smoking cessation. Health professionals working at primary health-care facilities should be updated by providing lifestyle modification education as part of continuing medical education.", "title": "They think they know but do they? Misalignment of perceptions of lifestyle modification knowledge among health professionals." } ]
5247
Efficient International money transfer
[ { "docid": "378972", "text": "Typical wire transfers are not with 4-5%; but it all depends on the bank that does the transfer. You can chose to send ('wire') the money in source currency or in US $; the former, the target bank in the US does the conversion (so pick one that adds no or little spread); the latter, the sending bank does the conversion (so ask about their fees/spreads). I have multiple times transferred money across the ocean (though not from Japan), and never paid more than 0.3% + ~40 $ flat. It should be possible to get te same range. Note that if you look around for current offers, you might be easily able to even make some money on it - some US banks are eager for new money, and offer 200+$ bonus if you open an account and bring (significant =15k$+) new money to them.", "title": "" }, { "docid": "490384", "text": "Wiring is the best way to move large amounts of money from one country to another. I am sure Japanese banks will allow you to exchange your Japanese Yen into USD and wire it to Canada. I am not sure if they will be able to convert directly from JPY to CND and wire funds in CND. If you can open a USD bank account in Canada, that might make things easier.", "title": "" } ]
[ { "docid": "773", "text": "For the US government, they've just credited Person B with a Million USD and haven't gained anything (afterall, those digits are intangible and don't really have a value, IMO). Two flaws in this reasoning: The US government didn't do anything. The receiving bank credited the recipient. If the digits are intangible, such that they haven't gained anything, they haven't lost anything either. In practice, the role of governments in the transfer is purely supervisory. The sending bank debits the sender's account and the receiving bank credits the recipient's account. Every intermediary makes some money on this transaction because the cost to the sender exceeds the credit to the recipient. The sending bank typically receives a credit to their account at a correspondent bank. The receiving bank typically receives a debit from their account at a correspondent bank. If a bank sends lots of money, eventually its account at its correspondent will run dry. If a bank receives lots of money, eventually its account at its correspondent will have too much money. This is resolved with domestic payments, sometimes handled by governmental or quasi-governmental agencies. In the US, banks have an account with the federal reserve and adjust balances there. The international component is handled by the correspondent bank(s). They also internally will credit and debit. If they get an imbalance between two currencies they can't easily correct, they will have to sell one currency to buy the other. Fortunately, worldwide currency exchange is extremely efficient.", "title": "" }, { "docid": "135675", "text": "You could use paypal to transfer money. You can pay with paypal and your UK contact could transfer the money to his bank account through paypal. I just received money this way from the US and paid 9 EUR for this. Receiving the funds is as quickly as clicking a button on the paypal site. Transfering it (without costs) took 1-3 days). It is by far the easiest way. If you are uncomfortable using paypal, the other option would be through your own bank account, where you would transfer using IBAN/SWIFT. The SWIFT bank account is usually the IBAN code plus a branch code. Often it is difficult to find the branch code, in that case you can use the IBAN+XXX. In the latter things might be delayed, but I actually haven't noticed the delay yet, since international transfer always seem to take between 1 and 10 days. The international transfering of money costs, except if it is within the EU region. The way to transfer money through Internet banking differs, from bank to bank. They keywords you need to look for are: SEPA, SWIFT, IBAN or international transfer.", "title": "" }, { "docid": "24612", "text": "Online money transfer facility from Axis Remit is a quick and easy way to transfer money from USA to India. AxisRemit is Axis Bank's flagship inward remittance service enables you to transfer money to your beneficiaries through the most efficient channels like online money transfer, exchange houses and money transfer operators.", "title": "" }, { "docid": "567273", "text": "There are restrictions on transferring money OUT OF Egypt (although less tight than previously: http://www.aawsat.net/2014/01/article55326839 ) but there aren't any such restrictions on sending money INTO Egypt. If you go to HSBC's retail UK banking pages and locate the page for International Money Transfers, http://www.hsbc.co.uk/1/2/international-money-transfer you can see that you can transfer up to £50,000 per day into Egypt via online banking, £10,000 via telephone banking, or unlimited by visiting the branch. I'm not sure exactly what question you asked them or exactly what they said to you in response, but it sounds like there was some misunderstanding along the way.", "title": "" }, { "docid": "378871", "text": "This is a wonderful comprehensive answer as it relates to transferring goods, and evaluating profitability. I would like to add to your post and comment about a few other costs that are transferred. First though, I disagree with your comment about transfer pricing being about opportunity cost. I think transfer pricing is first and primarily about the matching principal. Properly matching expenses incurred to the revenues generated from those expenditures, or in the case of period expenses, to those entities that received a benefit in the proper period. I don't work in tax, so I'm by no means an expert in this subject, but I am a CPA and I feel I have a solid understanding of the subject. Some additional items going through TP might be: interest, shared corporate services, the amortization of intellectual property, technology fees, and depreciation charges. This is not a comprehensive list, and please don't take it as such. None of these need apply to every company, and certain industries and even individual companies will have exceptions. For example, for various reasons, a multi-national conglomerate may choose to maintain separate treasury functions for it's vastly different businesses, so you may not see much interest TP. Interest is pretty straight forward, and is the interest a company is paying on a debt. Not all interest is transferable, but a classic example might be borrowed funds used for an acquisition. The interest cost associated with that should be transferred in part back to the original entity. Short term borrowing costs used for operating capital is another classic example. Shared corporate services are centralized functions like a legal department, accounting department, executive offices, and the like. This can also be an IT department or in the instance of an international website (maybe google), an operations team monitoring the server loads and up-times. IP could just be patents that have definite lives that a number of businesses are benefiting from. IP is a bit of a mess to get into for various reasons and I'm trying to stay focused in this post. Some reasons for complexity include: the valuation, life of the asset, benefit of use, is the entity even really using it?, etc. I would imagine this is where companies get away with A LOT. Technology fees can be software licenses (Windows ain't free). Depreciation can be capitalized proprietary software. I'm running out of gas and wanted to comment about OP's question. I don't think SLA's and Internal billing services are a matter of directly increasing efficiency, more a matter of not creating inefficiencies. Going anecdotal, anywhere I've worked, the best person to do the job has been whoever's closest to the work. It wouldn't make much sense to me to have accounting gather up internal support during the VERY time sensitive month-end close for something like one division's trade magazine that another division placed an ad in. On the other hand, I think the allocation of copy expenses on an activity basis is an absolute waste of time. It all depends on the specific transaction in question. Great post bctich. Don't mean to detract, just looking to help others understand.", "title": "" }, { "docid": "163685", "text": "For the first part of your question, I think the answer is a combination of three things: (1) Bigger companies have leverage to negotiate better deals due to volume. (2) Some of these companies are also taking bookings from outside the US for people traveling to the US (either directly or through affiliates). This means that they also have income in other currencies, so they may not actually be making as many wire transfers as you think. They simply keep a bank account in Europe, for example, in Euros to receive and send money in the Eurozone as needed. They balance the exchange on their books internally in this case, without actually sending funds through the international banking system. Similarly in other parts of the world. (3) These companies are not going to make a wire transfer for every transaction, in any case. They are going to transfer big sums of money to an account abroad to balance things on a longer-term basis (weekly, month, etc.) Then they will make individual payments to service providers out of the overseas account in between these larger, international transfers. For the second part of your question, I think there's probably no way for a new business to get the advantages of scale unless you've got significant capital backing your endeavor that would make it plausible that you'll be transferring in scale. I don't see any reason in principle that the new company could not establish bank accounts abroad and try to execute the plan outlined in #2 above except that it would require some set-up costs to do the proper paperwork in each country, probably to travel, and to initially fund the various accounts.", "title": "" }, { "docid": "79612", "text": "Credits are expensive, so it's a great advantage to pay in cash. Obviously, it's even more an advantage to pay in cash for a house or a car, of course if you can afford it. But, as annoying as it could be, there are some services, where you're out of option to pay in cash, or even to pay by bank transfer. One of the most prominent examples, Google Play (OK, as I've learned, there are prepaid cards. But Groundspeak, for example, has none.). With the further expansion of Internet and E-Economy there will be more cases like that, where paying in cash is no more an option. Booking of hotels or hostels is already mentioned. There are some that provide no other booking option that giving your credit card number. However, even if the do, for example bank transfer of, say, 20% as reservation fee, please note that international money transfer can be very expensive, and credit card is usually given only for security in case you don't come, and if you do come and pay in cash, no money is taken = no expensive fee for international money transfer and/or disadvantaging currency exchange rate.", "title": "" }, { "docid": "118383", "text": "It seems that your Organizers are not familiar with dealing transfers outside of Euro Zone. You are right IBAN is not used in India. A Bank in France can initiate an International Wire. There are few Banks that offer this online, for most one has to visit the Branch. See this https://expatriates.stackexchange.com/questions/2862/international-money-transfer-online-from-a-french-bank I am not aware of any other term used in France for International Wire, try explaining; Its also called BIC. It would help if you also provide your Correspondent Bank details [This will be a Bank in Europe]. This should be available on your Indian Bank's website.", "title": "" }, { "docid": "594252", "text": "\"I haven't seen anything specifically about how PayPal operates, but my guess is that they maintain relationships with banks in many countries via affiliates, and they settle the money transfers internally within the PayPal system. You basically have two types of bank transfers (there are others as well that I'm not getting into): I think PayPal is a hybrid -- they send and receive money using drafts to keep costs down, and manage the international stuff by operating a proprietary network. So if you send money from Indonesia to the US, you pay \"\"PayPal Indonesia\"\", who then tells \"\"PayPal USA\"\" to issue funds to your recipient. So they are cheaper than a wire, faster than a check, but limited in terms of transaction size and some other factors.\"", "title": "" }, { "docid": "41383", "text": "The money is transferred through an electronic funds transfer, which is an umbrella term that encompasses wire transfers, direct debits, etc. The application form for Key Trade Bank (the only place I can find that uses that exact phrasing) lists a SWIFT number. This usually indicates that the transfer of funds is done through an international wire transfer. In the most basic sense, the process works like this: Key Trade Bank uses the SWIFT number to notify your current bank of the transfer. Your bank instructs the settlement bank, e.g. the central bank of your country, where your bank is located, to transfer funds to Key Trade. If Key Trade is in another country from your current country, your central bank will send money to the central bank where Key Trade is located, which will in turn send the money to Key Trade. Otherwise, your central bank deposits the money into the account that Key Trade also has with them, and the transfer is complete.", "title": "" }, { "docid": "352649", "text": "I may be moving to Switzerland soon and would like to know if there's a similar system to move money between a Swiss bank account and a U.S bank account. There is no easy way. The most common method is International Wire or SWIFT. These kinds of transfer are generally charged in the range of USD 20 to USD 50 per transfer. It generally takes 2 to 5 days to move the money. Some Banks have not yet given the facility to initiate a International Wire from Internet banking platforms. One has to physically walk-in. So if this is going to be frequent, make sure both your banks offer this. As the volume between US and Switzerland is less, there may not be any dedicated remittance service providers [these are generally low cost].", "title": "" }, { "docid": "510485", "text": "Depending what country you are from, there may be better alternatives to transfer money internationally. Opening a bank account is complicated, costs money, and international bank transfers are remarkably expensive.", "title": "" }, { "docid": "327623", "text": "Most of the credit unions and small banks in USA do not have the connectivity to swift network and thus does not have a Swift Code, IBAN or other international routing codes. They can still receive international wire transfers. Sender's international financial institution should have a correspondent bank in the US (which acts as an intermediary bank) to which they can wire the money The intermediary bank will send the money domestically (within USA) using aba routing numbers of the small bank or credit union.", "title": "" }, { "docid": "132693", "text": "First, you'll need to find a service that can handle transferring that amount of money, whether it's using a bank, or wire transferring service. Any major Wall Street bank (Wells Fargo, Chase, Bank of America, etc.) should be able to handle it. You could also use services such as Western Union. As for your legal and tax obligations, according to Western Union: Individuals in Canada and the U.K. don’t have any tax considerations, unless international payments are received as income or in the form of capital gains. Only then must they report it on their income taxes, says Ilyas Patel, director at Ilyas Patel Chartered Certified Accountants based in Preston, U.K., and the director of Tax Expert, a tax advice website. To that end, when considering their tax obligations, individuals should take care to look into the reporting requirements on foreign income or gifts ranging up to a certain amount. For example, in the U.S., the Internal Revenue Service (IRS) requires individuals who receive more than $100,000 U.S. dollars from a foreign source to report it on a Form 3520. “You may not owe taxes on the money, but it informs the IRS that you received it,” Gragg says, stressing the importance of consulting with a professional. “They’re looking for certain terrorist activities and other illegal activity.” Due to the large sum of money your transferring, it would be in your best interest to speak with a banker (maybe even a lawyer or CPA) about this.", "title": "" }, { "docid": "57622", "text": "My current favorite service for this kind of transfer is Transferwise. The fees are quite low when compared to the 2.5-3% by high-street banks for currency conversion, to which you need to add the international wire transfer fee, and it's often a lot faster, as they split it into two domestic transfers while the international part + currency conversion happens internally to Transferwise.", "title": "" }, { "docid": "238503", "text": "No such law in existence or planning. There are no limits on what you can transfer in or out of the USA, as long as you're not doing tax evasion/money laundering, or violating embargo laws against specific countries and organizations. Explanation why Rob's answer is wrong: There's no, and never has been, withholding requirement when transferring money between own accounts. FATCA doesn't impose any new withholding. It reinforces the existing 30% withholding requirement, and suggests that the 30% withholding requirement may supersede treaty positions. Generally internal legislation cannot supersede international treaties, so I'm very skeptical about the US Gov't ability to enforce this. 30% withholding on payments to foreign people/entities has always been there. It's not new. Certain payments that are income sourced in the US and being remitted to foreign payees is subject to 30% withholding (unless treaty says otherwise). There's nothing new about it, been like that forever.", "title": "" }, { "docid": "263174", "text": "US banks are often helpless with international checks, so I would recommend to do a wire transfer instead. Otherwise you might end up being in the US with no money and a worthless piece of paper in your hand. First, set up your european account to allow wire transfers to the US, if that needs any action. Speak to someone in the bank in person, to make sure you can later initiate such a transfer remotely/online. After travelling, set up your US account, and then remote trigger a wire transfer. Costs are relatively small, for example with Postbank you pay less than 30 $, and get the bank currency exchange ratio (which is much better than the exchange ratio for paper money). The wire transfer cost is partly proportional to the amount, and partly constant, so don't split it in many pieces - make one larger transfer.", "title": "" }, { "docid": "372787", "text": "The ABA number you speak of is more accurately called the Routing Transit Number. http://en.wikipedia.org/wiki/Routing_transit_number A routing transit number (RTN) is a nine digit bank code, used in the United States, which appears on the bottom of negotiable instruments such as checks identifying the financial institution on which it was drawn. This code was designed to facilitate the sorting, bundling, and shipment of paper checks back to the drawer's (check writer's) account. The RTN is also used by Federal Reserve Banks to process Fedwire funds transfers, and by the Automated Clearing House to process direct deposits, bill payments, and other such automated transfers. The RTN number is derived from the bank's transit number originated by the American Bankers Association, which designed it in 1910.[1] I am going to assume that the euphemistic ABA Number has been shortened by whoever told you about it and called it the ABN. Perhaps American Bank Number. Either way, the technical term is RTN. Perhaps a comment or editor can straighten me out about the ABN. There is an international number known as the SWIFT number that serves the same purpose worldwide. http://en.wikipedia.org/wiki/ISO_9362 ISO 9362 (also known as SWIFT-BIC, BIC code, SWIFT ID or SWIFT code) defines a standard format of Business Identifier Codes approved by the International Organization for Standardization (ISO). It is a unique identification code for both financial and non-financial institutions.[1] The acronym SWIFT stands for the Society for Worldwide Interbank Financial Telecommunication. When assigned to a non-financial institution, the code may also be known as a Business Entity Identifier or BEI. These codes are used when transferring money between banks, particularly for international wire transfers, and also for the exchange of other messages between banks. The codes can sometimes be found on account statements.", "title": "" }, { "docid": "77972", "text": "Tax concerns aside, there are managerial pros and cons for internal billing. For cost control purposes it's common to break individual business activities into divisions/sections which have a P&amp;L or are cost centers. At that point, if you know (for example) that your quality control inspections cost on average 1% of your product cost then one might bill internally for use of this cost center. One argument for doing this is it makes those who are billed more cautious about using internal resources as there's a direct cost allocation. It also benchmarks that resource against outsourcing- for example it may be significantly cheaper to use an external resource. There can therefore be a 'healthy tension' between the cost center and user which in theory results in pressure for the cost center to improve efficiency. In practice I've found there are some significant cons. First issue is with cost allocation. The cost center in an attempt to make their service appear more efficient will battle to get minimal overhead costs allocated to them, creating friction between departments. Second and I think a major issue is a blanket cost for use of a service invariably winds up with a lot of exceptions. In the previous example there may be some very large programs where a 1% inspection fee winds up with a huge sum of money, one that the product team may argue unfairly reduces their net income and therefore compensation. Then there's the administrative cost of what essentially is passing money from the left hand to the right even if just on paper. Third issue is with some activities you might not want to provide a disincentive for people to use the service- for example charging a product team for quality assurance may result in skipped QA processes for the benefit of cost savings. What I've found works better is creation of cost centers with management of those centers. This is common in companies that have a matrix organizational structure. Using the same example again, QA costs are broken out and completely separated from other areas and QA management is benchmarked independently.", "title": "" }, { "docid": "536374", "text": "\"Re: Specifically, am I right in that everything I put on these is deducted from tax, or are there other rules? and Am I correctly understanding this as \"\"anything above £3,600 per year will not be deducted from your tax\"\"? Neither interpretation seems quite right… Unless what you mean is this: The contributions (to a pension, or to the share-save scheme) are deducted from your pay before it is taxed. That's how it works for employer-run pension schemes. In other words, you are paying the gross amount you earn into the pension, not the amount after tax. It's a tax-efficient way to save, because: compared to other forms of saving: (The bit about the £3,600: you can ignore this assuming you're earning more than £3,600 a year.) What happens to the pension if you decide to move back to France or another country? In some cases you can transfer tax free. Worst case, you'd pay some tax on the transfer but not more than 25%. [See here for the current rules: https://www.gov.uk/transferring-your-pension/transferring-to-an-overseas-pension-scheme. Re: the share scheme, if by 'salary exchange' you mean salary sacrifice (where your gross pay is officially reduced by that amount e.g. £150 a month), that's even more tax-efficient, because it saves you paying the National Insurance contribution too (approx 9% of the pay packet). Conclusion: Saving into pension and company share save schemes is supremely tax-efficient and, provided you're OK with your money being locked away until you're 57 (pension) or tied up in company shares, it's understandably many people's priority to make use of these schemes before considering other forms of saving where you pay into them from your salary after tax. Now, about this: I am trying to understand how much I should put into it Should I put money into these, or should look for another way to save (how will this work out if I go back to France or another country)? Nobody here can advise you what to do since individuals' goals and circumstances are different and we don't know enough of the picture. That said: FWIW, I'll tell you what I might do based solely on what you've told us in the question… First, I'd definitely contribute 6% to the company pension. This gets you the full employer match. That's free money (plus, remember the tax relief = more free money). If you're 27, a total of 12% salary into a pension a year is a decent rate to start saving for retirement. Actually, 14% would be generally advisable, and maybe more still – it's generally a case of 'the more the better' especially while young, as you have time for growth and you don't know what later priorities might change / financial needs might arise. Nevertheless, you said you might move overseas. So in your position I would then:\"", "title": "" }, { "docid": "275838", "text": "Because a wire transfer requires the individual bank to bank process, it is usually more expensive than an automated clearing house, which requires minimal involvement by individuals at financial institutions. Many ACH transactions come with only a small fee, or even no fee at all, since they are run with more efficiency. However, if you want a better guarantee that your money will arrive on time, it might be worth it to pay the wire transfer fee. With both cases, it is possible for errors to be made. However, since you often get to review the information before it is sent with a wire transfer, the method is a little more secure. Also, because identities are verified with wire transfers that take place between bank accounts, there is less chance of fraud. Wire transfers that take place between financial institutions are generally considered quite secure. from http://www.depositaccounts.com/blog/difference-between-wire-transfer-and-ach.html", "title": "" }, { "docid": "410252", "text": "Probably the easiest to do is to do an international transfer via online banking. You will need to give your IBAN and BIC/SWIFT code of your bank to your friend, he should then be able to transfer the money from his bank. At least, I think they use IBAN in Israel as well. The money will be converted to the currency of your account. There are some fees, but they are not too big I think, and depending on the choice of transfer they can be paid by sender, shared, or by receiver. Contact your bank for precise details. Edit: if you really need to be paid in USD this may not be the best option though.", "title": "" }, { "docid": "184386", "text": "\"I'm not sure I understand your question, but I'll try to answer what I think you're asking. I think you're asking this: \"\"A US bank receives a wire transfer from a Chinese bank. How does the US bank ensure there's any money in fact arriving before crediting the destination account?\"\" Well, the way wire transfers work is that the US bank would debit the senders' account with that US bank. So the US bank in fact transfers the money between two internal accounts: debit to the Chinese bank's account with that US bank and credit the destination customer account. If the Chinese bank doesn't have an account with the destination US bank - a third party intermediary is used that both banks have accounts with. Such third party will charge an additional fee (hence sometimes the wire transfer fees are slightly higher than you initially know when sending the money, the third party would debit from the transfer amount). \"\"Regular\"\" IBAN/ACH transfers work through regulatory channels that ensure integrity and essentially use a regulatory bank as that third party. But because they're done in batches and not on-line, they're much cheaper, and the accounting is for the whole batch and not each transfer separately. But batch processing means it will take a day or two of processing, while wire transfer takes hours at most.\"", "title": "" }, { "docid": "403556", "text": "I would open a taxable account with the same custodian that manages your Roth IRA (e.g., Vanguard, Fidelity, etc.). Then within the taxable account I would invest the extra money in low cost, broad market index funds that are tax efficient. Unlike in your 401(k) and Roth IRA, you will now have tax implications if your funds produce dividends or realize a capital gain. That is why tax-efficient funds are important to minimize this as much as possible. The 3-fund portfolio is a popular choice for taxable accounts because of simplicity and the tax efficiency of broad market index funds that are part of the three fund portfolio. The 3-fund portfolio normally consists of Depending on your tax bracket you may want to consider municipal bonds in your taxable instead of taxable bonds if your tax bracket is 25% or higher. Another option is to forgo bonds altogether in the taxable account and just hold bonds in retirement accounts while keeping tax efficient domestic and international tock funds in your taxable account. Then adjust the bond portion upward in your retirement accounts to account for the additional stocks in your taxable accounts. This will maintain the asset allocation that you've already chosen that is appropriate for your age and goals.", "title": "" }, { "docid": "369202", "text": "I don't believe there is any particular structural or financial reason that outgoing wire transfers cost so much in Canada, their costs are no higher than other countries (and lower than many). Wires seem to be an area where the Canadian banks have decided people don't comparison shop, so it's not a competitive advantage to offer a better price. The rates you quoted are on the low side: $80 for a largish international wire is not unusual, and HSBC charges up to $150! There are several alternative ways to transfer money domestically in Canada. If the recipient banks at the same bank, it's possible to go into a branch and transfer money directly from your own account to their account (I've never been charged for this). The transfer is immediate. But it couldn't be done online, last time I checked. For transfers where you don't know the recipients bank account, you can pay online with Interac E-Transfers, offered by most Canadian banks. It's basically e-mailing money. It usually costs $1 to $1.50 per transfer, and has limits on how much you can send per day/week. Each of the banks also have a bill-pay service, but unlike similar services in the US (where they mail a paper check if the recipient isn't on their system), each Canadian bank has a limited number of possible payees (mostly utilities, governments, major stores).", "title": "" }, { "docid": "25247", "text": "I think it really depends on how much you take out of your Nationwide account each month. At a certain point, it will become cheaper just to transfer your monthly rent + living allowance via an international bank transfer or using one of the currency transfer services like xe.com or Hifx. You will have to pay fees either way and/or you'll end up with a forex spread. If you have got enough money in your UK account to cover several months' worth of expenses in Germany, I would be tempted to make one big transfer every few months instead of a a monthly one; anything more than once a month is probably going to be too costly either way. It might also be worth comparing the transfer fees charged by the various banks, when I lived in the UK and had to regularly send money to Germany I found there was a massive difference between different banks for essentially the same service.", "title": "" }, { "docid": "185146", "text": "The best, cheapest and safe way is to wire transfer that money from their Bank Account to yours. Ask your bank about information regarding inbound international wire transfer and provide those details to your dad. About how much amounts can he do so : if the amount is more than $10K, you need to provide enough information about where the money is coming from, sources and other legal details. Whatever way you chose, never do transfers in small chunks (which is called structuring), to avoid the legal hassle - as that might result in more issues and every bank has checks in place to find out this way of structuring. I would suggest wire transfer all the money, through proper channel, through the banks. It's better to pay some fees, follow the law and live peacefully than to go through some improper channels to avoid paltry fees and get into serious issues.", "title": "" }, { "docid": "496385", "text": "\"You are right in insisting upon a proper B2B contract in any business relationship. You wish to reduce your risk and be compensated fairly. In addition to the cost and complexity of international wire transfers, the US companies may also be considering the fact that as an international contractor in a relatively hard-to-reach jurisdiction, payments to you place the company at higher risk than payments to a domestic contractor. By insisting upon PayPal or similar transmitters, they are reducing their internal complexity and reducing their financial exposure to unfulfilled/disputed contract terms. Therefore, wire payments are \"\"hard\"\" in an internal business sense, as well as in a remittance transfer reporting sense. The internal business procedure will likely be the hardest to overcome--changing risk management is harder than filling out forms.\"", "title": "" }, { "docid": "509799", "text": "If you held the shares directly, the transfer agent, Computershare, should have had you registered and your address from some point on file. I have some experience with Computershare, it turned out when Qwest restarted dividends and the checks mailed to the childhood home my parents no longer owned, they were able to reissue all to my new address with one telephone call. I can't tell you what their international transfer policies or fees might be, but if they have your money, at least its found. Transfer Agent Computershare Investor Services serves as the stock transfer agent for Tellabs. If you need to transfer stock, change ownership, report lost or stolen certificates, or change your address, please contact Computershare Investor Services at +1.312.360.5389.", "title": "" }, { "docid": "48530", "text": "I know this won't be a popular answer, but here goes: Bitcoin. Regardless of how you feel about the long term prospects of bitcoin, it actually works very well as a way to transfer money with hardly any fee. You can go online, buy bitcoin, transfer them for a very tiny fee, then the person on the other end can cash out in their own local currency. In fact, bitcoin is gaining a lot of popularity in some countries for this very reason. It is becoming more common for one family member to come to America or Eurpoe to work, then use bitcoin to transfer money to their family back home. This works so well because even international transfers have such low fees. The best place to get bitcoins will vary depending on where you live. I'm American, so I use Coinbase. I believe Bitstamp is popular in Europe. I'm not sure about other countries.", "title": "" } ]
PLAIN-1890
polycarbonate plastic
[ { "docid": "MED-4991", "text": "BACKGROUND: Epidemiological studies have shown positive findings associated with legume consumption and measures of cardiovascular disease and obesity. However, few observational trials have examined beans as a separate food variable when determining associations with health parameters. OBJECTIVE: To determine the association of consuming beans on nutrient intakes and physiological parameters using the National Health and Examination Survey (NHANES) 1999-2002. METHODS: Using data from NHANES 1999-2002, a secondary analysis was completed with a reliable 24-hour dietary recall where three groups of bean consumers were identified (N = 1,475). We determined mean nutrient intakes and physiological values between bean consumers and non-consumers. Least square means, standard errors and ANOVA were calculated using appropriate sample weights following adjustment for age, gender, ethnicity and energy. RESULTS: Relative to non-consumers, bean consumers had higher intakes of dietary fiber, potassium, magnesium, iron, and copper (p's < 0.05). Those consuming beans had a lower body weight (p = 0.008) and a smaller waist size (p = 0.043) relative to non-consumers. Additionally, consumers of beans had a 23% reduced risk of increased waist size (p = 0.018) and a 22% reduced risk of being obese (p = 0.026). Also, baked bean consumption was associated with a lower systolic blood pressure. CONCLUSIONS: Bean consumers had better overall nutrient intake levels, better body weights and waist circumferences, and lower systolic blood pressure in comparison to non-consumers. These data support the benefits of bean consumption on improving nutrient intake and health parameters.", "title": "Bean consumption is associated with greater nutrient intake, reduced systolic blood pressure, lower body weight, and a smaller waist circumference ..." }, { "docid": "MED-4992", "text": "Bisphenol A (BPA) and bisphenol B (BPB) concentrations were determined in peeled canned tomatoes of different brands bought in Italian supermarkets. Tomato samples analyzed were packaged in cans coated with either epoxyphenolic lacquer or low BADGE enamel. A solid phase extraction (SPE) was performed on C-18 Strata E cartridge followed by a step on Florisil cartridge. Detection and quantitation were performed by a reversed phase high-performance liquid chromatography (RP-HPLC) method with both UV and fluorescence detection (FD). On the total of 42 tested tomato samples, BPA was detected in 22 samples (52.4%), while BPB was detected in 9 samples (21.4%). BPA and BPB were simultaneously present in 8 of the analyzed samples. The levels of BPA found in this study are much lower than the European Union migration limits of 3 mg/kg food and reasonably unable to produce a daily intake exceeding the limit of 0.05 mg/kg body weight, established by European Food Safety Authority.", "title": "Determination of bisphenol a and bisphenol B residues in canned peeled tomatoes by reversed-phase liquid chromatography." }, { "docid": "MED-4186", "text": "Bisphenol A (BPA) is a chemical used for lining metal cans and in polycarbonate plastics, such as baby bottles. In rodents, BPA is associated with early sexual maturation, altered behavior, and effects on prostate and mammary glands. In humans, BPA is associated with cardiovascular disease, diabetes, and male sexual dysfunction in exposed workers. Food is a major exposure source. We know of no studies reporting BPA in U.S. fresh food, canned food, and food in plastic packaging in peer reviewed journals. We measured BPA levels in 105 fresh and canned foods, foods sold in plastic packaging, and in cat and dog foods in cans and plastic packaging. We detected BPA in 63 of 105 samples, including fresh turkey, canned green beans, and canned infant formula. Ninety-three of these samples were triplicates which had similar detected levels. Detected levels ranged from 0.23 to 65.0 ng/g ww and were not associated with type of food or packaging but did vary with pH. BPA levels were higher for foods of pH 5 compared to more acidic and alkaline foods. Detected levels were comparable to those found by others. Further research is indicated to determine BPA levels in U.S. food in larger, representative sampling.", "title": "Bisphenol A (BPA) in U.S. food." }, { "docid": "MED-4185", "text": "The adverse effect of bisphenol-A (BPA) on the male reproductive system observed in animal studies has not been well examined in human populations. BPA is potentially a serious public health problem because of its widely detected presence in the human body. This study was conducted among 427 male workers in regions where high levels of BPA exposure existed. All participants provided urine samples, which were tested for BPA concentration using high-performance liquid chromatography. Male sexual dysfunction was ascertained using standard male sexual function inventories. Male sexual dysfunction was measured in 4 domains using 7 indices. After controlling for potential confounders using linear regression, increasing urine BPA level was associated with worsening male sexual function on a continuous scale. All 7 indices demonstrated this negative linear correlation. Increasing urine BPA level was associated with decreased sexual desire (P < .001), more difficulty having an erection (P < .001), lower ejaculation strength (P < .001), and lower level of overall satisfaction with sex life (P < .01). A similar negative correlation was also observed among participants exposed to BPA from only environmental sources (no occupational exposure to BPA), although the estimates in this group were less stable because of a smaller sample size. Our results reveal a correlation between a biological measure of urine BPA level and declining male sexual function. This finding may enhance the understanding of the BPA effect in human populations, and may have important public health implications given the widespread human exposure to BPA.", "title": "Relationship between urine bisphenol-A level and declining male sexual function." } ]
[ { "docid": "MED-3173", "text": "Objectives Polyphenols, natural compounds found in plant-based foods, possess special properties that can battle oxidative stress and stimulate the activation of molecules that aid in synaptic plasticity, a process that underlies cognitive function. Unlike many traditional treatments, polyphenols affect a broad range of mechanisms in the brain that can assist in the maintenance of cognitive and mental health, as well as the recovery from neurodegenerative diseases. Examining the molecular basis underlying the link between food intake and brain function has presented the exciting possibility of using diet as a viable method to battle cognitive and psychiatric disorders. Methods We will discuss the molecular systems that link polyphenols, the gut, and the brain, as well as introduce published human and animal studies demonstrating the effects of polyphenol consumption on brain plasticity and cognition. Results By influencing cellular energy metabolism and modulating the signaling pathways of molecules involved with brain plasticity, dietary factors – formerly recognized for just their effects on bodily systems – have emerged as affecters of the brain. Conclusion Thus, the consumption of diets enriched with polyphenols may present the potential of dietary manipulation as a non-invasive, natural, and inexpensive therapeutic means to support a healthy brain.", "title": "Natural mood foods: The actions of polyphenols against psychiatric and cognitive disorders" }, { "docid": "MED-2644", "text": "Alkylphenols are widely used as plastic additives and surfactants. We report the identification of an alkylphenol, nonylphenol, as an estrogenic substance released from plastic centrifuge tubes. This compound was extracted with methanol, purified by flash chromatography and reverse-phase high performance liquid chromatography, and identified by gas chromatography-mass spectrometry. Nonylphenol induced both cell proliferation and progesterone receptor in human estrogen-sensitive MCF7 breast tumor cells. Nonylphenol also triggered mitotic activity in rat endometrium; this result confirms the reliability of the MCF7 cell proliferation bioassay. The estrogenic properties of alkylphenols, specifically nonylphenols, indicate that the use of plasticware containing these chemicals in experimental and diagnostic tests may lead to spurious results, and these compounds as well as alkylphenol polyethoxylates may also be potentially harmful to exposed humans and the environment at large.", "title": "p-Nonyl-phenol: an estrogenic xenobiotic released from \"modified\" polystyrene." }, { "docid": "MED-1312", "text": "The aim of this study was to evaluate the antiinflammatory effect of oatmeal extract oligomer on skin fragments stimulated by a neuromediator, vasoactive intestinal peptide (VIP). Skin fragments (from plastic surgery) were maintained in survival conditions for 6 h. To induce inflammation, VIP was placed in contact with dermis by culture medium. Histological analysis was then performed on hematoxylin- and eosin-stained slides. Edema was evaluated with semiquantitative scores. Vasodilation was studied by quantifying the percentage of dilated vessels according to scores and by measuring their surface by morphometrical image analysis. TNF-alpha dosage was made on culture supernatants. Vasodilation was significantly increased after application of VIP. After treatment with oatmeal extract oligomer, the mean surface of dilated vessels and edema were significantly decreased compared with VIP-treated skin. Moreover, treatment with this extract decreased TNF-alpha.", "title": "Inhibitory effect of oatmeal extract oligomer on vasoactive intestinal peptide-induced inflammation in surviving human skin." }, { "docid": "MED-2559", "text": "Inositol hexaphosphate (IP6) has anti-cancer properties, but recently other extracellular functions have been observed for IP6, including enhancing superoxide production and phagocytosis by neutrophils in the presence of microbial stimuli. This study investigated other inflammatory functions of IP6 on adherent neutrophils. The effect of IP6 on the release of IL-8, tumour necrosis factor (TNF-alpha) and IL-6 by neutrophils attached to either plastic or laminin for up to 6 hours in response to stimulation with lipopolysaccharide or N-formyl-Met-Leu-Phe (fMLP) was investigated. An increase in IL-8 secretion by stimulated cells occurred in the presence of IP6. The incubation of cells attached to laminin with IP6 alone (100-250 BM) did not effect cell morphology, but in the presence of 10(-7) M fMLP altered cell shape. A direct effect of IP6 on cell function was to trigger a sustained assembly of F-actin. Thus, exposure of neutrophils to low levels of IP6 appears to modulate selective neutrophil functions.", "title": "Effect of IP6 on human neutrophil cytokine production and cell morphology." }, { "docid": "MED-996", "text": "Polybrominated diphenyl ethers (PBDEs) are persistent organic chemicals used as flame retardants in textiles, plastics, and consumer products. Although PBDE accumulation in humans has been noted since the 1970s, few studies have investigated PBDEs within the gestational compartment, and none to date has identified levels in amniotic fluid. The present study reports congener-specific brominated diphenyl ether (BDE) concentrations in second-trimester clinical amniotic fluid samples collected in 2009 from fifteen women in southeast Michigan, USA. Twenty-one BDE congeners were measured by GC/MS/NCI. The average total PBDE concentration was 3795 pg/ml amniotic fluid (range: 337 – 21842 pg/ml). BDE-47 and BDE-99 were identified in all samples. Based on median concentrations, the dominant congeners were BDE-208, 209, 203, 206, 207, and 47 representing 23, 16, 12, 10, 9 and 6%, respectively, of the total detected PBDEs. PBDE concentrations were identified in all amniotic fluid samples from southeast Michigan, supporting a need for further investigations of fetal exposure pathways and potential impacts on perinatal health.", "title": "Concentrations and speciation of polybrominated diphenyl ethers in human amniotic fluid" }, { "docid": "MED-4602", "text": "The strategy of \"manufacturing uncertainty\" has been used with great success by polluters and manufacturers of dangerous products to oppose public health and environmental regulation. This strategy entails questioning the validity of scientific evidence on which the regulation is based. While this approach is most identified with the tobacco industry, it has been used by producers of asbestos, benzene, beryllium, chromium, diesel exhaust, lead, plastics, and other hazardous products to avoid environmental and occupational health regulation. It is also central to the debate on global warming. The approach is now so common that it is unusual for the science not to be challenged by an industry facing regulation. Manufacturing uncertainty has become a business in itself; numerous technical consulting firms provide a service often called \"product defense\" or \"litigation support.\" As these names imply, the usual objective of these activities is not to generate knowledge to protect public health but to protect a corporation whose products are alleged to have toxic properties. Evidence in the scientific literature of the funding effect--the close correlation between the results of a study desired by a study's funder and the reported results of that study--suggests that the financial interest of a study's sponsors should be taken into account when considering the study's findings. Similarly, the interpretation of data by scientists with financial conflicts should be seen in this light. Manufacturing uncertainty is antithetical to the public health principle that decisions be made using the best evidence currently available.", "title": "Manufactured uncertainty: protecting public health in the age of contested science and product defense." }, { "docid": "MED-2650", "text": "Over the last 40 years there have been constant reports concerning environmental chemicals with hormone-like effects in wildlife. An endocrine disruptor is an exogenous substance that causes adverse health effects in an intact organism or its progeny, secondary to changes in endocrine function. Endocrine disruptors of widely diverse chemical structures that have oestrogenic properties are known as oestrogenic xenobiotics or xenoestrogens. Some of these substances, such as phytoestrogens and mycoestrogens, can come from diet or from the environment. Although the oestrogenic activity of these substances is weaker than that of oestradiol, new chemicals with endocrine disrupting potential continue to be discovered, inadvertent forms of exposure are constantly being identified, and there is increasing concern about cumulative effects. Studies in the 1960s and 1970s characterized the oestrogenicity of a number of industrial compounds and the pesticides o,p-DDT, kepone, methoxychlor, phenolic derivatives and polychlorinated biphenyls (PCBs). In the last 5 years, several environmental chemicals have been added to the list of xenoestrogens, including the pesticides toxaphene, dieldrin and endosulphan, and several different compounds used in the food industry, antioxidants such a t-butylhydroxyanisole; plasticizers such as benzylbutylphthalate and 4-OH-alkylphenols; and substances used in dental restorations, such as bisphenol-A. The relevance of these newly discovered endocrine disruptors to human health is now starting to emerge. The few studies that have investigated their effect in humans point in the same direction: if there is indeed an association between exposure to substances with hormone-disruptive activity and certain disorders of endocrine organs, the incidence of such disorders would be greater in areas where exposure to agents with this activity is high. A closer scrutiny is required to determine whether these newly discovered endocrine disrupting chemicals contribute, together with oestrogenic pesticides, to the exposure of humans to xenoestrogens.", "title": "Inadvertent exposure to xenoestrogens." }, { "docid": "MED-4426", "text": "Riding in a shopping cart next to raw meat or poultry is a risk factor for Salmonella and Campylobacter infections in infants. To describe the frequency of, and factors associated with, this behavior, we surveyed parents of children aged younger than 3 years in Foodborne Disease Active Surveillance Network sites. We defined exposure as answering yes to one of a series of questions asking if packages of raw meat or poultry were near a child in a shopping cart, or if a child was in the cart basket at the same time as was raw meat or poultry. Among 1,273 respondents, 767 (60%) reported that their children visited a grocery store in the past week and rode in shopping carts. Among these children, 103 (13%) were exposed to raw products. Children who rode in the baskets were more likely to be exposed than were those who rode only in the seats (odds ratio [OR], 17.8; 95% confidence interval [CI], 11.0 to 28.9). In a multivariate model, riding in the basket (OR, 15.5; 95% CI, 9.2 to 26.1), income less than $55,000 (OR, 1.8; 95% CI, 1.0 to 3.1), and Hispanic ethnicity (OR, 2.3; 95% CI, 1.2 to 4.5) were associated with exposure. Our study shows that children can be exposed to raw meat and poultry products while riding in shopping carts. Parents should separate children from raw products and place children in the seats rather than in the baskets of the cart. Retailer use of leak-proof packaging, customer placement of product in a plastic bag and on the rack underneath the cart, use of hand sanitizers and wipes, and consumer education may also be helpful.", "title": "Riding in shopping carts and exposure to raw meat and poultry products: prevalence of, and factors associated with, this risk factor for salmonella..." }, { "docid": "MED-4996", "text": "Animal studies suggest that diets low in calories and rich in unsaturated fatty acids (UFA) are beneficial for cognitive function in age. Here, we tested in a prospective interventional design whether the same effects can be induced in humans. Fifty healthy, normal- to overweight elderly subjects (29 females, mean age 60.5 years, mean body mass index 28 kg/m2) were stratified into 3 groups: (i) caloric restriction (30% reduction), (ii) relative increased intake of UFAs (20% increase, unchanged total fat), and (iii) control. Before and after 3 months of intervention, memory performance was assessed under standardized conditions. We found a significant increase in verbal memory scores after caloric restriction (mean increase 20%; P < 0.001), which was correlated with decreases in fasting plasma levels of insulin and high sensitive C-reactive protein, most pronounced in subjects with best adherence to the diet (all r values < −0.8; all P values <0.05). Levels of brain-derived neurotrophic factor remained unchanged. No significant memory changes were observed in the other 2 groups. This interventional trial demonstrates beneficial effects of caloric restriction on memory performance in healthy elderly subjects. Mechanisms underlying this improvement might include higher synaptic plasticity and stimulation of neurofacilitatory pathways in the brain because of improved insulin sensitivity and reduced inflammatory activity. Our study may help to generate novel prevention strategies to maintain cognitive functions into old age.", "title": "From the Cover: Caloric restriction improves memory in elderly humans" }, { "docid": "MED-2951", "text": "Background A plant-based diet protects against chronic oxidative stress-related diseases. Dietary plants contain variable chemical families and amounts of antioxidants. It has been hypothesized that plant antioxidants may contribute to the beneficial health effects of dietary plants. Our objective was to develop a comprehensive food database consisting of the total antioxidant content of typical foods as well as other dietary items such as traditional medicine plants, herbs and spices and dietary supplements. This database is intended for use in a wide range of nutritional research, from in vitro and cell and animal studies, to clinical trials and nutritional epidemiological studies. Methods We procured samples from countries worldwide and assayed the samples for their total antioxidant content using a modified version of the FRAP assay. Results and sample information (such as country of origin, product and/or brand name) were registered for each individual food sample and constitute the Antioxidant Food Table. Results The results demonstrate that there are several thousand-fold differences in antioxidant content of foods. Spices, herbs and supplements include the most antioxidant rich products in our study, some exceptionally high. Berries, fruits, nuts, chocolate, vegetables and products thereof constitute common foods and beverages with high antioxidant values. Conclusions This database is to our best knowledge the most comprehensive Antioxidant Food Database published and it shows that plant-based foods introduce significantly more antioxidants into human diet than non-plant foods. Because of the large variations observed between otherwise comparable food samples the study emphasizes the importance of using a comprehensive database combined with a detailed system for food registration in clinical and epidemiological studies. The present antioxidant database is therefore an essential research tool to further elucidate the potential health effects of phytochemical antioxidants in diet.", "title": "The total antioxidant content of more than 3100 foods, beverages, spices, herbs and supplements used worldwide" }, { "docid": "MED-1826", "text": "PURPOSE: To investigate the association between intake of flaxseed-the richest source of dietary lignans (a class of phytoestrogens)-and breast cancer risk. METHODS: A food frequency questionnaire was used to measure the consumption of flaxseed and flax bread by 2,999 women with breast cancer and 3,370 healthy control women who participated in the Ontario Women's Diet and Health Study (2002-2003). Logistic regression was used to investigate associations between consumption of flaxseed and flax bread and breast cancer risk. Confounding by established and suspected breast cancer risk factors, as well as dietary factors, was assessed. RESULTS: Flaxseed or flax bread was consumed at least weekly by 21 % of control women. None of the 19 variables assessed were identified as confounders of the associations between flaxseed or flax bread and breast cancer risk. Consumption of flaxseed was associated with a significant reduction in breast cancer risk (odds ratio (OR) = 0.82, 95 % confidence interval (CI) 0.69-0.97), as was consumption of flax bread (OR = 0.77, 95 % CI 0.67-0.89). CONCLUSIONS: This Canadian study is, to our knowledge, the first to report on the association between flaxseed alone and breast cancer risk and has found that flaxseed intake is associated with a reduction in breast cancer risk. As dietary intake of flaxseed is modifiable, this finding may be of public health importance with respect to breast cancer prevention.", "title": "Consumption of flaxseed, a rich source of lignans, is associated with reduced breast cancer risk." }, { "docid": "MED-2587", "text": "Recent research has demonstrated that successful simultaneous treatment of multiple risk factors including cholesterol, triglycerides, homocysteine, lipoprotein (a) [Lp(a)], fibrinogen, antioxidants, endothelial dysfunction, inflammation, infection, and dietary factors can lead to the regression of coronary artery disease and the recovery of viable myocardium. However, preliminary work revealed that a number of individuals enrolled in the original study went on popular high-protein diets in an effort to lose weight. Despite increasing numbers of individuals following high-protein diets, little or no information is currently available regarding the effect of these diets on coronary artery disease and coronary blood flow. Twenty-six people were studied for 1 year by using myocardial perfusion imaging (MPI), echocardiography (ECHO), and serial blood work to evaluate the extent of changes in regional coronary blood flow, regional wall motion abnormalities, and several independent variables known to be important in the development and progression of coronary artery disease. Treatment was based on homocysteine, Lp (a), C-reactive protein (C-RP), triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and fibrinogen levels. Each variable was independently treated as previously reported. MPI and ECHO were performed at the beginning and end of the study for each individual. The 16 people (treatment group/TG) studied modified their dietary intake as instructed. Ten additional individuals elected a different dietary regimen consisting of a \"high-protein\" (high protein group/HPG) diet, which they believed would \"improve\" their overall health. Patients in the TG demonstrated a reduction in each of the independent variables studied with regression in both the extent and severity of coronary artery disease (CAD) as quantitatively measured by MPI. Recovery of viable myocardium was seen in 43.75% of myocardial segments in these patients, documented with both MPI and ECHO evaluations. Individuals in the HPG showed worsening of their independent variables. Most notably, fibrinogen, Lp (a), and C-RP increased by an average of 14%, 106%, and 61% respectively. Progression of the extent and severity of CAD was documented in each of the vascular territories with an overall cumulative progression of 39.7%. The differences between progression and extension of disease in the HPG and the regression of disease in the TG were statistically (p<0.001) significant. Patients following recommended treatment for each of the independent variables were able to regress both the extent and severity of their coronary artery disease (CAD), as well as improve their myocardial wall motion (function) while following the prescribed medical and dietary guidelines. However, individuals receiving the same medical treatment but following a high-protein diet showed a worsening of independent risk factors, in addition to progression of CAD. These results would suggest that high-protein diets may precipitate progression of CAI) through increases in lipid deposition and inflammatory and coagulation pathways.", "title": "The effect of high-protein diets on coronary blood flow." }, { "docid": "MED-1611", "text": "A growing body of evidence from observational studies and meta-analyses of the data suggest that diabetes mellitus is associated with an increased risk of cancer. Meta-analyses have shown that diabetes increases the risks of total cancer, and of site-specific cancers of the breast, endometrium, bladder, liver, colorectum and pancreas, and that it decreases the risk of prostate cancer. Insulin resistance and secondary hyperinsulinemia is the most frequently proposed hypothesis, and hyperglycemia itself might promote carcinogenesis. In addition to several facets of lifestyle including obesity, smoking and lack of exercise, treatment for diabetes might affect the risk of cancer. For instance, metformin, an insulin sensitizer, reportedly has a potential anticancer effect. In light of the exploding global epidemic of diabetes, even a modest increase in the cancer risk will translate into a substantial socioeconomic burden. The current insights underscore the need for clinical attention and better-designed studies of the complex interactions between diabetes and cancer.", "title": "Latest insights into the risk of cancer in diabetes" }, { "docid": "MED-1726", "text": "Pesticides are used throughout the world as mixtures called formulations. They contain adjuvants, which are often kept confidential and are called inerts by the manufacturing companies, plus a declared active principle, which is usually tested alone. We tested the toxicity of 9 pesticides, comparing active principles and their formulations, on three human cell lines (HepG2, HEK293, and JEG3). Glyphosate, isoproturon, fluroxypyr, pirimicarb, imidacloprid, acetamiprid, tebuconazole, epoxiconazole, and prochloraz constitute, respectively, the active principles of 3 major herbicides, 3 insecticides, and 3 fungicides. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. Fungicides were the most toxic from concentrations 300–600 times lower than agricultural dilutions, followed by herbicides and then insecticides, with very similar profiles in all cell types. Despite its relatively benign reputation, Roundup was among the most toxic herbicides and insecticides tested. Most importantly, 8 formulations out of 9 were up to one thousand times more toxic than their active principles. Our results challenge the relevance of the acceptable daily intake for pesticides because this norm is calculated from the toxicity of the active principle alone. Chronic tests on pesticides may not reflect relevant environmental exposures if only one ingredient of these mixtures is tested alone.", "title": "Major Pesticides Are More Toxic to Human Cells Than Their Declared Active Principles" }, { "docid": "MED-2155", "text": "Coffee, after water, is the most widely consumed beverage in the United States, and is the principal source of caffeine intake among adults. The biological effects of coffee may be substantial and are not limited to the actions of caffeine. Coffee is a complex beverage containing hundreds of biologically active compounds, and the health effects of chronic coffee intake are wide ranging. From a cardiovascular (CV) standpoint, coffee consumption may reduce the risk of type 2 diabetes mellitus and hypertension, as well as other conditions associated with CV risk such as obesity and depression; but it may adversely affect lipid profiles depending on how the beverage is prepared. Regardless, a growing body of data suggests that habitual coffee consumption is neutral to beneficial regarding the risks of a variety of adverse CV outcomes including coronary heart disease, congestive heart failure, arrhythmias, and stroke. Moreover, large epidemiological studies suggest that regular coffee drinkers have reduced risks of mortality, both CV and all-cause. The potential benefits also include protection against neurodegenerative diseases, improved asthma control, and lower risk of select gastrointestinal diseases. A daily intake of ∼2 to 3 cups of coffee appears to be safe and is associated with neutral to beneficial effects for most of the studied health outcomes. However, most of the data on coffee's health effects are based on observational data, with very few randomized, controlled studies, and association does not prove causation. Additionally, the possible advantages of regular coffee consumption have to be weighed against potential risks (which are mostly related to its high caffeine content) including anxiety, insomnia, tremulousness, and palpitations, as well as bone loss and possibly increased risk of fractures. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.", "title": "Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause mortality." }, { "docid": "MED-3865", "text": "INTRODUCTION: Sensitive skin is a complex dermatological condition, defined by abnormal sensory symptoms. The aim of this epidemiological survey was to assess the prevalence of sensitive skin and collect data on sensitive skin in the US population. METHODS: A phone survey was conducted in the USA by a poll institute in 2007. A sample was drawn from a representative national cohort of the American population at least 18years of age through the quota method. Data on demographic characteristics, environmental and climatic factors, skin characteristics, dermatological disorders, cosmetics use, and visits to the dermatologist were collected. RESULTS: Of 994 subjects who answered (495 men and 499 women), 44.6% declared having \"sensitive\" or \"very sensitive\" skin. Women were more concerned than men (50.9% vs. 38.2%, P<0.0001). There was no significant difference related to geographic localization, age, or ethnic distribution. Subjects with sensitive skin had mainly dry (34.5%) or mixed skin (35.7%), fair phototypes, dermatological disorders, higher skin reactivity to cosmetics and various environmental factors in comparison with subjects who stated having only a \"slightly\" sensitive or not sensitive skin. The dermatologist had a strong influence on subjects with \"sensitive\" or \"very sensitive\" skin through the prescription of skin care products. CONCLUSION: This study, based on a representative sample of the American population, reveals a high prevalence of sensitive skin in the USA. Sensitive skin is mainly associated with dry skin, fair phototype, reactivity to climatic and environmental factors, and cosmetics. American dermatologists seem largely involved in the care of this condition. © 2011 The International Society of Dermatology.", "title": "Sensitive skin in the American population: prevalence, clinical data, and role of the dermatologist." }, { "docid": "MED-719", "text": "In addition to causing embarrassment and unease, flatulence is linked to a variety of symptoms, some of which may be distressing. This review describes the origins of intestinal gas, its composition and methods which have been developed for its analysis. Emphasis is placed upon the effects of legumes in the diet in producing excessive intestinal gas and, particularly, on the role of raffinose-type oligosaccharides, containing alpha-galactosidic groupings. Suggestions for overcoming the problem are presented, including drug treatment, enzyme treatment, food processing and plant breeding. It is emphasised that removal of all raffinose-oligosaccharides from beans does not remove the problem of flatulence in animals and man; the compounds responsible--though assumed to be polysaccharides (or polysaccharide-derived oligomers formed by processing or cooking)--have yet to be characterised.", "title": "Flatulence--causes, relation to diet and remedies." }, { "docid": "MED-3543", "text": "Inhibition of monoamine oxidase is one way to treat depression and anxiety. The information now available on the pharmacokinetics of flavonoids and of the components of tobacco prompted an exploration of whether a healthy diet (with or without smoking) provides active compounds in amounts sufficient to partially inhibit monoamine oxidase. A literature search was used to identify dietary monoamine oxidase inhibitors, the levels of these compounds in foods, the pharmacokinetics of the absorption and distribution, and tissue levels observed. An estimated daily intake and the expected tissue concentrations were compared with the measured efficacies of the compounds as inhibitors of monoamine oxidases. Norharman, harman and quercetin dietary presence, pharmacokinetics, and tissue levels were consistent with significant levels reaching neuronal monoamine oxidase from the diet or smoking; 1,2,3,4-tetrahydroisoquinoline, eugenol, 1-piperoylpiperidine, and coumarin were not. Quercetin was equipotent with norharman as a monoamine oxidase A inhibitor and its metabolite, isorhamnetin, also inhibits. Total quercetin was the highest of the compounds in the sample diet. Although bioavailability was variable depending on the source, a healthy diet contains amounts of quercetin that might give sufficient amounts in brain to induce, by monoamine oxidase A inhibition, a small decrease in neurotransmitter breakdown.", "title": "Dietary inhibitors of monoamine oxidase A." }, { "docid": "MED-836", "text": "An optimal diet is one that not only prevents nutrient deficiencies by providing sufficient nutrients and energy for human growth and reproduction, but that also promotes health and longevity and reduces the risk of diet-related chronic diseases. The composition of the optimal diet for women with polycystic ovary syndrome (PCOS) is not yet known, but such a diet must not only assist short term with weight management, symptoms and fertility, but also specifically target the long-term risks of type 2 diabetes, CVD and certain cancers. With insulin resistance and compensatory hyperinsulinaemia now recognised as a key factor in the pathogenesis of PCOS, it has become clear that reducing insulin levels and improving insulin sensitivity are an essential part of management. Diet plays a significant role in the regulation of blood glucose and insulin levels, yet research into the dietary management of PCOS is lacking and most studies have focused on energy restriction rather than dietary composition per se. On the balance of evidence to date, a diet low in saturated fat and high in fibre from predominantly low-glycaemic-index-carbohydrate foods is recommended. Because PCOS carries significant metabolic risks, more research is clearly needed.", "title": "The optimal diet for women with polycystic ovary syndrome?" }, { "docid": "MED-4493", "text": "Processed meat intake may be involved in the etiology of colorectal cancer, a major cause of death in affluent countries. The epidemiologic studies published to date conclude that the excess risk in the highest category of processed meat-eaters is comprised between 20 and 50% compared with non-eaters. In addition, the excess risk per gram of intake is clearly higher than that of fresh red meat. Several hypotheses, which are mainly based on studies carried out on red meat, may explain why processed meat intake is linked to cancer risk. Those that have been tested experimentally are (i) that high-fat diets could promote carcinogenesis via insulin resistance or fecal bile acids; (ii) that cooking meat at a high temperature forms carcinogenic heterocyclic amines and polycyclic aromatic hydrocarbons; (iii) that carcinogenic N-nitroso compounds are formed in meat and endogenously; (iv) that heme iron in red meat can promote carcinogenesis because it increases cell proliferation in the mucosa, through lipoperoxidation and/or cytotoxicity of fecal water. Nitrosation might increase the toxicity of heme in cured products. Solving this puzzle is a challenge that would permit to reduce cancer load by changing the processes rather than by banning processed meat.", "title": "Processed meat and colorectal cancer: a review of epidemiologic and experimental evidence" }, { "docid": "MED-4884", "text": "In this study, magnetic resonance imaging (MRI) was applied to study the structural aspects of the tomato fruit. The main study was performed on tomatoes (cv. Tradiro) using a 0.2-T electromagnet scanner. Spin-echo images were acquired to visualize the tomato macrostructure. The air bubble content in tissues was evaluated by exploiting susceptibility effects using multiple gradient echo images. The microstructure was further studied by measuring spin-spin (T(2)) and spin-lattice (T(1)) relaxation time distributions. Nuclear magnetic resonance relaxometry, macro vision imaging and chemical analysis were used as complementary and independent experimental methods in order to emphasize the MRI results. MRI images showed that the air bubble content varied between tissues. The presence of gas was attested by macro vision images. Quantitative imaging showed that T(2) and T(1) maps obtained by MRI reflected the structural differences between tomato tissues and made it possible to distinguish between them. The results indicated that cell size and chemical composition contribute to the relaxation mechanism.", "title": "An investigation of the structural aspects of the tomato fruit by means of quantitative nuclear magnetic resonance imaging." }, { "docid": "MED-4806", "text": "Escherichia coli is probably the best-known bacterial species and one of the most frequently isolated organisms from clinical specimens. Despite this, underappreciation and misunderstandings exist among medical professionals and the lay public alike regarding E. coli as an extraintestinal pathogen. Underappreciated features include (i) the wide variety of extraintestinal infections E. coli can cause, (ii) the high incidence and associated morbidity, mortality, and costs of these diverse clinical syndromes, (iii) the pathogenic potential of different groups of E. coli strains for causing intestinal versus extraintestinal disease, and (iv) increasing antimicrobial resistance. In this era in which health news often sensationalizes uncommon infection syndromes or pathogens, the strains of E. coli that cause extraintestinal infection are an increasingly important endemic problem and underappreciated \"killers\". Billions of health care dollars, millions of work days, and hundreds of thousands of lives are lost each year to extraintestinal infections due to E. coli. New treatments and prevention measures will be needed for improved outcomes and a diminished disease burden.", "title": "Medical and economic impact of extraintestinal infections due to Escherichia coli: focus on an increasingly important endemic problem." }, { "docid": "MED-4126", "text": "Aspartame is a widely used artificial sweetener that has been linked to pediatric and adolescent migraines. Upon ingestion, aspartame is broken, converted, and oxidized into formaldehyde in various tissues. We present the first case series of aspartame-associated migraines related to clinically relevant positive reactions to formaldehyde on patch testing.", "title": "Formaldehyde, aspartame, and migraines: a possible connection." }, { "docid": "MED-4501", "text": "Beeturia, the passage of pink or red urine after the ingestion of beetroot, is said to occur in 10-14% of the population, and is more common in iron deficiency and malabsorption. A specific HPLC assay for betacyanins, the red beetroot pigments, in biological fluids was developed to study the prevalence of this apparent polymorphism in humans, and to investigate its basis in rats. Two major peaks were observed in chromatograms of extracts of unpickled beetroot. They had identical UV absorption spectra (lambda max = 535 nm) by diode array analysis, and mass spectrometry indicated that one (betacyanin 1) was betanin or its epimer and the other (betacyanin 2) a disaccharide of betacyanin 1. In a population of 100 normal subjects the 0-8 h urinary recoveries after an oral dose of 60 mg beetroot extract were 0.06-0.54% for betacyanin 1 and 0.01-0.6% for betacyanin 2. The distributions of these data were skewed but not clearly bimodal by visual inspection or by kernel density analysis. Four subjects produced visibly red urine and had betacyanin recoveries at the upper end of the population range. Studies using in situ isolated perfused rat jejunum and liver preparations indicated a negligible absorption of the pigments after 1 h and no detectable metabolism or biliary secretion. Intact anaesthetized rats given i.v. bolus doses of beetroot extract cleared both betacyanins from plasma at the rate of 3.3 +/- 0.9 (SD) ml min-1 (n = 5). The total urinary recovery of both pigments amounted to 80% of the dose, and their renal clearances approached their plasma clearances. These data suggest that beeturia does not arise from deficiencies in hepatic metabolism or renal excretion of betacyanins. After oral administration of beetroot extract to rats the betacyanin content of the stomach decreased rapidly with time but neither the intestines nor the bile duct were stained visibly red. These findings together with those showing instability of the betacyanins in acid conditions suggest that variability in the biological fate of beetroot pigments may be determined largely by gastric pH and emptying rate.", "title": "Beeturia and the biological fate of beetroot pigments." }, { "docid": "MED-3985", "text": "Deficiency of vitamin D is usually caused by dietary deficiency and/or lack of exposure to sunlight in dark skinned individuals living at northern latitudes. Simple vitamin D deficiency is commonly treated by prescribing a vitamin D containing calcium supplement. This report presents a patient who rejected this approach and instead, after researching alternative treatment options independently, opted to self-treat by consuming UVB-irradiated mushrooms. The beneficial effect of this on the patient's plasma biochemical markers is shown. Further research into the beneficial effect of consuming UVB-irradiated mushrooms is required.", "title": "Vitamin D deficiency treated by consuming UVB-irradiated mushrooms" }, { "docid": "MED-3621", "text": "Context Ionizing radiation is a consistently identified and potentially modifiable risk factor for meningioma, the most frequently reported primary brain tumor in the United States. Objective To examine the association between dental x-rays, the most common artificial source of ionizing radiation, and risk of intra-cranial meningioma. Design and Setting Population-based case-control study design. Participants The study includes 1433 intra-cranial meningioma cases aged 29-79 years diagnosed among residents of the states of Connecticut, Massachusetts, North Carolina, the San Francisco Bay Area and eight Houston, Texas counties between May 1, 2006 and April 28, 2011 and 1350 controls that were frequency-matched on age, sex and geography. Main Outcome Measure The association of intra-cranial meningioma diagnosis with self-report of bitewing, full-mouth, and panorex dental x-rays. Results Over a lifetime, cases were more than twice (Odds ratio (OR) = 2.0, 95% confidence interval (CI), 1.4-2.9) as likely as controls to report having ever had a bitewing exam. Regardless of the age at which the films were received, persons who reported receiving bitewing films on a yearly or greater frequency had an elevated risk with odds ratios of 1.4 (95%CI: 1.0-1.8), 1.6 (95%CI: 1.2-2.0), 1.9 (95%CI: 1.4-2.6), and 1.5 (95%CI: 1.1-2.0) for ages <10, 10-19, 20-49, and 50+ years, respectively. Increased risk of meningioma was also associated with panorex films taken at a young age or on a yearly or greater frequency with persons reporting receiving such films under the age of 10 years at 4.9 times (95%CI: 1.8-13.2) increased risk of meningioma. No association was appreciated with location of tumor above or below the tentorium. Conclusion Exposure to some dental x-rays performed in the past, when radiation exposure was greater than in the current era, appears to be associated with increased risk of intra-cranial meningioma. As with all sources of artificial ionizing radiation, considered use of this modifiable risk factor may be of benefit to patients.", "title": "Dental X-rays and Risk of Meningioma" }, { "docid": "MED-4873", "text": "The use of over-the-counter supplements is commonplace in today's health conscious society. We present an unusual case of intrahepatic cholestasis caused by vitamin A intoxication. The patient consumed one Herbalife shake with two multivitamin tablets of the same brand for 12 years. When calculated this equated to more than the recommended daily allowance for vitamin A consumption. Deranged liver function tests were consistent with a cholestatic process. Liver biopsy was obtained and revealed features pathognomonic of vitamin A toxicity, without the usual fibrosis. When the supplements were ceased, his jaundice and alkaline phosphatase completely normalized. This case highlights the importance of health care providers documenting non-prescribed dietary supplements and considering them in the etiology of cholestatic liver disease. Copyright 2009 Elsevier Inc. All rights reserved.", "title": "Hypervitaminosis A inducing intra-hepatic cholestasis--a rare case report." }, { "docid": "MED-2484", "text": "Paediatric asthma is a major clinical concern worldwide and represents a huge burden on family and society. It accounts for a large number of lost school days and may deprive the child of both academic achievement and social interaction. Childhood asthma also places strain on healthcare resources as a result of doctor and hospital visits and the cost of treatment. The prevalence of asthma varies worldwide, possibly because of different exposure to respiratory infection, indoor and outdoor pollution, and diet. Certain risk factors appear to predispose children to developing asthma and atopic disease, including incidence and severity of wheezing, atopy, maternal smoking, and number of fever episodes. This paper discusses the burden, prevalence, and risk factors associated with paediatric asthma.", "title": "The burden of childhood asthma" }, { "docid": "MED-3760", "text": "The authors sent a questionnaire to 772 randomly selected Danish clinicians and asked them about their use of placebo interventions. Sixty-five percent responded. Among the general practitioners, 86% (95% confidence interval 81-91) reported to have used placebo interventions at least once, and 48% (41-55) to have used placebo interventions more than ten times, within the last year. Hospital-based doctors and private specialists reported to have used placebo interventions less frequently (p < .001). The most important reason for the use of placebo interventions was to avoid a confrontation with the patient. Typical placebos were antibiotics for viral infections. Approximately 30% (28-36) of the clinicians believed in an effect of placebo interventions on objective outcomes, and 46% (42-50) found clinical placebo interventions generally ethically acceptable.", "title": "The use of placebo interventions in medical practice--a national questionnaire survey of Danish clinicians." }, { "docid": "MED-854", "text": "INTRODUCTION: Ingestion of a small amount of concentrated hydrogen peroxide can cause cerebral air gas embolism (CAGE). Hyperbaric oxygen therapy (HBOT) is the standard of care in the treatment of CAGE. We report a case of CAGE after accidental ingestion of 33%hydrogen peroxide treated with HBOT resulting in reversal of both the clinical and radiologic abnormalities. CASE REPORT: A 48 year-old male took two sips of 33% hydrogen peroxide. A short time later, he developed hematemesis, left sided hemiplegia, confusion, and left homonymous hemianopsia. Initial laboratory studies, chest x-ray, and brain CT were normal. MRI demonstrated areas of restricted diffusion and T2 hyper intensities in multiple vascular territories consistent with ischemia due to CAGE. Eighteen hours after arrival, the patient underwent HBOT at 3 atmospheres absolute (ATA) for 30 minutes and 2.5 ATA for 60 minutes with clinical improvement. Follow-up MRI at six months demonstrated resolution of the hyper intensities. DISCUSSION: A search of MEDLINE from 1950 to present revealed only two cases of CAGE from ingestion of concentrated hydrogen peroxide treated with HBOT. Both cases, similar to ours, had complete resolution of symptoms. Of the seven reported cases of CAGE from hydrogen peroxide that did not undergo HBOT, only in one patient was there a report of symptom resolution. CONCLUSION: Ingestion of even a small amount of concentrated hydrogen peroxide can result in cerebral air gas embolism. Hyperbaric oxygen therapy may be of benefit in reversing the symptoms and preventing permanent neurological impairment.", "title": "Cerebral air gas embolism from concentrated hydrogen peroxide ingestion." } ]
PLAIN-1241
garbanzo beans
[ { "docid": "MED-3580", "text": "The effects of the glycemic index (GI) of carbohydrate eaten the previous night on the glycemic response to a standard test meal eaten subsequently in the morning (breakfast) was studied. On separate evenings normal subjects ate low- or high-GI test meals of the same nutrient composition. The dinners consisted of single foods in two experiments and mixed meals containing several foods in the third. The differences between the observed glycemic responses to low- and high-GI dinners were predicted by their GIs. The glycemic responses to breakfast were significantly lower on mornings after low-GI dinners than after high-GI dinners. Eating, at dinner, foods with different fiber contents but the same GI had no effect on postbreakfast glycemia. We conclude that the GI predicts the difference between glycemic responses of mixed dinner meals; breakfast carbohydrate tolerance is improved when low-GI foods are eaten the previous evening.", "title": "Second-meal effect: low-glycemic-index foods eaten at dinner improve subsequent breakfast glycemic response." }, { "docid": "MED-4347", "text": "BACKGROUND: The nutritional composition of the dietary intake could produce specific effects on metabolic variables and inflammatory marker concentrations. This study assessed the effects of two hypocaloric diets (legume-restricted- vs. legume-based diet) on metabolic and inflammatory changes, accompanying weight loss. METHODS: Thirty obese subjects (17 M/13F; BMI: 32.5 ± 4.5 kg/m(2); 36 ± 8 years) were randomly assigned to one of the following hypocaloric treatments (8 weeks): Calorie-restricted legume-free diet (Control: C-diet) or calorie-restricted legume-based diet (L-diet), prescribing 4 weekly different cooked-servings (160-235 g) of lentils, chickpeas, peas or beans. Body composition, blood pressure (BP), blood biochemical and inflammatory marker concentrations as well as dietary intake were measured at baseline and after the nutritional intervention. RESULTS: The L-diet achieved a greater body weight loss, when compared to the C-diet (-7.8 ± 2.9% vs. -5.3 ± 2.7%; p = 0.024). Total and LDL cholesterol levels and systolic BP were improved only when consuming the L-diet (p < 0.05). L-diet also resulted in a significant higher reduction in C-reactive protein (CRP) and complement C3 (C3) concentrations (p < 0.05), compared to baseline and C-diet values. Interestingly, the reduction in the concentrations of CRP and C3 remained significantly higher to L-diet group, after adjusting by weight loss (p < 0.05). In addition, the reduction (%) in CRP concentrations was positively associated with decreases (%) in systolic BP and total cholesterol concentration specifically in the L-diet group, independent from weight loss (p < 0.05). CONCLUSION: The consumption of legumes (4 servings/week) within a hypocaloric diet resulted in a specific reduction in proinflammatory markers, such as CRP and C3 and a clinically significant improvement of some metabolic features (lipid profile and BP) in overweight/ obese subjects, which were in some cases independent from weight loss.", "title": "A legume-based hypocaloric diet reduces proinflammatory status and improves metabolic features in overweight/obese subjects." }, { "docid": "MED-4509", "text": "Hypercholesterolemia is a major modifiable risk factor for cardiovascular disease. Some, but not all, studies have shown that soy protein intake decreases total and low-density lipoprotein cholesterol and triglycerides and increases high-density lipoprotein cholesterol. The objective of this meta-analysis was to examine the effect of soy protein supplementation on serum lipid levels in adults. English language articles were retrieved by searching MEDLINE (1966 to February 2005) and the bibliographies of the retrieved articles. A total of 41 randomized controlled trials in which isolated soy protein supplementation was the only intervention and the net changes in serum lipids during intervention were reported. Information on study design, sample size, participant characteristics, intervention, follow-up duration, and treatment outcomes was independently abstracted using a standardized protocol. Using a random-effects model, data from each study were pooled and weighted by the inverse of their variance. Soy protein supplementation was associated with a significant reduction in mean serum total cholesterol (-5.26 mg/dl, 95% confidence interval [CI] -7.14 to -3.38), low-density lipoprotein cholesterol (-4.25 mg/dl, 95% CI -6.00 to -2.50), and triglycerides (-6.26 mg/dl, 95% CI -9.14 to -3.38) and a significant increase in high-density lipoprotein cholesterol (0.77 mg/dl, 95% CI 0.20 to 1.34). Meta-regression analyses showed a dose-response relation between soy protein and isoflavone supplementation and net changes in serum lipids. These results indicate that soy protein supplementation reduces serum lipids among adults with or without hypercholesterolemia. In conclusion, replacing foods high in saturated fat, trans-saturated fat, and cholesterol with soy protein may have a beneficial effect on coronary risk factors.", "title": "A meta-analysis of the effect of soy protein supplementation on serum lipids." }, { "docid": "MED-4350", "text": "Potatoes have the highest daily per capita consumption of all vegetables in the U.S. diet. Pigmented potatoes contain high concentrations of antioxidants, including phenolic acids, anthocyanins, and carotenoids. In a single-dose study six to eight microwaved potatoes with skins or a comparable amount of refined starch as cooked biscuits was given to eight normal fasting subjects; repeated samples of blood were taken over an 8 h period. Plasma antioxidant capacity was measured by ferric reducing antioxidant power (FRAP). A 24 h urine was taken before and after each regimen. Urine antioxidant capacity due to polyphenol was measured by Folin reagent after correction for nonphenolic interferences with a solid phase (Polyclar) procedure. Potato caused an increase in plasma and urine antioxidant capacity, whereas refined potato starch caused a decrease in both; that is, it acted as a pro-oxidant. In a crossover study 18 hypertensive subjects with an average BMI of 29 were given either six to eight small microwaved purple potatoes twice daily or no potatoes for 4 weeks and then given the other regimen for another 4 weeks. There was no significant effect of potato on fasting plasma glucose, lipids, or HbA1c. There was no significant body weight increase. Diastolic blood pressure significantly decreased 4.3%, a 4 mm reduction. Systolic blood pressure decreased 3.5%, a 5 mm reduction. This blood pressure drop occurred despite the fact that 14 of 18 subjects were taking antihypertensive drugs. This is the first study to investigate the effect of potatoes on blood pressure. Thus, purple potatoes are an effective hypotensive agent and lower the risk of heart disease and stroke in hypertensive subjects without weight gain.", "title": "High-antioxidant potatoes: acute in vivo antioxidant source and hypotensive agent in humans after supplementation to hypertensive subjects." }, { "docid": "MED-4316", "text": "The intestinal absorption of the essential trace element iron and its mobilization from storage sites in the body are controlled by systemic signals that reflect tissue iron requirements. Recent advances have indicated that the liver-derived peptide hepcidin plays a central role in this process by repressing iron release from intestinal enterocytes, macrophages and other body cells. When iron requirements are increased, hepcidin levels decline and more iron enters the plasma. It has been proposed that the level of circulating diferric transferrin, which reflects tissue iron levels, acts as a signal to alter hepcidin expression. In the liver, the proteins HFE, transferrin receptor 2 and hemojuvelin may be involved in mediating this signal as disruption of each of these molecules decreases hepcidin expression. Patients carrying mutations in these molecules or in hepcidin itself develop systemic iron loading (or hemochromatosis) due to their inability to down regulate iron absorption. Hepcidin is also responsible for the decreased plasma iron or hypoferremia that accompanies inflammation and various chronic diseases as its expression is stimulated by pro-inflammatory cytokines such as interleukin 6. The mechanisms underlying the regulation of hepcidin expression and how it acts on cells to control iron release are key areas of ongoing research. IUBMB Life, 57: 499-503, 2005.", "title": "Systemic regulation of intestinal iron absorption." }, { "docid": "MED-4627", "text": "The emerging role of chronic inflammation in the major degenerative diseases of modern society has stimulated research into the influence of nutrition and dietary patterns on inflammatory indices. Most human studies have correlated analyses of habitual dietary intake as determined by a food frequency questionnaire or 24-hour recall with systemic markers of inflammation like high-sensitivity C-reactive protein (HS-CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). An occasional study also includes nutrition analysis of blood components. There have been several controlled interventions which evaluated the effect of a change in dietary pattern or of single foods on inflammatory markers in defined populations. Most studies reveal a modest effect of dietary composition on some inflammatory markers in free-living adults, although different markers do not vary in unison. Significant dietary influences have been established for glycemic index (GI) and load (GL), fiber, fatty acid composition, magnesium, carotenoids, and flavonoids. A traditional Mediterranean dietary pattern, which typically has a high ratio of monounsaturated (MUFA) to saturated (SFA) fats and ω-3 to ω-6 polyunsaturated fatty acid (PUFAs) and supplies an abundance of fruits, vegetables, legumes, and grains, has shown anti-inflammatory effects when compared with typical North American and Northern European dietary patterns in most observational and interventional studies and may become the diet of choice for diminishing chronic inflammation in clinical practice.", "title": "Diet and inflammation." }, { "docid": "MED-3582", "text": "Breakfasts of lentils or wholemeal bread of identical carbohydrate content were taken by seven healthy volunteers. The lentils produced a significant 71% (p less than 0.001) reduction in the blood glucose area and flattened the plasma insulin and gastric inhibitory polypeptide responses by comparison with the bread. In addition, the lentil breakfast was followed by a significantly flatter blood glucose response to the standard bread lunch which followed 4 h later (by 38%, p less than 0.01). The blood glucose pattern was mimicked by feeding the bread breakfast slowly over the 4 h before lunch. Giving a bread breakfast containing a quarter of the carbohydrate reduced the breakfast glucose profile but resulted in a significantly impaired blood glucose response to lunch (168% of control, p less than 0.01). These results, together with breath hydrogen studies, performed on a separate group of four volunteers, indicate that the flattened response to lentils is not due to carbohydrate malabsorption. Slow release or \"lente\" carbohydrate foods such as lentils may form a useful part of the diets of those with impaired carbohydrate tolerance.", "title": "Slow release dietary carbohydrate improves second meal tolerance." }, { "docid": "MED-3584", "text": "Background: A high intake of white rice is associated with the metabolic syndrome and type 2 diabetes. Costa Ricans follow a staple dietary pattern that includes white rice and beans, yet the combined role of these foods on cardiometabolic risk factors has not been studied. Objective: We aimed to determine the association between intake of white rice and beans and the metabolic syndrome and its components in Costa Rican adults (n = 1879) without diabetes. Design: Multivariate-adjusted means were calculated for components of the metabolic syndrome by daily servings of white rice and beans (<1, 1, or >1) and by the ratio of beans to white rice. The OR for the metabolic syndrome was calculated by substituting one serving of beans for one serving of white rice. Results: An increase in daily servings of white rice was positively associated with systolic blood pressure (BP), triglycerides, and fasting glucose and inversely associated with HDL cholesterol (P-trend <0.01 for all). An increase in servings of beans was inversely associated with diastolic BP (P = 0.049). Significant trends for higher HDL cholesterol and lower BP and triglycerides were observed for 1:3, 1:2, 1:1, and 2:1 ratios of beans to white rice. Substituting one serving of beans for one serving of white rice was associated with a 35% (95% CI: 15%, 50%) lower risk of the metabolic syndrome. Conclusion: Increasing the ratio of beans to white rice, or limiting the intake of white rice by substituting beans, may lower cardiometabolic risk factors.", "title": "A higher ratio of beans to white rice is associated with lower cardiometabolic risk factors in Costa Rican adults" }, { "docid": "MED-3581", "text": "BACKGROUND: Low postprandial blood glucose is associated with low risk of metabolic diseases. A meal's ability to diminish the glucose response to carbohydrates eaten during the following meal is known as the \"second-meal effect\" (SME). The reduced glycemia elicited by low-glycemic-index (LGI) foods consumed during the first meal has been suggested as the main mechanism for SME. However, LGI foods often increase colonic fermentation because of the presence of fiber and resistant starch. OBJECTIVE: The objective was to study the SME of greater fermentation of high-glycemic-index (HGI) and LGI carbohydrates eaten during a previous meal. DESIGN: Ten healthy volunteers ate 3 breakfast test meals consisting of sponge cakes made with rapidly digestible, nonfermentable amylopectin starch plus cellulose (HGI meal), amylopectin starch plus the fermentable disaccharide lactulose (HGI-Lac meal), or slowly digestible, partly fermentable amylose starch plus cellulose (LGI meal). Five hours later, subjects were fed the same standard lunch containing 93 g available carbohydrates. Blood was collected for measurement of glucose, insulin, and nonesterified fatty acids (NEFAs). Breath hydrogen was measured as a marker of colonic fermentation. Postlunch gastric emptying was measured by using ultrasonography. RESULTS: Both the HGI-Lac and LGI meals improved glucose tolerance at lunch. In the case of the HGI-Lac meal, this effect was concomitant with low NEFA concentrations and delayed gastric emptying. CONCLUSION: Fermentable carbohydrates, independent of their effect on a food's glycemic index, have the potential to regulate postprandial responses to a second meal by reducing NEFA competition for glucose disposal and, to a minor extent, by affecting intestinal motility.", "title": "Colonic fermentation of indigestible carbohydrates contributes to the second-meal effect." }, { "docid": "MED-4510", "text": "Background and Aims Studies evaluating the effect of legume consumption on cholesterol have focused on soybeans, however non-soy legumes, such as a variety of beans, peas, and some seeds, are commonly consumed in Western countries. We conducted a meta-analysis of randomized controlled trials evaluating the effects of non-soy legume consumption on blood lipids. Methods and Results Studies were retrieved by searching MEDLINE (from January 1966 through July 2009), EMBASE (from January 1980 to July 2009), and the Cochrane Collaboration's Central Register of Controlled Clinical Trials using the following terms as medical subject headings and keywords: fabaceae not soybeans not isoflavones and diet or dietary fiber and cholesterol or hypercholesterolemia or triglycerides or cardiovascular diseases. Bibliographies of all retrieved articles were also searched. From 140 relevant reports, 10 randomized clinical trials were selected which compared a non-soy legume diet to control, had a minimum duration of 3 weeks, and reported blood lipid changes during intervention and control. Data on sample size, participant characteristics, study design, intervention methods, duration, and treatment results were independently abstracted by 2 investigators using a standardized protocol. Data from 10 trials representing 268 participants were examined using a random-effects model. Pooled mean net change in total cholesterol for those treated with a legume diet compared to control was −11.8 mg/dL (95% confidence interval [CI], −16.1 to −7.5); mean net change in low density lipoprotein cholesterol was −8.0 mg/dL (95% CI, −11.4 to −4.6). Conclusion These results indicate that a diet rich in legumes other than soy decreases total and LDL cholesterol.", "title": "Non-Soy Legume Consumption Lowers Cholesterol Levels: A Meta-Analysis of Randomized Controlled Trials" }, { "docid": "MED-4318", "text": "Preliminary data in the literature indicate that iron absorption from a meal may be increased when consumed with low-pH beverages such as cola, and it is also possible that sugar iron complexes may alter iron availability. A randomized, crossover trial was conducted to compare the bioavailability of nonheme iron from a vegetarian pizza meal when consumed with 3 different beverages (cola, diet cola, and mineral water). Sixteen women with serum ferritin concentrations of 11-54 µg/L were recruited and completed the study. The pizza meal contained native iron and added ferric chloride solution as a stable isotope extrinsic label; the total iron content of the meal was ~5.3 mg. Incorporation of iron from the meal into RBC was not affected by the type of drink (9.9% with cola, 9.4% with diet cola, and 9.6% with water). Serum ferritin and plasma hepcidin were correlated (r = 0.66; P<0.001) and both were significant predictors of iron bioavailability, but their combined effect explained only 30% of the inter-individual variation (P<0.001) and illustrates the current lack of understanding of mechanisms responsible for the fine-tuning of iron absorption. Although there was no effect of low-pH drinks on iron bioavailability in healthy women, their effect on absorption of fortification iron that requires solubilization in dilute acid, such as reduced iron, and in individuals with low gastric acid production, such as older people and individuals with Helicobacter pylori infection, warrants further investigation.", "title": "Low-pH cola beverages do not affect women's iron absorption from a vegetarian meal." }, { "docid": "MED-4349", "text": "Inflammation is a pathological condition underlying a number of diseases including cardiovascular diseases, cancer, and chronic inflammatory diseases. In addition, healthy, obese subjects also express markers of inflammation in their blood. Diet provides a variety of nutrients as well as non-nutritive bioactive constituents which modulate immunomodulatory and inflammatory processes. Epidemiological data suggest that dietary patterns strongly affect inflammatory processes. Primarily the intake of fruit and vegetables as well as of whole wheat is inversely associated with the risk of inflammation. In addition to observational studies there are also data from human intervention studies suggesting an anti-inflammatory potential of these plant foods. At the level of bioactive compounds occurring in plant foods, primarily carotenoids and flavonoids seem to modulate inflammatory as well as immunological processes. In conclusion, there is convincing evidence that plant foods and non-nutritive constituents associated with these foods modulate immunological and inflammatory processes. By means of anti-inflammatory activities a plant-based diet may contribute to the lower risk of cardiovascular diseases and cancer. A high intake of vegetables, fruit, and whole wheat as recommended by all international nutrition authorities provides a wide spectrum of bioactive compounds at health-promoting concentrations.", "title": "Anti-inflammatory effects of plant-based foods and of their constituents." }, { "docid": "MED-4149", "text": "Oxidative stress, i.e. excessive content of reactionary, oxygen, and nitrogen compounds (ROAC), including free radicals, is one of the causes of various dangerous diseases as well as premature aging. The adverse effect of free radicals can be neutralized by antioxidants. In order to carry out antioxidant therapy, one needs to know the contents of antioxidants in food products. We have created the databank for the contents of antioxidants in 1,140 food products, beverages, etc. Apart from water-soluble antioxidants, fat-soluble antioxidants in dairy and fish products, cacao, chocolate, nuts etc. were determined for the first time using an amperometric method.", "title": "Creation of a databank for content of antioxidants in food products by an amperometric method." }, { "docid": "MED-4317", "text": "Iron is an essential trace metal in human metabolism. However, imbalances in iron homeostasis are prevalent worldwide and have detrimental effects on human health. Humans do not have the ability to remove excess iron and therefore iron homeostasis is maintained by regulating the amount of iron entering the body from the diet. Iron is present in the human diet in number of different forms, including heme (from meat) and a variety of non-heme iron compounds. While heme is absorbed intact, the bioavailability of non-heme iron varies greatly depending on dietary composition. A number of dietary components are capable of interacting with iron to regulate its solubility and oxidation state. Interestingly, there is an emerging body of evidence suggesting that some nutrients also have direct effects on the expression and function of enterocyte iron transporters. In addition to dietary factors, body iron status is a major determinant of iron absorption. The roles of these important dietary and systemic factors in regulating iron absorption will be discussed in this review.", "title": "Intestinal iron absorption: regulation by dietary & systemic factors." }, { "docid": "MED-3583", "text": "Pulses are low-glycemic appetite-suppressing foods, but it is not known whether these properties persist after being consumed as part of a meal and after a second meal. The objective of this study was to determine the effects of a fixed-size pulse meal on appetite and blood glucose (BG) before and after an ad libitum test meal (pizza) and on food intake (FI) at the test meal. Males (n = 25; 21.3 ± 0.5 years; 21.6 ± 0.3 kg·m(-2)) randomly consumed 4 isocaloric meals: chickpea; lentil; yellow split pea; and macaroni and cheese (control). Commercially available canned pulses provided 250 kcal, and were consumed with macaroni and tomato sauce. FI was measured at a pizza meal 260 min after consumption of the isocaloric meal. BG and appetite were measured from 0 to 340 min. The lentil and yellow pea, but not chickpea, treatments led to lower appetite ratings during the 260 min prepizza meal period, and less FI at the pizza meal, compared with macaroni and cheese (p < 0.05). All pulse treatments lowered BG immediately following consumption (at 20 min) (p < 0.05), but there was no effect of treatment on prepizza meal BG AUC (p = 0.07). Immediately after the pizza meal, BG was lower following the chickpea and lentil treatments, but not the yellow pea treatment (p < 0.05). Postpizza meal BG AUC was lower following the chickpea and lentil treatments than in the yellow pea treatment (p < 0.05). The beneficial effects of consuming a pulse meal on appetite, FI at a later meal, and the BG response to a later meal are dependent on pulse type.", "title": "First and second meal effects of pulses on blood glucose, appetite, and food intake at a later meal." } ]
[ { "docid": "MED-2140", "text": "Background Around the world, beans and rice are commonly consumed together as a meal. With type 2 diabetes increasing, the effect of this traditional diet pattern on glycemic response has not been studied fully. Methods We evaluated the glycemic response of bean and rice traditional meals compared to rice alone in adults with type 2 diabetes. Seventeen men and women with type 2 diabetes controlled by metformin (n = 14) or diet/exercise (n = 3) aged 35–70 years participated in the randomized 4 × 4 crossover trial. The white long grain rice control, pinto beans/rice, black beans/rice, red kidney beans/rice test meals, matched for 50 grams of available carbohydrate, were consumed at breakfast after a 12 hour fast. Capillary blood glucose concentrations at baseline and at 30 minute intervals up to 180 minutes postprandial were collected. MANOVA for repeated measures established glucose differences between treatments. Paired t tests identified differences between bean types and the rice control following a significant MANOVA. Results Postprandial net glucose values were significantly lower for the three bean/rice treatments in contrast to the rice control at 90, 120 and 150 minutes. Incremental area under the curve values were significantly lower for the pinto and black bean/rice meals compared to rice alone, but not for kidney beans. Conclusions Pinto, dark red kidney and black beans with rice attenuate the glycemic response compared to rice alone. Promotion of traditional foods may provide non-pharmaceutical management of type 2 diabetes and improve dietary adherence with cultural groups. Trial registration Clinical Trials number NCT01241253", "title": "Bean and rice meals reduce postprandial glycemic response in adults with type 2 diabetes: a cross-over study" }, { "docid": "MED-4991", "text": "BACKGROUND: Epidemiological studies have shown positive findings associated with legume consumption and measures of cardiovascular disease and obesity. However, few observational trials have examined beans as a separate food variable when determining associations with health parameters. OBJECTIVE: To determine the association of consuming beans on nutrient intakes and physiological parameters using the National Health and Examination Survey (NHANES) 1999-2002. METHODS: Using data from NHANES 1999-2002, a secondary analysis was completed with a reliable 24-hour dietary recall where three groups of bean consumers were identified (N = 1,475). We determined mean nutrient intakes and physiological values between bean consumers and non-consumers. Least square means, standard errors and ANOVA were calculated using appropriate sample weights following adjustment for age, gender, ethnicity and energy. RESULTS: Relative to non-consumers, bean consumers had higher intakes of dietary fiber, potassium, magnesium, iron, and copper (p's < 0.05). Those consuming beans had a lower body weight (p = 0.008) and a smaller waist size (p = 0.043) relative to non-consumers. Additionally, consumers of beans had a 23% reduced risk of increased waist size (p = 0.018) and a 22% reduced risk of being obese (p = 0.026). Also, baked bean consumption was associated with a lower systolic blood pressure. CONCLUSIONS: Bean consumers had better overall nutrient intake levels, better body weights and waist circumferences, and lower systolic blood pressure in comparison to non-consumers. These data support the benefits of bean consumption on improving nutrient intake and health parameters.", "title": "Bean consumption is associated with greater nutrient intake, reduced systolic blood pressure, lower body weight, and a smaller waist circumference ..." }, { "docid": "MED-3138", "text": "Background Many consumers avoid eating beans because they believe legume consumption will cause excessive intestinal gas or flatulence. An increasing body of research and the 2010 Dietary Guidelines for Americans supports the benefits of a plant-based diet, and legumes specifically, in the reduction of chronic disease risks. The purpose of the current research was to investigate the perception of increased flatulence and gastrointestinal discomfort among participants who consumed a ½ cup of beans daily for 8 or 12 weeks. Methods Participants in three studies to test the effects of beans on heart disease biomarkers completed the same weekly questionnaire to assess gastrointestinal discomfort issues such as increased flatulence, stool changes, and bloating. Studies 1 and 2 were randomized crossover trials. Participants consumed ½ cup of pinto beans, black-eyed peas, and canned carrots as control (n = 17) in Study 1 for three randomized 8-week phases. For Study 2, participants ate ½ cup baked beans or canned carrots as control (n = 29) for two randomized 8-week phases. Study 3 was a parallel arm trial with 40 subjects receiving ½ cup pinto beans and 40 consuming a control soup for 12 weeks. Changes in the frequency of perceived flatulence, stool characteristics, and bloating were the primary outcome measures. Chi-square distributions were examined for the presence or absence of symptoms and demographic characteristics to determine differences by gender, age, body mass index (BMI), and bean type. Results Less than 50% reported increased flatulence from eating pinto or baked beans during the first week of each trial, but only 19% had a flatulence increase with black-eyed peas. A small percentage (3-11%) reported increased flatulence across the three studies even on control diets without flatulence-producing components. Conclusions People's concerns about excessive flatulence from eating beans may be exaggerated. Public health nutritionists should address the potential for gastrointestinal discomfort when increasing fiber intake from beans with clients. It is important to recognize there is individual variation in response to different bean types.", "title": "Perceptions of flatulence from bean consumption among adults in 3 feeding studies" }, { "docid": "MED-1880", "text": "Legumes are the basés diet in several countries. They hold a high nutritional value, but other properties related to human health are nowadays being studied. The aim of this work was to study the influence of processes (boiling or germination) on the phenolic composition of dark beans (Phaseolus vulgaris L. c.v. Tolosana) and their effect on their antioxidant, neuroprotective and anticancer ability. Phenolic composition of raw and processed dark beans was analysed by HPLC-PAD and HPLC-ESI/MS. The antioxidant activity was evaluated by ORAC. Astrocytes cultures (U-373) have been used to test their neuroprotective effect. Anticancer activities were evaluated on three different cell lines (renal adenocarcinoma (TK-10), breast adenocarcinoma (MCF-7) and melanoma (UACC-62)) by sulphorhodamine B method. Qualitative and quantitative differences in phenolic composition have been observed between raw and processed dark beans that influence the antioxidant activity, mainly for germinated samples which show a decrease of antioxidant capacity. Although every assayed extracts decreased reactive oxygen species release and exhibited cytotoxicity activities on cancer cell lines, raw beans proved to be the most active in neuroprotective and antitumoral effects; this sample is especially rich in phenolic compounds, mainly anthocyanins. This study further demonstrated that phenolic composition of dark beans is related with cooking process and so with their neuroprotective and anticancer activity; cooking of dark beans improves their digestion and absorption at intestinal level, while maintaining its protective ability on oxidative process at cellular level. Copyright © 2012 Elsevier Ltd. All rights reserved.", "title": "Effect of cooking and germination on phenolic composition and biological properties of dark beans (Phaseolus vulgaris L.)." }, { "docid": "MED-3141", "text": "OBJECTIVE: To evaluate the associations with chronic disease risk and mortality of the consequences of bean-free diets in Taiwanese adults with regard to gender. DESIGN: A sub-sample of the National Health Interview Survey (NHIS) in 2001 agreed to physical examination in the subsequent year. This group then took part in the Taiwanese Survey of Hyperglycaemia, Hyperlipidaemia and Hypertension (TwSHHH) in 2002. SETTING: Individual records were linked to the eventual death files from 2002 to 2008. SUBJECTS: Up to the end of 2008, a total of 2820 men and 2950 women were tracked by death registry over the 6·8 years of follow-up. RESULTS: Among 38,077 person-years, an average follow-up 6·5 years, 225 all-cause deaths were identified. Generalized linear models showed beans to be favourable for metabolic syndrome (other than for fasting glucose) in men; in women, beans were favourable for waist circumference and HbA1c. Cumulative logistic regression models for the effect of a bean-free diet on metabolic syndrome scores according to the Taiwanese-modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-tw) gave adjusted odds ratios of 1·83 in men and 1·45 in women. Cox regression models for the bean-free diet showed an increased hazard ratio for all-cause mortality among women (1·98, 95% CI 1·03, 3·81) but not men (1·28, 95% CI 0·76, 2·16). CONCLUSIONS: A bean-free diet may play a role in developing the metabolic syndrome in both genders, and is a significant predictor of all-cause mortality in Taiwanese women but not men.", "title": "A bean-free diet increases the risk of all-cause mortality among Taiwanese women: the role of the metabolic syndrome." }, { "docid": "MED-5079", "text": "OBJECTIVE: To determine effects of daily intake of 1/2 cup pinto beans, black-eyed peas or carrots (placebo) on risk factors for coronary heart disease (CHD) and diabetes mellitus (DM) in free-living, mildly insulin resistant adults over an 8 week period. METHODS: Randomized, crossover 3x3 block design. Sixteen participants (7 men, 9 women) received each treatment for eight-weeks with two-week washouts. Fasting blood samples collected at beginning and end of periods were analyzed for total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol, triacylglycerols, high-sensitivity C-reactive protein, insulin, glucose, and hemoglobin A1c. RESULTS: A significant treatment-by-time effect impacted serum TC (p = 0.026) and LDL (p = 0.033) after eight weeks. Paired t-tests indicated that pinto beans were responsible for this effect (p = 0.003; p = 0.008). Mean change of serum TC for pinto bean, black-eyed pea and placebo were -19 +/- 5, 2.5 +/- 6, and 1 +/- 5 mg/dL, respectively (p = 0.011). Mean change of serum LDL-C for pinto bean, black-eyed pea and placebo were -14 +/- 4, 4 +/- 5, and 1 +/- 4 mg/dL, in that order (p = 0.013). Pinto beans differed significantly from placebo (p = 0.021). No significant differences were seen with other blood concentrations across the 3 treatment periods. CONCLUSIONS: Pinto bean intake should be encouraged to lower serum TC and LDL-C, thereby reducing risk for CHD.", "title": "Pinto bean consumption reduces biomarkers for heart disease risk." }, { "docid": "MED-2570", "text": "The functional properties, including antioxidant and chemopreventative capacities as well as the inhibitory effects on angiotensin-converting enzyme (ACE), α-glucosidase and pancreatic lipase, of three Australian-grown faba bean genotypes (Nura, Rossa and TF(Ic*As)*483/13) were investigated using an array of in vitro assays. Chromatograms of on-line post column derivatisation assay coupled with HPLC revealed the existence of active phenolics (hump) in the coloured genotypes, which was lacking in the white-coloured breeding line, TF(Ic*As)*483/13. Roasting reduced the phenolic content, and diminished antioxidant activity by 10-40 % as measured by the reagent-based assays (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and oxygen radical absorbance capacity) in all genotypes. Cell culture-based antioxidant activity assay (cellular antioxidant activity) showed an increase of activity in the coloured genotypes after roasting. Faba bean extracts demonstrated cellular protection ability against H₂O₂-induced DNA damage (assessed using RAW264.7 cells), and inhibited the proliferation of all human cancer cell lines (BL13, AGS, Hep G2 and HT-29) evaluated. However, the effect of faba bean extracts on the non-transformed human cells (CCD-18Co) was negligible. Flow cytometric analyses showed that faba bean extracts successfully induced apoptosis of HL-60 (acute promyelocytic leukaemia) cells. The faba bean extracts also exhibited ACE, α-glucosidase and pancreatic lipase inhibitory activities. Overall, extracts from Nura (buff-coloured) and Rossa (red-coloured) were comparable, while TF(Ic*As)*483/13 (white-coloured) contained the lowest phenolic content and exhibited the least antioxidant and enzyme inhibition activities. These results are important to promote the utilisation of faba beans in human diets for various health benefits.", "title": "In vitro investigations of the potential health benefits of Australian-grown faba beans (Vicia faba L.): chemopreventative capacity and inhibitory ..." }, { "docid": "MED-3136", "text": "The objective of this study was to determine the influence of frequent and long-term consumption of legume seeds on colonic function. Two groups of subjects were studied--one group habitually consumed legume seeds as part of their normal diet, a second group only infrequently consumed legumes. No differences between these groups could be detected for fecal output and frequency, intestinal transit time, VFA excretion or fecal pH during 23-day study periods in which subjects consumed either their usual diet or 100 g red kidney beans, daily. However, the addition of beans to the diets of both groups provided significantly more dietary fiber, and produced greater fecal output and a higher concentration of VFA in feces. Fecal output appeared to be determined by two independent parameters--dietary fiber intake and VFA excretion. Beans provided a physiologically useful source of dietary fiber and favorably influenced colonic function.", "title": "Influence of frequent and long-term bean consumption on colonic function and fermentation." }, { "docid": "MED-2147", "text": "Consumption of Phaseolus vulgaris bean species such as pinto, black, navy or kidney may be beneficial in the prevention and treatment of chronic diseases. In particular, conditions that are promoted by increased glycaemic stress (hyperglycaemia and hyperinsulinaemia) including diabetes, CVD and cancer seem to be reduced in individuals who eat more of these beans. The present paper discusses the influence of P. vulgaris species on glycaemic response and the impact that relationship may have on the risk of developing diabetes, CVD and cancer.", "title": "Phaseolus beans: impact on glycaemic response and chronic disease risk in human subjects." }, { "docid": "MED-2580", "text": "Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial–based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18–0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial–based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence.", "title": "High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial" }, { "docid": "MED-2144", "text": "Bean pods (Phaseolus vulgaris) are among the most widely used traditional remedies against diabetes mellitus. Historical knowledge is summarized and compared to recent study results. Reports dating from the first half of the 20(th) century as well as recent publications show contradictory results. It seems that Phaseolus preparations should not be considered the first choice in phytopharmaceutical treatment of diabetes or lead structure research. To be effective, fairly high doses of aqueous extracts need to be given. Because of their fiber content and an alpha-amylase inhibitory effect, beans might be more useful as food components in preventing or ameliorating type 2 diabetes.", "title": "Beans and diabetes: Phaseolus vulgaris preparations as antihyperglycemic agents." }, { "docid": "MED-2010", "text": "Legumes (including alfalfa, clover, lupins, green beans and peas, peanuts, soybeans, dry beans, broad beans, dry peas, chickpeas, and lentils) represent an important component of the human diet in several areas of the world, especially in the developing countries, where they complement the lack of proteins from cereals, roots, and tubers. In some regions of the world, legume seeds are the only protein supply in the diet. The health benefits of legume consumption have received rising interest from researchers, and their consumption and production extends worldwide. Among European countries, higher legume consumption is observed around the Mediterranean, with per capita daily consumption between 8 and 23 g, while in Northern Europe, the daily consumption is less than 5 g per capita. The physiological effects of different legumes vary significantly. These differences may result from the polysaccharides composition, in particular, the quantity and variety of dietary fibers and starch, protein make-up, and variability in phytochemical content. The majority of legumes contain phytochemicals: bioactive compounds, including enzyme inhibitors, phytohemagglutinins (lectins), phytoestrogens, oligosaccharides, saponins, and phenolic compounds, which play metabolic roles in humans who frequently consume these foods. Dietary intake of phytochemicals may provide health benefits, protecting against numerous diseases or disorders, such as coronary heart disease, diabetes, high blood pressure and inflammation. The synergistic or antagonistic effects of these phytochemical mixtures from food legumes, their interaction with other components of the diet, and the mechanism of their action have remained a challenge with regard to understanding the role of phytochemicals in health and diseases. Their mitigating effects and the mechanism of their action need to be further addressed if we are to understand the role of phytochemicals in health and diseases. This review provides an overview of the nutritional quality of legumes and their potential contribution in cardiometabolic risk prevention.", "title": "Nutritional quality of legumes, and their role in cardiometabolic risk prevention: a review." }, { "docid": "MED-5078", "text": "In this study, solid fermentation of steamed black soybean with various GRAS (Generally recognized as safe) filamentious-fungi including Aspergillus awamori, Aspergillus oryzae BCRC 30222, Aspergillus sojae BCRC 30103, Rhizopus azygosporus BCRC 31158 and Rhizopus sp. No. 2 was performed. Mutagenicity and antimutagenicity of the methanol extracts of unfermented and fermented steamed black soybeans against 4-nitroquinoline-N-oxide (4-NQO), a direct mutagen and Benzo[a]pyrene (B[a]P), an indirect mutagen, on Salmonella Typhimurium TA100 and TA 98, were examined. The methanol extracts of unfermented and fermented steamed black soybeans show no mutagenic activity for either test strains at the doses tested. The extracts inhibited mutagenesis by either 4-NQO or B[a]P in S. Typhimurium TA100 and TA98. Fermentation with fungi also enhanced the antimutagenic effect of black soybean while the antimutagenic effect of the fermented black soybeans extract varied with the starter organism, mutagen, and test strain of S. Typhimurium examined. Generally, the extracts of A. awamori-fermented black soybean exhibited the highest antimutagenic effect. With strain TA100, the inhibitory effects of 5.0 mg of A. awamori-fermented black soybean extract per plate on the mutagenic effects of 4-NQO and B[a]P were 92% and 89%, respectively, while the corresponding rates for extract of unfermented were 41% and 63%, respectively. With strain 98, the inhibition rates were 94 and 81% for the fermented bean extract and 58% and 44% for the unfermented bean extracts. Testing of extracts prepared from black soybean by A. awamori at temperatures 25, 30 and 35 degrees C and for times of 1-5 days revealed that, generally, the extract prepared from beans fermented at 30 degrees C for 3 days exhibited the greatest inhibition against the mutagenic effects of 4-NQO and B[a]P.", "title": "Mutagenic and antimutagenic effects of methanol extracts of unfermented and fermented black soybeans." }, { "docid": "MED-2141", "text": "We investigated the association between dietary patterns and insulin resistance in the 3871 healthy Korean adults from the 2007 to 2008 Korea National Health and Nutrition Examination Survey. The whole grains and beans pattern was associated with lower prevalence of insulin resistance (OR for highest quintile=0.80, 95% CI=0.61-1.03, P for trend=0.013). Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.", "title": "High intake of whole grains and beans pattern is inversely associated with insulin resistance in healthy Korean adult population." }, { "docid": "MED-5080", "text": "Bioactivity-guided fractionation of black bean (Phaseolus vulgaris) seed coats was used to determine the chemical identity of bioactive constituents, which showed potent antiproliferative and antioxidative activities. Twenty-four compounds including 12 triterpenoids, 7 flavonoids, and 5 other phytochemicals were isolated using gradient solvent fractionation, silica gel and ODS columns, and semipreparative and preparative HPLC. Their chemical structures were identified using MS, NMR, and X-ray diffraction analysis. Antiproliferative activities of isolated compounds against Caco-2 human colon cancer cells, HepG2 human liver cancer cells, and MCF-7 human breast cancer cells were evaluated. Among the compounds isolated, compounds 1, 2, 6, 7, 8, 13, 14, 15, 16, 19, and 20 showed potent inhibitory activities against the proliferation of HepG2 cells, with EC50 values of 238.8 +/- 19.2, 120.6 +/- 7.3, 94.4 +/- 3.4, 98.9 +/- 3.3, 32.1 +/- 6.3, 306.4 +/- 131.3, 156.9 +/- 11.8, 410.3 +/- 17.4, 435.9 +/- 47.7, 202.3 +/- 42.9, and 779.3 +/- 37.4 microM, respectively. Compounds 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 14, 15, 19, and 20 showed potent antiproliferative activities against Caco-2 cell growth, with EC50 values of 179.9 +/- 16.9, 128.8 +/- 11.6, 197.8 +/- 4.2, 105.9 +/- 4.7, 13.9 +/- 2.8, 35.1 +/- 2.9, 31.2 +/- 0.5, 71.1 +/- 11.9, 40.8 +/- 4.1, 55.7 +/- 8.1, 299.8 +/- 17.3, 533.3 +/- 126.0, 291.2 +/- 1.0, and 717.2 +/- 104.8 microM, respectively. Compounds 5, 7, 8, 9, 11, 19, 20 showed potent antiproliferative activities against MCF-7 cell growth in a dose-dependent manner, with EC50 values of 129.4 +/- 9.0, 79.5 +/- 1.0, 140.1 +/- 31.8, 119.0 +/- 7.2, 84.6 +/- 1.7, 186.6 +/- 21.1, and 1308 +/- 69.9 microM, respectively. Six flavonoids (compounds 14-19) showed potent antioxidant activity. These results showed the phytochemical extracts of black bean seed coats have potent antioxidant and antiproliferative activities.", "title": "Phytochemicals of black bean seed coats: isolation, structure elucidation, and their antiproliferative and antioxidative activities." }, { "docid": "MED-3132", "text": "Little is known about dietitians current practice in counselling clients about the use of legumes in a low fat, high fibre diet. An exploratory e-mail questionnaire was sent to members of Dietitians of Canada to assess: dietitian use and preferences for legumes, dietitian practice, opinions about clients attitudes and preferences, and resource needs. Counsellors (n=256) had high personal use of legumes (64% > or = 1 serving/week) and frequently recommended legumes in counselling. The legumes most preferred by respondents and their clients were: peanuts, kidney beans, split peas, chickpeas, and lentils. Respondents often recommended canned bean products (76%) and tofu (61%), but other legume grocery products were less often recommended. The most common client issues identified were: flatulence (87% agreed), lack of familiarity (85%), and knowledge of preparation (82%). Dietitians were not satisfied with current resources to support practice, especially those respondents providing primarily clinical counselling services. The most requested resources were: recipes (90%), pamphlets (82%), food demonstrations (75%) and Internet sites (63%). Client level research is now needed to confirm the importance of the issues identified and to develop and test strategies for legume promotion in counselling.", "title": "Legume promotion in counselling: an e-mail survey of dietitians." }, { "docid": "MED-2085", "text": "A diet rich in fruits and vegetables is known to decrease the risk of cardiovascular disease. However, the information regarding the antithrombotic activity (antiplatelet, anticoagulant, and fibrinolytic) of fruits and vegetables is scarce. The aim of this study was to assess the antithrombotic activity of extracts from fruits and vegetables widely consumed in central Chile. The study included samples of 19 fruits and 26 vegetables, representative of the local diet. The extracts prepared from each sample included an aqueous (juice or pressed solubles) and/or methanol-soluble fraction. The extracts were evaluated for antiplatelet, anticoagulant, and fibrinolytic activity in vitro at a final concentration of 1 mg/ml. The antiplatelet activity was assessed by platelet aggregation inhibition; anticoagulant activity was measured by the prothrombin time (PT), diluted prothrombin time (dPT), activated partial thromboplastin time (APTT), kaolin clotting time (KCT), and thrombin time. The fibrinolytic effect was determined with the euglobin clot lysis time and fibrin plate methods. Extracts of green beans and tomatoes inhibited platelet aggregation induced by ADP and arachidonic acid, in a concentration-dependent manner. The methanolic extracts of grapes prolonged the PT and dPT. Finally, extracts of raspberry prolonged the APTT and also presented fibrinolytic activity. In conclusion, from a screening that included a variety of fruits and vegetables, we found antiplatelet activity in green beans and tomatoes, anticoagulant activities in grapes and raspberries, whereas fibrinolytic activity was observed only in raspberries. Further investigations are necessary to advance in knowledge of the active compounds of these fruits and vegetables and their mechanisms of action.", "title": "Antiplatelet, anticoagulant, and fibrinolytic activity in vitro of extracts from selected fruits and vegetables." }, { "docid": "MED-5118", "text": "OBJECTIVE: To compare the effects of two commercially available soy milks (one made using whole soy beans, the other using soy protein isolate) with low-fat dairy milk on plasma lipid, insulin, and glucose responses. DESIGN: Randomized clinical trial, cross-over design. SUBJECTS: Participants were 30-65 years of age, n = 28, with pre-study LDL-cholesterol (LDL-C) concentrations of 160-220 mg/dL, not on lipid lowering medications, and with an overall Framingham risk score of <or=10%. INTERVENTION: Participants were required to consume sufficient milk to provide 25 g protein/d from each source. The protocol included three 4-week treatment phases, each separated from the next by a wash-out period of >or=4 weeks. RESULTS: Mean LDL-C concentration at the end of each phase (+/- SD) was 161 +/- 20, 161 +/- 26 and 170 +/- 24 mg/dL for the whole bean soy milk, the soy protein isolate milk, and the dairy milk, respectively (p = 0.9 between soy milks, p = 0.02 for each soy milk vs. dairy milk). No significant differences by type of milk were observed for HDL-cholesterol, triacylglycerols, insulin, or glucose. CONCLUSION: A 25 g dose of daily soy protein from soy milk led to a modest 5% lowering of LDL-C relative to dairy milk among adults with elevated LDL-C. The effect did not differ by type of soy milk and neither soy milk significantly affected other lipid variables, insulin or glucose.", "title": "Effect of two types of soy milk and dairy milk on plasma lipids in hypercholesterolemic adults: a randomized trial." }, { "docid": "MED-3894", "text": "The purpose of this study was to examine the effects of a natural carbohydrate (CHO) source in the form of sun-dried raisins (SDRs) vs. Sports Jelly Beans™ (SJBs) on endurance performance in trained cyclists and triathletes. Ten healthy men (18-33 years) completed 1 water-only acclimatization exercise trial and 2 randomized exercise trials administered in a crossover fashion. Each trial consisted of a 120-minute constant-intensity glycogen depletion period followed by a 10-km time trial (TT). During each experimental trial, participants consumed isocaloric amounts of SDRs or SJBs in 20-minute intervals. Measurements included time to complete 10-km TT, power output during 10-km TT, blood glucose levels and respiratory exchange ratio during glycogen depletion period, rate of perceived exertion (RPE), 'flow' questionnaire responses, and a hedonic (i.e., pleasantness) sensory acceptance test. There were no significant differences in endurance performance for TT time (SDRs vs. SJBs, 17.3 ± 0.4 vs. 17.3 ± 0.4 seconds) or power (229.3 ± 13.0 vs. 232.0 ± 13.6 W), resting blood glucose levels (5.8 ± 04 mmol·L(-1) for SDRs and 5.4 ± 0.2 mmol·L(-1) for SJBs), RPE, or flow experiences between SDR and SJB trials. However, the mean sensory acceptance scores were significantly higher for the SDRs compared to the SJBs (50.7 ± 1.7 vs. 44.3 ± 2.7). Consuming SDRs or SJBs during 120 minutes of intense cycling results in similar subsequent TT performances and are equally effective in maintaining blood glucose levels during exercise. Therefore, SDRs are a natural, pleasant, cost-effective CHO alternative to commercial SJBs that can be used during moderate- to high-intensity endurance exercise.", "title": "Sun-dried raisins are a cost-effective alternative to Sports Jelly Beans in prolonged cycling." }, { "docid": "MED-4869", "text": "This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, including flavouring agents, with a view to recommending acceptable daily intakes (ADIs) and to preparing specifications for identity and purity. The first part of the report contains a general discussion of the principles governing the toxicological evaluation and assessment of intake of food additives (in particular, flavouring agents). A summary follows of the Committee's evaluations of technical, toxicological and intake data for certain food additives (asparaginase from Aspergillus niger expressed in A. niger, calcium lignosulfonate (40-65), ethyl lauroyl arginate, paprika extract, phospholipase C expressed in Pichia pastoris, phytosterols, phytostanols and their esters, polydimethylsiloxane, steviol glycosides and sulfites [assessment of dietary exposure]) and 10 groups of related flavouring agents (aliphatic branched-chain saturated and unsaturated alcohols, aldehydes, acids and related esters; aliphatic linear alpha,beta-unsaturated aldehydes, acids and related alcohols, acetals and esters; aliphatic secondary alcohols, ketones and related esters; alkoxy-substituted allylbenzenes present in foods and essential oils and used as flavouring agents; esters of aliphatic acyclic primary alcohols with aliphatic linear saturated carboxylic acids; furan-substituted aliphatic hydrocarbons, alcohols, aldehydes, ketones, carboxylic acids and related esters, sulfides, disulfides and ethers; miscellaneous nitrogen-containing substances; monocyclic and bicyclic secondary alcohols, ketones and related esters; hydroxy- and alkoxy-substituted benzyl derivatives; and substances structurally related to menthol). Specifications for the following food additives were revised: canthaxanthin; carob bean gum and carob bean gum (clarified); chlorophyllin copper complexes, sodium and potassium salts; Fast Green FCF; guar gum and guar gum (clarified); iron oxides; isomalt; monomagnesium phosphate; Patent Blue V; Sunset Yellow FCF; and trisodium diphosphate. Re-evaluation of flavouring agents for which estimated intake was based on anticipated poundage data was carried out for 2-isopropyl- N,2,3-trimethylbutyramide (No. 1595) and L-monomenthyl glutarate (No. 1414). Annexed to the report are tables summarizing the Committee's recommendations for intakes and toxicological evaluations of the food additives considered.", "title": "Evaluation of certain food additives." }, { "docid": "MED-2150", "text": "Previous investigations, of adolescent diet recalled in adulthood, found lower risk for benign breast disease (BBD) with higher intakes of vegetable fat and nuts during high school. We investigate whether vegetable protein and fat, derived from diets reported during pre-adolescence and adolescence, are associated with subsequent risk for BBD in young women. The Growing Up Today Study includes 9,039 females, 9–15 years in 1996, who completed questionnaires annually through 2001, and then in 2003, 2005, 2007, and 2010. Food frequency questionnaires (1996–2001) obtained intake data on a variety of foods. Beginning in 2005, women (18–30 years) reported whether they had ever been diagnosed with BBD that was confirmed by breast biopsy (n = 112 cases). Logistic regression estimated associations between intakes of vegetable protein and fat and biopsy-confirmed BBD. Those individual foods that were the largest contributors of protein and fat in this cohort were also investigated. In analyses of intakes from 1996 through 1998, when our cohort was youngest, vegetable fat (OR = 0.72/(10 gm/day), 95 % CI 0.53–0.98; p = 0.04) was inversely associated with BBD risk. The greatest sources of vegetable fat and protein in these girls were peanut butter, peanuts, nuts, beans (beans, lentils, and soybeans), and corn. A daily serving of any one of these was associated with lower risk (OR = 0.32/(serv/day), 95 % CI 0.13–0.79; p = 0.01). Peanut butter (and nuts) at age 11 years was inversely associated with risk (p = 0.01). In analyses of intakes at age 14 years, vegetable protein was associated with lower BBD risk (OR = 0.64/(10 gm/day), 95 % CI 0.43–0.95; p = 0.03). A daily serving at 14 years of any one of the foods was associated with lower risk (OR = 0.34, 95 % CI 0.16–0.75; p = 0.01), as was peanut butter (and nuts) (p = 0.02). Girls with a family history of breast cancer had significantly lower risk if they consumed these foods or vegetable fat. In conclusion, consumption of vegetable protein, fat, peanut butter, or nuts by older girls may help reduce their risk of BBD as young women.", "title": "Vegetable protein and vegetable fat intakes in pre-adolescent and adolescent girls, and risk for benign breast disease in young women" }, { "docid": "MED-719", "text": "In addition to causing embarrassment and unease, flatulence is linked to a variety of symptoms, some of which may be distressing. This review describes the origins of intestinal gas, its composition and methods which have been developed for its analysis. Emphasis is placed upon the effects of legumes in the diet in producing excessive intestinal gas and, particularly, on the role of raffinose-type oligosaccharides, containing alpha-galactosidic groupings. Suggestions for overcoming the problem are presented, including drug treatment, enzyme treatment, food processing and plant breeding. It is emphasised that removal of all raffinose-oligosaccharides from beans does not remove the problem of flatulence in animals and man; the compounds responsible--though assumed to be polysaccharides (or polysaccharide-derived oligomers formed by processing or cooking)--have yet to be characterised.", "title": "Flatulence--causes, relation to diet and remedies." }, { "docid": "MED-724", "text": "In addition to causing embarrassment and unease, flatulence is linked to a variety of symptoms, some of which may be distressing. This review describes the origins of intestinal gas, its composition and methods which have been developed for its analysis. Emphasis is placed upon the effects of legumes in the diet in producing excessive intestinal gas and, particularly, on the role of raffinose-type oligosaccharides, containing alpha-galactosidic groupings. Suggestions for overcoming the problem are presented, including drug treatment, enzyme treatment, food processing and plant breeding. It is emphasised that removal of all raffinose-oligosaccharides from beans does not remove the problem of flatulence in animals and man; the compounds responsible--though assumed to be polysaccharides (or polysaccharide-derived oligomers formed by processing or cooking)--have yet to be characterised.", "title": "Flatulence--causes, relation to diet and remedies." }, { "docid": "MED-890", "text": "A case-control study was carried out in Harbin city to assess the role of diet in the aetiology of colorectal cancer. A total of 336 incident cases of histologically confirmed colorectal cancer (111 colon cancer and 225 rectal cancer) and an equal number of controls with other non-neoplastic diseases were interviewed in hospital wards. Data concerning the average frequency of consumption and amount consumed of single food items were obtained by a dietary history questionnaire. Odds ratios and their confidence limits were computed. Multiple regression for risk status was also used. Vegetables, particularly green vegetables, chives and celery, have a strong protective effect against colorectal cancer. Reduced consumption of meat, eggs, bean products and grain was associated with increasing risk for cancer of the rectum. Alcohol intake was found to be an important risk factor for developing colon cancer and male rectal cancer.", "title": "Diet and cancer of the colon and rectum: a case-control study in China." }, { "docid": "MED-4165", "text": "Ergothioneine is a native membrane-impermeable thiol compound that is specifically accumulated in cells via the organic cation transporter OCTN1. In humans, OCTN1 and ergothioneine have been implicated in the etiopathogenesis of autoimmune disorders. However, available evidence about dietary sources and the functional role of ergothioneine in human physiology is scarce. Here, we analyzed the ergothioneine content in common foods using liquid chromatography tandem-mass spectrometry. Additionally, we assessed the protective potency of ergothioneine against various oxidative stressors in OCTN1-expressing cells in comparison with the main intracellular thiol antioxidant glutathione by evaluating cell viability with the MTT reduction assay. Only some food contained ergothioneine with highest concentrations detected in specialty mushrooms, kidney, liver, black and red beans, and oat bran. Ergothioneine exhibited cell protection only against copper(II)-induced toxicity but was far less potent than glutathione, indicting that ergothioneine is not involved in the intracellular antioxidant thiol defense system.", "title": "Dietary sources and antioxidant effects of ergothioneine." }, { "docid": "MED-875", "text": "AIMS: The purpose of this study was to search for a novel quorum sensing inhibitor and analyse its inhibitory activity. METHODS AND RESULTS: Quorum sensing inhibition was monitored using the Tn-5 mutant, Chromobacterium violaceum CV026. Vanilla beans (Vanilla planifolia Andrews) were extracted using 75% (v/v) aqueous methanol and added to C. violaceum CV026 cultures. Inhibitory activity was measured by quantifying violacein production using a spectrophotometer. The results have revealed that vanilla extract significantly reduced violacein production in a concentration-dependent manner, indicating inhibition of quorum sensing. CONCLUSIONS: Vanilla, a widely used spice and flavour, can inhibit bacterial quorum sensing. SIGNIFICANCE AND IMPACT OF THE STUDY: The results suggest that the intake of vanilla-containing food materials might promote human health by inhibiting quorum sensing and preventing bacterial pathogenesis. Further studies are required to isolate specific substances from vanilla extract acting as quorum sensing inhibitors.", "title": "Inhibition of bacterial quorum sensing by vanilla extract." }, { "docid": "MED-5354", "text": "This review focuses on the possible role in human health of the consumption of lignan-rich foods. Most of the plant lignans in human foods are converted by the intestinal microflora in the upper part of the large bowel to enterolactone and enterodiol, called mammalian or enterolignans. The protective role of these compounds, particularly in chronic Western diseases, is discussed. Evidence suggests that fiber- and lignan-rich whole-grain cereals, beans, berries, nuts, and various seeds are the main protective foods. Many factors, in addition to diet, such as intestinal microflora, smoking, antibiotics, and obesity affect circulating lignan levels in the body. Lignan-rich diets may be beneficial, particularly if consumed for life. Experimental evidence in animals has shown clear anticarcinogenic effects of flaxseed or pure lignans in many types of cancer. Many epidemiological results are controversial, partly because the determinants of plasma enterolactone are very different in different countries. The source of the lignans seems to play a role because other factors in the food obviously participate in the protective effects. The results are promising, but much work is still needed in this area of medicine.", "title": "Lignans and human health." }, { "docid": "MED-2195", "text": "The objective of this study was to evaluate the precursors of acrylamide formation in sweet potato (SP) (Ipomoea batatas L. Lam) chips and to determine the effect of different types of vegetable oils (VOs), that is, palm olein, coconut oil, canola oil, and soya bean oil, on acrylamide formation. The reducing sugars and amino acids in the SP slices were analyzed, and the acrylamide concentrations of SP chips were measured. SP chips that were fried in a lower degree of unsaturation oils contained a lower acrylamide concentration (1443 μg/kg), whereas those fried with higher degree of unsaturated oils contained a higher acrylamide concentration (2019 μg/kg). SP roots were found to contain acrylamide precursors, that is, 4.17 mg/g glucose and 5.05 mg/g fructose, and 1.63 mg/g free asparagine. The type of VO and condition used for frying, significantly influenced acrylamide formation. This study clearly indicates that the contribution of lipids in the formation of acrylamide should not be neglected. © 2013 Institute of Food Technologists®", "title": "The influence of deep frying using various vegetable oils on acrylamide formation in sweet potato (Ipomoea batatas L. Lam) chips." }, { "docid": "MED-1150", "text": "The “organic food” market is the fastest growing food sector, yet it is unclear whether organically raised food is nutritionally superior to conventionally grown food and whether consuming organic food bestows health benefits. In order to evaluate potential health benefits of organic foods, we used the well-characterized fruit fly Drosophila melanogaster as a model system. Fruit flies were raised on a diets consisting of extracts of either conventionally or organically raised produce (bananas, potatoes, raisins, soy beans). Flies were then subjected to a variety of tests designed to assess overall fly health. Flies raised on diets made from organically grown produce had greater fertility and longevity. On certain food sources, greater activity and greater stress resistance was additionally observed, suggesting that organic food bestows positive effects on fly health. Our data show that Drosophila can be used as a convenient model system to experimentally test potential health effects of dietary components. Using this system, we provide evidence that organically raised food may provide animals with tangible benefits to overall health.", "title": "Organically Grown Food Provides Health Benefits to Drosophila melanogaster" }, { "docid": "MED-720", "text": "Bloating, abdominal distention, and flatulence represent very frequent complaints in functional disorders but their pathophysiology and treatment are largely unknown. Patients frequently associate these symptoms with excessive intestinal gas and the reduction of gas production may represent an effective strategy. The aim was to evaluate the effect of alpha-galactosidase administration, in a randomized double-blind placebo-controlled protocol, on intestinal gas production and gas-related symptoms after a challenge test meal in healthy volunteers. Eight healthy volunteers ingested 300 or 1200 GalU of alpha-galactosidase or placebo during a test meal containing 420 g of cooked beans. Breath hydrogen excretion and occurrence of bloating, abdominal pain, discomfort, flatulence, and diarrhea were measured for 8 hr. The administration of 1200 GalU of alpha-galactosidase induced a significant reduction of both breath hydrogen excretion and severity of flatulence. A reduction in severity was apparent for all considered symptoms, but both 300 and 1200 GalU induced a significant reduction in the total symptom score. Alpha-galactosidase reduced gas production following a meal rich in fermentable carbohydrates and may be helpful in patients with gas-related symptoms.", "title": "The effect of oral alpha-galactosidase on intestinal gas production and gas-related symptoms." } ]
366
ERAP1 SNPs are epistatic to HLA alleles for ankylosing spondylitis.
[ { "docid": "13956305", "text": "Ankylosing spondylitis (AS) is a common, highly heritable, inflammatory arthritis for which HLA-B*27 is the major genetic risk factor, although its role in the aetiology of AS remains elusive. To better understand the genetic basis of the MHC susceptibility loci, we genotyped 7,264 MHC SNPs in 22,647 AS cases and controls of European descent. We impute SNPs, classical HLA alleles and amino-acid residues within HLA proteins, and tested these for association to AS status. Here we show that in addition to effects due to HLA-B*27 alleles, several other HLA-B alleles also affect susceptibility. After controlling for the associated haplotypes in HLA-B, we observe independent associations with variants in the HLA-A, HLA-DPB1 and HLA-DRB1 loci. We also demonstrate that the ERAP1 SNP rs30187 association is not restricted only to carriers of HLA-B*27 but also found in HLA-B*40:01 carriers independently of HLA-B*27 genotype.", "title": "Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1" } ]
[ { "docid": "97884", "text": "The term spondyloarthropathy (SpA) describes and defines a group of related inflammatory joint disease that share characteristic clinical features and a unique association with the major histocompatibility complex class I molecule HLA-B27. Five subgroups can be differentiated: ankylosing spondylitis, reactive arthritis, psoriatic arthritis, arthritis associated with inflammatory bowel disease, and undifferentiated SpA. The sacroiliac joints are centrally involved in the SpA, most clearly and pathognomonic in ankylosing spondylitis, in which most patients are affected early in the disease. Overcoming some of the diagnostic difficulties of early sacroiliitis, dynamic magnetic resonance imaging was shown to visualize both acute and chronic changes in the sacroiliac joints. The inflammation in the sacroiliac joints in patients with SpA was recently examined in more detail; using immunohistology and in situ hybridrization, T cells, macrophages, and various cytokines were found in infiltrates. Biopsy specimens were obtained under guided computed tomography, and in the same study, intra-articular corticosteroid treatment was successfully undertaken. Further investigation of such biopsy specimens showed the absence of DNA of reactive arthritis-associated bacteria. The pathogenesis of the SpA and the reason for the tropism for the sacroiliac joints is still obscure. The nature of the relation of the genetic background of SpA to initially triggering bacterial infections remains to be established. In chronic disease, autoimmune mechanisms might be more important.", "title": "The sacroiliac joint in the spondyloarthropathies." }, { "docid": "1265945", "text": "Genome-wide association studies of the related chronic inflammatory bowel diseases (IBD) known as Crohn's disease and ulcerative colitis have shown strong evidence of association to the major histocompatibility complex (MHC). This region encodes a large number of immunological candidates, including the antigen-presenting classical human leukocyte antigen (HLA) molecules. Studies in IBD have indicated that multiple independent associations exist at HLA and non-HLA genes, but they have lacked the statistical power to define the architecture of association and causal alleles. To address this, we performed high-density SNP typing of the MHC in >32,000 individuals with IBD, implicating multiple HLA alleles, with a primary role for HLA-DRB1*01:03 in both Crohn's disease and ulcerative colitis. Noteworthy differences were observed between these diseases, including a predominant role for class II HLA variants and heterozygous advantage observed in ulcerative colitis, suggesting an important role of the adaptive immune response in the colonic environment in the pathogenesis of IBD.", "title": "High density mapping of the MHC identifies a shared role for HLA-DRB1*01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis" }, { "docid": "34481589", "text": "Biological agents are widely used in rheumatology, dermatology and inflammatory bowel disease. Evidence about their efficacy and safety has been strengthened for all those therapeutic indications over the last decade. Biosimilar agents are monoclonal antibodies similar to previously approved biologics. In the European Union, they have been approved for all the indications in the management of immune-mediated inflammatory diseases (IMIDs), although data only in rheumatoid arthritis and ankylosing spondylitis are currently available. Direct evidence on efficacy, safety, and immunogenicity of biosimilars is mandatory in psoriasis, psoriatic arthritis, and inflammatory bowel disease, as well as in children. Based on the current evidence in the literature, we present the joint official position of the Italian Societies of Rheumatology, Dermatology and Inflammatory Bowel Disease on the use of biosimilars in IMIDs.", "title": "The use of biosimilars in immune-mediated disease: A joint Italian Society of Rheumatology (SIR), Italian Society of Dermatology (SIDeMaST), and Italian Group of Inflammatory Bowel Disease (IG-IBD) position paper." }, { "docid": "8428837", "text": "OBJECTIVE Ankylosing spondylitis (AS) and spondyloarthropathy (SpA) are inflammatory diseases of unknown etiology. Various exogenous and endogenous (inherited) factors play a role in their development. Sulfasalazine (SSZ) is generally accepted as a disease modifying drug in the treatment of AS and SpA. Which part of SSZ, 5-acetylsalicylic acid (5-ASA, mesalazine) or sulfapyridine (SP), is the effective moiety is unknown. As the bowel, colon, and the ileum play an important role in the development of AS and SpA, it may be possible that 5-ASA is the effective moiety, with a similar mode of action as in the treatment of inflammatory bowel disease. To determine the efficacy of 5-ASA an open pilot study was done in 2 groups of patients with SpA. METHODS Twenty patients with SpA, who were taking SSZ, were switched to 5-ASA (Pentasa), and 19 patients with active SpA were treated with 5-ASA without previous administration of SSZ. RESULTS In the first group, 17 (85%) patients responded with respect to the physician global clinical assessment compared to the previous SSZ treatment period; whereas in the second patient group a statistically significant improvement was obtained in erythrocyte sedimentation rate. CONCLUSION The results support our hypothesis that 5-ASA might be the active moiety of SSZ in the treatment of SpA.", "title": "Treatment of spondyloarthropathy with 5-aminosalicylic acid (mesalazine): an open trial." }, { "docid": "2095573", "text": "BACKGROUND LDL cholesterol has a causal role in the development of cardiovascular disease. Improved understanding of the biological mechanisms that underlie the metabolism and regulation of LDL cholesterol might help to identify novel therapeutic targets. We therefore did a genome-wide association study of LDL-cholesterol concentrations. METHODS We used genome-wide association data from up to 11,685 participants with measures of circulating LDL-cholesterol concentrations across five studies, including data for 293 461 autosomal single nucleotide polymorphisms (SNPs) with a minor allele frequency of 5% or more that passed our quality control criteria. We also used data from a second genome-wide array in up to 4337 participants from three of these five studies, with data for 290,140 SNPs. We did replication studies in two independent populations consisting of up to 4979 participants. Statistical approaches, including meta-analysis and linkage disequilibrium plots, were used to refine association signals; we analysed pooled data from all seven populations to determine the effect of each SNP on variations in circulating LDL-cholesterol concentrations. FINDINGS In our initial scan, we found two SNPs (rs599839 [p=1.7x10(-15)] and rs4970834 [p=3.0x10(-11)]) that showed genome-wide statistical association with LDL cholesterol at chromosomal locus 1p13.3. The second genome screen found a third statistically associated SNP at the same locus (rs646776 [p=4.3x10(-9)]). Meta-analysis of data from all studies showed an association of SNPs rs599839 (combined p=1.2x10(-33)) and rs646776 (p=4.8x10(-20)) with LDL-cholesterol concentrations. SNPs rs599839 and rs646776 both explained around 1% of the variation in circulating LDL-cholesterol concentrations and were associated with about 15% of an SD change in LDL cholesterol per allele, assuming an SD of 1 mmol/L. INTERPRETATION We found evidence for a novel locus for LDL cholesterol on chromosome 1p13.3. These results potentially provide insight into the biological mechanisms that underlie the regulation of LDL cholesterol and might help in the discovery of novel therapeutic targets for cardiovascular disease.", "title": "LDL-cholesterol concentrations: a genome-wide association study" }, { "docid": "2647374", "text": "INTRODUCTION Deregulated or excessive host immune responses contribute to the pathogenesis of sepsis. Toll-like receptor (TLR) signaling pathways and their negative regulators play a pivotal role in the modulation of host immune responses and the development of sepsis. The objective of this study was to investigate the association of variants in the TLR signaling pathway genes and their negative regulator genes with susceptibility to sepsis in the Chinese Han population. METHODS Patients with severe sepsis (n = 378) and healthy control subjects (n = 390) were enrolled. Five genes, namely TLR2, TLR4, TLR9, MyD88 and TOLLIP, were investigated for their association with sepsis susceptibility by a tag single nucleotide polymorphism (SNP) strategy. Twelve tag SNPs were selected based on the data of Chinese Han in Beijing from the HapMap project and genotyped by direct sequencing. The mRNA expression levels of TOLLIP were determined using real-time quantitative Polymerase Chain Reaction (PCR) assays, and concentrations of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS Our results showed that the minor C-allele of rs5743867 in TOLLIP was significantly associated with the decreased risk of sepsis (Padj = 0.00062, odds ratio (OR)adj = 0.71, 95% confidence interval (CI) 0.59 to 0.86) after adjustment for covariates in multiple logistic regression analysis. A 3-SNP haplotype block harboring the associated SNP rs5743867 also displayed strong association with omnibus test P value of 0.00049. Haplotype GTC showed a protective role against sepsis (Padj = 0.0012), while haplotype GCT showed an increased risk for sepsis (Padj = 0.00092). After exposure to lipopolysaccharide (LPS), TOLLIP mRNA expression levels in peripheral blood mononuclear cells (PBMCs) from homozygotes for the rs5743867C allele were significantly higher than in heterozygotes and homozygotes for the rs5743867T allele (P = 0.013 and P = 0.01, respectively). Moreover, the concentrations of TNF-α and IL-6 in culture supernatants were significantly lower in the subjects of rs5743867CC genotype than in CT and TT genotype subjects (P = 0.016 and P = 0.003 for TNF-α; P = 0.01 and P = 0.002 for IL-6, respectively). CONCLUSIONS Our findings indicated that the variants in TOLLIP were significantly associated with sepsis susceptibility in the Chinese Han population.", "title": "Variants in the Toll-interacting protein gene are associated with susceptibility to sepsis in the Chinese Han population" }, { "docid": "1388704", "text": "Single nucleotide polymorphisms (SNPs) are an abundant form of genome variation, distinguished from rare variations by a requirement for the least abundant allele to have a frequency of 1% or more. A wide range of genetics disciplines stand to benefit greatly from the study and use of SNPs. The recent surge of interest in SNPs stems from, and continues to depend upon, the merging and coincident maturation of several research areas, i.e. (i) large-scale genome analysis and related technologies, (ii) bio-informatics and computing, (iii) genetic analysis of simple and complex disease states, and (iv) global human population genetics. These fields will now be propelled forward, often into uncharted territories, by ongoing discovery efforts that promise to yield hundreds of thousands of human SNPs in the next few years. Major questions are now being asked, experimentally, theoretically and ethically, about the most effective ways to unlock the full potential of the upcoming SNP revolution.", "title": "The essence of SNPs." }, { "docid": "16734530", "text": "BACKGROUND Breast cancer is the most common malignancy in women. There is increasing evidence suggesting that ORAI1, components of store-operated calcium channel, play a pivotal role in breast cancer progression and metastasis. METHODS A total of 384 female patients with breast cancer were included in this study. We selected five representative tagging ORAI1 SNPs from HapMap database with minimum allele frequency (MAF) >10%. Genotyping was performed using TaqMan allelic discrimination assay. Chi-square (χ²) test was used to analyze statistical differences among control and patient groups in genotype and allelic frequencies. RESULTS Two of the ORAI1 SNPs (rs12320939 and rs12313273) were associated with estrogen receptors positive in breast cancer patients under the recessive model. When the Bonferroni correction was performed, the significance still existed. In addition, rs12320939 also associated with the lymph nodal involvement. CONCLUSION We showed that genetic polymorphisms of ORAI1 associated strongly with lymph nodal involvement and estrogen receptors (ERs) positive breast cancer patients in a Taiwanese population.", "title": "The Association between Single-Nucleotide Polymorphisms of ORAI1 Gene and Breast Cancer in a Taiwanese Population" }, { "docid": "1576955", "text": "Mutations in daf-2 and age-1 cause a dramatic increase in longevity as well as developmental arrest at the dauer diapause stage in Caenorhabditis elegans. daf-2 and age-1 encode components of an insulin-like signaling pathway. Both daf-2 and age-1 act at a similar point in the genetic epistasis pathway for dauer arrest and longevity and regulate the activity of the daf-16 gene. Mutations in daf-16 cause a dauer-defective phenotype and are epistatic to the diapause arrest and life span extension phenotypes of daf-2 and age-1 mutants. Here we show that mutations in this pathway also affect fertility and embryonic development. Weak daf-2 alleles, and maternally rescued age-1 alleles that cause life span extension but do not arrest at the dauer stage, also reduce fertility and viability. We find that age-1(hx546) has reduced both maternal and zygotic age-1 activity. daf-16 mutations suppress all of the daf-2 and age-1 phenotypes, including dauer arrest, life span extension, reduced fertility, and viability defects. These data show that insulin signaling, mediated by DAF-2 through the AGE-1 phosphatidylinositol-3-OH kinase, regulates reproduction and embryonic development, as well as dauer diapause and life span, and that DAF-16 transduces these signals. The regulation of fertility, life span, and metabolism by an insulin-like signaling pathway is similar to the endocrine regulation of metabolism and fertility by mammalian insulin signaling.", "title": "An insulin-like signaling pathway affects both longevity and reproduction in Caenorhabditis elegans." }, { "docid": "11884292", "text": "BACKGROUND AND AIMS We adopted the twin method to disentangle the genetic and environmental components of susceptibility to coeliac disease (CD). We estimated disease concordance rate by zygosity and HLA genotypes, discordance times, progression rates to disease, and heritability. METHODS We crosslinked the Italian Twin Registry with the membership lists of the Italian Coeliac Disease Association and recruited 23 monozygotic (MZ) and 50 dizygotic (DZ) twin pairs with at least one affected member. Zygosity was assigned by DNA fingerprinting, and HLA-DQ and DR alleles were genotyped. Disease status was ascertained by antiendomysial, anti-human tissue transglutaminase antibodies, and bowel biopsy. RESULTS Concordance was significantly higher in MZ (83.3% probandwise, 71.4% pairwise) than in DZ (16.7% probandwise, 9.1% pairwise) pairs. Concordance was not affected by sex or HLA genotype of the co-twin and being MZ was significantly associated with the occurrence of CD (Cox adjusted hazard ratio 14.3 (95% confidence interval 4.0-50.3)). In 90% of concordant pairs the discordance time was <or=2 years. MZ and DZ co-twins had 70% and 9% cumulative probability of having symptomatic or silent forms of CD, respectively, within five years. Under ACE (additive genetic, common, and unshared environmental factors) models, with CD population prevalences of 1/91 and 1/1000, heritability estimates were 87% and 57%, respectively. CONCLUSION MZ pairs have a high probability of being concordant, regardless of sex or HLA genotype. Most of the affected co-twins receive a diagnosis within two years. A remarkable proportion of phenotypic variance is due to genetic factors.", "title": "Concordance, disease progression, and heritability of coeliac disease in Italian twins." }, { "docid": "11527199", "text": "Background Current criteria for the selection of unrelated donors for hematopoietic cell transplantation (HCT) include matching for the alleles of each human leukocyte antigen (HLA) locus within the major histocompatibility complex (MHC). Graft-versus-host disease (GVHD), however, remains a significant and potentially life-threatening complication even after HLA-identical unrelated HCT. The MHC harbors more than 400 genes, but the total number of transplantation antigens is unknown. Genes that influence transplantation outcome could be identified by using linkage disequilibrium (LD)-mapping approaches, if the extended MHC haplotypes of the unrelated donor and recipient could be defined.", "title": "MHC Haplotype Matching for Unrelated Hematopoietic Cell Transplantation" }, { "docid": "380526", "text": "Hypospadias is a common congenital malformation of the male external genitalia. We performed a genome-wide association study using pooled DNA from 436 individuals with hypospadias (cases) and 494 controls of European descent and selected the highest ranked SNPs for individual genotyping in the discovery sample, an additional Dutch sample of 133 cases and their parents, and a Swedish series of 266 cases and 402 controls. Individual genotyping of two SNPs (rs1934179 and rs7063116) in DGKK, encoding diacylglycerol kinase κ, produced compelling evidence for association with hypospadias in the discovery sample (allele-specific odds ratio (OR) = 2.5, P = 2.5 × 10−11 and OR = 2.3, P = 2.9 × 10−9, respectively) and in the Dutch (OR = 3.9, P = 2.4 × 10−5 and OR = 3.8, P = 3.4 × 10−5) and Swedish (OR = 2.5, P = 2.6 × 10−8 and OR = 2.2, P = 2.7 × 10−6) replication samples. Expression studies showed expression of DGKK in preputial tissue of cases and controls, which was lower in carriers of the risk allele of rs1934179 (P = 0.047). We propose DGKK as a major risk gene for hypospadias.", "title": "Common variants in DGKK are strongly associated with risk of hypospadias" }, { "docid": "25571386", "text": "BACKGROUND Two inflammatory disorders, type 1 diabetes and celiac disease, cosegregate in populations, suggesting a common genetic origin. Since both diseases are associated with the HLA class II genes on chromosome 6p21, we tested whether non-HLA loci are shared. METHODS We evaluated the association between type 1 diabetes and eight loci related to the risk of celiac disease by genotyping and statistical analyses of DNA samples from 8064 patients with type 1 diabetes, 9339 control subjects, and 2828 families providing 3064 parent-child trios (consisting of an affected child and both biologic parents). We also investigated 18 loci associated with type 1 diabetes in 2560 patients with celiac disease and 9339 control subjects. RESULTS Three celiac disease loci--RGS1 on chromosome 1q31, IL18RAP on chromosome 2q12, and TAGAP on chromosome 6q25--were associated with type 1 diabetes (P<1.00x10(-4)). The 32-bp insertion-deletion variant on chromosome 3p21 was newly identified as a type 1 diabetes locus (P=1.81x10(-8)) and was also associated with celiac disease, along with PTPN2 on chromosome 18p11 and CTLA4 on chromosome 2q33, bringing the total number of loci with evidence of a shared association to seven, including SH2B3 on chromosome 12q24. The effects of the IL18RAP and TAGAP alleles confer protection in type 1 diabetes and susceptibility in celiac disease. Loci with distinct effects in the two diseases included INS on chromosome 11p15, IL2RA on chromosome 10p15, and PTPN22 on chromosome 1p13 in type 1 diabetes and IL12A on 3q25 and LPP on 3q28 in celiac disease. CONCLUSIONS A genetic susceptibility to both type 1 diabetes and celiac disease shares common alleles. These data suggest that common biologic mechanisms, such as autoimmunity-related tissue damage and intolerance to dietary antigens, may be etiologic features of both diseases.", "title": "Shared and distinct genetic variants in type 1 diabetes and celiac disease." }, { "docid": "991139", "text": "The CC genotype of the interleukin (IL)-28B.rs12979860 gene has been associated with spontaneous hepatitis C virus (HCV) clearance and treatment response. The distribution and correlation of an IL28B.rs12979860 single-nucleotide polymorphism (SNP) with HCV-specific cell-mediated immune (CMI) responses among Egyptian healthcare workers (HCWs) is not known. We determined this relationship in 402 HCWs who serve a patient cohort with ~85 % HCV prevalence. We enrolled 402 HCWs in four groups: group 1 (n = 258), seronegative aviremic subjects; group 2 (n = 25), seronegative viremic subjects; group 3 (n = 41), subjects with spontaneously resolved HCV infection; and group 4 (n = 78), chronic HCV patients. All subjects were tested for an HCV-specific CMI response using an ex-vivo interferon-gamma (IFNγ) ELISpot assay with nine HCV genotype-4a overlapping 15-mer peptide pools corresponding to all of the HCV proteins. All subjects were tested for IL28B.rs12979860 SNP by real-time PCR. An HCV-specific CMI was demonstrated in ~27 % of the seronegative aviremic HCWs (group 1), suggesting clearance of infection after low-level exposure to HCV. The frequency of IL28B.rs12979860 C allele homozygosity in the four groups was 49 %, 48 %, 49 %, and 23 %, while that of the T allele was 14 %, 16 %, 12 and 19 %, respectively, suggesting differential distributions among subjects with different HCV status. As reported, IL28B.rs12979860 predicted the outcome of HCV infection (p < 0.05), but we did not find any relationship between the IL28B genotypes and the outcome of HCV-specific CMI responses in the four groups (p > 0.05). The data show differential IL28B.rs12979860 genotype distribution among Egyptian HCWs with different HCV status and could not predict the outcome of HCV-specific CMI responses.", "title": "Differential distribution of IL28B.rs12979860 single-nucleotide polymorphism among Egyptian healthcare workers with and without a hepatitis C virus-specific cellular immune response" }, { "docid": "20399078", "text": "The recommended treatment for patients with chronic hepatitis C, pegylated interferon-α (PEG-IFN-α) plus ribavirin (RBV), does not provide sustained virologic response (SVR) in all patients. We report a genome-wide association study (GWAS) to null virological response (NVR) in the treatment of patients with hepatitis C virus (HCV) genotype 1 within a Japanese population. We found two SNPs near the gene IL28B on chromosome 19 to be strongly associated with NVR (rs12980275, P = 1.93 × 10−13, and rs8099917, 3.11 × 10−15). We replicated these associations in an independent cohort (combined P values, 2.84 × 10−27 (OR = 17.7; 95% CI = 10.0–31.3) and 2.68 × 10−32 (OR = 27.1; 95% CI = 14.6–50.3), respectively). Compared to NVR, these SNPs were also associated with SVR (rs12980275, P = 3.99 × 10−24, and rs8099917, P = 1.11 × 10−27). In further fine mapping of the region, seven SNPs (rs8105790, rs11881222, rs8103142, rs28416813, rs4803219, rs8099917 and rs7248668) located in the IL28B region showed the most significant associations (P = 5.52 × 10−28–2.68 × 10−32; OR = 22.3–27.1). Real-time quantitative PCR assays in peripheral blood mononuclear cells showed lower IL28B expression levels in individuals carrying the minor alleles (P = 0.015).", "title": "Genome-wide association of IL28B with response to pegylated interferon-α and ribavirin therapy for chronic hepatitis C" }, { "docid": "15716328", "text": "Endoplasmic reticulum (ER)-associated aminopeptidase (ERAP)1 has been implicated in the final proteolytic processing of peptides presented by major histocompatibility complex (MHC) class I molecules. To evaluate the in vivo role of ERAP1, we have generated ERAP1-deficient mice. Cell surface expression of the class Ia molecules H-2Kb and H-2Db and of the class Ib molecule Qa-2 was significantly reduced in these animals. Although cells from mutant animals exhibited reduced capacity to present several self- and foreign antigens to Kb-, Db-, or Qa-1b–restricted CD8+ cytotoxic T cells, presentation of some antigens was unaffected or significantly enhanced. Consistent with these findings, mice generated defective CD8+ T cell responses against class I–presented antigens. These findings reveal an important in vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules.", "title": "In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules" }, { "docid": "11090688", "text": "The weight lowering potential of glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) is inter-individually different and clinically unpredictable. The potential role of genetic variability of GLP-1R on body weight response to GLP-1 RAs in obese women with polycystic ovary syndrome (PCOS) has not yet been evaluated. Fifty-seven obese women with PCOS (aged 30.7 ± 7.0, BMI 38.6 ± 5.3 kg/m2) were assigned to liraglutide 1.2 mg QD s.c. for 12 weeks and classified as strong responders regarding weight loss if they lost 5 % or more of their initial body weight. They were genotyped for common GLP-1R single nucleotide polymorphisms (SNPs) rs6923761 and rs10305420. Changes of measures of obesity were measured before and at the end of the treatment. Twenty out of 57 subjects were strong responders and lost 7.38 ± 1.74 compared to 2.11 ± 2.17 kg lost in poor responders. Carriers of at least one polymorphic rs10305420 allele had poor treatment response compared to carriers of two wild type alleles (OR = 0.27, 95 % CI = 0.09–0.85, P = 0.025). Carriers of at least one polymorphic rs6923761 allele tended to have stronger treatment response compared to carriers of two wild type alleles (OR = 3.06, 95 % CI = 0.96–9.74, P = 0.058). Fasting glucose and glucose after oral glucose tolerance test (OGTT) comparably decreased in both groups when compared to baseline, whereas no within treatment differences were found in androgen profile. Gastrointestinal adverse events were transit and balanced between strong and poor responders. GLP-1R rs10305420 polymorphism explained some of the inter-individual differences in response to liraglutide regarding weight loss in obese PCOS women.", "title": "Genetic variability in GLP-1 receptor is associated with inter-individual differences in weight lowering potential of liraglutide in obese women with PCOS: a pilot study" }, { "docid": "13905670", "text": "The clinical course and eventual outcome, or prognosis, of complex diseases varies enormously between affected individuals. This variability critically determines the impact a disease has on a patient's life but is very poorly understood. Here, we exploit existing genome-wide association study data to gain insight into the role of genetics in prognosis. We identify a noncoding polymorphism in FOXO3A (rs12212067: T > G) at which the minor (G) allele, despite not being associated with disease susceptibility, is associated with a milder course of Crohn's disease and rheumatoid arthritis and with increased risk of severe malaria. Minor allele carriage is shown to limit inflammatory responses in monocytes via a FOXO3-driven pathway, which through TGFβ1 reduces production of proinflammatory cytokines, including TNFα, and increases production of anti-inflammatory cytokines, including IL-10. Thus, we uncover a shared genetic contribution to prognosis in distinct diseases that operates via a FOXO3-driven pathway modulating inflammatory responses.", "title": "Human SNP Links Differential Outcomes in Inflammatory and Infectious Disease to a FOXO3-Regulated Pathway" }, { "docid": "14938990", "text": "Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with complicated genetic inheritance. Programmed death 1 (PD-1), a negative T cell regulator to maintain peripheral tolerance, induces negative signals to T cells during interaction with its ligands and is therefore a candidate gene in the development of SLE. In order to examine whether expression levels of PD-1 contribute to the pathogenesis of SLE, 30 patients with SLE and 30 controls were recruited and their PD-1 expression levels in peripheral blood mononuclear cells (PBMCs) were measured via flow cytometry and quantitative real-time-reverse transcription polymerase chain reaction (RT-PCR). Also, whether PD-1 expression levels are associated with the variant of the SNP rs36084323 and the SLE Disease Activity Index (SLEDAI) was studied in this work. The PD-1 expression levels of SLE patients were significantly increased compared with those of the healthy controls. The upregulated PD-1 expression levels in SLE patients were greatly associated with SLEDAI scores. No significant difference was found between PD-1 expression levels and SNP rs36084323. The results suggest that increased expression of PD-1 may correlate with the pathogenesis of SLE, upregulated PD-1 expression may be a biomarker for SLE diagnosis, and PD-1 inhibitor may be useful to SLE treatment.", "title": "Upregulated PD-1 Expression Is Associated with the Development of Systemic Lupus Erythematosus, but Not the PD-1.1 Allele of the PDCD1 Gene" }, { "docid": "263364", "text": "BACKGROUND Genetic variation in the IL28B gene has been strongly associated with treatment outcomes, spontaneous clearance and progression of the hepatitis C virus infection (HCV). The aim of the present study was to investigate the role of polymorphisms at this locus with progression and outcome of HCV infection in a Moroccan population. METHODS We analyzed a cohort of 438 individuals among them 232 patients with persistent HCV infection, of whom 115 patients had mild chronic hepatitis and 117 had advanced liver disease (cirrhosis and hepatocellular carcinoma), 68 individuals who had naturally cleared HCV and 138 healthy subjects. The IL28B SNPs rs12979860 and rs8099917 were genotyped using a TaqMan 5' allelic discrimination assay. RESULTS The protective rs12979860-C and rs8099917-T alleles were more common in subjects with spontaneous clearance (77.9% vs 55.2%; p = 0.00001 and 95.6% vs 83.2%; p = 0.0025, respectively). Individuals with clearance were 4.69 (95% CI, 1.99-11.07) times more likely to have the C/C genotype for rs12979860 polymorphism (p = 0.0017) and 3.55 (95% CI, 0.19-66.89) times more likely to have the T/T genotype at rs8099917. Patients with advanced liver disease carried the rs12979860-T/T genotype more frequently than patients with mild chronic hepatitis C (OR = 1.89; 95% CI, 0.99-3.61; p = 0.0532) and this risk was even more pronounced when we compared them with healthy controls (OR = 4.27; 95% CI, 2.08-8.76; p = 0.0005). The rs8099917-G allele was also associated with advanced liver disease (OR = 2.34; 95% CI, 1.40-3.93; p = 0.0100). CONCLUSIONS In the Moroccan population, polymorphisms near the IL28B gene play a role both in spontaneous clearance and progression of HCV infection.", "title": "Genetic Variation in the Interleukin-28B Gene Is Associated with Spontaneous Clearance and Progression of Hepatitis C Virus in Moroccan Patients" }, { "docid": "37762357", "text": "Cytomegalovirus (CMV) has highly evolved mechanisms for avoiding detection by the host immune system. Recently, in the genomes of human and primate CMV, a novel gene comprising segments of noncontiguous open reading frames was identified and found to have limited predicted homology to endogenous cellular interleukin-10 (IL-10). Here we investigate the biological activities of the CMV IL-10-like gene product and show it to possess potent immunosuppressive properties. Both purified bacterium-derived recombinant CMV IL-10 and CMV IL-10 expressed in supernatants of human cells were found to inhibit proliferation of mitogen-stimulated peripheral blood mononuclear cells (PBMCs), with specific activity comparable to that of recombinant human IL-10. In addition, CMV IL-10 expressed from human cells inhibited cytokine synthesis, as treatment of stimulated PBMCs and monocytes with CMV IL-10 led to a marked decrease in production of proinflammatory cytokines. Finally, CMV IL-10 was observed to decrease cell surface expression of both major histocompatibility complex (MHC) class I and class II molecules, while conversely increasing expression of the nonclassical MHC allele HLA-G. These results demonstrate for the first time that CMV has a biologically active IL-10 homolog that may contribute to immune evasion during virus infection.", "title": "Potent immunosuppressive activities of cytomegalovirus-encoded interleukin-10." }, { "docid": "25045244", "text": "Our previous studies in volunteers immunized with Salmonella enterica serovar Typhi (S. Typhi) have suggested an important role for CD8+ T cells in host defense. In this study we describe a novel subset of nonclassical human HLA-E-restricted S. Typhi-specific CD8+ T cells derived from PBMC of Ty21a typhoid vaccinees. CD3+CD8+CD4-CD56- T cells effectively killed S. Typhi-infected targets regardless of whether they share classical HLA class I molecules with them, by a FAS-independent, granule-dependent mechanism, as evidenced by induction of granzyme B release and the blocking effects of concanamycin and strontium ions. The expression of HLA-E Ags, but not CD1-a, -b, or -c, on the membrane of S. Typhi-infected targets rendered them susceptible to lysis. Moreover, anti-HLA-E Abs partially blocked these responses. We also demonstrated that presentation of S. Typhi Ags via HLA-E could stimulate IFN-gamma production. Increases in the net frequency of IFN-gamma spot-forming cells were observed in the presence of targets coated with peptides that contain S. Typhi GroEL HLA-E binding motifs. These results demonstrate that HLA-E binds nonamer peptides derived from bacterial proteins and trigger CD8+-mediated lysis and IFN-gamma production when exposed to infected targets, raising the possibility that this novel effector mechanism might contribute to host defense against intracellular bacterial infections.", "title": "Identification of a human HLA-E-restricted CD8+ T cell subset in volunteers immunized with Salmonella enterica serovar Typhi strain Ty21a typhoid vaccine." }, { "docid": "7221410", "text": "The transmembrane protein CD33 is a sialic acid-binding immunoglobulin-like lectin that regulates innate immunity but has no known functions in the brain. We have previously shown that the CD33 gene is a risk factor for Alzheimer's disease (AD). Here, we observed increased expression of CD33 in microglial cells in AD brain. The minor allele of the CD33 SNP rs3865444, which confers protection against AD, was associated with reductions in both CD33 expression and insoluble amyloid beta 42 (Aβ42) levels in AD brain. Furthermore, the numbers of CD33-immunoreactive microglia were positively correlated with insoluble Aβ42 levels and plaque burden in AD brain. CD33 inhibited uptake and clearance of Aβ42 in microglial cell cultures. Finally, brain levels of insoluble Aβ42 as well as amyloid plaque burden were markedly reduced in APP(Swe)/PS1(ΔE9)/CD33(-/-) mice. Therefore, CD33 inactivation mitigates Aβ pathology and CD33 inhibition could represent a novel therapy for AD.", "title": "Alzheimer’s Disease Risk Gene CD33 Inhibits Microglial Uptake of Amyloid Beta" }, { "docid": "24825841", "text": "The likelihood for immunological rejection of Human Leukocyte Antigens (HLA)-mismatched induced pluripotent stem cells (iPSCs) limits their therapeutic potential. Here we show how a tissue bank from 150 selected homozygous HLA-typed volunteers could match 93% of the UK population with a minimal requirement for immunosuppression. Our model provides a practical approach for using existing HLA-typed samples to generate an iPSC stem cell bank that circumvents prospective typing of a large number of individuals.", "title": "Generating an iPSC bank for HLA-matched tissue transplantation based on known donor and recipient HLA types." }, { "docid": "5448119", "text": "Genome-wide association studies have recently identified at least 15 susceptibility loci for systemic lupus erythematosus (SLE). To confirm additional risk loci, we selected SNPs from 2,466 regions that showed nominal evidence of association to SLE (P < 0.05) in a genome-wide study and genotyped them in an independent sample of 1,963 cases and 4,329 controls. This replication effort identified five new SLE susceptibility loci (P < 5 × 10−8): TNIP1 (odds ratio (OR) = 1.27), PRDM1 (OR = 1.20), JAZF1 (OR = 1.20), UHRF1BP1 (OR = 1.17) and IL10 (OR = 1.19). We identified 21 additional candidate loci with P≤ 1 × 10−5. A candidate screen of alleles previously associated with other autoimmune diseases suggested five loci (P < 1 × 10−3) that may contribute to SLE: IFIH1, CFB, CLEC16A, IL12B and SH2B3. These results expand the number of confirmed and candidate SLE susceptibility loci and implicate several key immunologic pathways in SLE pathogenesis.", "title": "A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus" }, { "docid": "3222187", "text": "Genome-wide association studies (GWAS) have identified common polymorphisms in or near GC, CYP2R1, CYP24A1, and NADSYN1/DHCR7 genes to be associated with circulating levels of 25-hydroxyvitamin D [25(OH)D] in European populations. To replicate these GWAS findings, we examined six selected polymorphisms from these regions and their relation with circulating 25(OH)D levels in 1,605 Hispanic women (629 U.S. Hispanics and 976 Mexicans) and 354 non-Hispanic White (NHW) women. We also assessed the potential interactions between these variants and known non-genetic predictors of 25(OH)D levels, including body mass index (BMI), sunlight exposure and vitamin D intake from diet and supplements. The minor alleles of the two GC polymorphisms (rs7041 and rs2282679) were significantly associated with lower 25(OH)D levels in both Hispanic and NHW women. The CYP2R1 polymorphism, rs2060793, also was significantly associated with 25(OH)D levels in both groups. We found no significant associations for the polymorphisms in the CYP24A1. In Hispanic controls, 25(OH)D levels were significantly associated with the rs12785878T and rs1790349G haplotype in the NADSYN1/DHCR7 region. Significant interactions between GC rs2282679 and BMI and between rs12785878 and time spent in outdoor activities were observed. These results provide further support for the contribution of common genetic variants to individual variability in circulating 25(OH)D levels. The observed interactions between SNPs and non-genetic factors warrant confirmation.", "title": "Genetic variants and non-genetic factors predict circulating vitamin D levels in Hispanic and non-Hispanic White women: the Breast Cancer Health Disparities Study." }, { "docid": "20886584", "text": "Taxanes have resulted in improved survival for breast cancer patients, but often cause neurological toxicities. Identification of biomarkers related to toxicities could be important for dictating treatment regimen. We evaluated single nucleotide polymorphisms (SNPs) in the Fanconi Anemia (FA)/BRCA pathway in relation to grade 3/4 neurotoxicities in patients (n = 888) from SWOG0221, a phase III adjuvant trial for breast cancer of 4 dose/schedules of cyclophosphamide (C), doxorubicin (A), and paclitaxel (T). In a separate cohort, we measured the correlation of significant FANCD2 SNPs with corresponding gene expression. For FANCD2, permutation testing revealed that 4 (out of 20) SNPs were significantly associated with an almost two-fold increased risk of toxicity. Two FANCD2 haplotypes were also associated with neurological toxicity, with odds ratios (OR) in the overall population of 1.8 (95% confidence interval (CI) 1.3, 2.5) and 1.7 (95% CI, 1.2, 2.4). Although numbers were small, an African-American-specific haplotype was associated with an almost 3-fold increase in risk of neurologic toxicity (OR = 2.84, 95% CI = 1.2, 6.9). Expression analyses revealed that significant FANCD2 SNPs were associated with FANCD2 expression levels (P = 0.03). There were no associations between SNPs in BRCA1 and neurotoxicities. In this trial of CA+T for breast cancer, SNPs in FANCD2, but not in BRCA1, were associated with a 70–80% increase in the odds of grade 3/4 neurological toxicities and increased expression of the gene. If replicated, women with these genotypes should be closely monitored for toxicities and could be targeted for preventive measures or alternative therapeutic approaches.", "title": "Genetic predictors of taxane-induced neurotoxicity in a SWOG phase III intergroup adjuvant breast cancer treatment trial (S0221)" }, { "docid": "43048059", "text": "AIMS The present study aims to investigate the interaction between nitric oxide (NO) and hydrogen sulfide (H(2)S), the two important gaseous mediators in rat hearts. METHODS AND RESULTS Intracellular calcium in isolated cardiomyocytes was measured with a spectrofluorometric method using Fura-2. Myocyte contractility was measured with a video edge system. NaHS (50 µM, an H(2)S donor) had no significant effect on the resting calcium level, electrically induced (EI) calcium transients, and cell contractility in ventricular myocytes. Stimulating endogenous NO production with l-arginine or exogenous application of NO donors [sodium nitroprusside (SNP) and 2-(N,N-diethylamino)-diazenolate-2-oxide] decreased myocyte twitch amplitudes accompanied by slower velocities of both cell contraction and relaxation. Surprisingly, NaHS reversed the negative inotropic and lusitropic effects of the above three NO-increasing agents. In addition, the mixture of SNP + NaHS increased, whereas SNP alone decreased, the resting calcium level and the amplitudes of EI calcium transients. Angeli's salt, a nitroxyl anion (HNO) donor, mimicked the effect of SNP + NaHS on calcium handling and myocyte contractility. Three thiols, N-acetyl-cysteine, l-cysteine, and glutathione, abolished the effects of HNO and SNP + NaHS on myocyte contraction. Neither Rp-cAMP [a protein kinase A (PKA) inhibitor] nor Rp-cGMP [a protein kinase G (PKG) inhibitor] affected the effects of SNP + NaHS, suggesting a cAMP/PKA- or cGMP/PKG-independent mechanism. CONCLUSION H(2)S may interact with NO to form a thiol sensitive molecule (probably HNO) which produces positive inotropic and lusitropic effects. Our findings may shed light on the interaction of NO and H(2)S and provide new clues to treat cardiovascular diseases.", "title": "Hydrogen sulfide interacts with nitric oxide in the heart: possible involvement of nitroxyl." }, { "docid": "46277811", "text": "Background: The relationship of LPA single nucleotide polymorphisms (SNPs), apolipoprotein(a) isoforms, and lipoprotein(a) [Lp(a)] levels with major adverse cardiovascular events (MACE) in different ethnic groups is not well known. Methods: LPA SNPs, apolipoprotein(a) isoforms, Lp(a), and oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) levels were measured in 1792 black, 1030 white, and 597 Hispanic subjects enrolled in the Dallas Heart Study. Their interdependent relationships and prospective association with MACE after median 9.5-year follow-up were determined. Results: LPA SNP rs3798220 was most prevalent in Hispanics (42.38%), rs10455872 in whites (14.27%), and rs9457951 in blacks (32.92%). The correlation of each of these SNPs with the major apolipoprotein(a) isoform size was highly variable and in different directions among ethnic groups. In the entire cohort, Cox regression analysis with multivariable adjustment revealed that quartiles 4 of Lp(a) and OxPL-apoB were associated with hazard ratios (95% confidence interval) for time to MACE of 2.35 (1.50–3.69, P<0.001) and 1.89 (1.26–2.84, P=0.003), respectively, versus quartile 1. Addition of the major apolipoprotein(a) isoform and the 3 LPA SNPs to these models attenuated the risk, but significance was maintained for both Lp(a) and OxPL-apoB. Evaluating time to MACE in specific ethnic groups, Lp(a) was a positive predictor and the size of the major apolipoprotein(a) isoform was an inverse predictor in blacks, the size of the major apolipoprotein(a) isoform was an inverse predictor in whites, and OxPL-apoB was a positive predictor in Hispanics. Conclusions: The prevalence and association of LPA SNPs with size of apolipoprotein(a) isoforms, Lp(a), and OxPL-apoB levels are highly variable and ethnicity-specific. The relationship to MACE is best explained by elevated plasma Lp(a) or OxPL-apoB levels, despite significant ethnic differences in LPA genetic markers.", "title": "LPA Gene, Ethnicity, and Cardiovascular Events" }, { "docid": "13519661", "text": "Background Checkpoint kinase 2 (CHEK2) averts cancer development by promoting cell cycle arrest and activating DNA repair in genetically damaged cells. Previous investigation has established a role for the CHEK2 gene in breast cancer aetiology, but studies have largely been limited to the rare 1100delC mutation. Whether common polymorphisms in this gene influence breast cancer risk remains unknown. In this study, we aimed to assess the importance of common CHEK2 variants on population risk for breast cancer by capturing the majority of diversity in the gene using haplotype tagging single nucleotide polymorphisms (tagSNPs). Methods and Findings We analyzed 14 common SNPs spanning 52 kilobases (kb) of the CHEK2 gene in 92 Swedish women. Coverage evaluation indicated that these typed SNPs would efficiently convey association signal also from untyped SNPs in the same region. Six of the 14 SNPs predicted well both the haplotypic and single SNP variations within CHEK2. We genotyped these six tagSNPs in 1,577 postmenopausal breast cancer cases and 1,513 population controls, but found no convincing association between any common CHEK2 haplotype and breast cancer risk. The 1100delC mutation was rare in our Swedish population—0.7% in cases and 0.4% in controls— with a corresponding odds ratio for carriers versus noncarriers of 2.26 (95% confidence interval, 0.99–5.15). Estimates of the population frequency and the odds ratio of 1100delC indicate that our sample is representative of a Northern European population.", "title": "Linkage Disequilibrium Mapping of CHEK2: Common Variation and Breast Cancer Risk " } ]
920
“Occupation” field on IRS Form 1040
[ { "docid": "166245", "text": "\"It doesn't generally matter, and I'm not sure if it is in fact in use by the IRS other than for general statistics (like \"\"this year 20% of MFJ returns were with one spouse being a 'homemaker'\"\"). They may be able to try and match the occupation and the general levels and types of income, but for self-employed there's a more precise and reliable field on Schedule C and for employees they don't really need to do this since everything is reported on W2 anyway. So I don't think they even bother or give a lot of value to such a metric. So yes, I'm joining the non-authoritative \"\"doesn't matter\"\" crowd.\"", "title": "" } ]
[ { "docid": "174025", "text": "You are right that even if you do not receive a 1099-MISC, you still need to report all income to the IRS. Report the $40 on Schedule C or Schedule C-EZ. Since your net profit was less than $400, you do not need to file Schedule SE. From the IRS web site: Self-Employment Income It is a common misconception that if a taxpayer does not receive a Form 1099-MISC or if the income is under $600 per payer, the income is not taxable. There is no minimum amount that a taxpayer may exclude from gross income. All income earned through the taxpayer’s business, as an independent contractor or from informal side jobs is self-employment income, which is fully taxable and must be reported on Form 1040. Use Form 1040, Schedule C, Profit or Loss from Business, or Form 1040, Schedule C-EZ, Net Profit from Business (Sole Proprietorship) to report income and expenses. Taxpayers will also need to prepare Form 1040 Schedule SE for self-employment taxes if the net profit exceeds $400 for a year. Do not report this income on Form 1040 Line 21 as Other Income. Independent contractors must report all income as taxable, even if it is less than $600. Even if the client does not issue a Form 1099-MISC, the income, whatever the amount, is still reportable by the taxpayer.", "title": "" }, { "docid": "254151", "text": "\"If you receive a 1099-MISC from YouTube, that tells you what they stated to the IRS and leads into most tax preparation software guided interviews or wizards as a topic for you to enter. Whether or not you have a 1099-MISC, this discussion from the IRS is pertinent to your question. You could probably elect to report the income as a royalty on your copyrighted work of art on Schedule E, but see this note: \"\"In most cases you report royalties in Part I of Schedule E (Form 1040). However, if you ... are in business as a self-employed writer, inventor, artist, etc., report your income and expenses on Schedule C or Schedule C-EZ (Form 1040).\"\" Whether reporting on Schedule E or C is more correct or better for your specific circumstances is beyond the advice you should take from strangers on the internet based on a general question - however, know that there are potentially several paths for you. Note that this is revenue from a business, so if you paid for equipment or services that are 100% dedicated to your YouTubing (PC, webcam, upgraded broadband, video editing software, vehicle miles to a shoot, props, etc.) then these are a combination of depreciable capital investments and expenses you can report against the income, reducing the taxes you may owe. If the equipment/services are used for business and personal use, there are further guidelines from the IRS as to estimating the split. These apply whether you report on Sch. E, Sch. C, or Sch C-EZ. Quote: \"\"Self-Employment Income It is a common misconception that if a taxpayer does not receive a Form 1099-MISC or if the income is under $600 per payer, the income is not taxable. There is no minimum amount that a taxpayer may exclude from gross income. All income earned through the taxpayer’s business, as an independent contractor or from informal side jobs is self-employment income, which is fully taxable and must be reported on Form 1040. Use Form 1040, Schedule C, Profit or Loss from Business, or Form 1040, Schedule C-EZ, Net Profit from Business (Sole Proprietorship) to report income and expenses. Taxpayers will also need to prepare Form 1040 Schedule SE for self-employment taxes if the net profit exceeds $400 for a year. Do not report this income on Form 1040 Line 21 as Other Income. Independent contractors must report all income as taxable, even if it is less than $600. Even if the client does not issue a Form 1099-MISC, the income, whatever the amount, is still reportable by the taxpayer. Fees received for babysitting, housecleaning and lawn cutting are all examples of taxable income, even if each client paid less than $600 for the year. Someone who repairs computers in his or her spare time needs to report all monies earned as self-employment income even if no one person paid more than $600 for repairs.\"\"\"", "title": "" }, { "docid": "593938", "text": "\"This may be relevant: it suggests that IRS is lenient with the attachment of the form with 1040. To paraphrase: \"\"The ruling involved a taxpayer who timely filed the election with the IRS within 30 days of the property transfer but who did not attach a copy of the election to his or her Form 1040 for the year of the transfer. Fortunately for the taxpayer in question, the ruling indicated that the submission of the election to the IRS within 30 days of the property transfer fulfilled the requirements for a valid election, and the failure to attach the copy to the tax return did not affect the validity of the election. The IRS requested that the taxpayer forward a copy of the election to the IRS to be associated with the processing of the tax return. - See more at: http://www.bnncpa.com/services/employee_benefit_plans/blog/irs_rules_that_failure_to_attach_83b_election_to_form_1040_did_not_invalida#sthash.0c3h2nJY.dpuf\"\" If someone wants to grok the IRS ruling: http://www.irs.gov/pub/irs-wd/1405008.pdf And this is the article where I saw the above referenced. www.bnncpa.com/services/employee_benefit_plans/blog/irs_rules_that_failure_to_attach_83b_election_to_form_1040_did_not_invalida\"", "title": "" }, { "docid": "57707", "text": "\"Depending on what you need to explain, you can submit your electronic return without the supplemental information and subsequently mail a Form 8453 with the additional information. This is helpful for form 8489, for example, where you need to list every transaction reported by your stock broker on a 1099-B. See https://www.irs.gov/pub/irs-pdf/f8453.pdf for more details on this form. If the information you need to submit an attachment for doesn't follow one of the options on that form, you will likely need to file a paper return or use a paid tax preparation service/application. Limitations of FreeFile are explained here, along with a list of forms that are available: https://www.irs.gov/uac/List-of-Available-Free-File-Fillable-Forms The \"\"Attaching Statements\"\" and \"\"Write-in information\"\" sections seem like they might apply to your situation. Attaching Statements - If you need to add statements and you can't use Form 8453, U.S. Individual Income Tax Transmittal for an IRS e-file Return, to mail that information, you will not be able to use this program to efile your return Identity Protection PIN's (IP PIN) - This program only supports the entry of a Primary taxpayer's IP PIN. If the spouse or dependents have an IP PIN, you cannot use this program to efile the return. Writing In Information - Your ability to \"\"write in\"\" additional information to explain an entry is generally limited to the 1040 forms and some of the more frequently submitted forms. If you need to write in additional information on a form, other than the 1040 series, you may not be able to use this program to efile your tax return. E-filing Forms - To efile forms, (except Form 4868) they must be attached to a 1040 series form (1040, 1040A or 1040EZ). Form Limitations - There may be Known Limitations of forms you plan to complete. Please review them. A form limitation may keep you from completing or e-filing your return.\"", "title": "" }, { "docid": "211869", "text": "is it possible to file that single form aside from the rest of my return? Turbotax will generate all the forms necessary to file your return. I recommend you access these forms and file them manually. According to the IRS in order to report capital gains and losses you need to fill out Form 8949 and summarize them on Form 1040 D. Add these two forms to the stack that turbotax generates. Add the total capital gains to line 13 of the Form 1040 which turbotax generated, and adjust the totals on the form accordingly.", "title": "" }, { "docid": "219156", "text": "\"If you want an \"\"account statement\"\" from the IRS listing the taxes due and paid and confirming a zero balance remaining, you want what they call a Tax Account Transcript. It sounds like you tried to submit this online, but yes, it would require the actual taxpayer to submit it. The other option would be to fill out Form 4506-T requesting the Form 1040 Tax Account Transcript, have the taxpayer sign it, and mail it in. Presumably whatever method you used to have her sign the Form 1040 you prepared for her you could also use to have her sign the 4506-T. Another option could be to try to request the transcript over the phone. I don't know what authentication they require, or if you would need to have been listed on the 1040 as an authorized Third Party Designee. According to the IRS Transcript FAQ Page: Q19. What if I’m unable to use Get Transcript by Mail? If you are unable to use Get Transcript by Mail, you may try our automated phone transcript service at 800-908-9946 and also receive your transcript by mail. Please allow 5 to 10 calendar days for delivery. But unless there's a reason to think that the tax account wasn't credited properly or the IRS is sending another bill or the like, I don't think there's a lot of point in doing so. In general, the fact that the check cleared the bank should be sufficient documentation that the amount was paid.\"", "title": "" }, { "docid": "436960", "text": "They are four quarterly estimated tax payments. The IRS requires that you pay your taxes throughout the year (withholding in a W-2 job). You'll need to estimate how much taxes you think you might be owing and then pay roughly 1/4 at each of the 4 deadlines. From the IRS: How To Figure Estimated Tax To figure your estimated tax, you must figure your expected AGI, taxable income, taxes, deductions, and credits for the year. When figuring your 2011 estimated tax, it may be helpful to use your income, deductions, and credits for 2010 as a starting point. Use your 2010 federal tax return as a guide. You can use Form 1040-ES to figure your estimated tax. Nonresident aliens use Form 1040-ES (NR) to figure estimated tax. You must make adjustments both for changes in your own situation and for recent changes in the tax law. For 2011, there are several changes in the law. Some of these changes are discussed under What's New for 2011 beginning on page 2. For information about these and other changes in the law, visit the IRS website at IRS.gov. The instructions for Form 1040-ES include a worksheet to help you figure your estimated tax. Keep the worksheet for your records. You may find some value from hiring a CPA to help you setup your estimated tax payments and amounts.", "title": "" }, { "docid": "69333", "text": "\"There could be a few reasons for this, my first guess is that you didn't report the distribution on your return (indicated on line 15 of your 1040, pictured below), the IRS got a copy of the 1099-R, and assumes it's all taxable (or maybe the 1099-R indicates the full amount is taxable). If a 1099-R doesn't have an amount populated for 'taxable amount' it doesn't mean the distribution isn't taxable, and without any indication that it's not taxable the IRS assumes it is. It's not taxable if it's a withdrawal of your contribution. Here's a snippet from How to Calculate the Taxable Amount of an IRA Withdrawal: Withdrawals from a Roth IRA Since Roth IRA contributions are made on an after-tax basis, qualified withdrawals are completely tax-free. A \"\"qualified\"\" Roth withdrawal includes the following: If your 1099-R indicates a taxable amount, then you might need to contact the issuer to understand why. If it does not indicate a taxable amount and you failed to record the distribution on your return, you just need to file an amended return that shows the distribution on line 15a and shows no taxable amount on 15b along with a completed Form 8606. You may not need additional documentation to support of your claim that it's not taxable, but if you do it would be any statement showing that your contributions over the years exceed your withdrawal. What a 1040 with a non-taxable IRA withdrawal would show: Note: There'd also be a completed Form 8606, the 1040 lines above just show if it was entered in. The easiest path forward is probably to file an amended return using turbotax since you filed with them originally. I haven't dealt with an IRS letter in a few years, I can't recall if you need to contact them or simply file the amended return, but they're pretty good about including instructions so the letter probably indicates what you need to do. Don't delay in taking action, as the IRS can and will garnish wages if they are owed (or think they are owed) money. Update: OP contacted IRS and they didn't even want an amended return, just the completed Form 8606, so it's worth calling the IRS first with these letters.\"", "title": "" }, { "docid": "223624", "text": "Yes, you need to include income from your freelance work on your tax return. In the eyes of the IRS, this is self-employment income from your sole-proprietorship business. The reason you don't see it mentioned in the 1040EZ instructions is that you can't use the 1040EZ form if you have self-employment income. You'll need to use the full 1040 form. Your business income and expenses will be reported on a Schedule C or Schedule C-EZ, and the result will end up on Line 12 of the 1040. Take a look at the requirements at the top of the C-EZ form; you probably meet them and can use it instead of the more complicated C form. If you have any deductible business expenses related to your freelance business, this would be done on Schedule C or C-EZ. If your freelance income was more than $400, you'll also need to pay self-employment tax. To do this, you file Schedule SE, and the tax from that schedule lands on form 1040 Line 57.", "title": "" }, { "docid": "450808", "text": "\"One way to do these sorts of calculations is to use the spreadsheet version of IRS form 1040 available here. This is provided by a private individual and is not an official IRS tool, but in practice it is usually accurate enough for these purposes. You may have to spend some time figuring out where to enter the info. However, if you enter your self-employment income on Schedule C, this spreadsheet will calculate the self-employment tax as well as the income tax. An advantage is that it is the full 1040, so you can also select the standard deduction and the number of exemptions you are entitled to, enter ordinary W-2 income, even capital gains, etc. Of course you can also make use of other tax software to do this, but in my experience the \"\"Excel 1040\"\" is more convenient, as most websites and tax-prep software tend to be structured in a linear fashion and are more cumbersome to update in an ad-hoc way for purposes like tax estimation. You can do whatever works for you, but I would recommend taking a look at the Excel 1040. It is a surprisingly useful tool.\"", "title": "" }, { "docid": "216404", "text": "Generally stock trades will require an additional Capital Gains and Losses form included with a 1040, known as Schedule D (summary) and Schedule D-1 (itemized). That year I believe the maximum declarable Capital loss was $3000--the rest could carry over to future years. The purchase date/year only matters insofar as to rank the lot as short term or long term(a position held 365 days or longer), short term typically but depends on actual asset taxed then at 25%, long term 15%. The year a position was closed(eg. sold) tells you which year's filing it belongs in. The tiny $16.08 interest earned probably goes into Schedule B, typically a short form. The IRS actually has a hotline 800-829-1040 (Individuals) for quick questions such as advising which previous-year filing forms they'd expect from you. Be sure to explain the custodial situation and that it all recently came to your awareness etc. Disclaimer: I am no specialist. You'd need to verify everything I wrote; it was just from personal experience with the IRS and taxes.", "title": "" }, { "docid": "128861", "text": "Such activity is normally referred to as bartering income. From the IRS site - You must include in gross income in the year of receipt the fair market value of goods or services received from bartering. Generally, you report this income on Form 1040, Schedule C (PDF), Profit or Loss from Business (Sole Proprietorship), or Form 1040, Schedule C-EZ (PDF), Net Profit from Business (Sole Proprietorship). If you failed to report this income, correct your return by filing a Form 1040X (PDF), Amended U.S. Individual Income Tax Return. Refer to Topic 308 and Amended Returns for information on filing an amended return.", "title": "" }, { "docid": "466718", "text": "\"From the poster's description of this activity, it doesn't look like he is engaged in a business, so Schedule C would not be appropriate. The first paragraph of the IRS Instructions for Schedule C is as follows: Use Schedule C (Form 1040) to report income or loss from a business you operated or a profession you practiced as a sole proprietor. An activity qualifies as a business if your primary purpose for engaging in the activity is for income or profit and you are involved in the activity with continuity and regularity. For example, a sporadic activity or a hobby does not qualify as a business. To report income from a nonbusiness activity, see the instructions for Form 1040, line 21, or Form 1040NR, line 21. What the poster is doing is acting as a nominee or agent for his members. For instance, if I give you $3.00 and ask you to go into Starbucks and buy me a pumpkin-spice latte, you do not have income or receipts of $3.00, and you are not engaged in a business. The amounts that the poster's members are forwarding him are like this. Money that the poster receives for his trouble should be reported as nonbusiness income on Line 21 of Form 1040, in accordance with the instructions quoted above and the instructions for Form 1040. Finally, it should be noted that the poster cannot take deductions or losses relating to this activity. So he can't deduct any expenses of organizing the group buy on his tax return. Of course, this would not be the case if the group buy really is the poster's business and not just a \"\"hobby.\"\" Of course, it goes without saying that the poster should document all of this activity with receipts, contemporaneous emails (and if available, contracts) - as well as anything else that could possibly be relevant to proving the nature of this activity in the event of an audit.\"", "title": "" }, { "docid": "284085", "text": "You need to file IRS Form 1040-NR. The IRS's website provides instructions.", "title": "" }, { "docid": "55407", "text": "According to pages 6 & 7 of the instructions for form 1040 in 2009 AMT was only temporarily patched for the year. Congress can't politically afford to drastically cut AMT exemptions by 30 to 40%, and may even retroactively change it, if it isn't passed by the end of the year (despite the constitution forbidding ex post facto laws) : What’s New for 2009 ... Alternative minimum tax (AMT) exemption amount increased. The AMT exemption amount has increased to $46,700 ($70,950 if married filing jointly or a qualifying widow(er); $35,475 if married filing separately)... What’s New for 2010 ... Alternative minimum tax (AMT) exemption amount. The AMT exemption amount is scheduled to decrease to $33,750 ($45,000 if married filing jointly or a qualifying widow(er); $22,500 if married filing separately). So, if you are married, and several regular tax deductions push your income below the AMT exemption amount of $45,000, it's quite possible you would be required to pay AMT, even if you didn't last year. There is a work sheet for AMT in the instructions for line 43, but the IRS also provides an AMT calculator. According to page 146 (E-8) of the instructions for form 1040 AMT is paid as: the smallest amount you are allowed to report as your taxable income (Form 1040, line 43). It is also the smallest amount you are allowed to report as your alternative minimum taxable income (AMTI) on Form 6251, line 29. If the [AMT calculation] is larger than your taxable income would otherwise be, enter the amount from column (c) on Form 1040, line 43 [or ...] Form 6251, line 29. As always, congress finds ways to further complicate things by making a few credits and losses deductible against the absolute minimum you're expected to pay taxes on, making the AMT a misnomer.", "title": "" }, { "docid": "29300", "text": "It is true that with a job that pays you via payroll check that will result in a W-2 because you are an employee, the threshold that you are worried about before you have to file is in the thousands. Unless of course you make a lot of money from bank interest or you have income tax withheld and you want it refunded to you. Table 2 and table 3 in IRS pub 501, does a great job of telling you when you must. For you table 3 is most likely to apply because you weren't an employee and you will not be getting a W-2. If any of the five conditions listed below applied to you for 2016, you must file a return. You owe any special taxes, including any of the following. a. Alternative minimum tax. (See Form 6251.) b. Additional tax on a qualified plan, including an individual retirement arrangement (IRA), or other tax­favored account. (See Pub. 590­A, Contributions to Individual Retirement Arrangements (IRAs); Pub. 590­B, Distributions from Individual Retirement Arrangements (IRAs); and Pub. 969, Health Savings Accounts and Other Tax­Favored Health Plans.) But if you are filing a return only because you owe this tax, you can file Form 5329 by itself. c. Social security or Medicare tax on tips you didn't report to your employer (see Pub. 531, Reporting Tip Income) or on wages you received from an employer who didn't withhold these taxes (see Form 8919). d. Write­in taxes, including uncollected social security, Medicare, or railroad retirement tax on tips you reported to your employer or on group­term life insurance and additional taxes on health savings accounts. (See Pub. 531, Pub. 969, and the Form 1040 instructions for line 62.) e. Household employment taxes. But if you are filing a return only because you owe these taxes, you can file Schedule H (Form 1040) by itself. f. Recapture taxes. (See the Form 1040 instructions for lines 44, 60b, and 62.) You (or your spouse if filing jointly) received Archer MSA, Medicare Advantage MSA, or health savings account distributions. You had net earnings from self­employment of at least $400. (See Schedule SE (Form 1040) and its instructions.) You had wages of $108.28 or more from a church or qualified church­controlled organization that is exempt from employer social security and Medicare taxes. (See Schedule SE (Form 1040) and its instructions.) Advance payments of the premium tax credit were made for you, your spouse, or a dependent who enrolled in coverage through the Health Insurance Marketplace. You should have received Form(s) 1095­A showing the amount of the advance payments, if any. It appears that item 3: You had net earnings from self­employment of at least $400. (See Schedule SE (Form 1040) and its instructions.) would most likely apply. It obviously is not too late to file for 2016, because taxes aren't due for another month. As to previous years that would depend if you made money those years, and how much.", "title": "" }, { "docid": "201658", "text": "No, you don't have to have the money deducted from your paycheck. The IRS doesn't get a copy of your paycheck anyway. When you file your annual tax return (form 1040), there's a line there to write down the amount you contributed to the IRA. In fact, you can contribute to the IRA after the year ended, until the Tax Day of the next year, so that you can make sure your contribution will actually be deductible (not always they are). The IRA custodian (the brokerage firm/bank where you opened the IRA account) will provide you with a deposit confirmation and form 5498. A copy of form 5948 is also sent to the IRS.", "title": "" }, { "docid": "411063", "text": "Through your question and then clarification through the comments, it looks like you have a U.S. LLC with at least two members. If you did not elect some other tax treatment, your LLC will be treated as a partnership by the IRS. The partnership should file a tax return on Form 1065. Then each partner will get a Schedule K-1 from the partnership, which the partner should use to include their respective shares of the partnership income and expenses on their personal Forms 1040. You can also elect to be taxed as an S-Corp or a C-Corp instead of a partnership, but that requires you to file a form explicitly making such election. If you go S-Corp, then you will file a different form for the company, but the procedure is roughly the same - Income gets passed through to the owners via a Schedule K-1. If you go C-Corp, then the owners will pay no tax on their own Form 1040, but the C-Corp itself will pay income tax. As far as whether you should try to spend the money as business expense to avoid paying extra tax - That's highly dependent on your specific situation. I'd think you'd want to get tailored advice for that.", "title": "" }, { "docid": "268069", "text": "Generally, prize money is miscellaneous income, reported on line 21 of your 1040 and not subject to self employment tax. See IRS publication 525 for more details; under 'Prizes and Awards', they give an example of winning a photography contest. Now, there are a couple of exceptions. If your main occupation is participating in contests such as this - or you do it sufficiently that it could be considered such - then it may be considered something you should pay self employment taxes on. If it's your first one - you're fine. Also, it would have to be something that doesn't look like work for me to be confident it's self employment income. I'm not sure that winning the Netflix prize for improving on their algorithm by 10% wouldn't run the risk of being considered sort of employment. I'm not a tax advisor, but in that case I would hire one to be sure. I could imagine companies abusing 'prizes' otherwise to get out of paying employment taxes...", "title": "" }, { "docid": "442146", "text": "Yes, you can send in a 2012 1040-ES form with a check to cover your tax liability. However, you will likely have to pay penalties for not paying tax in timely fashion as well as interest on the late payment. You can have the IRS figure the penalty and bill you for it, or you can complete Form 2210 (on which these matters are figured out) yourself and file it with your Form 1040. The long version of Form 2210 often results in the smallest extra amount due but is considerably more time-consuming to complete correctly. Alternatively, if you or your wife have one or more paychecks coming before the end of 2012, it might be possible to file a new W-4 form with the HR Department with a request to withhold additional amounts as Federal income tax. I say might because if the last paycheck of the year will be issued in just a few days' time, it might already have been sent for processing, and HR might tell you it is too late. But, depending on the take-home pay, it might be possible to have the entire $2000 withheld as additional income tax instead of sending in a 1040-ES. The advantage of doing it through withholding is that you are allowed to treat the entire withholding for 2012 as satisfying the timely filing requirements. So, no penalty for late payment even though you had a much bigger chunk withheld in December, and no interest due either. If you do use this approach, remember that Form W-4 applies until it is replaced with another, and so HR will continue to withhold the extra amount on your January paychecks as well. So, file a new W-4 in January to get back to normal withholding. (Fix the extra exemption too so the problem does not recur in 2013).", "title": "" }, { "docid": "257443", "text": "I assume the OP is the US and that he is, like most people, a cash-basis tax payer and not an accrual basis tax payer. Suppose the value of the rental of the unit the OP is occupying was reported as income on the OP's 2010 and 2011 W-2 forms but the corresponding income tax was not withheld. If the OP correctly transcribed these income numbers onto his tax returns, correctly computed the tax on the income reported on his 2010 and 2011 1040 forms, and paid the amount due in timely fashion, then there is no tax or penalty due for 2010 and 2011. Nor is the company entitled to withhold tax on this income for 2010 and 2011 at this time; the tax on that income has already been paid by the OP directly to the IRS and the company has nothing to do with the matter anymore. Suppose the value of the rental of the unit the OP is occupying was NOT reported as income on the OP's 2010 and 2011 W-2 forms. If the OP correctly transcribed these income numbers onto his tax returns, correctly computed the tax on the income reported on his 2010 and 2011 1040 forms, and paid the amount due in timely fashion, then there is no tax or penalty due for 2010 and 2011. Should the OP have declared the value of the rental of the unit as additional income from his employer that was not reported on the W-2 form, and paid taxes on that money? Possibly, but it would be reasonable to argue that the OP did nothing wrong other than not checking his W-2 form carefully: he simply assumed the income numbers included the value of the rental and copied whatever the company-issued W-2 form said onto his 1040 form. At least as of now, there is no reason for the IRS to question his 2010 and 2011 returns because the numbers reported to the IRS on Copy A of the W-2 forms match the numbers reported by the OP on his tax returns. My guess is that the company discovered that it had not actually declared the value of the rental payments on the OP's W-2 forms for 2010 and 2011 and now wants to include this amount as income on subsequent W-2 forms. Now, reporting a lump-sum benefit of $38K (but no actual cash) would have caused a huge amount of income tax to need to be withheld, and the OP's next couple of paychecks might well have had zero take-home pay as all the money was going towards this tax withholding. Instead, the company is saying that it will report the $38K as income in 78 equal installments (weekly paychecks over 18 months?) and withhold $150 as the tax due on each installment. If it does not already do so, it will likely also include the value of the current rent as a benefit and withhold tax on that too. So the OP's take-home pay will reduce by $150 (at least) and maybe more if the current rental payments also start appearing on the paychecks and tax is withheld from them too. I will not express an opinion on the legality of the company withholding an additional $150 as tax from the OP's paycheck, but will suggest that the solution proposed by the company (have the money appear as taxable benefits over a 78-week period, have tax withheld, and declare the income on your 2012, 2013 and 2014 returns) is far more beneficial to the OP than the company declaring to the IRS that it made a mistake on the 2010 and 2011 W-2's issued to the OP, and that the actual income paid was higher. Not only will the OP have to file amended returns for 2010 and 2011 but the company will need to amend its tax returns too. In summary, the OP needs to know that He will have to pay taxes on the value of the waived rental payments for 2010 and 2011. The company's mistake in not declaring this as income to the OP for 2010 and 2011 does not absolve him of the responsibility for paying the taxes What the company is proposing is a very reasonable solution to the problem of recovering from the mistake. The alternative, as @mhoran_psprep points out, is to amend your 2010 and 2011 federal and state tax returns to declare the value of the rental during those years as additional income, and pay taxes (and possibly penalties) on the additional amount due. This takes the company completely out of the picture, but does require a lot more work and a lot more cash now rather than in the future.", "title": "" }, { "docid": "444246", "text": "If you have a one-time event, you are allowed to make a single estimated payment for that quarter on Form 1040-ES. People seem to fear that if they make one such payment they will need to do it forevermore, and that is not true. The IRS instructions do kind of read that way, but that's because most people who make estimated payment do so because of some repeating circumstance like being self-employed. In addition, you may qualify for one or more waivers on a potential underpayment penalty when you file your Form 1040 even if you don't make an estimated payment, and you may reduce or eliminate any penalty by annualizing your income - which is to say breaking it down by quarter rather than the full year. Check on the instructions for Form 2210 for more detail, including Schedule AI for annualizing income. This is some work, but it might be worthwhile depending on your situation. https://www.irs.gov/instructions/i2210/ch02.html", "title": "" }, { "docid": "574417", "text": "\"When you do your taxes, you have two choices for your deductions. You can take the standard deduction, or you can choose to itemize your deductions. If you itemize your deductions, you use Form 1040 Schedule A. By looking at Schedule A, you can see the list of deductions that are itemized: On Schedule A itself, you only list a total for each of these broad categories. In some cases, this is sufficient detail. However, for certain deductions, finer detail may be required, and you may have to submit additional forms showing this detail. For example, on the medical expense line, you generally only list a total of medical expenses; details are only supplied to the IRS upon request. For noncash gifts to charity, you need to supply more details on Form 8283 if your gifts are worth more than $500. These requirements can be found in the instructions for Schedule A. As noted by @Accumulation in the comments, the above deductions that are a part of your itemized deductions are called \"\"below the line\"\" deductions (because they are subtracted after the adjusted gross income line) and are only able to be deducted if you choose to decline the standard deduction. There are other deductions that are available whether or not you itemize. These \"\"above the line\"\" deductions are found on Form 1040 Lines 23-35. If you look at these lines on the form, you'll see the different types of deductions that are called out here. Some of these deductions require additional details on other forms; for example, the HSA deduction requires details on Form 8889. If you have a business, your business expenses are not part of your itemized deductions at all, and do not appear on Schedule A anywhere. Instead, your business expenses get subtracted from your business's revenue, and the resulting profit (or loss) is what is reported on your Form 1040. Different types of businesses report these expenses differently. If you have a sole proprietorship, the details of your business's expenses are reported on Schedule C. On this schedule, Part II is devoted to deductible business expenses. Take a look at Schedule C, and you'll see that Lines 8-27 are different categories of expenses that get called out on this schedule.\"", "title": "" }, { "docid": "206597", "text": "The rebate amount is a non-qualified distribution: IRS Pub 969 describes how the HSA works: Reporting Distributions on Your Return How you report your distributions depends on whether or not you use the distribution for qualified medical expenses (defined earlier). If you use a distribution from your HSA for qualified medical expenses, you do not pay tax on the distribution but you have to report the distribution on Form 8889. However, the distribution of an excess contribution taken out after the due date, including extensions, of your return is subject to tax even if used for qualified medical expenses. Follow the instructions for the form and file it with your Form 1040 or Form 1040NR. If you do not use a distribution from your HSA for qualified medical expenses, you must pay tax on the distribution. Report the amount on Form 8889 and file it with your Form 1040 or Form 1040NR. If you have a taxable HSA distribution, include it in the total on Form 1040 or Form 1040NR, line 21, and enter “HSA” and the amount on the dotted line next to line 21. You may have to pay an additional 20% tax on your taxable distribution. I looked at several plans regarding how to handle mistaken distributions: example A What if I accidentally use my HSA Visa debit card for a non-qualified expense? To fix this problem, just bring that same amount into any local branch and tell us it was a Mistaken Distribution. We can then put the funds back into your HSA and correct the problem. example B You’re allowed to correct mistaken HSA withdrawals when there is clear and convincing evidence that amounts were distributed from an HSA because of a mistake of fact due to reasonable cause. You can correct the mistake by repaying the withdrawal no later than April 15 following the first year that you knew or should have known that the withdrawal was a mistake. When a correction is made, the mistaken withdrawal does not have to be included in gross income or be subject to the 6 percent additional tax, and the repayment does not count as an excess contribution. If an error is made by SelectAccount in its role as the administrator, SelectAccount will be responsible for taking appropriate corrective action. Check with your plan trustee on their procedure to fix the mistaken withdrawal.", "title": "" }, { "docid": "496820", "text": "When you invest (say $1000) in (say 100 shares) of a mutual fund at $10 per share, and the price of the shares changes, you do not have a capital gain or loss, and you do not have to declare anything to the IRS or make any entry on any line on Form 1040 or tell anyone else about it either. You can brag about it at parties if the share price has gone up, or weep bitter tears into your cocktail if the price has gone down, but the IRS not only does not care, but it will not let you deduct the paper loss or pay taxes on the paper gain. What you put down on Form 1040 Schedules B and D is precisely what the mutual fund will tell you on Form 1099-DIV (and Form 1099-B), no more, no less. If you did not report any of these amounts on your previous tax returns, you need to file amended tax returns, both Federal as well as State, A stock mutual fund invests in stocks and the fund manager may buy and sell some stocks during the course of the year. If he makes a profit, that money will be distributed to the share holders of the mutual fund. That money can be re-invested in more shares of the same mutual fund or taken as cash (and possibly invested in some other fund). This capital gain distribution is reported to you on Form 1099-DIV and you have to report sit on your tax return even if you re-invested in more share of the same mutual fund, and the amount of the distribution is taxable income to you. Similarly, if the stocks owned by the mutual fund pay dividends, those will be passed on to you as a dividend distribution and all the above still applies. You can choose to reinvest, etc, the amount will be reported to you on Form 1099-DIV, and you need to report it to the IRS and include it in your taxable income. If the mutual fund manager loses money in the buying and selling he will not tell you that he lost money but it will be visible as a reduction in the price of the shares. The loss will not be reported to you on Form 1099-DIV and you cannot do anything about it. Especially important, you cannot declare to the IRS that you have a loss and you cannot deduct the loss on your income tax returns that year. When you finally sell your shares in the mutual fund, you will have a gain or loss that you can pay taxes on or deduct. Say the mutual fund paid a dividend of $33 one year and you re-invested the money into the mutual fund, buying 3 shares at the then cost of $11 per share. You declare the $33 on your tax return that year and pay taxes on it. Two years later, you sell all 103 shares that you own for $10.50 per share. Your total investment was $1000 + $33 = $1033. You get $1081.50 from the fund, and you will owe taxes on $1081.50 - $1033 = $48.50. You have a profit of $50 on the 100 shares originally bought and a loss of $1.50 on the 3 shares bought for $11: the net result is a gain of $48.50. You do not pay taxes on $81.50 as the profit from your original $1000 investment; you pay taxes only on $48.50 (remember that you already paid taxes on the $33). The mutual fund will report on Form 1099-B that you sold 103 shares for $1081.50 and that you bought the 103 shares for an average price of $1033/103 = $10.029 per share. The difference is taxable income to you. If you sell the 103 shares for $9 per share (say), then you get $927 out of an investment of $1033 for a capital loss of $106. This will be reported to you on Form 1099-B and you will enter the amounts on Schedule D of Form 1040 as a capital loss. What you actually pay taxes on is the net capital gain, if any, after combining all your capital gains and losses for the year. If the net is a loss, you can deduct up to $3000 in a year, and carry the rest forward to later years to offset capital gains in later years. But, your unrealized capital gains or losses (those that occur because the mutual fund share price goes up and down like a yoyo while you grin or grit your teeth and hang on to your shares) are not reported or deducted or taxed anywhere. It is more complicated when you don't sell all the shares you own in the mutual fund or if you sell shares within one year of buying them, but let's stick to simple cases.", "title": "" }, { "docid": "435405", "text": "\"(Insert the usual disclaimer that I'm not any sort of tax professional; I'm just a random guy on the Internet who occasionally looks through IRS instructions for fun. Then again, what you're doing here is asking random people on the Internet for help, so here goes.) The gigantic book of \"\"How to File Your Income Taxes\"\" from the IRS is called Publication 17. That's generally where I start to figure out where to report what. The section on Royalties has this to say: Royalties from copyrights, patents, and oil, gas, and mineral properties are taxable as ordinary income. In most cases, you report royalties in Part I of Schedule E (Form 1040). However, if you hold an operating oil, gas, or mineral interest or are in business as a self-employed writer, inventor, artist, etc., report your income and expenses on Schedule C or Schedule C-EZ (Form 1040). It sounds like you are receiving royalties from a copyright, and not as a self-employed writer. That means that you would report the income on Schedule E, Part I. I've not used Schedule E before, but looking at the instructions for it, you enter this as \"\"Royalty Property\"\". For royalty property, enter code “6” on line 1b and leave lines 1a and 2 blank for that property. So, in Line 1b, part A, enter code 6. (It looks like you'll only use section A here as you only have one royalty property.) Then in column A, Line 4, enter the royalties you have received. The instructions confirm that this should be the amount that you received listed on the 1099-MISC. Report on line 4 royalties from oil, gas, or mineral properties (not including operating interests); copyrights; and patents. Use a separate column (A, B, or C) for each royalty property. If you received $10 or more in royalties during 2016, the payer should send you a Form 1099-MISC or similar statement by January 31, 2017, showing the amount you received. Report this amount on line 4. I don't think that there's any relevant Expenses deductions you could take on the subsequent lines (though like I said, I've not used this form before), but if you had some specific expenses involved in producing this income it might be worth looking into further. On Line 21 you'd subtract the 0 expenses (or subtract any expenses you do manage to list) and put the total. It looks like there are more totals to accumulate on lines 23 and 24, which presumably would be equally easy as you only have the one property. Put the total again on line 26, which says to enter it on the main Form 1040 on line 17 and it thus gets included in your income.\"", "title": "" }, { "docid": "461527", "text": "No, always give the most current address information to the IRS, not least because they will use this address to send you important communications, such as refund checks or notices of deficiency. Per the 1040 Instructions, you should put in your address, with no mention of past addresses. Moreover, if you will change addresses after filing, the IRS has provided Form 8822 to notify them of the new address. There is a similar Form 8822-B for business addresses. They will use your Social Security Number (SSN), Individual Taxpayer Identification Number (ITIN), or Employer Identification Number (EIN) to track who you are. There's no point to purposely giving an invalid address, and in fact it's technically illegal since you will sign and certify the return as true and accurate to the best of your knowledge.", "title": "" }, { "docid": "14776", "text": "\"Yes, it is, but first let me address this sentence: my current withholding on my W4 is already at 0 so I can't make it lower You definitely can make it lower. On W4, in addition to the allowances (that what you meant by \"\"already at 0\"\"), there's also a line called \"\"additional withholding\"\". There, you put the dollar amount that you want your payroll to withhold from your paycheck each pay period. So the easiest way to \"\"send\"\" a one time payment to the IRS, if you're a W2 employee, would be to adjust that line with the amount you want to send, and change it back to 0 next pay period. You can also send a check directly to the IRS - follow the instructions to form 1040-ES. That is exactly what that form is designed to be used for.\"", "title": "" }, { "docid": "293687", "text": "\"Yes, you can do that, but you have to have the stocks issued in your name (stocks that you're holding through your broker are issued in \"\"street name\"\" to your broker). If you have a physical stock certificate issued in your name - you just endorse it like you would endorse a check and transfer the ownership. If the stocks don't physically exist - you let the stock registrar know that the ownership has been transferred to someone else. As to the price - the company doesn't care much about the price of private sales, but the taxing agency will. In the US, for example, you report such a transaction as either a gift (IRS form 709), if the transaction was at a price significantly lower than the FMV (or significantly higher, on the other end), or a sale (IRS form 1040, schedule D) if the transaction was at FMV.\"", "title": "" }, { "docid": "487728", "text": "I strongly recommend that you talk to an accountant right away because you could save some money by making a tax payment by January 15, 2014. You will receive Forms 1099-MISC from the various entities with whom you are doing business as a contractor detailing how much money they paid you. A copy will go to the IRS also. You file a Schedule C with your Form 1040 in which you detail how much you received on the 1099-MISC forms as well as any other income that your contracting business received (e.g. amounts less than $600 for which a 1099-MISc does not need to be issued, or tips, say, if you are a taxi-driver running your own cab), and you can deduct various expenses that you incurred in generating this income, including tools, books, (or gasoline!) etc that you bought for doing the job. You will need to file a Schedule SE that will compute how much you owe in Social Security and Medicare taxes on the net income on Schedule C. You will pay at twice the rate that employees pay because you get to pay not only the employee's share but also the employer's share. At least, you will not have to pay income tax on the employer's share. Your net income on Schedule C will transfer onto Form 1040 where you will compute how much income tax you owe, and then add on the Social Security tax etc to compute a final amount of tax to be paid. You will have to pay a penalty for not making tax payments every quarter during 2013, plus interest on the tax paid late. Send the IRS a check for the total. If you talk to an accountant right away, he/she will likely be able to come up with a rough estimate of what you might owe, and sending in that amount by January 15 will save some money. The accountant can also help you set up for the 2014 tax year during which you could make quarterly payments of estimated tax for 2014 and avoid the penalties and interest referred to above.", "title": "" } ]
178
Birth-weight is negatively associated with breast cancer.
[ { "docid": "16322674", "text": "BACKGROUND Birth size, perhaps a proxy for prenatal environment, might be a correlate of subsequent breast cancer risk, but findings from epidemiological studies have been inconsistent. We re-analysed individual participant data from published and unpublished studies to obtain more precise estimates of the magnitude and shape of the birth size-breast cancer association. METHODS AND FINDINGS Studies were identified through computer-assisted and manual searches, and personal communication with investigators. Individual participant data from 32 studies, comprising 22,058 breast cancer cases, were obtained. Random effect models were used, if appropriate, to combine study-specific estimates of effect. Birth weight was positively associated with breast cancer risk in studies based on birth records (pooled relative risk [RR] per one standard deviation [SD] [= 0.5 kg] increment in birth weight: 1.06; 95% confidence interval [CI] 1.02-1.09) and parental recall when the participants were children (1.02; 95% CI 0.99-1.05), but not in those based on adult self-reports, or maternal recall during the woman's adulthood (0.98; 95% CI 0.95-1.01) (p for heterogeneity between data sources = 0.003). Relative to women who weighed 3.000-3.499 kg, the risk was 0.96 (CI 0.80-1.16) in those who weighed < 2.500 kg, and 1.12 (95% CI 1.00-1.25) in those who weighed > or = 4.000 kg (p for linear trend = 0.001) in birth record data. Birth length and head circumference from birth records were also positively associated with breast cancer risk (pooled RR per one SD increment: 1.06 [95% CI 1.03-1.10] and 1.09 [95% CI 1.03-1.15], respectively). Simultaneous adjustment for these three birth size variables showed that length was the strongest independent predictor of risk. The birth size effects did not appear to be confounded or mediated by established breast cancer risk factors and were not modified by age or menopausal status. The cumulative incidence of breast cancer per 100 women by age 80 y in the study populations was estimated to be 10.0, 10.0, 10.4, and 11.5 in those who were, respectively, in the bottom, second, third, and top fourths of the birth length distribution. CONCLUSIONS This pooled analysis of individual participant data is consistent with birth size, and in particular birth length, being an independent correlate of breast cancer risk in adulthood.", "title": "Birth Size and Breast Cancer Risk: Re-analysis of Individual Participant Data from 32 Studies" }, { "docid": "23557241", "text": "BACKGROUND Emerging evidence suggests an association between female prenatal experience and her subsequent risk of developing breast cancer. Potential underlying mechanisms include variation in amounts of maternal endogenous sex hormones and growth hormones, germ-cell mutations, formation of cancer stem-cells, and other genetic or epigenetic events. We reviewed and summarised quantitatively the available data on intrauterine exposures and risk of breast cancer. METHODS We systematically searched for studies that assessed association between perinatal factors and risk of breast cancer. We reviewed separately each of the perinatal factors, including birthweight, birth length, parental age at delivery, gestational age, intrauterine exposure to diethylstilbestrol, twin membership, maternal pre-eclampsia or eclampsia, and other factors. FINDINGS We identified 57 studies published between Oct 1, 1980, and June 21, 2007. Increased risk of breast cancer was noted with increased birthweight (relative risk [RR] 1.15 [95% CI 1.09-1.21]), birth length (1.28 [1.11-1.48]), higher maternal age (1.13 [1.02-1.25]), and paternal age (1.12 [1.05-1.19]). Decreased risk of breast cancer was noted for maternal pre-eclampsia and eclampsia (0.48 [0.30-0.78]) and twin membership (0.93 [0.87-1.00]). No association was noted between risk of breast cancer and gestational age at birth (0.95 [0.71-1.26]) or maternal diethylstilbestrol treatment (1.40 [0.86-2.28]). INTERPRETATION The intrauterine environment contributes to the predisposition of women to breast cancer in adulthood. The in-utero mechanisms responsible for such predisposition need to be elucidated.", "title": "Intrauterine factors and risk of breast cancer: a systematic review and meta-analysis of current evidence." }, { "docid": "17450673", "text": "INTRODUCTION Various perinatal factors, including birth weight, birth order, maternal age, gestational age, twin status, and parental smoking, have been postulated to affect breast cancer risk in daughters by altering the hormonal environment of the developing fetal mammary glands. Despite ample biologic plausibility, epidemiologic studies to date have yielded conflicting results. We investigated the associations between perinatal factors and subsequent breast cancer risk through meta-analyses. METHODS We reviewed breast cancer studies published from January 1966 to February 2007 that included data on birth weight, birth order, maternal age, gestational age, twin status, and maternal or paternal smoking. Meta-analyses using random effect models were employed to summarize the results. RESULTS We found that heavier birth weights were associated with increased breast cancer risk, with studies involving five categories of birth weight identifying odds ratios (ORs) of 1.24 (95% confidence interval [CI] 1.04 to 1.48) for 4,000 g or more and 1.15 (95% CI 1.04 to 1.26) for 3,500 g to 3,999 g, relative to a birth weight of 2,500 to 2,599 g. These studies provided no support for a J-shaped relationship of birthweight to risk. Support for an association with birthweight was also derived from studies based on three birth weight categories (OR 1.15 [95% CI 1.01 to 1.31] for > or =4,000 g relative to <3,000 g) and two birth weight categories (OR 1.09 [95% CI 1.02 to 1.18] for > or =3,000 g relative to <3,000 g). Women born to older mothers and twins were also at some increased risk, but the results were heterogeneous across studies and publication years. Birth order, prematurity, and maternal smoking were unrelated to breast cancer risk. CONCLUSION Our findings provide some support for the hypothesis that in utero exposures reflective of higher endogenous hormone levels could affect risk for development of breast cancer in adulthood.", "title": "Intrauterine environments and breast cancer risk: meta-analysis and systematic review" }, { "docid": "27123743", "text": "Breast cancer may originate in utero. We reviewed the available evidence on the association between birthweight and the risk of breast cancer. To date, 26 research papers addressing this issue have been published. The majority of studies identified a positive link between birthweight and premenopausal, but not postmenopausal, breast cancer. The relative risk estimate for breast cancer comparing women with high birthweight to women with low birthweight combining all studies including both pre- and postmenopausal breast cancer was 1.23 (95% confidence interval 1.13-1.34). The mechanisms underlying this association likely include elevated levels of growth factors that may increase the number of susceptible stem cells in the mammary gland or initiate tumors through DNA mutations. Loss of imprinting (LOI) of growth hormone genes relevant for intrauterine growth, such as insulin-like growth factor 2 (IGF2), leads to abnormally high levels of these hormones evidenced by high birthweight. LOI of IGF2 has also been found in mammary tumor tissue. The role of environmental factors that stimulate such epigenetic regulation of gene expression remains to be elucidated.", "title": "Role of birthweight in the etiology of breast cancer." } ]
[ { "docid": "37480103", "text": "CONTEXT During pregnancy, serum levels of estrogen, progesterone, and other hormones are markedly higher than during other periods of life. Pregnancy hormones primarily are produced in the placenta, and signs of placental impairment may serve as indirect markers of hormone exposures during pregnancy. During pregnancy, these markers have been inconsistently associated with subsequent risk of breast cancer in the mother. OBJECTIVE To examine associations between indirect markers of hormonal exposures, such as placental weight and other pregnancy characteristics, and maternal risk of developing breast cancer. DESIGN AND SETTING Population-based cohort study using data from the Swedish Birth Register, the Swedish Cancer Register, the Swedish Cause of Death Register, and the Swedish Register of Population and Population Changes. PARTICIPANTS Women included in the Sweden Birth Register who delivered singletons between 1982 and 1989, with complete information on date of birth and gestational age. Women were followed up until the occurrence of breast cancer, death, or end of follow-up (December 31, 2001). Cox proportional hazards models were used to estimate associations between hormone exposures and risks of breast cancer. MAIN OUTCOME MEASURE Incidence of invasive breast cancer. RESULTS Of 314,019 women in the cohort, 2216 (0.7%) developed breast cancer during the follow-up through 2001, of whom 2100 (95%) were diagnosed before age 50 years. Compared with women who had placentas weighing less than 500 g in 2 consecutive pregnancies, the risk of breast cancer was increased among women whose placentas weighed between 500 and 699 g in their first pregnancy and at least 700 g in their second pregnancy (or vice versa) (adjusted hazard ratio, 1.82; 95% confidence interval [CI], 1.07-3.08), and the corresponding risk was doubled among women whose placentas weighed at least 700 g in both pregnancies (adjusted hazard ratio, 2.05; 95% CI, 1.15-3.64). A high birth weight (> or =4000 g) in 2 successive births was associated with an increased risk of breast cancer before but not after adjusting for placental weight and other covariates (adjusted hazard ratio, 1.10; 95% CI, 0.76-1.59). CONCLUSIONS Placental weight is positively associated with maternal risk of breast cancer. These results further support the hypothesis that pregnancy hormones are important modifiers of subsequent maternal breast cancer risk.", "title": "Pregnancy characteristics and maternal risk of breast cancer." }, { "docid": "5487448", "text": "Birth weight is a significant predictor of breast cancer risk in adult life and mammary gland mass could be an intermediate stage in this long process. We have studied the association of birth size measurements with mammographic density, a marker of mammary gland mass. For a population-based sample of 893 postmenopausal women without previous cancer in Sweden, we retrieved information on birth size from birth records and their most recent mammography. Film mammograms of the medio-lateral oblique view were digitized and the Cumulus software was used for computer-assisted semi-automated thresholding of mammographic density. Results were analyzed using generalized linear models controlling for possible confounders. Mean percent mammographic density increased when comparing the extreme categories of birth weight (from 15.6% to 18.6%) and head circumference (from 15.5% to 20.4%), and the corresponding linear trends were statistically significant (p values 0.02 and 0.007, respectively). The associations were particularly strong when the cutoff for high versus low mammographic density was set at the relatively high value of 50%. Compared to women weighing 3001-3500 grams at birth, women with birth weights >4000g were at almost 3-fold risk of developing high mammographic density (odds ratio: 2.9, 95% confidence interval 1.1 to 7.9). No association with mammographic density was evident with respect to birth length which, however, is known to be less accurately measured. These results indicate that adult breast density, a powerful predictor of breast cancer risk, has intrauterine roots, as reflected in birth size.", "title": "Birth weight and mammographic density among postmenopausal women in Sweden." }, { "docid": "38784540", "text": "Objective To determine whether risk factors in childhood and early adulthood affect later mammographic breast density. Methods: Subjects were 628 women who attended a medical examination at the University of Glasgow Student Health Service (1948–1968), responded to a questionnaire (2001) and had a screening mammogram in Scotland (1989–2002). Mammograms (median age of 59years) were classified using a six category classification (SCC) of breast density percent. Logistic regression was used to determine associations between risk factors and having a high-risk mammogram (≥25 dense). Results: In multi-variable analyses, high-risk mammograms were associated with parity (adjusted odds ratio (OR) per child: 0.77 (95 confidence interval (CI) 0.61–0.99)), age at first birth, OR per year: 1.05 (0.99–1.11), smoking at university, OR smokers versus non-smokers: 0.58 (0.36–0.92) and body mass index (BMI) while at university, OR per 1kg/m20.75 (0.69–0.82). No associations with SCC were found for age at menarche, birth weight, oral contraceptive (OC) use, height, leg length or exercise at age 20. Conclusions: We confirm previous findings that breast density is affected by reproductive events and some anthropometric measures, however most of the risk factors acting throughout the life course which we examined were not closely related to adult breast density.", "title": "Life course breast cancer risk factors and adult breast density (United Kingdom)" }, { "docid": "22007333", "text": "Menstrual and reproductive factors may increase breast cancer risk through a pathway that includes increased mammographic density. We assessed whether known or suspected menstrual and reproductive breast cancer risk factors were cross-sectionally associated with mammographic density, by measuring area of radiographic density and total breast area on mammograms from 801 participants in the Study of Women’s Health Across the Nation (SWAN), a multi-ethnic cohort of pre- and early perimenopausal women. From multivariable linear regression, the following menstrual or reproductive factors were independently associated with percent mammographic density (area of dense breast/breast area): older age at menarche (β = 10.3, P < 0.01, for >13 vs. <12 years), premenstrual cravings and bloating (β = −3.36, P = 0.02), younger age at first full-term birth (β = −8.12, P < 0.01 for ≤23 years versus no births), greater number of births (β = −6.80, P < 0.01 for ≥3 births versus no births), and premenopausal status (β = 3.78, P < 0.01 versus early perimenopausal). Only number of births remained associated with percent density after adjustment for age, race/ethnicity, study site, body mass index (BMI), and smoking. In addition, stratified analyses revealed that the association with number of births was confined to women within the lowest BMI tertile (β = −12.2, P < 0.01 for ≥3 births versus no births). Our data support a mechanism for parity and breast cancer that involves mammographic density among pre- and early perimenopausal women that may be modified by body size.", "title": "Menstrual and reproductive factors in relation to mammographic density: the Study of Women’s Health Across the Nation (SWAN)" }, { "docid": "13765757", "text": "Ages at menarche and first birth are established risk factors for breast cancer. The interval between these ages may also affect risk, since the breast is more susceptible to carcinogenic insults during this period than during the parous period. However, few investigators have studied this relation. Using logistic regression, the authors evaluated associations between the timing of reproductive events and breast cancer risk among 4,013 cases and 4,069 controls enrolled in a multicenter, population-based US case-control study of White and African-American women (1994-1998). For White, parous premenopausal and postmenopausal women, those who had an interval of > or =16 years between the ages of menarche and first birth had 1.5-fold (95% confidence interval (CI): 1.0, 2.2) and 1.4-fold (95% CI: 1.1, 1.8) increased risks of breast cancer, respectively, in comparison with those who had < or =5 years between these ages. Adjusting for age at first birth altered these risk estimates somewhat, to odds ratios of 1.5 (95% CI: 0.8, 2.9) and 1.0 (95% CI: 0.6, 1.5), respectively. These associations were stronger for lobular and hormone-receptor-positive tumors but were absent among premenopausal African-American women. The authors conclude that the interval between age at menarche and age at first birth is associated with the risk of hormonally sensitive types of breast cancer, particularly among White women.", "title": "Timing of menarche and first full-term birth in relation to breast cancer risk." }, { "docid": "16098747", "text": "Evaluate known breast cancer risk factors in relation to breast density. We examined factors in relation to breast density in 144,018 New Hampshire (NH) women with at least one mammogram recorded in a statewide mammography registry. Mammographic breast density was measured by radiologists using the BI-RADS classification; risk factors of interest were obtained from patient intake forms and questionnaires. Initial analyses showed a strong inverse influence of age and body mass index (BMI) on breast density. In addition, women with late age at menarche, late age at first birth, premenopausal women, and those currently using hormone therapy (HT) tended to have higher breast density, while those with greater parity tended to have less dense breasts. Analyses stratified on age and BMI suggested interactions, which were formally assessed in a multivariable model. The impact of current HT use, relative to nonuse, differed across age groups, with an inverse association in younger women, and a positive association in older women (p < 0.0001 for the interaction). The positive effects of age at menarche and age at first birth, and the inverse influence of parity were less apparent in women with low BMI than in those with high BMI (p = 0.04, p < 0.0001 and p = 0.01, respectively, for the interactions). We also noted stronger positive effects for age at first birth in postmenopausal women (p = 0.004 for the interaction). The multivariable model indicated a slight positive influence of family history of breast cancer. The influence of age at menarche and reproductive factors on breast density is less evident in women with high BMI. Density is reduced in young women using HT, but increased in HT users of age 50 or more.", "title": "Breast cancer risk factors in relation to breast density (United States)" }, { "docid": "13831842", "text": "The association between anthropometric indices and the risk of breast cancer was analyzed using pooled data from seven prospective cohort studies. Together, these cohorts comprise 337,819 women and 4,385 incident invasive breast cancer cases. In multivariate analyses controlling for reproductive, dietary, and other risk factors, the pooled relative risk (RR) of breast cancer per height increment of 5 cm was 1.02 (95% confidence interval (CI): 0.96, 1.10) in premenopausal women and 1.07 (95% CI: 1.03, 1.12) in postmenopausal women. Body mass index (BMI) showed significant inverse and positive associations with breast cancer among pre- and postmenopausal women, respectively; these associations were nonlinear. Compared with premenopausal women with a BMI of less than 21 kg/m2, women with a BMI exceeding 31 kg/m2 had an RR of 0.54 (95% CI: 0.34, 0.85). In postmenopausal women, the RRs did not increase further when BMI exceeded 28 kg/m2; the RR for these women was 1.26 (95% CI: 1.09, 1.46). The authors found little evidence for interaction with other breast cancer risk factors. Their data indicate that height is an independent risk factor for postmenopausal breast cancer; in premenopausal women, this relation is less clear. The association between BMI and breast cancer varies by menopausal status. Weight control may reduce the risk among postmenopausal women.", "title": "Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk." }, { "docid": "3285322", "text": "PURPOSE Mutations in the BRCA1 and BRCA2 genes confer greater risk of developing breast cancer. We determined whether tumor pathologic features and clinical features differ in patients with and without BRCA mutations. PATIENTS AND METHODS Tumor pathologic features and clinical characteristics were examined in 491 women with breast cancer who underwent genetic testing for BRCA mutations between 1997 and 2006. A retrospective review of medical records was conducted to determine clinical characteristics including ethnicity, age and clinical stage at diagnosis, age at parity, number of full-term pregnancies, use of oral contraceptives and hormone replacement therapy, and BRCA mutation status. Tumor pathology was reviewed to determine histologic type, tumor grade, and estrogen receptor, progesterone receptor, and HER-2/neu status. RESULTS Of the 491 patients with identified breast cancers, 391 patients were BRCA negative, and 86 patients were BRCA positive. Triple-negative breast cancer (ie, those with negative estrogen receptor, progesterone receptor, and HER-2/neu status) was diagnosed in 57.1% of the BRCA1-positive patients, 23.3% of the BRCA2-positive patients, and 13.8% of the BRCA-negative patients. BRCA1 mutation carriers had higher nuclear grade tumors than the other two groups (P < .001). Of the triple-negative cancer patients, BRCA2 mutation carriers were older when diagnosed than BRCA1 mutation carriers and noncarriers (P < .01). CONCLUSION These results suggest that tumors associated with BRCA1 mutations may be divided into two distinct groups, triple-negative and non-triple-negative groups. Future studies should seek to determine whether patients with BRCA1 mutations and triple-negative breast cancer respond to treatment better than BRCA-negative patients with similar tumor pathology.", "title": "Clinical and pathologic characteristics of patients with BRCA-positive and BRCA-negative breast cancer." }, { "docid": "13831558", "text": "BACKGROUND Extensive mammographic density is associated with an increased risk of breast cancer and makes the detection of cancer by mammography difficult, but the influence of density on risk according to method of cancer detection is unknown. METHODS We carried out three nested case-control studies in screened populations with 1112 matched case-control pairs. We examined the association of the measured percentage of density in the baseline mammogram with risk of breast cancer, according to method of cancer detection, time since the initiation of screening, and age. RESULTS As compared with women with density in less than 10% of the mammogram, women with density in 75% or more had an increased risk of breast cancer (odds ratio, 4.7; 95% confidence interval [CI], 3.0 to 7.4), whether detected by screening (odds ratio, 3.5; 95% CI, 2.0 to 6.2) or less than 12 months after a negative screening examination (odds ratio, 17.8; 95% CI, 4.8 to 65.9). Increased risk of breast cancer, whether detected by screening or other means, persisted for at least 8 years after study entry and was greater in younger than in older women. For women younger than the median age of 56 years, 26% of all breast cancers and 50% of cancers detected less than 12 months after a negative screening test were attributable to density in 50% or more of the mammogram. CONCLUSIONS Extensive mammographic density is strongly associated with the risk of breast cancer detected by screening or between screening tests. A substantial fraction of breast cancers can be attributed to this risk factor.", "title": "Mammographic density and the risk and detection of breast cancer." }, { "docid": "313403", "text": "The tumor microenvironment is composed of tumor cells, fibroblasts, endothelial cells and infiltrating immune cells, which may inhibit or promote tumor growth and progression. The objectives of this retrospective study were to characterize the density of tumor-associated macrophages (TAMs) in breast cancer, and to correlate the density of TAMs with clinicopathological parameters. Paraffin-embedded specimens and clinicopathological data, including up to 5 years follow-up information, were obtained from 172 breast cancer patients. Immunohistochemical staining for CD68 (marker for macrophages) was performed and evaluated in a blinded fashion. We found that TAMs were significantly frequent in high histopathological grade breast cancer patients. Breast cancer patients with a high density of TAMs had significantly lower rates of disease-free survival and 5-year overall survival than patients with low density of TAMs. Furthermore, high-infiltration of TAMs indicated worse survival rate for patients with node-negative breast cancer. In conclusion, the number of TAMs in the tumor stroma is an independent predictor of survival time for breast cancer patients. High-infiltration of TAMs is a significant unfavorable prognostic factor for patients with invasive breast cancer and, as such, is a potentially useful prognostic marker for breast cancer.", "title": "High-Infiltration of Tumor-Associated Macrophages Predicts Unfavorable Clinical Outcome for Node-Negative Breast Cancer" }, { "docid": "25973484", "text": "Obesity has a complicated relationship to both breast cancer risk and the clinical behavior of the established disease. In postmenopausal women, particularly the elderly, various measures of obesity have been positively associated with risk. However, before menopause increased body weight is inversely related to breast cancer risk. In both premenopausal and postmenopausal breast cancer, the mechanisms by which body weight and obesity affect risk have been related to estrogenic activity. Obesity has also been related to advanced disease at diagnosis and with a poor prognosis in both premenopausal and postmenopausal breast cancer. Breast cancer in African-American women, considering its relationship to obesity, exhibits some important differences from those described in white women, although the high prevalence of obesity in African-American women may contribute to the relatively poor prognosis compared with white American women. Despite the emphasis on estrogens to explain the effects of obesity on breast cancer, other factors may prove to be equally or more important, particularly as they relate to expression of an aggressive tumor phenotype. Among these, this review serves to stress insulin, insulin-like growth factor-I, and leptin, and their relationship to angiogenesis, and transcriptional factors.", "title": "Breast cancer and obesity: an update." }, { "docid": "1171121", "text": "A considerable subgroup of patients with early breast cancer does not address benefits of anthracycline based chemotherapy. The aim of this retrospective study was to investigate the effect of microvessel density (MVD) and status of p53 protein on 5-year disease free survival (DFS) in the group of breast cancer patients treated with anthracyclines in adjuvant setting. Correlations between MVD, p53 status and other clinicopathological parameters were also assessed. MVD and p53 status were analyzed immunohistochemically in the group of 172 women with breast cancer in clinical stage T1-2, N1-N2, M0. There were 123 tumors (71.5 %) with lower MVD (≤ 214.8 microvesells/mm(2)) and 49 (28.5 %) with higher MVD (>214.8 microvesells/mm(2)). The proportion of higher MVD tumors significantly increased in N2 (P = 0.000) and in estrogen (P = 0.046) or progesterone receptors (P = 0.029) negative tumors. p53 positivity was indicated in 50 cancers (29.1 %) and was significantly associated with higher grade (P = 0.000), steroid receptors negativity (P = 0.000), cytokeratin5/6 positivity (P = 0.026), topoisomerase IIα overexpression (P = 0.005) and higher proliferation rate (P = 0.001). In univariate analysis, higher MVD (P = 0.016) and p53 negativity (P = 0.023) were significantly related with longer DFS (median follow-up 36 months). In multivariate Cox regression analysis MVD was independently associated with DFS. These data suggest that higher MVD is favourable prognostic factors for early advanced breast cancer patients after adjuvant anthracycline based chemotherapy.", "title": "Microvessel Density and Status of p53 Protein as Potential Prognostic Factors for Adjuvant Anthracycline Chemotherapy in Retrospective Analysis of Early Breast Cancer Patients Group" }, { "docid": "20280410", "text": "Inherited mutations in the gene BRCA2 predispose carriers to early onset breast cancer, but such mutations account for fewer than 2% of all cases in East Anglia. It is likely that low penetrance alleles explain the greater part of inherited susceptibility to breast cancer; polymorphic variants in strongly predisposing genes, such as BRCA2, are candidates for this role. BRCA2 is thought to be involved in DNA double strand break-repair. Few mice in which Brca2 is truncated survive to birth; of those that do, most are male, smaller than their normal littermates and have high cancer incidence. Here we show that a common human polymorphism (N372H) in exon 10 of BRCA2 confers an increased risk of breast cancer: the HH homozygotes have a 1.31-fold (95% CI, 1.07–1.61) greater risk than the NN group. Moreover, in normal female controls of all ages there is a significant deficiency of homozygotes compared with that expected from Hardy-Weinberg equilibrium, whereas in males there is an excess of homozygotes: the HH group has an estimated fitness of 0.82 in females and 1.38 in males. Therefore, this variant of BRCA2 appears also to affect fetal survival in a sex-dependent manner.", "title": "A common variant in BRCA2 is associated with both breast cancer risk and prenatal viability" }, { "docid": "5222182", "text": "Understanding which factors influence mammographically dense and nondense areas is important because percent mammographic density adjusted for age is a strong, continuously distributed risk factor for breast cancer, especially when adjusted for weight or body mass index. Using computer-assisted methods, we measured mammographically dense areas for 571 monozygotic and 380 dizygotic Australian and North American twin pairs ages 40 to 70 years. We used a novel regression modeling approach in which each twin's measure of dense and nondense area was regressed against one or both of the twin's and co-twin's covariates. The nature of changes to regression estimates with the inclusion of the twin and/or co-twin's covariates can be evaluated for consistency with causal and/or other models. By causal, we mean that if it were possible to vary a covariate experimentally then the expected value of the outcome measure would change. After adjusting for the individual's weight, the co-twin associations with weight were attenuated, consistent with a causal effect of weight on mammographic measures, which in absolute log cm(2)/kg was thrice stronger for nondense than dense area. After adjusting for weight, later age at menarche, and greater height were associated with greater dense and lesser nondense areas in a manner inconsistent with causality. The associations of dense and nondense areas with parity are consistent with a causal effect and/or within-person confounding. The associations between mammographic density measures and height are consistent with shared early life environmental factors that predispose to both height and percent mammographic density and possibly breast cancer risk.", "title": "Predictors of mammographic density: insights gained from a novel regression analysis of a twin study." }, { "docid": "16701509", "text": "BACKGROUND The prevalence of metabolic syndrome (obesity, glucose intolerance, low serum high-density lipoprotein cholesterol [HDL-C], high serum triglycerides, hypertension) is high and increasing in parallel with an increasing breast cancer incidence worldwide. HDL-C represents an important aspect of the syndrome, yet its role in breast cancer is still undefined. METHODS In two population-based screening surveys during 1977-1983 and 1985-1987, serum HDL-C was assayed enzymatically among 38,823 Norwegian women aged 17-54 years at entry. Height, weight, blood pressure, serum lipids, fat and energy intake, physical activity, parity, oral contraceptive use, hormone therapy use, alcohol intake, and tobacco use were also assessed. We used Cox proportional hazards modeling to estimate the relative risk (RR) of breast cancer associated with serum HDL-C levels and to adjust for potential confounding variables. We performed stratified analyses to evaluate effect modification by body mass index (BMI) and menopausal status. All statistical tests were two-sided. RESULTS During a median follow-up of 17.2 years, we identified 708 cases of invasive breast cancer. In multivariable analysis, the risk of postmenopausal breast cancer was inversely related to quartile of HDL-C (P(trend) =.02). Among women with HDL-C above 1.64 mmol/L (highest quartile) versus below 1.20 mmol/L (lowest quartile), the relative risk was 0.75 (95% confidence interval [CI] = 0.58 to 0.97). The HDL-C association was confined to women in the heavier subgroup (BMI > or =25 kg/m2), for whom the relative risk of postmenopausal breast cancer in those with HDL-C above 1.64 mmol/L versus below 1.20 mmol/L was 0.43 (95% CI = 0.28 to 0.67; P(trend)<.001; P(interaction) =.001). CONCLUSION Low HDL-C, as part of the metabolic syndrome, is associated with increased postmenopausal breast cancer risk.", "title": "Serum high-density lipoprotein cholesterol, metabolic profile, and breast cancer risk." }, { "docid": "18340282", "text": "BACKGROUND Information is scarce about the combined effects on breast cancer incidence of low-penetrance genetic susceptibility polymorphisms and environmental factors (reproductive, behavioural, and anthropometric risk factors for breast cancer). To test for evidence of gene-environment interactions, we compared genotypic relative risks for breast cancer across the other risk factors in a large UK prospective study. METHODS We tested gene-environment interactions in 7610 women who developed breast cancer and 10 196 controls without the disease, studying the effects of 12 polymorphisms (FGFR2-rs2981582, TNRC9-rs3803662, 2q35-rs13387042, MAP3K1-rs889312, 8q24-rs13281615, 2p-rs4666451, 5p12-rs981782, CASP8-rs1045485, LSP1-rs3817198, 5q-rs30099, TGFB1-rs1982073, and ATM-rs1800054) in relation to prospectively collected information about ten established environmental risk factors (age at menarche, parity, age at first birth, breastfeeding, menopausal status, age at menopause, use of hormone replacement therapy, body-mass index, height, and alcohol consumption). FINDINGS After allowance for multiple testing none of the 120 comparisons yielded significant evidence of a gene-environment interaction. By contrast with previous suggestions, there was little evidence that the genotypic relative risks were affected by use of hormone replacement therapy, either overall or for oestrogen-receptor-positive disease. Only one of the 12 polymorphisms was correlated with any of the ten other risk factors: carriers of the high-risk C allele of MAP3K1-rs889312 were significantly shorter than non-carriers (mean height 162.4 cm [95% CI 162.1-162.7] vs 163.1 cm [162.9-163.2]; p=0.01 after allowance for multiple testing). INTERPRETATION Risks of breast cancer associated with low-penetrance susceptibility polymorphisms do not vary significantly with these ten established environmental risk factors. FUNDING Cancer Research UK and the UK Medical Research Council.", "title": "Gene–environment interactions in 7610 women with breast cancer: prospective evidence from the Million Women Study" }, { "docid": "27240667", "text": "PURPOSE Since 1990, overall breast cancer mortality rates in the United States decreased 24%. This decline has been attributed to mammography screening and adjuvant systemic therapy. However, the efficacy of these modalities may depend on estrogen receptor (ER) expression and age. We therefore examined breast cancer mortality trends in the United States according to ER status and age. METHODS Using the Surveillance, Epidemiology, and End Results (SEER) program (1990-2003), we calculated trends in incidence-based mortality (IBM), annual hazard rates for breast cancer deaths after diagnosis, and relative hazard rates for women with ER-positive and ER-negative tumors. Relative hazard rates were assessed with Cox proportional hazards models, adjusted for stage and grade, and stratified by age at diagnosis. RESULTS During the study period, IBM and annual hazard rates for breast cancer deaths decreased among women with ER-positive and ER-negative tumors, although declines were greater for those with ER-positive tumors. Among women younger than 70 years, relative hazard rates declined 38% for those with ER-positive tumors versus 19% for those with ER-negative tumors. Among women 70 years or older, relative hazard rates declined 14% for those with ER-positive tumors versus no significant decline for those with ER-negative tumors. CONCLUSION In the United States, breast cancer mortality rates have declined among women with ER-positive and ER-negative tumors, with greater declines among younger women and those with ER-positive tumors. Although mortality in all groups remains unacceptably high, additional emphasis should be placed on improving outcomes of breast cancer patients older than 70 years and those of all ages with ER-negative tumors.", "title": "Breast cancer mortality trends in the United States according to estrogen receptor status and age at diagnosis." }, { "docid": "12762485", "text": "AIM Several studies have investigated the expression of the cytokeratins (CKs), vimentin, the epithelial growth factor receptor (EGFR), the oestrogen receptor (ER), and the progesterone receptor (PgR), in breast cancer, but no study has directly compared p53 mutations with these phenotypic and differentiation markers in the same case. The present study was designed to provide some of this information. METHODS The expression of the p53 and bcl-2 proteins was evaluated by immunohistochemistry in relation to phenotypic characteristics and cellular kinetic parameters (mitotic index and apoptotic index) in 37 cases of ductal carcinoma in situ (DCIS) and 27 cases of infiltrating ductal carcinoma (IDC) of the breast. In addition, p53 gene mutation was examined by polymerase chain reaction single strand conformation polymorphism analysis (SSCP). RESULTS Thirteen cases (eight DCIS and five IDC) showed expression of CK8, CK14, CK18, vimentin, and EGFR, consistent with a stem cell phenotype, whereas 44 cases (27 DCIS and 17 IDC) showed expression of CK8 and CK1, weak or negative expression of CK18, but were negative for vimentin and EGFR, consistent with a luminal cell phenotype. DCIS and IDC cases with a stem cell phenotype were ER/PgR negative and intermediately or poorly differentiated. In contrast, the cases with luminal cell phenotype were ER/PgR positive and well or intermediately differentiated. In addition, intermediately or poorly differentiated cases with a stem cell phenotype showed higher proliferative activity (per cent of MIB-l positive cells) than did intermediately or well differentiated cases with a luminal cell phenotype. Both DCIS and IDC cases with a stem cell phenotype were p53 positive and bcl-2 negative by immunohistochemistry. In IDC, p53 expression was associated with a reduction of both mitotic index and apoptotic index compared with DCIS. Most of the tumours showing a more differentiated phenotype (luminal) were p53 negative and bcl-2 positive. In these cases, cell kinetic parameters increased from DCIS to IDC. These data suggest the existence of subsets of DCIS and IDC that, because of their phenotypic characteristics, could be derived from subpopulations of normal breast cells having different control mechanisms of cell proliferation and neoplastic progression. CONCLUSIONS These results are compatible with the hypothesis that the phenotype of the cell of origin constrains both tumour phenotype and the choice of genetic events; however, the occurrence of p53 mutants by chance during neoplastic transformation cannot be excluded.", "title": "p53 mutation in breast cancer. Correlation with cell kinetics and cell of origin." }, { "docid": "4828631", "text": "BACKGROUND High body-mass index (BMI) predisposes to several site-specific cancers, but a large-scale systematic and detailed characterisation of patterns of risk across all common cancers adjusted for potential confounders has not previously been undertaken. We aimed to investigate the links between BMI and the most common site-specific cancers. METHODS With primary care data from individuals in the Clinical Practice Research Datalink with BMI data, we fitted Cox models to investigate associations between BMI and 22 of the most common cancers, adjusting for potential confounders. We fitted linear then non-linear (spline) models; investigated effect modification by sex, menopausal status, smoking, and age; and calculated population effects. FINDINGS 5·24 million individuals were included; 166,955 developed cancers of interest. BMI was associated with 17 of 22 cancers, but effects varied substantially by site. Each 5 kg/m(2) increase in BMI was roughly linearly associated with cancers of the uterus (hazard ratio [HR] 1·62, 99% CI 1·56-1·69; p<0·0001), gallbladder (1·31, 1·12-1·52; p<0·0001), kidney (1·25, 1·17-1·33; p<0·0001), cervix (1·10, 1·03-1·17; p=0·00035), thyroid (1·09, 1·00-1·19; p=0·0088), and leukaemia (1·09, 1·05-1·13; p≤0·0001). BMI was positively associated with liver (1·19, 1·12-1·27), colon (1·10, 1·07-1·13), ovarian (1·09, 1.04-1.14), and postmenopausal breast cancers (1·05, 1·03-1·07) overall (all p<0·0001), but these effects varied by underlying BMI or individual-level characteristics. We estimated inverse associations with prostate and premenopausal breast cancer risk, both overall (prostate 0·98, 0·95-1·00; premenopausal breast cancer 0·89, 0·86-0·92) and in never-smokers (prostate 0·96, 0·93-0·99; premenopausal breast cancer 0·89, 0·85-0·94). By contrast, for lung and oral cavity cancer, we observed no association in never smokers (lung 0·99, 0·93-1·05; oral cavity 1·07, 0·91-1·26): inverse associations overall were driven by current smokers and ex-smokers, probably because of residual confounding by smoking amount. Assuming causality, 41% of uterine and 10% or more of gallbladder, kidney, liver, and colon cancers could be attributable to excess weight. We estimated that a 1 kg/m(2) population-wide increase in BMI would result in 3790 additional annual UK patients developing one of the ten cancers positively associated with BMI. INTERPRETATION BMI is associated with cancer risk, with substantial population-level effects. The heterogeneity in the effects suggests that different mechanisms are associated with different cancer sites and different patient subgroups. FUNDING National Institute for Health Research, Wellcome Trust, and Medical Research Council.", "title": "Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults" }, { "docid": "20839751", "text": "Apoptosis is a frequent phenomenon in breast cancer and it can be detected by light microscopy in conventional histopathological sections or by special staining techniques. The number of apoptotic cells as a percentage of cells present, or the number of apoptotic cells per square millimetre of neoplastic tissue, is usually described as the apoptotic index (AI). In breast cancer, the AI is not related to tumour size, axillary lymph node metastasis or distant metastasis at diagnosis. It is greater in invasive ductal carcinomas than in other histological types. High AI is also related to high histological grade, high nuclear grade, comedo-type necrosis, lack of tubule formation, and dense infiltration of the tumour by lymphocytes. Sex steroid receptor-negative tumours have greater AIs than the sex steroid receptor-positive ones. Aneuploid breast cancers with high S-phase fractions (SPFs) also have high AI values compared with diploid tumours with low SPFs. p53-Positive breast cancers have high AIs, whereas tumours that are Bcl-2 positive have low AIs. The AI shows a strong positive correlation to all direct or indirect indicators of cell proliferation, such as mitotic index and Ki67 immunolabelling. Univariate survival analyses show that a high AI is linked with unfavourable disease outcome in axillary lymph node-negative and -positive breast cancer, but multivariate analyses indicate that AI is not an independent prognostic factor. In conclusion, a high AI is related to malignant cellular features and indicators of invasiveness and cell proliferation in breast cancer.", "title": "Apoptosis in breast cancer: relationship with other pathological parameters." }, { "docid": "2425364", "text": "OBJECTIVE To assess the effect of 25-hydroxyvitamin D (25-OHD) levels on pregnancy outcomes and birth variables. DESIGN Systematic review and meta-analysis. DATA SOURCES Medline (1966 to August 2012), PubMed (2008 to August 2012), Embase (1980 to August 2012), CINAHL (1981 to August 2012), the Cochrane database of systematic reviews, and the Cochrane database of registered clinical trials. STUDY SELECTION Studies reporting on the association between serum 25-OHD levels during pregnancy and the outcomes of interest (pre-eclampsia, gestational diabetes, bacterial vaginosis, caesarean section, small for gestational age infants, birth weight, birth length, and head circumference). DATA EXTRACTION Two authors independently extracted data from original research articles, including key indicators of study quality. We pooled the most adjusted odds ratios and weighted mean differences. Associations were tested in subgroups representing different patient characteristics and study quality. RESULTS 3357 studies were identified and reviewed for eligibility. 31 eligible studies were included in the final analysis. Insufficient serum levels of 25-OHD were associated with gestational diabetes (pooled odds ratio 1.49, 95% confidence interval 1.18 to 1.89), pre-eclampsia (1.79, 1.25 to 2.58), and small for gestational age infants (1.85, 1.52 to 2.26). Pregnant women with low serum 25-OHD levels had an increased risk of bacterial vaginosis and low birthweight infants but not delivery by caesarean section. CONCLUSION Vitamin D insufficiency is associated with an increased risk of gestational diabetes, pre-eclampsia, and small for gestational age infants. Pregnant women with low 25-OHD levels had an increased risk of bacterial vaginosis and lower birth weight infants, but not delivery by caesarean section.", "title": "Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observational studies." }, { "docid": "3524352", "text": "High breast cancer mortality rates have been reported in the northeastern part of the United States, with recent attention focused on Long Island, New York. In this study, the authors investigate whether the high breast cancer mortality is evenly spread over the Northeast, in the sense that any observed clusters of deaths can be explained by chance alone, or whether there are clusters of statistical significance. Demographic data and age-specific breast cancer mortality rates for women were obtained for all 244 counties in 11 northeastern states and for the District of Columbia for 1988-1992. A recently developed spatial scan statistic is used, which searches for clusters of cases without specifying their size or location ahead of time, and which tests for their statistical significance while adjusting for the multiple testing inherent in such a procedure. The basic analysis is adjusted for age, with further analyses examining how the results are affected by incorporating race, urbanicity, and parity as confounding variables. There is a statistically significant and geographically broad cluster of breast cancer deaths in the New York City-Philadelphia, Pennsylvania, metropolitan area (p = 0.0001), which has a 7.4% higher mortality rate than the rest of the Northeast. The cluster remains significant when race, urbanicity, and/or parity are included as confounding variables. Four smaller subclusters within this area are also significant on their own strength: Philadelphia with suburbs (p = 0.0001), Long Island (p = 0.0001), central New Jersey (p = 0.0001), and northeastern New Jersey (p = 0.0001). The elevated breast cancer mortality on Long Island might be viewed less as a unique local phenomenon and more as part of a more general situation involving large parts of the New York City-Philadelphia metropolitan area. The several known and hypothesized risk factors for which we could not adjust and that may explain the detected cluster are most notably age at first birth, age at menarche, age at menopause, breastfeeding, genetic mutations, and environmental factors.", "title": "Breast cancer clusters in the northeast United States: a geographic analysis." }, { "docid": "8529693", "text": "In this paper we review the associations between maternal and child undernutrition with human capital and risk of adult diseases in low-income and middle-income countries. We analysed data from five long-standing prospective cohort studies from Brazil, Guatemala, India, the Philippines, and South Africa and noted that indices of maternal and child undernutrition (maternal height, birthweight, intrauterine growth restriction, and weight, height, and body-mass index at 2 years according to the new WHO growth standards) were related to adult outcomes (height, schooling, income or assets, offspring birthweight, body-mass index, glucose concentrations, blood pressure). We undertook systematic reviews of studies from low-income and middle-income countries for these outcomes and for indicators related to blood lipids, cardiovascular disease, lung and immune function, cancers, osteoporosis, and mental illness. Undernutrition was strongly associated, both in the review of published work and in new analyses, with shorter adult height, less schooling, reduced economic productivity, and--for women--lower offspring birthweight. Associations with adult disease indicators were not so clear-cut. Increased size at birth and in childhood were positively associated with adult body-mass index and to a lesser extent with blood pressure values, but not with blood glucose concentrations. In our new analyses and in published work, lower birthweight and undernutrition in childhood were risk factors for high glucose concentrations, blood pressure, and harmful lipid profiles once adult body-mass index and height were adjusted for, suggesting that rapid postnatal weight gain--especially after infancy--is linked to these conditions. The review of published works indicates that there is insufficient information about long-term changes in immune function, blood lipids, or osteoporosis indicators. Birthweight is positively associated with lung function and with the incidence of some cancers, and undernutrition could be associated with mental illness. We noted that height-for-age at 2 years was the best predictor of human capital and that undernutrition is associated with lower human capital. We conclude that damage suffered in early life leads to permanent impairment, and might also affect future generations. Its prevention will probably bring about important health, educational, and economic benefits. Chronic diseases are especially common in undernourished children who experience rapid weight gain after infancy.", "title": "Maternal and child undernutrition: consequences for adult health and human capital" }, { "docid": "24249915", "text": "To gain insights into the possible role of oestrogen receptor (ER) beta in breast carcinogenesis, immunohistochemical analysis of ER beta was performed on 512 breast specimens encompassing normal (n = 138), pure ductal carcinoma in situ (n = 16), invasive cancers (n = 319), lymph node metastases (n = 31), and recurrences (n = 8). Real-time polymerase chain reaction (PCR) was used to investigate the methylation status of the ER beta gene in the ER beta negative breast cancer cell lines SkBr3 and MDA-MB-435. A gradual reduction in, but not a complete loss of, ER beta expression was observed during the transition from normal and pre-invasive lesions to invasive cancers, where ER beta was lost in 21% of cases. This was more pronounced in invasive ductal than in lobular carcinomas, a significantly higher proportion of which were ER beta-positive (74% compared with 91%, respectively, p = 0.0004). Examination of paired primary cancers with their axillary lymph node metastases showed that if ER beta was present in the primary tumour, it persisted in the metastasis. Treatment of ER beta-negative cell lines with DNA methyl transferase inhibitors restored ER beta expression, providing experimental evidence that silencing of ER beta in breast carcinomas could be due to promoter hypermethylation. These results suggest that loss of ER beta expression is one of the hallmarks of breast carcinogenesis and that it may be a reversible process involving methylation.", "title": "Reduced expression of oestrogen receptor beta in invasive breast cancer and its re-expression using DNA methyl transferase inhibitors in a cell line model." }, { "docid": "11360768", "text": "OBJECTIVE To evaluate the effects of dietary and lifestyle interventions in pregnancy on maternal and fetal weight and to quantify the effects of these interventions on obstetric outcomes. DESIGN Systematic review and meta-analysis. DATA SOURCES Major databases from inception to January 2012 without language restrictions. STUDY SELECTION Randomised controlled trials that evaluated any dietary or lifestyle interventions with potential to influence maternal weight during pregnancy and outcomes of pregnancy. DATA SYNTHESIS Results summarised as relative risks for dichotomous data and mean differences for continuous data. RESULTS We identified 44 relevant randomised controlled trials (7278 women) evaluating three categories of interventions: diet, physical activity, and a mixed approach. Overall, there was 1.42 kg reduction (95% confidence interval 0.95 to 1.89 kg) in gestational weight gain with any intervention compared with control. With all interventions combined, there were no significant differences in birth weight (mean difference -50 g, -100 to 0 g) and the incidence of large for gestational age (relative risk 0.85, 0.66 to 1.09) or small for gestational age (1.00, 0.78 to 1.28) babies between the groups, though by itself physical activity was associated with reduced birth weight (mean difference -60 g, -120 to -10 g). Interventions were associated with a reduced the risk of pre-eclampsia (0.74, 0.60 to 0.92) and shoulder dystocia (0.39, 0.22 to 0.70), with no significant effect on other critically important outcomes. Dietary intervention resulted in the largest reduction in maternal gestational weight gain (3.84 kg, 2.45 to 5.22 kg), with improved pregnancy outcomes compared with other interventions. The overall evidence rating was low to very low for important outcomes such as pre-eclampsia, gestational diabetes, gestational hypertension, and preterm delivery. CONCLUSIONS Dietary and lifestyle interventions in pregnancy can reduce maternal gestational weight gain and improve outcomes for both mother and baby. Among the interventions, those based on diet are the most effective and are associated with reductions in maternal gestational weight gain and improved obstetric outcomes.", "title": "Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence" }, { "docid": "26611834", "text": "CONTEXT Maternal depressive symptoms during pregnancy have been reported in some, but not all, studies to be associated with an increased risk of preterm birth (PTB), low birth weight (LBW), and intrauterine growth restriction (IUGR). OBJECTIVE To estimate the risk of PTB, LBW, and IUGR associated with antenatal depression. DATA SOURCES AND STUDY SELECTION We searched for English-language and non-English-language articles via the MEDLINE, PsycINFO, CINAHL, Social Work Abstracts, Social Services Abstracts, and Dissertation Abstracts International databases (January 1980 through December 2009). We aimed to include prospective studies reporting data on antenatal depression and at least 1 adverse birth outcome: PTB (<37 weeks' gestation), LBW (<2500 g), or IUGR (<10th percentile for gestational age). Of 862 reviewed studies, 29 US-published and non-US-published studies met the selection criteria. DATA EXTRACTION Information was extracted on study characteristics, antenatal depression measurement, and other biopsychosocial risk factors and was reviewed twice to minimize error. DATA SYNTHESIS Pooled relative risks (RRs) for the effect of antenatal depression on each birth outcome were calculated using random-effects methods. In studies of PTB, LBW, and IUGR that used a categorical depression measure, pooled effect sizes were significantly larger (pooled RR [95% confidence interval] = 1.39 [1.19-1.61], 1.49 [1.25-1.77], and 1.45 [1.05-2.02], respectively) compared with studies that used a continuous depression measure (1.03 [1.00-1.06], 1.04 [0.99-1.09], and 1.02 [1.00-1.04], respectively). The estimates of risk for categorically defined antenatal depression and PTB and LBW remained significant when the trim-and-fill procedure was used to correct for publication bias. The risk of LBW associated with antenatal depression was significantly larger in developing countries (RR = 2.05; 95% confidence interval, 1.43-2.93) compared with the United States (RR = 1.10; 95% confidence interval, 1.01-1.21) or European social democracies (RR = 1.16; 95% confidence interval, 0.92-1.47). Categorically defined antenatal depression tended to be associated with an increased risk of PTB among women of lower socioeconomic status in the United States. CONCLUSIONS Women with depression during pregnancy are at increased risk for PTB and LBW, although the magnitude of the effect varies as a function of depression measurement, country location, and US socioeconomic status. An important implication of these findings is that antenatal depression should be identified through universal screening and treated.", "title": "A meta-analysis of depression during pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction." }, { "docid": "12438901", "text": "BACKGROUND For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years. METHODS In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12,894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633. FINDINGS Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0·90 [95% CI 0·79–1·02] during years 5–9 and 0·75 [0·62–0·90] in later years; breast cancer mortality RR 0·97 [0·79–1·18] during years 5–9 and 0·71 [0·58–0·88] in later years). The cumulative risk of recurrence during years 5–14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5–14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality reduction 2·8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12,894 women, mortality without recurrence from causes other than breast cancer was little affected (691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0·99 [0·89–1·10]; p=0·84). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1·87 (95% CI 1·13–3·07, p=0·01 [including 0·2% mortality in both treatment groups]), stroke 1·06 (0·83–1·36), ischaemic heart disease 0·76 (0·60–0·95, p=0·02), and endometrial cancer 1·74 (1·30–2·34, p=0·0002). The cumulative risk of endometrial cancer during years 5–14 was 3·1% (mortality 0·4%) for women allocated to continue versus 1·6% (mortality 0·2%) for controls (absolute mortality increase 0·2%). INTERPRETATION For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis. FUNDING Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU-Biomed.", "title": "Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial" }, { "docid": "16086778", "text": "The biological antagonism between Notch and Numb controls the proliferative/differentiative balance in development and homeostasis. Although altered Notch signaling has been linked to human diseases, including cancer, evidence for a substantial involvement of Notch in human tumors has remained elusive. Here, we show that Numb-mediated control on Notch signaling is lost in ∼50% of human mammary carcinomas, due to specific Numb ubiquitination and proteasomal degradation. Mechanistically, Numb operates as an oncosuppressor, as its ectopic expression in Numb-negative, but not in Numb-positive, tumor cells inhibits proliferation. Increased Notch signaling is observed in Numb-negative tumors, but reverts to basal levels after enforced expression of Numb. Conversely, Numb silencing increases Notch signaling in normal breast cells and in Numb-positive breast tumors. Finally, growth suppression of Numb-negative, but not Numb-positive, breast tumors can be achieved by pharmacological inhibition of Notch. Thus, the Numb/Notch biological antagonism is relevant to the homeostasis of the normal mammary parenchyma and its subversion contributes to human mammary carcinogenesis.", "title": "Loss of negative regulation by Numb over Notch is relevant to human breast carcinogenesis" }, { "docid": "36432234", "text": "Wedelolactone, a plant coumestan, was shown to act as anti-cancer agent for breast and prostate carcinomas in vitro and in vivo targeting multiple cellular proteins including androgen receptors, 5-lipoxygenase and topoisomerase IIα. It is cytotoxic to breast, prostate, pituitary and myeloma cancer cell lines in vitro at μM concentrations. In this study, however, a novel biological activity of nM dose of wedelolactone was demonstrated. Wedelolactone acts as agonist of estrogen receptors (ER) α and β as demonstrated by transactivation of estrogen response element (ERE) in cells transiently expressing either ERα or ERβ and by molecular docking of this coumestan into ligand binding pocket of both ERα and ERβ. In breast cancer cells, wedelolactone stimulates growth of estrogen receptor-positive cells, expression of estrogen-responsive genes and activates rapid non-genomic estrogen signalling. All these effects can be inhibited by pretreatment with pure ER antagonist ICI 182,780 and they are not observed in ER-negative breast cancer cells. We conclude that wedelolactone acts as phytoestrogen in breast cancer cells by stimulating ER genomic and non-genomic signalling pathways.", "title": "Wedelolactone induces growth of breast cancer cells by stimulation of estrogen receptor signalling." }, { "docid": "30786800", "text": "BACKGROUND The International Lipid-Based Nutrient Supplements Project developed a small-quantity (20 g/d) lipid-based nutrient supplement (LNS) for pregnant and lactating women. OBJECTIVE We evaluated the effects of prenatal LNS supplementation on fetal growth. DESIGN In a community-based, partially double-blind, individually randomized controlled trial, 1320 women ≤20 wk pregnant received 60 mg Fe/400 μg folic acid (IFA), or 1-2 Recommended Dietary Allowances of 18 micronutrients, including 20 mg Fe (MMN), or LNS with the same micronutrients as the MMN group, plus 4 minerals and macronutrients contributing 118 kcal (LNS) daily until delivery. Fetal growth was compared across groups by using intention-to-treat analysis. The primary outcome was birth length. RESULTS This analysis included 1057 women (IFA = 349, MMN = 354, LNS = 354). Groups did not differ significantly in mean birth length, length-for-age z score (LAZ), head circumference, or percentage low birth length but differed in mean birth weight (P = 0.044), weight-for-age z score (WAZ; P = 0.046), and BMI-for-age z score (BMIZ; P = 0.040), with a trend toward differences in low birth weight (P = 0.069). In pairwise comparisons, the LNS group had greater mean birth weight (+85 g; P = 0.040), WAZ (+0.19; P = 0.045), and BMIZ (+0.21; P = 0.035) and a lower risk of low birth weight (RR: 0.61, 95% CI: 0.39, 0.96; P = 0.032) than did the IFA group. The other group differences were not significant. The effect of intervention was modified by mother's parity, age, height, baseline hemoglobin, household food insecurity, and child sex, with parity being the most consistent modifier. Among primiparous women (IFA = 131; MMN = 110; LNS = 128), the LNS group had greater mean birth length (+0.91 cm; P = 0.001), LAZ (+0.47; P = 0.001), weight (+237 g; P < 0.001), WAZ (+0.56; P < 0.001), BMIZ (+0.52; P < 0.001), head circumference (0.50 cm; P = 0.017), and head circumference-for-age z score (+0.40; P = 0.022) than did the IFA group; similar differences were found when comparing the LNS and MMN groups among primiparous women, and no group differences were found among multiparous women. CONCLUSION Prenatal LNS supplementation can improve fetal growth among vulnerable women in Ghana, particularly primiparous women. This trial was registered at clinicaltrials.gov as NCT00970866.", "title": "Lipid-based nutrient supplement increases the birth size of infants of primiparous women in Ghana." } ]
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Depletion of T-helper 17 (Th17) cells during simian immunodeficiency virus (SIV) infection increases dissemination of Salmonella Typhimurium from the gut.
[ { "docid": "29023309", "text": "Salmonella typhimurium causes a localized enteric infection in immunocompetent individuals, whereas HIV-infected individuals develop a life-threatening bacteremia. Here we show that simian immunodeficiency virus (SIV) infection results in depletion of T helper type 17 (TH17) cells in the ileal mucosa of rhesus macaques, thereby impairing mucosal barrier functions to S. typhimurium dissemination. In SIV-negative macaques, the gene expression profile induced by S. typhimurium in ligated ileal loops was dominated by TH17 responses, including the expression of interleukin-17 (IL-17) and IL-22. TH17 cells were markedly depleted in SIV-infected rhesus macaques, resulting in blunted TH17 responses to S. typhimurium infection and increased bacterial dissemination. IL-17 receptor–deficient mice showed increased systemic dissemination of S. typhimurium from the gut, suggesting that IL-17 deficiency causes defects in mucosal barrier function. We conclude that SIV infection impairs the IL-17 axis, an arm of the mucosal immune response preventing systemic microbial dissemination from the gastrointestinal tract.", "title": "Simian immunodeficiency virus–induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut" } ]
[ { "docid": "8300657", "text": "Human and simian immunodeficiency virus (HIV and SIV) replicate optimally in activated memory CD4(+) T cells, a cell type that is abundant in the intestine. SIV infection of rhesus monkeys resulted in profound and selective depletion of CD4+ T cells in the intestine within days of infection, before any such changes in peripheral lymphoid tissues. The loss of CD4+ T cells in the intestine occurred coincident with productive infection of large numbers of mononuclear cells at this site. The intestine appears to be a major target for SIV replication and the major site of CD4+ T cell loss in early SIV infection.", "title": "Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection." }, { "docid": "1071991", "text": "Live attenuated simian immunodeficiency virus (SIV) vaccines (LAVs) remain the most efficacious of all vaccines in nonhuman primate models of HIV and AIDS, yet the basis of their robust protection remains poorly understood. Here we show that the degree of LAV-mediated protection against intravenous wild-type SIVmac239 challenge strongly correlates with the magnitude and function of SIV-specific, effector-differentiated T cells in the lymph node but not with the responses of such T cells in the blood or with other cellular, humoral and innate immune parameters. We found that maintenance of protective T cell responses is associated with persistent LAV replication in the lymph node, which occurs almost exclusively in follicular helper T cells. Thus, effective LAVs maintain lymphoid tissue-based, effector-differentiated, SIV-specific T cells that intercept and suppress early wild-type SIV amplification and, if present in sufficient frequencies, can completely control and perhaps clear infection, an observation that provides a rationale for the development of safe, persistent vectors that can elicit and maintain such responses.", "title": "Lymph node T cell responses predict the efficacy of live attenuated SIV vaccines" }, { "docid": "798152", "text": "Analysis of serum samples from 100 wild-caught or colony-born Sykes' monkeys (Cercopithecus mitis) in Kenya revealed that 59 animals had antibodies cross-reactive to human immunodeficiency virus type 2 (HIV-2) and to simian immunodeficiency viruses (SIVs). A lentivirus, designated SIVsyk, was isolated from five of six seropositive asymptomatic Sykes' monkeys, but in four cases isolation was possible only after depletion of CD8+ lymphocytes and cocultivation of the CD4(+)-enriched cell population with peripheral blood mononuclear cells from seronegative Sykes' monkeys. SIVsyk resembled other SIVs and HIVs morphologically, had an Mg2(+)-dependent reverse transcriptase enzyme, and replicated in and was cytopathic for CEMx174 and Sup-T1 cells. SIVsyk differred substantially from other SIVs, however, in that it failed to replicate in normal human, mangabey, and macaque peripheral blood mononuclear cells and serum from seropositive Sykes' monkeys immunoprecipitated env antigens from HIV-1 as well as from HIV-2, SIVsmm, and SIVagm. These data demonstrate a high prevalence of natural infection in Sykes' monkeys in Kenya with a lentivirus that appears to be unique with respect to its host range and antigenic cross-reactivity.", "title": "Isolation from African Sykes' monkeys (Cercopithecus mitis) of a lentivirus related to human and simian immunodeficiency viruses." }, { "docid": "44737533", "text": "METHODS To define potential common features of simian immunodeficiency virus (SIV) infections in different naturally infected host species, we compared the dynamics of viral replication in 31 African green monkeys (10 sabeus, 15 vervets and seven Caribbean AGMs), 14 mandrills and three sooty mangabeys (SMs) that were experimentally infected with their species-specific viruses. RESULTS After infection, these SIVs replicated rapidly reaching viral loads (VLs) of 10(5)-10(9) copies/ml of plasma between days 9-14 post-infection (p.i). Set point viremia was established between days 42 and 60 p.i., with levels of approximately 10(5)-10(6) copies/ml in SM and mandrills, and lower levels (10(3)-10(5) copies/ml) in AGMs. VL during the chronic phase did not correlate with viral genome structure: SIVmnd-2 (a vpx-containing virus) and SIVmnd-1 (which does not contain vpu or vpx) replicated to similar levels in mandrills. VL was dependent on virus strain: vervets infected with three different viral strains showed different patterns of viral replication. The pattern of viral replication of SIVagm.sab, which uses both CCR5 and CXCR4 co-receptors was similar to those of the other viruses. CONCLUSIONS Our results show a common pattern of SIV replication in naturally and experimentally infected hosts. This is similar overall to that observed in pathogenic SIV infection of macaques. This result indicates that differences in clinical outcome between pathogenic and non-pathogenic infections rely on host responses rather than the characteristics of the virus itself.", "title": "Simian immunodeficiency viruses replication dynamics in African non-human primate hosts: common patterns and species-specific differences." }, { "docid": "20357868", "text": "Primary simian immunodeficiency virus (SIV) isolated from sooty mangabey (SIVsm [n = 6]), stumptail (SIVstm [n = 1]), mandrill (SIVmnd [n = 1]), and African green (SIVagm [n = 1]) primates were examined for their ability to infect human cells and for their coreceptor requirements. All isolates infected human peripheral blood mononuclear cells (PBMCs) from a CCR5(+/+) donor, and seven of eight isolates tested also infected CCR5(-/-) PBMCs. Analysis of coreceptor utilization using GHOST and U87 cell lines revealed that all of the isolates tested used CCR5 and the orphan receptors STRL33 and GPR15. Coreceptors such as CCR2b, CCR3, CCR8, and CX3CR1 were also utilized by some primary SIV isolates. More importantly, we found that CXCR4 was used as a coreceptor by the SIVstm, the SIVagm, and four of the SIVsm isolates in GHOST and U87 cells. These data suggest that primary SIV isolates from diverse primate species can utilize CXCR4 for viral entry, similar to what has been described for human immunodeficiency viruses.", "title": "Simian immunodeficiency viruses of diverse origin can use CXCR4 as a coreceptor for entry into human cells." }, { "docid": "22705234", "text": "The African green monkey (AGM) is one of many African species endemically infected with simian immunodeficiency virus (SIV). Like the other natural hosts, AGMs do not succumb to AIDS and understanding the basis for this resistance to disease progression would be of enormous theoretical and practical importance. Early efforts by our group that concentrated on identifying immune mechanisms presumed to keep the virus under control failed to find any obvious candidates. The presumption of virus control was invalidated by the finding that SIVagm replicates in AGMs with the same vigor as HIV-1 does in humans. Focus therefore shifted to identifying possible immunopathologic features present in disease susceptible hosts but absent in the AGM natural host. The apparent immunologic tolerance of AGMs to the SIVagm core protein led to the development of a hypothesis implicating anti-Gag antibodies in the formation of immune complexes, virus trapping in the lymph nodes and immune dysfunction. The idea proved difficult to test in vivo and present work focuses on the possibility that Gag tolerance at the T-cell level plays an important role in preventing the catastrophic demise of the immune system characteristic of immunodeficiency virus infection of the heterologous primate host.", "title": "The role of the immune response during SIVagm infection of the African green monkey natural host." }, { "docid": "21274496", "text": "Simian immunodeficiency virus (SIV) naturally infects non-human primates in Africa. To date, 40 SIVs have been described both in natural hosts and in heterologous species. These viruses are highly diverse and the majority cluster in 6 relatively equidistant phylogenetic lineages. At least 8 SIVs are currently considered as recombinant viruses, based on different clustering patterns in different genomic regions. Only three types of genomes are known, based on the number of accessory genes: vpr-containing genomes, vpr-vpx containing genomes and vpr-vpu-containing genomes. vpx resulted by a duplication of the vpr gene following non-homologous recombination and is characteristic of SIVs infecting the Papionini tribe of monkeys and HIV-2 in humans. vpu is characteristic of SIVcpz and HIV-1 and may have originated from a recombination involving SIVs from cercopitecini monkeys. SIV seems to be non-pathogenic in the vast majority of natural hosts in spite of a high levels of viral replication. This is probably a consequence of virus-host adaptation, in which the incubation period of the disease generally exceeds the life span of the African primate host. SIVs also have a high propensity for cross-species transmission. In the new host, the outcome may vary from inapparent infection to highly pathogenic, the former being reported for African monkeys, whereas the latter being observed in macaques and humans. The high diversity of SIVs was generated by a high mutation rate due to a low fidelity of the reverse-transcriptase and active viral and host cell turnover, host-dependent evolution and recombination. Cross-species transmission is not rare, however preferential host switching may drive the majority of cross-species transmissions. Numerous SIVs tested so far are able to grow in vitro on human PBMC, therefore it has been postulated that SIV represents a threat for infection of humans in Central Africa and that AIDS is a zoonosis. However, although the simian origin of the two HIV types is broadly acknowledged, there are no data that AIDS is acquired like a zoonosis. SIV may undergo adaptation in the new human host in order to emerge in the general population. The study of SIV in their natural hosts should provide important clues to the real threat to human populations and also elucidate the mechanisms associated with a long-term persistent viral infection without clinical consequences for the host.", "title": "The history of SIVS and AIDS: epidemiology, phylogeny and biology of isolates from naturally SIV infected non-human primates (NHP) in Africa." }, { "docid": "42065070", "text": "Early events during human immunodeficiency virus infections are considered to reflect the capacity of the host to control infection. We have studied early virus and host parameters during the early phase of simian immunodeficiency virus SIVmnd-1 nonpathogenic infection in its natural host, Mandrillus sphinx. Four mandrills were experimentally infected with a primary SIVmnd-1 strain derived from a naturally infected mandrill. Two noninfected control animals were monitored in parallel. Blood and lymph nodes were collected at three time points before infection, twice a week during the first month, and at days 60, 180, and 360 postinfection (p.i.). Anti-SIVmnd-1 antibodies were detected starting from days 28 to 32 p.i. Neither elevated temperature nor increased lymph node size were observed. The viral load in plasma peaked between days 7 to 10 p.i. (2 x 10(6) to 2 x 10(8) RNA equivalents/ml). Viremia then decreased 10- to 1,000-fold, reaching the viral set point between days 30 to 60 p.i. The levels during the chronic phase of infection were similar to that in the naturally infected donor mandrill (2 x 10(5) RNA equivalents/ml). The CD4(+) cell numbers and percentages in blood and lymph nodes decreased slightly (<10%) during primary infection, and CD8(+) cell numbers increased transiently. All values returned to preinfection infection levels by day 30 p.i. CD8(+) cell numbers or percentages, in peripheral blood and lymph nodes, did not increase during the 1 year of follow-up. In conclusion, SIVmnd-1 has the capacity for rapid and extensive replication in mandrills. Despite high levels of viremia, CD4(+) and CD8(+) cell numbers remained stable in the post-acute phase of infection, raising questions regarding the susceptibility of mandrill T cells to activation and/or cell death in response to SIVmnd-1 infection in vivo.", "title": "High levels of viral replication contrast with only transient changes in CD4(+) and CD8(+) cell numbers during the early phase of experimental infection with simian immunodeficiency virus SIVmnd-1 in Mandrillus sphinx." }, { "docid": "22159299", "text": "Salmonella enterica serovar Typhimurium (S. Typhimurium) is a facultative intracellular pathogen that causes disease in a variety of hosts. S. Typhimurium actively invade host cells and typically reside within a membrane-bound compartment called the Salmonella-containing vacuole (SCV). The bacteria modify the fate of the SCV using two independent type III secretion systems (TTSS). TTSS are known to damage eukaryotic cell membranes and S. Typhimurium has been suggested to damage the SCV using its Salmonella pathogenicity island (SPI)-1 encoded TTSS. Here we show that this damage gives rise to an intracellular bacterial population targeted by the autophagy system during in vitro infection. Approximately 20% of intracellular S. Typhimurium colocalized with the autophagy marker GFP-LC3 at 1 h postinfection. Autophagy of S. Typhimurium was dependent upon the SPI-1 TTSS and bacterial protein synthesis. Bacteria targeted by the autophagy system were often associated with ubiquitinated proteins, indicating their exposure to the cytosol. Surprisingly, these bacteria also colocalized with SCV markers. Autophagy-deficient (atg5-/-) cells were more permissive for intracellular growth by S. Typhimurium than normal cells, allowing increased bacterial growth in the cytosol. We propose a model in which the host autophagy system targets bacteria in SCVs damaged by the SPI-1 TTSS. This serves to retain intracellular S. Typhimurium within vacuoles early after infection to protect the cytosol from bacterial colonization. Our findings support a role for autophagy in innate immunity and demonstrate that Salmonella infection is a powerful model to study the autophagy process.", "title": "Autophagy controls Salmonella infection in response to damage to the Salmonella-containing vacuole." }, { "docid": "20864487", "text": "Cytotoxic T-lymphocyte (CTL) responses to human immunodeficiency virus arise early after infection, but ultimately fail to prevent progression to AIDS. Human immunodeficiency virus may evade the CTL response by accumulating amino-acid replacements within CTL epitopes. We studied 10 CTL epitopes during the course of simian immunodeficiency virus disease progression in three related macaques. All 10 of these CTL epitopes accumulated amino-acid replacements and showed evidence of positive selection by the time the macaques died. Many of the amino-acid replacements in these epitopes reduced or eliminated major histocompatibility complex class I binding and/or CTL recognition. These findings strongly support the CTL 'escape' hypothesis.", "title": "Virus-specific cytotoxic T-lymphocyte responses select for amino-acid variation in simian immunodeficiency virus Env and Nef" }, { "docid": "37444589", "text": "Although 13 years have passed since identification of human immunodeficiency virus-1 (HIV-1) as the cause of AIDS, we do not yet know how HIV kills its primary target, the T cell that carries the CD4 antigen. We and others have shown an increase in the percentage of apoptotic cells among circulating CD4+ (and CD8+) T cells of HIV-seropositive individuals and an increase in frequency of apoptosis with disease progression. However, it is not known if this apoptosis occurs in infected or uninfected T cells. We show here, using in situ labelling of lymph nodes from HIV-infected children and SIV-infected macaques, that apoptosis occurs predominantly in bystander cells and not in the productively infected cells themselves. These data have implications for pathogenesis and therapy, namely, arguing that rational drug therapy may involve combination agents targeting viral replication in infected cells and apoptosis of uninfected cells.", "title": "Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV- and SIV-infected lymph nodes" }, { "docid": "13398997", "text": "The CD28/cytotoxic T-lymphocyte antigen 4 (CTLA-4)blocker belatacept selectively inhibits alloreactive T cell responses but is associated with a high incidence of acute rejection following renal transplantation,which led us to investigate the etiology of belatacept–resistant graft rejection. T cells can differentiate into functionally distinct subsets of memory T cellsthat collectively enable protection against diverse classes of pathogens and can cross-react with allogeneicantigen and mediate graft rejection. T helper 17(Th17) cells are a pro-inflammatory CD4+ lineage that provides immunity to pathogens and are pathogenic in autoimmune disease. We found that T helper 1 (Th1)and Th17 memory compartments contained a similar frequency of divided cells following allogeneic stimulation. Compared to Th1 cells, Th17 memory cells expressed significantly higher levels of the coinhibitory molecule CTLA-4. Stimulation in the presence of belatacept inhibited Th1 responses but augmented Th17 cells due to greater sensitivity to coinhibition by CTLA-4. Th17 cells from renal transplant recipients were resistant to ex vivo CD28/CTLA-4 blockade with belatacept, and an elevated frequency of Th17 memory cells was associated with acute rejection during belatacept therapy. These data highlight important differences in costimulatory and coinhibitory requirements of CD4+ memory subsets, and demonstrate that the heterogeneity of pathogen-derived memory has implications for immunomodulation strategies.", "title": "High CTLA-4 expression on Th17 cells results in increased sensitivity to CTLA-4 coinhibition and resistance to belatacept." }, { "docid": "11921405", "text": "The gut mucosal epithelium separates the host from the microbiota, but enteropathogens such as Salmonella Typhimurium (S.Tm) can invade and breach this barrier. Defenses against such acute insults remain incompletely understood. Using a murine model of Salmonella enterocolitis, we analyzed mechanisms limiting pathogen loads in the epithelium during early infection. Although the epithelium-invading S.Tm replicate initially, this intraepithelial replicative niche is restricted by expulsion of infected enterocytes into the lumen. This mechanism is compromised if inflammasome components (NAIP1-6, NLRC4, caspase-1/-11) are deleted, or ablated specifically in the epithelium, resulting in ∼100-fold higher intraepithelial loads and accelerated lymph node colonization. Interestingly, the cytokines downstream of inflammasome activation, interleukin (IL)-1α/β and IL-18, appear dispensable for epithelial restriction of early infection. These data establish the role of an epithelium-intrinsic inflammasome, which drives expulsion of infected cells to restrict the pathogen's intraepithelial proliferation. This may represent a general defense mechanism against mucosal infections.", "title": "Epithelium-intrinsic NAIP/NLRC4 inflammasome drives infected enterocyte expulsion to restrict Salmonella replication in the intestinal mucosa." }, { "docid": "35651106", "text": "Efficient T cell activation requires both TCR signals and costimulatory signals. CD28 is one of the molecules that provide costimulatory signals for T cells. We used mice deficient in CD28 expression (CD28-/- mice) to analyze the role of CD28 in the immune response against the intracellular bacterium Salmonella typhimurium, the causative agent of murine typhoid fever. CD28-/- mice were highly susceptible to infection with wild-type S. typhimurium and even failed to control infection with attenuated aroA- S. typhimurium. More detailed analysis revealed that CD28-/- animals did not mount a T-dependent Ab response and were highly impaired in the production of IFN-gamma. Thus, CD28 cosignaling is crucial for immunity against S. typhimurium. To our knowledge, this is the first report describing an essential role for CD28 in protective immunity against an intracellular microbial pathogen.", "title": "Critical role of CD28 in protective immunity against Salmonella typhimurium." }, { "docid": "11233339", "text": "T-helper 17 (Th17) cells are characterized by producing interleukin-17 (IL-17, also called IL-17A), IL-17F, IL-21, and IL-22 and potentially TNF- α and IL-6 upon certain stimulation. IL-23, which promotes Th17 cell development, as well as IL-17 and IL-22 produced by the Th17 cells plays essential roles in various inflammatory diseases, such as experimental autoimmune encephalomyelitis, rheumatoid arthritis, colitis, and Concanavalin A-induced hepatitis. In this review, we summarize the characteristics of the functional role of Th17 cells, with particular focus on the Th17 cell-related cytokines such as IL-17, IL-22, and IL-23, in mouse models and human inflammatory diseases.", "title": "Pivotal Roles of T-Helper 17-Related Cytokines, IL-17, IL-22, and IL-23, in Inflammatory Diseases" }, { "docid": "18546584", "text": "CD4(+) helper T (Th) cells play a crucial role in the delicate balance between host defense and autoimmune disease. Two important populations of helper T cells are the proinflammatory, interleukin-17 (IL-17)-producing (Th17) cells and the anti-inflammatory forkhead box P3-positive (FoxP3(+)) T regulatory (Treg) cells. Here we show that all-trans retinoic acid (ATRA) and other agonists of the retinoic acid receptor alpha (RARalpha) inhibit the formation of Th17 cells and promote FoxP3 expression. Conversely, inhibition of retinoic acid signaling constrains transforming growth factor beta (TGF-beta1) induction of FoxP3. The effect of ATRA is mediated independently of IL-2, signal transducer and activator of transcription 5 (Stat5) and Stat3, representing a novel mechanism for the induction of FoxP3 in CD4 T cells. As previous studies have shown that vitamin A derivatives are protective in animal models of autoimmune disease, the current data suggest a previously unrecognized role for RARalpha in the regulation of CD4(+) T-cell differentiation and provide a mechanism for the anti-inflammatory effects of retinoic acid.", "title": "Retinoic acid inhibits Th17 polarization and enhances FoxP3 expression through a Stat-3/Stat-5 independent signaling pathway." }, { "docid": "19005293", "text": "Inflammation induced by recognition of pathogen-associated molecular patterns markedly affects subsequent adaptive responses. We asked whether the adaptive immune system can also affect the character and magnitude of innate inflammatory responses. We found that the response of memory, but not naive, CD4+ T cells enhances production of multiple innate inflammatory cytokines and chemokines (IICs) in the lung and that, during influenza infection, this leads to early control of virus. Memory CD4+ T cell–induced IICs and viral control require cognate antigen recognition and are optimal when memory cells are either T helper type 1 (TH1) or TH17 polarized but are independent of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) production and do not require activation of conserved pathogen recognition pathways. This represents a previously undescribed mechanism by which memory CD4+ T cells induce an early innate response that enhances immune protection against pathogens.", "title": "Memory CD4+ T cells induce innate responses independently of pathogen" }, { "docid": "51952430", "text": "The toll-like receptor (TLR) and interleukin (IL)-1 family of receptors share several signaling components, including the most upstream adapter, MyD88. We previously reported the discovery of B cell adapter for phosphoinositide 3-kinase (BCAP) as a novel toll-IL-1 receptor homology domain-containing adapter that regulates inflammatory responses downstream of TLR signaling. Here we find that BCAP plays a critical role downstream of both IL-1 and IL-18 receptors to regulate T helper (Th) 17 and Th1 cell differentiation, respectively. Absence of T cell intrinsic BCAP did not alter development of naturally arising Th1 and Th17 lineages but led to defects in differentiation to pathogenic Th17 lineage cells. Consequently, mice that lack BCAP in T cells had reduced susceptibility to experimental autoimmune encephalomyelitis. More importantly, we found that BCAP is critical for IL-1R-induced phosphoinositide 3-kinase-Akt-mechanistic target of rapamycin (mTOR) activation, and minimal inhibition of mTOR completely abrogated IL-1β-induced differentiation of pathogenic Th17 cells, mimicking BCAP deficiency. This study establishes BCAP as a critical link between IL-1R and the metabolic status of activated T cells that ultimately regulates the differentiation of inflammatory Th17 cells.", "title": "BCAP links IL-1R to the PI3K–mTOR pathway and regulates pathogenic Th17 cell differentiation" }, { "docid": "8063697", "text": "Pertussis is a highly contagious respiratory illness caused by the bacterial pathogen Bordetella pertussis. Pertussis rates in the United States have been rising and reached a 50-y high of 42,000 cases in 2012. Although pertussis resurgence is not completely understood, we hypothesize that current acellular pertussis (aP) vaccines fail to prevent colonization and transmission. To test our hypothesis, infant baboons were vaccinated at 2, 4, and 6 mo of age with aP or whole-cell pertussis (wP) vaccines and challenged with B. pertussis at 7 mo. Infection was followed by quantifying colonization in nasopharyngeal washes and monitoring leukocytosis and symptoms. Baboons vaccinated with aP were protected from severe pertussis-associated symptoms but not from colonization, did not clear the infection faster than naïve animals, and readily transmitted B. pertussis to unvaccinated contacts. Vaccination with wP induced a more rapid clearance compared with naïve and aP-vaccinated animals. By comparison, previously infected animals were not colonized upon secondary infection. Although all vaccinated and previously infected animals had robust serum antibody responses, we found key differences in T-cell immunity. Previously infected animals and wP-vaccinated animals possess strong B. pertussis-specific T helper 17 (Th17) memory and Th1 memory, whereas aP vaccination induced a Th1/Th2 response instead. The observation that aP, which induces an immune response mismatched to that induced by natural infection, fails to prevent colonization or transmission provides a plausible explanation for the resurgence of pertussis and suggests that optimal control of pertussis will require the development of improved vaccines.", "title": "Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model." }, { "docid": "40312663", "text": "Inflammasome-mediated IL-1beta production is central to the innate immune defects that give rise to certain autoinflammatory diseases and may also be associated with the generation of IL-17-producing CD4(+) T (Th17) cells that mediate autoimmunity. However, the role of the inflammasome in driving adaptive immunity to infection has not been addressed. In this article, we demonstrate that inflammasome-mediated IL-1beta plays a critical role in promoting Ag-specific Th17 cells and in generating protective immunity against Bordetella pertussis infection. Using a murine respiratory challenge model, we demonstrated that the course of B. pertussis infection was significantly exacerbated in IL-1R type I-defective (IL-1RI(-/-)) mice. We found that adenylate cyclase toxin (CyaA), a key virulence factor secreted by B. pertussis, induced robust IL-1beta production by dendritic cells through activation of caspase-1 and the NALP3-containing inflammasome complex. Using mutant toxins, we demonstrate that CyaA-mediated activation of caspase-1 was not dependent on adenylate cyclase enzyme activity but was dependent on the pore-forming capacity of CyaA. In addition, CyaA promoted the induction of Ag-specific Th17 cells in wild-type but not IL-1RI(-/-) mice. Furthermore, the bacterial load was enhanced in IL-17-defective mice. Our findings demonstrate that CyaA, a virulence factor from B. pertussis, promotes innate IL-1beta production via activation of the NALP3 inflammasome and, thereby, polarizes T cell responses toward the Th17 subtype. In addition to its known role in subverting host immunity, our findings suggest that CyaA can promote IL-1beta-mediated Th17 cells, which promote clearance of the bacteria from the respiratory tract.", "title": "Inflammasome activation by adenylate cyclase toxin directs Th17 responses and protection against Bordetella pertussis." }, { "docid": "5398179", "text": "HIV-1 replication is concentrated within CD4(+) T cells in B cell follicles of secondary lymphoid tissues during asymptomatic disease. Limited data suggest that a subset of T follicular helper cells (TFH) within germinal centers (GC) is highly permissive to HIV-1. Whether GC TFH are the major HIV-1 virus-producing cells in vivo has not been established. In this study, we investigated TFH permissivity to HIV-1 ex vivo by spinoculating and culturing tonsil cells with HIV-1 GFP reporter viruses. Using flow cytometry, higher percentages of GC TFH (CXCR5(high)PD-1(high)) and CXCR5(+)programmed cell death-1 (PD-1)(low) cells were GFP(+) than non-GC TFH (CXCR5(+)PD-1(intermediate)) or extrafollicular (EF) (CXCR5(-)) cells. When sorted prior to spinoculation, however, GC TFH were substantially more permissive than CXCR5(+)PD-1(low) or EF cells, suggesting that many GC TFH transition to a CXCR5(+)PD-1(low) phenotype during productive infection. In situ hybridization on inguinal lymph node sections from untreated HIV-1-infected individuals without AIDS revealed higher frequencies of HIV-1 RNA(+) cells in GC than non-GC regions of follicle or EF regions. Superinfection of HIV-1-infected individuals' lymph node cells with GFP reporter virus confirmed the permissivity of follicular cells ex vivo. Lymph node immunostaining revealed 96% of CXCR5(+)CD4(+) cells were located in follicles. Within sorted lymph node cells from four HIV-infected individuals, CXCR5(+) subsets harbored 11-66-fold more HIV-1 RNA than CXCR5(-) subsets, as determined by RT PCR. Thus, GC TFH are highly permissive to HIV-1, but downregulate PD-1 and, to a lesser extent, CXCR5 during HIV-1 replication. These data further implicate GC TFH as the major HIV-1-producing cells in chronic asymptomatic HIV-1 infection.", "title": "Germinal Center T Follicular Helper Cells Are Highly Permissive to HIV-1 and Alter Their Phenotype during Virus Replication." }, { "docid": "46202852", "text": "Several recent reports indicate that cholesterol might play an important role in human immunodeficiency virus type 1 (HIV-1) replication. We investigated the effects of HIV-1 infection on cholesterol biosynthesis and uptake using microarrays. HIV-1 increased gene expression of cholesterol genes in both transformed T-cell lines and primary CD4(+) T cells. Consistent with our microarray data, (14)C-labeled mevalonate and acetate incorporation was increased in HIV-1-infected cells. Our data also demonstrate that changes in cholesterol biosynthesis and uptake are only observed in the presence of functional Nef, suggesting that increased cholesterol synthesis may contribute to Nef-mediated enhancement of virion infectivity and viral replication.", "title": "Nef induces multiple genes involved in cholesterol synthesis and uptake in human immunodeficiency virus type 1-infected T cells." }, { "docid": "2844490", "text": "PURPOSE OF REVIEW To encapsulate our current understanding of the proinflammatory cytokines responsible for the inflammation underlying Crohn's disease and the prospect of using this information to devise therapy for this condition based on inhibition of these cytokines. RECENT FINDINGS Current research is shedding new light on the role of both T helper cell (Th)1 and Th17 responses in the pathogenesis of Crohn's disease. Initial studies conducted a decade ago highlighted the view that Crohn's disease inflammation is caused by an interleukin-12-driven Th1 response, which resulted in the generation of interferon-gamma, which then served as the main inflammatory mediator. In recent years, however, this view has been largely eclipsed by studies, conducted mainly in murine models, showing that a Th17 response is the main cause of Crohn's disease inflammation through the production of interleukin-17. Now, a somewhat more balanced view is emerging, which holds that interferon-gamma is still a major proinflammatory cytokine in Crohn's disease, although it may arise from both the Th1 and Th17-mediated responses at different phases of the inflammatory process. SUMMARY The new findings continue to support the idea that anti-interleukin-12p40, an antibody that inhibits both the Th1 and Th17 response, is logically the most potent anticytokine for the treatment of Crohn's disease.", "title": "Proinflammatory cytokines underlying the inflammation of Crohn's disease." }, { "docid": "20996244", "text": "Productive infection by human immunodeficiency virus type 1 (HIV-1) requires the activation of target cells. Infection of quiescent peripheral CD4 lymphocytes by HIV-1 results in incomplete, labile, reverse transcripts. We have previously identified G1b as the cell cycle stage required for the optimal completion of the reverse transcription process in T lymphocytes. However, the mechanism(s) involved in the blockage of reverse transcription remains undefined. In this study we investigated whether nucleotide levels influence viral reverse transcription in G0 cells. For this purpose the role of the enzyme ribonucleotide reductase was bypassed, by adding exogenous deoxyribonucleosides to highly purified T cells in the G0 or the G1a phase of the cell cycle. Our data showed a significant increase in the efficiency of the reverse transcription process following the addition of the deoxyribonucleosides. To define the stability and functionality of these full reverse transcripts, we used an HIV-1 reporter virus that expresses the murine heat-stable antigen on the surfaces of infected cells. Following activation of infected quiescent cells treated with exogenous nucleosides, no increased rescue of productive infection was seen. Thus, in addition to failure to complete reverse transcription, there was an additional nonreversible blockage of productive infection in quiescent T cells. These experiments have important relevance in the gene therapy arena, in terms of improving the ability of lentivirus vectors to enter metabolically inactive cells, such as hematopoietic stem cells.", "title": "Nonproductive human immunodeficiency virus type 1 infection in nucleoside-treated G0 lymphocytes." }, { "docid": "696006", "text": "Patients with asthma, a major public health problem, are at high risk for serious disease from influenza virus infection, but the pathogenic mechanisms by which influenza A causes airway disease and asthma are not fully known. We show here in a mouse model that influenza infection acutely induced airway hyper-reactivity (AHR), a cardinal feature of asthma, independently of T helper type 2 (TH2) cells and adaptive immunity. Instead, influenza infection induced AHR through a previously unknown pathway that required the interleukin 13 (IL-13)–IL-33 axis and cells of the non-T cell, non-B cell innate lymphoid type called 'natural helper cells'. Infection with influenza A virus, which activates the NLRP3 inflammasome, resulted in much more production of IL-33 by alveolar macrophages, which in turn activated natural helper cells producing substantial IL-13.", "title": "Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity" }, { "docid": "25134146", "text": "Hepatitis C virus (HCV) is frequently encountered in human immunodeficiency virus (HIV)-infected patients because of common routes of transmission. Previous studies suggested that HIV infection impaired the natural course of chronic hepatitis C, with a more rapid progression to cirrhosis. However, these studies did not assess the HIV infection impact on chronic hepatitis C by taking into account the risk factors for liver fibrosis progression: alcohol, sex, age at the contamination, and duration of HCV infection. We studied liver biopsy specimens of 2 groups of 58 patients that were infected by both HCV and HIV or by HCV alone. The 2 groups were matched according those risk factors, and liver biopsy responses were evaluated with the METAVIR items. The METAVIR activity was higher in HIV-positive than HIV-negative patients. Cirrhosis was more frequent: (1) in HIV-positive patients with CD4 < or = 200 cells/microL (45%) than in HIV-negative patients (10%) (P = .003), (2) in HIV-positive patients with CD4 < or = 200 cells/microL (45%) than in HIV-positive patients with CD4 > 200 cells/microL (17%) (P = .04). These differences, which were linked to HIV status, might be related to the enhanced HCV replication during HIV infection or other immune mechanisms that need further studies.", "title": "Impact of human immunodeficiency virus infection on the histological features of chronic hepatitis C: a case-control study. The MULTIVIRC group." }, { "docid": "40323148", "text": "While inflammatory phagocytosis of microbial pathogens and non-inflammatory phagocytosis of apoptotic cells have each been studied extensively, the consequences of innate immune recognition of host cells undergoing apoptosis as a direct result of infection are unclear. In this situation, the innate immune system is confronted with mixed signals, those from apoptotic cells and those from the infecting pathogen. Nuclear receptor activation has been implicated downstream of apoptotic cell recognition while Toll-like receptors are the prototypical inflammatory receptors engaged during infection. When the two signals combine, a new set of events takes place beginning with transrepression of a subset of inflammatory-response genes and ending with the induction of a T helper-17 adaptive immune response. This response is best suited for clearing the infecting pathogen and repairing the damage that occurred to the host tissue during infection.", "title": "Infection and apoptosis as a combined inflammatory trigger." }, { "docid": "27602752", "text": "Encephalitis and dementia associated with acquired immunodeficiency syndrome (AIDS) are characterized by leukocyte infiltration into the CNS, microglia activation, aberrant chemokine expression, blood-brain barrier (BBB) disruption, and eventual loss of neurons. Little is known about whether human immunodeficiency virus 1 (HIV-1) infection of leukocytes affects their ability to transmigrate in response to chemokines and to alter BBB integrity. We now demonstrate that HIV infection of human leukocytes results in their increased transmigration across our tissue culture model of the human BBB in response to the chemokine CCL2, as well as in disruption of the BBB, as evidenced by enhanced permeability, reduction of tight junction proteins, and expression of matrix metalloproteinases (MMP)-2 and MMP-9. HIV-infected cells added to our model did not transmigrate in the absence of CCL2, nor did this condition alter BBB integrity. The chemokines CXCL10/interferon-gamma-inducible protein of 10 kDa, CCL3/macrophage inflammatory protein-1alpha, or CCL5/RANTES (regulated on activation normal T-cell expressed and secreted) did not enhance HIV-infected leukocyte transmigration or BBB permeability. The increased capacity of HIV-infected leukocytes to transmigrate in response to CCL2 correlated with their increased expression of CCR2, the chemokine receptor for CCL2. These data suggest that CCL2, but not other chemokines, plays a key role in infiltration of HIV-infected leukocytes into the CNS and the subsequent pathology characteristic of NeuroAIDS.", "title": "CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human immunodeficiency virus (HIV)-infected leukocytes across the blood-brain barrier: a potential mechanism of HIV-CNS invasion and NeuroAIDS." }, { "docid": "10559501", "text": "Studies with mice lacking the common plasma membrane receptor for type I interferon (IFN-αβR(-)(/)(-)) have revealed that IFN signaling restricts tropism, dissemination, and lethality after infection with West Nile virus (WNV) or several other pathogenic viruses. However, the specific functions of individual IFN subtypes remain uncertain. Here, using IFN-β(-)(/)(-) mice, we defined the antiviral and immunomodulatory function of this IFN subtype in restricting viral infection. IFN-β(-)(/)(-) mice were more vulnerable to WNV infection than wild-type mice, succumbing more quickly and with greater overall mortality, although the phenotype was less severe than that of IFN-αβR(-)(/)(-) mice. The increased susceptibility of IFN-β(-)(/)(-) mice was accompanied by enhanced viral replication in different tissues. Consistent with a direct role for IFN-β in control of WNV replication, viral titers in ex vivo cultures of macrophages, dendritic cells, fibroblasts, and cerebellar granule cell neurons, but not cortical neurons, from IFN-β(-)(/)(-) mice were greater than in wild-type cells. Although detailed immunological analysis revealed no major deficits in the quality or quantity of WNV-specific antibodies or CD8(+) T cells, we observed an altered CD4(+) CD25(+) FoxP3(+) regulatory T cell response, with greater numbers after infection. Collectively, these results suggest that IFN-β controls WNV pathogenesis by restricting infection in key cell types and by modulating T cell regulatory networks.", "title": "Beta interferon controls West Nile virus infection and pathogenesis in mice." }, { "docid": "39084565", "text": "Experimental autoimmune myocarditis (EAM) represents a Th17 T cell-mediated mouse model of postinflammatory heart disease. In BALB/c wild-type mice, EAM is a self-limiting disease, peaking 21 days after alpha-myosin H chain peptide (MyHC-alpha)/CFA immunization and largely resolving thereafter. In IFN-gammaR(-/-) mice, however, EAM is exacerbated and shows a chronic progressive disease course. We found that this progressive disease course paralleled persistently elevated IL-17 release from T cells infiltrating the hearts of IFN-gammaR(-/-) mice 30 days after immunization. In fact, IL-17 promoted the recruitment of CD11b(+) monocytes, the major heart-infiltrating cells in EAM. In turn, CD11b(+) monocytes suppressed MyHC-alpha-specific Th17 T cell responses IFN-gamma-dependently in vitro. In vivo, injection of IFN-gammaR(+/+)CD11b(+), but not IFN-gammaR(-/-)CD11b(+), monocytes, suppressed MyHC-alpha-specific T cells, and abrogated the progressive disease course in IFN-gammaR(-/-) mice. Finally, coinjection of MyHC-alpha-specific, but not OVA-transgenic, IFN-gamma-releasing CD4(+) Th1 T cell lines, together with MyHC-alpha-specific Th17 T cells protected RAG2(-/-) mice from EAM. In conclusion, CD11b(+) monocytes play a dual role in EAM: as a major cellular substrate of IL-17-induced inflammation and as mediators of an IFN-gamma-dependent negative feedback loop confining disease progression.", "title": "CD11b+ monocytes abrogate Th17 CD4+ T cell-mediated experimental autoimmune myocarditis." } ]
7483
Tanzania shares a land border with 8 countries.
[ { "docid": "Tanzania", "text": "Tanzania -LSB- ˌtænzəˈniːə -RSB- , officially the United Republic of Tanzania ( Jamhuri ya Muungano wa Tanzania ) , is a country in Eastern Africa within the African Great Lakes region . Parts of the country are in Southern Africa . It is bordered by Kenya and Uganda to the north ; Rwanda , Burundi , and the Democratic Republic of the Congo to the west ; Zambia , Malawi , and Mozambique to the south ; and by the Indian Ocean to the east . Mount Kilimanjaro , Africa 's highest mountain , is in northeastern Tanzania . Tanzania 's population of 51.82 million ( 2014 ) is diverse , composed of several ethnic , linguistic , and religious groups . Tanzania is a presidential constitutional republic , and since 1996 , its official capital city has been Dodoma , where the President 's Office , the National Assembly , and some government ministries are located . Dar es Salaam , the former capital , retains most government offices and is the country 's largest city , principal port , and leading commercial centre . Tanzania is a one party dominant state with the socialist-progressive Chama Cha Mapinduzi ( CCM ) party in power . From its formation until 1992 , it was the only legally permitted party in the country . This changed on 1 July 1992 , when amendments to the Constitution and a number of laws permitting and regulating the formation and operations of more than one political party were enacted by the National Assembly . Elections for president and all National Assembly seats were last held in October 2015 . The CCM holds approximately 75 % of the seats in the assembly . Prehistoric population migrations include Southern Cushitic speakers , who are ancestral to the Iraqw , Gorowa , and Burunge and who moved south from Ethiopia into Tanzania . Based on linguistic evidence , there may also have been two movements into Tanzania of Eastern Cushitic people at about 4,000 and 2,000 years ago , originating from north of Lake Turkana . Archaeological evidence supports the conclusion that Southern Nilotes , including the Datoog , moved south from the present-day South Sudan-Ethiopia border region into central northern Tanzania between 2,900 and 2,400 years ago . These movements took place at about the same time as the settlement of the iron-making Mashariki Bantu from West Africa in the Lake Victoria and Lake Tanganyika areas . They brought with them the west African planting tradition and the primary staple of yams . They subsequently migrated out of these regions across the rest of Tanzania , between 2,300 and 1,700 years ago . European colonialism began in mainland Tanzania during the late 19th century when Germany formed German East Africa , which gave way to British rule following World War I . The mainland was governed as Tanganyika , with the Zanzibar Archipelago remaining a separate colonial jurisdiction . Following their respective independence in 1961 and 1963 , the two entities merged in April 1964 to form the United Republic of Tanzania . Tanzania is mountainous and densely forested in the northeast , where Mount Kilimanjaro is located . Three of Africa 's Great Lakes are partly within Tanzania . To the north and west lie Lake Victoria , Africa 's largest lake , and Lake Tanganyika , the continent 's deepest lake , known for its unique species of fish . The eastern shore is hot and humid , with the Zanzibar Archipelago just offshore . The Kalambo water falls in the southwestern region of Rukwa are the second highest uninterrupted fall in Africa and are located near the southeastern shore of Lake Tanganyika on the border with Zambia . The Menai Bay Conservation Area is Zanzibar 's largest marine protected area . Over 100 different languages are spoken in Tanzania , making it the most linguistically diverse country in East Africa . Among the languages spoken in Tanzania are all four of Africa 's language families : Bantu , Cushitic , Nilotic , and Khoisan . Swahili and English are Tanzania 's official languages . A highly multilingual country , Swahili is used in parliamentary debate , in the lower courts , and as a medium of instruction in primary school ; and English is used in foreign trade , in diplomacy , in higher courts , and as a medium of instruction in secondary and higher education , although the Tanzanian government plans to discontinue English as a language of instruction altogether . In connection with his Ujamaa social policies , President Nyerere encouraged the use of Swahili ; as a means of unifying the country 's many ethnic groups . Approximately 10 % of Tanzanians speak Swahili as a first language , and up to 90 % speak it as a second language . Most Tanzanians thus speak both Swahili and a local language ; many educated Tanzanians are trilingual ; also speaking English . The widespread use and promotion of Swahili is contributing to the decline of smaller languages in the country . Young children increasingly speak Swahili as a first language , mostly in urban areas . Tanzania-Malawi relations have been tense because of a dispute over the countries ' Lake Nyasa ( Lake Malawi ) border . An unsuccessful mediation regarding this issue happened in March 2014 . The two countries agreed in 2013 to ask the International Court of Justice ( ICJ ) to resolve the dispute should mediation be unsuccessful . Malawi , but not Tanzania , has accepted the compulsory jurisdiction of the ICJ .", "title": "" } ]
[ { "docid": "Outline_of_Uganda", "text": "The following outline is provided as an overview of and topical guide to Uganda : Uganda -- commonly referred to as the Pearl by Churchill is a land-locked sovereign country located in East Africa , bordered on the east by Kenya , the north by South Sudan , on the west by the Democratic Republic of the Congo , on the southwest by Rwanda , and on the south by Tanzania . The southern part of the country includes a substantial portion of Lake Victoria , within which it shares borders with Kenya and Tanzania . Uganda takes its name from the Buganda kingdom , which encompassed a portion of the south of the country including the capital Kampala .", "title": "" }, { "docid": "Oman", "text": "Oman ( -LSB- oʊˈmɑːn -RSB- ; عمان -LSB- ʕʊˈmaːn -RSB- ) , officially the Sultanate of Oman , is an Arab country on the southeastern coast of the Arabian Peninsula . Holding a strategically important position at the mouth of the Persian Gulf , the country shares land borders with the United Arab Emirates to the northwest , Saudi Arabia to the west , and Yemen to the southwest , and shares marine borders with Iran and Pakistan . The coast is formed by the Arabian Sea on the southeast and the Gulf of Oman on the northeast . The Madha and Musandam exclaves are surrounded by the UAE on their land borders , with the Strait of Hormuz ( which it shares with Iran ) and Gulf of Oman forming Musandam 's coastal boundaries . From the late 17th century , the Omani Sultanate was a powerful empire , vying with Portugal and Britain for influence in the Persian Gulf and Indian Ocean . At its peak in the 19th century , Omani influence or control extended across the Strait of Hormuz to modern-day Iran and Pakistan , and as far south as Zanzibar ( today part of Tanzania , also former capital ) . As its power declined in the 20th century , the sultanate came under the influence of the United Kingdom . Historically , Muscat was the principal trading port of the Persian Gulf region . Muscat was also among the most important trading ports of the Indian Ocean . Oman 's official religion is Islam . Oman is an absolute monarchy . The Sultan Qaboos bin Said al Said has been the hereditary leader of the country since 1970 . Sultan Qaboos is the longest-serving current ruler in the Middle East , and sixth-longest current reigning monarch in the world . Oman has modest oil reserves , ranking 25th globally . Nevertheless , in 2010 the UNDP ranked Oman as the most improved nation in the world in terms of development during the preceding 40 years . A significant portion of its economy is tourism and trade of fish , dates , and certain agricultural produce . This sets it apart from its neighbors ' solely oil-dependent economies . Oman is categorized as a high-income economy and ranks as the 74th most peaceful country in the world according to the Global Peace Index .", "title": "" }, { "docid": "Borders_of_Brazil", "text": "Brazil is the largest country in South America and borders every country in South America with the exceptions of Chile and Ecuador . The borders of Brazil are the international borders that Brazil shares with neighbouring countries . Brazil has borders with ten different countries , totalling 16885 km , making it the country with the third longest land border behind only China and Russia . The lengths of the borders Brazil shares with different countries , running counter-clockwise around Brazil from French Guiana to Uruguay , are listed below :", "title": "" }, { "docid": "Tourism_in_Tanzania", "text": "Tanzania is a country with many tourist attractions . Approximately 38 percent of Tanzania 's land area is set aside in protected areas for conservation . There are 16 national parks , 29 game reserves , 40 controlled conservation areas ( including the Ngorongoro Conservation Area ) and marine parks . Tanzania is also home to Mount Kilimanjaro , the highest point in Africa . Travel and tourism contributed 12.7 percent of Tanzania 's gross domestic product and employed 11.0 percent of the country 's labor force ( 1,189,300 jobs ) in 2013 . The sector is growing rapidly , rising from US $ 1.74 billion in 2004 to US $ 4.48 billion in 2013 . In 2012 , 1,043,000 tourists arrived at Tanzania 's borders compared to 590,000 in 2005 .", "title": "" }, { "docid": "List_of_countries_and_territories_by_land_and_maritime_borders", "text": "This is a list of countries and territories by land and maritime borders . For each country or territory , the number and identity of other countries and territories that neighbor it are listed . Land borders and maritime boundaries are included and are tabulated separately and in combination . For purposes of this list , `` maritime boundary '' includes boundaries that are recognized by the United Nations Convention on the Law of the Sea , which includes boundaries of territorial waters , contiguous zones , and exclusive economic zones . However , it does not include lake or river boundaries , which are considered land boundaries . Also included is the number of unique sovereign states that a country or territory shares as neighbors . If the number is higher due to multiple dependencies or unrecognized states bordering the state , the larger number is shown in brackets . Footnotes are provided to provide clarity regarding the status of certain countries and territories .", "title": "" }, { "docid": "Natural_resource_and_waste_management_in_Tanzania", "text": "Tanzania , officially known as the United Republic of Tanzania , is a mid-sized country in southeastern Africa bordering the Indian Ocean . It is home to a population of about 43.1 million people . Since gaining its independence from the United Kingdom in 1961 , Tanzania has been continuously developing in terms of its economy and modern industry . However , the country 's economic success has been limited . Environmental obstacles , such as the mismanagement of natural resources and industrial waste , have been contributing factors and results of the relatively low economic status of the country . Tanzania 's annual output still falls below the average world GDP . In 2010 , the GDP for Tanzania was US $ 23.3 billion and the GDP per capita was US $ 1,515 . Comparatively , the GDP for the United States was $ 15.1 trillion and the GDP per capita was approximately $ 47,153 . Eighty percent of the workers accounting for this annual output in Tanzania work in agriculture , while the remaining 20 % work in industry , commerce , and government organizations . Such a heavy reliance on agriculture has placed a huge amount of strain on an already limited supply of viable land .", "title": "" }, { "docid": "Japan–Russia_border", "text": "The Japan -- Russia border is the de facto maritime boundary that separates the territorial waters of the two countries . According to the Russia border agency , the border 's length is 194.3 km . The two countries do not share a terrestrial border , although in 1905-1945 the Russian Empire , and , later , the USSR , did have a land border with Japan in Sakhalin Island .", "title": "" }, { "docid": "Northern_Province,_Zambia", "text": "Northern Province is one of Zambia 's ten provinces . It covers approximately one sixth of Zambia in land area . The provincial capital is Kasama . The province is made up of 8 districts , namely Kasama ( the provincial capital ) , Chilubi , Kaputa , Luwingu , Mbala , Mporokoso , Mpulungu and Mungwi . Currently , only Kasama and Mbala have attained municipal council status , while the rest are still district councils . It is widely considered to be the heartland of the Bemba , one of the largest tribes in Zambia . Since this article was published the new Muchinga Province has taken the Eastern districts of Northern Province and Chama district to form Zambia 's tenth province . Notable landmarks in Northern Province include Lake Tanganyika , Lake Bangweulu , and the corresponding wetlands , Lake Mweru-wa-Ntipa , and a number of waterfalls including Lumangwe Falls , Kabwelume Falls , Chishimba and Kalambo Falls . Efforts are being made by the Zambian government , along with a number of non-governmental organizations , to increase the visibility of the many natural and historical treasures in the Northern Province . Tourism has proven an effective way to bring economic growth in other parts of Zambia , i.e. Livingstone and Victoria Falls . However , a lack of infrastructure along the vast distances between major points of interest makes visiting this part of the country difficult . Northern Province , with a total area of 77,650 square kilometers , shares borders with two other provinces - Muchinga and Luapula , and also with two countries - the Democratic Republic of Congo in the north and Tanzania in the north-east .", "title": "" }, { "docid": "Masnaa_Border_Crossing", "text": "The Masnaa Border Crossing is an international border crossing between the countries of Lebanon and Syria . It is completely land-based and links the customs checkpoints of Masnaa , Lebanon , and Jdaidet Yabous , Syria . An 8 km no man 's land of desolate neutral territory buffers the distance between the border stations . It is the primary crossing point between the countries , linking the capital cities of Beirut and Damascus .", "title": "" }, { "docid": "Senegal", "text": "Senegal ( -LSB- sɛnᵻˈɡɔːl , _ - ˈɡɑːl -RSB- Sénégal ) , officially the Republic of Senegal ( -LSB- ʁepyblik dy seneɡal -RSB- ) , is a country in West Africa . Senegal is bordered by Mauritania in the north , Mali to the east , Guinea to the southeast , and Guinea-Bissau to the southwest . Senegal also borders The Gambia , a country occupying a narrow sliver of land along the banks of the Gambia River , which separates Senegal 's southern region of Casamance from the rest of the country . Senegal also shares a maritime border with Cape Verde . Senegal 's economic and political capital is Dakar . It is the westernmost country in the mainland of the Old World , or Afro-Eurasia , and owes its name to the Senegal River , which borders it to the east and north . The name `` Senegal '' comes from the Wolof `` Sunuu Gaal '' , which means `` Our Boat '' . Senegal covers a land area of almost 197000 km2 and has an estimated population of about 15 million . The climate is Sahelian , but there is a rainy season .", "title": "" }, { "docid": "Victoria_Cup_(rugby_union)", "text": "The Victoria Cup is a rugby union competition in Africa . Three teams , Kenya , Uganda ( The Rugby Cranes ) and Zimbabwe ( The Sables ) compete for this Cup in a format similar to that of the Tri Nations . The competition is administered by Confederation of African Rugby ( CAR ) . Just as the Bledisloe Cup ( Australia and New Zealand ) , Freedom Cup ( New Zealand and South Africa ) and Mandela Challenge Plate ( Australia and South Africa ) have been subsumed into the Tri Nations and as the Calcutta Cup ( England and Scotland ) is now part of the Six Nations , so the pre-existing Elgon Cup between Kenya and Uganda will , from now on , be played for within this new competition . The competition is well named ; two of the competing nations include part of Lake Victoria within their borders whilst the other can claim Victoria Falls as one of its major geographical features . The name also looks to the future ; Zambia could possibly be included if the quality of rugby in that country could be raised to its 1960s-1970s level ( Zambia shares the Victoria Falls with Zimbabwe ) and Tanzania are also making progress in their domestic competition ( Tanzania is the other country that shares Lake Victoria ) .", "title": "" }, { "docid": "Malawi-Tanzania_border", "text": "The Malawi-Tanzania border is an international boundary that separates Malawi and Tanzania in East Africa . Most of the border is formed by the river Songwe , whose source is found in the mountains to the south-west of Mount Rungwe and the town of Tukuyu . The Songwe is fast-flowing and changes its course regularly in a short period of time , forming new meanders and causing the precise border location to shift and become ambiguous . A dam is currently being constructed to regulate the river 's flow . The border follows the Songwe into Lake Malawi , where it meets the tripoint between Malawi , Mozambique and Tanzania . Following the Heligoland-Zanzbar Treaty of 1890 , the two colonial powers , the United Kingdom ( for Nyasaland , which later became Malawi ) and Germany ( for Tanganyika , which later became Tanzania ) agreed that the border would follow the Tanzanian shore of the lake . When Malawi and Tanzania respectively gained independence , the agreement was never modified . Oil-prospecting projects on the lake conducted by a British company have revived border disagreements between the two countries .", "title": "" }, { "docid": "Outline_of_Tanzania", "text": "The following outline is provided as an overview of and topical guide to Tanzania : Tanzania -- sovereign country located in East Africa . Tanzania borders Kenya and Uganda on the north , Rwanda , Burundi and the Democratic Republic of the Congo on the west , and Zambia , Malawi and Mozambique on the south . To the east it borders the Indian Ocean .", "title": "" }, { "docid": "Brunei–Malaysia_border", "text": "The border between Brunei and Malaysia consist of a 481.3 km land border and substantial lengths of maritime borders stretching from the coastline of the two countries to the edge of the continental shelf in the South China Sea . Except for its South China Sea coastline , Brunei is entirely surrounded by Malaysia 's Sarawak state and the country only shares a land boundary with Malaysia . Brunei 's unique shape where its territory consists of two non-contiguous portions results in its border with Malaysia being broken into two segments . Brunei 's 200 nautical mile continental shelfclaim makes it a claimant of a portion of the South China Sea that is subject to multiple overlapping claims by China , Taiwan and Vietnam . Malaysia is also a claimant in the area but a bilateral agreement with Brunei has solved the overlapping claims over Brunei 's territorial waters .", "title": "" }, { "docid": "Borders_of_China", "text": "The People 's Republic of China has international borders with 14 sovereign states . In addition , there is a 30-km border with the special administrative region of Hong Kong , which was a British dependency before 1997 , and a 3 km border with Macau , a Portuguese territory until 1999 . With a land border of 22117 km in total it also has the longest land border of any country . Below is a table of countries and territories who share a land border with China around its perimeter , counterclockwise from the east . The numbers in parenthesis are their lengths in miles . * In three sections , separated by Nepal and Bhutan . The length of China 's border with India depends on the resolution of territorial conflicts between India and China , and between India and Pakistan . ¹ The length of China 's border with North Korea depends on the resolution of the territorial conflict between China and North Korea over Mount Paektu and Jiandao . ² The length of China 's border with Bhutan depends on the resolution of various territorial conflicts between India and China , and also between Bhutan and China . ³ The length of China 's border with Nepal depends on the resolution of the territorial conflict between Nepal and India over the Kalapani territory . § The length of China 's border with Myanmar depends on the resolution of the territorial conflict between India and China over Arunachal Pradesh . ‡ The length of China 's border with Pakistan depends on the resolution of territorial conflicts between India and Pakistan . † In two sections , separated by Mongolia .", "title": "" }, { "docid": "Geography_of_the_United_Arab_Emirates", "text": "The United Arab Emirates is situated in Middle East/southwest Asia , bordering the Gulf of Oman and the Persian Gulf , between Oman and Saudi Arabia ; it is on a strategic location along northern approaches to the Strait of Hormuz , a vital transit point for world crude oil . The UAE lies between 22 ° 50 ′ and 26 ° north latitude and between 51 ° and 56 ° 25 ′ east longitude . It shares a 19-kilometer border with Qatar on the northwest , a 530-kilometer border with Saudi Arabia on the west , south , and southeast , and a 450-kilometer border with Oman on the southeast and northeast . The land border with Qatar in the Khawr al Udayd area is a source of ongoing dispute ( in fact , whether it even shares a land border with Qatar is in dispute ) . The total area of the UAE is approximately 83,600 square kilometers . The country 's exact size is unknown because of disputed claims to several islands in the Persian Gulf , because of the lack of precise information on the size of many of these islands , and because most of its land boundaries , especially with Saudi Arabia , remain undemarcated . The largest emirate , Abu Dhabi , accounts for 87 percent of the UAE 's total area ( 72,732 square kilometers ) . The smallest emirate , Ajman , encompasses only 259 square kilometers .", "title": "" }, { "docid": "Cambodia–Vietnam_relations", "text": "Cambodia -- Vietnam relations take place in the form of bilateral relations between the Kingdom of Cambodia and the Socialist Republic of Vietnam . The countries have shared a land border for the last thousand years and share more recent historical links through being part of the French colonial empire . Both countries are members of the Association of Southeast Asian Nations ( ASEAN ) .", "title": "" }, { "docid": "List_of_companies_of_Malawi", "text": "Malawi , officially the Republic of Malawi , is a landlocked country in southeast Africa that was formerly known as Nyasaland . It is bordered by Zambia to the northwest , Tanzania to the northeast , and Mozambique on the east , south and west . The country is separated from Tanzania and Mozambique by Lake Malawi . Malawi is among the world 's least-developed and most-densely populated countries . Around 85 % of the population live in rural areas . The economy is based on agriculture , and more than one-third of GDP and 90 % of export revenues come from this . In 2006 , in response to disastrously low agricultural harvests , Malawi , through an initiative by the late President Bingu Mutharika , an economist by profession , began a program of fertilizer subsidies that were designed to re-energize the land and boost crop production . It has been reported that this program , championed by the country 's president , is radically improving Malawi 's agriculture , and causing Malawi to become a net exporter of food to nearby countries . Economic grievances though took a downward slide during Mutharikas second term . Economic grivences was a catalyst that resulted in the 2011 economic protests in Malawi in July .", "title": "" }, { "docid": "Outline_of_Rwanda", "text": "The Republic of Rwanda is a small landlocked sovereign country located in the Great Lakes region of east-central Africa , bordered by Uganda , Burundi , the Democratic Republic of the Congo and Tanzania . Home to approximately 10.1 million people , Rwanda supports the densest population in continental Africa , with most of the population engaged in subsistence agriculture . A verdant country of fertile and hilly terrain , the small republic bears the title `` Land of a Thousand Hills '' . The country attracted international concern for the infamous Rwandan Genocide of 1994 . The following outline is provided as an overview of and topical guide to Rwanda :", "title": "" }, { "docid": "List_of_countries_and_territories_by_land_borders", "text": "This is a list of countries and territories by land borders . For each country or territory , the number of unique land boundaries and the identity of other countries and territories that neighbour it are listed . The length of each land border is included , as is the sum total of each country and territory 's total land boundaries . Countries or territories that are connected only by the bridges or other man-made causeways are not considered to have land borders . However , borders along lakes , rivers , and other internal waters are considered as land borders for the purposes of this article . Footnotes are included to provide clarity regarding the status of certain countries and territories .", "title": "" }, { "docid": "Lithuania–Poland_border", "text": "The current Lithuania -- Poland border has existed since the re-establishment of the independence of Lithuania on March 11 , 1990 . Until then the identical border was between Poland and Lithuanian SSR of the Soviet Union . The length of the border is 103 or . It runs from the Lithuania -- Poland -- Russia tripoint southeast to the Belarus -- Lithuania -- Poland tripoint . It is the only land border that the EU - and NATO-member Baltic states share with a country that is not a member of the Russian-aligned Commonwealth of Independent States . To the military planners of NATO , the border area is known as the Suwalki gap ( named after nearby town of Suwałki ) , because it represents a tough-to-defend flat narrow piece of land , a gap , that is between Belarus and Russia 's Kaliningrad enclave and that connects the NATO-member Baltic States to Poland and the rest of NATO .", "title": "" }, { "docid": "Postage_stamps_and_postal_history_of_Uganda", "text": "This is a survey of the postage stamps and postal history of Uganda . Uganda is a landlocked country in East Africa . It is bordered on the east by Kenya , on the north by South Sudan , on the west by the Democratic Republic of the Congo , on the southwest by Rwanda , and on the south by Tanzania . The southern part of the country includes a substantial portion of Lake Victoria , which is also bordered by Kenya and Tanzania .", "title": "" }, { "docid": "Mbinga_District", "text": "Mbinga District is one of the five districts of the Ruvuma Region of Tanzania . It is bordered to the north by the Njombe Region , to the east by Songea Rural District and Songea Urban District , to the south by Mozambique and to the west by Lake Nyasa . According to the 2002 Tanzania National Census , the population of the Mbinga District was 404,799 . Mbinga District covers an area of 11,396 square kilometres , about 18 percent of the land area of the Ruvuma Region and about 1 % of the land mass of Tanzania .", "title": "" }, { "docid": "United_Kingdom", "text": "The United Kingdom of Great Britain and Northern Ireland , commonly known as the United Kingdom ( UK ) or Britain , is a sovereign country in western Europe . Lying off the north-western coast of the European mainland , the United Kingdom includes the island of Great Britain , the north-eastern part of the island of Ireland and many smaller islands . Northern Ireland is the only part of the United Kingdom that shares a land border with another sovereign statethe Republic of Ireland.Although Northern Ireland is the only part of the UK that shares a land border with another sovereign state , two of its Overseas Territories also share land borders with other sovereign countries . Gibraltar shares a border with Spain , while the Sovereign Base Areas of Akrotiri and Dhekelia share borders with the Republic of Cyprus , the Turkish Republic of Northern Cyprus and the UN buffer zone separating the two Cypriot polities . Apart from this land border , the United Kingdom is surrounded by the Atlantic Ocean , with the North Sea to its east , the English Channel to its south and the Celtic Sea to its south-south-west , giving it the 12th-longest coastline in the world . The Irish Sea lies between Great Britain and Ireland . With an area of 242500 km2 , the United Kingdom is the 78th-largest sovereign state in the world and the 11th-largest in Europe . It is also the 21st-most populous country , with an estimated 65.1 million inhabitants . Together , this makes it the fourth-most densely populated country in the European Union ( EU ) . The United Kingdom is a constitutional monarchy with a parliamentary system of governance . The monarch is Queen Elizabeth II , who has reigned since 6 February 1952 . The capital of the United Kingdom and its largest city is London , a global city and financial centre with an urban area population of 10.3 million , the fourth-largest in Europe and second-largest in the European Union . Other major urban areas in the United Kingdom include the conurbations centred on Birmingham , Leeds , Glasgow , Liverpool and Manchester . The United Kingdom consists of four countries -- England , Scotland , Wales and Northern Ireland . The last three have devolved administrations , each with varying powers , based in their capitals , Edinburgh , Cardiff and Belfast , respectively . The nearby Isle of Man , Bailiwick of Guernsey and Bailiwick of Jersey are not part of the United Kingdom , being Crown dependencies with the British Government responsible for defence and international representation . The relationships among the countries of the UK have changed over time . Wales was annexed by the Kingdom of England under the Laws in Wales Acts 1535 and 1542 . A treaty between England and Scotland resulted in 1707 in a unified Kingdom of Great Britain , which merged in 1801 with the Kingdom of Ireland to form the United Kingdom of Great Britain and Ireland . Five-sixths of Ireland seceded from the UK in 1922 , leaving the present formulation of the United Kingdom of Great Britain and Northern Ireland.The Anglo-Irish Treaty was signed on 6 December 1921 to resolve the Irish War of Independence . When it took effect one year later , it established the Irish Free State as a separate dominion within the Commonwealth . The UK 's current name was adopted to reflect the change . There are fourteen British Overseas Territories . These are the remnants of the British Empire which , at its height in the 1920s , encompassed almost a quarter of the world 's land mass and was the largest empire in history . British influence can be observed in the language , culture and legal systems of many of its former colonies . The United Kingdom is a developed country and has the world 's fifth-largest economy by nominal GDP and ninth-largest economy by purchasing power parity . The UK is considered to have a high-income economy and is categorised as very high in the Human Development Index , ranking 16th in the world . It was the world 's first industrialised country and the world 's foremost power during the 19th and early 20th centuries . The UK remains a great power with considerable economic , cultural , military , scientific and political influence internationally . It is a recognised nuclear weapons state and is seventh in military expenditure in the world . The UK has been a permanent member of the United Nations Security Council since its first session in 1946 . It has been a leading member state of the EU and its predecessor , the European Economic Community ( EEC ) , since 1973 . However , on 23 June 2016 , a national referendum on the UK 's membership of the EU resulted in a decision to leave , and its exit from the EU is currently being negotiated . The UK is also a member of the Commonwealth of Nations , the Council of Europe , the G7 finance ministers , the G7 forum , the G20 , NATO , the Organisation for Economic Co-operation and Development ( OECD ) , and the World Trade Organization ( WTO ) .", "title": "" }, { "docid": "Oman–United_Arab_Emirates_relations", "text": "Oman -- United Arab Emirates relations are the relations between the United Arab Emirates and Oman . The U.A.E. has an embassy in Muscat while Oman maintains an embassy in Abu Dhabi and a consulate-general in Dubai . Both countries are part of the Middle East region and share close cultural ties . Oman and the U.A.E. also share very large borders with each other , including two exclaves of Oman accessible on land only through the U.A.E , and also seem to border the Gulf of Oman .", "title": "" }, { "docid": "List_of_airports_in_Uganda", "text": "This is a list of airports in Uganda , sorted by location . Uganda is a landlocked country in East Africa . It is bordered on the east by Kenya , on the north by South Sudan , on the west by the Democratic Republic of the Congo , on the southwest by Rwanda , and on the south by Tanzania . The southern part of the country includes a substantial portion of Lake Victoria , which is also bordered by Kenya and Tanzania . Uganda 's capital and largest city is Kampala . __ TOC __", "title": "" }, { "docid": "Finland–Norway_border", "text": "The border between Norway and Finland is 736 km long . It is a land and river border between two tripoints . The western tripoint is marked by Treriksröset , a stone cairn where both countries border Sweden . The eastern tripoint is marked by Treriksrøysa , a stone cairn where both countries border Russia . The border was defined in a treaty from 1751 , which also included the Swedish-Norwegian border . In the period 1738-1751 there were field investigations and negotiations on the border , although the Finnish part needed less negotiation . Cairns were erected after that with the last one at Nesseby in 1766 . A treaty in 1816 with Russia which possessed Finland , defined the easternmost part of the border . Between 1920-1944 , the Petsamo area belonged to Finland , so the Finland -- Norway border extended along the present Norway -- Russia border to the ocean . The 1751 treaty also granted the sami people the right to cross the border freely including their reindeers , like they always have done . In 1852 , the border Norway -- Finland/Russia was closed , causing trouble for the samis , who needed the Finnish forests for reindeer winter grazing . The Finland -- Norway border is open as both countries are part of the Schengen Area . It is legal to cross the border anywhere if no customs declaration or passport check is needed . There is an 8 m wide clear-cut zone along the land border . Almost half of the border follows the rivers Anarjohka and Tana .", "title": "" }, { "docid": "Malaysia–Thailand_border", "text": "The Malaysia -- Thailand border consists of both a land boundary across the Malay Peninsula and maritime boundaries in the Straits of Malacca and the Gulf of Thailand/South China Sea . Malaysia lies to the south of the border while Thailand lies to the north . The Golok River forms the easternmost 95 km stretch of the land border . The land border is based on the 1909 treaty between Thailand , then known as Siam , and the British which started to exert its influence over the northern Malay states of Kedah , Kelantan , Perlis , Perak and Terengganu in the early 20th century . The four states had earlier been under Siamese control . Four Malaysian states abut the border . They are ( from west to east ) Perlis , Kedah , Perak and Kelantan . The four Thai provinces which abut the border are ( again from west to east ) are Satun , Songkhla , Yala and Narathiwat . Malaysia and Thailand have a territorial sea and continental shelf boundary agreements for the Straits of Malacca which was signed in 1979 and 1971 respectively . The 1979 agreement also included Indonesia as a signatory as it also determined the common continental shelf border tripoint for the three countries . The 1979 agreement also established the territorial sea boundary in the Gulf of Thailand while a separate memorandum of understanding signed in 1979 established a short continental shelf boundary in the area . The boundary beyond that agreed is subject to dispute because of overlapping claims over the seabed . The overlapping claims led to the establishment of a joint development area in 1990 where both countries agreed to share mineral resources in a 7,250 square km wedge-shaped area .", "title": "" }, { "docid": "Australia–Papua_New_Guinea_relations", "text": "Australia -- Papua New Guinea relations are the foreign relations between Australia and Papua New Guinea . Papua New Guinea is Australia 's closest neighbour ( with 3.7 km separating the two countries at the nearest point , and with both nations sharing the same continent ) , and a former dependent territory of Australia . Papua New Guinea has developed much closer relations with Australia than with Indonesia , the only country with which it shares a land border . The two countries are Commonwealth realms , and Papua New Guinea benefits from economic development aid from Australia .", "title": "" }, { "docid": "List_of_companies_of_Senegal", "text": "Senegal is a country in West Africa . Senegal is bordered by Mauritania in the north , Mali to the east , Guinea to the southeast , and Guinea-Bissau to the southwest . Senegal also borders The Gambia , a country occupying a narrow sliver of land along the banks of the Gambia river , which separates Senegal 's southern region of Casamance from the rest of the country . Senegal also shares a maritime border with Cape Verde . Senegal 's economical and political capital is Dakar . It is the westernmost country in the mainland of the Old World , or Afro-Eurasia , and owes its name to the Senegal River , which borders it to the east and north . The main industries include food processing , mining , cement , artificial fertilizer , chemicals , textiles , refining imported petroleum , and tourism . Exports include fish , chemicals , cotton , fabrics , groundnuts , and calcium phosphate . The principal foreign market is India at 26.7 percent of exports ( as of 1998 ) . Other foreign markets include the United States , Italy and the United Kingdom .", "title": "" } ]
367
Early patent ductus ateriosus (PDA) screening decreases in-hospital mortality.
[ { "docid": "27099731", "text": "IMPORTANCE There is currently no consensus for the screening and treatment of patent ductus arteriosus (PDA) in extremely preterm infants. Less pharmacological closure and more supportive management have been observed without evidence to support these changes. OBJECTIVE To evaluate the association between early screening echocardiography for PDA and in-hospital mortality. DESIGN, SETTING, AND PARTICIPANTS Comparison of screened and not screened preterm infants enrolled in the EPIPAGE 2 national prospective population-based cohort study that included all preterm infants born at less than 29 weeks of gestation and hospitalized in 68 neonatal intensive care units in France from April through December 2011. Two main analyses were performed to adjust for potential selection bias, one using propensity score matching and one using neonatal unit preference for early screening echocardiography as an instrumental variable. EXPOSURES Early screening echocardiography before day 3 of life. MAIN OUTCOMES AND MEASURES The primary outcome was death between day 3 and discharge. The secondary outcomes were major neonatal morbidities (pulmonary hemorrhage, severe bronchopulmonary dysplasia, severe cerebral lesions, and necrotizing enterocolitis). RESULTS Among the 1513 preterm infants with data available to determine exposure, 847 were screened for PDA and 666 were not; 605 infants from each group could be paired. Exposed infants were treated for PDA more frequently during their hospitalization than nonexposed infants (55.1% vs 43.1%; odds ratio [OR], 1.62 [95% CI, 1.31 to 2.00]; absolute risk reduction [ARR] in events per 100 infants, -12.0 [95% CI, -17.3 to -6.7). Exposed infants had a lower hospital death rate (14.2% vs 18.5% ; OR, 0.73 [95% CI, 0.54 to 0.98]; ARR, 4.3 [95% CI, 0.3 to 8.3]) and a lower rate of pulmonary hemorrhage (5.6% vs 8.9%; OR, 0.60 [95% CI, 0.38 to 0.95]; ARR, 3.3 [95% CI, 0.4 to 6.3]). No differences in rates of necrotizing enterocolitis, severe bronchopulmonary dysplasia, or severe cerebral lesions were observed. In the overall cohort, instrumental variable analysis yielded an adjusted OR for in-hospital mortality of 0.62 [95% CI, 0.37 to 1.04]. CONCLUSIONS AND RELEVANCE In this national population-based cohort of extremely preterm infants, screening echocardiography before day 3 of life was associated with lower in-hospital mortality and likelihood of pulmonary hemorrhage but not with differences in necrotizing enterocolitis, severe bronchopulmonary dysplasia, or severe cerebral lesions. However, results of the instrumental variable analysis leave some ambiguity in the interpretation, and longer-term evaluation is needed to provide clarity.", "title": "Association Between Early Screening for Patent Ductus Arteriosus and In-Hospital Mortality Among Extremely Preterm Infants." } ]
[ { "docid": "9967265", "text": "BACKGROUND Patent ductus arteriosus (PDA) with significant left to right shunt in preterm infants increases morbidity and mortality. Early closure of the ductus arteriosus may be achieved pharmacologically using cyclooxygenase inhibitors or by surgery. The efficacy of both treatment modalities is well established. However, the preferred initial treatment of a symptomatic PDA in a preterm infant, surgical ligation or treatment with indomethacin, has not been well established. OBJECTIVES To compare the effect of surgical ligation of PDA vs. medical treatment with cyclooxygenase inhibitors (using indomethacin, ibuprofen, or mefenamic acid), each used as the initial treatment, on neonatal mortality in preterm infants with a symptomatic PDA. SEARCH STRATEGY The standard search strategy of the Cochrane Neonatal Review Group was used. This included search of electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2007), MEDLINE (1966 - July 2007), CINAHL (1982 - July 2007), EMBASE (1980 - July 2007); and hand search of abstracts of Pediatric Academic Societies annual meetings published in Pediatric Research (1990 - April 2002) or on line from May 2002 -July 2007. No language restrictions were applied. SELECTION CRITERIA All trials 1) using randomized or quasi-randomized patient allocation, 2) in preterm infants < 37 weeks gestational age or low-birth-weight infants (< 2500 grams) with symptomatic PDA in the neonatal period (< 28 days) and 3) comparing surgical ligation with medical treatment with cyclooxygenase inhibitors, each used as the initial treatment for closure of PDA. DATA COLLECTION AND ANALYSIS Assessment of methodological quality and extraction of data for included trials was undertaken independently by the authors. RevMan 4.1 was used for analysis of the data. MAIN RESULTS Only one study, trial B in the report of Gersony 1983, was found eligible. No additional studies were identified in the literature searches performed in July 2007. The trial compared the effect of surgical ligation of PDA vs. medical treatment with indomethacin, each used as the primary treatment. No trials comparing surgery to other cyclooxygenase inhibitors (ibuprofen, mefenamic acid) were found. Trial B of Gersony 1983 enrolled 154 infants. The study found no statistically significant difference between surgical closure and indomethacin treatment in mortality during hospital stay, chronic lung disease, other bleeding, necrotizing enterocolitis, sepsis, creatinine level, or intraventricular hemorrhage. There was a statistically significant increase in the surgical group in incidence of pneumothorax [RR 2.68 (95% CI 1.45, 4.93); RD 0.25 (95% CI 0.11, 0.38); NNH 4 (95% CI 3, 9)] and retinopathy of prematurity stage III and IV [RR 3.80 (95% CI 1.12, 12.93); RD 0.11 (95% CI 0.02, 0.20), NNH 9 (95% CI 5, 50] compared to the indomethacin group. There was as expected a statistically significant decrease in failure of ductal closure rate in the surgical group as compared to the indomethacin group: [RR 0.04 (95% CI 0.01, 0.27); RD -0.32 (95% CI -0.43, -0.21), NNT 3 (95% CI 2, 4)]. AUTHORS' CONCLUSIONS The data regarding net benefit/harm are insufficient to make a conclusion as to whether surgical ligation or medical treatment with indomethacin is preferred as initial treatment for symptomatic PDA in preterm infants. It should be noted that three recent observational studies indicated an increased risk for one or more of the following outcomes associated with PDA ligation; chronic lung disease, retinopathy of prematurity and neurosensory impairment . It is possible that the duration of the \"waiting-time\" and transport to another facility with surgical capacity to have the PDA ligated could adversely affect outcomes, as could the perioperative care.", "title": "Surgical versus medical treatment with cyclooxygenase inhibitors for symptomatic patent ductus arteriosus in preterm infants." }, { "docid": "25612629", "text": "Although a moderate-sized patent ductus arteriosus (PDA) needs to be closed by the time a child is 1-2 years old, there is great uncertainty about whether it needs to be closed during the neonatal period. Although 95% of neonatologists believe that a moderate-sized PDA should be closed if it persists in infants (born before 28 weeks) who still require mechanical ventilation, the number of neonatologists who treat a PDA when it occurs in infants who do not require mechanical ventilation varies widely. Both the high likelihood of spontaneous ductus closure and the absence of randomized controlled trials, specifically addressing the risks and benefits of neonatal ductus closure, add to the current uncertainty. New information suggests that early pharmacologic treatment has several important short-term benefits for the preterm newborn. By contrast, ductus ligation, while eliminating the detrimental effects of a PDA on lung development, may create its own set of morbidities that counteract many of the benefits derived from ductus closure.", "title": "Patent ductus arteriosus: are current neonatal treatment options better or worse than no treatment at all?" }, { "docid": "34544514", "text": "BACKGROUND Indomethacin is used as standard therapy to close a patent ductus arteriosus (PDA) but is associated with reduced blood flow to several organs. Ibuprofen, another cyclo-oxygenase inhibitor, may be as effective as indomethacin with fewer adverse effects. OBJECTIVES To determine the effectiveness and safety of ibuprofen compared with indomethacin, other cyclo-oxygenase inhibitor, placebo or no intervention for closing a patent ductus arteriosus in preterm, low birth weight, or preterm and low birth weight infants. SEARCH METHODS We searched The Cochrane Library, MEDLINE, EMBASE, Clincialtrials.gov, Controlled-trials.com, and www.abstracts2view.com/pas in May 2014. SELECTION CRITERIA Randomised or quasi-randomised controlled trials of ibuprofen for the treatment of a PDA in newborn infants. DATA COLLECTION AND ANALYSIS Data collection and analysis conformed to the methods of the Cochrane Neonatal Review Group. MAIN RESULTS We included 33 studies enrolling 2190 infants. Two studies compared intravenous (iv) ibuprofen versus placebo (270 infants). In one study (134 infants) ibuprofen reduced the incidence of failure to close a PDA (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.51 to 0.99; risk difference (RD) -0.18, 95% CI -0.35 to -0.01; number needed to treat for an additional beneficial outcome (NNTB) 6, 95% CI 3 to 100). In one study (136 infants), ibuprofen reduced the composite outcome of infant mortality, infants who dropped out, or infants who required rescue treatment (RR 0.58, 95% CI 0.38 to 0.89; RD -0.22, 95% CI -0.38 to -0.06; NNTB 5, 95% CI 3 to 17). One study (64 infants) compared oral ibuprofen with placebo and noted a significant reduction in failure to close a PDA (RR 0.26, 95% CI 0.11 to 0.62; RD -0.44, 95% CI -0.65 to -0.23; NNTB 2, 95% CI 2 to 4).Twenty-one studies (1102 infants) reported failure rates for PDA closure with ibuprofen (oral or iv) compared with indomethacin (oral or iv). There was no significant difference between the groups (typical RR 1.00, 95% CI 0.84 to 1.20; I(2) = 0%; typical RD 0.00, 95% CI -0.05 to 0.05; I(2) = 0%). The risk of developing necrotising enterocolitis (NEC) was reduced for ibuprofen (16 studies, 948 infants; typical RR 0.64, 95% CI 0.45 to 0.93; typical RD -0.05, 95% CI -0.08 to -0.01; NNTB 20, 95% CI 13 to 100; I(2) = 0% for both RR and RD). The duration of ventilatory support was reduced with ibuprofen (oral or iv) compared with iv or oral indomethacin (six studies, 471 infants; mean difference (MD) -2.4 days, 95% CI -3.7 to -1.0; I(2) = 19%).Eight studies (272 infants) reported on failure rates for PDA closure in a subgroup of the above studies comparing oral ibuprofen with indomethacin (oral or iv). There was no significant difference between the groups (typical RR 0.96, 95% CI 0.73 to 1.27; typical RD -0.01, 95% CI -0.12 to 0.09). The risk of NEC was reduced with oral ibuprofen compared with indomethacin (oral or iv) (seven studies, 249 infants; typical RR 0.41, 95% CI 0.23 to 0.73; typical RD -0.13, 95% CI -0.22 to -0.05; NNTB 8, 95% CI 5 to 20; I(2) = 0% for both RR and RD). There was a decreased risk of failure to close a PDA with oral ibuprofen compared with iv ibuprofen (four studies, 304 infants; typical RR 0.41, 95% CI 0.27 to 0.64; typical RD -0.21, 95% CI -0.31 to -0.12; NNTB 5, 95% CI 3 to 8). Transient renal insufficiency was less common in infants who received ibuprofen compared with indomethacin. High dose versus standard dose of iv ibuprofen, early versus expectant administration of iv ibuprofen, echocardiographically guided iv ibuprofen treatment vs. standard iv ibuprofen treatment and continuous infusion of ibuprofen vs. intermittent boluses of ibuprofen and long-term follow-up were studied in too few trials to draw any conclusions. AUTHORS' CONCLUSIONS Ibuprofen is as effective as indomethacin in closing a PDA and currently appears to be the drug of choice. Ibuprofen reduces the risk of NEC and transient renal insufficiency. Oro-gastric administration of ibuprofen appears as effective as iv administration. To make further recommendations, studies are needed to assess the effectiveness of high-dose versus standard-dose ibuprofen, early versus expectant administration of ibuprofen, echocardiographically guided versus standard iv ibuprofen, and continuous infusion versus intermittent boluses of ibuprofen. Studies are lacking evaluating the effect of ibuprofen on longer-term outcomes in infants with PDA.", "title": "Ibuprofen for the treatment of patent ductus arteriosus in preterm or low birth weight (or both) infants." }, { "docid": "25691541", "text": "How to manage the preterm patent ductus arteriosus (PDA) remains a conundrum. On the one hand, physiology and statistical association with adverse outcomes suggest that it is pathological. On the other hand, clinical trials of treatment strategies have failed to show any long-term benefit. Ultrasound studies of PDA have suggested that the haemodynamic impact may be much earlier after birth than previously thought (in the first hours); however, we still do not know when to treat PDA. Studies that have tested symptomatic or pre-symptomatic treatment are mainly historical and have not tested the effect of no treatment. Prophylactic treatment is the best-studied regimen but improvements in some short-term outcomes do not translate to any difference in longer-term outcomes. Neonatologists have been reluctant to engage in trials that test treatment against almost never treating. Observations of very early postnatal haemodynamic significance suggest that targeting treatment on the basis of the early postnatal constrictive response of the duct may optimize benefits. A pilot trial of this strategy showed reduction in the incidence of pulmonary haemorrhage but more trials of this strategy are needed.", "title": "Preterm patent ductus arteriosus: A continuing conundrum for the neonatologist?" }, { "docid": "14831629", "text": "Patent ductus arteriosus (PDA) is a common diagnosis among extremely premature infants, especially in those with lung disease. Treatments are often used to close the PDA. Despite nearly three decades of research, the question of whether the benefits of treatments to prevent ductal patency or promote closure outweigh the risks of these treatments remains unanswered. The authors rarely use treatments designed to close the PDA. This article reviews three considerations in support of this restrained approach: rates of spontaneous closure of the ductus arteriosus; adverse effect of persistent ductal patency; and benefits and risks of treatments for closure.", "title": "Patent ductus arteriosus: lack of evidence for common treatments." }, { "docid": "36355784", "text": "OBJECTIVE To describe the efficacy of the Finnish mass screening program for cervical squamous carcinoma and adenocarcinoma, as reflected by changes of incidence and mortality rate. METHODS Cervical cancer incidence and mortality data were obtained from the Finnish Cancer Registry. Data were available from the year 1953, when the registry was established. The nationwide mass screening program in Finland was started in the mid-1960s. A centralized organization administers this program. Women age 30-60 years are notified for screening every 5 years. RESULTS The mean incidence of cervical carcinoma in the early 1960s was 15.4 per 10(5) woman-years. In 1991, it was only 2.7 per 10(5) woman-years. The mortality rate has decreased in the same proportion since the mass screening program. In the early 1960s, the mortality was 6.6 and in 1991 1.4 per 10(5) woman-years. However, the decrease of the incidence is seen almost exclusively in squamous cell carcinomas. The mortality caused by adenocarcinoma has decreased in screened birth cohorts, but the incidence rate has remained the same. CONCLUSIONS The Finnish mass screening program has been effective and its continuation is of utmost importance. In the future more attention should be given to glandular cell atypias in cervical smears. Thus, it might be possible to decrease the incidence of cervical adenocarcinoma.", "title": "The effect of mass screening on incidence and mortality of squamous and adenocarcinoma of cervix uteri." }, { "docid": "32084655", "text": "Mass-screening for lung cancer is rather a unique system in Japan. This study illustrates time from finding abnormality on mass-screening to final diagnosis of lung cancer. Among the 517 patients with lung cancer who were admitted to our hospital over a 10-year period up to December 2001, 83 (16.1%) were detected by mass-screening. We reviewed medical records of the 83 patients and determined the intervals from the mass-screening to the pathological diagnosis with clinical staging. Time from the mass-screening to the date of hospital visit was <2 months in 62 (74.7%) cases. Five (6.0%) patients visited hospital more than 6 months after the mass-screening. With respect to the interval, there was no statistical difference in gender (p=0.0680) and age (p=0.1532). Among 60 patients who were referred from outside, on average, patients visited our hospital 0.5 month after they first sought medical attention at nearby clinic, and at our hospital 0.5 month was required to make a pathological diagnosis of lung cancer with TNM staging. There was a statistical difference in survival between the patients who were diagnosed <4 months and the patients who were diagnosed >4 months from the screening (p=0.0487). The interval in most cases was acceptable. However, further improvements are still needed to minimize the delay and to maximize the benefits of early cancer detection.", "title": "Time from finding abnormality on mass-screening to final diagnosis of lung cancer." }, { "docid": "38243984", "text": "PURPOSE The goal of this study was to evaluate prospectively the engraftment rate, factors influencing engraftment, and predictability of clinical outcome of low-passage xenografts from patients with resectable pancreatic ductal adenocarcinoma (PDA) and to establish a bank of PDA xenografts. EXPERIMENTAL DESIGN Patients with resectable PDA scheduled for resection at the Johns Hopkins Hospital were eligible. Representative pieces of tumor were implanted in nude mice. The status of the SMAD4 gene and content of tumor-generating cells were determined by immunohistochemistry. Gene expression was carried out by using a U133 Plus 2.0 array. Patients were followed for progression and survival. RESULTS A total of 94 patients with PDA were resected, 69 tumors implanted in nude mice, and 42 (61%) engrafted. Engrafted carcinomas were more often SMAD4 mutant, and had a metastatic gene expression signature and worse prognosis. Tumors from patients resistant to gemcitabine were enriched in stroma-related gene pathways. Tumors sensitive to gemcitabine were enriched in cell cycle and pyrimidine gene pathways. The time to progression for patients who received treatment with gemcitabine for metastatic disease (n = 7) was double in patients with xenografts sensitive to gemcitabine. CONCLUSION A successful xenograft was generated in 61% of patients attempted, generating a pool of 42 PDA xenografts with significant biological information and annotated clinical data. Patients with PDA and SMAD4 inactivation have a better engraftment rate. Engraftment is a poor prognosis factor, and engrafted tumors have a metastatic gene expression signature. Tumors from gemcitabine-resistant patients were enriched in stromal pathways.", "title": "Tumor engraftment in nude mice and enrichment in stroma- related gene pathways predict poor survival and resistance to gemcitabine in patients with pancreatic cancer." }, { "docid": "24088502", "text": "CONTEXT A number of countries have implemented a policy of universal leukoreduction of their blood supply, but the potential role of leukoreduction in decreasing postoperative mortality and infection is unclear. OBJECTIVE To evaluate clinical outcomes following adoption of a national universal prestorage leukoreduction program for blood transfusions. DESIGN, SETTING, AND POPULATION Retrospective before-and-after cohort study conducted from August 1998 to August 2000 in 23 academic and community hospitals throughout Canada, enrolling 14 786 patients who received red blood cell transfusions following cardiac surgery or repair of hip fracture, or who required intensive care following a surgical intervention or multiple trauma. INTERVENTION Universal prestorage leukoreduction program introduced by 2 Canadian blood agencies. A total of 6982 patients were enrolled during the control period and 7804 patients were enrolled following prestorage leukoreduction. MAIN OUTCOME MEASURES All-cause in-hospital mortality and serious nosocomial infections (pneumonia, bacteremia, septic shock, all surgical site infections) occurring after first transfusion and at least 2 days after index procedure or intensive care unit admission. Secondary outcomes included rates of posttransfusion fever and antibiotic use. RESULTS Unadjusted in-hospital mortality rates were significantly lower following the introduction of leukoreduction compared with the control period (6.19% vs 7.03%, respectively; P =.04). Compared with the control period, the adjusted odds of death following leukoreduction were reduced (odds ratio [OR], 0.87; 95% confidence interval [CI], 0.75-0.99), but serious nosocomial infections did not decrease (adjusted OR, 0.97; 95% CI, 0.87-1.09). The frequency of posttransfusion fevers decreased significantly following leukoreduction (adjusted OR, 0.86; 95% CI, 0.79-0.94), as did antibiotic use (adjusted OR, 0.90; 95% CI, 0.82-0.99). CONCLUSION A national universal leukoreduction program is potentially associated with decreased mortality as well as decreased fever episodes and antibiotic use after red blood cell transfusion in high-risk patients.", "title": "Clinical outcomes following institution of the Canadian universal leukoreduction program for red blood cell transfusions." }, { "docid": "7595742", "text": "Frailty has long been considered synonymous with disability and comorbidity, to be highly prevalent in old age and to confer a high risk for falls, hospitalization and mortality. However, it is becoming recognized that frailty may be a distinct clinical syndrome with a biological basis. The frailty process appears to be a transitional state in the dynamic progression from robustness to functional decline. During this process, total physiological reserves decrease and become less likely to be sufficient for the maintenance and repair of the ageing body. Central to the clinical concept of frailty is that no single altered system alone defines it, but that multiple systems are involved. Clinical consensus regarding the phenotype which constitutes frailty, drawing upon the opinions of numerous authors, shows the characteristics to include wasting (loss of both muscle mass and strength and weight loss), loss of endurance, decreased balance and mobility, slowed performance, relative inactivity and, potentially, decreased cognitive function. Frailty is a distinct entity easily recognized by clinicians, with multiple manifestations and with no single symptom being sufficient or essential in its presentation. Manifestations include appearance (consistent or not with age), nutritional status (thin, weight loss), subjective health rating (health perception), performance (cognition, fatigue), sensory/physical impairments (vision, hearing, strength) and current care (medication, hospital). Although the early stages of the frailty process may be clinically silent, when depleted reserves reach an aggregate threshold leading to serious vulnerability, the syndrome may become detectable by looking at clinical, functional, behavioral and biological markers. Thus, a better understanding of these clinical changes and their underlying mechanisms, beginning in the pre-frail state, may confirm the impression held by many geriatricians that increasing frailty is distinguishable from ageing and in consequence is potentially reversible. We therefore provide an update of the physiopathology and clinical and biological characteristics of the frailty process and speculate on possible preventative approaches.", "title": "Frailty Syndrome: A Transitional State in a Dynamic Process" }, { "docid": "26067999", "text": "The U.S. Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific preventive care services for patients without related signs or symptoms. It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment. The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms. Summary of Recommendation and Evidence The USPSTF recommends annual screening for lung cancer with low-dose computed tomography (LDCT) in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery. (B recommendation) See the Clinical Considerations section for suggestions for implementation in practice. See the Figure for a summary of the recommendation and suggestions for clinical practice. Figure. Screening for lung cancer: clinical summary of U.S. Preventive Services Task Force recommendation. Appendix Table 1 describes the USPSTF grades, and Appendix Table 2 describes the USPSTF classification of levels of certainty about net benefit. Appendix Table 1. What the USPSTF Grades Mean and Suggestions for Practice Appendix Table 2. USPSTF Levels of Certainty Regarding Net Benefit Supplement. Consumer Fact Sheet. Rationale Importance Lung cancer is the third most common cancer and the leading cause of cancer-related death in the United States (1). The most important risk factor for lung cancer is smoking, which results in approximately 85% of all U.S. lung cancer cases (2). Although the prevalence of smoking has decreased, approximately 37% of U.S. adults are current or former smokers (2). The incidence of lung cancer increases with age and occurs most commonly in persons aged 55 years or older. Increasing age and cumulative exposure to tobacco smoke are the 2 most common risk factors for lung cancer. Lung cancer has a poor prognosis, and nearly 90% of persons with lung cancer die of the disease. However, early-stage nonsmall cell lung cancer (NSCLC) has a better prognosis and can be treated with surgical resection. Detection Most lung cancer cases are NSCLC, and most screening programs focus on the detection and treatment of early-stage NSCLC. Although chest radiography and sputum cytologic evaluation have been used to screen for lung cancer, LDCT has greater sensitivity for detecting early-stage cancer (3). Benefits of Detection and Early Treatment Although lung cancer screening is not an alternative to smoking cessation, the USPSTF found adequate evidence that annual screening for lung cancer with LDCT in a defined population of high-risk persons can prevent a substantial number of lung cancerrelated deaths. Direct evidence from a large, well-conducted, randomized, controlled trial (RCT) provides moderate certainty of the benefit of lung cancer screening with LDCT in this population (4). The magnitude of benefit to the person depends on that person's risk for lung cancer because those who are at highest risk are most likely to benefit. Screening cannot prevent most lung cancerrelated deaths, and smoking cessation remains essential. Harms of Detection and Early Intervention and Treatment The harms associated with LDCT screening include false-negative and false-positive results, incidental findings, overdiagnosis, and radiation exposure. False-positive LDCT results occur in a substantial proportion of screened persons; 95% of all positive results do not lead to a diagnosis of cancer. In a high-quality screening program, further imaging can resolve most false-positive results; however, some patients may require invasive procedures. The USPSTF found insufficient evidence on the harms associated with incidental findings. Overdiagnosis of lung cancer occurs, but its precise magnitude is uncertain. A modeling study performed for the USPSTF estimated that 10% to 12% of screen-detected cancer cases are overdiagnosedthat is, they would not have been detected in the patient's lifetime without screening. Radiation harms, including cancer resulting from cumulative exposure to radiation, vary depending on the age at the start of screening; the number of scans received; and the person's exposure to other sources of radiation, particularly other medical imaging. USPSTF Assessment The USPSTF concludes with moderate certainty that annual screening for lung cancer with LDCT is of moderate net benefit in asymptomatic persons who are at high risk for lung cancer based on age, total cumulative exposure to tobacco smoke, and years since quitting smoking. The moderate net benefit of screening depends on limiting screening to persons who are at high risk, the accuracy of image interpretation being similar to that found in the NLST (National Lung Screening Trial), and the resolution of most false-positive results without invasive procedures (4). Clinical Considerations Patient Population Under Consideration The risk for lung cancer increases with age and cumulative exposure to tobacco smoke and decreases with time since quitting smoking. The best evidence for the benefit of screening comes from the NLST, which enrolled adults aged 55 to 74 years who had at least a 30 pack-year smoking history and were current smokers or had quit within the past 15 years. As with all screening trials, the NLST tested a specific intervention over a finite period. Because initial eligibility extended through age 74 years and participants received 3 annual screening computed tomographic scans, the oldest participants in the trial were aged 77 years. The USPSTF used modeling studies to predict the benefits and harms of screening programs that use different screening intervals, age ranges, smoking histories, and times since quitting. A program that annually screens adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years is projected to have a reasonable balance of benefits and harms. The model assumes that persons who achieve 15 years of smoking cessation during the screening program discontinue screening. This model predicts the outcomes of continuing the screening program used in the NLST through age 80 years. Screening may not be appropriate for patients with substantial comorbid conditions, particularly those at the upper end of the screening age range. The NLST excluded persons who were unlikely to complete curative lung cancer surgery and those with medical conditions that posed a substantial risk for death during the 8-year trial. The baseline characteristics of the NLST showed a relatively healthy sample, and fewer than 10% of enrolled participants were older than 70 years (5). Persons with serious comorbid conditions may experience net harm, no net benefit, or at least substantially less net benefit. Similarly, persons who are unwilling to have curative lung surgery are unlikely to benefit from a screening program. Assessment of Risk Age, total exposure to tobacco smoke, and years since quitting smoking are important risk factors for lung cancer and were used to determine eligibility in the NLST. Other risk factors include specific occupational exposures, radon exposure, family history, and history of pulmonary fibrosis or chronic obstructive lung disease. The incidence of lung cancer is relatively low in persons younger than 50 years but increases with age, especially after age 60 years. In current and former smokers, age-specific incidence rates increase with age and cumulative exposure to tobacco smoke. Smoking cessation substantially reduces a person's risk for developing and dying of lung cancer. Among persons enrolled in the NLST, those who were at highest risk because of additional risk factors or a greater cumulative exposure to tobacco smoke experienced most of the benefit (6). A validated multivariate model showed that persons in the highest 60% of risk accounted for 88% of all deaths preventable by screening. Screening Tests Low-dose computed tomography has shown high sensitivity and acceptable specificity for the detection of lung cancer in high-risk persons. Chest radiography and sputum cytologic evaluation have not shown adequate sensitivity or specificity as screening tests. Therefore, LDCT is currently the only recommended screening test for lung cancer. Treatment Surgical resection is the current standard of care for localized NSCLC. This type of cancer is treated with surgical resection when possible and also with radiation and chemotherapy. Annual LDCT screening may not be useful for patients with life-limiting comorbid conditions or poor functional status who may not be candidates for surgery. Other Approaches to Prevention Smoking cessation is the most important intervention to prevent NSCLC. Advising smokers to stop smoking and preventing nonsmokers from being exposed to tobacco smoke are the most effective ways to decrease the morbidity and mortality associated with lung cancer. Current smokers should be informed of their continuing risk for lung cancer and offered cessation treatments. Screening with LDCT should be viewed as an adjunct to tobacco cessation interventions. Useful Resources Clinicians have many resources to help patients stop smoking. The Centers for Disease Control and Prevention has developed a Web site with many such resources, including information on tobacco quit lines, available in several languages (www.cdc.gov/tobacco/campaign/tips). Quit l", "title": "Screening for Lung Cancer: U.S. Preventive Services Task Force Recommendation Statement" }, { "docid": "9167230", "text": "BACKGROUND The annual number of hospital admissions and in-hospital deaths due to severe acute lower respiratory infections (ALRI) in young children worldwide is unknown. We aimed to estimate the incidence of admissions and deaths for such infections in children younger than 5 years in 2010. METHODS We estimated the incidence of admissions for severe and very severe ALRI in children younger than 5 years, stratified by age and region, with data from a systematic review of studies published between Jan 1, 1990, and March 31, 2012, and from 28 unpublished population-based studies. We applied these incidence estimates to population estimates for 2010, to calculate the global and regional burden in children admitted with severe ALRI in that year. We estimated in-hospital mortality due to severe and very severe ALRI by combining incidence estimates with case fatality ratios from hospital-based studies. FINDINGS We identified 89 eligible studies and estimated that in 2010, 11·9 million (95% CI 10·3-13·9 million) episodes of severe and 3·0 million (2·1-4·2 million) episodes of very severe ALRI resulted in hospital admissions in young children worldwide. Incidence was higher in boys than in girls, the sex disparity being greatest in South Asian studies. On the basis of data from 37 hospital studies reporting case fatality ratios for severe ALRI, we estimated that roughly 265,000 (95% CI 160,000-450,000) in-hospital deaths took place in young children, with 99% of these deaths in developing countries. Therefore, the data suggest that although 62% of children with severe ALRI are treated in hospitals, 81% of deaths happen outside hospitals. INTERPRETATION Severe ALRI is a substantial burden on health services worldwide and a major cause of hospital referral and admission in young children. Improved hospital access and reduced inequities, such as those related to sex and rural status, could substantially decrease mortality related to such infection. Community-based management of severe disease could be an important complementary strategy to reduce pneumonia mortality and health inequities. FUNDING WHO.", "title": "Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: a systematic analysis" }, { "docid": "11880289", "text": "BACKGROUND Age-specific effects of mammographic screening, and the timing of such effects, are a matter of debate. The results of the UK Age trial, which compared the effect of invitation to annual mammographic screening from age 40 years with commencement of screening at age 50 years on breast cancer mortality, have been reported at 10 years of follow-up and showed no significant difference in mortality between the trial groups. Here, we report the results of the UK Age trial after 17 years of follow-up. METHODS Women aged 39-41 from 23 UK NHS Breast Screening Programme units years were randomly assigned by individual randomisation (1:2) to either an intervention group offered annual screening by mammography up to and including the calendar year of their 48th birthday or to a control group receiving usual medical care (invited for screening at age 50 years and every 3 years thereafter). Both groups were stratified by general practice. We compared breast cancer incidence and mortality by time since randomisation. Analyses included all women randomly assigned who could be traced with the National Health Service Central Register and who had not died or emigrated before entry. The primary outcome measures were mortality from breast cancer (defined as deaths with breast cancer coded as the underlying cause of death) and breast cancer incidence, including in-situ, invasive, and total incidence. Because there is an interest in the timing of the mortality effect, we analysed the results in different follow-up periods. This trial is registered, number ISRCTN24647151. FINDINGS Between Oct 14, 1990, and Sept 25, 1997, 160 921 participants were randomly assigned; 53 883 women in the intervention group and 106 953 assigned to usual medical care were included in this analysis. After a median follow-up of 17 years (IQR 16·8-18·8), the rate ratio (RR) for breast cancer mortality was 0·88 (95% CI 0·74-1·04) from tumours diagnosed during the intervention phase. A significant reduction in breast cancer mortality was noted in the intervention group compared with the control group in the first 10 years after diagnosis (RR 0·75, 0·58-0·97) but not thereafter (RR 1·02, 0·80-1·30) from tumours diagnosed during the intervention phase. The overall breast cancer incidence during 17 year follow-up was similar between the intervention group and the control group (RR 0·98, 0·93-1·04). INTERPRETATION Our results support an early reduction in mortality from breast cancer with annual mammography screening in women aged 40-49 years. Further data are needed to fully understand long-term effects. Cumulative incidence figures suggest at worst a small amount of overdiagnosis. FUNDING National Institute for Health Research Health Technology Assessment programme and the American Cancer Society. Past funding was received from the Medical Research Council, Cancer Research UK, the UK Department of Health, and the US National Cancer Institute.", "title": "Effect of mammographic screening from age 40 years on breast cancer mortality in the UK Age trial at 17 years' follow-up: a randomised controlled trial." }, { "docid": "32423829", "text": "Cervix and Breast cancers are the most common cancers among women worldwide and extract a large toll in developing countries. In May 1998, supported by a grant from the NCI (US), the Tata Memorial Hospital, Mumbai, India, started a cluster-randomized, controlled, screening-trial for cervix and breast cancer using trained primary health workers to provide health-education, visual-inspection of cervix (with 4% acetic acid-VIA) and clinical breast examination (CBE) in the screening arm, and only health education in the control arm. Four rounds of screening at 2-year intervals will be followed by 8 years of monitoring for incidence and mortality from cervix and breast cancers. The methodology and interim results after three rounds of screening are presented here. Good randomization was achieved between the screening (n = 75360) and control arms (n = 76178). In the screening arm we see: High screening participation rates; Low attrition; Good compliance to diagnostic confirmation; Significant downstaging; Excellent treatment completion rate; Improving case fatality ratios. The ever-screened and never-screened participants in the screening arm show significant differences with reference to the variables religion, language, age, education, occupation, income and health-seeking behavior for gynecological and breast-related complaints. During the same period, in the control arm we see excellent participation rate for health education; Low attrition and a good number of symptomatic referrals for both cervix and breast.", "title": "A cluster randomized, controlled trial of breast and cervix cancer screening in Mumbai, India: methodology and interim results after three rounds of screening." }, { "docid": "20606520", "text": "OBJECTIVES To assess mortality, quality of life (QOL), and quality-adjusted life-years (QALYs) for critically ill elderly patients. DESIGN Cross-sectional survey. SETTING A ten-bed medical-surgical intensive care unit (ICU) in a tertiary care university hospital. PATIENTS The study group included 882 elderly patients (> or =65 yrs of age) and 1,827 controls (<65 yrs of age) treated during the period of 1995 to 2000. INTERVENTION None. MEASUREMENTS AND MAIN RESULTS Mortality was assessed during the ICU and hospital stays, and 12, 24, and 36 months after ICU discharge. The cumulative 3-yr mortality rate among the elderly (57%) was higher (p < .05) than that among the controls (40%). The majority (66%) of the elderly nonsurvivors died within 1 month after intensive care discharge. All elderly patients with day-1 Sequential Organ Failure (SOFA) scores >15 died during the ICU stay. QOL was assessed with EQ-5D and RAND-36 measures from 10 months to 7 yrs after discharge. The majority (88%) of the elderly survivors assessed their present health state as good or satisfactory; 66% found it to be similar or better than 12 months earlier, and 48% similar or better than their preadmission state. QOL measures by RAND-36 revealed that aging decreased their competencies most in physical functioning, physical role limitations, and vitality, but the elderly had better values in mental health than the controls. However, QALYs of the elderly respondents were 21% to 35% lower than the mean QALY minus 2 sd units of the age- and gender-adjusted general population. CONCLUSIONS High age alone is not a valid reason to refuse intensive care, but the benefits perceived by intensive care seem to decrease with aging, if reflected as QALYs. However, 97% of the elderly survivors lived at home and 88% of them considered their QOL satisfactory or good after hospital discharge. Therefore, more reliable information on the outcome for the elderly is clearly needed.", "title": "Long-term survival, quality of life, and quality-adjusted life-years among critically ill elderly patients." }, { "docid": "4824840", "text": "Importance Estimates from claims-based analyses suggest that the incidence of sepsis is increasing and mortality rates from sepsis are decreasing. However, estimates from claims data may lack clinical fidelity and can be affected by changing diagnosis and coding practices over time. Objective To estimate the US national incidence of sepsis and trends using detailed clinical data from the electronic health record (EHR) systems of diverse hospitals. Design, Setting, and Population Retrospective cohort study of adult patients admitted to 409 academic, community, and federal hospitals from 2009-2014. Exposures Sepsis was identified using clinical indicators of presumed infection and concurrent acute organ dysfunction, adapting Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria for objective and consistent EHR-based surveillance. Main Outcomes and Measures Sepsis incidence, outcomes, and trends from 2009-2014 were calculated using regression models and compared with claims-based estimates using International Classification of Diseases, Ninth Revision, Clinical Modification codes for severe sepsis or septic shock. Case-finding criteria were validated against Sepsis-3 criteria using medical record reviews. Results A total of 173 690 sepsis cases (mean age, 66.5 [SD, 15.5] y; 77 660 [42.4%] women) were identified using clinical criteria among 2 901 019 adults admitted to study hospitals in 2014 (6.0% incidence). Of these, 26 061 (15.0%) died in the hospital and 10 731 (6.2%) were discharged to hospice. From 2009-2014, sepsis incidence using clinical criteria was stable (+0.6% relative change/y [95% CI, −2.3% to 3.5%], P = .67) whereas incidence per claims increased (+10.3%/y [95% CI, 7.2% to 13.3%], P < .001). In-hospital mortality using clinical criteria declined (−3.3%/y [95% CI, −5.6% to −1.0%], P = .004), but there was no significant change in the combined outcome of death or discharge to hospice (−1.3%/y [95% CI, −3.2% to 0.6%], P = .19). In contrast, mortality using claims declined significantly (−7.0%/y [95% CI, −8.8% to −5.2%], P < .001), as did death or discharge to hospice (−4.5%/y [95% CI, −6.1% to −2.8%], P < .001). Clinical criteria were more sensitive in identifying sepsis than claims (69.7% [95% CI, 52.9% to 92.0%] vs 32.3% [95% CI, 24.4% to 43.0%], P < .001), with comparable positive predictive value (70.4% [95% CI, 64.0% to 76.8%] vs 75.2% [95% CI, 69.8% to 80.6%], P = .23). Conclusions and Relevance In clinical data from 409 hospitals, sepsis was present in 6% of adult hospitalizations, and in contrast to claims-based analyses, neither the incidence of sepsis nor the combined outcome of death or discharge to hospice changed significantly between 2009-2014. The findings also suggest that EHR-based clinical data provide more objective estimates than claims-based data for sepsis surveillance.", "title": "Incidence and Trends of Sepsis in US Hospitals Using Clinical vs Claims Data, 2009-2014" }, { "docid": "35495268", "text": "BACKGROUND Weight loss is recommended for overweight or obese patients with type 2 diabetes on the basis of short-term studies, but long-term effects on cardiovascular disease remain unknown. We examined whether an intensive lifestyle intervention for weight loss would decrease cardiovascular morbidity and mortality among such patients. METHODS In 16 study centers in the United States, we randomly assigned 5145 overweight or obese patients with type 2 diabetes to participate in an intensive lifestyle intervention that promoted weight loss through decreased caloric intake and increased physical activity (intervention group) or to receive diabetes support and education (control group). The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina during a maximum follow-up of 13.5 years. RESULTS The trial was stopped early on the basis of a futility analysis when the median follow-up was 9.6 years. Weight loss was greater in the intervention group than in the control group throughout the study (8.6% vs. 0.7% at 1 year; 6.0% vs. 3.5% at study end). The intensive lifestyle intervention also produced greater reductions in glycated hemoglobin and greater initial improvements in fitness and all cardiovascular risk factors, except for low-density-lipoprotein cholesterol levels. The primary outcome occurred in 403 patients in the intervention group and in 418 in the control group (1.83 and 1.92 events per 100 person-years, respectively; hazard ratio in the intervention group, 0.95; 95% confidence interval, 0.83 to 1.09; P=0.51). CONCLUSIONS An intensive lifestyle intervention focusing on weight loss did not reduce the rate of cardiovascular events in overweight or obese adults with type 2 diabetes. (Funded by the National Institutes of Health and others; Look AHEAD ClinicalTrials.gov number, NCT00017953.).", "title": "Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes." }, { "docid": "19464037", "text": "OBJECTIVE To describe outcomes and identify variables associated with hospital and 1-year survival for patients admitted to an intensive care unit (ICU) with an acute exacerbation of chronic obstructive pulmonary disease (COPD). DESIGN Prospective, multicenter, inception cohort study. SETTING Forty-two ICUs at 40 US hospitals. PATIENTS A total of 362 admissions for COPD exacerbation selected from the Acute Physiology and Chronic Health Evaluation (APACHE) III database of 17,440 ICU admissions. MEASUREMENTS AND RESULTS Hospital mortality for the 362 admissions was 24%. For the 167 patients aged 65 years or older, mortality was 30% at hospital discharge, 41% at 90 days, 47% at 180 days, and 59% at 1 year. Median survival for all patients was 224 days, and median survival for the patients who died within 1 year was 30.5 days. On multiple regression analysis, variables associated with hospital mortality included age, severity of respiratory and nonrespiratory organ system dysfunction, and hospital length of stay before ICU admission. Development of nonrespiratory organ system dysfunction was the major predictor of hospital mortality (60% of total explanatory power) and 180-day outcomes (54% of explanatory power). Respiratory physiological variables (respiratory rate, serum pH, PaCO2, PaO2, and alveolar-arterial difference in partial pressure of oxygen [PAO2-PaO2]) indicative of advanced dysfunction were more strongly associated with 180-day mortality rates (22% of explanatory power) than hospital death rates (4% of explanatory power). After controlling for severity of illness, mechanical ventilation at ICU admission was not associated with either hospital mortality or subsequent survival. CONCLUSIONS Patients with COPD admitted to an ICU for an acute exacerbation have a substantial hospital mortality (24%). For patients aged 65 years or older, mortality doubles in 1 year from 30% to 59%. Hospital and longer-term mortality is closely associated with development of nonrespiratory organ system dysfunction; severity of the underlying respiratory function substantially influences mortality following hospital discharge. The need for mechanical ventilation at ICU admission did not influence either short- or long-term outcomes. Physicians should be aware of these relationships when making treatment decisions or evaluating new therapies.", "title": "Hospital and 1-year survival of patients admitted to intensive care units with acute exacerbation of chronic obstructive pulmonary disease." }, { "docid": "7317051", "text": "Pancreatic ductal adenocarcinoma (PDA) represents an unmet therapeutic challenge. PDA is addicted to the activity of the mutated KRAS oncogene which is considered so far an undruggable therapeutic target. We propose an approach to target KRAS effectively in patients using RNA interference. To meet this challenge, we have developed a local prolonged siRNA delivery system (Local Drug EluteR, LODER) shedding siRNA against the mutated KRAS (siG12D LODER). The siG12D LODER was assessed for its structural, release, and delivery properties in vitro and in vivo. The effect of the siG12D LODER on tumor growth was assessed in s.c. and orthotopic mouse models. KRAS silencing effect was further assessed on the KRAS downstream signaling pathway. The LODER-encapsulated siRNA was stable and active in vivo for 155 d. Treatment of PDA cells with siG12D LODER resulted in a significant decrease in KRAS levels, leading to inhibition of proliferation and epithelial-mesenchymal transition. In vivo, siG12D LODER impeded the growth of human pancreatic tumor cells and prolonged mouse survival. We report a reproducible and safe delivery platform based on a miniature biodegradable polymeric matrix, for the controlled and prolonged delivery of siRNA. This technology provides the following advantages: (i) siRNA is protected from degradation; (ii) the siRNA is slowly released locally within the tumor for prolonged periods; and (iii) the siG12D LODER elicits a therapeutic effect, thereby demonstrating that mutated KRAS is indeed a druggable target.", "title": "Mutant KRAS is a druggable target for pancreatic cancer." }, { "docid": "14021596", "text": "BACKGROUND The objective of the study was to test the hypothesis that elevated red cell distribution width (RDW) at admission increases the risk of mortality in older patients admitted to the emergency department (ED). METHODS We performed a retrospective analysis of patients admitted to the ED between May 2013 and October 2013. We included patients who were older than 65 years who visited the ED with any medical problems. Baseline RDW values were measured at the time of admission to the ED. The primary outcome was all-cause in-hospital mortality. Multivariate logistic analysis was performed. RESULTS A total of 1,990 patients were finally included in this study. The mean age was 75 years (SD 7), and 936 (47 %) subjects were male. The in-hospital mortality rate was 3.76 % (74 patients). RDW values higher in non-survivors than in survivors (15.9 ± 2.5 vs. 13.8 ± 1.7, p < 0.001). Multivariate logistic analysis showed that RDW was associated with all-cause in-hospital mortality after adjusting for other confounding factors. DISCUSSION RDW value at admission is an independent predictor of all-cause in-hospital mortality among patients older than 65 years. After adjustment for multiple confounders, the all-cause in-hospital mortality rate increased by 21.8% for each 1% increase in RDW. CONCLUSION These results show that RDW at admission is associated with in-hospital mortality among patients older than 65. Thus, RDW at admission may represent a surrogate marker of disease severity. We caution against using these findings to aid clinical decision-making process until they are externally validated.", "title": "The association of Red cell distribution width and in-hospital mortality in older adults admitted to the emergency department" }, { "docid": "27240667", "text": "PURPOSE Since 1990, overall breast cancer mortality rates in the United States decreased 24%. This decline has been attributed to mammography screening and adjuvant systemic therapy. However, the efficacy of these modalities may depend on estrogen receptor (ER) expression and age. We therefore examined breast cancer mortality trends in the United States according to ER status and age. METHODS Using the Surveillance, Epidemiology, and End Results (SEER) program (1990-2003), we calculated trends in incidence-based mortality (IBM), annual hazard rates for breast cancer deaths after diagnosis, and relative hazard rates for women with ER-positive and ER-negative tumors. Relative hazard rates were assessed with Cox proportional hazards models, adjusted for stage and grade, and stratified by age at diagnosis. RESULTS During the study period, IBM and annual hazard rates for breast cancer deaths decreased among women with ER-positive and ER-negative tumors, although declines were greater for those with ER-positive tumors. Among women younger than 70 years, relative hazard rates declined 38% for those with ER-positive tumors versus 19% for those with ER-negative tumors. Among women 70 years or older, relative hazard rates declined 14% for those with ER-positive tumors versus no significant decline for those with ER-negative tumors. CONCLUSION In the United States, breast cancer mortality rates have declined among women with ER-positive and ER-negative tumors, with greater declines among younger women and those with ER-positive tumors. Although mortality in all groups remains unacceptably high, additional emphasis should be placed on improving outcomes of breast cancer patients older than 70 years and those of all ages with ER-negative tumors.", "title": "Breast cancer mortality trends in the United States according to estrogen receptor status and age at diagnosis." }, { "docid": "3898784", "text": "Importance Although non–vitamin K antagonist oral anticoagulants (NOACs) are increasingly used to prevent thromboembolic disease, there are limited data on NOAC-related intracerebral hemorrhage (ICH). Objective To assess the association between preceding oral anticoagulant use (warfarin, NOACs, and no oral anticoagulants [OACs]) and in-hospital mortality among patients with ICH. Design, Setting, and Participants Retrospective cohort study of 141 311 patients with ICH admitted from October 2013 to December 2016 to 1662 Get With The Guidelines–Stroke hospitals. Exposures Anticoagulation therapy before ICH, defined as any use of OACs within 7 days prior to hospital arrival. Main Outcomes and Measures In-hospital mortality. Results Among 141 311 patients with ICH (mean [SD] age, 68.3 [15.3] years; 48.1% women), 15 036 (10.6%) were taking warfarin and 4918 (3.5%) were taking NOACs preceding ICH, and 39 585 (28.0%) and 5783 (4.1%) were taking concomitant single and dual antiplatelet agents, respectively. Patients with prior use of warfarin or NOACs were older and had higher prevalence of atrial fibrillation and prior stroke. Acute ICH stroke severity (measured by the National Institutes of Health Stroke Scale) was not significantly different across the 3 groups (median, 9 [interquartile range, 2-21] for warfarin, 8 [2-20] for NOACs, and 8 [2-19] for no OACs). The unadjusted in-hospital mortality rates were 32.6% for warfarin, 26.5% for NOACs, and 22.5% for no OACs. Compared with patients without prior use of OACs, the risk of in-hospital mortality was higher among patients with prior use of warfarin (adjusted risk difference [ARD], 9.0% [97.5% CI, 7.9% to 10.1%]; adjusted odds ratio [AOR], 1.62 [97.5% CI, 1.53 to 1.71]) and higher among patients with prior use of NOACs (ARD, 3.3% [97.5% CI, 1.7% to 4.8%]; AOR, 1.21 [97.5% CI, 1.11-1.32]). Compared with patients with prior use of warfarin, patients with prior use of NOACs had a lower risk of in-hospital mortality (ARD, −5.7% [97.5% CI, −7.3% to −4.2%]; AOR, 0.75 [97.5% CI, 0.69 to 0.81]). The difference in mortality between NOAC-treated patients and warfarin-treated patients was numerically greater among patients with prior use of dual antiplatelet agents (32.7% vs 47.1%; ARD, −15.0% [95.5% CI, −26.3% to −3.8%]; AOR, 0.50 [97.5% CI, 0.29 to 0.86]) than among those taking these agents without prior antiplatelet therapy (26.4% vs 31.7%; ARD, −5.0% [97.5% CI, −6.8% to −3.2%]; AOR, 0.77 [97.5% CI, 0.70 to 0.85]), although the interaction P value (.07) was not statistically significant. Conclusions and Relevance Among patients with ICH, prior use of NOACs or warfarin was associated with higher in-hospital mortality compared with no OACs. Prior use of NOACs, compared with prior use of warfarin, was associated with lower risk of in-hospital mortality.", "title": "Association of Intracerebral Hemorrhage Among Patients Taking Non–Vitamin K Antagonist vs Vitamin K Antagonist Oral Anticoagulants With In-Hospital Mortality" }, { "docid": "10577574", "text": "BACKGROUND In the year 2000, the organizational structure of the ICU in the Zaandam Medical Centre (ZMC) changed from an open to a closed format ICU. The objective of this study was to evaluate the effect of this organizational change on outcome in high risk surgical patients. METHODS The medical records of all consecutive high risk surgical patients admitted to the ICU from 1996 to 1998 (open format) and from 2003 to 2005 (closed format), were reviewed. High-risk patients were defined according to the Identification of Risk in Surgical patients (IRIS) score. Parameters studied were: mortality, morbidity, ICU length of stay (LOS) and hospital LOS. RESULTS Mortality of ICU patients was 25.7% in the open format group and 15.8% in the closed format group (p = 0.01). Morbidity decreased from 48.6% to 46.1% (p = 0.6). The average length of hospital stay was 17 days in the open format group, and 21 days in the closed format group (p = 0.03). CONCLUSIONS High risk surgical patients in the ICU are patients that have undergone complex and often extensive surgery. These patients are in need of specialized treatment and careful monitoring for maximum safety and optimal care. Our results suggest that closed format is a more favourable setting than open format to minimize the effects of high risk surgery, and to warrant safe outcome in this patient group.", "title": "The impact of open versus closed format ICU admission practices on the outcome of high risk surgical patients: a cohort analysis" }, { "docid": "25420421", "text": "Little is known about the changes in white blood cells and platelets in children with falciparum malaria in endemic areas. We measured the white cell count (WCC) and platelets of 230 healthy children from the community, 1369 children admitted to hospital with symptomatic malaria, and 1461 children with other medical conditions. Children with malaria had a higher WCC compared with community controls, and leucocytosis was strongly associated with younger age, deep breathing, severe anaemia, thrombocytopenia and death. The WCC was not associated with a positive blood culture. In children with malaria, high lymphocyte and low monocyte counts were independently associated with mortality. A platelet count of less than 150 x 109/l was found in 56.7% of children with malaria, and was associated with age, prostration and parasite density, but not with bleeding problems or mortality. The mean platelet volume was also higher in children with malaria compared with other medical conditions. This may reflect early release from the bone marrow in response to peripheral platelet destruction. Thus, leucocytosis was associated with both severity and mortality in children with falciparum malaria, irrespective of bacteraemia, whereas thrombocytopenia, although very common, was not associated with adverse outcome.", "title": "Changes in white blood cells and platelets in children with falciparum malaria: relationship to disease outcome." }, { "docid": "2488880", "text": "CONTEXT While it is established that management strategies and outcomes differ by gender for many diseases, its effect on infection has not been adequately studied. OBJECTIVE To investigate the role of gender among hospitalized patients treated for infection. DESIGN Observational cohort study conducted during a 26-month period from December 1996 through January 1999. SETTING University-affiliated hospital. PARTICIPANTS A total of 892 patients in the surgical units of the hospital with 1470 consecutive infectious episodes (782 in men and 688 in women). MAIN OUTCOME MEASURES Mortality during hospitalization by gender for infection episodes overall and for specific infectious sites, including lung, peritoneum, bloodstream, catheter, urine, surgical site, and skin/soft tissue. RESULTS Among all infections, there was no significant difference in mortality based on gender (men, 11.1% vs women, 14.2%; P = .07). After logistic regression analysis, factors independently associated with mortality included higher APACHE (Acute Physiology and Chronic Health Evaluation) II score, older age, malignancy, blood transfusion, and diagnosis of infection more than 7 days after admission, but not gender (female odds ratio [OR] for death, 1.32; 95% confidence interval [CI], 0.90-1.94; P = .16). Mortality was higher in women for lung (men, 18% vs women, 34%; P = .002) and soft tissue (men, 2% vs women, 10%; P < or = .05) infection; for other infectious sites, mortality did not differ by gender. Factors associated with mortality due to pneumonia by logistic regression included higher APACHE II score, malignancy, diabetes mellitus, diagnosis of infection more than 7 days after admission, older age, transplantation, and female gender (OR for death, 2.25; 95% CI, 1.17-4.32; P = .02). CONCLUSIONS Although gender may not be predictive of mortality among all infections, women appear to be at increased risk for death from hospital-acquired pneumonia, even after controlling for other comorbidities.", "title": "Gender-dependent differences in outcome after the treatment of infection in hospitalized patients." }, { "docid": "26611094", "text": "BACKGROUND An increased volume of patients is associated with improved survival in numerous high-risk medical and surgical conditions. The relationship between the number of patients admitted (hospital volume) and outcome among patients with critical illnesses is unknown. METHODS We analyzed data from 20,241 nonsurgical patients receiving mechanical ventilation at 37 acute care hospitals in the Acute Physiology and Chronic Health Evaluation clinical information system from 2002 through 2003. Multivariate analyses were performed to adjust for the severity of illness and other differences in the case mix. RESULTS An increase in hospital volume was associated with improved survival among patients receiving mechanical ventilation in the intensive care unit (ICU) and in the hospital. Admission to a hospital in the highest quartile according to volume (i.e., >400 patients receiving mechanical ventilation per year) was associated with a 37 percent reduction in the adjusted odds of death in the ICU as compared with admission to hospitals in the lowest quartile (< or =150 patients receiving mechanical ventilation per year, P<0.001). In-hospital mortality was similarly reduced (adjusted odds ratio, 0.66; 95 percent confidence interval, 0.52 to 0.83; P<0.001). A typical patient in a hospital in a low-volume quartile would have an adjusted in-hospital mortality of 34.2 percent as compared with 25.5 percent in a hospital in a high-volume quartile. Among survivors, there were no significant trends in the length of stay in the ICU or the hospital. CONCLUSIONS Mechanical ventilation of patients in a hospital with a high case volume is associated with reduced mortality. Further research is needed to determine the mechanism of the relationship between volume and outcome among patients with a critical illness.", "title": "Hospital volume and the outcomes of mechanical ventilation." }, { "docid": "39059143", "text": "CONTEXT The association of an adult tele-intensive care unit (ICU) intervention with hospital mortality, length of stay, best practice adherence, and preventable complications for an academic medical center has not been reported. OBJECTIVE To quantify the association of a tele-ICU intervention with hospital mortality, length of stay, and complications that are preventable by adherence to best practices. DESIGN, SETTING, AND PATIENTS Prospective stepped-wedge clinical practice study of 6290 adults admitted to any of 7 ICUs (3 medical, 3 surgical, and 1 mixed cardiovascular) on 2 campuses of an 834-bed academic medical center that was performed from April 26, 2005, through September 30, 2007. Electronically supported and monitored processes for best practice adherence, care plan creation, and clinician response times to alarms were evaluated. MAIN OUTCOME MEASURES Case-mix and severity-adjusted hospital mortality. Other outcomes included hospital and ICU length of stay, best practice adherence, and complication rates. RESULTS The hospital mortality rate was 13.6% (95% confidence interval [CI], 11.9%-15.4%) during the preintervention period compared with 11.8% (95% CI, 10.9%-12.8%) during the tele-ICU intervention period (adjusted odds ratio [OR], 0.40 [95% CI, 0.31-0.52]). The tele-ICU intervention period compared with the preintervention period was associated with higher rates of best clinical practice adherence for the prevention of deep vein thrombosis (99% vs 85%, respectively; OR, 15.4 [95% CI, 11.3-21.1]) and prevention of stress ulcers (96% vs 83%, respectively; OR, 4.57 [95% CI, 3.91-5.77], best practice adherence for cardiovascular protection (99% vs 80%, respectively; OR, 30.7 [95% CI, 19.3-49.2]), prevention of ventilator-associated pneumonia (52% vs 33%, respectively; OR, 2.20 [95% CI, 1.79-2.70]), lower rates of preventable complications (1.6% vs 13%, respectively, for ventilator-associated pneumonia [OR, 0.15; 95% CI, 0.09-0.23] and 0.6% vs 1.0%, respectively, for catheter-related bloodstream infection [OR, 0.50; 95% CI, 0.27-0.93]), and shorter hospital length of stay (9.8 vs 13.3 days, respectively; hazard ratio for discharge, 1.44 [95% CI, 1.33-1.56]). The results for medical, surgical, and cardiovascular ICUs were similar. CONCLUSION In a single academic medical center study, implementation of a tele-ICU intervention was associated with reduced adjusted odds of mortality and reduced hospital length of stay, as well as with changes in best practice adherence and lower rates of preventable complications.", "title": "Hospital mortality, length of stay, and preventable complications among critically ill patients before and after tele-ICU reengineering of critical care processes." }, { "docid": "27054878", "text": "BACKGROUND Preoperative C-reactive protein (CRP) levels more than 10 mg/l have been shown to be associated with increased morbidity and mortality after cardiac surgery. We examine the value of preoperative CRP levels less than 10 mg/l for predicting long-term, all-cause mortality and hospital length of stay in surgical patients undergoing primary, nonemergent coronary artery bypass graft-only surgery. METHODS We examined the association between preoperative CRP levels stratified into four categories (< 1, 1-3, 3-10, and > 10 mg/l), and 7-yr all-cause mortality and hospital length of stay in 914 prospectively enrolled primary, nonemergent coronary artery bypass graft-only surgical patients using a proportional hazards regression model. RESULTS Eighty-seven patients (9.5%) died during a mean follow-up period of 4.8 +/- 1.5 yr. After proportional hazards adjustment, the 3-10 and > 10 mg/l preoperative CRP groups were associated with long-term, all-cause mortality (hazards ratios [95% CI]: 2.50 [1.22-5.16], P = 0.01 and 2.66 [1.21-5.80], P = 0.02, respectively) and extended hospital length of stay (1.32 [1.07-1.63], P < 0.001 and 1.27 [1.02-1.62], P = 0.001, respectively). CONCLUSION We demonstrate that preoperative CRP levels as low as 3 mg/l are associated with increased long-term mortality and extended hospital length of stay in relatively lower-acuity patients undergoing primary, nonemergent coronary artery bypass graft-only surgery. These important findings may allow for more objective risk stratification of patients who present for uncomplicated surgical coronary revascularization.", "title": "Preoperative C-reactive protein predicts long-term mortality and hospital length of stay after primary, nonemergent coronary artery bypass grafting." }, { "docid": "25742130", "text": "With respect to cervical cancer management, Finland and the Netherlands are comparable in relevant characteristics, e.g., fertility rate, age-of-mother at first birth and a national screening programme for several years. The aim of this study is to compare trends in incidence of and mortality from cervical cancer in Finland and the Netherlands in relation to the introduction and intensity of the screening programmes. Therefore, incidence and mortality rates were calculated using the Cancer Registries of Finland and the Netherlands. Data on screening intensity were obtained from the Finnish Cancer Registry and the Dutch evaluation centre at ErasmusMC-Rotterdam. Women aged 30-60 have been screened every 5 years, in Finland since 1992 and in the Netherlands since 1996. Screening protocols for smear taking and referral to the gynaecologist are comparable. Incidence and mortality rates have declined more in Finland. In 2003, age-adjusted incidence and mortality in Finland were 4.0 and 0.9 and in the Netherlands 4.9 and 1.4 per 100,000 woman-years, respectively. Excess smear use in the Netherlands was estimated to be 24 per 1,000 women during a 5-year interval compared to 121 in Finland. The decline in mortality in Finland seems to be almost completely related to the screening programme whereas in the Netherlands it was initially considered to be a natural decline. Differences in risk factors might also play a role: the Netherlands has higher population density and higher percentages of immigrants and (female) smokers. The greater excess smear use in Finland might also have affected incidence.", "title": "Mass screening programmes and trends in cervical cancer in Finland and the Netherlands." }, { "docid": "12209494", "text": "BACKGROUND The case-fatality for intentional self-poisoning in the rural developing world is 10-50-fold higher than that in industrialised countries, mostly because of the use of highly toxic pesticides and plants. We therefore aimed to assess whether routine treatment with multiple-dose activated charcoal, to interrupt enterovascular or enterohepatic circulations, offers benefit compared with no charcoal in such an environment. METHODS We did an open-label, parallel group, randomised, controlled trial of six 50 g doses of activated charcoal at 4-h intervals versus no charcoal versus one 50 g dose of activated charcoal in three Sri Lankan hospitals. 4632 patients were randomised to receive no charcoal (n=1554), one dose of charcoal (n=1545), or six doses of charcoal (n=1533); outcomes were available for 4629 patients. 2338 (51%) individuals had ingested pesticides, whereas 1647 (36%) had ingested yellow oleander (Thevetia peruviana) seeds. Mortality was the primary outcome measure. Analysis was by intention to treat. The trial is registered with controlled-trials.com as ISRCTN02920054. FINDINGS Mortality did not differ between the groups. 97 (6.3%) of 1531 participants in the multiple-dose group died, compared with 105 (6.8%) of 1554 in the no charcoal group (adjusted odds ratio 0.96, 95% CI 0.70-1.33). No differences were noted for patients who took particular poisons, were severely ill on admission, or who presented early. INTERPRETATION We cannot recommend the routine use of multiple-dose activated charcoal in rural Asia Pacific; although further studies of early charcoal administration might be useful, effective affordable treatments are urgently needed.", "title": "Multiple-dose activated charcoal in acute self-poisoning: a randomised controlled trial" } ]
164698
Bradley Cooper's middle name is Charles.
[ { "docid": "Bradley_Cooper", "text": "Bradley Charles Cooper ( born January 5 , 1975 ) is an American actor and producer . He was one of the world 's highest-paid actors for three years , and has been nominated for various accolades , including four Academy Awards , two BAFTA Awards and two Golden Globe Awards . Cooper appeared in Forbes Celebrity 100 on two occasions and Time list of 100 most influential people in the world in 2015 . Cooper enrolled in the MFA program at the Actors Studio , New York City in 2000 . His career began with a guest role in the television series Sex and the City in 1999 and his film debut came two years later in Wet Hot American Summer . He first gained recognition as Will Tippin in the spy-action television show Alias ( 2001 -- 2006 ) , and achieved minor success with a supporting part in the comedy film Wedding Crashers ( 2005 ) . His breakthrough role came in 2009 with The Hangover , a commercially successful comedy which spawned two sequels in 2011 and 2013 . Cooper 's portrayal of a struggling writer in the thriller Limitless ( 2011 ) and a rookie police officer in the crime drama The Place Beyond the Pines ( 2012 ) drew praise from critics . He found greater success with the romantic comedy-drama Silver Linings Playbook ( 2012 ) , the black comedy crime film American Hustle ( 2013 ) , and the biopic American Sniper ( 2014 ) . For his work in these films , Cooper was nominated for Academy Awards -- two Best Actor , one Best Supporting Actor , and one Best Picture . Cooper became the tenth actor to receive an Academy Award nomination in three consecutive years . In 2014 , he portrayed Joseph Merrick in a Broadway revival of The Elephant Man , garnering a nomination for the Tony Award for Best Actor in a Play .", "title": "" } ]
[ { "docid": "Bradley_Cooper_(disambiguation)", "text": "Bradley Cooper ( born 1975 ) is an American actor Bradley or Brad Cooper may also refer to : Bradley Cooper ( athlete ) ( 1957 ) , Bahamanian discus thrower Brad Cooper ( born 1954 ) , Australian swimmer Brad Cooper ( born 1959 ) , Australian businessman ( see HIH Insurance ) Brad Cooper ( born 1984 ) , American rapper better known by his stage name B. Cooper", "title": "" }, { "docid": "Charles_Bradley", "text": "Charles Bradley may refer to : Charles Bradley ( basketball ) ( born 1959 ) , retired American basketball player Charles Bradley ( doctor ) ( 1902 -- 1979 ) , American physician who did early work on using stimulants for behavioural disorders Charles Bradley ( footballer ) ( 1922 -- 1984 ) , English professional footballer Charles Bradley ( preacher ) ( 1789 -- 1871 ) , preacher and sermon writer Charles Bradley ( sailor ) ( 1838 -- ? ) , Irish sailor who fought in the American Civil War Charles Bradley ( singer ) ( born 1948 ) , funk/soul/R & B singer Charles C. Bradley ( 1911 -- 2002 ) , professor of geology Charles H. Bradley , Jr. ( 1899 -- 1972 ) , American businessman Charles S. Bradley ( 1819 -- 1888 ) , American judge", "title": "" }, { "docid": "Justice_Bradley", "text": "Justice Bradley may refer to : Ann Walsh Bradley , an Associate Justice of the Wisconsin Supreme Court Charles S. Bradley , a Chief Justice of the Rhode Island Supreme Court James Bradley ( judge ) , an Associate Justice of the Nebraska Supreme Court Rebecca Bradley ( judge ) , an Associate Justice of the Wisconsin Supreme Court Stephen R. Bradley , an Associate Justice of the Vermont Supreme Court Category : Title and name disambiguation pages", "title": "" }, { "docid": "Great_Bradley", "text": "Great Bradley is a village in Suffolk , England . According to Eilert Ekwall the meaning of the village name is the `` wide clearing '' . The population is about 400 and includes Little Bradley . There is evidence that people have lived in and around Great Bradley by the River Stour since the middle stone age over 5,000 years ago .", "title": "" }, { "docid": "Harold_C._Bradley", "text": "Harold C. Bradley ( 1878 -- 1976 ) was a professor in biochemistry at the University of Wisconsin . He was the grandson of the American medical missionary to Siam , Dan Beach Bradley , and the father of geology professor Charles C. Bradley . He was instrumental in encouraging outdoor education through the Wisconsin Hoofers Clubs at the University of Wisconsin ; a lounge at the Wisconsin Union is named for him .", "title": "" }, { "docid": "William_John_Cooper_Academy", "text": "William John Cooper Academy is a middle school in Fresno , California operated by the Fresno Unified School District . The school implements the International Baccalaureate Middle Years Program . The IB program was given to Cooper Middle School ( the name of the school before it was Cooper Academy ) , since most students from Cooper Middle School would later on attend Fresno High School , a high school that implements the IB Diploma Program . During the 2012-2013 school year , there were about 430 students attending Cooper Academy . The school was first approved to be built by the Fresno City Board of Education in November 1956 and opened as a junior high school ( grades 7 , 8 and 9 ) in the fall of 1959 with John Solo as the inaugural principal . In the fall of 1978 , William John Cooper Junior High School officially became William John Cooper Middle School ( grades 7 and 8 ) , when Hamilton Junior High School was made into a new `` freshman school , '' educating only ninth graders . The school is named for William John Cooper , a Californian , who served as United States Commissioner of Education under Presidents Coolidge , Hoover and Roosevelt from 1929 to 1933 . In August 2012 , Cooper Middle School became Cooper Academy , starting with the 6th and 7th grade levels only . In August 2013 the 8th grade level was added . Author William Saroyan lived two blocks from the school from 1964 to 1981 , sometimes interacting with students .", "title": "" }, { "docid": "Changes_(Charles_Bradley_album)", "text": "Changes is the third album released by American funk/soul singer Charles Bradley , released on 1 April 2016 on Daptone Records . The title track on the album is a cover of the Black Sabbath song of the same name and was first released as a Record Store Day Black Friday single in 2013 .", "title": "" }, { "docid": "Hugh_Bradley_(Arkansas)", "text": "Hugh Bradley ( 1783 -- 1854 ) was among the early settlers of South Arkansas and the namesake of Bradley County , Arkansas . Captain Bradley is best known for his part in the migration of several families from the military district of middle Tennessee during the 1810s-1820s . His leadership and continuing influence in the establishment of the town of Warren , led to the naming of the county in his honor when it was formed in 1840 .", "title": "" }, { "docid": "Bradley_Ridge", "text": "Bradley Ridge is a rock ridge in Antarctica , about 7 nmi southeast of Mount Peter in the Athos Range , Prince Charles Mountains . It was plotted from Australian National Antarctic Research Expeditions air photos , and named for R.G. Bradley , a weather observer at Mawson Station in 1964 .", "title": "" }, { "docid": "Bradley_Prairie", "text": "Bradley Prairie is the name of a prairie in Southwest Angelina County , Texas , in the United States . It is located in the vicinity of the town of Burke , Texas . Bradley Prairie was named for Tom Bradley , a native of San Augustine , Texas , who built a trading post there in 1835 to trade among the Muscogee ( Creek people ) , Biloxi , Alabama ( people ) , and Coushatta on the nearby Neches River and the Shawnee in the southeastern part of the county . All these tribes were emigrants from other parts of the country who occupied land formerly held by the Caddo , who had been wiped out three centuries earlier by smallpox borne by European explorers . A branch of the Opelousas Cattle Trail connecting Opelousas , Louisiana and Crockett , Texas passed just south of Burke , and cattle ranching was the primary industry in the area in the middle 19th Century . However , after the American Civil War , Bradley Prairie 's fertile soil attracted farmers mainly from the devastated Deep South . When the Houston , East and West Texas Railroad arrived and the town of Burke was founded in 1881 on the western edge of Bradley Prairie , the area became an important cotton raising area . With the founding of Lufkin , Texas and Diboll , Texas to serve the emerging lumber industry , Bradley Prairie and Burke declined in importance . In 1951 the Angelina County Airport was located at Burke in the midst of Bradley Prairie . After Burke was founded , the name Bradley Prairie fell into disuse and is now largely forgotten .", "title": "" }, { "docid": "Bradley_Cooper_(athlete)", "text": "Bradley `` Brad '' Cooper ( born June 30 , 1957 ) is a retired male discus thrower and shot putter from the Bahamas . He competed for his native country in two consecutive Summer Olympics , starting in 1984 . Cooper set his personal best , 67.10 m , in the discus event on June 14 , 1986 in Nassau .", "title": "" }, { "docid": "Charles_Cooper", "text": "Charles Cooper may refer to : Charles D. Cooper ( 1769 -- 1831 ) , New York Secretary of State , 1817 -- 1818 Charles Purton Cooper ( 1793 -- 1873 ) , English lawyer and antiquary Charles Cooper ( judge ) ( 1795 -- 1887 ) , first Chief Justice of South Australia , 1856 -- 1861 Charles Henry Cooper ( 1808 -- 1866 ) , English antiquarian Charles Alfred Cooper ( 1829 -- 1916 ) , British newspaper editor and author Charles F. Cooper ( politician ) ( 1852 -- 1919 ) , English-born Free Baptist clergyman and political figure in Nova Scotia , Canada Charles Merian Cooper ( 1856 -- 1923 ) , U.S. Representative from Florida Charles Cooper ( cricketer ) ( 1868 -- 1943 ) , English cricketer Charles Cooper ( motor manufacturer ) ( 1893 -- 1964 ) , co-founder of the Cooper Car Company Tarzan Cooper ( 1907 -- 1980 ) , basketball player for New York Renaissance Charles F. Cooper ( ecologist ) ( 1924 -- 1994 ) , American ecologist Chuck Cooper ( basketball ) ( 1926 -- 1984 ) , basketball player for the Boston Celtics Charles Cooper ( actor ) ( 1926 -- 2013 ) , television and movie actor Charles J. Cooper ( born 1955 ) , American appellate attorney and litigator in Washington , D.C.", "title": "" }, { "docid": "Three_Brooks_Local_Nature_Reserve", "text": "The Three Brooks Nature Reserve is a Local Nature Reserve of about 60 ha in Bradley Stoke , South Gloucestershire , England . It is named after the Hortham , Patchway , and Stoke Brooks which run through it , meeting at Three Brooks Lake before flowing eastwards back under the M4 motorway as Bradley Brook . The town of Bradley Stoke was built in the 1980s on low-grade farmland , and a number of natural features such as Savage 's Wood , Webb 's Wood , and Sherbourne 's Brake were incorporated into the town to form the Three Brooks Local Nature Reserve . This tranquil area in the middle of the busy community of Bradley Stoke is made up of the three previously named bluebell woods , linked by an important wildlife corridor that includes brooks , ponds , areas of rough grassland , species-rich hedgerows , and a lake . The site is owned by the South Gloucestershire Council .", "title": "" }, { "docid": "Bradley_Elementary_School_District_61", "text": "Bradley Elementary School District 61 is an elementary school district based in Bradley , a village located in central Kankakee County , Illinois . The district is composed of three schools : two elementary schools and one middle school . No two schools cover the same grade levels . Education in the district starts at Bradley East Elementary School , where prekindergarteners , kindergarteners , and students in grades one and two are educated . The school is headed by principal Mike Hahs . Graduates move on to Bradley West Elementary School , which educates those in grades three through five . The school is headed by principal David Andriano . Graduates of Bradley West move on to Bradley Central Middle School under principal Mark Kohl , where students in grades six through eight will be educated . The district superintendent is Dr. Scott Goselin .", "title": "" }, { "docid": "Middle_Lake", "text": "Middle Lake may refer to : Middle Lake , Saskatchewan , a village in Saskatchewan , Canada Middle Lake ( Nova Scotia ) , a lake in Richmond County , Nova Scotia , Canada Middle Lake Trail , a hiking trail in Eagle County , Colorado , United States Middle Lake ( Bradley County , Arkansas ) , a lake in Bradley County , Arkansas Middle Lake in Nicollet County , Minnesota , United States Middle Lake in Ravalli County , Montana , United States", "title": "" }, { "docid": "Francis_Bradley_Bradley-Birt", "text": "Francis Bradley Bradley-Birt , B.A. ( Oxon . ) , ICS , FRGS ( 25 June 1874 -- 11 June 1963 ) , diplomat and writer , began his career as an English member of the Indian Civil Service . His duty in India began in 1896 , and he started as an assistant magistrate and collector . He was originally assigned to Khulna , Midnapore , Hooghly and Calcutta . At some point he was re-assigned to the commander-in-chief in India , and later served in the British legation in Tehran . Bradley-Birt wrote both fiction and non-fiction about his travels in India , Persia and the Middle East . In India he was attached to the Archaeological service , and this formed the basis for some of his non-fiction work . He wrote under his own name and under the pseudonym `` Shelland Bradley . '' Ramananda Chatterjee credited Bradley-Birt with `` resuscitating '' the literary study of Henry Louis Vivian Derozio . Bradley-Birt married ( 1 December 1920 ) Norah Spencer-Churchill , daughter of George Spencer-Churchill , 8th Duke of Marlborough ( she was , therefore , a cousin of Winston Churchill ) . Bradley-Birt owned a property known as Birtsmorton Court , which he acquired from his uncle , F. R. Bradley-Birt , who bought it in 1911 , re-uniting it with the neighboring property of Berrow , which was already under his ownership .", "title": "" }, { "docid": "Cooper_Middle_School", "text": "Cooper Middle School may refer to : William John Cooper Academy , a middle school in Fresno , California James Fenimore Cooper Middle School , a school in Fairfax county Cooper Middle School ( Georgia ) , a school in Austell , Georgia Cooper Middle School ( Oklahoma City ) , a middle school in Oklahoma City , Oklahoma in the Putnam City School District . Cooper Middle School ( Illinois )", "title": "" }, { "docid": "A_Star_Is_Born_(2018_film)", "text": "A Star Is Born is an upcoming American musical romantic drama film directed by Bradley Cooper and written by Will Fetters , Cooper , Eric Roth , Irene Mecchi , Stephen J. Rivele , and Christopher Wilkinson . It is a remake of the 1937 film of the same name . The film stars Cooper , Stefani Germanotta , Sam Elliott , Andrew Dice Clay and Dave Chappelle . It will be released on September 28 , 2018 by Warner Bros. . Pictures . It is one of three remakes of the original 1937 version , with the first released in 1954 starring Judy Garland and James Mason and the second released in 1976 starring Barbra Streisand and Kris Kristofferson .", "title": "" }, { "docid": "Charles_Bradley_(footballer)", "text": "Charles Bradley ( 15 May 1922 -- 23 July 1984 ) , also known as Charlie Bradley , was an English professional footballer who played as an inside forward in the Football League for York City , in non-League football for York Railway Institute and Scarborough , and played wartime football for York .", "title": "" }, { "docid": "Chief_Charles_A._Joshua_Plaza", "text": "Chief Charles A. Joshua Plaza is a .22 - acre public space located at the crossroads of Ralph Avenue , Fulton Street and Macdougal Street in the Bedford-Stuyvesant neighborhood of Brooklyn . The plaza 's namesake , Chief Charles Adebowale Joshua ( 1924-1999 ) was a community activist who led efforts to stimulate cooperation among the neighborhood 's numerous nonprofit organizations , including programs serving foster children , people with mental disabilities and people living with HIV and AIDS . Beginning in 1973 , as Executive Director of the Central Brooklyn Coordinating Council , he worked to stimulate cooperation among more than 135 community agencies in implementing social programs benefiting local residents . Joshua was also a founder of the Caribbean-American Chamber of Commerce and Industry , an organization founded in 1985 to provide assistance to small businesses within the city 's Caribbean immigrant community . In 1989 , Joshua 's tireless activism earned him praise from Nigeria , where a Yoruba prince bestowed the title Chief on Joshua in a formal ceremony . In conjunction with the title , he adopted the middle name Adebowale , which in Yoruba translates to `` the crown has come home . '' Following his death in 1999 , community leaders and local elected officials selected this plaza as a fitting location to honor Joshua . In 2001 , the City Council passed legislation designating Chief Charles A. Joshua Plaza . This plaza was reconstructed in 1997 , providing a concrete border , four trees and the Freedom 's Gate sculpture by Charles Searles ( 1934-2004 ) . Born in Philadelphia , his art captures the history and feelings of the African-American experience .", "title": "" }, { "docid": "Charles_Bradley_(basketball)", "text": "Charles Warnell Bradley ( born May 16 , 1959 ) is a retired American professional basketball player . He was selected by the Boston Celtics in the 1st round ( 23rd overall ) of the 1981 NBA Draft . Born in Havre de Grace , Maryland , Bradley was a 6 ' 5 '' shooting guard from the University of Wyoming . He played in 3 NBA seasons from 1981 -- 1984 . He played for the Celtics and Seattle SuperSonics . In his NBA career , Bradley played in 110 games and scored a total of 347 points .", "title": "" }, { "docid": "The_Shops_at_Atlas_Park", "text": "The Shops at Atlas Park is an open-air lifestyle center located in the Glendale neighborhood of Queens , New York City , United States . The center is located at the intersection of Cooper Avenue and 80th Street . The Shops at Atlas Park was opened in April 2006 by ATCO Properties , encompassing the site of the former 25 acre Atlas Terminals industrial park , both of which were named after bodybuilder Charles Atlas who resided in nearby Middle Village .", "title": "" }, { "docid": "Cooper_Car_Company", "text": "The Cooper Car Company is a car manufacturer founded in December 1947 by Charles Cooper and his son John Cooper . Together with John 's boyhood friend , Eric Brandon , they began by building racing cars in Charles 's small garage in Surbiton , Surrey , England , in 1946 . Through the 1950s and early 1960s they reached motor racing 's highest levels as their rear-engined , single-seat cars altered the face of Formula One and the Indianapolis 500 , and their Mini Cooper dominated rally racing . Due in part to Cooper 's legacy , Great Britain remains the home of a thriving racing industry , and the Cooper name lives on in the Cooper versions of the Mini production cars that are still built in England , but are now owned and marketed by BMW .", "title": "" }, { "docid": "Charles_Bradley_(preacher)", "text": "Charles Bradley ( 1789 -- 1871 ) was eminent as a preacher and writer of sermons published between 1818 and 1853 .", "title": "" }, { "docid": "Charles_H._Bradley,_Jr.", "text": "Charles Harvey Bradley ( April 20 , 1899 , Dubuque , Iowa -- September 1 , 1972 , Indianapolis )", "title": "" }, { "docid": "Charles_Bradley_(sailor)", "text": "Boatswain 's Mate Charles Bradley ( born 1838 ) was an Irish sailor who fought in the American Civil War . Bradley received the country 's highest award for bravery during combat , the Medal of Honor , for his action aboard the USS Louisville and the Battle of Fort Hindman on January 10 and 11 , 1863 . He was honored with the award on 3 April 1863 .", "title": "" }, { "docid": "Charles_J._Cooper", "text": "Charles J. Cooper ( born 1955 ) is an appellate attorney and litigator in Washington , D.C. , where he is a founding member and chairman of the law firm Cooper & Kirk , PLLC . He was named by The National Law Journal as one of the 10 best civil litigators in Washington . Cooper has more than 25 years of legal experience in government and private practice , with numerous cases in trial and appellate court . He has argued several cases before the United States Supreme Court .", "title": "" }, { "docid": "Victim_of_Love_(Charles_Bradley_album)", "text": "Victim of Love is the second studio album by American soul singer Charles Bradley . It was released on April 2 , 2013 , by Daptone Records .", "title": "" }, { "docid": "Charles_Cooper_(judge)", "text": "Sir Charles Cooper ( 1795 -- 24 May 1887 ) was a politician and the first Chief Justice of South Australia . Cooper was born in Henley-on-Thames , the third son of Thomas Cooper , under-sheriff of Oxfordshire . Charles entered the Inner Temple in 1822 and was called to the bar in February 1827 . He practised on the Oxford circuit until 1838 , and was then appointed judge at Adelaide . He and his sister Sarah Ann Cooper landed there in March 1839 in the Katherine Stewart Forbes , and was for many years the sole judge , then senior judge , and in June 1856 was appointed the first South Australian chief justice . In September 1860 he was sworn in as a member of the Executive Council . Cooper retired from the bench in November 1861 and from the Executive Council in August 1862 owing to ill-health and was given a pension of # 1000 a year . He returned to England in 1862 , resided at Bath , Somerset , and improving much in his health lived to be 92 years of age . He died at London on 24 May 1887 . He married in 1853 Emily Grace Newenham , daughter of Charles Burton Newenham ( Sheriff of South Australia 1839-1856 ) . He was knighted in 1857 . Cooper 's Creek , ( now Cooper Creek ) , in central Australia was named after him by his friend , Captain Sturt . Cooper was a thoroughly capable judge who earned the esteem of the colonists . He held courts at first in his own house , which had the advantage that he was constantly on the premises . He was a sound lawyer and framed the first insolvency legislation of the colony . Though not robust looking , he was hospitable and interested in the social and intellectual life of the colony .", "title": "" }, { "docid": "Scotland_Yard_(board_game)", "text": "Scotland Yard is a board game in which a team of players , as police , cooperate to track down a player controlling a criminal around a board representing the streets of London . It is named after Scotland Yard , the headquarters of London 's Metropolitan Police Service . Scotland Yard is an asymmetric board game , with the detective players cooperatively solving a variant of the pursuit-evasion problem . The game is published by Ravensburger in most of Europe and Canada and by Milton Bradley in the United States . It received the Spiel des Jahres ( Game of the Year ) award in 1983 . A sequel to Scotland Yard was released called `` Mister X '' .", "title": "" } ]
358
During non-homologous end joining, the ligation step is not as tolerant of disrepairs and other distortions when joining 5' of strand breaks as compared to 3' strand breaks.
[ { "docid": "18111172", "text": "Nonhomologous end joining (NHEJ) can effectively resolve chromosome breaks despite diverse end structures; however, it is unclear how the steps employed for resolution are determined. We sought to address this question by analysing cellular NHEJ of ends with systematically mispaired and damaged termini. We show NHEJ is uniquely proficient at bypassing subtle terminal mispairs and radiomimetic damage by direct ligation. Nevertheless, bypass ability varies widely, with increases in mispair severity gradually reducing bypass products from 85 to 6%. End-processing by nucleases and polymerases is increased to compensate, although paths with the fewest number of steps to generate a substrate suitable for ligation are favoured. Thus, both the frequency and nature of end processing are tailored to meet the needs of the ligation step. We propose a model where the ligase organizes all steps during NHEJ within the stable paired-end complex to limit end processing and associated errors.", "title": "The fidelity of the ligation step determines how ends are resolved during Nonhomologous end joining" } ]
[ { "docid": "20821402", "text": "Nonhomologous end joining (NHEJ) is essential for efficient repair of chromosome breaks. However, the NHEJ ligation step is often obstructed by break-associated nucleotide damage, including base loss (abasic site or 5'-dRP/AP sites). Ku, a 5'-dRP/AP lyase, can excise such damage at ends in preparation for the ligation step. We show here that this activity is greatest if the abasic site is within a short 5' overhang, when this activity is necessary and sufficient to prepare such termini for ligation. In contrast, Ku is less active near 3' strand termini, where excision would leave a ligation-blocking α,β-unsaturated aldehyde. The Ku AP lyase activity is also strongly suppressed by as little as two paired bases 5' of the abasic site. Importantly, in vitro end joining experiments show that abasic sites significantly embedded in double-stranded DNA do not block the NHEJ ligation step. Suppression of the excision activity of Ku in this context therefore is not essential for ligation and further helps NHEJ retain terminal sequence in junctions. We show that the DNA between the 5' terminus and the abasic site can also be retained in junctions formed by cellular NHEJ, indicating that these sites are at least partly resistant to other abasic site-cleaving activities as well. High levels of the 5'-dRP/AP lyase activity of Ku are thus restricted to substrates where excision of an abasic site is required for ligation, a degree of specificity that promotes more accurate joining.", "title": "Specificity of the dRP/AP lyase of Ku promotes nonhomologous end joining (NHEJ) fidelity at damaged ends." }, { "docid": "12207340", "text": "The repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) is initiated by nucleolytic degradation of the 5'-terminated strands in a process termed end resection. End resection generates 3'-single-stranded DNA tails, substrates for Rad51 to catalyze homologous pairing and DNA strand exchange, and for activation of the DNA damage checkpoint. The commonly accepted view is that end resection occurs by a two-step mechanism. In the first step, Sae2/CtIP activates the Mre11-Rad50-Xrs2/Nbs1 (MRX/N) complex to endonucleolytically cleave the 5'-terminated DNA strands close to break ends, and in the second step Exo1 and/or Dna2 nucleases extend the resected tracts to produce long 3'-ssDNA-tailed intermediates. Initiation of resection commits a cell to repair a DSB by HR because long ssDNA overhangs are poor substrates for non-homologous end joining (NHEJ). Thus, the initiation of end resection has emerged as a critical control point for repair pathway choice. Here, I review recent studies on the mechanism of end resection and how this process is regulated to ensure the most appropriate repair outcome.", "title": "Mechanism and regulation of DNA end resection in eukaryotes." }, { "docid": "12552297", "text": "DNA polymerase lambda (polλ) is a recently identified DNA polymerase whose cellular function remains elusive. Here we show, that polλ participates at the molecular level in a chromosomal context, in the repair of DNA double strand breaks (DSB) via non-homologous end joining (NHEJ) in mammalian cells. The expression of a catalytically inactive form of polλ (polλDN) decreases the frequency of NHEJ events in response to I-Sce-I-induced DSB whereas inactivated forms of its homologues polβ and polμ do not. Only events requiring DNA end processing before ligation are affected; this defect is associated with large deletions arising in the vicinity of the induced DSB. Furthermore, polλDN-expressing cells exhibit increased sensitization and genomic instability in response to ionizing radiation similar to that of NHEJ-defective cells. Our data support a requirement for polλ in repairing a subset of DSB in genomic DNA, thereby contributing to the maintenance of genetic stability mediated by the NHEJ pathway.", "title": "The DNA polymerase λ is required for the repair of non-compatible DNA double strand breaks by NHEJ in mammalian cells" }, { "docid": "41403996", "text": "DNA double strand breaks (DSBs) can be rejoined directly by the nonhomologous end-joining (NHEJ) pathway of repair. Nucleases and polymerases are required to promote accurate NHEJ when the terminal bases of the DSB are damaged. The same enzymes also participate in imprecise rejoining and joining of incompatible ends, important mutagenic events. Previous work has shown that the Pol X family polymerase Pol4 is required for some but not all NHEJ events that require gap filling in Saccharomyces cerevisiae. Here, we systematically analyzed DSB end configurations and found that gaps on both strands and overhang polarity are the principal factors that determine whether a joint requires Pol4. DSBs with 3'-overhangs and a gap on each strand strongly depended on Pol4 for repair, DSBs with 5'-overhangs of the same sequence did not. Pol4 was not required when 3'-overhangs contained a gap on only one strand, however. Pol4 was equally required at 3'-overhangs of all lengths within the NHEJ-dependent range but was dispensable outside of this range, indicating that Pol4 is specific to NHEJ. Loss of Pol4 did not affect the rejoining of DSBs that utilized a recessed microhomology or DSBs bearing 5'-hydroxyls but no gap. Finally, mammalian Pol X polymerases were able to differentially complement a pol4 mutation depending on the joint structure, demonstrating that these polymerases can participate in yeast NHEJ but with distinct properties.", "title": "DNA joint dependence of pol X family polymerase action in nonhomologous end joining." }, { "docid": "13791206", "text": "Defective DNA repair by homologous recombination (HR) is thought to be a major contributor to tumorigenesis in individuals carrying Brca1 mutations. Here, we show that DNA breaks in Brca1-deficient cells are aberrantly joined into complex chromosome rearrangements by a process dependent on the nonhomologous end-joining (NHEJ) factors 53BP1 and DNA ligase 4. Loss of 53BP1 alleviates hypersensitivity of Brca1 mutant cells to PARP inhibition and restores error-free repair by HR. Mechanistically, 53BP1 deletion promotes ATM-dependent processing of broken DNA ends to produce recombinogenic single-stranded DNA competent for HR. In contrast, Lig4 deficiency does not rescue the HR defect in Brca1 mutant cells but prevents the joining of chromatid breaks into chromosome rearrangements. Our results illustrate that HR and NHEJ compete to process DNA breaks that arise during DNA replication and that shifting the balance between these pathways can be exploited to selectively protect or kill cells harboring Brca1 mutations.", "title": "53BP1 Inhibits Homologous Recombination in Brca1-Deficient Cells by Blocking Resection of DNA Breaks" }, { "docid": "27635177", "text": "Mammalian DNA polymerase mu (pol mu) is related to terminal deoxynucleotidyl transferase, but its biological role is not yet clear. We show here that after exposure of cells to ionizing radiation (IR), levels of pol mu protein increase. pol mu also forms discrete nuclear foci after IR, and these foci are largely coincident with IR-induced foci of gammaH2AX, a previously characterized marker of sites of DNA double-strand breaks. pol mu is thus part of the cellular response to DNA double-strand breaks. pol mu also associates in cell extracts with the nonhomologous end-joining repair factor Ku and requires both Ku and another end-joining factor, XRCC4-ligase IV, to form a stable complex on DNA in vitro. pol mu in turn facilitates both stable recruitment of XRCC4-ligase IV to Ku-bound DNA and ligase IV-dependent end joining. In contrast, the related mammalian DNA polymerase beta does not form a complex with Ku and XRCC4-ligase IV and is less effective than pol mu in facilitating joining mediated by these factors. Our data thus support an important role for pol mu in the end-joining pathway for repair of double-strand breaks.", "title": "Association of DNA polymerase mu (pol mu) with Ku and ligase IV: role for pol mu in end-joining double-strand break repair." }, { "docid": "21793890", "text": "The oncogenic BCR/ABL tyrosine kinase facilitates the repair of DNA double-strand breaks (DSBs). We find that after gamma-irradiation BCR/ABL-positive leukemia cells accumulate more DSBs in comparison to normal cells. These lesions are efficiently repaired in a time-dependent fashion by BCR/ABL-stimulated non-homologous end-joining (NHEJ) followed by homologous recombination repair (HRR) mechanisms. However, mutations and large deletions were detected in HRR and NHEJ products, respectively, in BCR/ABL-positive leukemia cells. We propose that unfaithful repair of DSBs may contribute to genomic instability in the Philadelphia chromosome-positive leukemias.", "title": "BCR/ABL modifies the kinetics and fidelity of DNA double-strand breaks repair in hematopoietic cells." }, { "docid": "25838286", "text": "Werner syndrome (WS) predisposes patients to cancer and premature aging, owing to mutations in WRN. The WRN protein is a RECQ-like helicase and is thought to participate in DNA double-strand break (DSB) repair by non-homologous end joining (NHEJ) or homologous recombination (HR). It has been previously shown that non-homologous DNA ends develop extensive deletions during repair in WS cells, and that this WS phenotype was complemented by wild-type (wt) WRN. WRN possesses both 3' --> 5' exonuclease and 3' --> 5' helicase activities. To determine the relative contributions of each of these distinct enzymatic activities to DSB repair, we examined NHEJ and HR in WS cells (WRN-/-) complemented with either wtWRN, exonuclease-defective WRN (E-), helicase-defective WRN (H-) or exonuclease/helicase-defective WRN (E-H-). The single E-and H- mutants each partially complemented the NHEJ abnormality of WRN-/- cells. Strikingly, the E-H- double mutant complemented the WS deficiency nearly as efficiently as did wtWRN. Similarly, the double mutant complemented the moderate HR deficiency of WS cells nearly as well as did wtWRN, whereas the E- and H- single mutants increased HR to levels higher than those restored by either E-H- or wtWRN. These results suggest that balanced exonuclease and helicase activities of WRN are required for optimal HR. Moreover, WRN appears to play a structural role, independent of its enzymatic activities, in optimizing HR and efficient NHEJ repair. Another human RECQ helicase, BLM, suppressed HR but had little or no effect on NHEJ, suggesting that mammalian RECQ helicases have distinct functions that can finely regulate recombination events.", "title": "WRN, the protein deficient in Werner syndrome, plays a critical structural role in optimizing DNA repair." }, { "docid": "21561474", "text": "Methods to introduce targeted double-strand breaks (DSBs) into DNA enable precise genome editing by increasing the rate at which externally supplied DNA fragments are incorporated into the genome through homologous recombination. The efficiency of these methods is limited by nonhomologous end joining (NHEJ), an alternative DNA repair pathway that competes with homology-directed repair (HDR). To promote HDR at the expense of NHEJ, we targeted DNA ligase IV, a key enzyme in the NHEJ pathway, using the inhibitor Scr7. Scr7 treatment increased the efficiency of HDR-mediated genome editing, using Cas9 in mammalian cell lines and in mice for all four genes examined, up to 19-fold. This approach should be applicable to other customizable endonucleases, such as zinc finger nucleases and transcription activator–like effector nucleases, and to nonmammalian cells with sufficiently conserved mechanisms of NHEJ and HDR.", "title": "Increasing the efficiency of precise genome editing with CRISPR-Cas9 by inhibition of nonhomologous end joining" }, { "docid": "21221346", "text": "In eukaryotic cells, nonhomologous DNA end joining (NHEJ) is a major pathway for repair of double-strand DNA breaks (DSBs). Artemis and the 469kDa DNA-dependent protein kinase (DNA-PKcs) together form a key nuclease for NHEJ in vertebrate organisms. The structure-specific endonucleolytic activity of Artemis is activated by binding to and phosphorylation by DNA-PKcs. We tested various DNA structures in order to understand the range of structural features that are recognized by the Artemis:DNA-PKcs complex. We find that all tested substrates that contain single-to-double-strand transitions can be cleaved by the Artemis:DNA-PKcs complex near the transition region. The cleaved substrates include heterologous loops, stem-loops, flaps, and gapped substrates. Such versatile activity on single-/double-strand transition regions is important in understanding how reconstituted NHEJ systems that lack DNA polymerases can join incompatible DNA ends and yet preserve 3' overhangs. Additionally, the flexibility of the Artemis:DNA-PKcs nuclease may be important in removing secondary structures that hinder processing of DNA ends during NHEJ.", "title": "The Artemis:DNA-PKcs endonuclease cleaves DNA loops, flaps, and gaps." }, { "docid": "15472716", "text": "DNA-PKcs and Ku are essential components of the complex that catalyzes non-homologous end joining (NHEJ) of DNA double-strand breaks (DSBs). Ku, a heterodimeric protein, binds to DNA ends and facilitates recruitment of the catalytic subunit, DNA-PKcs. We have investigated the effect of DNA strand orientation and sequence bias on the activation of DNA-PK. In addition, we assessed the effect of the position and strand orientation of cisplatin adducts on kinase activation. A series of duplex DNA substrates with site-specific cisplatin–DNA adducts placed in three different orientations on the duplex DNA were prepared. Terminal biotin modification and streptavidin (SA) blocking was employed to direct DNA-PK binding to the unblocked termini with a specific DNA strand orientation and cisplatin–DNA adduct position. DNA-PK kinase activity was measured and the results reveal that DNA strand orientation and sequence bias dramatically influence kinase activation, only a portion of which could be attributed to Ku-DNA binding activity. In addition, cisplatin–DNA adduct position resulted in differing degrees of inhibition depending on distance from the terminus as well as strand orientation. These results highlight the importance of how local variations in DNA structure, chemistry and sequence influence DNA-PK activation and potentially NHEJ.", "title": "Differential activation of DNA-PK based on DNA strand orientation and sequence bias" }, { "docid": "23698769", "text": "DNA polymerase μ (Pol μ) is the only template-dependent human DNA polymerase capable of repairing double-strand DNA breaks (DSBs) with unpaired 3′ ends in nonhomologous end joining (NHEJ). To probe this function, we structurally characterized Pol μ's catalytic cycle for single-nucleotide incorporation. These structures indicate that, unlike other template-dependent DNA polymerases, Pol μ shows no large-scale conformational changes in protein subdomains, amino acid side chains or DNA upon dNTP binding or catalysis. Instead, the only major conformational change is seen earlier in the catalytic cycle, when the flexible loop 1 region repositions upon DNA binding. Pol μ variants with changes in loop 1 have altered catalytic properties and are partially defective in NHEJ. The results indicate that specific loop 1 residues contribute to Pol μ's unique ability to catalyze template-dependent NHEJ of DSBs with unpaired 3′ ends.", "title": "Sustained active site rigidity during synthesis by human DNA polymerase μ" }, { "docid": "13023410", "text": "The oncogenic BCR/ABL tyrosine kinase induces constitutive DNA damage in Philadelphia chromosome (Ph)-positive leukemia cells. We find that BCR/ABL-induced reactive oxygen species (ROSs) cause chronic oxidative DNA damage resulting in double-strand breaks (DSBs) in S and G(2)/M cell cycle phases. These lesions are repaired by BCR/ABL-stimulated homologous recombination repair (HRR) and nonhomologous end-joining (NHEJ) mechanisms. A high mutation rate is detected in HRR products in BCR/ABL-positive cells, but not in the normal counterparts. In addition, large deletions are found in NHEJ products exclusively in BCR/ABL cells. We propose that the following series of events may contribute to genomic instability of Ph-positive leukemias: BCR/ABL --> ROSs --> oxidative DNA damage --> DSBs in proliferating cells --> unfaithful HRR and NHEJ repair.", "title": "BCR/ABL oncogenic kinase promotes unfaithful repair of the reactive oxygen species-dependent DNA double-strand breaks." }, { "docid": "20420780", "text": "DNA double-strand breaks (DSBs) are repaired via nonhomologous end-joining (NHEJ) or homologous recombination (HR), but cellular repair processes remain elusive. We show here that the ATP-dependent chromatin-remodeling factors, ACF1 and SNF2H, accumulate rapidly at DSBs and are required for DSB repair in human cells. If the expression of ACF1 or SNF2H is suppressed, cells become extremely sensitive to X-rays and chemical treatments producing DSBs, and DSBs remain unrepaired. ACF1 interacts directly with KU70 and is required for the accumulation of KU proteins at DSBs. The KU70/80 complex becomes physically more associated with the chromatin-remodeling factors of the CHRAC complex, which includes ACF1, SNF2H, CHRAC15, and CHRAC17, after treatments producing DSBs. Furthermore, the frequency of NHEJ as well as HR induced by DSBs in chromosomal DNA is significantly decreased in cells depleted of either of these factors. Thus, ACF1 and its complexes play important roles in DSBs repair.", "title": "The ACF1 complex is required for DNA double-strand break repair in human cells." }, { "docid": "1941721", "text": "Cells deficient in a major DNA double-strand break repair pathway (nonhomologous DNA end joining [NHEJ]) have increased spontaneous chromosome breaks; however, the source of these chromosome breaks has remained undefined. Here, we show that the observed spontaneous chromosome breaks are partially suppressed by reducing the cellular oxygen tension. Conversely, elevating the level of reactive oxygen species by overexpressing the antioxidant enzyme superoxide dismutase 1 (SOD1), in a transgenic mouse, increases chromosome breakage. The effect of SOD1 can also be modulated by cellular oxygen tension. The elevated chromosome breakage correlates histologically with a significant increase in the amount of neuronal cell death in Ku86(-/-) SOD1 transgenic embryos over that seen in Ku86(-/-) embryos. Therefore, oxygen metabolism is a major source of the genomic instability observed in NHEJ-deficient cells and, presumably, in all cells.", "title": "Oxygen Metabolism Causes Chromosome Breaks and Is Associated with the Neuronal Apoptosis Observed in DNA Double-Strand Break Repair Mutants" }, { "docid": "15478227", "text": "The wild species of the genus Oryza contain a largely untapped reservoir of agronomically important genes for rice improvement. Here we report the 261-Mb de novo assembled genome sequence of Oryza brachyantha. Low activity of long-terminal repeat retrotransposons and massive internal deletions of ancient long-terminal repeat elements lead to the compact genome of Oryza brachyantha. We model 32,038 protein-coding genes in the Oryza brachyantha genome, of which only 70% are located in collinear positions in comparison with the rice genome. Analysing breakpoints of non-collinear genes suggests that double-strand break repair through non-homologous end joining has an important role in gene movement and erosion of collinearity in the Oryza genomes. Transition of euchromatin to heterochromatin in the rice genome is accompanied by segmental and tandem duplications, further expanded by transposable element insertions. The high-quality reference genome sequence of Oryza brachyantha provides an important resource for functional and evolutionary studies in the genus Oryza.", "title": "Whole-genome sequencing of Oryza brachyantha reveals mechanisms underlying Oryza genome evolution" }, { "docid": "44172171", "text": "The RNA-guided DNA endonuclease Cas9 is a powerful tool for genome editing. Little is known about the kinetics and fidelity of the double-strand break (DSB) repair process that follows a Cas9 cutting event in living cells. Here, we developed a strategy to measure the kinetics of DSB repair for single loci in human cells. Quantitative modeling of repaired DNA in time series after Cas9 activation reveals variable and often slow repair rates, with half-life times up to ∼10 hr. Furthermore, repair of the DSBs tends to be error prone. Both classical and microhomology-mediated end joining pathways contribute to the erroneous repair. Estimation of their individual rate constants indicates that the balance between these two pathways changes over time and can be altered by additional ionizing radiation. Our approach provides quantitative insights into DSB repair kinetics and fidelity in single loci and indicates that Cas9-induced DSBs are repaired in an unusual manner.", "title": "Kinetics and Fidelity of the Repair of Cas9-Induced Double-Strand DNA Breaks" }, { "docid": "5765455", "text": "Myelodysplastic syndromes (MDS) comprise a heterogeneous group of disorders characterized by ineffective hematopoiesis, with an increased propensity to develop acute myelogenous leukemia (AML). The molecular basis for MDS progression is unknown, but a key element in MDS disease progression is loss of chromosomal material (genomic instability). Using our two-step mouse model for myeloid leukemic disease progression involving overexpression of human mutant NRAS and BCL2 genes, we show that there is a stepwise increase in the frequency of DNA damage leading to an increased frequency of error-prone repair of double-strand breaks (DSB) by nonhomologous end-joining. There is a concomitant increase in reactive oxygen species (ROS) in these transgenic mice with disease progression. Importantly, RAC1, an essential component of the ROS-producing NADPH oxidase, is downstream of RAS, and we show that ROS production in NRAS/BCL2 mice is in part dependent on RAC1 activity. DNA damage and error-prone repair can be decreased or reversed in vivo by N-acetyl cysteine antioxidant treatment. Our data link gene abnormalities to constitutive DNA damage and increased DSB repair errors in vivo and provide a mechanism for an increase in the error rate of DNA repair with MDS disease progression. These data suggest treatment strategies that target RAS/RAC pathways and ROS production in human MDS/AML.", "title": "Reactive oxygen species, DNA damage, and error-prone repair: a model for genomic instability with progression in myeloid leukemia?" }, { "docid": "34559336", "text": "Three Pol X family members have been linked to nonhomologous end joining (NHEJ) in mammals. Template-independent TdT promotes diversity during NHEJ-dependent repair of V(D)J recombination intermediates, but the roles of the template-dependent polymerases mu and lambda in NHEJ remain unclear. We show here that pol mu and pol lambda are similarly recruited by NHEJ factors to fill gaps when ends have partially complementary overhangs, suggesting equivalent roles promoting accuracy in NHEJ. However, only pol mu promotes accuracy during immunoglobulin kappa recombination. This distinctive in vivo role correlates with the TdT-like ability of pol mu, but not pol lambda, to act when primer termini lack complementary bases in the template strand. However, unlike TdT, synthesis by pol mu in this context is primarily instructed by a template from another DNA molecule. This apparent gradient of template dependence is largely attributable to a small structural element that is present but different in all three polymerases.", "title": "A gradient of template dependence defines distinct biological roles for family X polymerases in nonhomologous end joining." }, { "docid": "4444861", "text": "Cells deficient in the Brca1 and Brca2 genes have reduced capacity to repair DNA double-strand breaks by homologous recombination and consequently are hypersensitive to DNA-damaging agents, including cisplatin and poly(ADP-ribose) polymerase (PARP) inhibitors. Here we show that loss of the MLL3/4 complex protein, PTIP, protects Brca1/2-deficient cells from DNA damage and rescues the lethality of Brca2-deficient embryonic stem cells. However, PTIP deficiency does not restore homologous recombination activity at double-strand breaks. Instead, its absence inhibits the recruitment of the MRE11 nuclease to stalled replication forks, which in turn protects nascent DNA strands from extensive degradation. More generally, acquisition of PARP inhibitors and cisplatin resistance is associated with replication fork protection in Brca2-deficient tumour cells that do not develop Brca2 reversion mutations. Disruption of multiple proteins, including PARP1 and CHD4, leads to the same end point of replication fork protection, highlighting the complexities by which tumour cells evade chemotherapeutic interventions and acquire drug resistance.", "title": "Replication Fork Stability Confers Chemoresistance in BRCA-deficient Cells" }, { "docid": "25462689", "text": "We have investigated HO endonuclease-induced double-strand break (DSB) recombination and repair in a LACZ duplication plasmid in yeast. A 117-bp MATa fragment, embedded in one copy of LACZ, served as a site for initiation of a DSB when HO endonuclease was expressed. The DSB could be repaired using wild-type sequences located on a second, promoterless, copy of LACZ on the same plasmid. In contrast to normal mating-type switching, crossing-over associated with gene conversion occurred at least 50% of the time. The proportion of conversion events accompanied by exchange was greater when the two copies of LACZ were in direct orientation (80%), than when inverted (50%). In addition, the fraction of plasmids lost was significantly greater in the inverted orientation. The kinetics of appearance of intermediates and final products were also monitored. The repair of the DSB is slow, requiring at least an hour from the detection of the HO-cut fragments to completion of repair. Surprisingly, the appearance of the two reciprocal products of crossing over did not occur with the same kinetics. For example, when the two LACZ sequences were in the direct orientation, the HO-induced formation of a large circular deletion product was not accompanied by the appearance of a small circular reciprocal product. We suggest that these differences may reflect two kinetically separable processes, one involving only one cut end and the other resulting from the concerted participation of both ends of the DSB.", "title": "Genetic and physical analysis of double-strand break repair and recombination in Saccharomyces cerevisiae." }, { "docid": "30122260", "text": "DNA double-strand breaks (DSBs) are highly hazardous for genome integrity because they have the potential to cause mutations, chromosomal rearrangements and genomic instability. The cellular response to DSBs is orchestrated by signal transduction pathways, known as DNA damage checkpoints, which are conserved from yeasts to humans. These pathways can sense DNA damage and transduce this information to specific cellular targets, which in turn regulate cell cycle transitions and DNA repair. The mammalian protein kinases ATM and ATR, as well as their budding yeast corresponding orthologs Tel1 and Mec1, act as master regulators of the checkpoint response to DSBs. Here, we review the early steps of DSB processing and the role of DNA-end structures in activating ATM/Tel1 and ATR/Mec1 in an orderly and reciprocal manner.", "title": "Interplays between ATM/Tel1 and ATR/Mec1 in sensing and signaling DNA double-strand breaks." }, { "docid": "4401289", "text": "Homology-directed DNA repair is essential for genome maintenance through templated DNA synthesis. Alternative lengthening of telomeres (ALT) necessitates homology-directed DNA repair to maintain telomeres in about 10–15% of human cancers. How DNA damage induces assembly and execution of a DNA replication complex (break-induced replisome) at telomeres or elsewhere in the mammalian genome is poorly understood. Here we define break-induced telomere synthesis and demonstrate that it utilizes a specialized replisome, which underlies ALT telomere maintenance. DNA double-strand breaks enact nascent telomere synthesis by long-tract unidirectional replication. Proliferating cell nuclear antigen (PCNA) loading by replication factor C (RFC) acts as the initial sensor of telomere damage to establish predominance of DNA polymerase δ (Pol δ) through its POLD3 subunit. Break-induced telomere synthesis requires the RFC–PCNA–Pol δ axis, but is independent of other canonical replisome components, ATM and ATR, or the homologous recombination protein Rad51. Thus, the inception of telomere damage recognition by the break-induced replisome orchestrates homology-directed telomere maintenance.", "title": "Break-induced telomere synthesis underlies alternative telomere maintenance" }, { "docid": "2904102", "text": "RecQ family helicases function as safeguards of the genome. Unlike Escherichia coli, the Gram-positive Bacillus subtilis bacterium possesses two RecQ-like homologues, RecQ[Bs] and RecS, which are required for the repair of DNA double-strand breaks. RecQ[Bs] also binds to the forked DNA to ensure a smooth progression of the cell cycle. Here we present the first biochemical analysis of recombinant RecQ[Bs]. RecQ[Bs] binds weakly to single-stranded DNA (ssDNA) and blunt-ended double-stranded DNA (dsDNA) but strongly to forked dsDNA. The protein exhibits a DNA-stimulated ATPase activity and ATP- and Mg(2+)-dependent DNA helicase activity with a 3' → 5' polarity. Molecular modeling shows that RecQ[Bs] shares high sequence and structure similarity with E. coli RecQ. Surprisingly, RecQ[Bs] resembles the truncated Saccharomyces cerevisiae Sgs1 and human RecQ helicases more than RecQ[Ec] with regard to its enzymatic activities. Specifically, RecQ[Bs] unwinds forked dsDNA and DNA duplexes with a 3'-overhang but is inactive on blunt-ended dsDNA and 5'-overhung duplexes. Interestingly, RecQ[Bs] unwinds blunt-ended DNA with structural features, including nicks, gaps, 5'-flaps, Kappa joints, synthetic replication forks, and Holliday junctions. We discuss these findings in the context of RecQ[Bs]'s possible functions in preserving genomic stability.", "title": "Characterization of biochemical properties of Bacillus subtilis RecQ helicase." }, { "docid": "5572127", "text": "The role of ataxia telangiectasia mutated (ATM), a DNA double-strand break recognition and response protein, in inflammation and inflammatory diseases is unclear. We have previously shown that high levels of systemic DNA damage are induced by intestinal inflammation in wild-type mice. To determine the effect of Atm deficiency in inflammation, we induced experimental colitis in Atm(-/-), Atm(+/-), and wild-type mice via dextran sulfate sodium (DSS) administration. Atm(-/-) mice had higher disease activity indices and rates of mortality compared with heterozygous and wild-type mice. Systemic DNA damage and immune response were characterized in peripheral blood throughout and after three cycles of treatment. Atm(-/-) mice showed increased sensitivity to levels of DNA strand breaks in peripheral leukocytes, as well as micronucleus formation in erythroblasts, compared with heterozygous and wild-type mice, especially during remission periods and after the end of treatment. Markers of reactive oxygen and nitrogen species-mediated damage, including 8-oxoguanine and nitrotyrosine, were present both in the distal colon and in peripheral leukocytes, with Atm(-/-) mice manifesting more 8-oxoguanine formation than wild-type mice. Atm(-/-) mice showed greater upregulation of inflammatory cytokines and significantly higher percentages of activated CD69+ and CD44+ T cells in the peripheral blood throughout treatment. ATM, therefore, may be a critical immunoregulatory factor dampening the deleterious effects of chronic DSS-induced inflammation, necessary for systemic genomic stability and homeostasis of the gut epithelial barrier.", "title": "Atm-deficient mice exhibit increased sensitivity to dextran sulfate sodium-induced colitis characterized by elevated DNA damage and persistent immune activation." }, { "docid": "14446279", "text": "In the yeast Saccharomyces cerevisiae that lacks lamins, the nuclear pore complex (NPC) has been proposed to serve a role in chromatin organization. Here, using fluorescence microscopy in living cells, we show that nuclear pore proteins of the Nup84 core complex, Nup84p, Nup145Cp, Nup120p, and Nup133p, serve to anchor telomere XI-L at the nuclear periphery. The integrity of this complex is shown to be required for repression of a URA3 gene inserted in the subtelomeric region of this chromosome end. Furthermore, altering the integrity of this complex decreases the efficiency of repair of a DNA double-strand break (DSB) only when it is generated in the subtelomeric region, even though the repair machinery is functional. These effects are specific to the Nup84 complex. Our observations thus confirm and extend the role played by the NPC, through the Nup84 complex, in the functional organization of chromatin. They also indicate that anchoring of telomeres is essential for efficient repair of DSBs occurring therein and is important for preserving genome integrity.", "title": "Telomere tethering at the nuclear periphery is essential for efficient DNA double strand break repair in subtelomeric region" }, { "docid": "7151961", "text": "Double-strand breaks (DSBs) occur frequently during DNA replication. They are also caused by ionizing radiation, chemical damage or as part of the series of programmed events that occur during meiosis. In yeast, DSB repair requires RAD52, a protein that plays a critical role in homologous recombination. Here we describe the actions of human RAD52 protein in a model system for single-strand annealing (SSA) using tailed (i.e. exonuclease resected) duplex DNA molecules. Purified human RAD52 protein binds resected DSBs and promotes associations between complementary DNA termini. Heteroduplex intermediates of these recombination reactions have been visualized by electron microscopy, revealing the specific binding of multiple rings of RAD52 to the resected termini and the formation of large protein complexes at heteroduplex joints formed by RAD52-mediated annealing.", "title": "Visualization of recombination intermediates produced by RAD52-mediated single-strand annealing." }, { "docid": "17553026", "text": "Human DNA polymerase mu (Polμ) is a family X member that has terminal transferase activity but, in spite of a non-orthodox selection of the template information, displays its maximal catalytic efficiency in DNA-templated reactions. As terminal deoxynucleotidyl transferase (TdT), Polμ has a specific loop (loop1) that could provide this enzyme with its terminal transferase activity. When loop1 was deleted, human Polμ lacked TdT activity but improved DNA-binding and DNA template-dependent polymerization. Interestingly, when loop1 from TdT was inserted in Polμ (substituting its cognate loop1), the resulting chimaera displayed TdT activity, preferentially inserting dGTP residues, but had a strongly reduced template-dependent polymerization activity. Therefore, a specialized loop in Polμ, that could adopt alternative conformations, appears to provide this enzyme with a dual capacity: (i) template independency to create new DNA information, in which loop1 would have an active role by acting as a ‘pseudotemplate’; (ii) template-dependent polymerization, in which loop1 must allow binding of the template strand. Recent in vivo and in vitro data suggest that such a dual capacity could be advantageous to resolve microhomology-mediated end-joining reactions.", "title": "A specific loop in human DNA polymerase mu allows switching between creative and DNA-instructed synthesis" }, { "docid": "35004872", "text": "Asbestos has been described as a physical carcinogen in that its carcinogenic effects appear to be related primarily to fiber dimensions. It has been hypothesized that long asbestos fibers may interfere with chromosome distribution during cell division, causing genomic changes that lead to cell transformation and neoplastic progression. Using high-resolution time-lapse light microscopy and serial-section electron microscopy, we have followed individual crocidolite asbestos fibers through the later stages of cell division in LLC-MK2 epithelial cells, and have detailed for the first time their effect on cytokinesis. We found that long fibers (15-55 microgram), trapped by the cleavage furrow, sterically blocked cytokinesis, sometimes resulting in the formation of a binucleated cell. The ends of blocking fibers were usually found within invaginations of the newly formed nuclei. Nuclear envelope-fiber attachment was evident when a chromatin strand ran with the fiber into the intercellular bridge. Such strands may break, causing chromosome structural rearrangements. Our data are the first to show that individual crocidolite fibers can cause genomic changes by sterically blocking cytokinesis and that fiber length and affinity for the nuclear envelope are important factors. Such genomic changes may be among the initial events leading to asbestos-induced cancers.", "title": "Long crocidolite asbestos fibers cause polyploidy by sterically blocking cytokinesis." }, { "docid": "25813706", "text": "Nuclear extracts derived from HeLa and Drosophila melanogaster KC cell lines have been found to correct single base-base mispairs within open circular DNA heteroduplexes containing a strand-specific, site-specific incision located 808 base pairs from the mismatch. Correction in both extract systems is strand specific, being highly biased to the incised DNA strand. Different mispairs within a homologous set of heteroduplexes were processed with different efficiencies (G.T greater than G.G approximately equal to A.C greater than C.C), and correction was accompanied by mismatch-dependent DNA synthesis localized to the region spanning the mispair and the strand break, thus demonstrating that mismatch recognition is associated with the repair reaction. Correction of each of these heteroduplexes was abolished by aphidicolin but was relatively insensitive to the presence of high concentrations of ddTTP, indicating probable involvement of alpha and/or delta class DNA polymerase(s). These findings suggest that higher eukaryotic cells possess a general, strand-specific mismatch repair system analogous to the Escherichia coli mutHLS and the Streptococcus pneumoniae hexAB pathways, systems that contribute in a major way to the genetic stability of these bacterial species.", "title": "Strand-specific mismatch correction in nuclear extracts of human and Drosophila melanogaster cell lines." } ]
456
Genes regulated by Esrrb transcription factor are sensitive to Mbd3 function.
[ { "docid": "30507607", "text": "Transcription factors, such as Oct4, are critical for establishing and maintaining pluripotent cell identity. Whereas the genomic locations of several pluripotency transcription factors have been reported, the spectrum of their interaction partners is underexplored. Here, we use an improved affinity protocol to purify Oct4-interacting proteins from mouse embryonic stem cells (ESCs). Subsequent purification of Oct4 partners Sall4, Tcfcp2l1, Dax1, and Esrrb resulted in an Oct4 interactome of 166 proteins, including transcription factors and chromatin-modifying complexes with documented roles in self-renewal, but also many factors not previously associated with the ESC network. We find that Esrrb associated with the basal transcription machinery and also detect interactions between transcription factors and components of the TGF-beta, Notch, and Wnt signaling pathways. Acute depletion of Oct4 reduced binding of Tcfcp2l1, Dax1, and Esrrb to several target genes. In conclusion, our purification protocol allowed us to bring greater definition to the circuitry controlling pluripotent cell identity.", "title": "An Oct4-Centered Protein Interaction Network in Embryonic Stem Cells" } ]
[ { "docid": "6826100", "text": "Induced pluripotent stem cells (iPSCs) are commonly generated by transduction of Oct4, Sox2, Klf4, and Myc (OSKM) into cells. Although iPSCs are pluripotent, they frequently exhibit high variation in terms of quality, as measured in mice by chimera contribution and tetraploid complementation. Reliably high-quality iPSCs will be needed for future therapeutic applications. Here, we show that one major determinant of iPSC quality is the combination of reprogramming factors used. Based on tetraploid complementation, we found that ectopic expression of Sall4, Nanog, Esrrb, and Lin28 (SNEL) in mouse embryonic fibroblasts (MEFs) generated high-quality iPSCs more efficiently than other combinations of factors including OSKM. Although differentially methylated regions, transcript number of master regulators, establishment of specific superenhancers, and global aneuploidy were comparable between high- and low-quality lines, aberrant gene expression, trisomy of chromosome 8, and abnormal H2A.X deposition were distinguishing features that could potentially also be applicable to human.", "title": "The developmental potential of iPSCs is greatly influenced by reprogramming factor selection." }, { "docid": "42565477", "text": "The molecular mechanism underlying G1/S checkpoint bypass in mouse embryonic stem cells (ESCs) remains unknown. DNA damage blocks S phase entry by inhibiting the CDK2 kinase through destruction of its activator, the Cdc25A phosphatase. We observed high Cdc25A levels in G1 that persist even after DNA damage in mouse ESCs. We also found higher expression of Dub3, a deubiquitylase that controls Cdc25A protein abundance. Moreover, we demonstrate that the Dub3 gene is a direct target of Esrrb, a key transcription factor of the self-renewal machinery. We show that Dub3 expression is strongly downregulated during neural conversion and precedes Cdc25A destabilization, while forced Dub3 expression in ESCs becomes lethal upon differentiation, concomitant to cell-cycle remodeling and lineage commitment. Finally, knockdown of either Dub3 or Cdc25A induced spontaneous differentiation of ESCs. Altogether, these findings couple the self-renewal machinery to cell-cycle control through a deubiquitylase in ESCs.", "title": "High Dub3 expression in mouse ESCs couples the G1/S checkpoint to pluripotency." }, { "docid": "26596106", "text": "In the yeast S. cerevisiae, ribosome assembly is linked to environmental conditions by the coordinate transcriptional regulation of genes required for ribosome biogenesis. In this study we show that two nonessential stress-responsive genes, YAR1 and LTV1, function in 40S subunit production. We provide genetic and biochemical evidence that Yar1, a small ankyrin-repeat protein, physically interacts with RpS3, a component of the 40S subunit, and with Ltv1, a protein recently identified as a substoichiometric component of a 43S preribosomal particle. We demonstrate that cells lacking YAR1 or LTV1 are hypersensitive to particular protein synthesis inhibitors and exhibit aberrant polysome profiles, with a reduced absolute number of 40S subunits and an excess of free 60S subunits. Surprisingly, both mutants are also hypersensitive to a variety of environmental stress conditions. Overexpression of RPS3 suppresses both the stress sensitivity and the ribosome biogenesis defect of Deltayar1 mutants, but does not suppress either defect in Deltaltv1 mutants. We propose that YAR1 and LTV1 play distinct, nonessential roles in 40S subunit production. The stress-sensitive phenotypes of strains lacking these genes reveal a hitherto unknown link between ribosome biogenesis factors and environmental stress sensitivity.", "title": "Genetic and biochemical interactions among Yar1, Ltv1 and Rps3 define novel links between environmental stress and ribosome biogenesis in Saccharomyces cerevisiae." }, { "docid": "4324278", "text": "The rapamycin-sensitive TOR signalling pathway in Saccharomyces cerevisiae activates a cell-growth program in response to nutrients such as nitrogen and carbon. The TOR1 and TOR2 kinases (TOR) control cytoplasmic protein synthesis and degradation through the conserved TAP42 protein. Upon phosphorylation by TOR, TAP42 binds and possibly inhibits type 2A and type-2A-related phosphatases; however, the mechanism by which TOR controls nuclear events such as global repression of starvation-specific transcription is unknown. Here we show that TOR prevents transcription of genes expressed upon nitrogen limitation by promoting the association of the GATA transcription factor GLN3 with the cytoplasmic protein URE2. The binding of GLN3 to URE2 requires TOR-dependent phosphorylation of GLN3. Phosphorylation and cytoplasmic retention of GLN3 are also dependent on the TOR effector TAP42, and are antagonized by the type-2A-related phosphatase SIT4. TOR inhibits expression of carbon-source-regulated genes by stimulating the binding of the transcriptional activators MSN2 and MSN4 to the cytoplasmic 14-3-3 protein BMH2. Thus, the TOR signalling pathway broadly controls nutrient metabolism by sequestering several transcription factors in the cytoplasm.", "title": "The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors." }, { "docid": "14116046", "text": "Retinoic acid-related orphan receptors RORα and RORγ play a regulatory role in lipid/glucose homeostasis and various immune functions, and have been implicated in metabolic syndrome and several inflammatory diseases. RORα-deficient mice are protected against age- and diet-induced obesity, hepatosteatosis, and insulin resistance. The resistance to hepatosteatosis in RORα-deficient mice is related to the reduced expression of several genes regulating lipid synthesis, transport, and storage. Adipose tissue-associated inflammation, which plays a critical role in the development of insulin resistance, is considerably diminished in RORα-deficient mice as indicated by the reduced infiltration of M1 macrophages and decreased expression of many proinflammatory genes. Deficiency in RORγ also protects against diet-induced insulin resistance by a mechanism that appears different from that in RORα deficiency. Recent studies indicated that RORs provide an important link between the circadian clock machinery and its regulation of metabolic genes and metabolic syndrome. As ligand-dependent transcription factors, RORs may provide novel therapeutic targets in the management of obesity and associated metabolic diseases, including hepatosteatosis, adipose tissue-associated inflammation, and insulin resistance.", "title": "Retinoic acid-related orphan receptors α and γ: key regulators of lipid/glucose metabolism, inflammation, and insulin sensitivity" }, { "docid": "8290760", "text": "During cellular reprogramming, only a small fraction of cells become induced pluripotent stem cells (iPSCs). Previous analyses of gene expression during reprogramming were based on populations of cells, impeding single-cell level identification of reprogramming events. We utilized two gene expression technologies to profile 48 genes in single cells at various stages during the reprogramming process. Analysis of early stages revealed considerable variation in gene expression between cells in contrast to late stages. Expression of Esrrb, Utf1, Lin28, and Dppa2 is a better predictor for cells to progress into iPSCs than expression of the previously suggested reprogramming markers Fbxo15, Fgf4, and Oct4. Stochastic gene expression early in reprogramming is followed by a late hierarchical phase with Sox2 being the upstream factor in a gene expression hierarchy. Finally, downstream factors derived from the late phase, which do not include Oct4, Sox2, Klf4, c-Myc, and Nanog, can activate the pluripotency circuitry.", "title": "Single-Cell Expression Analyses during Cellular Reprogramming Reveal an Early Stochastic and a Late Hierarchic Phase" }, { "docid": "13958154", "text": "Pancreatic β-cell dysfunction and death are central in the pathogenesis of type 2 diabetes (T2D). Saturated fatty acids cause β-cell failure and contribute to diabetes development in genetically predisposed individuals. Here we used RNA sequencing to map transcripts expressed in five palmitate-treated human islet preparations, observing 1,325 modified genes. Palmitate induced fatty acid metabolism and endoplasmic reticulum (ER) stress. Functional studies identified novel mediators of adaptive ER stress signaling. Palmitate modified genes regulating ubiquitin and proteasome function, autophagy, and apoptosis. Inhibition of autophagic flux and lysosome function contributed to lipotoxicity. Palmitate inhibited transcription factors controlling β-cell phenotype, including PAX4 and GATA6. Fifty-nine T2D candidate genes were expressed in human islets, and 11 were modified by palmitate. Palmitate modified expression of 17 splicing factors and shifted alternative splicing of 3,525 transcripts. Ingenuity Pathway Analysis of modified transcripts and genes confirmed that top changed functions related to cell death. Database for Annotation, Visualization and Integrated Discovery (DAVID) analysis of transcription factor binding sites in palmitate-modified transcripts revealed a role for PAX4, GATA, and the ER stress response regulators XBP1 and ATF6. This human islet transcriptome study identified novel mechanisms of palmitate-induced β-cell dysfunction and death. The data point to cross talk between metabolic stress and candidate genes at the β-cell level.", "title": "RNA sequencing identifies dysregulation of the human pancreatic islet transcriptome by the saturated fatty acid palmitate." }, { "docid": "20052986", "text": "Circadian rhythms are oscillations of physiology, behavior, and metabolism that have period lengths near 24 hours. In several model organisms and humans, circadian clock genes have been characterized and found to be transcription factors. Because of this, researchers have used microarrays to characterize global regulation of gene expression and algorithmic approaches to detect cycling. This article presents a new algorithm, JTK_CYCLE, designed to efficiently identify and characterize cycling variables in large data sets. Compared with COSOPT and the Fisher's G test, two commonly used methods for detecting cycling transcripts, JTK_CYCLE distinguishes between rhythmic and nonrhythmic transcripts more reliably and efficiently. JTK_CYCLE's increased resistance to outliers results in considerably greater sensitivity and specificity. Moreover, JTK_CYCLE accurately measures the period, phase, and amplitude of cycling transcripts, facilitating downstream analyses. Finally, JTK_CYCLE is several orders of magnitude faster than COSOPT, making it ideal for large-scale data sets. JTK_CYCLE was used to analyze legacy data sets including NIH3T3 cells, which have comparatively low amplitude oscillations. JTK_CYCLE's improved power led to the identification of a novel cluster of RNA-interacting genes whose abundance is under clear circadian regulation. These data suggest that JTK_CYCLE is an ideal tool for identifying and characterizing oscillations in genome-scale data sets.", "title": "JTK_CYCLE: an efficient nonparametric algorithm for detecting rhythmic components in genome-scale data sets." }, { "docid": "34071621", "text": "Vascular disease progression is associated with marked changes in vascular smooth muscle cell (SMC) phenotype and function. SMC contractile gene expression and, thus differentiation, is under direct transcriptional control by the transcription factor, serum response factor (SRF); however, the mechanisms dynamically regulating SMC phenotype are not fully defined. Here we report that the lipid and protein phosphatase, PTEN, has a novel role in the nucleus by functioning as an indispensible regulator with SRF to maintain the differentiated SM phenotype. PTEN interacts with the N-terminal domain of SRF and PTEN-SRF interaction promotes SRF binding to essential promoter elements in SM-specific genes. Factors inducing phenotypic switching promote loss of nuclear PTEN through nucleo-cytoplasmic translocation resulting in reduced myogenically active SRF, but enhanced SRF activity on target genes involved in proliferation. Overall decreased expression of PTEN was observed in intimal SMCs of human atherosclerotic lesions underlying the potential clinical importance of these findings.", "title": "Nuclear PTEN functions as an essential regulator of SRF-dependent transcription to control smooth muscle differentiation" }, { "docid": "22362025", "text": "Small regulatory RNAs are key regulators of gene expression. One class of small regulatory RNAs, termed the endogenous small interfering RNAs (endo siRNAs), is thought to negatively regulate cellular transcripts via an RNA interference (RNAi)-like mechanism termed endogenous RNAi (endo RNAi). A complex of proteins composed of ERI-1/3/5, RRF-3, and DICER (the ERI/DICER complex) mediates endo RNAi processes in Caenorhabditis elegans. We conducted a genetic screen to identify additional components of the endo RNAi machinery. Our screen recovered alleles of eri-9, which encodes a novel DICER-interacting protein, and a missense mutation within the helicase domain of DICER [DCR-1(G492R)]. ERI-9(-) and DCR-1(G492) animals exhibit defects in endo siRNA expression and a concomitant failure to regulate mRNAs that exhibit sequence homology to these endo siRNAs, indicating that ERI-9 and the DCR-1 helicase domain function in the C. elegans endo RNAi pathway. We define a subset of Eri mutant animals (including eri-1, rrf-3, eri-3, and dcr-1, but not eri-9 or ergo-1) that exhibit temperature-sensitive, sperm-specific sterility and defects in X chromosome segregation. Among these mutants we find multiple aberrations in sperm development beginning with cytokinesis and extending through terminal differentiation. These results identify novel components of the endo RNAi machinery, demonstrate differential requirements for the Eri factors in the sperm-producing germline, and begin to delineate the functional requirement for the ERI/DICER complex in sperm development.", "title": "Requirement for the ERI/DICER complex in endogenous RNA interference and sperm development in Caenorhabditis elegans." }, { "docid": "30933307", "text": "It is generally accepted that, following primary infection, human cytomegalovirus (HCMV) establishes lifelong latency in CD34(+) progenitor cells and other derivative cells of the myeloid lineage. In this study, we show that the viral UL144 gene is expressed during latent infection in two cell types of the myeloid lineage, CD34(+) and CD14(+) monocytes, and that the UL144 protein is functional in latently infected monocytes. However, this latency-associated expression of UL144 occurs only in certain isolates of HCMV and depends on the presence of functional GATA-2 transcription factor binding sites in the UL144 promoter, in contrast to the viral latency-associated gene LUNA, which we also show is regulated by GATA-2 but expressed uniformly during latent infection independent of the virus isolate. Taken together, these data suggest that the HCMV latency-associated transcriptome may be virus isolate specific and dependent on the repertoire of transcription factor binding sites in the promoters of latency-associated genes.", "title": "The myeloid transcription factor GATA-2 regulates the viral UL144 gene during human cytomegalovirus latency in an isolate-specific manner." }, { "docid": "21622715", "text": "Transcriptional factors binding to cAMP-responsive elements (CREs) in the promoters of various genes belong to the basic domain-leucine zipper superfamily and are composed of three genes in mammals, CREB, CREM, and ATF-1. A large number of CREB, CREM, and ATF-1 proteins are generated by posttranscriptional events, mostly alternative splicing, and regulate gene expression by acting as activators or repressors. Activation is classically brought about by signaling-dependent phosphorylation of a key acceptor site (Ser133 in CREB) by a number of possible kinases, including PKA, CamKIV, and Rsk-2. Phosphorylation is the prerequisite for the interaction of CBP (CREB-binding protein), a co-activator that has also histone acetyltransferase activity. Repression may involve dynamic dephosphorylation of the activators and thus decreased association with CBP. Another pathway of transcriptional repression on CRE sites implicates the inducible repressor ICER (inducible cAMP early repressor), a product of the CREM gene. Being an inducible repressor, ICER is involved in autoregulatory feedback loops of transcription that govern the down-regulation of early response genes, such as the proto-oncogene c-fos. The liver represents a remarkable physiological setting where cAMP-responsive signaling plays a major role. Indeed, a finely tuned program of gene expression is triggered by partial hepatectomy, so that through specific checkpoints a coordinated regeneration of the tissue is obtained. Temporal kinetics of transcriptional activation after hepatectomy reveals a pattern of early induction for several genes, some of them controlled by the CREB/CREM transcription factors. An important role of CREM in liver physiology was suggested by the robust induction of ICER after partial hepatectomy. The delay in tissue regeneration in CREM-deficient mice confirmed the important function of this factor in regulating hepatocyte proliferation. As gene induction is accompanied by critical changes in chromatin organization, the deciphering of the specific modification codes that histones display during liver regeneration and physiology will provide exciting new insights into the dynamics of chromatin architecture.", "title": "Coupling cAMP signaling to transcription in the liver: pivotal role of CREB and CREM." }, { "docid": "27693891", "text": "Gene regulatory factors encoded by the nuclear genome are essential for mitochondrial biogenesis and function. Some of these factors act exclusively within the mitochondria to regulate the control of mitochondrial transcription, translation, and other functions. Others govern the expression of nuclear genes required for mitochondrial metabolism and organelle biogenesis. The peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1) family of transcriptional coactivators play a major role in transducing and integrating physiological signals governing metabolism, differentiation, and cell growth to the transcriptional machinery controlling mitochondrial functional capacity. Thus, the PGC-1 coactivators serve as a central component of the transcriptional regulatory circuitry that coordinately controls the energy-generating functions of mitochondria in accordance with the metabolic demands imposed by changing physiological conditions, senescence, and disease.", "title": "Transcriptional integration of mitochondrial biogenesis." }, { "docid": "12315072", "text": "At the cellular level, development progresses through successive regulatory states, each characterized by their specific gene expression profile. However, the molecular mechanisms regulating first the priming and then maintenance of gene expression within one developmental pathway are essentially unknown. The hematopoietic system represents a powerful experimental model to address these questions and here we have focused on a regulatory circuit playing a central role in myelopoiesis: the transcription factor PU.1, its target gene colony-stimulating-factor 1 receptor (Csf1r), and key upstream regulators such as RUNX1. We find that during ontogeny, chromatin unfolding precedes the establishment of active histone marks and the formation of stable transcription factor complexes at the Pu.1 locus and we show that chromatin remodeling is mediated by the transient binding of RUNX1 to Pu.1 cis-elements. By contrast, chromatin reorganization of Csf1r requires prior expression of PU.1 together with RUNX1 binding. Once the full hematopoietic program is established, stable transcription factor complexes and active chromatin can be maintained without RUNX1. Our experiments therefore demonstrate how individual transcription factors function in a differentiation stage-specific manner to differentially affect the initiation versus maintenance of a developmental program.", "title": "Early chromatin unfolding by RUNX1: a molecular explanation for differential requirements during specification versus maintenance of the hematopoietic gene expression program." }, { "docid": "18924534", "text": "The mammalian genome harbors thousands of long noncoding RNA (lncRNA) genes. Recent studies have indicated the involvement of several of these lncRNAs in the regulation of gene expression. lncRNAs play crucial roles in various biological processes ranging from epigenetic gene regulation, transcriptional control, to post-transcriptional regulation. lncRNAs are localized in various subcellular compartments, and major proportion of these are retained in the cell nucleus and could be broadly classified as nuclear-retained lncRNAs (nrRNAs). Based on the identified functions, members of the nrRNAs execute diverse roles, including providing architectural support to the hierarchical subnuclear organization and influencing the recruitment of chromatin modifier factors to specific chromatin sites. In this review, we will summarize the recently described roles of mammalian nrRNAs in controlling gene expression by influencing chromatin organization, transcription, pre-mRNA processing, nuclear organization, and their involvement in disease.", "title": "Functional insights into the role of nuclear-retained long noncoding RNAs in gene expression control in mammalian cells" }, { "docid": "20179918", "text": "Both signal transducer and activator of transcription 3 (STAT3) and SALL4 are important in maintaining the pluripotent and self-renewal state of embryonic stem cells. We hypothesized that STAT3, a latent transcriptional factor, may regulate the gene expression of SALL4. In support of this hypothesis, DNA sequence analysis of the SALL4 gene promoter revealed four putative STAT3-binding sites. Using a SALL4-luciferase reporter gene assay, we found that modulation of the STAT3 activity significantly up-regulated the luciferase activity. By chromatin immunoprecipitation, the segment of the SALL4 promoter showing the highest affinity to STAT3 was localized to -366 to -163, in which there was only one putative STAT3 binding site starting at -199. Site-directed mutagenesis of all four putative STAT3-binding sites in the SALL4 promoter significantly reduced its responsiveness to STAT3, although the most dramatic effect was seen at the binding site starting at -199. We further tested the functional relationship between STAT3 and SALL4 using MDA-MB-231, a breast cell line carrying constitutive SALL4 expression and STAT3 activity. Down-regulation of the STAT3 activity using a dominant-negative construct resulted in a significant decrease in the expression of SALL4. To conclude, our data suggest that STAT3 and SALL4 probably cooperate in both physiological and pathological states.", "title": "Signal transducer and activator of transcription 3 is a transcriptional factor regulating the gene expression of SALL4." }, { "docid": "2452989", "text": "KLF1 regulates a diverse suite of genes to direct erythroid cell differentiation from bipotent progenitors. To determine the local cis-regulatory contexts and transcription factor networks in which KLF1 operates, we performed KLF1 ChIP-seq in the mouse. We found at least 945 sites in the genome of E14.5 fetal liver erythroid cells which are occupied by endogenous KLF1. Many of these recovered sites reside in erythroid gene promoters such as Hbb-b1, but the majority are distant to any known gene. Our data suggests KLF1 directly regulates most aspects of terminal erythroid differentiation including production of alpha- and beta-globin protein chains, heme biosynthesis, coordination of proliferation and anti-apoptotic pathways, and construction of the red cell membrane and cytoskeleton by functioning primarily as a transcriptional activator. Additionally, we suggest new mechanisms for KLF1 cooperation with other transcription factors, in particular the erythroid transcription factor GATA1, to maintain homeostasis in the erythroid compartment.", "title": "A global role for KLF1 in erythropoiesis revealed by ChIP-seq in primary erythroid cells." }, { "docid": "4418070", "text": "Regulatory T (Treg) cells, characterized by expression of the transcription factor forkhead box P3 (Foxp3), maintain immune homeostasis by suppressing self-destructive immune responses. Foxp3 operates as a late-acting differentiation factor controlling Treg cell homeostasis and function, whereas the early Treg-cell-lineage commitment is regulated by the Akt kinase and the forkhead box O (Foxo) family of transcription factors. However, whether Foxo proteins act beyond the Treg-cell-commitment stage to control Treg cell homeostasis and function remains largely unexplored. Here we show that Foxo1 is a pivotal regulator of Treg cell function. Treg cells express high amounts of Foxo1 and display reduced T-cell-receptor-induced Akt activation, Foxo1 phosphorylation and Foxo1 nuclear exclusion. Mice with Treg-cell-specific deletion of Foxo1 develop a fatal inflammatory disorder similar in severity to that seen in Foxp3-deficient mice, but without the loss of Treg cells. Genome-wide analysis of Foxo1 binding sites reveals ∼300 Foxo1-bound target genes, including the pro-inflammatory cytokine Ifng, that do not seem to be directly regulated by Foxp3. These findings show that the evolutionarily ancient Akt–Foxo1 signalling module controls a novel genetic program indispensable for Treg cell function.", "title": "Novel Foxo1-dependent transcriptional programs control Treg cell function" }, { "docid": "22150633", "text": "Embryonic stem (ES) cells are unique in their ability to self-renew indefinitely and maintain pluripotency. These properties require transcription factors that specify the gene expression programme of ES cells. It has been possible to reverse the highly differentiated state of somatic cells back to a pluripotent state with a combination of four transcription factors: Klf4 is one of the reprogramming factors required, in conjunction with Oct4, Sox2 and c-Myc. Maintenance of self-renewal and pluripotency of ES cells requires Oct4, Sox2 and c-Myc, but Klf4 is dispensable. Here, we show that Krüppel-like factors are required for the self-renewal of ES cells. Simultaneous depletion of Klf2, Klf4 and Klf5 lead to ES cell differentiation. Chromatin immunoprecipitation coupled to microarray assay reveals that these Klf proteins share many common targets of Nanog, suggesting a close functional relationship between these factors. Expression analysis after triple RNA interference (RNAi) of the Klfs shows that they regulate key pluripotency genes, such as Nanog. Taken together, our study provides new insight into how the core Klf circuitry integrates into the Nanog transcriptional network to specify gene expression that is unique to ES cells.", "title": "A core Klf circuitry regulates self-renewal of embryonic stem cells" }, { "docid": "13639330", "text": "Nuclear receptors undergo ligand-dependent conformational changes that are required for corepressor-coactivator exchange, but whether there is an actual requirement for specific epigenetic landmarks to impose ligand dependency for gene activation remains unknown. Here we report an unexpected and general strategy that is based on the requirement for specific cohorts of inhibitory histone methyltransferases (HMTs) to impose gene-specific gatekeeper functions that prevent unliganded nuclear receptors and other classes of regulated transcription factors from binding to their target gene promoters and causing constitutive gene activation in the absence of stimulating signals. This strategy, based at least in part on an HMT-dependent inhibitory histone code, imposes a requirement for specific histone demethylases, including LSD1, to permit ligand- and signal-dependent activation of regulated gene expression. These events link an inhibitory methylation component of the histone code to a broadly used strategy that circumvents pathological constitutive gene induction by physiologically regulated transcription factors.", "title": "Histone Methylation-Dependent Mechanisms Impose Ligand Dependency for Gene Activation by Nuclear Receptors" }, { "docid": "1065627", "text": "Stiffness is a biophysical property of the extracellular matrix that modulates cellular functions, including proliferation, invasion, and differentiation, and it also may affect therapeutic responses. Therapeutic durability in cancer treatments remains a problem for both chemotherapies and pathway-targeted drugs, but the reasons for this are not well understood. Tumor progression is accompanied by changes in the biophysical properties of the tissue, and we asked whether matrix rigidity modulated the sensitive versus resistant states in HER2-amplified breast cancer cell responses to the HER2-targeted kinase inhibitor lapatinib. The antiproliferative effect of lapatinib was inversely proportional to the elastic modulus of the adhesive substrata. Down-regulation of the mechanosensitive transcription coactivators YAP and TAZ, either by siRNA or with the small-molecule YAP/TEAD inhibitor verteporfin, eliminated modulus-dependent lapatinib resistance. Reduction of YAP in vivo in mice also slowed the growth of implanted HER2-amplified tumors, showing a trend of increasing sensitivity to lapatinib as YAP decreased. Thus we address the role of stiffness in resistance to and efficacy of a HER2 pathway-targeted therapeutic via the mechanotransduction arm of the Hippo pathway.", "title": "Microenvironment rigidity modulates responses to the HER2 receptor tyrosine kinase inhibitor lapatinib via YAP and TAZ transcription factors." }, { "docid": "29429111", "text": "Forkhead box transcription factor, class O (FOXO) is a mammalian homologue of DAF-16, which is known to regulate the lifespan of Caenorhabditis elegans and includes subfamilies of forkhead transcription factors such as AFX, FKHRL1, and FKHR. FKHR is phosphorylated on three sites (Thr-24, Ser-256, and Ser-319) in a phosphatidylinositol 3-kinase (PI3K)/Akt-dependent manner, thereby inhibiting death signals. We here documented dephosphorylation of FKHR following transient forebrain ischemia with its concomitant translocation into the nucleus in neurons in gerbil and mouse brains. The activation of FKHR preceded delayed neuronal death in the vulnerable hippocampal regions following ischemic brain injury. The FKHR activation was accompanied by an increase in DNA binding activity for FKHR-responsive element on the Fas ligand promoter. We also defined FKHR-induced downstream targets such as Fas ligand and Bim in brain ischemia. Therefore, we propose a new strategy to rescue neurons from delayed neuronal death by promoting the survival signaling. Sodium orthovanadate, a protein tyrosine phosphatase inhibitor, up-regulated Akt activity in the brain and in turn rescue neurons from delayed neuronal death by inhibiting FKHR-dependent or -independent death signals in neurons.", "title": "Transcriptional regulation of neuronal genes and its effect on neural functions: expression and function of forkhead transcription factors in neurons." }, { "docid": "33030946", "text": "Summary Hypoxia augments inflammatory responses and osteoclastogenesis by incompletely understood mechanisms. We identified COMMD1 as a cell‐intrinsic negative regulator of osteoclastogenesis that is suppressed by hypoxia. In human macrophages, COMMD1 restrained induction of NF‐&kgr;B signaling and a transcription factor E2F1‐dependent metabolic pathway by the cytokine RANKL. Downregulation of COMMD1 protein expression by hypoxia augmented RANKL‐induced expression of inflammatory and E2F1 target genes and downstream osteoclastogenesis. E2F1 targets included glycolysis and metabolic genes including CKB that enabled cells to meet metabolic demands in challenging environments, as well as inflammatory cytokine‐driven target genes. Expression quantitative trait locus analysis linked increased COMMD1 expression with decreased bone erosion in rheumatoid arthritis. Myeloid deletion of Commd1 resulted in increased osteoclastogenesis in arthritis and inflammatory osteolysis models. These results identify COMMD1 and an E2F‐metabolic pathway as key regulators of osteoclastogenic responses under pathological inflammatory conditions and provide a mechanism by which hypoxia augments inflammation and bone destruction. Graphical Abstract Figure. No Caption available. HighlightsCOMMD1 is a negative regulator of osteoclast differentiationCOMMD1 suppresses bone loss in RA and inflammatory arthritis and osteolysis modelsCOMMD1 negatively regulates E2F1‐dependent metabolic pathways in macrophagesHypoxia suppresses COMMD1 expression to augment osteoclastogenesis &NA; Pathways that promote osteoclastogenesis are well characterized but less is known about negative regulators that suppress pathological bone loss. Murata et al. identify COMMD1 as an inhibitor of osteoclastogenesis that restrains NF‐&kgr;B‐ and E2F1‐CKB‐mediated metabolic pathways in macrophages.", "title": "Hypoxia‐Sensitive COMMD1 Integrates Signaling and Cellular Metabolism in Human Macrophages and Suppresses Osteoclastogenesis" }, { "docid": "14191255", "text": "The embryonic stem (ES) cell transcriptional and chromatin-modifying networks are critical for self-renewal maintenance. However, it remains unclear whether these networks functionally interact and, if so, what factors mediate such interactions. Here, we show that WD repeat domain 5 (Wdr5), a core member of the mammalian Trithorax (trxG) complex, positively correlates with the undifferentiated state and is a regulator of ES cell self-renewal. We demonstrate that Wdr5, an \"effector\" of H3K4 methylation, interacts with the pluripotency transcription factor Oct4. Genome-wide protein localization and transcriptome analyses demonstrate overlapping gene regulatory functions between Oct4 and Wdr5. The Oct4-Sox2-Nanog circuitry and trxG cooperate in activating transcription of key self-renewal regulators, and furthermore, Wdr5 expression is required for the efficient formation of induced pluripotent stem (iPS) cells. We propose an integrated model of transcriptional and epigenetic control, mediated by select trxG members, for the maintenance of ES cell self-renewal and somatic cell reprogramming.", "title": "Wdr5 Mediates Self-Renewal and Reprogramming via the Embryonic Stem Cell Core Transcriptional Network" }, { "docid": "30908508", "text": "Objective: To investigate the regulation of CD4+CD25+ Regulatory T cells (Tregs) on pro-inflammatory adhesion molecules, Krüppel-Like Factor-2 (KLF-2) and its downstream transcriptional targets in human umbilical vein endothelial cells (HUVECs) impaired by ox-LDL and the mechanisms of it. Methods and results: HUVECs were cultured in the continuous presence of ox-LDL(0 mg/L,25 mg/L,50 mg/L,100 mg/L) for 4, 6, 12 and 24 hours to allow identification of early-and late-induced genes, respectively, whereas non-stimulated controls were taken at 0 hours. The expression of pro-inflammatory adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), E-selectin, KLF-2 and its target genes eNOS, PAI-1 were determined by real time RT-PCR and/or western-blot analysis. Expression of pro-inflammatory adhesion molecules, KLF-2, eNOS and PAI-1 in HUVEC cultured alone or with anti-CD3 mAbs activated Tregs, followed by addition of ox-LDL (50 mg/L) for 6 hours, are compared to expression levels in control cultures. Ox-LDL treated HUVECs increased pro-inflammatory adhesion molecules expression, as well as increased PAI-1 but decreased eNOS expression accompanied with significant downregulating of KLF-2 at a dose and time dependent manner. Furthermore, ox-LDL increased pro-inflammatory adhesion molecules but inhibited KLF2 expression was reversed by addition of Tregs. Small interfering RNA reduced endogenous KLF-2 expression and partly reversed the suppressive effect of Tregs on HUVECs activation, which strongly implicate KLF-2 as a transcriptional regulator of the Tregs-mediated effects in endothelial cells. Mechanism studies reveal that Treg-mediated KLF2 expression in HUVECs impaired by ox-LDL requires cell contact as well as soluble factors. Conclusions: Tregs could protect endothelial function that is largely dependent on KLF2 and its downstream transcriptional targets regulation involving cell-to-cell contact and soluble factors.", "title": "CD4+CD25+Foxp3+Regulatory T Cells Protect Endothelial Function Impaired by Oxidized Low Density Lipoprotein via the KLF-2 Transcription Factor" }, { "docid": "25022826", "text": "AFF1 and AFF4 belong to the AFF (AF4/FMR2) family of proteins, which function as scaffolding proteins linking two different transcription elongation factors, positive elongation factor b (P-TEFb) and ELL1/2, in super elongation complexes (SECs). Both AFF1 and AFF4 regulate gene transcription through elongation and chromatin remodeling. However, their function in the osteogenic differentiation of mesenchymal stem cells (MSCs) is unknown. In this study, we show that small interfering RNA (siRNA)-mediated depletion of AFF1 in human MSCs leads to increased alkaline phosphatase (ALP) activity, enhanced mineralization and upregulated expression of osteogenic-related genes. On the contrary, depletion of AFF4 significantly inhibits the osteogenic potential of MSCs. In addition, we confirm that overexpression of AFF1 and AFF4 differentially affects osteogenic differentiation in vitro and MSC-mediated bone formation in vivo. Mechanistically, we find that AFF1 regulates the expression of DKK1 via binding to its promoter region. Depletion of DKK1 in HA-AFF1-overexpressing MSCs abrogates the impairment of osteogenic differentiation. Moreover, we detect that AFF4 is enriched in the promoter region of ID1. AFF4 knockdown blunts the BRE luciferase activity, SP7 expression and ALP activity induced by BMP2 treatment. In conclusion, our data indicate that AFF1 and AFF4 differentially regulate the osteogenic differentiation of human MSCs.", "title": "AFF1 and AFF4 differentially regulate the osteogenic differentiation of human MSCs" }, { "docid": "42106119", "text": "The transcription factor Oct4 is key in embryonic stem cell identity and reprogramming. Insight into its partners should illuminate how the pluripotent state is established and regulated. Here, we identify a considerably expanded set of Oct4-binding proteins in mouse embryonic stem cells. We find that Oct4 associates with a varied set of proteins including regulators of gene expression and modulators of Oct4 function. Half of its partners are transcriptionally regulated by Oct4 itself or other stem cell transcription factors, whereas one-third display a significant change in expression upon cell differentiation. The majority of Oct4-associated proteins studied to date show an early lethal phenotype when mutated. A fraction of the human orthologs is associated with inherited developmental disorders or causative of cancer. The Oct4 interactome provides a resource for dissecting mechanisms of Oct4 function, enlightening the basis of pluripotency and development, and identifying potential additional reprogramming factors.", "title": "An Expanded Oct4 Interaction Network: Implications for Stem Cell Biology, Development, and Disease" }, { "docid": "3152612", "text": "A novel differentiation-dependent cDNA (DIF-2) has been isolated from human mononuclear phagocytes by differential display. The full-length cDNA was cloned and sequenced. DIF-2 consists of 156 amino acids and has a predicted isoelectric point of 8.84. The mRNA is expressed in freshly isolated monocytes and is downregulated significantly when monocytes are subjected to differentiation. A similar differentiation-dependent downregulation is observed in normal hepatocytes compared to undifferentiated HepG2 cells. The mRNA expression in monocytes is sensitive to lipopolysaccharide and ceramide which both strongly increase DIF-2 transcription, while lysophosphatidylcholine results in a weaker upregulation of DIF-2 expression. A DIF-2 homologous gene has been previously isolated from mouse fibroblasts and was shown to be a serum growth factor-inducible immediate early gene. Our results indicate that DIF-2 represents a gene which is regulated in differentiation processes and strongly responsive to lipopolysaccharide, ceramide and lysophosphatidylcholine.", "title": "Identification and characterization of a novel monocyte/macrophage differentiation-dependent gene that is responsive to lipopolysaccharide, ceramide, and lysophosphatidylcholine." }, { "docid": "52873726", "text": "The Hippo pathway controls organ size and tissue homeostasis, with deregulation leading to cancer. The core Hippo components in mammals are composed of the upstream serine/threonine kinases Mst1/2, MAPK4Ks and Lats1/2. Inactivation of these upstream kinases leads to dephosphorylation, stabilization, nuclear translocation and thus activation of the major functional transducers of the Hippo pathway, YAP and its paralogue TAZ. YAP/TAZ are transcription co-activators that regulate gene expression primarily through interaction with the TEA domain DNA-binding family of transcription factors (TEAD). The current paradigm for regulation of this pathway centres on phosphorylation-dependent nucleocytoplasmic shuttling of YAP/TAZ through a complex network of upstream components. However, unlike other transcription factors, such as SMAD, NF-κB, NFAT and STAT, the regulation of TEAD nucleocytoplasmic shuttling has been largely overlooked. In the present study, we show that environmental stress promotes TEAD cytoplasmic translocation via p38 MAPK in a Hippo-independent manner. Importantly, stress-induced TEAD inhibition predominates YAP-activating signals and selectively suppresses YAP-driven cancer cell growth. Our data reveal a mechanism governing TEAD nucleocytoplasmic shuttling and show that TEAD localization is a critical determinant of Hippo signalling output.", "title": "Regulation of Hippo pathway transcription factor TEAD by p38 MAPK-induced cytoplasmic translocation" }, { "docid": "1449692", "text": "Whether and how gestational protein restriction (PR) affects placental development and function remain unknown. To test the hypothesis that PR can affect trophoblast differentiation in mid-and late pregnancy, rats were fed a 20% or an isocaloric 6% protein diet from Day 1 to 14 or 18 of pregnancy and effects of PR on trophoblast differentiation were determined by changes in expressions of marker gene(s) for trophoblast lineages. At Day 18 of pregnancy, PR increased expressions of Esrrb, Id1 andId2 (trophoblast stem cell markers), decreased expressions of Ascl2 (spongiotrophblast cell marker) and Prl2c1 (trophoblast giant cell marker), but did not alter expressions of Gjb3 and Pcdh12(glycogen cell markers) in the junctional zone (JZ). In the labyrinth zone (LZ), PR did not change expressions of Prl2b1 (trophoblast giant cell marker), Gcm1 and Syna (syncytiotrophoblast cell markers), but decrease expression of Ctsq (sinusoidal trophoblast giant cell marker). These results indicate that PR impairs the differentiation of trophoblast stem cell into spongiotrophoblast and trophoblast giant cells in JZ, and formation of sinusoidal trophoblast giant cells in LZ.", "title": "Gestational protein restriction affects trophoblast differentiation." } ]
174147
Jimmy Carter was the 39th President of the United States.
[ { "docid": "Jimmy_Carter", "text": "James Earl Carter Jr. ( born October 1 , 1924 ) is an American politician who served as the 39th President of the United States from 1977 to 1981 . A member of the Democratic Party , he served as the Governor of Georgia prior to his election as president . Carter has remained active in public life during his post-presidency , and in 2002 he was awarded the Nobel Peace Prize for his work with the Carter Center . Carter joined the United States Navy after graduating high school , serving on nuclear submarines . He left the Navy in 1953 to return to Georgia , where he worked as a peanut farmer . From 1963 to 1967 , Carter served in the Georgia State Senate . In 1970 , Carter won election as Governor of Georgia , defeating former Governor Carl Sanders in the Democratic primary . He served as governor from 1971 to 1975 . Despite being little-known outside of Georgia at the start of the campaign , Carter won the 1976 Democratic presidential nomination . In the general election , Carter defeated incumbent Republican President Gerald Ford in a relatively close election . On his second day in office , Carter pardoned all evaders of the Vietnam War drafts . During Carter 's term as President , two new cabinet-level departments , the Department of Energy and the Department of Education , were established . He established a national energy policy that included conservation , price control , and new technology . In foreign affairs , Carter pursued the Camp David Accords , the Panama Canal Treaties , the second round of Strategic Arms Limitation Talks ( SALT II ) , and the return of the Panama Canal Zone to Panama . On the economic front he confronted persistent `` stagflation '' , a combination of high inflation , high unemployment and slow growth . The end of his presidential tenure was marked by the 1979 -- 1981 Iran hostage crisis , the 1979 energy crisis , the Three Mile Island nuclear accident , and the Soviet invasion of Afghanistan . In response to the invasion , Carter ended détente , escalated the Cold War , and led the international boycott of the 1980 Summer Olympics in Moscow . In 1980 , Carter faced a primary challenge from Senator Ted Kennedy , but Carter won re-nomination at the 1980 Democratic National Convention . Carter lost the general election in an electoral landslide to Republican nominee Ronald Reagan . Polls of historians and political scientists usually rank Carter as a below average president . In 2012 , he surpassed Herbert Hoover as the longest-retired president in U.S. history , and he is also the first president to mark the 40th anniversary of his inauguration . He set up the Carter Center in 1982 as his base for advancing human rights . He has also traveled extensively to conduct peace negotiations , observe elections , and advance disease prevention and eradication in developing nations . Additionally , Carter is a key figure in the Habitat for Humanity project and he has written several books about various topics . In reference to current political views , he has criticized some of Israel 's actions and policies in regards to the Israeli -- Palestinian conflict and has advocated for a two-state solution . He has vigorously opposed the Supreme Court 's decision in Citizens United v. FEC to strike down limits on campaign spending by corporations and unions , saying that the U.S. is `` no longer a functioning democracy '' and now has a system of `` unlimited political bribery . ''", "title": "" } ]
[ { "docid": "USS_Jimmy_Carter", "text": "USS Jimmy Carter ( SSN-23 ) is the third and last Seawolf-class submarine in the United States Navy . She is named for Jimmy Carter , the 39th President of the United States ; Carter is the only President who had qualified in submarines , having served as a Communications Officer , Sonar Officer , Electronics Officer , Weapons Officer , and Supply Officer while on board . Jimmy Carter is one of the few ships of the United States Navy ( and only the third submarine ) to have been named for a person who was alive at the time of the ship 's naming , and the only submarine to be named for a living former president .", "title": "" }, { "docid": "Inauguration_of_Jimmy_Carter", "text": "The Inauguration of Jimmy Carter as the 39th President of the United States was held on Thursday , January 20 , 1977 , on the East Portico of the United States Capitol in Washington D.C. . The inauguration marked the commencement of the only four-year term of Jimmy Carter as President and of Walter Mondale as Vice President . Chief Justice Warren E. Burger administered the presidential oath of office to Carter , and Speaker of the House Tip O'Neill administered the vice presidential oath of office to Mondale . This was the last inauguration held on the East Portico of the Capitol building to date .", "title": "" }, { "docid": "United_States_presidential_election_in_Missouri,_1976", "text": "The 1976 United States presidential election in Missouri took place on November 2 , 1976 , as part of the 1976 United States presidential election . Voters chose twelve representatives , or electors , to the Electoral College , who voted for President and Vice President . Missouri was won by Jimmy Carter ( D -- Georgia ) , with 51.10 % of the popular vote . Carter defeated incumbent President Gerald Ford ( R -- Michigan ) , who finished with 47.47 % of the popular vote . Jimmy Carter went on to become the 39th President of the United States .", "title": "" }, { "docid": "United_States_presidential_election_in_Rhode_Island,_1976", "text": "The 1976 United States presidential election in Rhode Island took place on November 2 , 1976 , as part of the 1976 United States presidential election . Voters chose four representatives , or electors , to the Electoral College , who voted for President and Vice President . Rhode Island was won by Jimmy Carter ( D -- Georgia ) , with 55.36 % of the popular vote . Carter defeated incumbent President Gerald Ford ( R -- Michigan ) , who finished with 44.08 % of the popular vote . No third party candidate received any votes . Jimmy Carter went on to become the 39th President of the United States .", "title": "" }, { "docid": "United_States_presidential_election_in_Delaware,_1976", "text": "The 1976 United States presidential election in Delaware took place on November 2 , 1976 , as part of the 1976 United States presidential election . Voters chose three representatives , or electors , to the Electoral College , who voted for President and Vice President . Delaware was won by Jimmy Carter ( D -- Georgia ) , with 51.98 % of the popular vote . Carter defeated incumbent President Gerald Ford ( R -- Michigan ) , who finished with 46.57 % of the popular vote . No third party candidate amounted 1 % of the vote , but Eugene McCarthy ( Independent -- Minnesota ) finished third in Delaware with 1.03 % of the statewide popular vote . Jimmy Carter went on to become the 39th President of the United States .", "title": "" }, { "docid": "United_States_presidential_election_in_Louisiana,_1976", "text": "The 1976 United States presidential election in Louisiana took place on November 2 , 1976 , as part of the 1976 United States presidential election . Voters chose ten representatives , or electors , to the Electoral College , who voted for President and Vice President . Louisiana was won by Jimmy Carter ( D -- Georgia ) , with 51.73 % of the popular vote . Carter defeated incumbent President Gerald Ford ( R -- Michigan ) , who finished with 45.95 % of the popular vote . No third party candidate amounted 1 % of the vote ; American Independent Party candidate Lester Maddox cane the closest with 0.79 % . Jimmy Carter went on to become the 39th President of the United States .", "title": "" }, { "docid": "United_States_presidential_election_in_Kentucky,_1976", "text": "The 1976 United States presidential election in Kentucky took place on November 2 , 1976 , as part of the 1976 United States presidential election . Voters chose nine representatives , or electors , to the Electoral College , who voted for President and Vice President . Kentucky was won by Jimmy Carter ( D -- Georgia ) , with 52.75 % of the popular vote . Carter defeated incumbent President Gerald Ford ( R -- Michigan ) , who finished with 45.57 % of the popular vote , and did so by winning all major demographic groups in the Commonwealth . No third party candidate amounted 1 % of the vote ; American Party candidate Thomas Anderson cane the closest with 0.71 % . Jimmy Carter went on to become the 39th President of the United States .", "title": "" }, { "docid": "Jimmy_Carter_National_Historic_Site", "text": "The Jimmy Carter National Historic Site , located in Plains , Georgia , preserves sites associated with James Earl `` Jimmy '' Carter , Jr. ( 1924 -- present ) , 39th President of the United States . These include his residence , boyhood farm , school , and the town railroad depot , which served as his campaign headquarters during the 1976 election . The building which used to be Plains High School ( opened in 1921 and closed in 1979 ) serves as the park 's museum and visitor center . As President Carter lives in Plains , the area surrounding the residence is under the protection of the United States Secret Service and is not open to the public . The Carters returned to Plains in January 1981 . The former President and First Lady Rosalynn Carter pursue many of the goals of his administration through the Carter Center in Atlanta , which has programs to alleviate human suffering and to promote human rights and world peace . When they are in Plains , Carter teaches Sunday school at Maranatha Baptist Church , which is open to the public .", "title": "" }, { "docid": "Bibliography_of_Jimmy_Carter", "text": "Books authored by Jimmy Carter , the 39th President of the United States ( 1977 -- 1981 ) . A historical novel about the American Revolution , and the first work of fiction written by a U.S. President . Won a Grammy Award for best spoken-word album . UK edition of Our Endangered Values .", "title": "" }, { "docid": "United_States_presidential_election_in_Wyoming,_1976", "text": "The 1976 United States presidential election in Wyoming took place on November 2 , 1976 as part of the 1976 United States presidential election . Voters chose three representatives , or electors , to the Electoral College , who voted for President and Vice President . Wyoming was won by incumbent President Gerald Ford ( R -- Michigan ) , with 59.3 % of the popular vote , against Jimmy Carter ( D -- Georgia ) , with 39.8 % of the popular vote . Despite losing in Wyoming , Carter went on to win the national election and became the 39th President of the United States .", "title": "" }, { "docid": "Presidency_of_Jimmy_Carter", "text": "The presidency of Jimmy Carter began on January 20 , 1977 at noon Eastern Standard Time , when Jimmy Carter was inaugurated as President of the United States , and ended on January 20 , 1981 . A Democrat , he took office after defeating Republican incumbent President Gerald Ford in the 1976 presidential election . His presidency ended with his defeat in the 1980 presidential election by Republican Ronald Reagan . Carter , the 39th United States president , sought to make the government `` competent and compassionate '' but , in the midst of an economic crisis produced by rising energy prices and stagflation , met with difficulty in achieving its objectives . At the end of his administration , Carter had seen a substantial decrease in unemployment and a partial reduction of the deficit , but the recession ultimately continued . Carter created the United States Department of Education and United States Department of Energy , established a national energy policy and pursued civil service and social security reform . In foreign affairs , Carter strongly emphasized human rights throughout his career . He signed the second round of the Strategic Arms Limitation Talks ( SALT II ) with the Soviet Union and , in an effort to end the Arab -- Israeli conflict , initiated the Camp David Accords . With the Torrijos -- Carter Treaties , he guaranteed the transfer of the Panama Canal to Panama in 1999 . His administration also established official diplomatic relations with the People 's Republic of China , while he signed the Taiwan Relations Act to define relations with Taiwan . The final year of his presidential tenure was marked by several major crises , including the 1979 takeover of the American embassy in Iran and holding of hostages by Iranian students , an unsuccessful rescue attempt of the hostages , serious fuel shortages , and the Soviet invasion of Afghanistan . In the 1980 election , Carter defeated a primary challenge from Ted Kennedy , a prominent liberal Democrat . However , Carter lost the general election in a landslide to Reagan . In polls of historians and political scientists , Carter is usually ranked as a below-average president .", "title": "" }, { "docid": "United_States_presidential_election_in_Kansas,_1976", "text": "The 1976 United States presidential election in Kansas took place on November 2 , 1976 , as part of the 1976 United States presidential election . Kansas voters chose seven representatives , or electors , to the Electoral College , who voted for President and Vice President . Kansas was won by incumbent President Gerald Ford ( R -- Michigan ) . with 52.49 % of the popular vote , against Jimmy Carter ( D -- Georgia ) , with 44.94 % of the popular vote . None of the third party candidates amounted a significant portion of the vote , but Eugene McCarthy ( I -- Minnesota ) won 1.38 % of the popular vote in Kansas , finishing third in the state . Despite losing in Kansas , Carter went on to win the national election and became the 39th President of the United States .", "title": "" }, { "docid": "Plains,_Georgia", "text": "Plains is a town in Sumter County , Georgia , United States . The population was 776 at the 2010 census . It is part of the Americus Micropolitan Statistical Area . Plains is known as the birthplace and home of Jimmy Carter , the 39th president of the United States .", "title": "" }, { "docid": "United_States_presidential_election_in_Nebraska,_1976", "text": "The 1976 United States presidential election in Nebraska took place on November 2 , 1976 , as part of the 1976 United States presidential election . Voters chose five representatives , or electors , to the Electoral College , who voted for President and Vice President . Nebraska was won by incumbent President Gerald Ford ( R -- Michigan ) , with 59.19 % of the popular vote , against Jimmy Carter ( D -- Georgia ) , with 38.46 % of the popular vote . None of the third party candidates amounted a significant portion of the vote , but Eugene McCarthy ( I -- Minnesota ) won 1.55 % of Nebraska 's popular vote and came third overall in the nation . Despite losing in Nebraska , Carter went on to win the national election and became the 39th President of the United States .", "title": "" }, { "docid": "United_States_presidential_election_in_North_Dakota,_1976", "text": "The 1976 United States presidential election in North Dakota took place on November 2 , 1976 , as part of the 1976 United States presidential election . North Dakota voters chose three representatives , or electors , to the Electoral College , who voted for President and Vice President . North Dakota was won by the Republican candidate and incumbent President , Gerald Ford , with 51.66 % of the popular vote , against the Democratic candidate , Jimmy Carter , with 45.80 % of the popular vote . American Party candidate Thomas Anderson finished highest among third parties ; finishing with 1.24 % of North Dakota 's popular vote . Despite losing in North Dakota , Carter went on to win the national election and became the 39th President of the United States .", "title": "" }, { "docid": "Rosalynn_Carter", "text": "Eleanor Rosalynn Carter ( née Smith ; born August 18 , 1927 ) is the wife of the 39th President of the United States , Jimmy Carter , and served as the First Lady of the United States from 1977 to 1981 . She has for decades been a leading advocate for numerous causes , perhaps most prominently for mental health research . She was politically active during her White House years , sitting in on Cabinet and policy meetings as well as serving as her husband 's closest adviser . She also served as an envoy abroad , to Latin America in particular .", "title": "" }, { "docid": "United_States_presidential_election_in_Colorado,_1976", "text": "The 1976 United States presidential election in Colorado took place on November 2 , 1976 , as part of the 1976 United States presidential election . Voters chose seven representatives , or electors , to the Electoral College , who voted for President and Vice President . Colorado was won by incumbent President Gerald Ford ( R -- Michigan ) . with 54.1 % of the popular vote , against Jimmy Carter ( D -- Georgia ) , with 41.6 % of the popular vote . None of the third party candidates amounted a significant portion of the vote , but Eugene McCarthy ( I -- Minnesota ) won 2.4 % of the popular vote and came third overall in the nation . Despite losing in Colorado , Carter went on to win the national election and became the 39th President of the United States . Colorado had previously voted Republican fifteen times , Democrat nine times , and Populist once ( for James B. Weaver in 1892 ) .", "title": "" }, { "docid": "United_States_presidential_election_in_Idaho,_1976", "text": "The 1976 United States presidential election in Idaho took place on November 2 , 1976 , as part of the 1976 United States presidential election . Voters chose four representatives , or electors , to the Electoral College , who voted for President and Vice President . Idaho was won by incumbent President Gerald Ford ( R -- Michigan ) , with 59.9 % of the popular vote , against Jimmy Carter ( D -- Georgia ) , with 37.1 % of the popular vote . Two third party candidates amounted a portion of the vote greater than 1 % : Lester Maddox ( AIA -- Georgia ) and Roger MacBride ( L -- Vermont ) . Despite losing in Idaho , Carter went on to win the national election and became the 39th President of the United States . Idaho had previously voted Republican ten times , Democrat ten times , and Populist once .", "title": "" }, { "docid": "United_States_presidential_election_in_Iowa,_1976", "text": "The 1976 United States presidential election in Iowa took place on November 2 , 1976 , as part of the 1976 United States presidential election . Voters chose eight representatives , or electors , to the Electoral College , who voted for President and Vice President . Iowa was won by incumbent President Gerald Ford ( R -- Michigan ) . with 49.47 % of the popular vote , against Jimmy Carter ( D -- Georgia ) , with 48.46 % of the popular vote . This race was one of the tightest in the nation , with the two men being separated by just 1.01 % of the vote and a mere thirteen thousand votes . None of the third party candidates amounted a significant portion of the vote , but Eugene McCarthy ( I -- Minnesota ) won 1.57 % of the popular vote and came third overall in the nation . Despite losing in Iowa , Carter went on to win the national election and became the 39th President of the United States .", "title": "" }, { "docid": "International_Emergency_Economic_Powers_Act", "text": "The International Emergency Economic Powers Act ( IEEPA ) , Title II of , is a United States federal law authorizing the President to regulate commerce after declaring a national emergency in response to any unusual and extraordinary threat to the United States which has a foreign source . The H.R. 7738 legislation was passed by the United States 95th Congressional session and signed by the 39th President of the United States Jimmy E. Carter on December 28 , 1977 .", "title": "" }, { "docid": "United_States_presidential_election_in_Nevada,_1976", "text": "The 1976 United States presidential election in Nevada took place on November 2 , 1976 , as part of the 1976 United States presidential election . Voters chose three representatives , or electors , to the Electoral College , who voted for President and Vice President . Nevada was won by incumbent President Gerald Ford ( R -- Michigan ) , with 50.17 % of the popular vote , against Jimmy Carter ( D -- Georgia ) , with 45.81 % of the popular vote . None of the third party candidates amounted a significant portion of the vote , as 2.53 % of the voters either wrote-in another candidate or selected `` no preference '' . Despite losing in Nevada , Carter went on to win the national election and became the 39th President of the United States . Although Nevada has generally been a bellwether state since the early 20th century , this election marked the first time since 1908 whereby Nevada was carried by the losing presidential candidate .", "title": "" }, { "docid": "United_States_presidential_election_in_Oregon,_1976", "text": "The 1976 United States presidential election in Oregon took place on November 2 , 1976 , as part of the 1976 United States presidential election . Voters chose six representatives , or electors , to the Electoral College , who voted for President and Vice President . Oregon was won by incumbent President Gerald Ford ( R -- Michigan ) . with 47.78 % of the popular vote , against Jimmy Carter ( D -- Georgia ) , with 47.62 % of the popular vote . Oregon was to prove the closest state in the nation , and this also is the closest presidential election in Oregon since statehood in 1859 . None of the third party candidates amounted a significant portion of the vote , but Eugene McCarthy ( I -- Minnesota ) won 3.9 % of the popular vote and came third overall in the nation . Despite losing in Oregon , Carter went on to win the national election and became the 39th President of the United States . This is the last occasion when Crook County , Wheeler County and Linn County have voted for a Democratic presidential candidate . It was to end almost a century as a bellwether for Crook County , which was to become solidly Republican following the `` Reagan Revolution '' .", "title": "" }, { "docid": "Nuclear_Non-Proliferation_Act_of_1978", "text": "Nuclear Non-Proliferation Act of 1978 , 22 U.S.C. § 3201 , is a United States federal law declaring that nuclear explosive devices pose a perilous threat to the security interests of the United States and continued international progress towards world peace and the development of nations . The H.R. 8638 legislation was passed by the 95th U.S. Congressional session and signed into law by the 39th President of the United States Jimmy Carter on March 10 , 1978 .", "title": "" }, { "docid": "Bluegrass_darter", "text": "The bluegrass darter ( Etheostoma jimmycarter ) is found in the Green River drainage in Kentucky and Tennessee . It was named after the 39th president of the United States Jimmy Carter for his environmental leadership and accomplishments in the areas of national energy policy and wilderness protection , and his lifelong commitment to social justice and basic human rights .", "title": "" }, { "docid": "We_Can_Have_Peace_in_the_Holy_Land", "text": "We Can Have Peace In The Holy Land : A Plan That Will Work is a New York Times Best Seller book written by Jimmy Carter , 39th President of the United States ( 1977 -- 1981 ) and winner of the 2002 Nobel Peace Prize . It was published by Simon & Schuster in February 2009 . It came as a sequel to his previous book Palestine : Peace Not Apartheid believing that U.S president Barack Obama said he will make a personal effort for Middle East Peace from the beginning of his administration . While President , Carter hosted talks between Menachem Begin of Israel and Anwar Sadat of Egypt that led to the Israel-Egypt Peace Treaty . In this book Carter argues that Israel 's continued control of Palestinian land has been the primary obstacle to a comprehensive peace agreement in the Middle East .", "title": "" }, { "docid": "National_Energy_Conservation_Policy_Act", "text": "The National Energy Conservation Policy Act of 1978 ( NECPA , ) is a United States statute which was enacted as part of the National Energy Act . The H.R. 5037 legislation was passed by the 95th U.S. Congressional session and enacted into law by the 39th President of the United States Jimmy Carter on November 9 , 1978 . Energy demand management programs had been legislated earlier in California and Wisconsin as early as 1975 .", "title": "" }, { "docid": "Public_Rangelands_Improvement_Act_of_1978", "text": "The Public Rangelands Improvement Act of 1978 ( PRIA ) defines the current grazing fee formula and establishes rangeland monitoring and inventory procedures for Bureau of Land Management and United States Forest Service rangelands . The National Grasslands are exempt from PRIA . The H.R. 10587 legislation was passed by the 95th U.S. Congressional session and enacted into law by the 39th President of the United States Jimmy Carter on October 25 , 1978 .", "title": "" }, { "docid": "Timeline_of_the_presidency_of_Jimmy_Carter", "text": "The presidency of Jimmy Carter began on January 20 , 1977 when Jimmy Carter was inaugurated as President of the United States , and ended on January 20 , 1981 .", "title": "" }, { "docid": "Palestine:_Peace_Not_Apartheid", "text": "Palestine : Peace Not Apartheid is a New York Times Best Seller book written by Jimmy Carter , 39th President of the United States ( 1977 -- 1981 ) and laureate of the 2002 Nobel Peace Prize . It was published by Simon & Schuster in November 2006 . During his presidency , Carter hosted talks between Menachem Begin of Israel and Anwar Sadat of Egypt that led to the Egypt -- Israel Peace Treaty . In this book Carter argues that Israel 's continued control and colonization of Palestinian land have been the primary obstacles to a comprehensive peace agreement in the Middle East . That perspective , coupled with Apartheid in the titular phrase Peace Not Apartheid ( which many regard as a subtitle ) and allegations of errors and misstatements in the book , sparked criticism . Carter has defended his book and countered that response to it `` in the real world ... has been overwhelmingly positive . '' The documentary , Man from Plains ( 2007 ) , explores the former president 's post -- White House role in the Israeli -- Palestinian conflict .", "title": "" }, { "docid": "1980_State_of_the_Union_Address", "text": "The 1980 State of the Union address was given by President Jimmy Carter , the 39th President of the United States , to a joint session of the 96th United States Congress on January 21 , 1980 . He addressed the Iran Hostage Crisis and the Soviet invasion of Afghanistan : `` At this time in Iran , 50 Americans are still held captive , innocent victims of terrorism and anarchy . Also at this moment , massive Soviet troops are attempting to subjugate the fiercely independent and deeply religious people of Afghanistan . '' The speech lasted 32 minutes and 4 seconds . and contained 3412 words . The Republican Party response was delivered by Senator Ted Stevens ( AK ) and Representative John Rhodes ( AZ ) .", "title": "" } ]
PLAIN-99
Quadrupling Breast Cancer Survival
[ { "docid": "MED-4457", "text": "Sulforaphane (SFR), an isothiocyanate from cruciferous vegetables, possesses growth-inhibiting and apoptosis-inducing activities in cancer cell lines. Recently, SFR has been shown to promote the mitochondrial formation of reactive oxygen species (ROS) in human cancer cell lines. The present study was undertaken to see whether SFR-derived ROS might cause DNA damage in cultured human cells, namely T limphoblastoid Jurkat and human umbilical vein endothelial cells (HUVEC). 1-3 h treatments with 10-30 microM SFR elicited intracellular ROS formation (as assayed with dihydrorhodamine, DHR, oxidation) as well as DNA breakage (as assessed with fast halo assay, FHA). These effects lacked cell-type specificity, since could be observed in both Jurkat and HUVEC. Differential-pH FHA analysis of damaged DNA showed that SFR causes frank DNA single strand breaks (SSBs); no DNA double strand breaks (DSBs) were found within the considered treatment times (up to 3 h). SFR-derived ROS were formed at the mitochondrial respiratory chain (MRC) level: indeed rotenone or myxothiazol (MRC Complex I and III inhibitors, respectively) abrogated ROS formation. Furthermore ROS were not formed in Jurkat cells pharmacologically depleted of respiring mitochondria (MRC-/Jurkat). Formation of ROS was causally linked to the induction of SSBs: indeed all the experimental conditions capable of preventing ROS formation also prevented the damage of nuclear DNA from SFR-intoxicated cells. As to the toxicological relevance of SSBs, we found that their prevention slightly but significantly attenuated SFR cytotoxicity, suggesting that high-dose SFR toxicity is the result of a complex series of events among which GSH depletion seems to play a pivotal role. In conclusion, the present study identifies a novel mechanism contributing to SFR toxicity which - since DNA damage is a prominent mechanism underlying the cytotoxic activity of established antineoplastic agents - might help to exploit the therapeutic value of SFR in anticancer drug protocols. Copyright 2010 Elsevier B.V. All rights reserved.", "title": "Sulforaphane induces DNA single strand breaks in cultured human cells." }, { "docid": "MED-4463", "text": "Naturally-occurring chemopreventive agent phenethyl isothiocyanate (PEITC), derived primarily from watercress, has been shown to inhibit cell growth and induce apoptosis in cancer cells. In this study, we examined the potential of PEITC in enhancing cisplatin-induced apoptosis in cervical cancer cells. HeLa cells were exposed to PEITC, cisplatin or both. Pretreatment of cells with PEITC strongly enhanced cisplatin-induced cytotoxicity. PEITC activated the mitogen-activated protein kinases, including JNK, ERK, and p38. The synergistic induction of apoptosis was significantly attenuated by MEK1/2 inhibitor U0126, but not by JNK or p38 inhibitor, suggesting that ERK activation is responsible for the synergistic effect. We found that NF-κB signaling pathway is not involved in the synergistic effect. Sulforaphane and benzyl isothiocyanate, two other members of the isothiocyanate family, also sensitize HeLa cells to apoptosis induced by cisplatin. Furthermore, we found that the synergistic effect was not seen in normal cells. Finally, we demonstrated that Noxa induction was associated with apoptosis induced by PEITC plus cisplatin. Taken together, this study shows that PEITC can sensitize cancer cells to apoptosis induced by cisplatin and this effect is mediated through ERK activation, suggesting the potential of PEITC to be used as an adjuvant with cisplatin in combination therapeutic treatments.", "title": "Phenethyl isothiocyanate sensitizes human cervical cancer cells to apoptosis induced by cisplatin" }, { "docid": "MED-5327", "text": "OBJECTIVE: To investigate the associations between dietary patterns and mental health in early adolescence. METHOD: The Western Australian Pregnancy Cohort (Raine) Study is a prospective study of 2900 pregnancies recruited from 1989-1992. At 14 years of age (2003-2006; n=1324), the Child Behaviour Checklist (CBCL) was used to assess behaviour (characterising mental health status), with higher scores representing poorer behaviour. Two dietary patterns (Western and Healthy) were identified using factor analysis and food group intakes estimated by a 212-item food frequency questionnaire. Relationships between dietary patterns, food group intakes and behaviour were examined using general linear modelling following adjustment for potential confounding factors at age 14: total energy intake, body mass index, physical activity, screen use, family structure, income and functioning, gender and maternal education at pregnancy. RESULTS: Higher total (b=2.20, 95% CI=1.06, 3.35), internalizing (withdrawn/depressed) (b=1.25, 95% CI=0.15, 2.35) and externalizing (delinquent/aggressive) (b=2.60, 95% CI=1.51, 3.68) CBCL scores were significantly associated with the Western dietary pattern, with increased intakes of takeaway foods, confectionary and red meat. Improved behavioural scores were significantly associated with higher intakes of leafy green vegetables and fresh fruit (components of the Healthy pattern). CONCLUSION: These findings implicate a Western dietary pattern in poorer behavioural outcomes for adolescents. Better behavioural outcomes were associated with a higher intake of fresh fruit and leafy green vegetables.", "title": "The association between dietary patterns and mental health in early adolescence." }, { "docid": "MED-5341", "text": "The present study investigated the effects of a diet and exercise intervention on known breast cancer (BCa) risk factors, including estrogen, obesity, insulin, and insulin-like growth factor-I (IGF-I), in overweight/obese, postmenopausal women. In addition, using the subjects' pre- and postintervention serum in vitro, serum-stimulated growth and apoptosis of three estrogen receptor-positive BCa cell lines were studied. The women where placed on a low-fat (10-15% kcal), high-fiber (30-40 g per 1,000 kcal/day) diet and attended daily exercise classes for 2 wk. Serum estradiol was reduced in the women on hormone treatment (HT; n = 28) as well as those not on HT (n = 10). Serum insulin and IGF-I were significantly reduced in all women, whereas IGF binding protein-1 was increased significantly. In vitro growth of the BCa cell lines was reduced by 6.6% for the MCF-7 cells, 9.9% for the ZR-75-1 cells, and 18.5% for the T-47D cells. Apoptosis was increased by 20% in the ZR-75-1 cells, 23% in the MCF-7 cells, and 30% in the T-47D cells (n = 12). These results show that a very-low-fat, high-fiber diet combined with daily exercise results in major reductions in risk factors for BCa while subjects remained overweight/obese. These in vivo serum changes slowed the growth and induced apoptosis in serum-stimulated BCa cell lines in vitro.", "title": "Effects of a low-fat, high-fiber diet and exercise program on breast cancer risk factors in vivo and tumor cell growth and apoptosis in vitro." }, { "docid": "MED-4452", "text": "Background: Evidence for the role of diet and physical activity in cancer incidence is well documented, but owing to increased cancer survivorship, an understanding of these lifestyle factors after a cancer diagnosis is of crucial importance. The purpose of this review was to update the literature in a review undertaken for the National Cancer Survivorship Initiative and to include observational studies that were not included in the WCRF survivorship systematic review. Methods: Evidence was initially gathered from pre-defined searches of the Cochrane Library Database and PubMed from March 2006 to February 2010. After a comprehensive review regarding lifestyle and cancer, for the purpose of this article, any studies not related to diet and physical activity, prognostic outcomes, and breast, colorectal or prostate cancers were excluded. Another search of 2011 literature was conducted to update the evidence. Results: A total of 43 records were included in this review. Evidence from observational studies suggests that a low-fat, high-fibre diet might be protective against cancer recurrence and progression. However, there is a paucity of RCTs substantiating this. There is more support for physical activity, with a dose response for better outcomes. When synthesized with findings from the World Cancer Research Fund review of RCTs investigating the effect of diet and physical activity interventions on cancer survival, evidence suggests that the mechanism of benefit from diet and physical activity pertains to body weight, with excess body weight being a risk factor, which is modifiable through lifestyle. Implications: Cancer survivors would like to have a more active role in their health care and to know how to look after themselves after diagnosis, including what diet and lifestyle changes they should make. The challenge is in integrating lifestyle support into standardised models of aftercare.", "title": "The role of diet and physical activity in breast, colorectal, and prostate cancer survivorship: a review of the literature" }, { "docid": "MED-4461", "text": "The objective of this study was to investigate, whether the plant-derived isothiocyanate Sulforaphane (SFN) enhances the antitumor activities of the chemotherapeutic agent oxaliplatin (Ox) in a cell culture model of colorectal cancer. Caco-2 cells were cultured under standard conditions and treated with increasing concentrations of SFN [1-20 μM] and/or Ox [100 nM-10 μM]. For co-incubation, cells were pre-treated with SFN for 24 h. Cell growth was determined by BrdU incorporation. Drug interactions were assessed using the combination-index method (CI) (Cl < 1 indicates synergism). Apoptotic events were characterized by different ELISA techniques. Protein levels were examined by Western blot analysis. Annexin V- and propidium iodide (PI) staining followed by FACS analysis was used to differentiate between apoptotic and necrotic events. SFN and Ox alone inhibited cell growth of Caco-2 cells in a dose-dependent manner, an effect, which could be synergistically enhanced, when cells were incubated with the combination of both agents. Co-treated cells further displayed distinctive morphological changes that occurred during the apoptotic process, such as cell surface exposure of phosphatidylserine, membrane blebbing as well as the occurence of cytoplasmic histone-associated DNA fragments. Further observations thereby pointed toward simultaneous activation of both extrinsic and intrinsic apoptotic pathways. With increasing concentrations and treatment duration, a shift from apoptotic to necrotic cell death could be observed. In conclusion, the data suggest that the isothiocyanate SFN sensitizes colon cancer cells to Ox-induced cell growth inhibition via induction of different modes of cell death.", "title": "Sulforaphane potentiates oxaliplatin-induced cell growth inhibition in colorectal cancer cells via induction of different modes of cell death." }, { "docid": "MED-4459", "text": "Ultraviolet (UV) of sunlight is a complete carcinogen that can burn skin, enhance inflammation, and drive skin carcinogenesis. Previously, we have shown that sulforaphane (SFN) inhibited chemically induced skin carcinogenesis via nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and others have shown that broccoli sprout extracts containing high SFN protected against UV-induced skin carcinogenesis in SKH-1 hairless mice. A recent study showed that there was no difference between Nrf2 knockout (Nrf2 KO) and Nrf2 wild-type (WT) BALB/C mice after exposing to high dose of UVB. Since Nrf2 plays critical roles in the anti-oxidative stress/anti-inflammatory responses, it is relevant to assess the role of Nrf2 for photoprotection against UV. In this context, the role of Nrf2 in UVB-induced skin inflammation in Nrf2 WT and Nrf2 KO C57BL/6 mice was studied. A single dose of UVB (300 mJ/cm(2)) resulted in skin inflammation in both WT and Nrf2 KO (-/-) mice (KO mice) at 8 h and 8 d following UVB irradiation. In the WT mice inflammation returned to the basal level to a greater extent when compared to the KO mice. SFN treatment of Nrf2 WT but not Nrf2 KO mice restored the number of sunburn cells back to their basal level by 8 d after UVB irradiation. Additionally, UVB-induced short-term inflammatory biomarkers (interleukin-1β and interleukin-6) were increased in the KO mice and UVB-induced apoptotic cells in the KO mice were significantly higher as compared to that in the WT. Taken together, our results show that functional Nrf2 confers a protective effect against UVB-induced inflammation, sunburn reaction, and SFN-mediated photoprotective effects in the skin. Copyright © 2010 Wiley-Liss, Inc.", "title": "Impact of Nrf2 on UVB-induced skin inflammation/photoprotection and photoprotective effect of sulforaphane." }, { "docid": "MED-5339", "text": "Recently, it has been suggested that the Escherichia coli causing urinary tract infection (UTI) may come from meat and animals. The purpose was to investigate if a clonal link existed between E. coli from animals, meat and UTI patients. Twenty-two geographically and temporally matched B2 E. coli from UTI patients, community-dwelling humans, broiler chicken meat, pork, and broiler chicken, previously identified to exhibit eight virulence genotypes by microarray-detection of approximately 300 genes, were investigated for clonal relatedness by PFGE. Nine isolates were selected and tested for in vivo virulence in the mouse model of ascending UTI. UTI and community-dwelling human strains were closely clonally related to meat strains. Several human derived strains were also clonally interrelated. All nine isolates regardless of origin were virulent in the UTI model with positive urine, bladder and kidney cultures. Further, isolates with the same gene profile also yielded similar bacterial counts in urine, bladder and kidneys. This study showed a clonal link between E. coli from meat and humans, providing solid evidence that UTI is zoonosis. The close relationship between community-dwelling human and UTI isolates may indicate a point source spread, e.g. through contaminated meat.", "title": "Is Escherichia coli urinary tract infection a zoonosis? Proof of direct link with production animals and meat." }, { "docid": "MED-4458", "text": "Background Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine with keto-enol tautomerase activity, rises rapidly in response to inflammation, and is elevated in many chronic diseases. Isothiocyanates, such as sulforaphane from broccoli, are very potent inactivators of MIF tautomerase activity. A simple rapid method for determining this activity in tissues and body fluids may therefore be valuable for assessing severity of inflammation and efficacy of intervention. Methods Existing spectrophotometric assays of MIF, based on conversion of methyl L-dopachrome to methyl 5,6-dihydroxyindole-2-carboxylate and associated loss of absorption at 475 nm, lack sensitivity. Assay sensitivity and efficiency were markedly improved by reducing the nonenzymatic rate, by lowering pH to 6.2, replacing phosphate (which catalyzes the reaction) with Bis-Tris buffer, and converting to a microtiter plate format. Results A structure-potency study of MIF tautomerase inactivation by isothiocyanates showed that sulforaphane, benzyl, n-hexyl, and phenethyl isothiocyanates were especially potent. MIF tautomerase could be readily quantified in human urine concentrated by ultrafiltration. This activity comprised: (i) a heat-labile, sulforaphane-inactivated macromolecular fraction (presumably MIF) that was concentrated during ultrafiltration; (ii) a flow-through fraction, with constant activity during filtration, that was heat-stable, and insensitive to sulforaphane. Administration of the sulforaphane precursor glucoraphanin to human volunteers almost completely abolished urinary tautomerase activity, which was recovered over many hours. Conclusions A simple, rapid, quantitative MIF tautomerase assay has been developed as a potential biomarker for assessing inflammatory severity and effectiveness of intervention. Impact An improved assay for measuring MIF tautomerase activity and its applications are described.", "title": "Inactivation of Tautomerase Activity of Macrophage Migration Inhibitory Factor by Sulforaphane: A Potential Biomarker for Anti-inflammatory Intervention" }, { "docid": "MED-5335", "text": "Three recent case-control studies conclude that diets high in animal fat or cholesterol are associated with a substantial increase in risk for Parkinson's disease (PD); in contrast, fat of plant origin does not appear to increase risk. Whereas reported age-adjusted prevalence rates of PD tend to be relatively uniform throughout Europe and the Americas, sub-Saharan black Africans, rural Chinese, and Japanese, groups whose diets tend to be vegan or quasi-vegan, appear to enjoy substantially lower rates. Since current PD prevalence in African-Americans is little different from that in whites, environmental factors are likely to be responsible for the low PD risk in black Africans. In aggregate, these findings suggest that vegan diets may be notably protective with respect to PD. However, they offer no insight into whether saturated fat, compounds associated with animal fat, animal protein, or the integrated impact of the components of animal products mediates the risk associated with animal fat consumption. Caloric restriction has recently been shown to protect the central dopaminergic neurons of mice from neurotoxins, at least in part by induction of heat-shock proteins; conceivably, the protection afforded by vegan diets reflects a similar mechanism. The possibility that vegan diets could be therapeutically beneficial in PD, by slowing the loss of surviving dopaminergic neurons, thus retarding progression of the syndrome, may merit examination. Vegan diets could also be helpful to PD patients by promoting vascular health and aiding blood-brain barrier transport of L-dopa. Copyright 2001 Harcourt Publishers Ltd.", "title": "Does a vegan diet reduce risk for Parkinson's disease?" }, { "docid": "MED-5322", "text": "BACKGROUND/AIMS: This study aimed to investigate the quantitative and qualitative changes of bacteria, Bacteroides, Bifidobacterium and Clostridium cluster IV in faecal microbiota associated with a vegetarian diet. METHODS: Bacterial abundances were measured in faecal samples of 15 vegetarians and 14 omnivores using quantitative PCR. Diversity was assessed with PCR-DGGE fingerprinting, principal component analysis (PCA) and Shannon diversity index. RESULTS: Vegetarians had a 12% higher abundance of bacterial DNA than omnivores, a tendency for less Clostridium cluster IV (31.86 +/- 17.00%; 36.64 +/- 14.22%) and higher abundance of Bacteroides (23.93 +/- 10.35%; 21.26 +/- 8.05%), which were not significant due to high interindividual variations. PCA suggested a grouping of bacteria and members of Clostridium cluster IV. Two bands appeared significantly more frequently in omnivores than in vegetarians (p < 0.005 and p < 0.022). One was identified as Faecalibacterium sp. and the other was 97.9% similar to the uncultured gut bacteriumDQ793301. CONCLUSIONS: A vegetarian diet affects the intestinal microbiota, especially by decreasing the amount and changing the diversity of Clostridium cluster IV. It remains to be determined how these shifts might affect the host metabolism and disease risks. Copyright 2009 S. Karger AG, Basel.", "title": "Characterization of bacteria, clostridia and Bacteroides in faeces of vegetarians using qPCR and PCR-DGGE fingerprinting." }, { "docid": "MED-4462", "text": "Chondrocyte cell death can contribute to cartilage degeneration in articular diseases, such as osteoarthritis (OA). Sulforaphane (SFN), a natural compound derived from cruciferous aliment, is well known as an anti-carcinogen, but according to recent evidence it also shows cytoprotective effects on a variety of non-tumoral cells. Therefore we have tested the ability of SFN to protect chondrocytes from cell death in vitro. Treatment of growing monolayer cultures of human C-28/I2 chondrocytes with SFN in the low micro-molecular range for a few days, reduced cell growth without affecting cell survival or inducing apoptosis. However it decreased cell death in C-28/I2 chondrocytes exposed to stimuli previously reported to promptly trigger apoptosis, that is, the cytokine tumor necrosis factor-α (TNF) plus cycloheximide (CHX) or the polyamine analogue N(1),N(11)-diethylnorspermine (DENSPM) plus CHX. In particular pre-treatment with SFN reduced effector and initiator caspase activities and the associated activation of JNK kinases. SFN exerted a cytoprotective action even versus H(2)O(2) , which differently from the previous stimuli induced cell death without producing an evident caspase activation. SFN pre-treatment also prevented caspase activation in three-dimensional micromass cultures of OA chondrocytes stimulated with growth-related oncogene α (GROα), a pro-apoptotic chemokine. The suppression of caspase activation in micromasses appeared to be related to the inhibition of p38 MAPK phosphorylation. In conclusion, the present work shows that low micro-molecular SFN concentrations exert pro-survival and anti-apoptotic actions and influence signaling pathways in a variety of experimental conditions employing chondrocyte cell lines and OA chondrocytes treated with a range of death stimuli. Copyright © 2010 Wiley-Liss, Inc.", "title": "Sulforaphane protects human chondrocytes against cell death induced by various stimuli." }, { "docid": "MED-5324", "text": "Obesity has important health consequences, including elevating risk for heart disease, diabetes, and cancer. A high-fat diet is known to contribute to obesity. Little is known regarding the effect of a high-fat diet on pulmonary function, despite the dramatic increase in the prevalence of respiratory ailments (e.g., asthma). The purpose of our study was to determine whether a high-fat meal (HFM) would increase airway inflammation and decrease pulmonary function in healthy subjects. Pulmonary function tests (PFT) (forced expiratory volume in 1-s, forced vital capacity, forced expiratory flow at 25-75% of vital capacity) and exhaled nitric oxide (eNO; airway inflammation) were performed in 20 healthy (10 men, 10 women), inactive subjects (age 21.9 +/- 0.4 years) pre and 2 h post HFM (1 g fat/1 kg body weight; 74.2 +/- 4.1 g fat). Total cholesterol, triglycerides, and C-reactive protein (CRP; systemic inflammation) were determined via a venous blood sample pre and post HFM. Body composition was measured via dual energy X-ray absorptiometry. The HFM significantly increased total cholesterol by 4 +/- 1%, and triglycerides by 93 +/- 3%. ENO also increased (p < 0.05) due to the HFM by 19 +/- 1% (pre 17.2 +/- 1.6; post 20.6 +/- 1.7 ppb). ENO and triglycerides were significantly related at baseline and post-HFM (r = 0.82, 0.72 respectively). Despite the increased eNO, PFT or CRP did not change (p > 0.05) with the HFM. These results demonstrate that a HFM, which leads to significant increases in total cholesterol, and especially triglycerides, increases exhaled NO. This suggests that a high-fat diet may contribute to chronic inflammatory diseases of the airway and lung.", "title": "Effects of a high-fat meal on pulmonary function in healthy subjects." }, { "docid": "MED-3238", "text": "The protective effect of vegetables on the risk of breast cancer recurrence is uncertain. We sought to evaluate the association between breast cancer recurrence and vegetable intake including analyses stratified on tamoxifen use. Experimental evidence of anti-carcinogenic activity of phytochemicals in cruciferous vegetables in combination with tamoxifen led to specific evaluation of this class of vegetables as well. To assess the association between vegetable intake and breast cancer recurrence, vegetable intake from repeat 24-h dietary recalls were examined as a secondary analysis of 3,080 breast cancer survivors enrolled in the Women's Healthy Eating and Living (WHEL) Study. At the time of enrollment women were, on average, 23.5 months post-diagnosis. The hazard of recurrence, controlling for relevant and significant clinical and demographic variables, with vegetable intake was assessed overall and separately for women taking tamoxifen. WHEL participants reported mean baseline intakes (⁻x, SE) of 3.1 ± 0.05 and 0.5 ± 0.02 servings/day of total and cruciferous vegetables, respectively. Baseline vegetable intake in the highest as compared to lowest tertiles was associated with an overall lower adjusted hazard ratios (HR) for recurrence of 0.69, 95% CI 0.55-0.87. Among women taking tamoxifen, the HRs were 0.56, 95% CI 0.41-0.77 for total vegetables and 0.65, 95% CI 0.47-0.89 for cruciferous vegetable intake. The hazard in women using tamoxifen who reported cruciferous vegetable intake above the median and who were within the highest tertile of total vegetable intake was HR 0.48; 95% CI 0.32-0.70. This secondary analysis in over 3,000 breast cancer survivors suggests that baseline vegetable intake may be associated with a reduction in the risk of breast cancer recurrent or new events particularly for those using tamoxifen. Such associations should be explored further as the possibility that vegetable intake is simply a surrogate for other health-promoting behaviors cannot be ruled out.", "title": "Vegetable intake is associated with reduced breast cancer recurrence in tamoxifen users: a secondary analysis from the Women's Healthy Eating and L..." }, { "docid": "MED-5342", "text": "Background The physical health status of vegetarians has been extensively reported, but there is limited research regarding the mental health status of vegetarians, particularly with regard to mood. Vegetarian diets exclude fish, the major dietary source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), critical regulators of brain cell structure and function. Omnivorous diets low in EPA and DHA are linked to impaired mood states in observational and experimental studies. Methods We examined associations between mood state and polyunsaturated fatty acid intake as a result of adherence to a vegetarian or omnivorous diet in a cross-sectional study of 138 healthy Seventh Day Adventist men and women residing in the Southwest. Participants completed a quantitative food frequency questionnaire, Depression Anxiety Stress Scale (DASS), and Profile of Mood States (POMS) questionnaires. Results Vegetarians (VEG:n = 60) reported significantly less negative emotion than omnivores (OMN:n = 78) as measured by both mean total DASS and POMS scores (8.32 ± 0.88 vs 17.51 ± 1.88, p = .000 and 0.10 ± 1.99 vs 15.33 ± 3.10, p = .007, respectively). VEG reported significantly lower mean intakes of EPA (p < .001), DHA (p < .001), as well as the omega-6 fatty acid, arachidonic acid (AA; p < .001), and reported higher mean intakes of shorter-chain α-linolenic acid (p < .001) and linoleic acid (p < .001) than OMN. Mean total DASS and POMS scores were positively related to mean intakes of EPA (p < 0.05), DHA (p < 0.05), and AA (p < 0.05), and inversely related to intakes of ALA (p < 0.05), and LA (p < 0.05), indicating that participants with low intakes of EPA, DHA, and AA and high intakes of ALA and LA had better mood. Conclusions The vegetarian diet profile does not appear to adversely affect mood despite low intake of long-chain omega-3 fatty acids.", "title": "Vegetarian diets are associated with healthy mood states: a cross-sectional study in Seventh Day Adventist adults" }, { "docid": "MED-4455", "text": "The importance of dietary sulforaphane in helping maintain good health continues to gain support within the health-care community and awareness among U.S. consumers. In addition to the traditional avenue for obtaining sulforaphane, namely, the consumption of appropriate cruciferous vegetables, other consumer products containing added glucoraphanin, the natural precursor to sulforaphane, are now appearing in the United States. Crucifer seeds are a likely source for obtaining glucoraphanin, owing to a higher concentration of glucoraphanin and the relative ease of processing seeds as compared to vegetative parts. Seeds of several commonly consumed crucifers were analyzed not only for glucoraphanin but also for components that might have negative health implications, such as certain indole-containing glucosinolates and erucic acid-containing lipids. Glucoraphanin, 4-hydroxyglucobrassicin, other glucosinolates, and lipid erucic acid were quantified in seeds of 33 commercially available cultivars of broccoli, 4 cultivars each of kohlrabi, radish, cauliflower, Brussels sprouts, kale, and cabbage, and 2 cultivars of raab.", "title": "Glucoraphanin and 4-hydroxyglucobrassicin contents in seeds of 59 cultivars of broccoli, raab, kohlrabi, radish, cauliflower, brussels sprouts, kal..." }, { "docid": "MED-5337", "text": "PURPOSE: Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS AND METHODS: Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group. RESULTS: None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. CONCLUSIONS: Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.", "title": "Intensive lifestyle changes may affect the progression of prostate cancer." }, { "docid": "MED-5330", "text": "Although there is a well-established relation between serum cholesterol and coronary artery disease risk, individual and national variations in this association suggest that other factors are involved in atherogenesis. High-fat diet associated triglyceride-rich lipoproteins have also been suggested to be atherogenic. To assess the direct effect of postprandial triglyceride-rich lipoproteins on endothelial function, an early factor in atherogenesis--10 healthy, normocholesterolemic volunteers--were studied before and for 6 hours after single isocaloric high- and low-fat meals (900 calorie; 50 and 0 g fat, respectively). Endothelial function, in the form of flow-mediated vasoactivity, was assessed in the brachial artery using 7.5-MHz ultrasound as percent arterial diameter change 1 minute after 5 minutes of upper-arm arterial occlusion. Serum lipoproteins and glucose were determined before eating and 2 and 4 hours postprandially. Serum triglycerides increased from 94 +/- 55 mg/dl preprandially to 147 +/- 80 mg/dl 2 hours after the high-fat meal (p = 0.05). Flow-dependent vasoactivity decreased from 21 +/- 5% preprandially to 11 +/- 4%, 11 +/- 6%, and 10 +/- 3% at 2, 3, and 4 hours after the high-fat meal, respectively (all p <0.05 compared with low-fat meal data). No changes in lipoproteins or flow-mediated vasoactivity were observed after the low-fat meal. Fasting low-density lipoprotein cholesterol correlated inversely (r = -0.47, p = 0.04) with preprandial flow-mediated vasoactivity, but triglyceride level did not. Mean change in postprandial flow-mediated vasoactivity at 2, 3, and 4 hours correlated with change in 2-hour serum triglycerides (r = -0.51, p = 0.02). These results demonstrate that a single high-fat meal transiently impairs endothelial function. These findings identify a potential process by which a high-fat diet may be atherogenic independent of induced changes in cholesterol.", "title": "Effect of a single high-fat meal on endothelial function in healthy subjects." }, { "docid": "MED-4460", "text": "BACKGROUND: The multistep process of carcinogenesis is characterized by progressive disorganization and occurrence of initiation, promotion, and progression events. Several new strategies such as chemoprevention are being developed for treatment and prevention at various stages of carcinogenesis. Sulforaphane, a potential chemopreventive agent, possesses anti-proliferative, anti-inflammatory, anti-oxidant and anti-cancer activities and has attracted extensive interest for better cancer management. METHODS: We evaluated the effect of sulforaphane alone or in combination with gemcitabine on HeLa cells by cell viability assay and confirmed the results by apoptosis assay. Further we analyzed the effect of sulforaphane on the expression of Bcl-2, COX-2 and IL-1β by RT-PCR on HeLa cells. RESULTS: In the present study, sulforaphane was found to induce dose-dependent selective cytotoxicity in HeLa cells in comparison to normal cells pointing to its safe cytotoxicity profile. Additionally, a combination of sulforaphane and gemcitabine was found to increase the growth inhibition in a synergistic manner in HeLa cells compared to the individual drugs. Also, the expression analysis of genes involved in apoptosis and inflammation revealed significant downregulation of Bcl-2, COX-2 and IL-1β upon treatment with sulforaphane. CONCLUSION: Our results suggest that sulforaphane exerts its anticancer activities via apoptosis induction and anti-inflammatory properties and provides the first evidence demonstrating synergism between sulforaphane and gemcitabine which may enhance the therapeutic index of prevention and/or treatment of cervical cancer. Copyright © 2010 Elsevier Ltd. All rights reserved.", "title": "Anti-carcinogenic effects of sulforaphane in association with its apoptosis-inducing and anti-inflammatory properties in human cervical cancer cells." }, { "docid": "MED-4454", "text": "The aim of this study was to determine the bioavailability and kinetics of the supposed anticarcinogen sulforaphane, the hydrolysis product of glucoraphanin, from raw and cooked broccoli. Eight men consumed 200 g of crushed broccoli, raw or cooked, with a warm meal in a randomized, free-living, open cross-over trial. Higher amounts of sulforaphane were found in the blood and urine when broccoli was eaten raw (bioavailability of 37%) versus cooked (3.4%, p ) 0.002). Absorption of sulforaphane was delayed when cooked broccoli was consumed (peak plasma time ) 6 h) versus raw broccoli (1.6 h, p ) 0.001). Excretion half-lives were comparable, 2.6 and 2.4 h on average, for raw and cooked broccoli, respectively (p ) 0.5). This study gives complete kinetic data and shows that consumption of raw broccoli results in faster absorption, higher bioavailability, and higher peak plasma amounts of sulforaphane, compared to cooked broccoli.", "title": "Bioavailability and kinetics of sulforaphane in humans after consumption of cooked versus raw broccoli." }, { "docid": "MED-5363", "text": "OBJECTIVE: Although several studies have reported associations of depressive state with specific nutrients and foods, few studies examined the association with dietary patterns in adults. We investigated the association between major dietary patterns and depressive symptoms in Japanese. METHODS: Subjects were 521 municipal employees (309 men and 212 women), aged 21-67 years, who participated in a health survey at the time of periodic checkup. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale. Dietary patterns were derived by using principal component analysis of the consumption of 52 food and beverage items, which was assessed by a validated brief diet history questionnaire. Logistic regression analysis was used to estimate odds ratios of depressive symptoms (CES-D >or=16) with adjustment for potential confounding variables. RESULTS: We identified three dietary patterns. A healthy Japanese dietary pattern characterized by high intakes of vegetables, fruit, mushrooms and soy products was associated with fewer depressive symptoms. The multivariate-adjusted odds ratios (95% confidence intervals) of having depressive symptoms for the lowest through highest tertiles of the healthy Japanese dietary pattern score were 1.00 (reference), 0.99 (0.62-1.59) and 0.44 (0.25-0.78), respectively (P for trend=0.006). Other dietary patterns were not appreciably associated with depressive symptoms. CONCLUSIONS: Our findings suggest that a healthy Japanese dietary pattern may be related to decreased prevalence of depressive status.", "title": "Dietary patterns and depressive symptoms among Japanese men and women." }, { "docid": "MED-5325", "text": "Objective Previous work studying vegetarians has often found that they have lower blood pressure (BP). Reasons may include their lower BMI and higher intake levels of fruit and vegetables. Here we seek to extend this evidence in a geographically diverse population containing vegans, lacto-ovo vegetarians and omnivores. Design Data are analysed from a calibration sub-study of the Adventist Health Study-2 (AHS-2) cohort who attended clinics and provided validated FFQ. Criteria were established for vegan, lacto-ovo vegetarian, partial vegetarian and omnivorous dietary patterns. Setting Clinics were conducted at churches across the USA and Canada. Dietary data were gathered by mailed questionnaire. Subjects Five hundred white subjects representing the AHS-2 cohort. Results Covariate-adjusted regression analyses demonstrated that the vegan vegetarians had lower systolic and diastolic BP (mmHg) than omnivorous Adventists (β =−6·8, P<0·05 and β = −6·9, P<0·001). Findings for lacto-ovo vegetarians (β = −9·1, P<0·001 and β = −5·8, P<0·001) were similar. The vegetarians (mainly the vegans) were also less likely to be using antihypertensive medications. Defining hypertension as systolic BP > 139 mmHg or diastolic BP > 89 mmHg or use of antihypertensive medications, the odds ratio of hypertension compared with omnivores was 0·37 (95 % CI 0·19, 0·74), 0·57 (95 % CI 0·36, 0·92) and 0·92 (95 % CI 0·50, 1·70), respectively, for vegans, lacto-ovo vegetarians and partial vegetarians. Effects were reduced after adjustment for BMI. Conclusions We conclude from this relatively large study that vegetarians, especially vegans, with otherwise diverse characteristics but stable diets, do have lower systolic and diastolic BP and less hypertension than omnivores. This is only partly due to their lower body mass.", "title": "Vegetarian diets and blood pressure among white subjects: results from the Adventist Health Study-2 (AHS-2)" }, { "docid": "MED-5328", "text": "Aim To evaluate the relationship of diet to incident diabetes among non-Black and Black participants in the Adventist Health Study-2. Methods and Results Participants were 15,200 men and 26,187 women (17.3% Blacks) across the U.S. and Canada who were free of diabetes and who provided demographic, anthropometric, lifestyle and dietary data. Participants were grouped as vegan, lacto ovo vegetarian, pesco vegetarian, semi-vegetarian or non-vegetarian (reference group). A follow-up questionnaire after two years elicited information on the development of diabetes. Cases of diabetes developed in 0.54% of vegans, 1.08% of lacto ovo vegetarians, 1.29% of pesco vegetarians, 0.92% of semi-vegetarians and 2.12% of non-vegetarians. Blacks had an increased risk compared to non-Blacks (odds ratio [OR] 1.364; 95% confidence interval [CI], 1.093–1.702). In multiple logistic regression analysis controlling for age, gender, education, income, television watching, physical activity, sleep, alcohol use, smoking and BMI, vegans (OR 0.381; 95% CI 0.236–0.617), lacto ovo vegetarians (OR 0.618; 95% CI 0.503–0.760) and semi-vegetarians (OR 0.486, 95% CI 0.312–0.755) had a lower risk of diabetes than non-vegetarians. In non-Blacks vegan, lacto ovo and semi-vegetarian diets were protective against diabetes (OR 0.429, 95% CI 0.249–0.740; OR 0.684, 95% CI 0.542–0.862; OR 0.501, 95% CI 0.303–0.827); among Blacks vegan and lacto ovo vegetarian diets were protective (OR 0.304, 95% CI 0.110–0.842; OR 0.472, 95% CI 0.270–0.825). These associations were strengthened when BMI was removed from the analyses. Conclusion Vegetarian diets (vegan, lacto ovo, semi-) were associated with a substantial and independent reduction in diabetes incidence. In Blacks the dimension of the protection associated with vegetarian diets was as great as the excess risk associated with Black ethnicity.", "title": "Vegetarian diets and incidence of diabetes in the Adventist Health Study-2" }, { "docid": "MED-5323", "text": "This study reviewed the literature on the relations between exposure to chemicals with endocrine-disrupting abilities and obesity in humans. The studies generally indicated that exposure to some of the endocrine-disrupting chemicals was associated with an increase in body size in humans. The results depended on the type of chemical, exposure level, timing of exposure and gender. Nearly all the studies investigating dichlorodiphenyldichloroethylene (DDE) found that exposure was associated with an increase in body size, whereas the results of the studies investigating polychlorinated biphenyl (PCB) exposure were depending on dose, timing and gender. Hexachlorobenzene, polybrominated biphenyls, beta-hexachlorocyclohexane, oxychlordane and phthalates were likewise generally associated with an increase in body size. Studies investigating polychlorinated dibenzodioxins and polychlorinated dibenzofurans found either associations with weight gain or an increase in waist circumference, or no association. The one study investigating relations with bisphenol A found no association. Studies investigating prenatal exposure indicated that exposure in utero may cause permanent physiological changes predisposing to later weight gain. The study findings suggest that some endocrine disruptors may play a role for the development of the obesity epidemic, in addition to the more commonly perceived putative contributors. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.", "title": "Endocrine-disrupting chemicals and obesity development in humans: a review." }, { "docid": "MED-5331", "text": "A global health transition is currently underway. The burden of non-communicable diseases (NCDs) is increasing rapidly in the developing world, very much as a result of changes in lifestyles. In addition to changes in tobacco use and physical activity, major changes are taking place in diets, contributing greatly to the growing epidemic of NCD. Thus, a huge global public health challenge is how to influence the trends in diet and nutrition for effective global NCD prevention. The health transition took place rapidly in Finland after World War II and mortality from cardiovascular disease (CVD) was exceptionally high. The North Karelia Project was launched in 1972 as a community-based, and later as a national, programme to influence diet and other lifestyles that are crucial in the prevention of CVD. The intervention had a strong theory base and it employed comprehensive strategies. Broad community organisation and the strong participation of people were the key elements. Evaluation has shown how the diet (particularly fat consumption) has changed and how these changes have led to a major reduction in population serum cholesterol and blood pressure levels. It has also shown how ischaemic heart disease mortality in a working-age population has declined by 73% in North Karelia and by 65% in the whole country from 1971 to 1995. Although Finland is an industrialised country, North Karelia was rural, of rather low socio-economic level and with many social problems in the 1970s and 1980s. The project was based on low-cost intervention activities, where people's participation and community organisations played a key role. Comprehensive interventions in the community were eventually supported by national activities--from expert guidelines and media activities to industry collaboration and policy. Similar principles for nutrition intervention programmes could be used in developing countries, obviously tailored to the local conditions. This paper discusses the experiences of the North Karelia Project in the light of needs from the less-industrialised countries and makes some general recommendations.", "title": "Influencing public nutrition for non-communicable disease prevention: from community intervention to national programme--experiences from Finland." }, { "docid": "MED-5340", "text": "In Asia, vegetarianism is a well-established eating behavior. It appears that the adoption of a vegan diet leads to a lessening of several health risk factors. Although vegetarianism has some notable effects on the hematological system, the effect on the nephrological system has not been well clarified. The pattern of renal function parameters was studied in 25 Thai vegans compared with 25 non-vegetarians. Of the studied parameters, it was found that urine protein was significantly different (p < 0.05) in vegans and controls. Vegans had significantly lower urine protein level.", "title": "Renal function parameters of Thai vegans compared with non-vegans." }, { "docid": "MED-4465", "text": "Adult stem cells of the mammary gland (MaSCs) are a highly dynamic population of cells that are responsible for the generation of the gland during puberty and its expansion during pregnancy. In recent years significant advances have been made in understanding how these cells are regulated during these developmentally important processes both in humans and in mice. Understanding how MaSCs are regulated is becoming a particularly important area of research, given that they may be particularly susceptible targets for transformation in breast cancer. Here, we summarize the identification of MaSCs, how they are regulated and the evidence for their serving as the origins of breast cancer. In particular, we focus on how changes in MaSC populations may explain both the increased risk of developing aggressive ER/PR(−) breast cancer shortly after pregnancy and the long-term decreased risk of developing ER/PR(+) tumors.", "title": "From milk to malignancy: the role of mammary stem cells in development, pregnancy and breast cancer" }, { "docid": "MED-4464", "text": "Over the last decade, the notion that tumors are maintained by their own stem cells, the so-called cancer stem cells, has created great excitement in the research community. This review attempts to summarize the underlying concepts of this notion, to distinguish hard facts from beliefs and to define the future challenges of the field.", "title": "The cancer stem cell: premises, promises and challenges." }, { "docid": "MED-3697", "text": "BACKGROUND: Many studies have analyzed the effect of behavioral risk factors such as common lifestyle patterns on the risk of disease. The aim of this study was to assess the effect of a healthy lifestyle index on the risk of breast cancer. METHODS: A population-based case-control study was conducted in Mexico from 2004 to 2007. One thousand incident cases and 1,074 controls, matched to cases by 5-year age category, region, and health institution, participated in the study. A healthy lifestyle index was developed by means of principal components by using dietary pattern, physical activity, alcohol consumption, and tobacco smoking. A conditional logistic regression model was used to assess this association. RESULTS: The healthy lifestyle index was defined as the combined effect of moderate and/or vigorous-intensity physical activity, low consumption of fat, processed foods, refined cereals, complex sugars, and the avoidance of tobacco smoking and alcohol consumption. Results showed a protective effect on both pre- (OR = 0.50, 95% CI: 0.29-0.84) and postmenopausal women (OR = O.20, 95% CI: 0.11-0.37) when highest versus lowest index quintiles were compared. CONCLUSIONS: Healthy lifestyle was associated with a reduction in the odds of having breast cancer. Primary prevention of this disease should be promoted in an integrated manner. Effective strategies need to be identified to engage women in healthy lifestyles. IMPACT: This study is the first to assess a healthy lifestyle index in relation to the risk of breast cancer. ©2011 AACR.", "title": "Healthy lifestyle on the risk of breast cancer." }, { "docid": "MED-4456", "text": "Broccoli sprouts are widely consumed in many parts of the world. There have been no reported concerns with respect to their tolerance and safety in humans. A formal phase I study of safety, tolerance, and pharmacokinetics appeared justified because these sprouts are being used as vehicles for the delivery of the glucosinolate glucoraphanin and its cognate isothiocyanate sulforaphane [1-isothiocyanato-(4R)-(methylsulfinyl)butane] in clinical trials. Such trials have been designed to evaluate protective efficacy against development of neoplastic and other diseases. A placebo-controlled, double-blind, randomized clinical study of sprout extracts containing either glucosinolates (principally glucoraphanin, the precursor of sulforaphane) or isothiocyanates (principally sulforaphane) was conducted on healthy volunteers who were in-patients on our clinical research unit. The subjects were studied in three cohorts, each comprising three treated individuals and one placebo recipient. Following a 5-day acclimatization period on a crucifer-free diet, the broccoli sprout extracts were administered orally at 8-h intervals for 7 days (21 doses), and the subjects were monitored during this period and for 3 days after the last treatment. Doses were 25 micromol of glucosinolate (cohort A), 100 micromol of glucosinolate (cohort B), or 25 micromol of isothiocyanate (cohort C). The mean cumulative excretion of dithiocarbamates as a fraction of dose was very similar in cohorts A and B (17.8 +/- 8.6% and 19.6 +/- 11.7% of dose, respectively) and very much higher and more consistent in cohort C (70.6 +/- 2.0% of dose). Thirty-two types of hematology or chemistry tests were done before, during, and after the treatment period. Indicators of liver (transaminases) and thyroid [thyroid-stimulating hormone, total triiodothyronine (T3), and free thyroxine (T4)] function were examined in detail. No significant or consistent subjective or objective abnormal events (toxicities) associated with any of the sprout extract ingestions were observed.", "title": "Safety, tolerance, and metabolism of broccoli sprout glucosinolates and isothiocyanates: a clinical phase I study." }, { "docid": "MED-5333", "text": "BACKGROUND/AIM: A vegetarian diet is known to prevent a series of diseases but may influence the balance of carbohydrate and fat metabolism as well as collagen synthesis. This study compares expression patterns of relevant genes in oral mucosa of omnivores and vegetarians. METHODS: Quantitative reverse transcriptase polymerase chain reaction was applied for analysis of mRNA levels from carnitine transporter OCTN2, hepatic CPT1A and nonhepatic CPT1B isoforms of carnitine palmitoyltransferase and collagen (CCOL2A1) in oral mucosa. RESULTS: Compared with volunteers with traditional eating habits, carbohydrate consumption was significantly higher (+22%) in vegetarians. This was associated with a significant stimulation of CPT1A (+50%) and OCTN2 (+10%) and a lowered collagen synthesis (-10%). CONCLUSION: These novel findings provide further insight into the association of a changed fat metabolism and reduced collagen synthesis in vegetarians, which could also play a role in the aging process. Copyright 2008 S. Karger AG, Basel.", "title": "Vegetarian diet affects genes of oxidative metabolism and collagen synthesis." }, { "docid": "MED-5332", "text": "The gastrointestinal microbiota produces short-chain fatty acids, especially butyrate, which affect colonic health, immune function and epigenetic regulation. To assess the effects of nutrition and aging on the production of butyrate, the butyryl-CoA:acetate CoA-transferase gene and population shifts of Clostridium clusters lV and XlVa, the main butyrate producers, were analysed. Faecal samples of young healthy omnivores (24 ± 2.5 years), vegetarians (26 ± 5 years) and elderly (86 ± 8 years) omnivores were evaluated. Diet and lifestyle were assessed in questionnaire-based interviews. The elderly had significantly fewer copies of the butyryl-CoA:acetate CoA-transferase gene than young omnivores (P=0.014), while vegetarians showed the highest number of copies (P=0.048). The thermal denaturation of the butyryl-CoA:acetate CoA-transferase gene variant melting curve related to Roseburia/Eubacterium rectale spp. was significantly more variable in the vegetarians than in the elderly. The Clostridium cluster XIVa was more abundant in vegetarians (P=0.049) and in omnivores (P<0.01) than in the elderly group. Gastrointestinal microbiota of the elderly is characterized by decreased butyrate production capacity, reflecting increased risk of degenerative diseases. These results suggest that the butyryl-CoA:acetate CoA-transferase gene is a valuable marker for gastrointestinal microbiota function. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.", "title": "Quantification of butyryl CoA:acetate CoA-transferase genes reveals different butyrate production capacity in individuals according to diet and age." }, { "docid": "MED-5334", "text": "Until recently, intact protein that is rich in tryptophan was not seen as an alternative to pharmaceutical-grade tryptophan because protein also contains large neutral amino acids (LNAAs) that compete for transport sites across the blood-brain barrier. Recent evidence indicates that when deoiled gourd seed (a rich source of tryptophan with approximately 22 mg/g protein) is combined with glucose (a carbohydrate that reduces serum levels of competing LNAAs) a clinical effect similar to that of pharmaceutical-grade tryptophan is achieved. Objective and subjective measures of anxiety in those suffering from social phobia (also known as social anxiety disorder) were employed to measure changes in anxiety in response to a stimulus as part of a double-blind, placebo-controlled, crossover study with a wash-out period of 1 week between study sessions. Subjects were randomly assigned to start with either (i) protein-source tryptophan (deoiled gourd seed) in combination with carbohydrate or (ii) carbohydrate alone. One week after the initial session, subjects returned for a follow-up session and received the opposite treatment of that received at the first session. All 7 subjects who began the study completed the 2-week protocol. Protein-source tryptophan with carbohydrate, but not carbohydrate alone, resulted in significant improvement on an objective measure of anxiety. Protein-source tryptophan combined with a high glycemic carbohydrate is a potential anxiolytic to those suffering from social phobia.", "title": "Protein-source tryptophan as an efficacious treatment for social anxiety disorder: a pilot study." }, { "docid": "MED-5326", "text": "The effect of meat consumption on cancer risk is a controversial issue. However, recent meta-analyses show that high consumers of cured meats and red meat are at increased risk of colorectal cancer. This increase is significant but modest (20-30%). Current WCRF-AICR recommendations are to eat no more than 500 g per week of red meat, and to avoid processed meat. Moreover, our studies show that beef meat and cured pork meat promote colon carcinogenesis in rats. The major promoter in meat is heme iron, via N-nitrosation or fat peroxidation. Dietary additives can suppress the toxic effects of heme iron. For instance, promotion of colon carcinogenesis in rats by cooked, nitrite-treated and oxidized high-heme cured meat was suppressed by dietary calcium and by α-tocopherol, and a study in volunteers supported these protective effects in humans. These additives, and others still under study, could provide an acceptable way to prevent colorectal cancer. Copyright © 2011 Elsevier B.V. All rights reserved.", "title": "Red meat and colon cancer: should we become vegetarians, or can we make meat safer?" }, { "docid": "MED-3699", "text": "BACKGROUND: In 2007 the World Cancer Research Fund (WCRF) and the American Institute of Cancer Research (AICR) issued 8 recommendations (plus 2 special recommendations) on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence. OBJECTIVE: We aimed to investigate whether concordance with the WCRF/AICR recommendations was related to cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. DESIGN: The present study included 386,355 EPIC participants from 9 European countries. At recruitment, dietary, anthropometric, and lifestyle information was collected. A score was constructed based on the WCRF/AICR recommendations on weight management, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, alcoholic drinks, and breastfeeding for women; the score range was 0-6 for men and 0-7 for women. Higher scores indicated greater concordance with WCRF/AICR recommendations. The association between the score and cancer risk was estimated by using multivariable Cox regression models. RESULTS: Concordance with the score was significantly associated with decreased risk of cancer. A 1-point increment in the score was associated with a risk reduction of 5% (95% CI: 3%, 7%) for total cancer, 12% (95% CI: 9%, 16%) for colorectal cancer, and 16% (95% CI: 9%, 22%) for stomach cancer. Significant associations were also observed for cancers of the breast, endometrium, lung, kidney, upper aerodigestive tract, liver, and esophagus but not for prostate, ovarian, pancreatic, and bladder cancers. CONCLUSION: Adherence to the WCRF/AICR recommendations for cancer prevention may lower the risk of developing most types of cancer.", "title": "Is concordance with World Cancer Research Fund/American Institute for Cancer Research guidelines for cancer prevention related to subsequent risk o..." }, { "docid": "MED-3241", "text": "The diagnosis of cancer can motivate survivors to alter their lifestyle habits. Healthcare providers need to be aware of what changes patients are likely to make in order to derive more pertinent recommendations; however, few studies have reported pre- and post-diagnostic lifestyle behaviours. Semi-quantitative food frequency questionnaires (FFQs) completed approximately 1 year after diagnosis were used to evaluate dietary intake and supplement use before and after diagnosis in a cohort of 1,560 breast cancer patients participating in the UK, prospective DietCompLyf study. Intake of fruit and vegetables, wholegrains and lean sources of protein increased significantly post-diagnosis (P < 0.05, each). Conversely, after diagnosis consumption of high-fat, high-sugar products, red meat, coffee, some alcoholic drinks and refined grains significantly decreased (P < 0.05, each). Post-diagnostic changes in diet were accompanied by changes in the intake of macronutrients and a number of vitamins and minerals. Supplement use was highly prevalent (56.1%) pre-diagnosis, increasing to 62.8% after diagnosis (P = 0.001). Fish oils, multivitamin and minerals, and evening primrose oil were most often used and the proportion of users significantly increased (P < 0.05, each) after diagnosis. The percentage of women using oestrogenic botanical supplements (OBSs) was small but more than doubled to 8.4% after diagnosis (P < 0.05). British women participating in the DietCompLyf study reported significant changes in dietary intake and supplement use after their breast cancer diagnosis. These findings contribute to our understanding of female cancer survivors' dietary behaviours which is crucial for developing and implementing recommendations.", "title": "Significant changes in dietary intake and supplement use after breast cancer diagnosis in a UK multicentre study." }, { "docid": "MED-5338", "text": "Summary Background and objectives Patients with advanced chronic kidney disease (CKD) are in positive phosphorus balance, but phosphorus levels are maintained in the normal range through phosphaturia induced by increases in fibroblast growth factor-23 (FGF23) and parathyroid hormone (PTH). This provides the rationale for recommendations to restrict dietary phosphate intake to 800 mg/d. However, the protein source of the phosphate may also be important. Design, setting, participants, & measurements We conducted a crossover trial in nine patients with a mean estimated GFR of 32 ml/min to directly compare vegetarian and meat diets with equivalent nutrients prepared by clinical research staff. During the last 24 hours of each 7-day diet period, subjects were hospitalized in a research center and urine and blood were frequently monitored. Results The results indicated that 1 week of a vegetarian diet led to lower serum phosphorus levels and decreased FGF23 levels. The inpatient stay demonstrated similar diurnal variation for blood phosphorus, calcium, PTH, and urine fractional excretion of phosphorus but significant differences between the vegetarian and meat diets. Finally, the 24-hour fractional excretion of phosphorus was highly correlated to a 2-hour fasting urine collection for the vegetarian diet but not the meat diet. Conclusions In summary, this study demonstrates that the source of protein has a significant effect on phosphorus homeostasis in patients with CKD. Therefore, dietary counseling of patients with CKD must include information on not only the amount of phosphate but also the source of protein from which the phosphate derives.", "title": "Original Articles: Vegetarian Compared with Meat Dietary Protein Source and Phosphorus Homeostasis in Chronic Kidney Disease" }, { "docid": "MED-5329", "text": "OBJECTIVE: This study was conducted to demonstrate the effectiveness of a strictly vegetarian, very low-fat diet on cardiac risk factor modification. METHODS: Five hundred men and women, participants in an intensive 12-day live-in program, were studied. The program focused on dietary modification, moderate exercise, and stress management at a hospital-based health-center. RESULTS: During this short time period, cardiac risk factors improved: there was an average reduction of total serum cholesterol of 11% (p < 0.001), of blood pressure of 6% (p < 0.001) and a weight loss of 2.5 kg for men and 1 kg for women. Serum triglycerides did not increase except for two subgroups: females age > or = 65 years with serum cholesterol < 6.5 mmol/L and for females 50 to 64 years with baseline serum cholesterol between 5.2-6.5 mmol/L. High-density lipoprotein cholesterol measured on 66 subjects decreased by 19%. CONCLUSION: A strict, very low-fat vegetarian diet free from all animal products combined with lifestyle changes that include exercise and weight loss is an effective way to lower serum cholesterol and blood pressure.", "title": "Rapid reduction of serum cholesterol and blood pressure by a twelve-day, very low fat, strictly vegetarian diet." } ]
[ { "docid": "MED-4450", "text": "Little is known about the effects of diet after breast cancer diagnosis on survival. We prospectively examined the relation between post-diagnosis dietary factors and breast cancer and all-cause survival in women with a history of invasive breast cancer diagnosed between 1987 and 1999 (at ages 20–79 years). Diet after breast cancer diagnosis was measured using a 126-item food frequency questionnaire. Among 4,441 women without a history of breast cancer recurrence prior to completing the questionnaire, 137 subsequently died from breast cancer within 7 years of enrollment. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for intake of macronutrients as well as selected micronutrients and food groups from Cox proportional hazards regression models. After adjustment for factors at diagnosis (age, state of residence, menopausal status, smoking, breast cancer stage, alcohol, history of hormone replacement therapy), interval between diagnosis and diet assessment, and at follow-up (energy intake, breast cancer treatment, body mass index, and physical activity), women in the highest compared to lowest quintile of intake of saturated fat and trans fat had a significantly higher risk of dying from any cause (HR = 1.41, 95% CI = 1.06 to 1.87, P-trend = 0.03) for saturated fat; (HR = 1.78, 95% CI = 1.35 to 2.32, P-trend = 0.01) for trans fat intake. Associations were similar, though did not achieve statistical significance, for breast cancer survival. This study suggests that lower intake of saturated and trans fat in the post-diagnosis diet is associated with improved survival after breast cancer diagnosis.", "title": "Post-diagnosis dietary factors and survival after invasive breast cancer" }, { "docid": "MED-3127", "text": "AIM: Isoflavones in soy foods are part of a larger class of flayonoid compounds that have have been demonstrated to be potent dietary anti-cancer agents, and the effect of soy intake on the survival of ovarian cancer is conflicting. Therefore, we aimed to explore the whether soy intake is related to the risk of death of breast cancer. METHODS: A prospective study was conducted. A total of 256 patients included in this study had breast cancer and were recruited between January 2004 and January 2006. All of them were followed up from since January 2011. A univariate Cox's regression analysis was used to assess the association between soy intake and survival. RESULTS: The education level, menopausal status, ER/PR status and TNM stage were significant difference in the survival of breast cancer. The highest soy isoflavone was associated with a decreased death risk of breast cancer (OR=0.25, 95% CI=0.09-0.54). Moreover, the higher consumption of soy protein also presented a trend decreased breast cancer risk, and the highest consumption significantly reduced the cancer risk compared with the lowest consumption (OR=0.38, 95% CI=0.17-0.86). CONCLUSION: The present study suggests soy intake is associated with a significant reduced death risk of breast cancer in Chinese population. Further large sample studies are warranted to confirm the inverse association of soy consumption and breast cancer survival by menopausal status.", "title": "Study on soy isoflavone consumption and risk of breast cancer and survival." }, { "docid": "MED-4445", "text": "Background: Alcohol intake has consistently been associated with increased breast cancer incidence in epidemiological studies. However, the relation between alcohol and survival after breast cancer diagnosis is less clear. Methods: We investigated whether alcohol intake was associated with survival among 3146 women diagnosed with invasive breast cancer in the Swedish Mammography Cohort. Alcohol consumption was estimated using a food frequency questionnaire. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). Results: From 1987 to 2008 there were 385 breast cancer-specific deaths and 860 total deaths. No significant association was observed between alcohol intake and breast cancer-specific survival. Women who consumed 10 g per day (corresponding to approximately 0.75 to 1 drinks) or more of alcohol had an adjusted HR (95% CI) of breast cancer-specific death of 1.36 (0.82–2.26;ptrend=0.47) compared with non-drinkers. A significant inverse association was observed between alcohol and non-breast cancer deaths. Those who consumed 3.4–9.9 g per day of alcohol had a 33% lower risk of death compared with non-drinkers (95% CI 0.50–0.90;ptrend=0.04). Conclusion: Our findings suggest that alcohol intake up to approximately one small drink per day does not negatively impact breast cancer-specific survival and a half drink per day is associated with a decreased risk of mortality from other causes.", "title": "Alcohol intake and mortality among women with invasive breast cancer" }, { "docid": "MED-3855", "text": "Background: Lignans – oestrogenic substances present in various foods – are associated with postmenopausal breast cancer risk, but not much is known regarding their effects on survival. Methods: In a follow-up study of 2653 postmenopausal breast cancer patients diagnosed between 2001 and 2005, vital status and causes of death were verified through end of 2009. Hazard ratios (HRs) and 95% confidence intervals (CIs) for estimated enterolignans, lignan-rich foods, and dietary fibre in relation to overall survival (OS) and breast cancer-specific survival (BCSS) were assessed using Cox proportional hazards models stratified by age at diagnosis and adjusted for prognostic/confounding factors. Results: Median follow-up time was 6.4 years, and 321 women died, 235 with breast cancer. High estimated enterolactone and enterodiol levels were associated with significantly lower overall mortality (highest quintile, HR=0.60, 95% CI=0.40–0.89, PTrend=0.02 and HR=0.63, 95% CI=0.42–0.95, PTrend=0.02, respectively). Fibre intake was also associated with a significantly lower overall mortality. Differentiated by median fibre intake, associations with estimated enterolignans were still evident at low but not high fibre intake. There was no effect modification by oestrogen receptor status and menopausal hormone therapy. Conclusion: Postmenopausal breast cancer patients with high estimated enterolignans may have a better survival.", "title": "Estimated enterolignans, lignan-rich foods, and fibre in relation to survival after postmenopausal breast cancer" }, { "docid": "MED-3830", "text": "Dietary lignan intakes have been associated with reduced breast cancer risks; however, no previous studies have investigated whether lignan intake might be associated with breast cancer survival. We examined the association of dietary lignan intakes with survival in 1122 women with primary, incident, histologically confirmed breast cancer identified between 1996 and 2001, and with vital status determined through December 31, 2006. Diet in the 12–24 months before diagnosis was assessed with an extensive food frequency questionnaire, and potential confounders assessed from an extensive epidemiologic interview and abstracted clinical data. Lignan intake was calculated using published food composition data. Hazard ratios (HR), and 95% confidence intervals (CIs) for dietary lignan intakes with all cause, and breast cancer mortality were estimated using Cox proportional hazards adjusting for age, education, race, total energy intake, tumor stage, and body mass index. Of the 1122 women with complete dietary data, 160 had died by the end of follow-up. Among postmenopausal women only, those in the highest versus lowest quartile of lignan intakes had a statistically significant reduction in the risk of all cause mortality (HR 0.49, 95% CI 0.26–0.91) and a significantly reduced risk of breast cancer mortality (HR 0.29, 95% CI 0.11–0.76). Higher intakes of dried beans (HR 0.61, 95% CI 0.36–1.03), but not fruits, vegetables, or grains, were also weakly associated with overall mortality. In summary, our results suggest that higher lignan intakes may be associated with improved survival among postmenopausal women with breast cancer.", "title": "Dietary lignan intakes in relation to survival among women with breast cancer: the Western New York Exposures and Breast Cancer (WEB) Study" }, { "docid": "MED-3834", "text": "Dietary lignan intakes have been associated with reduced breast cancer risks; however, no previous studies have investigated whether lignan intake might be associated with breast cancer survival. We examined the association of dietary lignan intakes with survival in 1122 women with primary, incident, histologically confirmed breast cancer identified between 1996 and 2001, and with vital status determined through December 31, 2006. Diet in the 12–24 months before diagnosis was assessed with an extensive food frequency questionnaire, and potential confounders assessed from an extensive epidemiologic interview and abstracted clinical data. Lignan intake was calculated using published food composition data. Hazard ratios (HR), and 95% confidence intervals (CIs) for dietary lignan intakes with all cause, and breast cancer mortality were estimated using Cox proportional hazards adjusting for age, education, race, total energy intake, tumor stage, and body mass index. Of the 1122 women with complete dietary data, 160 had died by the end of follow-up. Among postmenopausal women only, those in the highest versus lowest quartile of lignan intakes had a statistically significant reduction in the risk of all cause mortality (HR 0.49, 95% CI 0.26–0.91) and a significantly reduced risk of breast cancer mortality (HR 0.29, 95% CI 0.11–0.76). Higher intakes of dried beans (HR 0.61, 95% CI 0.36–1.03), but not fruits, vegetables, or grains, were also weakly associated with overall mortality. In summary, our results suggest that higher lignan intakes may be associated with improved survival among postmenopausal women with breast cancer.", "title": "Dietary lignan intakes in relation to survival among women with breast cancer: the Western New York Exposures and Breast Cancer (WEB) Study" }, { "docid": "MED-3832", "text": "Oestrogen is an important determinant of breast cancer risk. Oestrogen-mimicking plant compounds called phytoestrogens can bind to oestrogen receptors and exert weak oestrogenic effects. Despite this activity, epidemiological studies suggest that the incidence of breast cancer is lower in countries where the intake of phytoestrogens is high, implying that these compounds may reduce breast cancer risk, and possibly have an impact on survival. Isoflavones and lignans are the most common phytoestrogens in the diet. In this article, we present findings from human observational and intervention studies related to both isoflavone and lignan exposure and breast cancer risk and survival. In addition, the clinical implications of these findings are examined in the light of a growing dietary supplement market. An increasing number of breast cancer patients seek to take supplements together with their standard treatment in the hope that these will either prevent recurrence or treat their menopausal symptoms. Observational studies suggest a protective effect of isoflavones on breast cancer risk and the case may be similar for increasing lignan consumption although evidence so far is inconsistent. In contrast, short-term intervention studies suggest a possible stimulatory effect on breast tissue raising concerns of possible adverse effects in breast cancer patients. However, owing to the dearth of human studies investigating effects on breast cancer recurrence and survival the role of phytoestrogens remains unclear. So far, not enough clear evidence exists on which to base guidelines for clinical use, although raising patient awareness of the uncertain effect of phytoestrogens is recommended.", "title": "Do phytoestrogens reduce the risk of breast cancer and breast cancer recurrence? What clinicians need to know." }, { "docid": "MED-3698", "text": "Purpose Single-variable analyses have associated physical activity, diet, and obesity with survival after breast cancer. This report investigates interactions among these variables. Patients and Methods A prospective study was performed of 1,490 women diagnosed and treated for early-stage breast cancer between 1991 and 2000. Enrollment was an average of 2 years postdiagnosis. Only seven women were lost to follow-up through December 2005. Results In univariate analysis, reduced mortality was weakly associated with higher vegetable-fruit consumption, increased physical activity, and a body mass index that was neither low weight nor obese. In a multivariate Cox model, only the combination of consuming five or more daily servings of vegetables-fruits, and accumulating 540+ metabolic equivalent tasks-min/wk (equivalent to walking 30 minutes 6 d/wk), was associated with a significant survival advantage (hazard ratio, 0.56; 95% CI, 0.31 to 0.98). The approximate 50% reduction in risk associated with these healthy lifestyle behaviors was observed in both obese and nonobese women, although fewer obese women were physically active with a healthy dietary pattern (16% v 30%). Among those who adhered to this healthy lifestyle, there was no apparent effect of obesity on survival. The effect was stronger in women who had hormone receptor–positive cancers. Conclusion A minority of breast cancer survivors follow a healthy lifestyle that includes both recommended intakes of vegetables-fruits and moderate levels of physical activity. The strong protective effect observed suggests a need for additional investigation of the effect of the combined influence of diet and physical activity on breast cancer survival.", "title": "Greater Survival After Breast Cancer in Physically Active Women With High Vegetable-Fruit Intake Regardless of Obesity" }, { "docid": "MED-10", "text": "Recent studies have suggested that statins, an established drug group in the prevention of cardiovascular mortality, could delay or prevent breast cancer recurrence but the effect on disease-specific mortality remains unclear. We evaluated risk of breast cancer death among statin users in a population-based cohort of breast cancer patients. The study cohort included all newly diagnosed breast cancer patients in Finland during 1995–2003 (31,236 cases), identified from the Finnish Cancer Registry. Information on statin use before and after the diagnosis was obtained from a national prescription database. We used the Cox proportional hazards regression method to estimate mortality among statin users with statin use as time-dependent variable. A total of 4,151 participants had used statins. During the median follow-up of 3.25 years after the diagnosis (range 0.08–9.0 years) 6,011 participants died, of which 3,619 (60.2%) was due to breast cancer. After adjustment for age, tumor characteristics, and treatment selection, both post-diagnostic and pre-diagnostic statin use were associated with lowered risk of breast cancer death (HR 0.46, 95% CI 0.38–0.55 and HR 0.54, 95% CI 0.44–0.67, respectively). The risk decrease by post-diagnostic statin use was likely affected by healthy adherer bias; that is, the greater likelihood of dying cancer patients to discontinue statin use as the association was not clearly dose-dependent and observed already at low-dose/short-term use. The dose- and time-dependence of the survival benefit among pre-diagnostic statin users suggests a possible causal effect that should be evaluated further in a clinical trial testing statins’ effect on survival in breast cancer patients.", "title": "Statin Use and Breast Cancer Survival: A Nationwide Cohort Study from Finland" }, { "docid": "MED-3123", "text": "DietCompLyf is a multi-centre prospective study designed to investigate associations between phytoestrogens - naturally occurring plant compounds with oestrogenic properties - and other diet and lifestyle factors with breast cancer recurrence and survival. 3159 women with grades I-III breast cancer were recruited 9-15 months post-diagnosis from 56 UK hospitals. Detailed information on clinico-pathological, diet, lifestyle and quality of life is collected annually up to 5 years. Biological samples have also been collected as a resource for subsequent evaluation. The characteristics of the patients and associations between pre-diagnosis intake of phytoestrogens (isoflavones and lignans; assessed using the EPIC-Norfolk UK 130 question food frequency questionnaire) and breast cancer (i) risk factors and (ii) prognostic factors are described for 1797 women who had complete data for all covariates and phytoestrogens of interest. Isoflavone intakes were higher in the patients who were younger at diagnosis, in the non-smokers, those who had breast-fed and those who took supplements. Lignan intakes were higher in patients with a higher age at diagnosis, in ex-smokers, those who had breast-fed, who took supplements, had a lower BMI at diagnosis, lower age at menarche and were nulliparous. No significant associations between pre-diagnosis phytoestrogen intake and factors associated with improved breast cancer prognosis were observed. The potential for further exploration of the relationship between phytoestrogens and breast cancer recurrence and survival, and for the establishment of evidence to improve dietary and lifestyle advice offered to patients following breast cancer diagnosis using DietCompLyf data is discussed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.", "title": "The DietCompLyf study: a prospective cohort study of breast cancer survival and phytoestrogen consumption." }, { "docid": "MED-5116", "text": "BACKGROUND: Laboratory research and a growing number of epidemiologic studies have provided evidence for a reduced risk of breast cancer associated with dietary intake of certain classes of flavonoids. However, the effects of flavonoids on survival are not known. In a population-based cohort of breast cancer patients, we investigated whether dietary flavonoid intake before diagnosis is associated with subsequent survival. METHODS: Women ages 25 to 98 years who were newly diagnosed with a first primary invasive breast cancer between August 1, 1996, and July 31, 1997, and participated in a population-based, case-control study (n=1,210) were followed for vital status through December 31, 2002. At the case-control interview conducted shortly after diagnosis, respondents completed a FFQ that assessed dietary intake in the previous 12 months. All-cause mortality (n=173 deaths) and breast cancer-specific mortality (n=113 deaths) were determined through the National Death Index. RESULTS: Reduced hazard ratios [age- and energy-adjusted hazard ratio (95% confidence interval)] for all-cause mortality were observed among premenopausal and postmenopausal women for the highest quintile of intake, compared with the lowest, for flavones [0.63 (0.41-0.96)], isoflavones [0.52 (0.33-0.82)], and anthocyanidins [0.64 (0.42-0.98)]. No significant trends in risk were observed. Results were similar for breast cancer-specific mortality only. CONCLUSION: Mortality may be reduced in association with high levels of dietary flavones and isoflavones among postmenopausal U.S. breast cancer patients. Larger studies are needed to confirm our findings.", "title": "Dietary flavonoid intake and breast cancer survival among women on Long Island." }, { "docid": "MED-2436", "text": "The content of low density lipoprotein (LDL) receptors in tissue from primary breast cancers was determined and its prognostic information compared with that of variables of established prognostic importance. Frozen tumour specimens were selected, and tissue from 72 patients (32 of whom had died) were studied. The LDL receptor content showed an inverse correlation with the survival time. Analysis by a multivariate statistical method showed that the presence of axillary metastasis, content of receptors for oestrogen and LDL, diameter of the tumour, and DNA pattern were all of prognostic value with regard to patient survival. Improved methods of predicting survival time in patients with breast cancer may be of value in the choice of treatment for individual patients.", "title": "Content of low density lipoprotein receptors in breast cancer tissue related to survival of patients." }, { "docid": "MED-2437", "text": "BACKGROUND: Breast cancer is the most commonly diagnosed cancer among women in the United States. Extensive research has been completed to evaluate the relationship between dietary factors and breast cancer risk and survival after breast cancer; however, a summary report with clinical inference is needed. Materials and METHODS: This review summarizes the current epidemiological and clinical trial evidence relating diet to breast cancer incidence, recurrence, survival, and mortality. The review includes emerging epidemiological studies that assess risk within breast cancer subtypes as well as a summary of previous and ongoing dietary intervention trials designed to modify breast cancer risk. RESULTS: The available literature suggests that both low-fat and high-fiber diets may be weakly protective against breast cancer, whereas total energy intake and alcohol appear to be positively associated. Fiber may be weakly protective possibly through modulation of estrogen, whereas fruit and vegetable intake is not clearly associated with risk. Obesity is a risk factor for postmenopausal disease, and adult weight gain should be avoided to reduce risk. In survivors, diet has the greatest potential influence on overall mortality rather than breast cancer-specific events. CONCLUSION: Diet is modestly associated with breast cancer risk; associations appear more pronounced for postmenopausal disease, and healthy choices after diagnosis and treatment likely support longevity more so than reduced risk for recurrent disease.", "title": "Diet and breast cancer: understanding risks and benefits." }, { "docid": "MED-3853", "text": "PURPOSE: Lignans--plant-derived compounds with estrogen-dependent and -independent anticarcinogenic properties--have been associated with postmenopausal breast cancer risk, but data are limited regarding their effect on survival. Dietary lignans are metabolized to enterolignans, which are subsequently absorbed and become bioavailable. PATIENTS AND METHODS: We assessed the prognosis of 1,140 postmenopausal patients with breast cancer age 50 to 74 years who were diagnosed between 2002 and 2005. Vital status through the end of 2009 was ascertained via local population registries, and deaths were verified by death certificates. Information on recurrences and secondary tumors was verified by clinical records and attending physicians. Associations of postdiagnostic serum enterolactone (a biomarker for dietary lignans) with overall survival and distant disease-free survival were assessed by using Cox proportional hazards models stratified by age at diagnosis and adjusted for prognostic factors. RESULTS: Median enterolactone levels for deceased patients and those still alive were 17.0 and 21.4 nmol/L, respectively. During a median of 6.1 years of follow-up after diagnosis, 162 deaths were confirmed. Higher serum enterolactone levels were associated with significantly reduced hazard ratios (HRs) for death (HR per 10 nmol/L increment, 0.94; P = .04; HR for the highest quartile, 0.58; 95% CI, 0.34 to 0.99). For distant disease, HR was 0.94 per 10 nmol/L increment (P = .08) and 0.62 (95% CI, 0.35 to 1.09) for the highest quartile. The highest quartile of serum enterolactone was associated with a significantly reduced risk of death only for estrogen receptor-negative tumors (HR, 0.27; 95% CI, 0.08 to 0.87) but not for estrogen receptor-positive tumors (HR, 0.91; 95% CI, 0.45 to 1.84: P for heterogeneity = .09). CONCLUSION: Postmenopausal patients with breast cancer who have high serum enterolactone levels may have better survival.", "title": "Serum enterolactone and prognosis of postmenopausal breast cancer." }, { "docid": "MED-3142", "text": "AIM: Soy foods are the major source of isoflavones, which are believed to play important roles in genesis of breast cancer and its progression. We here conducted a prospective study to evaluate the association of soy isoflavone food consumption with breast cancer prognosis. METHODS: A prospective study was performed from January 2004 and January 2006 in China. Trained interviewers conducted face-to-face interviews using a structured questionnaire to collect information on dietary habits and potential confounding factors. The relative risk [hazard ratio (HR)] and 95% CI were calculated from the Cox regression model for all significant predictors from cancer diagnosis to the endpoint of the study (event). RESULTS: After a median follow up of 52.1 months (range, 9-60 months), a total of 79 breast cancer related deaths were recorded in our study, risk being inversely associated with a high intake of soy isoflavone. With an average intake of soy isoflavone above 17.3 mg/day, the mortality of breast cancer can be reduced by about 38-36%. We also found the decreased breast cancer death with high soy protein intake, with a HR (95% CI) of 0.71 (0.52-0.98). Stratified analysis with reference to the ER status, further demonstrated a better prognosis of ER positive breast cancer with a high intake of soy isoflavone (HR 0.59, 0.40-0.93). CONCLUSION: Our study shows the soy food intake is associated with longer survival and low recurrence among breast cancer patients. A cohort study with a larger sample size and long term follow-up is now needed.", "title": "Positive effects of soy isoflavone food on survival of breast cancer patients in China." }, { "docid": "MED-2139", "text": "The mammalian target of rapamycin (mTOR) plays a key role in the regulation of cellular metabolism, growth and proliferation. It forms two multi-protein complexes known as complex 1 (mTORC1) and 2 (mTORC2). Raptor and Rictor are the core proteins for mTORC1 and mTORC2, respectively. This study examines the relationship between mTORC1, Rictor and Raptor mRNA expression and human breast cancer. Furthermore, the correlation between mTORC1 and hTERT was investigated. Breast cancer tissues (n=150) and normal tissues (n=31) were analysed using reverse transcription and quantitative PCR. Transcript levels were correlated with clinicopathological data. Higher mTOR expression was noted in breast cancer tissue (P=0.0018), higher grade tumours (grade 2 vs. 3, P=0.047), in ductal tumours (P=0.0014), and was associated with worse overall survival (P=0.01). Rictor expression was significantly higher in background breast tissues compared with tumours and was inversely related to the Nottingham Prognostic Index (NPI1 vs. 2, P=0.03) and tumour grade (grade 1 vs. 3, P=0.01) and was associated with better overall (P=0.037) and disease-free survival (P=0.048). The mRNA expression of Raptor was higher in tumours compared with normal tissues. Furthermore, the expression of Raptor was associated with a higher tumour grade (grade 1 vs. 3, P=0.027). A highly significant positive correlation between mTOR and hTERT (P<0.00001) was observed. These observations are consistent with the role of mTORC1 in the anti-apoptosis pathway and suggest that selective inhibitors of mTORC1 may be more efficacious in human breast cancer. Our findings support the hypothesis that mTORC1 is an important upregulator of telomerase in breast cancer.", "title": "Prognostic and therapeutic implications of mTORC1 and Rictor expression in human breast cancer." }, { "docid": "MED-14", "text": "BACKGROUND: Preclinical studies have shown that statins, particularly simvastatin, can prevent growth in breast cancer cell lines and animal models. We investigated whether statins used after breast cancer diagnosis reduced the risk of breast cancer-specific, or all-cause, mortality in a large cohort of breast cancer patients. METHODS: A cohort of 17,880 breast cancer patients, newly diagnosed between 1998 and 2009, was identified from English cancer registries (from the National Cancer Data Repository). This cohort was linked to the UK Clinical Practice Research Datalink, providing prescription records, and to the Office of National Statistics mortality data (up to 2013), identifying 3694 deaths, including 1469 deaths attributable to breast cancer. Unadjusted and adjusted hazard ratios (HRs) for breast cancer-specific, and all-cause, mortality in statin users after breast cancer diagnosis were calculated using time-dependent Cox regression models. Sensitivity analyses were conducted using multiple imputation methods, propensity score methods and a case-control approach. RESULTS: There was some evidence that statin use after a diagnosis of breast cancer had reduced mortality due to breast cancer and all causes (fully adjusted HR = 0.84 [95% confidence interval = 0.68-1.04] and 0.84 [0.72-0.97], respectively). These associations were more marked for simvastatin 0.79 (0.63-1.00) and 0.81 (0.70-0.95), respectively. CONCLUSIONS: In this large population-based breast cancer cohort, there was some evidence of reduced mortality in statin users after breast cancer diagnosis. However, these associations were weak in magnitude and were attenuated in some sensitivity analyses.", "title": "Statin use after diagnosis of breast cancer and survival: a population-based cohort study." }, { "docid": "MED-4096", "text": "A variety of statistics are used to quantify the burden (occurrence and outcome) of cancer generally and of breast cancer specifically. When undertaking any cancer control program, understanding these statistics, their source, and their quality is important for assessing the current situation, allocating resources to different control strategies, and evaluating progress. Two core statistics are the cancer incidence rate and the cancer mortality rate, which provide estimates of the average risk of acquiring and of dying from the disease, respectively. About 16% of the world's population is covered by registration systems that produce cancer incidence statistics, while mortality data are available for about 29%. Breast cancer incidence and mortality vary considerably by world region. In general, the incidence is high (greater than 80 per 100,000) in developed regions of the world and low (less than 30 per 100,000), though increasing, in developing regions; the range of mortality rates is much less (approximately 6-23 per 100,000) because of the more favorable survival of breast cancer in (high-incidence) developed regions. The incidence of breast cancer is increasing almost everywhere. This unfavorable trend is due in part to increases in risk factors (decreased childbearing and breast-feeding, increased exogenous hormone exposure, and detrimental dietary and lifestyle changes, including obesity and less physical activity). On the other hand, mortality is now decreasing in many high-risk countries due to a combination of intensified early detection efforts and the introduction of mammographic screening, resulting in the diagnosis of more small, early stage tumors, and advances in treatment.", "title": "Use of statistics to assess the global burden of breast cancer." }, { "docid": "MED-3139", "text": "Background: Soy isoflavones have antiestrogenic and anticancer properties but also possess estrogen-like properties, which has raised concern about soy food consumption among breast cancer survivors. Objective: We prospectively evaluated the association between postdiagnosis soy food consumption and breast cancer outcomes among US and Chinese women by using data from the After Breast Cancer Pooling Project. Design: The analysis included 9514 breast cancer survivors with a diagnosis of invasive breast cancer between 1991 and 2006 from 2 US cohorts and 1 Chinese cohort. Soy isoflavone intake (mg/d) was measured with validated food-frequency questionnaires. HRs and 95% CIs were estimated by using delayed-entry Cox regression models, adjusted for sociodemographic, clinical, and lifestyle factors. Results: After a mean follow-up of 7.4 y, we identified 1171 total deaths (881 from breast cancer) and 1348 recurrences. Despite large differences in soy isoflavone intake by country, isoflavone consumption was inversely associated with recurrence among both US and Chinese women, regardless of whether data were analyzed separately by country or combined. No heterogeneity was observed. In the pooled analysis, consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of all-cause (HR: 0.87; 95% CI: 0.70, 1.10) and breast cancer–specific (HR: 0.83; 95% CI: 0.64, 1.07) mortality and a statistically significant reduced risk of recurrence (HR: 0.75; 95% CI: 0.61, 0.92). Conclusion: In this large study of combined data on US and Chinese women, postdiagnosis soy food consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of breast cancer–specific mortality and a statistically significant reduced risk of recurrence. One of the studies included in the After Breast Cancer Pooling Project, the Women's Healthy Eating & Living Study, was registered at clinicaltrials.gov as NCT00003787.", "title": "Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women" }, { "docid": "MED-2426", "text": "Acrylamide is a probable human carcinogen, with industrial contact, tobacco smoking and foods processed at high temperatures as the main routes of exposure. In animal studies oral intake of acrylamide has been related to cancer development, with indications that the increased cancer occurrence especially regards endocrine related tumors. In human epidemiological studies, dietary exposure to acrylamide has also been suggested related to higher risk of endocrine related tumors, like estrogen sensitive breast cancer. The aim of the present study was to evaluate if pre-diagnostic acrylamide exposure, measured by acrylamide and glycidamide hemoglobin adducts (AA-Hb and GA-Hb), were associated to mortality in breast cancer cases. Among 24,697 postmenopausal women included into a Danish cohort between 1993 and 1997, 420 developed breast cancer before 2001 and 110 died before 2009. AA-Hb and GA-Hb concentrations measured in blood samples were related to mortality by Cox proportional hazard models. Estimates are given per 25 pmol/g globin higher levels. Among non-smokers, higher concentrations of GA-Hb were associated to a higher hazard rate of breast cancer specific mortality (HR (95% CI): 1.63 (1.06-2.51)), the hazard rate among women diagnosed with estrogen receptor positive tumors was (HR (95% CI): 2.23 (1.38-3.61)). For AA-Hb the tendency was similar, but only statistically significant among those with estrogen receptor positive tumors (HR (95% CI): 1.31 (1.02-1.69)). In conclusion, the present study indicates that pre-diagnostic exposure to acrylamide may be related to mortality among breast cancer patients and that this may especially concern the most endocrine related type of breast cancer. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.", "title": "Pre-diagnostic acrylamide exposure and survival after breast cancer among postmenopausal Danish women." }, { "docid": "MED-5195", "text": "We performed a survival analysis to assess the effect of meat consumption and meat type on the risk of breast cancer in the UK Women's Cohort Study. Between 1995 and 1998 a cohort of 35 372 women was recruited, aged between 35 and 69 years with a wide range of dietary intakes, assessed by a 217-item food frequency questionnaire. Hazard ratios (HRs) were estimated using Cox regression adjusted for known confounders. High consumption of total meat compared with none was associated with premenopausal breast cancer, HR=1.20 (95% CI: 0.86–1.68), and high non-processed meat intake compared with none, HR=1.20 (95% CI: 0.86–1.68). Larger effect sizes were found in postmenopausal women for all meat types, with significant associations with total, processed and red meat consumption. Processed meat showed the strongest HR=1.64 (95% CI: 1.14–2.37) for high consumption compared with none. Women, both pre- and postmenopausal, who consumed the most meat had the highest risk of breast cancer.", "title": "Meat consumption and risk of breast cancer in the UK Women's Cohort Study" }, { "docid": "MED-5066", "text": "Context Evidence is lacking that a dietary pattern high in vegetables, fruit, and fiber and low in total fat can influence breast cancer recurrence or survival. Objective To assess whether a major increase in vegetable, fruit, and fiber intake and a decrease in dietary fat intake reduces the risk of recurrent and new primary breast cancer and all-cause mortality among women with previously treated early stage breast cancer. Design, Setting, and Participants Multi-institutional randomized controlled trial of dietary change in 3088 women previously treated for early stage breast cancer who were 18 to 70 years old at diagnosis. Women were enrolled between 1995 and 2000 and followed up through June 1, 2006. Intervention The intervention group (n=1537) was randomly assigned to receive a telephone counseling program supplemented with cooking classes and newsletters that promoted daily targets of 5 vegetable servings plus 16 oz of vegetable juice; 3 fruit servings; 30 g of fiber; and 15% to 20% of energy intake from fat. The comparison group (n=1551) was provided with print materials describing the \"5-A-Day\" dietary guidelines. Main Outcome Measures Invasive breast cancer event (recurrence or new primary) or death from any cause. Results From comparable dietary patterns at baseline, a conservative imputation analysis showed that the intervention group achieved and maintained the following statistically significant differences vs the comparison group through 4 years: servings of vegetables, +65%; fruit, +25%; fiber, +30%, and energy intake from fat, −13%. Plasma carotenoid concentrations validated changes in fruit and vegetable intake. Throughout the study, women in both groups received similar clinical care. Over the mean 7.3-year follow-up, 256 women in the intervention group (16.7%) vs 262 in the comparison group (16.9%) experienced an invasive breast cancer event (adjusted hazard ratio, 0.96; 95% confidence interval, 0.80–1.14; P=.63), and 155 intervention group women (10.1%) vs 160 comparison group women (10.3%) died (adjusted hazard ratio, 0.91; 95% confidence interval, 0.72–1.15; P=.43). No significant interactions were observed between diet group and baseline demographics, characteristics of the original tumor, baseline dietary pattern, or breast cancer treatment. Conclusion Among survivors of early stage breast cancer, adoption of a diet that was very high in vegetables, fruit, and fiber and low in fat did not reduce additional breast cancer events or mortality during a 7.3-year follow-up period. Trial Registration clinicaltrials.gov Identifier: NCT00003787", "title": "Influence of a Diet Very High in Vegetables, Fruit, and Fiber and Low in Fat on Prognosis Following Treatment for Breast Cancer" }, { "docid": "MED-5001", "text": "We examine the possible evidence that the phytochemical curcumin may overcome resistance to hormonal and cytotoxic agents in breast cancer. We present our observations on MCF-7R, a multidrug-resistant (MDR) variant of the MCF-7 breast cancer cell line. In contrast to MCF-7, MCF-7R lacks aromatase and estrogen receptor alpha (ERalpha) and overexpresses the multidrug transporter ABCB1 and the products of different genes implicated in cell proliferation and survival, like c-IAP-1, NAIP, survivin, and COX-2. Nevertheless, in cytotoxicity and cell death induction assays, we found that the antitumor activity of curcumin is substantial both in MCF-7 and in MCF-7R. We elaborated the diketone system of curcumin into different analogues; the benzyloxime and the isoxazole and pyrazole heterocycles showed remarkable increases in the antitumor potency both in the parental and in the MDR MCF-7 cells. Furthermore, curcumin or, more potently, the isoxazole analogue, produced early reductions in the amounts of relevant gene transcripts that were diverse (i.e., they were relative to Bcl-2 and Bcl-X(L) in MCF-7 and the inhibitory of apoptosis proteins and COX-2 in MCF-7R) in the two cell lines. Thus, the two compounds exhibited the remarkable property of being able to modify their molecular activities according to the distinct characteristics of the parental and MDR cells. We discuss also how curcumin may (1) exert antitumor effects in breast cancer through ER-dependent and ER-independent mechanisms; and (2) act as a drug transporter-mediated MDR reversal agent. Overall, the structure of curcumin may represent the basis for the development of new, effective anticancer agents in hormone-independent MDR breast cancer.", "title": "Curcumin as a possible lead compound against hormone-independent, multidrug-resistant breast cancer." }, { "docid": "MED-4690", "text": "Physiological and pharmacological blood concentrations of melatonin inhibit tumorigenesis in a variety of in vivo and in vitro experimental models of neoplasia. Evidence indicates that melatonin's anticancer effects are exerted via inhibition of cell proliferation and a stimulation of differentiation and apoptosis. A new mechanism by which physiological and pharmacological blood levels of melatonin inhibit cancer growth in vivois via a melatonin-induced suppression of tumor linoleic acid (LA) uptake and its metabolism to the important mitogenic signaling molecule 13-hydroxyoctadecadienoic acid (13-HODE). Melatonin suppresses cAMP formation and inhibits tumor uptake of LA and its metabolism to 13-HODE via a melatonin receptor-mediated mechanism in both tissue-isolated rat hepatoma 7288 CTC and human breast cancer xenografts. It has been postulated that in industrialized societies, light at night, by suppressing melatonin production, poses a new risk for the development of breast cancer and, perhaps, other cancers as well. In support of this hypothesis, light during darkness suppresses nocturnal melatonin production and stimulates the LA metabolism and growth of rat hepatoma and human breast cancer xenografts. Nocturnal dietary supplementation with melatonin, at levels contained in a melatonin-rich diet, inhibits rat hepatoma growth via the mechanisms described above. The nocturnal melatonin signal organizes tumor metabolism and growth within circadian time structure that can be further reinforced by appropriately timed melatonin supplementation. Dietary melatonin supplementation working in concert with the endogenous melatonin signal has the potential to be a new preventive/therapeutic strategy to optimize the host/cancer balance in favor of host survival and quality of life.", "title": "Putting cancer to sleep at night: the neuroendocrine/circadian melatonin signal." }, { "docid": "MED-1720", "text": "BACKGROUND: Insulin-like growth factor (IGF)-I and its main binding protein, IGFBP-3, modulate cell growth and survival, and are thought to be important in tumour development. Circulating concentrations of IGF-I might be associated with an increased risk of cancer, whereas IGFBP-3 concentrations could be associated with a decreased cancer risk. METHODS: We did a systematic review and meta-regression analysis of case-control studies, including studies nested in cohorts, of the association between concentrations of IGF-I and IGFBP-3 and prostate, colorectal, premenopausal and postmenopausal breast, and lung cancer. Study-specific dose-response slopes were obtained by relating the natural log of odds ratios for different exposure levels to blood concentrations normalised to a percentile scale. FINDINGS: We identified 21 eligible studies (26 datasets), which included 3609 cases and 7137 controls. High concentrations of IGF-I were associated with an increased risk of prostate cancer (odds ratio comparing 75th with 25th percentile 1.49, 95% CI 1.14-1.95) and premenopausal breast cancer (1.65, 1.26-2.08) and high concentrations of IGFBP-3 were associated with increased risk of premenopausal breast cancer (1.51, 1.01-2.27). Associations were larger in assessments of plasma samples than in serum samples, and in standard case-control studies compared with nested studies. INTERPRETATION: Circulating concentrations of IGF-I and IGFBP-3 are associated with an increased risk of common cancers, but associations are modest and vary between sites. Although laboratory methods need to be standardised, these epidemiological observations could have major implications for assessment of risk and prevention of cancer.", "title": "Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis." }, { "docid": "MED-4089", "text": "Studies have shown an inverse relationship between the consumption of apples and the risk of several cancers. The peels of apple, which have been shown to possess exceptionally high concentrations of antioxidants, are often discarded. In this study, we evaluated the antiproliferative effects of apple peel extract (APE) in variety of cancer cell types. Our data demonstrated that APE, obtained from organic Gala apples, imparted significant reduction in the viability of a variety of cancer cell lines. Further, our data showed a significant decrease in growth and clonogenic survival of human prostate carcinoma CWR22Rnu1 and DU145 cells and breast carcinoma Mcf-7 and Mcf-7:Her18 cells. Also, the antiproliferative effects of APE were found to be accompanied by a G0-G1 phase arrest of prostate and breast cancer cells. Furthermore, APE treatment resulted in a marked concentration-dependent decrease in the protein levels of proliferative cell nuclear antigen, a marker for proliferation. In addition, APE treatment resulted in a marked increase in maspin, a tumor suppressor protein that negatively regulates cell invasion, metastasis, and angiogenesis. Our data suggested that APE possesses strong antiproliferative effects against cancer cells, and apple peels should not be discarded from the diet. Detailed mechanistic studies, especially in appropriate in vivo animal models, are needed to further examine the antiproliferative and preventive effects of APE against cancer.", "title": "Antiproliferative effects of apple peel extract against cancer cells." }, { "docid": "MED-5052", "text": "OBJECTIVE: Habitual green tea consumption has long been associated with health benefits including chemoprevention and cardiovascular protection. This non-systematic literature review presents the clinical evidence to date. METHOD: A literature review of peer-reviewed articles on observational and interventional studies was conducted to include green tea, its extract or its purified polyphenol (-)-epigallocatechin-3-gallate (EGCG). Electronic databases searched included PubMed (1966-2009) and the Cochrane Library (Issue 4, 2008). RESULTS: Observational studies are inconclusive on the benefits of habitual consumption of green tea in the prevention of most cancers. However, there are trends towards prevention in breast and prostate cancers. Interventional studies have demonstrated reduction in relapses following surgical resection in colorectal adenomas and increased survival rates in epithelial ovarian cancer. Observational studies indicate that green tea may provide protection against hypertension and reduce the risk for stroke, and interventional studies are providing biochemical and physiological evidence. CONCLUSION: Although the overall clinical evidence is inconclusive, habitual green tea consumption may be providing some level of chemoprevention in prostate and breast cancer. Green tea may also attenuate the risk factors association with the development of atherosclerosis thus reducing the incidence of cardiovascular events and stoke.", "title": "Can green tea do that? A literature review of the clinical evidence." }, { "docid": "MED-2427", "text": "Lipid rafts/caveolae are membrane platforms for signaling molecules that regulate various cellular functions, including cell survival. To better understand the role of rafts in tumor progression and therapeutics, we investigated the effect of raft disruption on cell viability and compared raft levels in human cancer cell lines versus their normal counterparts. Here, we report that cholesterol depletion using methyl-β cyclodextrin caused anoikis-like apoptosis, which in A431 cells involved decreased raft levels, Bcl-xL down-regulation, caspase-3 activation, and Akt inactivation regardless of epidermal growth factor receptor activation. Cholesterol repletion replenished rafts on the cell surface and restored Akt activation and cell viability. Moreover, the breast cancer and the prostate cancer cell lines contained more lipid rafts and were more sensitive to cholesterol depletion-induced cell death than their normal counterparts. These results indicate that cancer cells contain increased levels of rafts and suggest a potential use of raft-modulating agents as anti-cancer drugs.", "title": "Elevated Levels of Cholesterol-Rich Lipid Rafts in Cancer Cells Are Correlated with Apoptosis Sensitivity Induced by Cholesterol-Depleting Agents" }, { "docid": "MED-2824", "text": "Cancer is primarily a disease of old age, and that life style plays a major role in the development of most cancers is now well recognized. While plant-based formulations have been used to treat cancer for centuries, current treatments usually involve poisonous mustard gas, chemotherapy, radiation, and targeted therapies. While traditional plant-derived medicines are safe, what are the active principles in them and how do they mediate their effects against cancer is perhaps best illustrated by curcumin, a derivative of turmeric used for centuries to treat a wide variety of inflammatory conditions. Curcumin is a diferuloylmethane derived from the Indian spice, turmeric (popularly called \"curry powder\") that has been shown to interfere with multiple cell signaling pathways, including cell cycle (cyclin D1 and cyclin E), apoptosis (activation of caspases and down-regulation of antiapoptotic gene products), proliferation (HER-2, EGFR, and AP-1), survival (PI3K/AKT pathway), invasion (MMP-9 and adhesion molecules), angiogenesis (VEGF), metastasis (CXCR-4) and inflammation (NF-kappaB, TNF, IL-6, IL-1, COX-2, and 5-LOX). The activity of curcumin reported against leukemia and lymphoma, gastrointestinal cancers, genitourinary cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers, and sarcoma reflects its ability to affect multiple targets. Thus an \"old-age\" disease such as cancer requires an \"age-old\" treatment.", "title": "Curcumin and cancer: an \"old-age\" disease with an \"age-old\" solution." }, { "docid": "MED-1820", "text": "Background This study aims to comprehensively summarize the currently available evidences on the efficacy and safety of gemcitabine plus erlotinib for treating advanced pancreatic cancer. Methodology/Principal Findings PubMed, EMBASE, The Cochrane Library and abstracts of recent major conferences were systematically searched to identify relevant publications. Studies that were conducted in advanced pancreatic cancer patients treated with gemcitabine plus erlotinib (with or without comparison with gemcitabine alone) and reporting objective response rate, disease control rate, progression-free survival, time-to-progression, overall survival, 1-year survival rate and/or adverse events were included. Data on objective response rate, disease control rate, 1-year survival rate and adverse events rate, respectively, were combined mainly by using Meta-Analyst software with a random-effects model. Data on progression-free survival, time-to-progression and overall survival were summarized descriptively. Sixteen studies containing 1,308 advanced pancreatic cancer patients treated with gemcitabine plus erlotinib were included. The reported median progression-free survival (or time-to-progression), median overall survival, 1-year survival rates, objective response rates and disease control rates were 2–9.6 months, 5–12.5 months, 20%–51%, 0%–28.6% and 25.0%–83.3%, respectively. The weighted 1-year survival rate, objective response rate and disease control rate based on studies reporting robust results were 27.9%, 9.1% and 57.0%, respectively. According to the studies with relevant data, the incidences of total and severe adverse events were 96.3% and 62.9%, respectively. The most frequently reported adverse events were leucopenia, rash, diarrhea, vomitting, neutropenia, thrombocytopenia, anaemia, stomatitis, drug-induced liver injury, fatigue and fever. Compared with gemcitabine alone, the progression-free survival and overall survival with gemcitabine plus erlotinib were significantly longer, but there were also more deaths and interstitial lung disease-like syndrome related to this treatment. Conclusions/Significance Gemcitabine plus erlotinib represent a new option for the treatment of advanced pancreatic cancer, with mild but clinically meaningful additive efficacy compared with gemcitabine alone. Its safety profile is generally acceptable, although careful management is needed for some specific adverse events.", "title": "Gemcitabine Plus Erlotinib for Advanced Pancreatic Cancer: A Systematic Review with Meta-Analysis" } ]
225573
The 84th Academy Awards winners included The Help and The Shore.
[ { "docid": "84th_Academy_Awards", "text": "The 84th Academy Awards ceremony , presented by the Academy of Motion Picture Arts and Sciences ( AMPAS ) , honored the best films of 2011 in the United States and took place on February 26 , 2012 , at the Hollywood and Highland Center Theatre in Hollywood , Los Angeles beginning at 5:30 p.m. PST / 8:30 p.m. EST. . During the ceremony , the Academy of Motion Picture Arts and Sciences presented Academy Awards ( commonly referred to as Oscars ) in 24 categories . The ceremony was televised in the United States by ABC , and produced by Brian Grazer and Don Mischer , with Mischer also serving as director . Actor Billy Crystal hosted the show for the ninth time . He first presided over the 62nd ceremony held in 1990 and had last hosted the 76th ceremony held in 2004 . On June 14 , 2011 , Academy president Tom Sherak announced at a press conference that , in an attempt to further revitalize interest surrounding the awards , the 2012 ceremony would feature between five and ten Best Picture nominees depending on voting results , as opposed to a set number of nominees . In related events , the Academy held its third annual Governors Awards ceremony at the Grand Ballroom of the Hollywood and Highland Center on November 12 , 2011 . On February 11 , 2012 , in a ceremony at the Beverly Wilshire Hotel in Beverly Hills , California , the Academy Awards for Technical Achievement were presented by host Milla Jovovich . The Artist won five awards , including Best Actor for Jean Dujardin , Best Director for Michel Hazanavicius , and Best Picture , the first silent feature to win an Academy Award for Best Picture since 1927 's Wings , the inaugural winner in 1929 . Other winners included Hugo also with five awards , The Iron Lady with two awards , and Beginners , The Descendants , The Fantastic Flying Books of Mr. Morris Lessmore , The Girl with the Dragon Tattoo , The Help , Midnight in Paris , The Muppets , Rango , Saving Face , A Separation , The Shore , and Undefeated with one . The telecast garnered more than 39 million viewers in the United States .", "title": "" } ]
[ { "docid": "List_of_submissions_to_the_84th_Academy_Awards_for_Best_Foreign_Language_Film", "text": "This is a list of submissions to the 84th Academy Awards for Best Foreign Language Film . The Academy of Motion Picture Arts and Sciences ( AMPAS ) has invited the film industries of various countries to submit their best film for the Academy Award for Best Foreign Language Film every year since the award was created in 1956 . The award is presented annually by the Academy to a feature-length motion picture produced outside the United States that contains primarily non-English dialogue . The Foreign Language Film Award Committee oversees the process and reviews all the submitted films . Nine shortlisted contenders will be revealed a week before the announcement of the Oscar nominations . The deadline for all countries to send in their submissions was 3 October 2011 . The submitted motion pictures must be first released theatrically in their respective countries between 1 October 2010 and 30 September 2011 . On 13 October , AMPAS announced that 63 countries had been accepted to participate in the competition for the 2012 Best Foreign Language Film Oscar , including a first-time submission from New Zealand . On 18 January 2012 the nine shortlisted entries were announced . Six days later , the five nominees were announced . The Iranian entry , A Separation , was announced as the winner at the 84th Academy Awards on 26 February 2012 .", "title": "" }, { "docid": "List_of_Canadian_submissions_for_the_Academy_Award_for_Best_Foreign_Language_Film", "text": "Canada has submitted films for the Academy Award for Best Foreign Language Film since 1971 . The award is handed out annually by the United States Academy of Motion Picture Arts and Sciences to a feature-length motion picture produced outside the United States that contains primarily non-English dialogue . It was not created until the 1956 Academy Awards , in which a competitive Academy Award of Merit , known as the Best Foreign Language Film Award , was created for non-English speaking films , and has been given annually since . As of 2016 , seven Canadian films have been nominated , including one winner , for the Academy Award for Best Foreign Language Film . Of these films , three have been directed by Denys Arcand : Jesus of Montreal , nominated at the 62nd Academy Awards ; The Decline of the American Empire , nominated at the 59th Academy Awards ; and its sequel , The Barbarian Invasions , which was the winner at the 76th Academy Awards . Arcand 's Days of Darkness was shortlisted for the Oscar , but was not nominated . The other four Canadian directors to have their films nominated are Deepa Mehta for Water at the 79th Academy Awards , Denis Villeneuve for Incendies at the 83rd Academy Awards , Philippe Falardeau for Monsieur Lazhar at the 84th Academy Awards , and Kim Nguyen for War Witch at the 85th Academy Awards . Of the 42 films selected to date as Canada 's submission to the Academy Awards , 18 of them have also won the Academy of Canadian Cinema and Television Award for Best Motion Picture .", "title": "" }, { "docid": "Maggie_Cronin", "text": "Maggie Cronin is an Irish actress and playwright . The Short film The Shore directed by Terry George , in which she appears with Ciarán Hinds , Conleth Hill and Kerry Condon , won the Academy award in the Short Film , Live Action category at 84th Academy Awards in February 2012 . She appeared in Doctors ( BBC1 TV ) from 2000 -2004 playing the role of Kate McGuire for over 600 episodes . In 2006 she briefly returned when Christopher Timothy 's character Brendan `` Mac '' McGuire left the series In 2016 she appeared as Ellen Quinn in My Mother And Other Strangers and also in The Frankenstein Chronicles ITV Encore .", "title": "" }, { "docid": "2012_Academy_Awards", "text": "2012 Academy Awards may refer to : 84th Academy Awards , the Academy Awards ceremony which took place in 2012 85th Academy Awards , the Academy Awards ceremony which took place in February 2013 honoring the best in film for 2012", "title": "" }, { "docid": "2011_Academy_Awards", "text": "2011 Academy Awards may refer to : 83rd Academy Awards , the Academy Awards ceremony which took place in 2011 honouring the best in film for 2010 84th Academy Awards , the Academy Awards ceremony which took place in 2012 honouring the best in film for 2011", "title": "" }, { "docid": "Black_Reel_Award_for_Best_Actress", "text": "This page lists the winners and nominees for the Black Reel Award for Best Actress in a Motion Picture . Quvenzhane Wallis is currently the youngest winner in this category . Academy Award-nominated or winning performances also honored with nominations or wins at the Black Reel Awards include Quvenzhane Wallis ( Beasts of the Southern Wild ) , Viola Davis ( The Help ) , Gabourey Sidibe ( Precious ) , Sophie Okonedo ( Hotel Rwanda ) and Halle Berry ( Monster 's Ball ) .", "title": "" }, { "docid": "Black_Reel_Award_for_Outstanding_Actress", "text": "This page lists the winners and nominees for the Black Reel Award for Outstanding Actress in a Motion Picture . Quvenzhane Wallis is currently the youngest winner in this category . Academy Award-nominated or winning performances also honored with nominations or wins at the Black Reel Awards include Quvenzhane Wallis ( Beasts of the Southern Wild ) , Viola Davis ( The Help ) , Gabourey Sidibe ( Precious ) , Sophie Okonedo ( Hotel Rwanda ) and Halle Berry ( Monster 's Ball ) .", "title": "" }, { "docid": "List_of_posthumous_Academy_Award_winners_and_nominees", "text": "This is a list of posthumous Academy Award winners and nominees . The Academy of Motion Picture Arts and Sciences annually presents Academy Awards in both competitive and honorary categories . This list includes posthumous winners and nominees of the Academy 's competitive awards , as well as posthumous winners of its honorary awards . This list is current as of the 86th Academy Awards ceremony held on March 2 , 2014 .", "title": "" }, { "docid": "Kohl_McCormick_Early_Childhood_Teaching_Awards", "text": "The Kohl McCormick Early Childhood Teaching Awards honors five outstanding Chicago area early childhood educators each year . The selection process begins each fall with an open call for nominees . Each nominee must be a full-time Chicago early childhood teacher with at least five years experience with students eight years old or younger . They may work in preschools , home day care centers , childcare centers , Head Start programs , State Prekindergartens , and kindergarten through third-grade classrooms in public , private , and parochial schools . The awards have been restricted to teachers in Cook County in Illinois , but beginning in 2008 , the honor will be extended to DuPage County as well . A committee of leaders in the field of early childhood education reviews all nominees and then conducts site visits to a select group of the nominees . From their observations , the committee members select a group of finalists . Five of those finalists are then chosen to represent the best of the field , following a final application process that includes additional site visits and interviews by fellows from the Kohl McCormick Academy of Outstanding Educators . The five award winners are honored at a June luncheon ceremony . Each winner receives : A $ 5,000 cash prize ; A $ 1,000 cash prize for his or her school or center ; A visit and workshop from the Kohl McCormick StoryBus providing hands-on learning for early literacy ; A field trip and workshop at the Kohl Children 's Museum ; A graduate-level course at Chicago 's renowned Erikson Institute ; Induction into the Kohl McCormick Academy of Outstanding Educators . The awards program seeks to raise public awareness of the importance of quality early childhood education and to raise the self-esteem of early childhood educators . As a result , the program also hopes to encourage better funding for early childhood education ; encourage qualified candidates to enter the field ; help in the retention of highly qualified teachers ; and help parents to support their children 's learning . Begun in 1996 , the awards are a joint project of the Dolores Kohl Education Foundation and the McCormick Tribune Foundation . All winners are admitted into membership in the Kohl McCormick Academy of Outstanding Educators . The academy also includes recipients of the Kohl International Teaching Awards , which were given from 1985 to 1994 .", "title": "" }, { "docid": "List_of_African_Academy_Award_winners_and_nominees", "text": "This is a list of African Academy Award winners and nominees , including Academy Award winners and nominees who are from Africa by birth or citizenship .", "title": "" }, { "docid": "Lists_of_Hispanic_Academy_Award_winners_and_nominees_by_country", "text": "These are the lists of Hispanic Academy Award winners and nominees by country ( except for the United States ) . Each list details the performances of Hispanic filmmakers , actors , actresses and films that have either been submitted , nominated or have won an Academy Award . These lists are current as of the 85th Academy Awards ceremony held on February 24 , 2013 . List of Argentine Academy Award winners and nominees List of Chilean Academy Award winners and nominees List of Colombian Academy Award winners and nominees List of Cuban Academy Award winners and nominees List of Mexican Academy Award winners and nominees List of Puerto Rican Academy Award winners and nominees List of Spanish Academy Award winners and nominees List of Uruguayan Academy Award winners and nominees List of Hispanic-American ( U.S. ) Academy Award winners and nominees Category : Latin American cinema Hispanic", "title": "" }, { "docid": "List_of_Academy_Award-winning_families", "text": "This is a list of Academy Award winners related to other winners . Honorary awards are included . In many instances , family members shared awards . These awards are counted only once for each family . Results reflect awards through the 89th Academy Awards for 2016 .", "title": "" }, { "docid": "Shine_Global", "text": "Shine Global Inc. is a 501 ( c ) ( 3 ) non-profit media company that was founded in 2005 by Susan MacLaury , a licensed social worker and former health professor at Kean University , and her husband , Albie Hecht , an entertainment executive and founder of Worldwide Biggies and current head of HLN ( TV channel ) . Shine Global has produced or helped produce 7 films including War/Dance , a 2008 Academy Award Nominee for Best Documentary and Inocente the Academy Award Winner for Best Documentary Short Subject in 2013 .", "title": "" }, { "docid": "Black_Reel_Award_for_Outstanding_Breakthrough_Performance", "text": "This page lists the winners and nominees for the Black Reel Award for Outstanding Breakthrough Performance . Academy Award-nominated or winning performances also honored with nominations or wins at the Black Reel Awards include Jennifer Hudson ( Dreamgirls ) , Octavia Spencer ( The Help ) , Quvenzhane Wallis ( Beasts of the Southern Wild ) and Gabourey Sidibe ( Precious ) . During the 2014 ceremony , the category was divided into gender specific categories ( Outstanding Breakthrough Performance , Male and Outstanding Breakthrough Performance , Female ) .", "title": "" }, { "docid": "Scott_Benza", "text": "Scott Benza is an Oscar nominated visual effects supervisor . His first nomination was for the film Transformers at the 80th Academy Awards . His 2nd was at the 84th Academy Awards for the film Transformers : Dark of the Moon .", "title": "" }, { "docid": "Sue_Goffe", "text": "Sue Goffe is a film maker . On 24 January 2012 she was nominated for an Academy Award for the animated short film A Morning Stroll . She shared her nomination with Grant Orchard at the 84th Academy Awards .", "title": "" }, { "docid": "Black_Reel_Award_for_Best_Supporting_Actress", "text": "This page lists the winners and nominees for the Black Reel Award for Best Supporting Actress in a Motion Picture . Academy Award-nominated or winning performances also honored with nominations or wins at the Black Reel Awards include Lupita Nyong ' o ( 12 Years a Slave ) , Queen Latifah ( Chicago ) , Jennifer Hudson ( Dreamgirls ) , Penélope Cruz ( Vicky Cristina Barcelona ) , Taraji P. Henson ( The Curious Case of Benjamin Button ) , Viola Davis ( Doubt ) , Mo'Nique ( Precious ) , and Octavia Spencer ( The Help ) .", "title": "" }, { "docid": "Black_Reel_Award_for_Outstanding_Supporting_Actress", "text": "This page lists the winners and nominees for the Black Reel Award for Outstanding Supporting Actress in a Motion Picture . Academy Award-nominated or winning performances also honored with nominations or wins at the Black Reel Awards include Lupita Nyong ' o ( 12 Years a Slave ) , Queen Latifah ( Chicago ) , Jennifer Hudson ( Dreamgirls ) , Penélope Cruz ( Vicky Cristina Barcelona ) , Taraji P. Henson ( The Curious Case of Benjamin Button ) , Viola Davis ( Doubt ) , Mo'Nique ( Precious ) , and Octavia Spencer ( The Help ) .", "title": "" }, { "docid": "List_of_Latin_American_Academy_Award_winners_and_nominees", "text": "A list of Latin American Academy Award winners and nominees appears below . This account does not include individuals born in the continental United States , and is current as of the 88th Academy Awards ceremony held on February 28 , 2016 .", "title": "" }, { "docid": "Hanny_Saputra", "text": "Hanny R. Saputra ( born 11 May 1965 ) is an Indonesian director . One of his films , Under the Protection of Ka'Bah , was Indonesia 's submission for the Academy Award for Best Foreign Language Film in the 84th Academy Awards .", "title": "" }, { "docid": "1997_CFL_Dispersal_Draft", "text": "The 1997 CFL dispersal draft took place on March 12 , 1997 , to distribute players who were under contract to the Ottawa Rough Riders at the time of their disbandment . The Saskatchewan Roughriders were awarded a bonus selection as well as the first selection in the first round . Otherwise the order of selection was determined based on priority waiver ( reverse standings from 1996 , with the 84th Grey Cup loser selecting second last and 84th Grey Cup winner selecting last in each round ) . Teams were permitted to trade selections , consequently , Winnipeg traded their first selection to Edmonton for Cody Ledbetter . 32 players were selected in the five-round draft , including 20 import players .", "title": "" }, { "docid": "List_of_Polish_Academy_Award_winners_and_nominees", "text": "This is a list of Polish Academy Award winners and nominees . This list details the performances of Polish actors , actresses , and films that have either been submitted or nominated for , or have won , an Academy Award . This list is current as of the 80th Academy Awards ceremony held on February 24 , 2008 . There were 12 Academy Awards given to Polish filmmakers or their work ( see Foreign Film category ) , including two Honorary Academy Awards and a Technical Achievement Award . The category of Cinematography has the strongest presence of Polish filmmakers , with two wins ( both by Janusz Kaminski ) and five other nominations ( including two noms for Kaminski ) . As of that , the cinematographer Janusz Kaminski is the most Oscar-awarded Polish filmmaker . The second most-awarded Pole was designer Anton Grot , who won one Academy Award and was nominated to the Oscars five times more . The director Roman Polanski won an Oscar and was nominated four more times ( additionally , Knife in the Water , film directed and written by him was also nominated ) . The composer Bronislau Kaper was awarded an Oscar and was nominated three times more .", "title": "" }, { "docid": "Matthew_E._Butler", "text": "Matthew E. Butler is a visual effects supervisor . He was nominated at the 84th Academy Awards in the category of Academy Award for Best Visual Effects for the film Transformers : Dark of the Moon . His nomination was shared with Scott Benza , Scott Farrar and John Frazier .", "title": "" }, { "docid": "Rich_Middlemas", "text": "Rich Middlemas is a documentary film maker . On January 24 , 2012 , he was nominated for an Academy Award for the film Undefeated . Undefeated won the Oscar for Best Documentary at the 84th Academy Awards . Rich Middlemas optioned the film rights to thriller/horror eBook PenPal in 2012 .", "title": "" }, { "docid": "Michel_Hazanavicius", "text": "Michel Hazanavicius ( -LSB- mi.ʃɛl a.za.na.vi.sjys -RSB- ; born 29 March 1967 ) is a French film director , producer , screenwriter and film editor best known for his 2011 film , The Artist , which won the Academy Award for Best Picture at the 84th Academy Awards . It also won him the Academy Award for Best Director . He also directed spy film parodies OSS 117 : Cairo , Nest of Spies ( 2006 ) and OSS 117 : Lost in Rio ( 2009 ) .", "title": "" }, { "docid": "Volcano_(2011_film)", "text": "Volcano ( Eldfjall ) is a 2011 Icelandic drama film directed by Rúnar Rúnarsson . The film was selected as the Icelandic entry for the Best Foreign Language Film at the 84th Academy Awards , but it did not make the final shortlist . At the 2012 Edda Awards , the film was nominated in 14 categories , winning in 5 . The film screened within many international film festivals , including the 2011 Toronto International Film Festival and the 2012 Maryland Film Festival .", "title": "" }, { "docid": "BET_Award_for_Best_Movie", "text": "The BET Award for Best Movie was first awarded in 2010 . 1 BET Award winner ( Precious ) and 3 nominees ( The Blind Side , Avatar , The Help ) also earned Academy Award for Best Picture nominations .", "title": "" }, { "docid": "Amanda_Knight", "text": "Amanda Knight is a make-up artist . On January 24 , 2012 , she was nominated for an Academy Award for the movie Harry Potter and the Deathly Hallows : Part 2 . This was at the 84th Academy Awards in the category of Best Makeup . She shared her nomination with Nick Dudman and Lisa Tomblin .", "title": "" }, { "docid": "List_of_Primetime_Emmy_Award_winners", "text": "This list showcases the Primetime Emmy Award winners in the comedy program , drama program , variety program , and lead actors categories . In the early days of the Primetime Emmy Awards , categories awarded by the Academy of Television Arts & Sciences changed year-to-year , causing irregularities in the continuity of the listed awards . For several years , in the late 1950s and early 1960s , the Academy did not differentiate between comedy and dramas in the individual performance categories , issuing only a catch-all `` Best Continuing Performance '' or `` Outstanding ( Actor/Actress ) in a Series '' . During the mid-1950s , the Academy split Outstanding Drama into several categories , including `` One Hour or More '' , `` Half Hour or Less '' , and `` Western or Adventure Series '' . Each winner is indicated below . In 1965 , Academy President Rod Serling initiated `` Area Awards '' that narrowed the categories to a select few and allowed for multiple winners in an attempt to foster less competition in favor of more programs and individuals receiving credit for their work . The experiment lasted for only one awards season .", "title": "" }, { "docid": "Little_Golden_Guy", "text": "Little Golden Guy is a website which presents statistical data related to the Academy Awards ( also known as the Oscars ) . Launched by Brian Barney in 1999 , the search engine provides a method of tabulating the films and individuals holding records for the most nominations and awards within a particular category or within a specified timeframe . The website maintains data from the 1st Academy Awards ceremony , honoring films from 1927 and 1928 , to the 84th Academy Awards ceremony , honoring films from 2011 . The site 's search results also provide internal links to annual summaries , as well as statistical breakdowns of individual awards categories . The site has not been updated since the 2013 Academy Awards .", "title": "" } ]
PLAIN-3215
Asian Paradox
[ { "docid": "MED-4097", "text": "The identification of modifiable lifestyle factors that could reduce the risk of breast cancer is a research priority. Despite the enormous chemo preventive potential of green tea and compelling evidence from animal studies, its role in breast cancer development in humans is still unclear. Part of the uncertainty is related to the relatively small number of epidemiological studies on green tea and breast cancer and that the overall results from case-control studies and prospective cohort studies are discordant. In addition, the mechanisms by which green tea intake may influence risk of breast cancer in humans remains not well studied. We review the human studies that have evaluated the relationship between green tea intake and four biomarkers (sex steroid hormones, mammographic density, insulin-like growth factor, adiponectin) that are believed to be important in breast cancer development. Results from these biomarker studies are also inconclusive. Limitations of human studies and areas of further investigations are discussed.", "title": "Green Tea and Breast Cancer" }, { "docid": "MED-4776", "text": "Tea (Camellia sinensis, Theaceae) and tea polyphenols have been studied for the prevention of chronic diseases, including obesity. Obesity currently affects >20% of adults in the United States and is a risk factor for chronic diseases such as type II diabetes, cardiovascular disease, and cancer. Given this increasing public health concern, the use of dietary agents for the prevention of obesity would be of tremendous benefit. Whereas many laboratory studies have demonstrated the potential efficacy of green or black tea for the prevention of obesity, the underlying mechanisms remain unclear. The results of human intervention studies are mixed and the role of caffeine has not been clearly established. Finally, there is emerging evidence that high doses of tea polyphenols may have adverse side effects. Given that the results of scientific studies on dietary components, including tea polyphenols, are often translated into dietary supplements, understanding the potential toxicities of the tea polyphenols is critical to understanding their potential usefulness in preventing obesity. In this review, we will critically evaluate the evidence for the prevention of obesity by tea, discuss the relevance of proposed mechanisms in light of tea polyphenol bioavailability, and review the reports concerning the toxic effects of high doses of tea polyphenols and the implication that this has for the potential use of tea for the prevention of obesity. We hope that this review will expose areas for further study and encourage research on this important public health issue.", "title": "Laboratory, Epidemiological, and Human Intervention Studies Show That Tea (Camellia sinensis) May Be Useful in the Prevention of Obesity" }, { "docid": "MED-4780", "text": "OBJECTIVE: To examine the association between green tea consumption and tooth loss. METHODS: We analyzed cross-sectional data from the Ohsaki Cohort 2006 Study. Usable self-administered questionnaires about green tea consumption and tooth loss were returned from 25,078 persons (12,019 men and 13,059 women) aged 40 to 64 years in Japan. Multivariate logistic regression analysis was used to calculate odds ratios (ORs) for tooth loss using 3 cut-off points of 10, 20, and 25 teeth relative to each category of green tea consumption. RESULTS: Consumption of > or = 1 cup/day of green tea was significantly associated with decreased odds for tooth loss, and the association appeared to fit a threshold model. In men, the multivariate-adjusted ORs for tooth loss with a cut-off point of <20 teeth associated with different frequencies of green tea consumption were 1.00 (reference) for <1 cup/day, 0.82 (95% CI, 0.74-0.91) for 1-2 cups/day, 0.82 (95% CI, 0.73-0.92) for 3-4 cups/day, and 0.77 (95% CI, 0.66-0.89) for > or = 5 cups/day. The corresponding data for women and the results for cut-off points of 10 and 25 teeth were essentially the same. CONCLUSIONS: The present findings indicate an association of green tea consumption with decreased odds for tooth loss. Copyright 2010 Elsevier Inc. All rights reserved.", "title": "Association between green tea consumption and tooth loss: cross-sectional results from the Ohsaki Cohort 2006 Study." }, { "docid": "MED-4096", "text": "A variety of statistics are used to quantify the burden (occurrence and outcome) of cancer generally and of breast cancer specifically. When undertaking any cancer control program, understanding these statistics, their source, and their quality is important for assessing the current situation, allocating resources to different control strategies, and evaluating progress. Two core statistics are the cancer incidence rate and the cancer mortality rate, which provide estimates of the average risk of acquiring and of dying from the disease, respectively. About 16% of the world's population is covered by registration systems that produce cancer incidence statistics, while mortality data are available for about 29%. Breast cancer incidence and mortality vary considerably by world region. In general, the incidence is high (greater than 80 per 100,000) in developed regions of the world and low (less than 30 per 100,000), though increasing, in developing regions; the range of mortality rates is much less (approximately 6-23 per 100,000) because of the more favorable survival of breast cancer in (high-incidence) developed regions. The incidence of breast cancer is increasing almost everywhere. This unfavorable trend is due in part to increases in risk factors (decreased childbearing and breast-feeding, increased exogenous hormone exposure, and detrimental dietary and lifestyle changes, including obesity and less physical activity). On the other hand, mortality is now decreasing in many high-risk countries due to a combination of intensified early detection efforts and the introduction of mammographic screening, resulting in the diagnosis of more small, early stage tumors, and advances in treatment.", "title": "Use of statistics to assess the global burden of breast cancer." }, { "docid": "MED-4332", "text": "There is growing interest in the potential health benefits of tea, including the antimutagenic properties. Four varieties of white tea, which represent the least processed form of tea, were shown to have marked antimutagenic activity in the Salmonella assay, particularly in the presence of S9. The most active of these teas, Exotica China white tea, was significantly more effective than Premium green tea (Dragonwell special grade) against 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and four other heterocyclic amine mutagens, namely 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline (4,8-DiMeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). Mechanism studies were performed using rat liver S9 in assays for methoxyresorufin O-demethylase (MROD), a marker for the enzyme cytochrome P4501A2 that activates heterocyclic amines, as well as Salmonella assays with the direct-acting mutagen 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline (N-hydroxy-IQ). White tea at low concentrations in the assay inhibited MROD activity, and attenuated the mutagenic activity of N-hydroxy-IQ in the absence of S9. Nine of the major constituents found in green tea also were detected in white tea, including high levels of epigallocatechin-3-gallate (EGCG) and several other polyphenols. When these major constituents were mixed to produce \"artificial\" teas, according to their relative levels in white and green teas, the complete tea exhibited higher antimutagenic potency compared with the corresponding artificial tea. The results suggest that the greater inhibitory potency of white versus green tea in the Salmonella assay might be related to the relative levels of the nine major constituents, perhaps acting synergistically with other (minor) constituents, to inhibit mutagen activation as well as \"scavenging\" the reactive intermediate(s).", "title": "Potent antimutagenic activity of white tea in comparison with green tea in the Salmonella assay." }, { "docid": "MED-4777", "text": "The current practice of introducing phytochemicals to support the immune system or fight against diseases is based on centuries old traditions. Nutritional support is a recent advancement in the domain of diet-based therapies; green tea and its constituents are one of the important components of these strategies to prevent and cure various malignancies. The anti-carcinogenic and anti-mutagenic activities of green tea were highlighted some years ago suggesting that it could reduce the prevalence of cancer and even provide protection. The pharmacological actions of green tea are mainly attributed to polyphenols that includes epigallocatechin-3-gallate (EGCG), epicatechin, epicatechin-3-gallate, epigallocatechin. Green tea and its components effectively mitigate cellular damage arising due to oxidative stress. Green tea is supposed to enhance humoral and cell-mediated immunity, decreasing the risk of certain cancers, and may have certain advantage in treating inflammatory disorders. Much of the cancer chemopreventive properties of green tea are mediated by EGCG that induces apoptosis and promotes cell growth arrest, by altering the expression of cell cycle regulatory proteins, activating killer caspases, and suppressing nuclear factor kappa-B activation. Besides, it regulates and promotes IL-23 dependent DNA repair and stimulates cytotoxic T cells activities in a tumor microenvironment. It also blocks carcinogenesis by modulating the signal transduction pathways involved in cell proliferation, transformation, inflammation and metastasis. The review is intended to highlight the chemistry of green tea, its antioxidant potential, its immunopotentiating properties and mode of action against various cancer cell lines that showed its potential as a chemopreventive agent against colon, skin, lung, prostate, and breast cancer.", "title": "Green tea: nature's defense against malignancies." }, { "docid": "MED-4055", "text": "Heterocyclic amines (HCAs) are formed when meat products such as beef, chicken, pork and fish are cooked at high temperatures. The most abundant HCA found in the human diet is 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP). PhIP causes mammary carcinomas in female rats and mice, and is associated with an increased risk of developing colon, breast, and prostate cancer in humans. PhIP is metabolized by cytochrome P-450s producing N-OH-PhIP. The N-OH-PhIP can be esterified by phase II enzymes forming an arylnitrenium ion that binds to DNA causing adducts. Furthermore, N-OH-PhIP may be reduced by cytochrome b5 reductase producing superoxide anions and hydroxyl radicals causing DNA strand breaks. Diallyl sulfide (DAS) has been shown to prevent cancer in several animal models, presumably by metabolic modulation. We hypothesize that PhIP produces reactive oxygen species causing DNA strand breaks and that DAS will inhibit the formation of PhIP induced DNA strand breaks. To test this hypothesis we treated normal breast epithelial (MCF-10A) cells with PhIP, DAS and a combination of PhIP and DAS. The detection of lipid peroxides was used as a surrogate for ROS. Lipid peroxides were detected using a PeroxiDetect kit (Sigma). PhIP increased the production of lipid peroxides and DAS decreased the PhIP-induced peroxidation by 47%. To determine if PhIP causes DNA strand breaks in MCF-10A cells, cells were treated for 3, 6, 9, and 24 h with PhIP (100 microM), DAS (100 microM) and a combination of PhIP (100 microM) and DAS (100 microM). DNA strand breaks were evaluated using the Comet assay. PhIP produced DNA strand breaks in a dose- and time-dependent fashion. We have shown that DAS inhibits PhIP-induced DNA strand breaks by inhibiting the production of reactive oxygen species. Therefore, we propose that DAS can prevent PhIP-induced breast cancer.", "title": "Diallyl sulfide inhibits PhIP-induced DNA strand breaks in normal human breast epithelial cells." }, { "docid": "MED-4779", "text": "ABSTRACT BACKGROUND Tea consumption has been extensively studied in relation to various diseases, several epidemiologic studies have been performed to investigate the association of tea consumption with type 2 diabetes; however, the results of these studies were not entirely consistent. OBJECTIVE To conduct a meta-analysis of studies that assessed the association of tea consumption and the risk of type 2 diabetes. RESEARCH DESIGN AND METHODS We performed a systematic literature search through November 2008 in PUBMED, MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews. The search was limited to English-language studies. Studies were excluded if they were type 1 diabetes, animal studies. Nine cohort studies were identified by two authors, and summary relative risks (RRs) were calculated using a random-effects model. RESULTS We identified nine cohort studies, including 324,141 participants and 11,400 incident cases of type 2 diabetes with follow-up ranging from 5 to 18 years. The summary adjusted RR did not show that tea consumption was associated with a reduced type 2 diabetes risk (RR, 0.96; 95% confidence interval (CI), 0.92–1.01). Evidence from the results of our stratified analyses revealed that tea consumption ≥4 cups per day (RR, 0.8; 95% CI, 0.7–0.93) might play a role in the prevention of type 2 diabetes. However, no statistically significant association was observed for sex and the follow-up durations stratified between tea consumption and type 2 diabetes. CONCLUSIONS This meta-analysis indicates that tea consumption ≥4 cups per day may lower the risk of type 2 diabetes.", "title": "Tea Consumption and Risk of Type 2 Diabetes: A Meta-Analysis of Cohort Studies" }, { "docid": "MED-4050", "text": "Green tea is a commonly consumed beverage in Asia and has been suggested to have anti-inflammatory and possible anti-carcinogenic properties in laboratory studies. We sought to examine the association between green tea consumption and risk of breast cancer incidence or recurrence, using all available epidemiologic evidence to date. We conducted a systematic search of five databases and performed a meta-analysis of studies of breast cancer risk and recurrence published between 1998 and 2009, encompassing 5,617 cases of breast cancer. Summary relative risks (RR) were calculated using a fixed effects model, and tests of heterogeneity across combined studies were conducted. We identified two studies of breast cancer recurrence and seven studies of breast cancer incidence. Increased green tea consumption (more than three cups a day) was inversely associated with breast cancer recurrence (Pooled RR = 0.73, 95% CI: 0.56-0.96). An analysis of case-control studies of breast cancer incidence suggested an inverse association with a pooled RR of 0.81 (95% CI: 0.75, 0.88) while no association was found among cohort studies of breast cancer incidence. Combining all studies of breast cancer incidence resulted in significant heterogeneity. Available epidemiologic evidence supports the hypothesis that increased green tea consumption may be inversely associated with risk of breast cancer recurrence. The association between green tea consumption and breast cancer incidence remains unclear based on the current evidence.", "title": "Green tea consumption and breast cancer risk or recurrence: a meta-analysis." }, { "docid": "MED-4051", "text": "The food mutagens IQ (2-amino-3-methylimidazo[4,5-f]quinoline) and PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) are heterocyclic amines (HCA), generated when heating proteinaceous food. This study investigates the protective potential of the flavonoids quercetin (Q) and rutin (R) against oxidative stress induced in vitro by IQ and PhIP in lymphocytes from healthy individuals and untreated, newly diagnosed colon cancer patients using the Comet assay. In the presence of up to 500μM Q and R, the DNA damage resulting from a high dose of PhIP (75μM) or IQ (150μM) was significantly reduced (P<0.001) to levels comparable to six times lower IQ or 7.5 times lower PhIP doses. Lymphocytes from colon cancer patients had greater baseline DNA damage than those from healthy individuals (P<0.01) and this higher level of damage was also observed throughout in vitro treatment. Except for the >50years of age group and male gender, confounding factors such as smoking, drinking and/or dietary habits were not found to be significant. In conclusion, flavonoids reduced oxidative stress caused by food mutagens in vitro in lymphocytes of healthy individuals and colon cancer patients. Thus, dietary supplementation with flavonoid-rich vegetables and fruits may prove very effective in protecting against oxidative stress. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "The protective effect of the flavonoids on food-mutagen-induced DNA damage in peripheral blood lymphocytes from colon cancer patients." }, { "docid": "MED-4778", "text": "The methanolic extract of fresh tea leaves of Camellia sinensis L. (Theaceae) (CS) was assayed for its potential to inhibit enzymes with hydrolytic activity in Naja naja kaouthia Lesson (Elapidae) and Calloselasma rhodostoma Kuhl (Viperidae) venoms. These snake venom enzymes are responsible for the early effects of envenomation, such as local tissue damage and inflammation. The CS extract inhibited phospholipase A(2), proteases, hyaluronidase and L-amino acid oxidase in both venoms by in vitro neutralization and inhibited the hemorrhagic and the dermonecrotic activities of the venoms in vivo. It is suggested that the inhibitory potential of the CS extract against local tissue damage induced by snake venoms may be attributed to complexation and chelation between the venom proteins and the phenolic contents of the extract.", "title": "Inhibitory effect of tea polyphenols on local tissue damage induced by snake venoms." }, { "docid": "MED-4049", "text": "More than 85% of breast cancers are sporadic and attributable to long-term exposure to environmental carcinogens, such as those in the diet, through a multistep disease process progressing from non-cancerous to premalignant and malignant stages. The chemical carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is one of the most abundant heterocyclic amines found in high-temperature cooked meats and is recognized as a mammary carcinogen. However, the PhIP’s mechanism of action in breast cell carcinogenesis is not clear. Here, we demonstrated, for the first time, that cumulative exposures to PhIP at physiologically achievable, pico to nanomolar concentrations effectively induced progressive carcinogenesis of human breast epithelial MCF10A cells from a non-cancerous stage to premalignant and malignant stages in a dose- and exposure-dependent manner. Progressive carcinogenesis was measured by increasingly- acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth, acinar-conformational disruption, proliferation, migration, invasion, tumorigenicity with metastasis and increased stem-like cell populations. These biological changes were accompanied by biochemical and molecular changes, including upregulated H-Ras gene expression, extracellular signal-regulated kinase (ERK) pathway activation, Nox-1 expression, reactive oxygen species (ROS) elevation, increased HIF-1α, Sp1, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2, MMP-9, aldehyde dehydrogenase activity and reduced E-cadherin. The Ras-ERK-Nox-ROS pathway played an important role in not only initiation but also maintenance of cellular carcinogenesis induced by PhIP. Using biological, biochemical and molecular changes as targeted endpoints, we identified that the green tea catechin components epicatechin-3-gallate and epigallocatechin-3-gallate, at non-cytotoxic doses, were capable of suppressing PhIP-induced cellular carcinogenesis and tumorigenicity.", "title": "Intervention of human breast cell carcinogenesis chronically induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine" }, { "docid": "MED-4098", "text": "To investigate effects of dietary mushrooms and joint effects of mushrooms and green tea on breast cancer, a case-control study was conducted in southeast China in 2004-2005. The incident cases were 1,009 female patients aged 20-87 years with histologically confirmed breast cancer. The 1,009 age-matched controls were healthy women randomly recruited from outpatient breast clinics. Information on frequency and quantity of dietary intake of mushrooms and tea consumption, usual diet, and lifestyle were collected by face-to-face interview using a validated and reliable questionnaire. Compared with nonconsumers, the Odds ratios (Ors) were 0.36 (95% CI = 0.25-0.51) and 0.53 (0.38-0.73) for daily intake of >or=10 g fresh mushrooms and >or=4 g dried mushrooms, based on multivariate logistic regression analysis adjusting for established and potential confounders. There were dose-response relationships with significant tests for trend (p < 0.001). The inverse association was found in both pre- and postmenopausal women. Compared with those who consumed neither mushrooms nor green tea, the ORs were 0.11 (0.06-0.20) and 0.18 (0.11-0.29) for daily high intake of fresh and dried mushrooms combined with consuming beverages made from >or=1.05 g dried green tea leaves per day. The corresponding linear trends were statistically significant for joint effect (p < 0.001). We conclude that higher dietary intake of mushrooms decreased breast cancer risk in pre- and postmenopausal Chinese women and an additional decreased risk of breast cancer from joint effect of mushrooms and green tea was observed. More research is warranted to examine the effects of dietary mushrooms and mechanism of joint effects of phytochemicals on breast cancer.", "title": "Dietary intakes of mushrooms and green tea combine to reduce the risk of breast cancer in Chinese women." } ]
[ { "docid": "MED-4531", "text": "Traditional herbal preparations used in Ayurveda, traditional Chinese medicine, traditional Tibetan medicine, and other Asian traditional medicine systems may contain significant amounts of mercury, arsenic or lead. Though deliberately incorporated in Asian traditional herbal preparations for therapeutic purposes, these constituents have caused intoxications worldwide. The aim of this study was therefore to determine mercury, arsenic, and lead levels in Asian traditional herbal preparations on the Dutch market. A total of 292 traditional herbal preparations used in Ayurveda, traditional Chinese medicine, and traditional Tibetan medicine were sampled between 2004 and 2007. Samples were mostly multi-ingredient traditional herbal preparations containing herbs and minerals. The labeling of less than 20% of the traditional herbal preparations suggested the presence of mercury, arsenic or lead. These elements were shown by inductively coupled mass spectrometry (ICP-MS) in 186 (64%) of 292 traditional herbal preparations. Estimated weekly mercury, arsenic, and lead intake levels were calculated for each traditional herbal preparation from the analytically determined concentrations and the recommended dose. A total of 59 traditional herbal preparations (20%) were likely to result in intakes of these elements significantly exceeding safety limits. Of these 59 traditional herbal preparations, intake estimates for 50 traditional herbal preparations significantly exceeded the safety limit for mercury (range = 1.4-1747 mg week(-1)); intake estimates for 26 traditional herbal preparations significantly exceeded the safety limit for arsenic (range = 0.53-427 mg week(-1)) and intake estimates for eight traditional herbal preparations were significantly above the safety limit for lead (range = 2.6-192 mg week(-1)). It is concluded that the mercury, arsenic, and lead contents of traditional herbal preparations used in Ayurveda, traditional Chinese medicine, and traditional Tibetan medicine remain a cause for concern and require strict control.", "title": "Monitoring of mercury, arsenic, and lead in traditional Asian herbal preparations on the Dutch market and estimation of associated risks." }, { "docid": "MED-1942", "text": "Curcumin, from the curry spice turmeric, has been shown to possess potent antioxidant and antiinflammatory properties and to reduce beta-amyloid and plaque burden in experimental studies, but epidemiologic evidence is lacking. The authors investigated the association between usual curry consumption level and cognitive function in elderly Asians. In a population-based cohort (n = 1,010) of nondemented elderly Asian subjects aged 60-93 years in 2003, the authors compared Mini-Mental State Examination (MMSE) scores for three categories of regular curry consumption, taking into account known sociodemographic, health, and behavioral correlates of MMSE performance. Those who consumed curry \"occasionally\" and \"often or very often\" had significantly better MMSE scores than did subjects who \"never or rarely\" consumed curry. The authors reported tentative evidence of better cognitive performance from curry consumption in nondemented elderly Asians, which should be confirmed in future studies.", "title": "Curry consumption and cognitive function in the elderly." }, { "docid": "MED-2409", "text": "Background Prospective cohort studies in relation to the associations between n-3 polyunsaturated fatty acids (PUFA) and risk of type 2 diabetes (T2D) were inconsistent. Differences in tissue n-3 PUFA compositions in subjects with and without T2D were also inconsistent in both cohort and case-control studies. We conducted a systematic review and meta-analysis of prospective cohort studies to examine the associations of fish and n-3 PUFA intake with T2D risk. The differences in tissue n-3 PUFA compositions in subjects with and without T2D were investigated based on cohort and case-control studies. Methods and Findings PubMed, Embase, Cochrane library, China National Knowledge Infrastructure (CNKI) and Chinese VIP database up to January 2012 was used to identify relevant studies, and reference lists from retrieved studies were reviewed. Two authors independently extracted the data. Random-effects models were used to pool the summary relative risk (RR). Twenty-four studies including 24,509 T2D patients and 545,275 participants were identified. For cohort studies, the summary RR of T2D for the highest vs lowest categories of total fish, marine n-3 PUFA and alpha-linolenic acid intake was 1.07 (95% CI: 0.91, 1.25), 1.07 (95% CI: 0.95, 1.20) and 0.93 (95% CI: 0.81, 1.07), respectively. Subgroup analyses indicated that summary RR (highest vs lowest category) of T2D for fish and marine n-3 PUFA intake was 0.89 (95% CI: 0.81, 0.98) and 0.87 (95% CI: 0.79, 0.96) for Asian populations, and 1.20 (95% CI: 1.01, 1.44) and 1.16 (95% CI: 1.04, 1.28) for Western populations. Asian subjects with T2D had significantly lower tissue compositions of C22∶6n-3 (SMD: −1.43; 95% CI: −1.75, −1.12) and total n-3 PUFA (SMD: −1.41; 95% CI: −2.23, −0.59) compared with those without T2D. Conclusion This systematic review and meta-analysis provides evidence that marine n-3 PUFA have beneficial effects on the prevention of T2D in Asian populations.", "title": "Marine N-3 Polyunsaturated Fatty Acids Are Inversely Associated with Risk of Type 2 Diabetes in Asians: A Systematic Review and Meta-Analysis" }, { "docid": "MED-3099", "text": "This review reconsiders a major cause of cardiovascular diseases, tobacco smoking, as the activation of the Aryl hydrocarbon Receptor (AhR), also known as the dioxin receptor, by aryl hydrocarbons from the tar fraction of tobacco in various organs of the cardiovascular domain. This concept sheds new light on well-known albeit controversial epidemiological concepts such as the Mediterranean diet and the French paradox. We also review the discovery that resveratrol, a natural AhR antagonist, may be of interest in the prevention and treatment of cardiovascular diseases.", "title": "The aryl hydrocarbon receptor and its xenobiotic ligands: a fundamental trigger for cardiovascular diseases." }, { "docid": "MED-5216", "text": "Vitamin A deficiency (VAD) has been recognized as a public-health issue in developing countries. Economic constraints, sociocultural limitations, insufficient dietary intake, and poor absorption leading to depleted vitamin A stores in the body have been regarded as potential determinants of the prevalence of VAD in South Asian developing countries. VAD is exacerbated by lack of education, poor sanitation, absence of new legislation and enforcement of existing food laws, and week monitoring and surveillance system. Several recent estimates confirmed higher morbidly and mortality rate among children and pregnant and non-pregnant women of childbearing age. Xerophthalmia is the leading cause of preventable childhood blindness with its earliest manifestations as night blindness and Bitot's spots, followed by blinding keratomalacia, all of which are the ocular manifestations of VAD. Children need additional vitamin A because they do not consume enough in their normal diet. There are three general ways for improving vitamin A status: supplementation, fortification, and dietary diversification. These approaches have not solved the problem in South Asian countries to the desired extent because of poor governmental support and supervision of vitamin A supplementation twice a year. An extensive review of the extant literature was carried out, and the data under various sections were identified by using a computerized bibliographic search via PubMed, Web of Science, and Google Scholar. All abstracts and full-text articles were examined, and the most relevant articles were selected for screening and inclusion in this review. Conclusively, high prevalence of VAD in South Asian developing countries leads to increased morbidity and mortality among infants, children, and pregnant women. Therefore, stern efforts are needed to address this issue of public-health significance at local and international level in lower- and middle-income countries of South Asia.", "title": "Prevalence of Vitamin A Deficiency in South Asia: Causes, Outcomes, and Possible Remedies" }, { "docid": "MED-748", "text": "Questions of medical ethics are often treated as especially difficult casuistical problems or as difficult cases illustrative of paradoxes or advantages in global moral theories. I argue here, in opposition to such approaches, for the inseparability of questions of social history and social theory from any normative assessment of medical practices. The focus of the discussion is the question of the legitimacy of the social authority exercised by physicians, and the insufficiency of traditional defences of such authority in liberal societies (voluntarist, informed consent approaches), as well as traditional attacks on such strategies (ideology critique). Seeing such authority as institution bound and role based, it is argued, can help reframe, more broadly and more adequately, what is an \"ethical problem\" in medical practice and why.", "title": "Medical practice and social authority." }, { "docid": "MED-2127", "text": "The mammalian target of rapamycin (mTOR) is a conserved protein kinase involved in a multitude of cellular processes including cell growth. Increased mTOR activation is observed in multiple human cancers and inhibition of mTOR has proven efficacious in numerous clinical trials. mTOR comprises two complexes, termed mTORC1 and mTORC2. Both complexes respond to growth factors, whereas only mTORC1 is controlled by nutrients, such as glucose and amino acids. Since the discovery of mTOR, extensive studies have intricately detailed the molecular mechanisms by which mTORC1 is regulated. Somewhat paradoxically, amino acid induced mTORC1 activation—arguably the most essential stimulus leading to mTORC1 activation—is the least understood. Here we review the current knowledge of nutrient dependent regulation of mTORC1.", "title": "Nutrient Signaling to mTOR and Cell Growth" }, { "docid": "MED-4963", "text": "Because of the worldwide popularization of Japanese cuisine, the traditional Japanese fish dishes sushi and sashimi that are served in Japanese restaurants and sushi bars have been suspected of causing fishborne parasitic zoonoses, especially anisakiasis. In addition, an array of freshwater and brackish-water fish and wild animal meats, which are important sources of infection with zoonotic parasites, are served as sushi and sashimi in rural areas of Japan. Such fishborne and foodborne parasitic zoonoses are also endemic in many Asian countries that have related traditional cooking styles. Despite the recent increase in the number of travelers to areas where these zoonoses are endemic, travelers and even infectious disease specialists are unaware of the risk of infection associated with eating exotic ethnic dishes. The aim of this review is to provide practical background information regarding representative fishborne and foodborne parasitic zoonoses endemic in Asian countries.", "title": "Sushi delights and parasites: the risk of fishborne and foodborne parasitic zoonoses in Asia." }, { "docid": "MED-5286", "text": "Obesity remains a major public health challenge, and its prevalence is dramatically increasing. Diet and exercise are typically recommended to prevent and manage obesity; however, the results are often conflicting. Polyphenols, a class of phytochemicals that have been shown to reduce the risk factors for diabetes type II and cardiovascular diseases, are recently suggested as complementary agents in the management of obesity through several mechanisms such as decreasing fat absorption and/or fat synthesis. Dark chocolate, a high source of polyphenols, and flavanols in particular, has lately received attention for its possible role in modulating obesity because of its potential effect on fat and carbohydrate metabolism, as well as on satiety. This outcome was investigated in animal models of obesity, cell cultures and few human observational and clinical studies. The research undertaken to date has shown promising results, with the possible implication of cocoa/dark chocolate in the modulation of obesity and body weight through several mechanisms including decreasing the expression of genes involved in fatty acid synthesis, reducing the digestion and absorption of fats and carbohydrates and increasing satiety. Copyright © 2013 John Wiley & Sons, Ltd.", "title": "Dark chocolate: an obesity paradox or a culprit for weight gain?" }, { "docid": "MED-4239", "text": "BACKGROUND: Prostate cancer is the most common solid-tumor cancer in US males but is rare in Asian males. When Asian men adopt the US lifestyle, clinical prostate cancer increases greatly. Epidemiological data from men in the US indicate that regular activity may reduce the risk for prostate cancer. METHODS: Serum was obtained from three groups of similar-aged men, Control, Diet and Exercise, and Exercise alone were used to stimulate LNCaP cells in culture. Growth and apoptosis of tumor cells were measured. Serum samples were also used to measure insulin, IGF-1, IGFBP-1. RESULTS: The Diet and Exercise and the Exercise alone groups had lower serum insulin and IGF-1 but higher IGFBP-1 compared to Controls. LNCaP cell growth was reduced in both groups compared to Control and there was a major increase in apoptosis of tumor cells. CONCLUSIONS: A low-fat diet and/or intensive exercise results in change in serum hormones and growth factors in vivo that can reduce growth and induce apoptosis of LNCaP prostate tumor cells in vitro. Copyright 2003 Wiley-Liss, Inc.", "title": "A low-fat diet and/or strenuous exercise alters the IGF axis in vivo and reduces prostate tumor cell growth in vitro." }, { "docid": "MED-4660", "text": "Dietary seaweeds, common in Asia and in Asian restaurants, have become established as part of popular international cuisine. To understand the possibility for iodine-induced thyroid dysfunction better, we collected samples of the most common dietary seaweeds available from commercial sources in the United States, as well as harvester-provided samples from Canada, Tasmania, and Namibia. Altogether, 12 different species of seaweeds were analyzed for iodine content, and found to range from 16 microg/g (+/-2) in nori (Porphyra tenera) to over 8165 +/- 373 microg/g in one sample of processed kelp granules (a salt substitute) made from Laminaria digitata. We explored variation in preharvest conditions in a small study of two Namibian kelps (Laminaria pallida and Ecklonia maxima), and found that iodine content was lowest in sun-bleached blades (514 +/- 42 microg/g), and highest amount in freshly cut juvenile blades (6571 +/- 715 microg/g). Iodine is water-soluble in cooking and may vaporize in humid storage conditions, making average iodine content of prepared foods difficult to estimate. It is possible some Asian seaweed dishes may exceed the tolerable upper iodine intake level of 1100 microg/d.", "title": "Variability of iodine content in common commercially available edible seaweeds." }, { "docid": "MED-5114", "text": "Most of the early studies published on soy and breast cancer were not designed to test the effect of soy; the assessment of soy intake was usually crude and few potential confounders were considered in the analysis. In this review, we focused on studies with relatively complete assessment of dietary soy exposure in the targeted populations and appropriate consideration for potential confounders in the statistical analysis of study data. Meta-analysis of the 8 (1 cohort, 7 case–control) studies conducted in high-soy-consuming Asians show a significant trend of decreasing risk with increasing soy food intake. Compared to the lowest level of soy food intake (⩽5 mg isoflavones per day), risk was intermediate (OR=0.88, 95% confidence interval (CI)=0.78–0.98) among those with modest (∼10 mg isoflavones per day) intake and lowest (OR=0.71, 95% CI=0.60–0.85) among those with high intake (⩾20 mg isoflavones per day). In contrast, soy intake was unrelated to breast cancer risk in studies conducted in the 11 low-soy-consuming Western populations whose average highest and lowest soy isoflavone intake levels were around 0.8 and 0.15 mg per day, respectively. Thus, the evidence to date, based largely on case–control studies, suggest that soy food intake in the amount consumed in Asian populations may have protective effects against breast cancer.", "title": "Epidemiology of soy exposures and breast cancer risk" }, { "docid": "MED-4203", "text": "Oxygen is vital for most organisms but, paradoxically, damages key biological sites. Oxygenic threat is met by antioxidants that evolved in parallel with our oxygenic atmosphere. Plants employ antioxidants to defend their structures against reactive oxygen species (ROS; oxidants) produced during photosynthesis. The human body is exposed to these same oxidants, and we have also evolved an effective antioxidant system. However, this is not infallible. ROS breach defences, oxidative damage ensues, accumulates with age, and causes a variety of pathological changes. Plant-based, antioxidant-rich foods traditionally formed the major part of the human diet, and plant-based dietary antioxidants are hypothesized to have an important role in maintaining human health. This hypothesis is logical in evolutionary terms, especially when we consider the relatively hypoxic environment in which humans may have evolved. In this paper, the human diet is discussed briefly in terms of its evolutionary development, different strategies of antioxidant defence are outlined, and evolution of dietary antioxidants is discussed from the perspectives of plant need and our current dietary requirements. Finally, possibilities in regard to dietary antioxidants, evolution, and human health are presented, and an evolutionary cost-benefit analysis is presented in relation to why we lost the ability to make ascorbic acid (vitamin C) although we retained an absolute requirement for it.", "title": "Evolution of dietary antioxidants." }, { "docid": "MED-4783", "text": "INTRODUCTION: Historically, breast cancer incidence has been substantially higher in the United States than in Asia. When Asian women migrate to the United States, their breast cancer risk increases over several generations and approaches that for U.S. Whites. Thus, modifiable factors, such as diet, may be responsible. METHODS: In this population-based case-control study of breast cancer among women of Chinese, Japanese, and Filipino descent, ages 20 to 55 years, and living in San Francisco-Oakland (California), Los Angeles (California) and Oahu (Hawaii), we interviewed 597 cases (70% of those eligible) and 966 controls (75%) about adolescent and adult diet and cultural practices. For subjects with mothers living in the United States (39% of participants), we interviewed mothers of 99 cases (43% of eligible) and 156 controls (40%) about the daughter's childhood exposures. Seventy-three percent of study participants were premenopausal at diagnosis. RESULTS: Comparing highest with lowest tertiles, the multivariate relative risks (95% confidence interval) for childhood, adolescent, and adult soy intake were 0.40 (0.18-0.83; P(trend) = 0.03), 0.80 (0.59-1.08; P(trend) = 0.12), and 0.76 (0.56-1.02; P(trend) = 0.04), respectively. Inverse associations with childhood intake were noted in all three races, all three study sites, and women born in Asia and the United States. Adjustment for measures of westernization attenuated the associations with adolescent and adult soy intake but did not affect the inverse relationship with childhood soy intake. DISCUSSION: Soy intake during childhood, adolescence, and adult life was associated with decreased breast cancer risk, with the strongest, most consistent effect for childhood intake. Soy may be a hormonally related, early-life exposure that influences breast cancer incidence.", "title": "Childhood soy intake and breast cancer risk in Asian American women." }, { "docid": "MED-831", "text": "Approximately 20-30% of PCOS women demonstrate excess adrenal precursor androgen (APA) production, primarily using DHEAS as a marker of APA in general and more specifically DHEA, synthesis. The role of APA excess in determining or causing PCOS is unclear, although observations in patients with inherited APA excess (e.g., patients with 21-hydroxylase deficient congenital classic or non-classic adrenal hyperplasia) demonstrate that APA excess can result in a PCOS-like phenotype. Inherited defects of the enzymes responsible for steroid biosynthesis, or defects in cortisol metabolism, account for only a very small fraction of women suffering from hyperandrogenism or APA excess. Rather, women with PCOS and APA excess appear to have a generalized exaggeration in adrenal steroidogenesis in response to ACTH stimulation, although they do not have an overt hypothalamic-pituitary-adrenal axis dysfunction. In general, extra-adrenal factors, including obesity, insulin and glucose levels, and ovarian secretions, play a limited role in the increased APA production observed in PCOS. Substantial heritabilities of APAs, particularly DHEAS, have been found in the general population and in women with PCOS; however, the handful of SNPs discovered to date account only for a small portion of the inheritance of these traits. Paradoxically, and as in men, elevated levels of DHEAS appear to be protective against cardiovascular risk in women, although the role of DHEAS in modulating this risk in women with PCOS remains unknown. In summary, the exact cause of APA excess in PCOS remains unclear, although it may reflect a generalized and inherited exaggeration in androgen biosynthesis of an inherited nature. Copyright © 2014 Elsevier Ltd. All rights reserved.", "title": "DHEA, DHEAS and PCOS." }, { "docid": "MED-4533", "text": "CONTEXT: Lead, mercury, and arsenic intoxication have been associated with the use of Ayurvedic herbal medicine product (HMPs). OBJECTIVES: To determine the prevalence and concentration of heavy metals in Ayurvedic HMPs manufactured in South Asia and sold in Boston-area stores and to compare estimated daily metal ingestion with regulatory standards. DESIGN AND SETTING: Systematic search strategy to identify all stores 20 miles or less from Boston City Hall that sold Ayurvedic HMPs from South Asia by searching online Yellow Pages using the categories markets, supermarkets, and convenience stores, and business names containing the word India, Indian cities, and Indian words. An online national directory of Indian grocery stores, a South Asian community business directory, and a newspaper were also searched. We visited each store and purchased all unique Ayurvedic HMPs between April 25 and October 24, 2003. MAIN OUTCOME MEASURES: Concentrations (microg/g) of lead, mercury, and arsenic in each HMP as measured by x-ray fluorescence spectroscopy. Estimates of daily metal ingestion for adults and children estimated using manufacturers' dosage recommendations with comparisons to US Pharmacopeia and US Environmental Protection Agency regulatory standards. RESULTS: A total of 14 (20%) of 70 HMPs (95% confidence interval, 11%-31%) contained heavy metals: lead (n = 13; median concentration, 40 microg/g; range, 5-37,000), mercury (n = 6; median concentration, 20,225 microg/g; range, 28-104,000), and/or arsenic (n = 6; median concentration, 430 microg/g; range, 37-8130). If taken as recommended by the manufacturers, each of these 14 could result in heavy metal intakes above published regulatory standards. CONCLUSIONS: One of 5 Ayurvedic HMPs produced in South Asia and available in Boston South Asian grocery stores contains potentially harmful levels of lead, mercury, and/or arsenic. Users of Ayurvedic medicine may be at risk for heavy metal toxicity, and testing of Ayurvedic HMPs for toxic heavy metals should be mandatory.", "title": "Heavy metal content of ayurvedic herbal medicine products." }, { "docid": "MED-2357", "text": "Patients with cancer have circulating heterophile antibodies that agglutinate animal red cells via recognition of the mammalian cell surface sialic acid N-glycolylneuraminic acid (Neu5Gc), which was long considered an oncofetal antigen in humans. However, humans are genetically deficient in Neu5Gc production and instead metabolically accumulate Neu5Gc from dietary sources, particularly red meats and milk products. Moreover, mice with a human-like defect showed no alternate pathway for Neu5Gc synthesis and even normal humans express anti-Neu5Gc antibodies. We show here that human tumors accumulate Neu5Gc that is covalently attached to multiple classes of glycans. The paradox of human tumor Neu5Gc accumulation in the face of circulating anti-Neu5Gc antibodies was hypothesized to be due to facilitation of tumor progression by the resulting low-grade chronic inflammation. Indeed, murine tumors expressing human-like levels of Neu5Gc show accelerated growth in syngeneic mice with a human-like Neu5Gc deficiency, coincident with the induction of anti-Neu5Gc antibodies and increased infiltration of inflammatory cells. Transfer of polyclonal monospecific syngeneic mouse anti-Neu5Gc serum also enhanced growth of transplanted syngeneic tumors bearing human-like levels of Neu5Gc, with tumors showing evidence for antibody deposition, enhanced angiogenesis and chronic inflammation. These effects were suppressed by a cyclooxygenase-2 inhibitor, a drug type known to reduce human carcinoma risk. Finally, affinity-purified human anti-Neu5Gc antibodies also accelerate growth of Neu5Gc-containing tumors in Neu5Gc-deficient mice. Taken together, the data suggest that the human propensity to develop diet-related carcinomas is contributed to by local chronic inflammation, resulting from interaction of metabolically-accumulated dietary Neu5Gc with circulating anti-Neu5Gc antibodies.", "title": "Evidence for a human-specific mechanism for diet and antibody-mediated inflammation in carcinoma progression" }, { "docid": "MED-5265", "text": "BACKGROUND: Persons following current dietary guidelines have a lower risk of mortality from coronary heart disease. OBJECTIVE: The objective was to compare the short-term effect of a high-fat meal and a high-carbohydrate meal, with and without dietary antioxidants, on vasomotor, antiplatelet, and hemostatic functions of the endothelium in healthy subjects. DESIGN: In an observer-blinded, randomized crossover study, 25 (13 men and 12 women) healthy subjects were given each of 3 meals in random order at 1-wk intervals: a high-fat meal (760 kcal), an isoenergetic high-carbohydrate meal, and a high-fat meal with dietary antioxidants from vegetables (865 kcal). Endothelial functions, as assessed by hemodynamic and rheologic responses to L-arginine--the natural precursor of nitric oxide--were evaluated before and 4 h after each meal. RESULTS: Unlike the high-carbohydrate meal, the high-fat meal increased the plasma concentrations of triacylglycerol (P < 0.01); both meals activated hemostasis. The high-carbohydrate meal did not modify blood pressure, and platelet aggregation decreased in response to the L-arginine load (-7.1 +/- 2.3 mm Hg and -8.5 +/- 4.5%, respectively). After the high-fat meal, the decrease in blood pressure in response to L-arginine was reduced (-1 +/- 0.8 mm Hg), and platelet aggregation showed a paradoxical increase (4.1 +/- 2.1%; P < 0.01 compared with the high-carbohydrate meal). The high-fat meal with antioxidants partially restored the vascular response to L-arginine. CONCLUSION: Compared with a high-carbohydrate meal, a high-fat meal can modify endothelial functions toward a more atherogenetic profile, which is partially prevented by dietary antioxidants.", "title": "Effect of dietary antioxidants on postprandial endothelial dysfunction induced by a high-fat meal in healthy subjects." }, { "docid": "MED-2581", "text": "A hospital-based case-control study of diet and colorectal cancer was conducted among Chinese in Singapore (who constitute 77% of the population). A total of 203 cases and 425 controls were included. A history of the usual dietary intake one year prior to interview was taken using a quantitative food frequency questionnaire. Daily intakes of nutrients and selected food items were computed and stratified by tertiles of the control range, to assess risk in low-, medium- and high-intake categories. Effects were adjusted in analysis for age, sex, Chinese dialect group and occupation. For cancers of colon and rectum combined, significant observations were a protective effect of high cruciferous vegetable intake (OR = 0.50, p less than 0.01) and a predisposing effect of a high meat/vegetable consumption ratio (OR = 1.77, p less than 0.05). Similar results were observed for colon cancer alone. For rectal cancer alone (only 71 cases), significant (p less than 0.05) protective effects were observed for high intakes of protein (OR = 0.61), fibre (OR = 0.46), beta-carotene (OR = 0.54), cruciferous vegetables (OR = 0.51) and total vegetables (OR = 0.51). When further assessed by multiple logistic regression, tests for trend and assessment of risk in the extreme highest and lowest quintiles of the control range, the factors consistently significant were cruciferous vegetable intake and the meat/vegetable ratio. A particularly high relative risk was also noted in association with low coffee consumption (OR = 1.59, with p less than 0.05 for trend). No consistent trends were noted for fat or fibre intakes. For non-dietary variables investigated, a history of cholecystectomy increased the risk of both cancers combined (OR = 3.43, p less than 0.05) and colon cancer alone (OR = 4.39, p less than 0.01). This study in an Asian population of countries of Southern and Eastern Asia newly undergoing industrialization and in which rapid economic change is reflected in changing cancer patterns, suggests that the protective effects of certain dietary constituents, notably the cruciferous vegetables, may be more important than the hitherto stressed carcinogenic potential of fat and protein.", "title": "Colorectal cancer and diet in an Asian population--a case-control study among Singapore Chinese." }, { "docid": "MED-3876", "text": "BACKGROUND: Chinese men have lower incidences of prostate cancer compared to men from Europe and North America. Asians consume large quantities of soya, a rich source of isoflavanoids phyto-oestrogens and have high plasma and urinary levels of these compounds. The mammalian lignans, enterolactone and enterodiol, are another group of weak plant oestrogens and are derived from seeds, cereals and grains. Vegetarians have high plasma and urinary concentrations of lignans. METHODS: The concentrations lignans and isoflavonic phyto-oestrogens were determined by gas chromatography-mass spectrometry (GC-MS) in plasma and prostatic fluid from Portuguese, Chinese and British men consuming their traditional diets. RESULTS: In prostatic fluid the mean concentrations of enterolactone were 31, 162 and 20.3 ng/ml for Hong Kong, Portugal and Britain respectively. Very high levels of enterolactone (> 600 ng/ml) were observed in the prostatic fluid of some of the men from Portugal. High concentrations of equol (3270 ng/ml) and daidzein (532 ng/ml) were found in a sample of prostatic fluid from Hong Kong. Higher mean levels of daidzein were observed in prostatic fluid from Hong Kong at 70 ng/ml, compared to 4.6 and 11.3 ng/ml in samples from Portugal and Britain respectively. Mean levels of daidzein were higher in the plasma samples from Hong Kong (31.3 ng/ml) compared to those from Portugal (1.3 ng/ml) and Britain (8.2 ng/ml). In general, the mean plasma concentrations of enterolactone from the three centres were similar, at 6.2, 3.9 and 3.9 ng/ml in samples from Hong Kong Portugal and Britain respectively. CONCLUSIONS: Higher concentrations of the isoflavanoid phyto-oestrogens, daidzein and equol, were found in the plasma and prostatic fluid of men from Hong Kong compared to those from Britain and Portugal. However, the levels of the lignan, enterolactone, were very much higher in prostatic fluid of Portuguese men. Isoflavanoids and lignans have many interesting properties and may, in part, be responsible for lower incidences of prostate cancer in men from Asia and also some Mediterranean countries. The isoflavanoids from soya, which are present in high concentrations in the prostatic fluid of Asian men, may be protective against prostate disease.", "title": "Lignans and isoflavonoids in plasma and prostatic fluid in men: samples from Portugal, Hong Kong, and the United Kingdom." }, { "docid": "MED-4767", "text": "We previously reported that chickens infected with the avian adenovirus SMAM-1 developed a unique syndrome characterized by excessive intra-abdominal fat deposition accompanied by paradoxically low serum cholesterol and triglyceride levels. There have been no previous reports of avian adenoviruses infecting humans. We screened the serum of 52 humans with obesity in Bombay, India, for antibodies against SMAM-1 virus using the agar gel precipitation test (AGPT) method. Bodyweights and serum cholesterol and triglyceride levels were compared in SMAM-1-positive (P-AGPT) and SMAM-1-negative (N-AGPT) groups. Ten subjects were positive for antibodies to SMAM-1, and 42 subjects did not have antibodies. The P-AGPT group had a significantly higher bodyweight (p < 0.02) and body mass index (p < 0.001) (95.1 +/- 2.1 kg and 35.3 +/- 1.5 kg/m2, respectively) compared with the N-AGPT group (80.1 +/- 0.6 kg and 30.7 +/- 0.6 kg/m2, respectively). Also, the P-AGPT group had significantly lower serum cholesterol (p < 0.02) and triglyceride (p < 0.001) values (4.65 mmol/L and 1.45 mmol/L, respectively) compared with the N-AGPT group (5.51 mmol/L and 2.44 mmol/L, respectively). Two subjects positive for SMAM-1 antibodies had antibodies against each others' serum, suggesting the presence of antigens in one or both. When these two serum samples were inoculated into chicken embryos, macroscopic lesions compatible with SMAM-1 infection developed. The inoculation of serum from N-AGPT subjects did not produce such lesions. The presence of increased obesity, antibodies to SMAM-1, reduced levels of blood lipids, and viremia that produces a typical infection in chicken embryos suggests that SMAM-1, or a serologically similar human virus, may be involved in the cause of obesity in some humans.", "title": "Association of adenovirus infection with human obesity." }, { "docid": "MED-5002", "text": "BACKGROUND/AIMS: Cell culture studies suggest that phytoestrogens, abundant in soy products such as tempe and tofu, could protect against cognitive decline. Paradoxically, the Honolulu Asia Aging Study reported an increased risk for cognitive impairment and other dementia markers with high tofu (soybean curd) intake. METHODS: A cross-sectional study was carried out in 2 rural sites (Borobudur and Sumedang) and 1 urban site (Jakarta) among mainly Javanese and Sundanese elderly (n = 719, 52-98 years of age). Memory was measured using a word learning test sensitive to dementia and soy consumption was assessed using Food Frequency Questionnaire items. RESULTS: High tofu consumption was associated with worse memory (beta = -0.18, p < 0.01, 95% CI = -0.34 to -0.06), while high tempe consumption (a fermented whole soybean product) was independently related to better memory (beta = 0.12, p < 0.05, 95% CI = 0.00-0.28), particularly in participants over 68 years of age. Fruit consumption also had an independent positive association. The analyses were controlled for age, sex, education, site and intake of other foods. CONCLUSION: The results for tofu consumption as a risk factor for low memory function may tie in with the Honolulu Asia Aging Study data. It is unclear whether these negative associations could be attributed to potential toxins or to its phytoestrogen levels. Estrogen (through which receptors phytoestrogens can exert effects) was found to increase dementia risk in women over 65 years of age. Tempe contains high levels of phytoestrogens, but (due to fermentation) also exhibits high folate levels which may exert protective effects. Future studies should validate these findings and investigate potential mechanisms. Copyright 2008 S. Karger AG, Basel.", "title": "High tofu intake is associated with worse memory in elderly Indonesian men and women." }, { "docid": "MED-1810", "text": "BACKGROUND: We previously reported that human adenovirus Ad-36 induces adiposity and paradoxically lower levels of serum cholesterol (CHOL) and triglycerides (TG) in animals. OBJECTIVE: To evaluate the transmissibility of Ad-36 and Ad-36 induced adiposity using a chicken model. DESIGN: Experiment 1--four chickens were housed (two per cage) and one from each cage was inoculated with Ad-36. Duration of presence of Ad-36 DNA in the blood of all chickens was monitored. Experiment 2--two groups of chickens were intranasally inoculated with Ad-36 (infected donors, I-D) or media (control donors, C-D). Blood drawn 36 h later from I-D and C-D groups was inoculated into wing veins of recipient chickens (infected receivers, I-R, and control receivers, C-R, respectively). On sacrifice, 5 weeks post-inoculation, blood was drawn, body weight noted and visceral fat was separated and weighed. RESULTS: Experiment 1--Ad-36 DNA appeared in the blood of the inoculated chickens and that of uninoculated chickens (cage mates) within 12 h of inoculation and the viral DNA persisted up to 25 days in the blood. Experiment 2--compared with C-D, visceral and total body fat were significantly greater and CHOL significantly lower for the I-D and I-R. TG were significantly lower for the I-D. Ad-36 was isolated from 12 out of 16 blood samples of the I-D that were used for inoculating I-R chickens. Ad-36 DNA was present in the blood and the adipose tissue of the I-D and I-R but not in the skeletal muscles of animals selected randomly for testing. CONCLUSION: As seen in experiment 1, Ad-36 infection can be transmitted horizontally from an infected chicken to another chicken sharing the cage. Additionally, experiment 2 demonstrated blood-borne transmission of Ad-36-induced adiposity in chickens. Transmissibility of Ad-36-induced adiposity in chicken model raises serious concerns about such a possibility in humans that needs further investigation.", "title": "Transmissibility of adenovirus-induced adiposity in a chicken model." }, { "docid": "MED-4662", "text": "Mild iodine deficiency is a recognised problem in Australia and New Zealand. However, iodine excess can cause hypothyroidism in some infants. We highlight two cases which illustrate the risks of excess dietary iodine intake during pregnancy and breastfeeding. They also describe a cultural practice of consuming seaweed soup to promote breast milk supply. Although most attention recently has been on the inadequacy of iodine in Australian diets, the reverse situation should not be overlooked. Neither feast nor famine is desirable. © 2011 The Authors. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).", "title": "Iodine-induced neonatal hypothyroidism secondary to maternal seaweed consumption: a common practice in some Asian cultures to promote breast milk s..." }, { "docid": "MED-3854", "text": "Phytoestrogens are polyphenolic secondary plant metabolites that have structural and functional similarities to 17beta-oestradiol and have been associated with a protective effect against hormone-related cancers. Most foods in the UK only contain small amounts of phytoestrogens (median content 21 microg/100 g) and the highest content is found in soya and soya-containing foods. The highest phytoestrogen content in commonly consumed foods is found in breads (average content 450 microg/100 g), the main source of isoflavones in the UK diet. The phytoestrogen consumption in cases and controls was considerably lower than in Asian countries. No significant associations between phytoestrogen intake and breast cancer risk in a nested case-control study in EPIC Norfolk were found. Conversely, colorectal cancer risk was inversely associated with enterolignan intake in women but not in men. Prostate cancer risk was positively associated with enterolignan intake, however this association became non-significant when adjusting for dairy intake, suggesting that enterolignans can act as a surrogate marker for dairy or calcium intake. 2010 Elsevier Inc. All rights reserved.", "title": "Phytoestrogen consumption and association with breast, prostate and colorectal cancer in EPIC Norfolk." }, { "docid": "MED-1993", "text": "Type 2 diabetes mellitus is emerging as a new clinical problem within pediatric practice. Recent reports indicate an increasing prevalence of type 2 diabetes mellitus in children and adolescents around the world in all ethnicities, even if the prevalence of obesity is not increasing any more. The majority of young people diagnosed with type 2 diabetes mellitus was found in specific ethnic subgroups such as African-American, Hispanic, Asian/Pacific Islanders and American Indians. Clinicians should be aware of the frequent mild or asymptomatic manifestation of type 2 diabetes mellitus in childhood. Therefore, a screening seems meaningful especially in high risk groups such as children and adolescents with obesity, relatives with type 2 diabetes mellitus, and clinical features of insulin resistance (hypertension, dyslipidemia, polycystic ovarian syndrome, or acanthosis nigricans). Treatment of choice is lifestyle intervention followed by pharmacological treatment (e.g., metformin). New drugs such as dipeptidyl peptidase inhibitors or glucagon like peptide 1 mimetics are in the pipeline for treatment of youth with type 2 diabetes mellitus. However, recent reports indicate a high dropout of the medical care system of adolescents with type 2 diabetes mellitus suggesting that management of children and adolescents with type 2 diabetes mellitus requires some remodeling of current healthcare practices.", "title": "Type 2 diabetes mellitus in children and adolescents" }, { "docid": "MED-1381", "text": "Perhaps one of the most unexpected and novel findings in nutritional epidemiology in the past 5 y has been that nut consumption seems to protect against ischemic heart disease (IHD). Frequency and quantity of nut consumption have been documented to be higher in vegetarian than in nonvegetarian populations. Nuts also constitute an important part of other plant-based diets, such as Mediterranean and Asian diets. In a large, prospective epidemiologic study of Seventh-day Adventists in California, we found that frequency of nut consumption had a substantial and highly significant inverse association with risk of myocardial infarction and death from IHD. The Iowa Women's Health Study also documented an association between nut consumption and decreased risk of IHD. The protective effect of nuts on IHD has been found in men and women and in the elderly. Importantly, nuts have similar associations in both vegetarians and nonvegetarians. The protective effect of nut consumption on IHD is not offset by increased mortality from other causes. Moreover, frequency of nut consumption has been found to be inversely related to all-cause mortality in several population groups such as whites, blacks, and the elderly. Thus, nut consumption may not only offer protection against IHD, but also increase longevity.", "title": "Nut consumption, vegetarian diets, ischemic heart disease risk, and all-cause mortality: evidence from epidemiologic studies." }, { "docid": "MED-2009", "text": "Chickpea (Cicer arietinum L.) is an important pulse crop grown and consumed all over the world, especially in the Afro-Asian countries. It is a good source of carbohydrates and protein, and protein quality is considered to be better than other pulses. Chickpea has significant amounts of all the essential amino acids except sulphur-containing amino acids, which can be complemented by adding cereals to the daily diet. Starch is the major storage carbohydrate followed by dietary fibre, oligosaccharides and simple sugars such as glucose and sucrose. Although lipids are present in low amounts, chickpea is rich in nutritionally important unsaturated fatty acids such as linoleic and oleic acids. β-Sitosterol, campesterol and stigmasterol are important sterols present in chickpea oil. Ca, Mg, P and, especially, K are also present in chickpea seeds. Chickpea is a good source of important vitamins such as riboflavin, niacin, thiamin, folate and the vitamin A precursor β-carotene. As with other pulses, chickpea seeds also contain anti-nutritional factors which can be reduced or eliminated by different cooking techniques. Chickpea has several potential health benefits, and, in combination with other pulses and cereals, it could have beneficial effects on some of the important human diseases such as CVD, type 2 diabetes, digestive diseases and some cancers. Overall, chickpea is an important pulse crop with a diverse array of potential nutritional and health benefits.", "title": "Nutritional quality and health benefits of chickpea (Cicer arietinum L.): a review." }, { "docid": "MED-3930", "text": "Studies that have addressed the association between the intake of coffee or caffeine and Parkinson's disease (PD) were conducted mainly in Western countries. Little is known about this relationship in an Asian population. Therefore, we performed an assessment of the association of the intake of coffee, other caffeine-containing beverages, and caffeine with the risk of PD in Japan. The study involved 249 PD cases and 368 control subjects. Information on dietary factors was obtained through a self-administered diet history questionnaire. Adjustment was made for sex, age, region of residence, educational level, pack-years of smoking, body mass index, the dietary glycemic index, and intake of cholesterol, vitamin E, β-carotene, vitamin B(6,) alcohol, and iron. Intake of coffee, black tea, and Japanese and Chinese teas was significantly inversely associated with the risk of PD: the adjusted odds ratios in comparison of the highest with the lowest quartile were 0.52, 0.58, and 0.59, respectively (95% confidence intervals = 0.30-0.90, 0.35-0.97, and 0.35-0.995, respectively). A clear inverse dose-response relationship between total caffeine intake and PD risk was observed. We confirmed that the intake of coffee and caffeine reduced the risk of PD. Furthermore, this is the first study to show a significant inverse relationship between the intake of Japanese and Chinese teas and the risk of PD. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Intake of Japanese and Chinese teas reduces risk of Parkinson's disease." }, { "docid": "MED-4755", "text": "OBJECTIVE: To critically evaluate the clinical evidence, and when not available, the animal data, most relevant to concerns that isoflavone exposure in the form of supplements or soy foods has feminizing effects on men. DESIGN: Medline literature review and cross-reference of published data. RESULT(S): In contrast to the results of some rodent studies, findings from a recently published metaanalysis and subsequently published studies show that neither isoflavone supplements nor isoflavone-rich soy affect total or free testosterone (T) levels. Similarly, there is essentially no evidence from the nine identified clinical studies that isoflavone exposure affects circulating estrogen levels in men. Clinical evidence also indicates that isoflavones have no effect on sperm or semen parameters, although only three intervention studies were identified and none were longer than 3 months in duration. Finally, findings from animal studies suggesting that isoflavones increase the risk of erectile dysfunction are not applicable to men, because of differences in isoflavone metabolism between rodents and humans and the excessively high amount of isoflavones to which the animals were exposed. CONCLUSION(S): The intervention data indicate that isoflavones do not exert feminizing effects on men at intake levels equal to and even considerably higher than are typical for Asian males. Copyright 2010. Published by Elsevier Inc.", "title": "Soybean isoflavone exposure does not have feminizing effects on men: a critical examination of the clinical evidence." } ]
5733
APR for a Loan Paid Off Monthly
[ { "docid": "220176", "text": "The periodic rate (here, the interest charged per month), as you would enter into a finance calculator is 9.05%. Multiply by 12 to get 108.6% or calculate APR at 182.8%. Either way it's far more than 68%. If the $1680 were paid after 365 days, it would be simple interest of 68%. For the fact that payment are made along the way, the numbers change. Edit - A finance calculator has 5 buttons to cover the calculations: N = number of periods or payments %i = the interest per period PV = present value PMT = Payment per period FV= Future value In your example, you've given us the number of periods, 12, present value, $1000, future value, 0, and payment, $140. The calculator tells me this is a monthly rate of 9%. As Dilip noted, you can compound as you wish, depending on what you are looking for, but the 9% isn't an opinion, it's the math. TI BA-35 Solar. Discontinued, but available on eBay. Worth every cent. Per mhoran's comment, I'll add the spreadsheet version. I literally copied and pasted his text into a open cell, and after entering the cell shows, which I rounded to 9.05%. Note, the $1000 is negative, it starts as an amount owed. And for Dilip - 1.0905^12 = 2.8281 or 182.8% effective rate. If I am the loanshark lending this money, charging 9% per month, my $1000 investment returns $2828 by the end of the year, assuming, of course, that the payment is reinvested immediately. The 108 >> 182 seems disturbing, but for lower numbers, even 12% per year, the monthly compounding only results in 12.68%", "title": "" }, { "docid": "170167", "text": "If your APR is quoted as nominal rate compounded monthly, the APR is 108.6 %. Here is the calculation, (done in Mathematica ). The sum of the discounted future payments (p) are set equal to the present value (pv) of the loan, and solved for the periodic interest rate (r). Details of the effective interest rate calculation can be found here. http://en.wikipedia.org/wiki/Effective_interest_rate#Calculation", "title": "" } ]
[ { "docid": "487621", "text": "So my advice for your financial situation depends on your aims. Are you aiming to: - Completely clear your debt - Clear one card to free up more monthly income. - Clear some debt to allow further controlled spending - Clear one card and focus on just using one, having 2nd as emergency. There are other things you may wish to do but you said to pay off some / all of 2 credit card bills. If you want to contact me I can plan this more precisely. Some seem the same but other factors can come into play as well. Differing rates of interest make the options clearer. My first advice would be to call the card companies and see if you can get better rates first. SCENARIO (some figures made up for visual) Credit Card Debts 8,000 8,000 Monthly payment 100 100 APR % 10 10 Ignoring APR this will be 80 months to repay (otherwise 140 months using my example amounts above) £28,000 repaid over 11 years 8 months. Your Suggestion As per your suggestion originally, paying off cards equally will allow smaller debt on both cards. Credit Card Debt 3,000 3,000 Monthly payment 100 100 APR % 10 10 With a 0% APR this would be paid off in 2 years 6 months. Cards are available to get free balance transfers, need to look into this. With the 10% APR this would take 3 years 1 month. £10,000 lump and £7,400 repaid over 3 years 1 month (saving £10,600 and 8 years 7 months) AIM: To clear debt completely. My advice here is to use the £10,000 lump sum to pay off one credit card, the remaining £2,000 can then come off the other card. This will free up your outgoings (was 2 x £100) by £100. But then use this £100 to pay off the card, this will result in the following: Credit Card Debt 6,000 Monthly payment 200 APR % 10 With a 0% APR this would be paid off in 2 years 6 months. Cards are available to get free balance transfers, need to look into this. With 10% APR this would take roughly 3 years 1 month. £10,000 lump and £7,400 repaid over 3 years 1 month (saving £10,600 and 8 years 7 months). This option is the same as above, but you have the options on the odd tight month to reduce payments to £100. This also will allow the 2nd card to be used interest free for an emergency purchase (to be paid off without any interest charge) If rates are different, pay of the one with the higher APR AIM: Clear one card to free up more monthly income. AIM: Clear one card and focus on just using one, having 2nd as emergency. Same as above, but don’t increase to £200, leave monthly payment at £100. Credit Card Debt 6,000 Monthly payment 100 APR % 10 With a 0% APR this would be paid off in 5 years. With the 10% APR this would take 88 months (7 years 4 months) £10,000 lump and £8,800 repaid over 7 years and 4 months (saving £9,200 and 4 years 4 months). This also allows for some extra spending (even racking back up the debt – although not advised) AIM: Clear some debt to allow further controlled spending As above apart from this will allow you to spend to get back up to full £16,000 debt. NOTE My figures are theoretical, paying off £500 (£250x2) a month instead of the £100 (10%APR) would take: Lump sum 10,000, remaining 6,000 – 14 months (£17,000 paid) Lump sum 5,000, remaining 2 x 5,500 – 26 months (£18,000 paid) Lump Sum 0, remaining 2 x 8,000 – 40 months (£20,000 paid) Now I have finished waffling, I hope you have an idea on what you are aiming to achieve and a better idea of what to do when you receive the income  Stephen.", "title": "" }, { "docid": "445290", "text": "The question states :- Our insurance company is offering a 30% discount on an $8200/year commercial policy, if we install sprinklers. The insurance is paid in two installments. ... This appears to mean six-monthly payments, so I'll make some comparison calculations using six-monthly loan repayments to keep things simple. Without the loan or sprinklers the insurance costs $4100 every six months. Using this loan payment formula, the calculation below shows, with the 30% discounted insurance, sprinkler maintenance and loan repayment, you would be paying $4655.28 every six months. The discount required to break even is 43.5%. I.e. rearranging the equation :- Alternatively, with the discount of 30% you would break even if the six-monthly repayment amount was $1030. Solving the payment equation for s gives an equation for the loan :- So with the 30% discount you would break even if the loan required was $25989. Checking by back-calculating the periodic payment amount, a :- Likewise we can keep the loan at $40000 and solve for t to find the break-even loan term :- (Note, in this formula Log denotes the natural logarithm.) Now we can set some values :- So with break-even payments the $40000 loan is paid off in just under 65.5 years. I.e. checking :- This just beats the $4100 cost of proceeding without the sprinklers. Notes If your loan repayment was monthly it would reduce the cost of the loan slightly. The periodic interest rate is calculated from the APR according to the method used in the EU and in some cases in US. The calculations above were run using Mathematica.", "title": "" }, { "docid": "372921", "text": "\"Basically, the easiest way to do this is to chart out the \"\"what-ifs\"\". Applying the amortization formula (see here) using the numbers you supplied and a little guesswork, I calculated an interest rate of 3.75% (which is good) and that you've already made 17 semi-monthly payments (8 and a half months' worth) of $680.04, out of a 30-year, 720-payment loan term. These are the numbers I will use. Let's now suppose that tomorrow, you found $100 extra every two weeks in your budget, and decided to put it toward your mortgage starting with the next payment. That makes the semi-monthly payments $780 each. You would pay off the mortgage in 23 years (making 557 more payments instead of 703 more). Your total payments will be $434,460, down from $478.040, so your interest costs on the loan were reduced by $43,580 (but, my mistake, we can't count this amount as money in the bank; it's included in the next amount of money to come in). Now, after the mortgage is paid off, you have $780 semi-monthly for the remaining 73 months of your original 30-year loan (a total of $113,880) which you can now do something else with. If you stuffed it in your mattress, you'd earn 0% and so that's the worst-case scenario. For anything else to be worth it, you must be getting a rate of return such that $100 payments, 24 times a year for a total of 703 payments must equal $113,880. We use the future value annuity formula (here): v = p*((i+1)n-1)/i, plugging in v ($113880, our FV goal), $100 for P (the monthly payment) and 703 for n (total number of payments. We're looking for i, the interest rate. We're making 24 payments per year, so the value of i we find will be 1/24 of the stated annual interest rate of any account you put it into. We find that in order to make the same amount of money on an annuity that you save by paying off the loan, the interest rate on the account must average 3.07%. However, you're probably not going to stuff the savings from the mortgage in your mattress and sleep on it for 6 years. What if you invest it, in the same security you're considering now? That would be 146 payments of $780 into an interest-bearing account, plus the interest savings. Now, the interest rate on the security must be greater, because you're not only saving money on the mortgage, you're making money on the savings. Assuming the annuity APR stays the same now vs later, we find that the APR on the annuity must equal, surprise, 3.75% in order to end up with the same amount of money. Why is that? Well, the interest growing on your $100 semi-monthly exactly offsets the interest you would save on the mortgage by reducing the principal by $100. Both the loan balance you would remove and the annuity balance you increase would accrue the same interest over the same time if they had the same rate. The main difference, to you, is that by paying into the annuity now, you have cash now; by paying into the mortgage now, you don't have money now, but you have WAY more money later. The actual real time-values of the money, however, are the same; the future value of $200/mo for 30 years is equal to $0/mo for 24 years and then $1560/mo for 6 years, but the real money paid in over 30 years is $72,000 vs $112,320. That kind of math is why analysts encourage people to start retirement saving early. One more thing. If you live in the United States, the interest charges on your mortgage are tax-deductible. So, that $43,580 you saved by paying down the mortgage? Take 25% of it and throw it away as taxes (assuming you're in the most common wage-earner tax bracket). That's $10895 in potential tax savings that you don't get over the life of the loan. If you penalize the \"\"pay-off-early\"\" track by subtracting those extra taxes, you find that the break-even APR on the annuity account is about 3.095%.\"", "title": "" }, { "docid": "16051", "text": "The formula for determining the number of payments (months) you'll need to make on your loan is: where i=monthly interest rate (annual rate / 12), A=loan amount (principal), and P=monthly payment. To determine the total interest that you will pay, you can use the following formula: where P=monthly payment, N=number of payments (from above formula), and A=loan amount (principal). A quick example: using the numbers in the screenshot above ($10,000 loan, $500 monthly payment, 10% APR), the number of payments ends up to be 21.97 (which means that payment number 22 is slightly less than the rest). In the second formula, you take that number times your $500 payment and determine that you have paid $10,984.81 over the course of the entire loan period. Subtracting the principal, you have paid $984.81 in total interest. On your spreadsheet, the function you are looking for is NPER: NPER(rate, payment_amount, present_value, [future_value, end_or_beginning]) rate - The interest rate. (This should be the monthly rate, or the annual rate divided by 12.) payment_amount - The amount of each payment made. (For a loan payment, this should be a negative number.) present_value - The current value of the annuity. (The initial principal of the loan) future_value - [ OPTIONAL ] - The future value remaining after the final payment has been made. (This should be 0, the default if omitted.) end_or_beginning - [ OPTIONAL - 0 by default ] - Whether payments are due at the end (0) or beginning (1) of each period.", "title": "" }, { "docid": "395376", "text": "Withdrawing from your 401(k) may include a 10% withdrawal penalty. There are ways to avoid the withdrawal penalty for early disbursements. The idea is to reduce your interest expense by leveraging free loans (0% APR purchases). This will help you pay down your debt more. If you have 0% APR on purchases, you can make purchases on things you already buy. Then use that money towards other debt, while making monthly payments on the 0% APR card. This way, you pay off the credit card before the 0% APR changes. You can then rinse and repeat on another 0% APR card offer. If your credit score is 800, you can do this multiple times. Citi Simplicity gives you 18 months 0% APR. Chase Slate and Chase Freedom gives you 15 months 0% APR. Others typically give you 12 months or less.", "title": "" }, { "docid": "550457", "text": "\"Outstanding principal balance is the amount you owe at any given time, not including the amount of interest you need to pay as soon as possible. The \"\"capitalized interest\"\" shown is consistent with an average of 13.5 months between when each dollar is borrowed and when the repayment period begins. Suppose you borrow the first half of the money on September 1, 2017 and the second half of the money on February 1, 2017 (5 months later). At that point, half the money has been accruing interest for 5 months. On January 1, 2018, half the money accrued interest for 16 months, and half the money accrued interest for 11 months. The lender now expects you to start repaying the loan, with the first payment due at the end of January 2018 or the beginning of February 2018. If you make the minimum payments on time, the lender expects you to make 120 monthly payments. The last monthly payment would be at the end of December 2027 or the beginning of January 2028. The lender (or the website) should provide details about the actual payment plan, grace periods, provisions for handling inability to pay due to unemployment, and other terms. In the United States, most installment loans pretend that (for purposes of calculating interest) every month has 30 days -- even February and July! Each month, 1/12 of the \"\"annual percentage rate\"\" (APR) is charged as interest. If you do the compounding, a 6.8 percent APR corresponds to (1 + 0.068 / 12)^12 - 1 = 7.016 percent \"\"annual percentage yield\"\" (APY). Also, the APR is understated. The 6.8 percent applies to the full balance (including the loan fees), even though the borrower only gets the amount minus the loan fees. The 6.8 percent rate is useful for doing calculations after the loan fees have been charged, though. These calculations include the capitalized interest and the monthly payment amounts. A true calculation of the APR would take the loan fees into account, and give a higher number than 6.8 percent. But the corrected APR would not be useful for calculating the capitalized interest, nor for calculating the monthly payment amounts.\"", "title": "" }, { "docid": "390900", "text": "Your desire to travel before starting work is smart and something you should do. There are very few opportunities in life where you will have a chunk of time to do such travelling. Having said that, your life plans may or may not pan out the way you expect. Ideally, you'd take the 0% APR for 18 months and max it out. A 3% balance transfer (BT) fee breaks out to 1.5% APR, but due in 1.5 years. That's a very good loan rate if you can pay it before the APR changes. Say, you take 6 months to travel. When you return, you have one year to pay off your credit card bill. Calculate how much you will borrow and how much your monthly payments will be. $1,500 across 12 months is $125. Can you add that as a monthly expense? What will your life circumstances be when you return from travel? Do you know what your income will be? Do you know what your expected expenses will be? How much padding will you have for emergencies?", "title": "" }, { "docid": "293501", "text": "\"Taking the last case first, this works out exactly. (Note the Bank of England interest rate has nothing to do with the calculation.) The standard loan formula for an ordinary annuity can be used (as described by BobbyScon), but the periodic interest rate has to be calculated from an effective APR, not a nominal rate. For details, see APR in the EU and UK, where the definition is only valid for effective APR, as shown below. 2003 BMW 325i £7477 TYPICAL APR 12.9% 60 monthly payments £167.05 How does this work? See the section Calculating the Present Value of an Ordinary Annuity. The payment formula is derived from the sum of the payments, each discounted to present value. I.e. The example relates to the EU APR definition like so. Next, the second case doesn't make much sense (unless there is a downpayment). 2004 HONDA CIVIC 1.6 i-VTEC SE 5 door Hatchback £6,999 £113.15 per month \"\"At APR 9.9% [as quoted in advert], 58 monthly payments\"\" 58 monthly payments at 9.9% only amount to £5248.75 which is £1750.25 less than the price of the car. Finally, the first case is approximate. 2005 TOYOTA COROLLA 1.4 VVTi 5 door hatchback £7195 From £38 per week \"\"16.1% APR typical, a 60 month payment, 260 weekly payments\"\" A weekly payment of £38 would imply an APR of 14.3%.\"", "title": "" }, { "docid": "40897", "text": "The breakdown between how much of your payment is going toward principal and interest is very important. The principal balance remaining on your loan is the payoff amount. Once the principal is paid off, your loan is finished. Each month, some of your payment goes to pay off the principal, and some goes to pay interest (profit for the bank). Using your example image, let's say that you've just taken out a $300k mortgage at 5% interest for 30 years. You can click here to see the amortization schedule on that loan. The monthly payment is $1610.46. On your first payment, only $360 went to pay off your principal. The rest ($1250) went to interest. That money is lost. If you were to pay off your $300k mortgage after making one payment, it would cost you $299,640, even though you had just made a payment of $1250. Interest accrues on the principal balance, so as time goes on and more of the principal has been paid, the interest payment is less, meaning that more of your monthly payment can go toward the principal. 15 years into your 30-year mortgage, your monthly payment is paying $762 of your principal, and only $849 is going toward interest. Your principal balance at that time would be about $203k. Even though you are halfway done with your mortgage in terms of time, you've only paid off about a third of your house. Toward the end of your mortgage, when your principal balance is very low, almost all of your payment goes toward principal. In the last year, only $513 of your payments goes toward interest for the whole year. You can think of your monthly loan payment as a minimum payment. If you continue to make the regular monthly payments, your mortgage will be paid off in 30 years. However, if you pay more than that, your mortgage will be paid off much sooner. The extra that you pay above your regular monthly payment all goes toward principal. Even if you have no plans to pay your mortgage ahead of schedule, there are other situations where the principal balance matters. The principal balance of your mortgage affects the amount of equity that you have in your home, which is important if you sell the house. If you decide to refinance your mortgage, the principal balance is the amount that will need to be paid off by the new loan to close the old loan.", "title": "" }, { "docid": "351044", "text": "I would strongly encourage you to either find specifically where in your written contract the handling of early/over payments are defined and post it for us to help you, or that you go and visit a licensed real estate attorney. Even at a ridiculously high price of 850 pounds per hour for a top UK law firm (and I suspect you can find a competent lawyer for 10-20% of that amount), it would cost you less than a year of prepayment penalty to get professional advice on what to do with your mortgage. A certified public accountant (CPA) might be able to advise you, as well, if that's any easier for you to find. I have the sneaking suspicion that the company representatives are not being entirely forthcoming with you, thus the need for outside advice. Generally speaking, loans are given an interest rate per period (such as yearly APR), and you pay a percentage (the interest) of the total amount of money you owe (the principle). So if you owe 100,000 at 5% APR, you accrue 5,000 in interest that year. If you pay only the interest each year, you'll pay 50,000 in interest over 10 years - but if you pay everything off in year 8, at a minimum you'd have paid 10,000 less in interest (assuming no prepayment penalties, which you have some of those). So paying off early does not change your APR or your principle amount paid, but it should drastically reduce the interest you pay. Amortization schedules don't change that - they just keep the payments even over the scheduled full life of the loan. Even with prepayment penalties, these are customarily billed at less than 6 months of interest (at the rate you would have payed if you kept the loan), so if you are supposedly on the hook for more than that again I highly suspect something fishy is going on - in which case you'd probably want legal representation to help you put a stop to it. In short, something is definitely and most certainly wrong if paying off a loan years in advance - even after taking into account pre-payment penalties - costs you the same or more than paying the loan off over the full term, on schedule. This is highly abnormal, and frankly even in the US I'd consider it scandalous if it were the case. So please, do look deeper into this - something isn't right!", "title": "" }, { "docid": "105345", "text": "An amortization schedule is often used to produce identical payments for the term (repayment period) of a loan, resulting in the principal being paid off and the debt retired at the end of the loan. This is in contrast to an interest only, or balloon loan. These loans require little or no payment against the balance of the loan, requiring the loan to be paid indefinitely if there is no term, or requiring the loan to be entirely paid off from cash or a new loan at the end of the term. A basic amortization formula can be derived from the compound interest formula: This formula comes from the Wikipedia article on amortization. The basics of the formula are the periodic payment amount, A (your monthly payment), can be determined by the principal loan, P, the rate, r, and the number of payments, n. Lenders lend money to make a profit on the interest. They'd like to get back all the money they lent out. Amortization schedules are popular because the fixed low payments make it easier for borrowers to pay the loan off eventually. They also tend to be very profitable for lenders, especially at the start of the term, because they make a lot of profit on interest, just like the start of your mortgage. The principal of a mortgage has more meaning than the principal of a revolving debt credit card. The mortgage principal is fixed at the start, and represents the value of the collateral property that is your home. You could consider the amount of principal paid to be the percentage of your home that you actually own (as part of your net worth calculation). A credit card has a new balance each month depending on how much you charge and how much you pay off. Principal has less meaning in this case, because there is no collateral to compare against, and the balance will change monthly. In this case, the meaning of the amortization schedule on your credit card is how long it will take you to pay off the balance if you stop charging and pay at the proscribed payment level over the term described. Given the high interest rate on credit cards, you may end up paying twice as much for goods in the long run if you follow your lenders schedule. Amortizing loans are common for consumer loans, unless a borrower is seeking out the lowest possible monthly payment. Lenders recognize that people will eventually die, and want to be paid off before that happens. Balloon and interest only bonds and loans are more commonly issued by businesses and governments who are (hopefully) investing in capital improvements that will pay off in the long run. Thousands of people and businesses have gone bankrupt in this financial crisis because their interest only loans reached term, and no one was willing to lend them money anymore to replace their existing loan.", "title": "" }, { "docid": "167213", "text": "I don't understand the calculations in the comments by the OP. He says My monthly savings after mandatory expense is around USD 2000. This includes rent, expenses, emergency fund savings, and the monthly required payment of my auto loan. (emphasis added) He has $2000 USD left over after monthly expenses (which includes rent, food, utilities etc, contribution towards emergency funds, and the required monthly payment on the auto loan). He claims that by applying the $2000 USD per month towards reducing the debt, it would take him 30-36 months to be debt-free. But is it not the case that applying the $2000 to the student loan of $18K+ (while continuing to make the auto loan payments) will pay the student loan off in less than 10 months? If no payments are made on that $18K+ student loan, the accrued interest of about $2K in 10 months (this is (18.25*13.7%*)(10/12) for a total of $20K+). In actuality, with the loan being paid down, the interest will be much less. Once the student loan is paid off, the extra $2000 can go towards what is left of the $10K auto loan each month and pay it off in another 4 or 5 months or so. So we are talking of 15 months max instead of 30-36 months. Of course, as Carlos Briebiescas points out, the car is more valuable as an asset than can be sold in case of job loss creating a need for cash etc, and so paying it off first might be better, but that is a different calculation.", "title": "" }, { "docid": "117602", "text": "\"Basically, your CC is (if normal) compounded monthly, based on a yearly APR. To calculate the amount of interest you'd pay on each of these accounts in a year, pull up a spreadsheet like Office Excel. Put in your current balance, then multiply it by the annual interest rate divided by 12, and add that quantity to the balance. Subtract any payment you make, and the result is your new balance. You can project this out for several months to get a good estimate of what you'll pay; in accounting or finance terms, what you're creating is an \"\"amortization table\"\". So, with a $10,000 balance, at 13.99% interest and making payments of $200/mo, the amortization table for one year's payments might look like: As you can see, $200 isn't paying down this card very quickly. In one year, you will have paid $2,400, of which $1,332.25 went straight into the bank's pockets in interest charges, reducing your balance by only $1,067.75. Up the payments to $300/mo, and in 1 year you will have paid $3,600, and only been charged $1,252.24 in interest, so you'll have reduced your balance by $2,347.76 to only $7,652.24, which further reduces interest charges down the line. You can track the differences in the Excel sheet and play \"\"what-ifs\"\" very easily to see the ramifications of spending your $5,000 in various ways. Understand that although, for instance, 13.99% may be your base interest rate, if the account has become delinquent, or you made any cash advances or balance transfers, higher or lower interest rates may be charged on a portion of the balance or the entire balance, depending on what's going on with your account; a balance transfer may get 0% interest for a year, then 19.99% interest after that if not paid off. Cash advances are ALWAYS charged at exorbitantly high rates, up to 40% APR. Most credit card bills will include what may be called an \"\"effective APR\"\", which is a weighted average APR of all the various sub-balances of your account and the interest rates they currently have. Understand that your payment first pays off interest accrued during the past cycle, then pays down the principal on the highest-interest portion of the balance first, so if you have made a balance transfer to another card and are using that card for purchases, the only way to avoid interest on the transfer at the post-incentive rates is to pay off the ENTIRE balance in a year. The minimum payment on a credit card USED to be just the amount of accrued interest or sometimes even less; if you paid only the minimum payment, the balance would never decrease (and may increase). In the wake of the 2008 credit crisis, most banks now enforce a higher minimum payment such that you would pay off the balance in between 3 and 5 years by making only minimum payments. This isn't strictly required AFAIK, but because banks ARE required by the CARD Act to disclose the payoff period at the minimum payment (which would be \"\"never\"\" under most previous policies), the higher minimum payments give cardholders hope that as long as they make the minimum payments and don't charge any more to the card, they will get back to zero.\"", "title": "" }, { "docid": "209238", "text": "The general concept is that your money will grow at an accelerating rate because you start getting interest paid on your returns in addition to the original investment. As a simple example, assume you invest $100 and get 10% interest per year paid annually. -At the end of the first year you have your $100 + $10 interest for a total of $110. -So you start the second year with $110 and so 10% would be $11 for a total of $121. -The third year you start with $121 so 10% would be $12.10 for a total of $133.10 See how the amount it goes up each year increases? If we were talking a higher initial amount or a larger number of years that can really add up. That is essence is compound interest. Most of the complicated looking formulas you see out there for compound interest are just shortcuts so you don't have to iteratively go through the above exercise a bunch of times to find out how much you would have after some number of years. This formula tells you how much you would have(A) after a certain number of years(t) at a given interest rate(r) assuming they pay interest n times per year, for example you would use 12 for n if it paid interest monthly instead of yearly. P represents the amount you started out with. If you keep investing monthly (as shown in your example) instead of just depositing it and letting it sit, you have to use a more complicated formula. Finance people refer to this as calculating the future value of an annuity. That formula looks like this: A = PMT [((1 + r)N - 1) / r] x (1+r) A : Is the amount you would have at the end of the time period. N : The number of compounding periods (months if you get interest calculated monthly) PMT : The total amount you are putting in each period (N) r: Just like before, the interest rate you are getting paid. Be sure to adjust this to a monthly number if N represents months (divide APR by 12)* *Most interest rates are quoted as APR, which is the annualized interest rate not counting compounding. Don't confuse this with APY, which has compounding built into it and is not appropriate for use in this formula. Inserting your example: r (monthly interest rate) = 15% APR / 12 = .0125 n = 30 years * 12 months/year = 360 months A = $150 x [((1 + .0125)360 - 1) / .0125] x (1+.0125) A = $1,051,473.09 (rounded)", "title": "" }, { "docid": "366869", "text": "There is no interest outstanding, per se. There is only principal outstanding. Initially, principal outstanding is simply your initial loan amount. The first two sections discuss the math needed - just some arithmetic. The interest that you owe is typically calculated on a monthly basis. The interested owed formula is simply (p*I)/12, where p is the principal outstanding, I is your annual interest, and you're dividing by 12 to turn annual to monthly. With a monthly payment, take out interest owed. What you have left gets applied into lowering your principal outstanding. If your actual monthly payment is less than the interest owed, then you have negative amortization where your principal outstanding goes up instead of down. Regardless of how the monthly payment comes about (eg prepay, underpay, no payment), you just apply these two calculations above and you're set. The sections below will discuss these cases in differing payments in detail. For a standard 30 year fixed rate loan, the monthly payment is calculated to pay-off the entire loan in 30 years. If you pay exactly this amount every month, your loan will be paid off, including the principal, in 30 years. The breakdown of the initial payment will be almost all interest, as you have noticed. Of course, there is a little bit of principal in that payment or your principal outstanding would not decrease and you would never pay off the loan. If you pay any amount less than the monthly payment, you extend the duration of your loan to longer than 30 years. How much less than the monthly payment will determine how much longer you extend your loan. If it's a little less, you may extend your loan to 40 years. It's possible to extend the loan to any duration you like by paying less. Mathematically, this makes sense, but legally, the loan department will say you're in breach of your contract. Let's pay a little less and see what happens. If you pay exactly the interest owed = (p*I)/12, you would have an infinite duration loan where your principal outstanding would always be the same as your initial principal or the initial amount of your loan. If you pay less than the interest owed, you will actually owe more every month. In other words, your principal outstanding will increase every month!!! This is called negative amortization. Of course, this includes the case where you make zero payment. You will owe more money every month. Of course, for most loans, you cannot pay less than the required monthly payments. If you do, you are in default of the loan terms. If you pay more than the required monthly payment, you shorten the duration of your loan. Your principal outstanding will be less by the amount that you overpaid the required monthly payment by. For example, if your required monthly payment is $200 and you paid $300, $100 will go into reducing your principal outstanding (in addition to the bit in the $200 used to pay down your principal outstanding). Of course, if you hit the lottery and overpay by the entire principal outstanding amount, then you will have paid off the entire loan in one shot! When you get to non-standard contracts, a loan can be structured to have any kind of required monthly payments. They don't have to be fixed. For example, there are Balloon Loans where you have small monthly payments in the beginning and large monthly payments in the last year. Is the math any different? Not really - you still apply the one important formula, interest owed = (p*I)/12, on a monthly basis. Then you break down the amount you paid for the month into the interest owed you just calculated and principal. You apply that principal amount to lowering your principal outstanding for the next month. Supposing that what you have posted is accurate, the most likely scenario is that you have a structured 5 year car loan where your monthly payments are smaller than the required fixed monthly payment for a 5 year loan, so even after 2 years, you owe as much or more than you did in the beginning! That means you have some large balloon payments towards the end of your loan. All of this is just part of the contract and has nothing to do with your prepay. Maybe I'm incorrect in my thinking, but I have a question about prepaying a loan. When you take out a mortgage on a home or a car loan, it is my understanding that for the first years of payment you are paying mostly interest. Correct. So, let's take a mortgage loan that allows prepayment without penalty. If I have a 30 year mortgage and I have paid it for 15 years, by the 16th year almost all the interest on the 30 year loan has been paid to the bank and I'm only paying primarily principle for the remainder of the loan. Incorrect. It seems counter-intuitive, but even in year 16, about 53% of your monthly payment still goes to interest!!! It is hard to see this unless you try to do the calculations yourself in a spreadsheet. If suddenly I come into a large sum of money and decide I want to pay off the mortgage in the 16th year, but the bank has already received all the interest computed for 30 years, shouldn't the bank recompute the interest for 16 years and then recalculate what's actually owed in effect on a 16 year loan not a 30 year loan? It is my understanding that the bank doesn't do this. What they do is just tell you the balance owed under the 30 year agreement and that's your payoff amount. Your last sentence is correct. The payoff amount is simply the principal outstanding plus any interest from (p*I)/12 that you owe. In your example of trying to payoff the rest of your 30 year loan in year 16, you will owe around 68% of your original loan amount. That seems unfair. Shouldn't the loan be recalculated as a 16 year loan, which it actually has become? In fact, you do have the equivalent of a 15 year loan (30-15=15) at about 68% of your initial loan amount. If you refinanced, that's exactly what you would see. In other words, for a 30y loan at 5% for $10,000, you have monthly payments of $53.68, which is exactly the same as a 15y loan at 5% for $6,788.39 (your principal outstanding after 15 years of payments), which would also have monthly payments of $53.68. A few years ago I had a 5 year car loan. I wanted to prepay it after 2 years and I asked this question to the lender. I expected a reduction in the interest attached to the car loan since it didn't go the full 5 years. They basically told me I was crazy and the balance owed was the full amount of the 5 year car loan. I didn't prepay it because of this. That is the wrong reason for not prepaying. I suspect you have misunderstood the terms of the loan - look at the Variable Monthly Payments section above for a discussion. The best thing to do with all loans is to read the terms carefully and do the calculations yourself in a spreadsheet. If you are able to get the cashflows spelled out in the contract, then you have understood the loan.", "title": "" }, { "docid": "99865", "text": "\"New car loans, used car loans, and refinances have different rates because they have different risks associated with them, different levels of ability to recoup losses if there is a default, and different customer profiles. (I'm assuming third party lender for all of these questions, not financing the dealer arranges, as that has other considerations built into it.) A new car loan is both safer to some extent (as the car is a \"\"known\"\" risk, having no risk of damage/etc. prior to purchase), but also harder to recoup losses (because new cars immediately devalue significantly, while used cars keep more of their value). Thus the APRs are a little different; in general for the same amount a new car will be a bit lower APR, but of course used car loans are typically lower amounts. Refinance is also different; customer profile wise, the customer who is refinancing in these times is likely someone who is a higher risk (as why are they asking for a loan when they're mostly paid off their car?). Otherwise it's fairly similar to a used car, though probably a bit newer than the average used car.\"", "title": "" }, { "docid": "564408", "text": "\"Assuming the numbers in your comments are accurate, you have $2400/month \"\"extra\"\" after paying your expenses. I assume this includes loan payments. You said you have $3k in savings and a $2900 \"\"monthly nut\"\", so only one month of living expenses in savings. In my opinion, your first goal should be to put 100% of your extra money towards savings each month, until you have six months of living expenses saved. That's $2,900 * 6 or $17,400. Since you have $3K already that means you need $14,400 more, which is exactly six months @ $2,400/month. Next I would pay off your $4K for the bedroom furniture. I don't know the terms you got, but usually if you are not completely paid off when it comes time to pay interest, the rate is very high and you have to pay interest not just going forward, but from the inception of the loan (YMMV--check your loan terms). You may want to look into consolidating your high interest loans into a single loan at a lower rate. Barring that, I would put 100% of my extra monthly income toward your 10% loan until its paid off, and then your 9.25% loan until that's paid off. I would not consider investing in any non-tax-advantaged vehicle until those two loans (at minimum) were paid off. 9.25% is a very good guaranteed return on your money. After that I would continue the strategy of aggressively paying the maximum per month toward your highest interest loans until they are all paid off (with the possible exception of the very low rate Sallie Mae loans). However, I'm probably more conservative than your average investor, and I have a major aversion to paying interest. :)\"", "title": "" }, { "docid": "116930", "text": "There are a few ways to look at this question. Assumptions. Per the original post's assumptions, this answer: In other words, if the owner paid the mortgage on its original schedule, the deal could boil down to a $ 40,000 up-front payment, in exchange for $ 200,000 of equity after 30 years. Or the deal could boil down to a $ 40,000 up-front payment, in exchange for a $ 810.70 monthly payment starting in 30 years. While the owner is paying down the mortgage, the return on equity is the principal payment divided by the equity. The principal payment is the net rent minus non-financing costs and interest, so it is actually a profit. The initial return on equity is 6.321 % APR, or 6.507 % APY. This is calculated by dividing the $ 210.70 monthly principal payment by the initial $ 40,000 equity, and converting from monthly return to annual return. After 30 years, the return on equity is 4.864 % APR, or 4.974 % APY. This is calculated by dividing the $ 810.70 monthly cash flow (which is no longer reduced by mortgage payments) by the $ 200,000 equity after 30 years, and converting from monthly return to annual return. The cap rate is the same as the return on equity in the absence of debt. In this example, 4.864 % APR, or 4.974 % APY. The return on equity declines from 6.507 % APY initially to 4.974 % APY after 30 years. This is because the cap rate exceeds the note rate (4.974 % APY vs. 4.594 % APY), and the leverage decreases from 5x to 1x. The weighted average compound annual growth rate of the equity during the 30 years is 5.511 % APY. Per the original poster's answer, this is computed by taking the 30th root of the 5-fold increase in equity. Because the owner made no extra principal payments (besides those already discussed), the relevant amounts are the initial $ 40,000 owner payment and the final $ 200,000 owner equity. 5.511 % APY corresponds to a 5.377 % APR. The internal rate of return if the owner never sells can be computed by treating the deal as a $ 40,000 up-front payment, in exchange for an $ 810.70 monthly payment starting in 30 years. The internal rate of return (IRR) is not a very useful number, because it assumes that you can somehow reinvest the eventual dividends at the same rate. In this example, the IRR is 5.172 % APR, or 5.296  % APY. In this example, the IRR is calculated by (iteratively) finding an interest rate for which (initial investment) * (1 + IRR) ^ (number periods before dividends start) = (periodic dividend) / (IRR - growth rate of dividend). For example: $ 40,000 * (1.004309687)^360 = $ 810.70 / (0.004309687 - 0) = $ 188,111 I then converted the 0.431 % monthly IRR to an annual IRR. The deal can be thought of as a return on equity, plus a return on paying down the mortgage. When computing the return from paying down the mortgage, the initial equity is irrelevant. It does not matter whether you start with a $ 160,000 mortgage on a $ 160,000 property, a $ 160,000 mortgage on a $ 200,000 property, or a $ 160,000 mortgage on a $ 1,000,000 property. All that matters is the note rate on the mortgage, which is the applicable compound interest rate. The return on paying down the mortgage equals the note rate of the mortgage. For a 4.5% note rate, this works out to a 4.594% annual percentage yield (APY). You can confirm this by looking at your amortization schedule. Suppose you have a $ 160,000 mortgage with a fixed 4.5% APR note rate for 360 months. Your monthly payment is $ 810.70. In the first month, $ 600 goes toward interest, and $ 210.70 reduces the principal. In other words, the $ 210.70 principal payment eliminated the need for a $ 810.70 payment 30 years later. Notice that: . $ 210.70 * (1 + 0.045 / 12)^360 = $ 210.70 * (1.00375)^360 = $ 210.70 * 3.8477 = $ 810.71 which is within rounding error of $ 810.70. The interest rate is 3/8 % per month, which is an APR of 4.5%, and an APY of 4.594 %.", "title": "" }, { "docid": "249006", "text": "\"This summer I used a loan from my 401(k) to help pay for the down payment of a new house. We planned on selling a Condo a few months later, so we only needed the loan for a short period but wanted to keep monthly payments low since we would be paying two mortgages for a few months. I also felt like the market might take a dip in the future, so I liked the idea of trying to cash out high and buy back low (spoiler alert: this didn't happen). So in July 2017 I withdrew $17,000 from my account (Technically $16,850.00 principal and $150 processing fee) at an effective 4.19% APR (4% rate and then the fee), with 240 scheduled payments of $86.00 (2 per month for 10 years). Over the lifetime of the loan the total finance charge was $3,790, but that money would be paid back into my account. I was happy with the terms, and it helped tide things over until the condo was sold a few months later. But then I decided to change jobs, and ended up having to pay back the loan ~20 weeks after it was issued (using the proceeds from the sale of the condo). During this time the market had done well, so when I paid back the funds the net difference in shares that I now owned (including shares purchased with the interest payments) was $538.25 less than today's value of the original count of shares that were sold to fund the loan. Combined with the $150 fee, the overall \"\"cost\"\" of the 20 week loan was about 4.05%. That isn't the interest rate (interest was paid back to my account balance), but the value lost due to the principal having been withdrawn. On paper, my account would be worth that much more if I hadn't withdrawn the money. Now if you extrapolate the current market return into 52 weeks, you can think of that loan having an APR \"\"cost\"\" of around 10.5% (Probably not valid for a multi year calculation, but seems accurate for a 12 month projection). Again, that is not interest paid back to the account, but instead the value lost due to the money not being in the account. Sure, the market could take a dip and I may be able to buy the shares back at a reduced cost, but that would require keeping sizable liquid assets around and trying to time the market. It also is not something you can really schedule very well, as the loan took 6 days to fund (not including another week of clarifying questions back/forth before that) and 10 day to repay (from the time I initiated the paperwork to when the check was cashed and shares repurchased). So in my experience, the true cost of the loan greatly depends on how the market does, and if you have the ability to pay back the loan it probably is worth doing so. Especially since you may be forced to do so at any time if you change jobs or your employment is terminated.\"", "title": "" }, { "docid": "255703", "text": "\"Which option will save you the most money in the long run? That is tough. Assuming you stay healthy, don't lose your job, don't experience a pay cut or any major emergency that drains your savings, then applying the $6000 to the higher interest loan will save you more money in the long run. However, the difference in savings is a few hundred dollars. Not much really. So, in this case, I'd put the $6k towards the smaller loan. Why? Because then you'd pay it off faster. Once that's done, you open up your cash flow by the minimum monthly payment you would have had on that loan. Assuming they both have the same or similar number of months left, by paying the smaller loan off sooner, you'd open up $X month, where $X is your minimum monthly payment. This could be useful to you if you want to take on some other debt (like buying a house) because it lowers your debt to income ratio. If you put that money towards the higher loan, your DTI won't change until the normal time you would have paid off the smaller loan. Even if you are not looking to purchase anything that requires you to have a lower DTI, paying the smaller loan off sooner increases your cash flow sooner (because your monthly payment on the higher loan doesn't change just because you lowered the balance by $6k). So you'd be more robust to emergencies if your current income doesn't allow for much savings. A major emergency could wipe out all savings from paying down the bigger balance. So, I'd suggest: Edit: TripeHound asked a question, pretty much requesting more details for why I was biased towards paying off the smaller loan first. What follows is my response, with a bit of reorganization: Typically, people asking these questions don't have so much wealth that \"\"which loan to pay first?\"\" is an academic question. They need to make smart financial decisions. While paying the highest interest loan saves the most money in interest - that only occurs under the assumption that nothing bad will ever happen to you until the loans are paid off. In reality, other things happen. Tires blow out, children get sick, you get laid off and so the \"\"best\"\" thing to do is the one that maximizes your long term financial health, even if it comes at the expense of a few $k more interest. Each loan has a minimum monthly payment. Let's assume, barring any windfalls of additional cash, you will just make the minimum payments each month towards a loan. If you pay off the smaller loan first, that increases your available monthly cash flow. At that point, you can put extra towards the other loan. However, if an emergency should come up, or you need to save for a vacation, you can do that, without negatively impacting the second loan, because you'd just drop back to its minimum payment. Putting the money towards the higher balance loan would mean it takes you longer to reach this point as the time to reach payoff on the first loan will not change ($6k only reduces the $25.6k loan to $19.6k) so you never gain the flexibility of additional cash flow until the time you would have paid off the $13.5k originally. I'd rather have a few hundred dollars each month that I can choose to use to make additional loan payments, eat out, pay for car repairs, pay for emergencies than be forced to dip into credit or worse, pay day loans, should an emergency happen.\"", "title": "" }, { "docid": "48454", "text": "does that mean that 30% of my monthly payment goes to interest? No, it's much worse then that. The APR is the annual percentage rate. An APR of 30% on $23,000 in debt that means you'll be charged $6,900 in interest for the year. You'll actually owe slightly less since you are reducing your principal slightly over the course of the year. If your monthly payment is $800, $575 of that will be going to interest. That means that over 70% of your monthly payment is going just to interest. This deal makes no sense at all! You'd be better off simply transferring all of your balances on to the credit card with the highest interest rate. You'd be paying almost $200 a month for the 'convenience' of writing one check rather than three.", "title": "" }, { "docid": "160110", "text": "Yes, by paying double the amount each month you would have in effect paid the loan off in less than half the time. For $13000 at 3% over 60 months your monthly repayments would be $233.59. If you double your monthly repayments to $467.18 you would end up paying the loan off by the end of the 29th months, more than halving your loan term, as long as there are no penalties for paying the loan off early.", "title": "" }, { "docid": "254245", "text": "What's the present value of using the payment plan? In all common sense the present value of a loan is the value that you can pay in the present to avoid taking a loan, which in this case is the lump sum payment of $2495. That rather supposes the question is a trick, providing irrelevant information about the stock market. However, if some strange interpretation is required which ignores the lump sum and wants to know how much you need in the present to pay the loan while being able to make 8% on the stock market that can be done. I will initially assume that since the lender's APR works out about 9.6% per month that the 8% from the stock market is also per month, but will also calculate for 8% annual effective and an 8% annual nominal rate. The calculation If you have $x in hand (present value) and it is exactly enough to take the loan while investing in the stock market, the value in successive months is $x plus the market return less the loan payment. In the third month the loan is paid down so the balance is zero. I.e. So the present value of using the payment plan while investing is $2569.37. You would need $2569.37 to cover the loan while investing, which is more than the $2495 lump sum payment requires. Therefore, it would be advisable to make the lump sum payment because it is less expensive: If you have $2569.37 in hand it would be best to pay the lump sum and invest the remaining $74.37 in the stock market. Otherwise you invest $2569.37 (initially), pay the loan and end up with $0 in three months. One might ask, what rate of return would the stock market need to yield to make it worth taking the loan? The APR proposed by the loan can be calculated. The present value of a loan is equal to the sum of the payments discounted to present value. I.e. with ∴ by induction So by comparing the $2495 lump sum payment with $997 over 3 x monthly instalments the interest rate implied by the loan can be found. Solving for r If you could obtain 9.64431% per month on the stock market the $x cash in hand required would be calculated by This is equal to the lump sum payment, so the calculated interest is comparable to the stock market rate of return. If you could gain more than 9.64431% per month on the stock market it would be better to invest and take the loan. Recurrence Form Solving the recurrence form shows the calculation is equivalent to the loan formula, e.g. becomes v[m + 1] = (1 + y) v[m] - p where v[0] = pv where In the final month v[final] = 0, i.e. when m = 3 Compare with the earlier loan formula: s = (d - d (1 + r)^-n) / r They are exactly equivalent, which is quite interesting, (because it wasn't immediately obvious to me that what the lender charges is the mirror opposite of what you gain by investing). The present value can be now be calculated using the formula. Still assuming the 8% stock market return is per month. If the stock market yield is 8% per annum effective rate and if it is given as a nominal annual yield, 8% compounded monthly", "title": "" }, { "docid": "110371", "text": "There are a few things you should keep in mind when getting another vehicle: DON'T use dealership financing. Get an idea of the price range you're looking for, and go to your local bank or find a local credit union and get a pre-approval for a loan amount (that will also let you know what kind of interest rates you'll get). Your credit score is high enough that you shouldn't have any problems securing a decent APR. Check your financing institution's rules on financing beyond the vehicle's value. The CU that refinanced my car noted that between 100% and 120% of the vehicle's value means an additional 2% APR for the life of the loan. Value between 120% and 130% incurred an additional 3% APR. Your goal here is to have the total amount of the loan less than or equal to the value of the car through the sale / trade-in of your current vehicle, and paying off whatever's left out of pocket (either as a down-payment, or simply paying off the existing loan). If you can't manage that, then you're looking at immediately being upside-down on the new vehicle, with a potential APR penalty.", "title": "" }, { "docid": "408308", "text": "I have a job and would like to buy equipment for producing music at home and it would be easier for me to pay for the equipment monthly I just want to address your contention that it would be easier to pay monthly, with an interest calculation. Lets say you get a credit card with a very reasonable rate of 12% and you buy $2,500 of equipment. A typical credit card minimum payment is interest charges + 1% of the principle. You can see how this is going. You've paid nearly $200 to clear about $100 off your principle. Obviously paying the minimum payment will take forever to wipe out this debt. So you pay more, or maybe you get 0% interest for a while and take advantage of that. Paying $100 per month against $2,500 at 12% per year will take 29 months and cost about $390 in interest. At $200 per month it'll take 14 months and cost $184 in interest. Also note, you'll probably get an interest rate closer to 16 or 17%. It's always easier to pay small amounts frequently than it is to pay a lot of money all at once, that ease has a cost. If you're buying the gear to start a little business, or you already have a little business going and want to upgrade some gear, great; disciplined debt handling is a wonderful skill to have in business. If you want to start yourself in to a new hobby, you should not do that with debt. If interest rates are low enough financing something can make sense. 0.9% apr on a car, sure; 15% apr on a mixing board, no. Credit card interest rates are significant and really should not be trifled with.", "title": "" }, { "docid": "450783", "text": "\"Basically, the money you pay in student loan interest is tax deductible, which means as far as the IRS is concerned, you didn't make that money. However, what that saves you on your taxes is a percentage of a percentage; you save the amount of your current marginal rate on the money you paid as interest. Simple example with made-up numbers: Let's say you had a student loan outstanding, and you were making payments of $150 monthly on it. Total payments to said loan in one tax year would be $1800. Of that amount, let's for the sake of argument say that half, $900, was interest. You get your 1098-E with that number on it, and reduce your taxable income by that amount. You're currently doing well, not outstanding but OK, so you're in the 25% tax bracket that most single middle-classers are in. So, your reduction in taxable income of $900 saves you the 25% that those 900 simoleons would have been taxed at, which is $225. So, all told, this loan is a net drain on your disposable income of $1,575, of which $675 is pure cost of capital; you never received a dollar in disbursements to match this amount you're paying, so it's money lost now in return for previous gains. 10 years later, you pay off the debt. Now that $1800 is yours to keep, and to pay full taxes on. You pay $225 more in taxes (actually, because of amortization, the amount of additional taxes has been steadily increasing as the interest portion of the loan payments has reduced) but have the remaining $1575 in your pocket to do something else. While there is good debt and bad debt, debt is debt; whether deductible or not, the IRS will never credit your tax bill in the amount of interest owed (AFAIK; if someone knows of a loan whose interest is a credit instead of a deduction I'm all ears). So, the deduction on this loan reduces your cost of capital to an effective APR of 4.5%, and because it's a student loan and not a mortgage, you don't have to itemize so this is in effect a \"\"free\"\" deduction (even with an FHA mortgage allowing me to deduct interest, property taxes and PMI, and the residual medical costs after insurance of having our new baby, the $11,900 standard deduction for my wife and I was still the better deal this year). But, you're still losing 4.5% per year to interest. That's your break-even; if the money you could use to pay your debt could earn a better return than 4.5%, then invest it, but if not, pay off the loan. Right now, investments that could make you 4.5% are at the bottom edge of a steep increase in risk and variance, so if your expected ROI is close, I'd lean toward paying off the debt.\"", "title": "" }, { "docid": "257046", "text": "I concur with the other answers about not mixing family and money: the one whose loans are paid off second will be taking the credit risk of the other not paying/being able to pay. There may also be tax implications. That said, if you do still want to do this, I think there's a fairly straightforward way to account for the payments. With your scenario, your brother should make you a personal loan at some interest rate inbetween 5% and 10%. That loan would be tracked independently of the actual student loans. Any money that your brother transfers to you to pay off your loans, add to that personal loan, and later on once your loans are paid off you start repaying the loan to him and he uses the proceeds for his own loans. The interest rate will determine how the benefit of paying off the 10% loans is shared: if the rate is set at 10% then your brother will get all the benefit, if 5% you will get all the benefit, and 7.5% would roughly share it out. This means that you can still manage your own student loans separately. Your brother can choose how little or much to commit to the snowball rather than his own loans (of course he should first make the minimum payments on his own loans). Anything he does loan you benefits you both if we ignore the credit and tax issues - he gets more than the 5% interest on his own loans, and you pay less than the 10% interest on your loans. You'll need to track the payments each way on this personal loan and apply interest to it every so often, I'd suggest monthly (beware that the monthly equivalent of 5% annual interest is not 5%/12, because of compounding).", "title": "" }, { "docid": "538014", "text": "Not that I doubted everyone's assumption but I wanted to see the math so I did some spreadsheet hacking. I assumed a monthly payments for 30 years which left us with total payments of 483.89. I then assumed we'd pay an extra $200/month in one of two scenarios. Scenario 1 we just paid that $200 directly to the lender. In scenario 2 we set the extra $200 aside every month until we were able to pay off the $10k at 7%. I assumed that the minimum payments were allocated proportionately and the overpayments were allocated evenly. That meant we paid off loan 5 at about month 77, loan 4 in month 88, loan 3 in month 120, loan 2 in month 165, and loan 1 in month 170. Getting over to scenario 2 where we pay $483.89 to lender and save $200 separately. In month 48 we've saved $9600 relative to the principle remaining in loan 3 of $9547. We pay that off and we're left with loan 1,2,4,5 with a combined principle of about $60930. At this point we are now going to make payments of 683.89 instead of saving towards principle. Now our weighted average interest rate is 6.800% instead of 6.824%. We can calculate the number of payments left given a principle of 60930, interest of 6.8%, and payment of 683.89 to be 124.4 months left for a total of 172.4 months Conclusion: Scenario 1 pays off the debt 3 months sooner with the same monthly expenditure as scenario 2.", "title": "" }, { "docid": "509075", "text": "I have a CapitalOne credit card, and every two or three weeks, CapitalOne Bank sends me checks that can be used almost anywhere (including a deposit into my own checking account if I wish, or to pay taxes or utility bills etc)). The amount thus borrowed is counted as a balance transfer (as if I were paying off another credit-card balance) and it will be charged 0% interest for a year. The catch is that unless I pay off the next monthly statement in full by the due date, I will be charged interest on all new purchases from the day that they post to the account till the day they are paid off. No more grace period etc. All this will continue until that loan amount is paid off in full. So, I either would have to (i) pay off all the purchases made this month plus the minimum monthly payment shown on the next monthly statement and give up use of the card till that 0% balance is all repaid, or (ii) pay interest on new purchases. It might be worth checking on the CapitalOne Credit Card site if such an offer is available to you. If so, get a check from them, pay off the invoice using that check (actually, I would strongly recommend depositing the money in your local bank and writing them your personal check for the amount to be paid), and then pay off next month's bill in full, etc.", "title": "" }, { "docid": "490529", "text": "\"To expand on @JoeTaxpayer's answer, the devil is actually in the fine print. All the \"\"credit-card checks\"\" that I have ever received in the mail explicitly says that the checks cannot be used to pay off (or pay down) the balance on any other credit card issued by the same bank, whether the card is branded with the bank logo or is branded with a department-store or airline logo etc. The checks can be used to pay utilities, or even taxes, without paying the \"\"service fee\"\" that is charged for using a credit card for such payments. The payee is paid the face amount of the check, in contrast to charges on a credit card from a merchant who gets to collect only about 95%-98% of the amount on the \"\"charge slip\"\". Generally speaking, balance transfer offers are a bad deal regardless of whether you pay only the minimum amount due each month or whether you pay each month's statement balance in full by the due date or anything in between. The rest of this answer is an explanation in support of the above assertion. Feel free to TL;DR it if you like. If you make only the minimum payment due each month and some parts of the balance that you are carrying has different interest rates applicable than other parts, then your payment can be applied to any part of the balance at the bank's discretion. It need hardly be said that the bank invariably chooses to apply it to pay off the lowest-rate portion. By law (CARD Act of 2009), anything above the minimum payment due must be applied to pay off the highest-rate part (and then the next highest rate part, etc), but minimum payment or less is at the bank's discretion. As an illustration, suppose that you are not using your credit cards any more and are conscientiously paying down the balances due by making the minimum payment due each month. Suppose also that you have a balance of $1000 carrying 12% APR on Card A, and pay off the entire balance of $500 on Card B, transferring the amount at 0% APR to Card A for which you are billed a 2% fee. Your next minimum payment will be likely be $35; computed as $10 (interest on $1000) + $10 transfer fee + $15 (1% of balance of $1500). If you make only the minimum payment due, that payment will go towards paying off the $500, and so for next month, your balance will be $1500 of which $1035 will be charged 1% interest, and $465 will be charged 0% interest. In the months that follow, the balance on which you owe 1% interest per month will grow and the 0% balance will shrink. You have to pay more than the minimum amount due to reduce the amount that you owe. In this example, in the absence of the balance transfer, the minimum payment would have been $20 = $10 (interest on $1000 at 1% per month) + $10 (1% of balance) and would have left you with $990 due for next month. To be at the same point with the balance transfer offer, you would need to pay $30 more than the minimum payment of $35 due. This extra $30 will pay off the interest and transfer fee ($20) and the rest will be applied to the $1000 balance to reduce it to $990. There would be no balance transfer fee in future months and so the extra that you need to pay will be a little bit smaller etc. If you avoid paying interest charges on credit cards by never taking any cash advances and by paying off the monthly balance (consisting only of purchases made within the past month) in full by the due date, then the only way to avoid paying interest on the purchases made during the month of the balance transfer offer is to pay off that month's statement in full (including the balance just transferred over and the balance transfer fee) by the due date. So, depending on when in the billing cycle the transfer occurs, you are getting a loan of the balance transfer amount for 25 to 55 days and being charged 2% or 3% for the privilege. If you are getting offers of 2% balance transfer fees instead of 3%, you are probably among those who pay their balances in full each month, and the bank is trying to tempt you into doing a balance transfer by offering a lower fee. (It is unlikely that they will make a no-transfer-fee offer.) They would prefer laughing all the way to themselves by collecting a 2% transfer fee from you (and possibly interest too if you fail to read the fine print) than having you decline such offers at 3% as being too expensive. Can you make a balance transfer offer work in your favor? Sure. Don't make any purchases on the card in the month of the balance transfer or during the entire time that the 0% APR is being offered. In the month of the transfer, pay the minimum balance due plus the balance transfer fee. In succeeding months, pay the minimum balance due (typically 1% of the balance owed) each month. All of it will go to reducing the 0% APR balance because that is the only amount owing. Just before the 0% APR expires (anywhere from 6 to 24 months), pay off the remaining balance in full. But remember that you are losing the use of this card for this whole period of time. Put it away in a locked trunk in the attic because using the card to make a purchase will mean paying interest on charges from the day they post, something that might be totally alien to you.\"", "title": "" } ]
PLAIN-118
Pills vs. Diet For Erectile Dysfunction
[ { "docid": "MED-3417", "text": "The aim of this work is to assess the association between vasculogenic erectile dysfunction (ED) and coronary artery disease in men above the age of 40 y. The study included 40 patients above 40 y of age with vasculogenic ED of more than 3 months duration. A dynamic duplex study after intracavernosal injection of a bimix solution (60 mg papaverine + 2 mg phentolamine mesylate) was carried out using a color ultrasound machine. The patients underwent a stress ECG test, carried out on a motor-driven treadmill according to the 'Bruce Protocol'. A total of 12 patients were diagnosed with positive ischemic heart disease (IHD). Their mean peak systolic velocity (PSV) was PSV = 19.58 cm/s. In all, patients were diagnosed with negative IHD; their mean PSV was 36.21 cm/s. A statistically significant difference was observed between patients with positive IHD and patients with negative IHD regarding PSV (P = 0.003). The sensitivity of a PSV of less than 35 cm/s in predicting IHD was 50% with a specificity of 100%. Positive predictive value for abnormal stress ECG to predict a PSV of less than 35 cm/s was 100%. In conclusion, the PSV of cavernosal arteries is a reliable measure for predicting IHD in patients with vasculogenic ED. Patients with a PSV of less than 35 cm/s should be referred for cardiologic assessment as they carry a real risk of having silent IHD.", "title": "Correlation between penile duplex findings and stress electrocardiography in men with erectile dysfunction." }, { "docid": "MED-5327", "text": "OBJECTIVE: To investigate the associations between dietary patterns and mental health in early adolescence. METHOD: The Western Australian Pregnancy Cohort (Raine) Study is a prospective study of 2900 pregnancies recruited from 1989-1992. At 14 years of age (2003-2006; n=1324), the Child Behaviour Checklist (CBCL) was used to assess behaviour (characterising mental health status), with higher scores representing poorer behaviour. Two dietary patterns (Western and Healthy) were identified using factor analysis and food group intakes estimated by a 212-item food frequency questionnaire. Relationships between dietary patterns, food group intakes and behaviour were examined using general linear modelling following adjustment for potential confounding factors at age 14: total energy intake, body mass index, physical activity, screen use, family structure, income and functioning, gender and maternal education at pregnancy. RESULTS: Higher total (b=2.20, 95% CI=1.06, 3.35), internalizing (withdrawn/depressed) (b=1.25, 95% CI=0.15, 2.35) and externalizing (delinquent/aggressive) (b=2.60, 95% CI=1.51, 3.68) CBCL scores were significantly associated with the Western dietary pattern, with increased intakes of takeaway foods, confectionary and red meat. Improved behavioural scores were significantly associated with higher intakes of leafy green vegetables and fresh fruit (components of the Healthy pattern). CONCLUSION: These findings implicate a Western dietary pattern in poorer behavioural outcomes for adolescents. Better behavioural outcomes were associated with a higher intake of fresh fruit and leafy green vegetables.", "title": "The association between dietary patterns and mental health in early adolescence." }, { "docid": "MED-3439", "text": "Erectile dysfunction (ED) is common, affecting 40% of men over 40 years of age (so-called 40 over 40) and 1 in 3 men over 70 years of age. It is predominantly a vascular condition, often preceding a cardiovascular event by 3-5 years. ED is associated as a consequence with acute coronary syndromes and increased cardiovascular and all-cause mortality. Its early identification therefore offers a window of opportunity for cardiovascular risk reduction. ED has for many a devastating impact on a couple's relationship. Its treatment is often successful, maintaining quality of life in the middle aged and elderly. ED should always be queried as part of the ongoing health care worker and patient relationship - its early detection may prevent early death. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.", "title": "Erectile dysfunction and coronary disease: evaluating the link." }, { "docid": "MED-3407", "text": "The Princeton Consensus (Expert Panel) Conference is a multispecialty collaborative tradition dedicated to optimizing sexual function and preserving cardiovascular health. The third Princeton Consensus met November 8 to 10, 2010, and had 2 primary objectives. The first objective focused on the evaluation and management of cardiovascular risk in men with erectile dysfunction (ED) and no known cardiovascular disease (CVD), with particular emphasis on identification of men with ED who may require additional cardiologic work-up. The second objective focused on reevaluation and modification of previous recommendations for evaluation of cardiac risk associated with sexual activity in men with known CVD. The Panel's recommendations build on those developed during the first and second Princeton Consensus Conferences, first emphasizing the use of exercise ability and stress testing to ensure that each man's cardiovascular health is consistent with the physical demands of sexual activity before prescribing treatment for ED, and second highlighting the link between ED and CVD, which may be asymptomatic and may benefit from cardiovascular risk reduction.", "title": "The Princeton III Consensus Recommendations for the Management of Erectile Dysfunction and Cardiovascular Disease" }, { "docid": "MED-5341", "text": "The present study investigated the effects of a diet and exercise intervention on known breast cancer (BCa) risk factors, including estrogen, obesity, insulin, and insulin-like growth factor-I (IGF-I), in overweight/obese, postmenopausal women. In addition, using the subjects' pre- and postintervention serum in vitro, serum-stimulated growth and apoptosis of three estrogen receptor-positive BCa cell lines were studied. The women where placed on a low-fat (10-15% kcal), high-fiber (30-40 g per 1,000 kcal/day) diet and attended daily exercise classes for 2 wk. Serum estradiol was reduced in the women on hormone treatment (HT; n = 28) as well as those not on HT (n = 10). Serum insulin and IGF-I were significantly reduced in all women, whereas IGF binding protein-1 was increased significantly. In vitro growth of the BCa cell lines was reduced by 6.6% for the MCF-7 cells, 9.9% for the ZR-75-1 cells, and 18.5% for the T-47D cells. Apoptosis was increased by 20% in the ZR-75-1 cells, 23% in the MCF-7 cells, and 30% in the T-47D cells (n = 12). These results show that a very-low-fat, high-fiber diet combined with daily exercise results in major reductions in risk factors for BCa while subjects remained overweight/obese. These in vivo serum changes slowed the growth and induced apoptosis in serum-stimulated BCa cell lines in vitro.", "title": "Effects of a low-fat, high-fiber diet and exercise program on breast cancer risk factors in vivo and tumor cell growth and apoptosis in vitro." }, { "docid": "MED-3427", "text": "Lifestyle and nutrition have been increasingly recognized as central factors influencing vascular nitric oxide (NO) production and erectile function. This review underscores the importance of NO as the principal mediator influencing cardiovascular health and erectile function. Erectile dysfunction (ED) is associated with smoking, excessive alcohol intake, physical inactivity, abdominal obesity, diabetes, hypertension, and decreased antioxidant defenses, all of which reduce NO production. Better lifestyle choices; physical exercise; improved nutrition and weight control; adequate intake of or supplementation with omega-3 fatty acids, antioxidants, calcium, and folic acid; and replacement of any testosterone deficiency will all improve vascular and erectile function and the response to phosphodiesterase-5 inhibitors, which also increase vascular NO production. More frequent penile-specific exercise improves local endothelial NO production. Excessive intake of vitamin E, calcium, l-arginine, or l-citrulline may impart significant cardiovascular risks. Interventions discussed also lower blood pressure or prevent hypertension. Certain angiotensin II receptor blockers improve erectile function and reduce oxidative stress. In men aged <60 years and in men with diabetes or hypertension, erectile dysfunction can be a critical warning sign for existing or impending cardiovascular disease and risk for death. The antiarrhythmic effect of omega-3 fatty acids may be particularly crucial for these men at greatest risk for sudden death. In conclusion, by better understanding the complex factors influencing erectile and overall vascular health, physicians can help their patients prevent vascular disease and improve erectile function, which provides more immediate motivation for men to improve their lifestyle habits and cardiovascular health. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "The link between erectile and cardiovascular health: the canary in the coal mine." }, { "docid": "MED-3391", "text": "Aim: To review special safety topics associated with sildenafil and to document the tolerability of 50- and 100-mg doses, overall and by age, in men with erectile dysfunction (ED). Methods: Data were collated from 67 double-blind placebo-controlled (DBPC) trials (> 14,000 men) conducted by the manufacturer and from the manufacturer’s postmarketing safety database (39,277 patients). The DBPC data were stratified by dose, starting dose and age (≥ 65 and ≥ 75 years). Special safety topics included cardiovascular risk, priapism, non-arteritic anterior ischaemic optic neuropathy (NAION), impaired renal and hepatic function, drug interactions (i.e. nitrates, cytochrome P3A4 inhibitors, other ED therapies and α-blockers) and incorrect use. Results: Sildenafil was well tolerated at a dose of 50 or 100 mg in men with ED, overall, in those aged ≥ 65 years, and in those aged ≥ 75 years. Analyses of the databases did not reveal any causal link between sildenafil and cardiovascular events, or any new safety risks relating to cardiovascular events, priapism, NAION, hearing loss or drug interactions. In the small number of men with moderate impairment of renal function or hepatic function who were treated with sildenafil in DBPC trials, the safety profile was similar to that in men with no impairment of renal or hepatic function. Overdose with sildenafil was rare in the ED population. No new safety issues, emerging trends or adverse reactions were identified in conjunction with overdose, dependence, abuse or misuse. Conclusion: This collated review confirms generally the good tolerability and established safety profile of sildenafil 50 and 100 mg in men with ED and reveals no new safety issues.", "title": "Safety of sildenafil citrate: review of 67 double-blind placebo-controlled trials and the postmarketing safety database" }, { "docid": "MED-3421", "text": "INTRODUCTION: Although penile blood flow (PBF) has been recommended as an additional diagnostic test in identifying erectile dysfunction (ED) patients at risk for latent cardiovascular disease, no study has ever assessed the possible association of PBF and the relational component of sexual function with incident major cardiovascular events (MACE). AIM: The aim of this study is to investigate whether severity of ED, PBF, and other factors related to a couple's relationship predict incident MACE. METHODS: A consecutive series of 1,687 patients was studied. Different clinical, biochemical, and instrumental (penile flow at color Doppler ultrasound) parameters were evaluated. MAIN OUTCOME MEASURES: Information on MACE was obtained through the City of Florence Registry Office. RESULTS: During a mean follow-up of 4.3 +/- 2.6 years, 139 MACE, 15 of which were fatal, were observed. Cox regression analysis, after adjustment for age and Chronic Disease Score, showed that severe ED predicted MACE (hazard ratio [HR] 1.75; 95% confidence interval 1.10-2.78; P < 0.05). In addition, lower PBF, evaluated both in flaccid (before) and dynamic (after prostaglandin-E1 stimulation) conditions, was associated with an increased risk of MACE (HR = 2.67 [1.42-5.04] and 1.57 [1.01-2.47], respectively, for flaccid [<13 cm/second] and dynamic [<25 cm/second] peak systolic velocity; both P < 0.05). Reported high sexual interest in the partner and low sexual interest in the patient proved to have a protective effect against MACE. CONCLUSIONS: The investigation of male sexuality, and in particular PBF, and sexual desire, could provide insights not only into present cardiovascular status but also into prospective risk.", "title": "Male sexuality and cardiovascular risk. A cohort study in patients with erectile dysfunction." }, { "docid": "MED-4352", "text": "Changes in the concentration and composition of serum VLDL, LDL, and HDL were studied in rabbits transferred from Chow diets to cholesterol-free, semipurified diets containing casein or isolated soy protein. During the first week on the casein diet, there was a marked increase in LDL-cholesterol and these higher levels were maintained during the subsequent 3 weeks of the study. Similar but less marked changes were obtained with the soy protein diet. When the percent composition of the particles was determined, both VLDL and LDL had a higher proportion of cholesterol. Turnover studies indicated that the FCRs for radiolabelled VLDL and LDL were reduced in casein-fed animals compared to those fed soy protein. The elevated LDL levels in casein-fed rabbits were primarily due to a reduction in receptor-mediated catabolism of LDL-apo B. Receptor-independent removal in the two groups was similar. These studies show that the hypercholesterolemia in casein-fed rabbits, compared to those fed soy protein, is associated with cholesterol enrichment of LDL and impaired receptor-dependent removal of LDL-apo B.", "title": "Effects of dietary protein on composition and metabolism of plasma lipoproteins in rabbits." }, { "docid": "MED-4425", "text": "INTRODUCTION: No reported studies exist assessing the relationship between sexual function and hyperlipidemia in women. AIM: In this study, we assessed the domains of sexual function in a representative sample of sexually active premenopausal women with hyperlipidemia, but without cardiovascular disease, as compared with an age-matched female population without hyperlipidemia. METHODS: To be enrolled in the study, women had to meet at least one of the following criteria for the diagnosis of hyperlipidemia: low-density lipoprotein (LDL) cholesterol levels >160 mg/dL; high-density lipoprotein (HDL) cholesterol levels <50 mg/dL; or triglyceride levels >150 mg/dL. Lipid parameters were assessed and verified on blood taken at least twice in the hospital during the screening phase. Four hundred forty-one premenopausal women with hyperlipidemia were compared with 115 age-matched premenopausal women without hyperlipidemia. MAIN OUTCOME MEASURES: We used the Female Sexual Function Index (FSFI) for assessing the key dimensions of female sexual function. RESULTS: The two groups were well matched for age and smoking prevalence. Compared with women of the control group, women with hyperlipidemia had reduced mean global FSFI score (22.8 +/- 6.8 vs. 29.4 +/- 4.9, P < 0.001). Individual analysis of the different domains showed that women with hyperlipidemia reported significantly lower arousal, orgasm, lubrication, and satisfaction scores than control women. Based on the total FSFI score, 51% of women with hyperlipidemia had scores of 26 or less, indicating sexual dysfunction, as compared with 21% of women without hyperlipidemia (P < 0.001). Based on a more conservative analysis including women under the lower quartile of the distribution of FSFI score, 32% of women with hyperlipidemia had scores of 23 or less, as compared with 9% of women without hyperlipidemia (P < 0.001). Multiple regression analysis identified age, body mass index, HDL-cholesterol and triglycerides as independent predictors of FSFI score. CONCLUSIONS: Women with hyperlipidemia have significantly lower FSFI-domain scores as compared with age-matched women without hyperlipidemia. HDL cholesterol and triglyceride levels were independently associated with the FSFI score.", "title": "Hyperlipidemia and sexual function in premenopausal women." }, { "docid": "MED-4616", "text": "In a prospective, randomised, controlled trial to determine whether comprehensive lifestyle changes affect coronary atherosclerosis after 1 year, 28 patients were assigned to an experimental group (low-fat vegetarian diet, stopping smoking, stress management training, and moderate exercise) and 20 to a usual-care control group. 195 coronary artery lesions were analysed by quantitative coronary angiography. The average percentage diameter stenosis regressed from 40.0 (SD 16.9)% to 37.8 (16.5)% in the experimental group yet progressed from 42.7 (15.5)% to 46.1 (18.5)% in the control group. When only lesions greater than 50% stenosed were analysed, the average percentage diameter stenosis regressed from 61.1 (8.8)% to 55.8 (11.0)% in the experimental group and progressed from 61.7 (9.5)% to 64.4 (16.3)% in the control group. Overall, 82% of experimental-group patients had an average change towards regression. Comprehensive lifestyle changes may be able to bring about regression of even severe coronary atherosclerosis after only 1 year, without use of lipid-lowering drugs.", "title": "Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial." }, { "docid": "MED-5339", "text": "Recently, it has been suggested that the Escherichia coli causing urinary tract infection (UTI) may come from meat and animals. The purpose was to investigate if a clonal link existed between E. coli from animals, meat and UTI patients. Twenty-two geographically and temporally matched B2 E. coli from UTI patients, community-dwelling humans, broiler chicken meat, pork, and broiler chicken, previously identified to exhibit eight virulence genotypes by microarray-detection of approximately 300 genes, were investigated for clonal relatedness by PFGE. Nine isolates were selected and tested for in vivo virulence in the mouse model of ascending UTI. UTI and community-dwelling human strains were closely clonally related to meat strains. Several human derived strains were also clonally interrelated. All nine isolates regardless of origin were virulent in the UTI model with positive urine, bladder and kidney cultures. Further, isolates with the same gene profile also yielded similar bacterial counts in urine, bladder and kidneys. This study showed a clonal link between E. coli from meat and humans, providing solid evidence that UTI is zoonosis. The close relationship between community-dwelling human and UTI isolates may indicate a point source spread, e.g. through contaminated meat.", "title": "Is Escherichia coli urinary tract infection a zoonosis? Proof of direct link with production animals and meat." }, { "docid": "MED-3424", "text": "The purpose of this study is to investigate the possible underlying pathogenesis of erectile dysfunction(ED) in young men with low risk of coronary heart disease and no well-known aetiology. To conduct this study, 122 patients with ED under the age of 40 were enrolled, along with 33 age-matched normal control subjects. The patients with ED had significantly higher levels of systolic blood pressure (SBP), total cholesterol and triglyceride, high sensitivity C-reactive protein (hs-CRP), greater carotid intima-media thickness (CIMT) and Framingham risk score (FRS) than the control group, though all of these values were within the respective normal range. Further, the brachial artery flow- mediated vasodilation (FMD) values were significantly lower in ED patients and correlated positively with the severity of ED (r = 0.714, p < 0.001). When these significant factors were studied in the multivariate logistic regression model, FMD, SBP, hs-CRP and FRS remained the statistical significance. The receiver-operating characteristic (ROC) analysis demonstrated that FMD had a high ability to predict ED in young male with low FRS [area under the curve (AUC) 0.921, p < 0.001]. The cutoff value of FMD <10.25% had sensitivity of 82.8% and specificity of 100% for diagnosis of ED. FRS and hs- CRP were also proven to be predictors of ED (AUC 0.812, p < 0.001; AUC 0.645, p = 0.011, respectively). The results of this study validated that subclinical endothelial dysfunction and low-grade inflammation may be the underlying pathogenesis of ED with no well-known aetiology. Young patients complaining of ED should be screened for cardiovascular risk factors and possible subclinical atherosclerosis. Measurement of FMD, hs-CRP and FRS can improve our ability to predict and treat ED, as well as subclinical cardiovascular disease early for young male. © 2012 The Authors. International Journal of Andrology © 2012 European Academy of Andrology.", "title": "Subclinical endothelial dysfunction and low-grade inflammation play roles in the development of erectile dysfunction in young men with low risk of ..." }, { "docid": "MED-3438", "text": "Erectile dysfunction (ED) is defined as the inability to achieve or maintain an erection satisfactory for sexual performance. Evidence is accumulating to consider ED as a vascular disorder. Common risk factors for atherosclerosis are frequently found in association with ED, and ED is frequently reported in vascular syndromes, such as coronary artery disease (CAD), hypertension, cerebrovascular disease, peripheral arterial disease, and diabetes mellitus. Finally, similar early impairment of endothelium-dependent vasodilatation and late obstructive vascular changes has been reported in both ED and other vascular syndromes. Recently, we proposed a pathophysiologic mechanism to explain the link between ED and CAD called the artery size hypothesis. Given the systemic nature of atherosclerosis, all major vascular beds should be affected to the same extent. However, symptoms rarely become evident at the same time. This difference in rate of occurrence of different symptoms is proposed to be caused by the different size of the arteries supplying different vascular beds that allow a larger vessel to better tolerate the same amount of plaque compared with a smaller one. According to this hypothesis, because penile arteries are smaller in diameter than coronary arteries, patients with ED will seldom have concomitant symptoms of CAD, whereas patients with CAD will frequently complain of ED. Available clinical evidence appears to support this hypothesis.", "title": "The artery size hypothesis: a macrovascular link between erectile dysfunction and coronary artery disease." }, { "docid": "MED-3422", "text": "In the present study, we tested the effect of a Mediterranean-style diet on sexual function in women with the metabolic syndrome. Women were identified in our database of subjects participating in controlled trials evaluating the effect of lifestyle changes and were included if they had a diagnosis of female sexual dysfunction (FSD) associated with a diagnosis of metabolic syndrome, a complete follow-up in the study trial and an intervention focused mainly on dietary changes. Fifty-nine women met the inclusion/exclusion criteria; 31 out of them were assigned to the Mediterranean-style diet and 28 to the control diet. After 2 years, women on the Mediterranean diet consumed more fruits, vegetables, nuts, whole grain and olive oil as compared with the women on the control diet. Female sexual function index (FSFI) improved in the intervention group, from a mean basal value of 19.7+/-3.1 to a mean post-treatment value of 26.1+/-4.1 (P=0.01), and remained stable in the control group. C-reactive protein (CRP) levels were significantly reduced in the intervention group (P<0.02). No single sexual domain (desire, arousal, lubrication, orgasm, satisfaction, pain) was significantly ameliorated by the dietary treatment, suggesting that the whole female sexuality may find benefit from lifestyle changes. A Mediterranean-style diet might be effective in ameliorating sexual function in women with metabolic syndrome.", "title": "Mediterranean diet improves sexual function in women with the metabolic syndrome." }, { "docid": "MED-3431", "text": "OBJECTIVE: To assess the association between erectile dysfunction (ED) and the long-term risk of coronary artery disease (CAD) and the role of age as a modifier of this association. PARTICIPANTS AND METHODS: From January 1, 1996, to December 31, 2005, we biennially screened a random sample of 1402 community-dwelling men with regular sexual partners and without known CAD for the presence of ED. Incidence densities of CAD were calculated after age stratification and adjusted for potential confounders by time-dependent Cox proportional hazards models. RESULTS: The prevalence of ED was 2% for men aged 40 to 49 years, 6% for men aged 50 to 59 years, 17% for men aged 60 to 69 years, and 39% for men aged 70 years or older. The CAD incidence densities per 1000 person-years for men without ED in each age group were 0.94 (40-49 years), 5.09 (50-59 years), 10.72 (60-69 years), and 23.30 (≥70 years). For men with ED, the incidence densities of CAD for each age group were 48.52 (40-49 years), 27.15 (50-59 years), 23.97 (60-69 years), and 29.63 (≥70 years). CONCLUSION: ED and CAD may be differing manifestations of a common underlying vascular pathology. When ED occurs in a younger man, it is associated with a marked increase in the risk of future cardiac events, whereas in older men, ED appears to be of little prognostic importance. Young men with ED may be ideal candidates for cardiovascular risk factor screening and medical intervention.", "title": "A Population-Based, Longitudinal Study of Erectile Dysfunction and Future Coronary Artery Disease" }, { "docid": "MED-5335", "text": "Three recent case-control studies conclude that diets high in animal fat or cholesterol are associated with a substantial increase in risk for Parkinson's disease (PD); in contrast, fat of plant origin does not appear to increase risk. Whereas reported age-adjusted prevalence rates of PD tend to be relatively uniform throughout Europe and the Americas, sub-Saharan black Africans, rural Chinese, and Japanese, groups whose diets tend to be vegan or quasi-vegan, appear to enjoy substantially lower rates. Since current PD prevalence in African-Americans is little different from that in whites, environmental factors are likely to be responsible for the low PD risk in black Africans. In aggregate, these findings suggest that vegan diets may be notably protective with respect to PD. However, they offer no insight into whether saturated fat, compounds associated with animal fat, animal protein, or the integrated impact of the components of animal products mediates the risk associated with animal fat consumption. Caloric restriction has recently been shown to protect the central dopaminergic neurons of mice from neurotoxins, at least in part by induction of heat-shock proteins; conceivably, the protection afforded by vegan diets reflects a similar mechanism. The possibility that vegan diets could be therapeutically beneficial in PD, by slowing the loss of surviving dopaminergic neurons, thus retarding progression of the syndrome, may merit examination. Vegan diets could also be helpful to PD patients by promoting vascular health and aiding blood-brain barrier transport of L-dopa. Copyright 2001 Harcourt Publishers Ltd.", "title": "Does a vegan diet reduce risk for Parkinson's disease?" }, { "docid": "MED-5322", "text": "BACKGROUND/AIMS: This study aimed to investigate the quantitative and qualitative changes of bacteria, Bacteroides, Bifidobacterium and Clostridium cluster IV in faecal microbiota associated with a vegetarian diet. METHODS: Bacterial abundances were measured in faecal samples of 15 vegetarians and 14 omnivores using quantitative PCR. Diversity was assessed with PCR-DGGE fingerprinting, principal component analysis (PCA) and Shannon diversity index. RESULTS: Vegetarians had a 12% higher abundance of bacterial DNA than omnivores, a tendency for less Clostridium cluster IV (31.86 +/- 17.00%; 36.64 +/- 14.22%) and higher abundance of Bacteroides (23.93 +/- 10.35%; 21.26 +/- 8.05%), which were not significant due to high interindividual variations. PCA suggested a grouping of bacteria and members of Clostridium cluster IV. Two bands appeared significantly more frequently in omnivores than in vegetarians (p < 0.005 and p < 0.022). One was identified as Faecalibacterium sp. and the other was 97.9% similar to the uncultured gut bacteriumDQ793301. CONCLUSIONS: A vegetarian diet affects the intestinal microbiota, especially by decreasing the amount and changing the diversity of Clostridium cluster IV. It remains to be determined how these shifts might affect the host metabolism and disease risks. Copyright 2009 S. Karger AG, Basel.", "title": "Characterization of bacteria, clostridia and Bacteroides in faeces of vegetarians using qPCR and PCR-DGGE fingerprinting." }, { "docid": "MED-5324", "text": "Obesity has important health consequences, including elevating risk for heart disease, diabetes, and cancer. A high-fat diet is known to contribute to obesity. Little is known regarding the effect of a high-fat diet on pulmonary function, despite the dramatic increase in the prevalence of respiratory ailments (e.g., asthma). The purpose of our study was to determine whether a high-fat meal (HFM) would increase airway inflammation and decrease pulmonary function in healthy subjects. Pulmonary function tests (PFT) (forced expiratory volume in 1-s, forced vital capacity, forced expiratory flow at 25-75% of vital capacity) and exhaled nitric oxide (eNO; airway inflammation) were performed in 20 healthy (10 men, 10 women), inactive subjects (age 21.9 +/- 0.4 years) pre and 2 h post HFM (1 g fat/1 kg body weight; 74.2 +/- 4.1 g fat). Total cholesterol, triglycerides, and C-reactive protein (CRP; systemic inflammation) were determined via a venous blood sample pre and post HFM. Body composition was measured via dual energy X-ray absorptiometry. The HFM significantly increased total cholesterol by 4 +/- 1%, and triglycerides by 93 +/- 3%. ENO also increased (p < 0.05) due to the HFM by 19 +/- 1% (pre 17.2 +/- 1.6; post 20.6 +/- 1.7 ppb). ENO and triglycerides were significantly related at baseline and post-HFM (r = 0.82, 0.72 respectively). Despite the increased eNO, PFT or CRP did not change (p > 0.05) with the HFM. These results demonstrate that a HFM, which leads to significant increases in total cholesterol, and especially triglycerides, increases exhaled NO. This suggests that a high-fat diet may contribute to chronic inflammatory diseases of the airway and lung.", "title": "Effects of a high-fat meal on pulmonary function in healthy subjects." }, { "docid": "MED-3426", "text": "OBJECTIVES: The purpose of our study was to assess the prevalence and extent of coronary artery atherosclerosis in asymptomatic patients with vascular erectile dysfunction (ED). BACKGROUND: An association between ED and ischemic heart disease has been suggested, but it is unknown if it represents a marker of subclinical coronary atherosclerosis. METHODS: We studied 70 consecutive patients with vascular ED, evaluated by penile Doppler, and 73 control subjects with no history of coronary artery disease. We measured traditional coronary risk factors, circulating levels of C-reactive protein (CRP), endothelial function by ultrasound of brachial artery, and coronary artery calcification by multi-slice computed tomography. RESULTS: The patients and the control group were similar for age, race, and coronary risk score. Patients with ED had significantly higher high-sensitivity C-reactive protein levels (2.62 vs. 1.03 mg/l, p < 0.001). Flow-mediated dilation of the brachial artery was more impaired in patients with ED than in controls (2.36 vs. 3.92, p < 0.001). Coronary artery calcification was more frequent in individuals with ED than in control subjects (p = 0.01). Multiple logistic regression analysis showed that patients with ED had an overall odds ratio of 3.68 for having calcium score above the 75th percentile, compared to the controls. CONCLUSIONS: Coronary atherosclerosis is more severe in patients with vascular ED; ED predicts the presence and extent of subclinical atherosclerosis independent of traditional risk factors for cardiovascular disease. Thus, ED may be considered an additional, early warning sign of coronary atherosclerosis.", "title": "Subclinical coronary artery atherosclerosis in patients with erectile dysfunction." }, { "docid": "MED-3398", "text": "Although erectile dysfunction is frequently seen in patients with manifestations of arteriosclerotic disease, the independent contribution of serum cholesterol in predicting erectile dysfunction is unclear. The aim of this study was to examine the relation between serum cholesterol and erectile dysfunction. Medical histories, physical examinations, and blood tests were obtained at Cooper Clinic, Dallas, Texas, from 3,250 men aged 26-83 years (mean, 51 years) without erectile dysfunction at their first visit, who had one more clinic visit, all between 1987 and 1991. These men were followed 6-48 months after the first clinic visit (mean, 22 months). Erectile dysfunction was reported in 71 men (2.2%) during follow-up. Every mmol/liter of increase in total cholesterol was associated with 1.32 times the risk of erectile dysfunction (95% confidence interval 1.04-1.68), while every mmol/liter of increase in high density lipoprotein cholesterol was associated with 0.38 times the risk (95% confidence interval 0.18-0.80). Men with a high density lipoprotein cholesterol measurement over 1.55 mmol/liter (60 mg/dl) had 0.30 times the risk (95% confidence interval 0.09-1.03) as did men with less than 0.78 mmol/liter (30 mg/dl). Men with total cholesterol over 6.21 mmol/liter (240 mg/dl) had 1.83 times the risk (95% confidence interval 1.00-3.37) as did men with less than 4.65 mmol/liter (180 mg/dl). Those differences remained essentially unchanged after adjustment for other potential confounders. The authors conclude that a high level of total cholesterol and a low level of high density lipoprotein cholesterol are important risk factors for erectile dysfunction.", "title": "Total cholesterol and high density lipoprotein cholesterol as important predictors of erectile dysfunction." }, { "docid": "MED-5342", "text": "Background The physical health status of vegetarians has been extensively reported, but there is limited research regarding the mental health status of vegetarians, particularly with regard to mood. Vegetarian diets exclude fish, the major dietary source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), critical regulators of brain cell structure and function. Omnivorous diets low in EPA and DHA are linked to impaired mood states in observational and experimental studies. Methods We examined associations between mood state and polyunsaturated fatty acid intake as a result of adherence to a vegetarian or omnivorous diet in a cross-sectional study of 138 healthy Seventh Day Adventist men and women residing in the Southwest. Participants completed a quantitative food frequency questionnaire, Depression Anxiety Stress Scale (DASS), and Profile of Mood States (POMS) questionnaires. Results Vegetarians (VEG:n = 60) reported significantly less negative emotion than omnivores (OMN:n = 78) as measured by both mean total DASS and POMS scores (8.32 ± 0.88 vs 17.51 ± 1.88, p = .000 and 0.10 ± 1.99 vs 15.33 ± 3.10, p = .007, respectively). VEG reported significantly lower mean intakes of EPA (p < .001), DHA (p < .001), as well as the omega-6 fatty acid, arachidonic acid (AA; p < .001), and reported higher mean intakes of shorter-chain α-linolenic acid (p < .001) and linoleic acid (p < .001) than OMN. Mean total DASS and POMS scores were positively related to mean intakes of EPA (p < 0.05), DHA (p < 0.05), and AA (p < 0.05), and inversely related to intakes of ALA (p < 0.05), and LA (p < 0.05), indicating that participants with low intakes of EPA, DHA, and AA and high intakes of ALA and LA had better mood. Conclusions The vegetarian diet profile does not appear to adversely affect mood despite low intake of long-chain omega-3 fatty acids.", "title": "Vegetarian diets are associated with healthy mood states: a cross-sectional study in Seventh Day Adventist adults" }, { "docid": "MED-5337", "text": "PURPOSE: Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS AND METHODS: Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group. RESULTS: None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. CONCLUSIONS: Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.", "title": "Intensive lifestyle changes may affect the progression of prostate cancer." }, { "docid": "MED-5330", "text": "Although there is a well-established relation between serum cholesterol and coronary artery disease risk, individual and national variations in this association suggest that other factors are involved in atherogenesis. High-fat diet associated triglyceride-rich lipoproteins have also been suggested to be atherogenic. To assess the direct effect of postprandial triglyceride-rich lipoproteins on endothelial function, an early factor in atherogenesis--10 healthy, normocholesterolemic volunteers--were studied before and for 6 hours after single isocaloric high- and low-fat meals (900 calorie; 50 and 0 g fat, respectively). Endothelial function, in the form of flow-mediated vasoactivity, was assessed in the brachial artery using 7.5-MHz ultrasound as percent arterial diameter change 1 minute after 5 minutes of upper-arm arterial occlusion. Serum lipoproteins and glucose were determined before eating and 2 and 4 hours postprandially. Serum triglycerides increased from 94 +/- 55 mg/dl preprandially to 147 +/- 80 mg/dl 2 hours after the high-fat meal (p = 0.05). Flow-dependent vasoactivity decreased from 21 +/- 5% preprandially to 11 +/- 4%, 11 +/- 6%, and 10 +/- 3% at 2, 3, and 4 hours after the high-fat meal, respectively (all p <0.05 compared with low-fat meal data). No changes in lipoproteins or flow-mediated vasoactivity were observed after the low-fat meal. Fasting low-density lipoprotein cholesterol correlated inversely (r = -0.47, p = 0.04) with preprandial flow-mediated vasoactivity, but triglyceride level did not. Mean change in postprandial flow-mediated vasoactivity at 2, 3, and 4 hours correlated with change in 2-hour serum triglycerides (r = -0.51, p = 0.02). These results demonstrate that a single high-fat meal transiently impairs endothelial function. These findings identify a potential process by which a high-fat diet may be atherogenic independent of induced changes in cholesterol.", "title": "Effect of a single high-fat meal on endothelial function in healthy subjects." }, { "docid": "MED-3428", "text": "OBJECTIVES: The aim of this study was to assess erectile dysfunction prevalence, time of onset and association with risk factors in patients with acute chest pain and angiographically documented coronary artery disease. METHODS: 300 consecutive patients with acute chest pain and angiographically documented coronary artery disease were assessed using a semi-structured interview investigating their medical and sexual histories, the International Index of Erectile Function and other instruments. RESULTS: Patient mean age was 62.5+/-8 years (range 33-86 years). Mean duration of symptoms or signs of myocardial ischaemia prior to enrollment in the study was 49 months (range 1-200). Coronary angiography showed 1-, 2- and 3-vessel disease in 98 (32.6%), 88 (29.3%) and 114 (38%) patients, respectively. The prevalence of ED among all patients was 49% (147/300). Erectile dysfunction was scored as mild, mild to moderate, moderate and severe in 21 (14%), 31 (21%), 20 (14%), and 75 (51%) of patients, respectively. There was no significant difference between patients with ED (n=147) or without ED (n=153) as far as clinical and angiographic characteristics were concerned. In the 147 patients with co-existing ED and CAD, ED symptoms were reported as having become clinically evident prior to CAD symptoms by 99/147 (67%) patients. The mean time interval between the onset of ED and CAD was 38.8 months (range 1-168). There was no significant difference in terms of risk factor distribution and clinical and angiographic characteristics between patients with the onset of ED before vs. after CAD diagnosis. Interestingly, all patients with type I diabetes and ED actually developed sexual dysfunction before CAD onset (p<0.001). CONCLUSIONS: Our study suggests that a significant proportion of patients with angiographically documented coronary artery disease have erectile dysfunction and that this latter condition may become evident prior to angina symptoms in almost 70% of cases. Future studies including a control group of patients with coronary artery disease and normal erectile function are required in order to verify whether erectile dysfunction may be considered a real predictor of ischemic heart disease.", "title": "Erectile dysfunction prevalence, time of onset and association with risk factors in 300 consecutive patients with acute chest pain and angiographic..." }, { "docid": "MED-5363", "text": "OBJECTIVE: Although several studies have reported associations of depressive state with specific nutrients and foods, few studies examined the association with dietary patterns in adults. We investigated the association between major dietary patterns and depressive symptoms in Japanese. METHODS: Subjects were 521 municipal employees (309 men and 212 women), aged 21-67 years, who participated in a health survey at the time of periodic checkup. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale. Dietary patterns were derived by using principal component analysis of the consumption of 52 food and beverage items, which was assessed by a validated brief diet history questionnaire. Logistic regression analysis was used to estimate odds ratios of depressive symptoms (CES-D >or=16) with adjustment for potential confounding variables. RESULTS: We identified three dietary patterns. A healthy Japanese dietary pattern characterized by high intakes of vegetables, fruit, mushrooms and soy products was associated with fewer depressive symptoms. The multivariate-adjusted odds ratios (95% confidence intervals) of having depressive symptoms for the lowest through highest tertiles of the healthy Japanese dietary pattern score were 1.00 (reference), 0.99 (0.62-1.59) and 0.44 (0.25-0.78), respectively (P for trend=0.006). Other dietary patterns were not appreciably associated with depressive symptoms. CONCLUSIONS: Our findings suggest that a healthy Japanese dietary pattern may be related to decreased prevalence of depressive status.", "title": "Dietary patterns and depressive symptoms among Japanese men and women." }, { "docid": "MED-5325", "text": "Objective Previous work studying vegetarians has often found that they have lower blood pressure (BP). Reasons may include their lower BMI and higher intake levels of fruit and vegetables. Here we seek to extend this evidence in a geographically diverse population containing vegans, lacto-ovo vegetarians and omnivores. Design Data are analysed from a calibration sub-study of the Adventist Health Study-2 (AHS-2) cohort who attended clinics and provided validated FFQ. Criteria were established for vegan, lacto-ovo vegetarian, partial vegetarian and omnivorous dietary patterns. Setting Clinics were conducted at churches across the USA and Canada. Dietary data were gathered by mailed questionnaire. Subjects Five hundred white subjects representing the AHS-2 cohort. Results Covariate-adjusted regression analyses demonstrated that the vegan vegetarians had lower systolic and diastolic BP (mmHg) than omnivorous Adventists (β =−6·8, P<0·05 and β = −6·9, P<0·001). Findings for lacto-ovo vegetarians (β = −9·1, P<0·001 and β = −5·8, P<0·001) were similar. The vegetarians (mainly the vegans) were also less likely to be using antihypertensive medications. Defining hypertension as systolic BP > 139 mmHg or diastolic BP > 89 mmHg or use of antihypertensive medications, the odds ratio of hypertension compared with omnivores was 0·37 (95 % CI 0·19, 0·74), 0·57 (95 % CI 0·36, 0·92) and 0·92 (95 % CI 0·50, 1·70), respectively, for vegans, lacto-ovo vegetarians and partial vegetarians. Effects were reduced after adjustment for BMI. Conclusions We conclude from this relatively large study that vegetarians, especially vegans, with otherwise diverse characteristics but stable diets, do have lower systolic and diastolic BP and less hypertension than omnivores. This is only partly due to their lower body mass.", "title": "Vegetarian diets and blood pressure among white subjects: results from the Adventist Health Study-2 (AHS-2)" }, { "docid": "MED-5328", "text": "Aim To evaluate the relationship of diet to incident diabetes among non-Black and Black participants in the Adventist Health Study-2. Methods and Results Participants were 15,200 men and 26,187 women (17.3% Blacks) across the U.S. and Canada who were free of diabetes and who provided demographic, anthropometric, lifestyle and dietary data. Participants were grouped as vegan, lacto ovo vegetarian, pesco vegetarian, semi-vegetarian or non-vegetarian (reference group). A follow-up questionnaire after two years elicited information on the development of diabetes. Cases of diabetes developed in 0.54% of vegans, 1.08% of lacto ovo vegetarians, 1.29% of pesco vegetarians, 0.92% of semi-vegetarians and 2.12% of non-vegetarians. Blacks had an increased risk compared to non-Blacks (odds ratio [OR] 1.364; 95% confidence interval [CI], 1.093–1.702). In multiple logistic regression analysis controlling for age, gender, education, income, television watching, physical activity, sleep, alcohol use, smoking and BMI, vegans (OR 0.381; 95% CI 0.236–0.617), lacto ovo vegetarians (OR 0.618; 95% CI 0.503–0.760) and semi-vegetarians (OR 0.486, 95% CI 0.312–0.755) had a lower risk of diabetes than non-vegetarians. In non-Blacks vegan, lacto ovo and semi-vegetarian diets were protective against diabetes (OR 0.429, 95% CI 0.249–0.740; OR 0.684, 95% CI 0.542–0.862; OR 0.501, 95% CI 0.303–0.827); among Blacks vegan and lacto ovo vegetarian diets were protective (OR 0.304, 95% CI 0.110–0.842; OR 0.472, 95% CI 0.270–0.825). These associations were strengthened when BMI was removed from the analyses. Conclusion Vegetarian diets (vegan, lacto ovo, semi-) were associated with a substantial and independent reduction in diabetes incidence. In Blacks the dimension of the protection associated with vegetarian diets was as great as the excess risk associated with Black ethnicity.", "title": "Vegetarian diets and incidence of diabetes in the Adventist Health Study-2" }, { "docid": "MED-5323", "text": "This study reviewed the literature on the relations between exposure to chemicals with endocrine-disrupting abilities and obesity in humans. The studies generally indicated that exposure to some of the endocrine-disrupting chemicals was associated with an increase in body size in humans. The results depended on the type of chemical, exposure level, timing of exposure and gender. Nearly all the studies investigating dichlorodiphenyldichloroethylene (DDE) found that exposure was associated with an increase in body size, whereas the results of the studies investigating polychlorinated biphenyl (PCB) exposure were depending on dose, timing and gender. Hexachlorobenzene, polybrominated biphenyls, beta-hexachlorocyclohexane, oxychlordane and phthalates were likewise generally associated with an increase in body size. Studies investigating polychlorinated dibenzodioxins and polychlorinated dibenzofurans found either associations with weight gain or an increase in waist circumference, or no association. The one study investigating relations with bisphenol A found no association. Studies investigating prenatal exposure indicated that exposure in utero may cause permanent physiological changes predisposing to later weight gain. The study findings suggest that some endocrine disruptors may play a role for the development of the obesity epidemic, in addition to the more commonly perceived putative contributors. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.", "title": "Endocrine-disrupting chemicals and obesity development in humans: a review." }, { "docid": "MED-3435", "text": "INTRODUCTION: Previous cross-sectional studies have suggested that erectile dysfunction (ED) represents an independent risk factor for future cardiovascular events. However, very few studies have attempted to examine the association between ED and subsequent stroke. AIM: The aim of this study is to estimate the risk of stroke during a 5-year follow-up period after the first ambulatory care visit for the treatment of ED using nationwide, population-based data and a retrospective case-control cohort design in Taiwan. METHODS: This study used data sourced from the \"Longitudinal Health Insurance Database.\" The study cohort comprised 1,501 patients who received a principal diagnosis of ED between 1997 and 2001 and 7,505 randomly selected subjects as the comparison cohort. Each patient (N = 9,006) was then individually tracked for 5 years from their index ambulatory care visit to identify those who had diagnosed episodes of stroke. MAIN OUTCOME MEASURE: Stratified Cox proportional hazard regressions were performed as a means of comparing the 5-year stroke-free survival rate for the two cohorts. RESULTS: Of the sampled patients, 918 (10.2%) developed stroke within the 5-year follow-up period, that is, 188 individuals (12.5% of the patients with ED) from the study cohort and 730 individuals (9.7% of patients in the comparison cohort) from the comparison cohort. The log-rank test indicated that patients with ED had significantly lower 5-year stroke-free survival rates than those in the comparison cohort (P < 0.001). After adjusting for the patient's monthly income, geographical location, hypertension, diabetes, coronary heart disease, peripheral vascular disease, atrial fibrillation, and hyperlipidemia, patients with ED were more likely to have a stroke during the 5-year follow-up period than patients in the comparison cohort (hazard ratio = 1.29, 95% confidence interval = 1.08 - 1.54, P < 0.01). CONCLUSIONS: These results suggest that ED is a surrogate marker for future stroke in men. © 2010 International Society for Sexual Medicine.", "title": "Increased risk of stroke among men with erectile dysfunction: a nationwide population-based study." }, { "docid": "MED-5331", "text": "A global health transition is currently underway. The burden of non-communicable diseases (NCDs) is increasing rapidly in the developing world, very much as a result of changes in lifestyles. In addition to changes in tobacco use and physical activity, major changes are taking place in diets, contributing greatly to the growing epidemic of NCD. Thus, a huge global public health challenge is how to influence the trends in diet and nutrition for effective global NCD prevention. The health transition took place rapidly in Finland after World War II and mortality from cardiovascular disease (CVD) was exceptionally high. The North Karelia Project was launched in 1972 as a community-based, and later as a national, programme to influence diet and other lifestyles that are crucial in the prevention of CVD. The intervention had a strong theory base and it employed comprehensive strategies. Broad community organisation and the strong participation of people were the key elements. Evaluation has shown how the diet (particularly fat consumption) has changed and how these changes have led to a major reduction in population serum cholesterol and blood pressure levels. It has also shown how ischaemic heart disease mortality in a working-age population has declined by 73% in North Karelia and by 65% in the whole country from 1971 to 1995. Although Finland is an industrialised country, North Karelia was rural, of rather low socio-economic level and with many social problems in the 1970s and 1980s. The project was based on low-cost intervention activities, where people's participation and community organisations played a key role. Comprehensive interventions in the community were eventually supported by national activities--from expert guidelines and media activities to industry collaboration and policy. Similar principles for nutrition intervention programmes could be used in developing countries, obviously tailored to the local conditions. This paper discusses the experiences of the North Karelia Project in the light of needs from the less-industrialised countries and makes some general recommendations.", "title": "Influencing public nutrition for non-communicable disease prevention: from community intervention to national programme--experiences from Finland." }, { "docid": "MED-5340", "text": "In Asia, vegetarianism is a well-established eating behavior. It appears that the adoption of a vegan diet leads to a lessening of several health risk factors. Although vegetarianism has some notable effects on the hematological system, the effect on the nephrological system has not been well clarified. The pattern of renal function parameters was studied in 25 Thai vegans compared with 25 non-vegetarians. Of the studied parameters, it was found that urine protein was significantly different (p < 0.05) in vegans and controls. Vegans had significantly lower urine protein level.", "title": "Renal function parameters of Thai vegans compared with non-vegans." }, { "docid": "MED-3420", "text": "Introduction Erectile dysfunction (ED) and cardiovascular disease (CVD) share pathophysiological mechanisms and often co-occur. Yet it is not known whether ED provides an early warning for increased CVD or other causes of mortality. Aim We sought to examine the association of ED with all-cause and cause-specific mortality. Methods Prospective, population-based study of 1,709 men (of 3,258 eligible) aged 40–70 years. ED was measured by self-report. Subjects were followed for a mean of 15 years. Hazard ratios (HR) were calculated using the Cox proportional hazards regression model. Main outcome measures Mortality due to all causes, CVD, malignant neoplasms, and other causes. Results Of 1,709 men, 1,284 survived to the end of 2004 and had complete ED and age data. Of 403 men who died, 371 had complete data. After adjustment for age, body mass index, alcohol consumption, physical activity, cigarette smoking, self-assessed health, and self-reported heart disease, hypertension, and diabetes, ED was associated with HRs of 1.26 [95% confidence interval (CI), 1.01–1.57] for all-cause mortality and 1.43 (95% CI, 1.00–2.05) for CVD mortality. The HR for CVD mortality associated with ED is of comparable magnitude to HRs of some conventional CVD risk factors. Conclusions These findings demonstrate that ED is significantly associated with increased all-cause mortality, primarily through its association with CVD mortality.", "title": "Erectile Dysfunction and Mortality" }, { "docid": "MED-3437", "text": "INTRODUCTION: The use of the penile peak systolic velocity (PSV) measured in the flaccid state during penile color Doppler ultrasound (PCDU) examination has been questioned without substantial evidence. AIM: To assess the validity of PSV measured in the flaccid state during PCDU, in patients consulting for erectile dysfunction (ED). METHODS: A consecutive series of 1,346 (mean age 55.0 +/- 12.0 years) male patients was studied. MAIN OUTCOMES MEASURES: All patients underwent PCDU performed both in the flaccid state and dynamic (after prostaglandin E1 stimulation) conditions. A subset of 20 subjects with uncomplicated type 2 diabetes underwent diagnostic testing for silent coronary heart disease by means of adenosine stress myocardial perfusion scintigraphy (SPECT). In these subjects penile arterial flow was simultaneously assessed by PCDU before and after systemic adenosine administration. RESULTS: Flaccid PSV showed a significant (r = 0.513, P < 0.0001) correlation with dynamic PSV. Receiver operating characteristic (ROC) curve analysis demonstrated that when a threshold of 13 cm/seconds was chosen, flaccid PSV was predictive for dynamic PSV < 25 and <35 cm/seconds with an accuracy of 89% and 82%, respectively. Among the subset of patients who underwent SPECT, an impaired coronary flow reserve (ICFR) occurred in nine cases (45%). When the same threshold of <13 cm/seconds was chosen, PSV before SPECT was predictive of ICFR with an accuracy of 80% (area under the ROC curve = 0.798 +/- 0.10; P < 0.05). After adjustment for confounders, anxiety symptoms were related to dynamic PSV (Adj. r = -0.154, P < 0.05) but not to flaccid PSV. CONCLUSIONS: Our results show that flow in the cavernosal arteries can be routinely evaluated by PCDU in the flaccid state. Performing PCDU only in the flaccid state allows identifying subjects with pathological dynamic PSV with accuracy higher than 80%. Furthermore, our preliminary data suggest that the same examination could identify diabetic subjects with ICFR with an accuracy of 80%.", "title": "Penile doppler ultrasound in patients with erectile dysfunction (ED): role of peak systolic velocity measured in the flaccid state in predicting ar..." }, { "docid": "MED-3395", "text": "The available large prospective studies supporting an inverse association between better adherence to the Mediterranean diet and lower mortality have mainly included older adults. It is not clear whether this inverse association is also present among younger individuals at lower mortality risk. Our aim was to assess the association between adherence to the Mediterranean diet and total mortality in middle-aged adults from the Seguimiento Universidad de Navarra (SUN) Project. We followed 15,535 Spanish university graduates for a mean of 6.8 y. Their mean age was 38 ± 12 y, 59.6% were females, and all were initially free of cardiovascular disease, cancer, and diabetes. A validated FFQ was used to assess dietary habits. Adherence to the Mediterranean diet was categorized into 3 groups according to the Mediterranean Diet Score (low, 0-2 points; moderate, 3-5 points; and high, 6-9 points). The outcome variable was total mortality. Cox proportional hazards models were used to estimate HR and 95% CI. We adjusted the estimates for sex, age, years of university education, BMI, smoking, physical activity, television watching, history of depression and baseline hypertension, and hypercholesterolemia. We observed 125 deaths during 105,980 person-years of follow-up. The fully adjusted HR for moderate and high adherence were 0.58 (95% CI: 0.34, 0.99; P = 0.05) and 0.38 (95% CI: 0.21, 0.70; P = 0.002), respectively. For each 2-point increment in the Mediterranean Diet Score, the HR of death was 0.72 (95% CI: 0.58, 0.91; P = 0.006). Among highly educated, middle-aged adults, adherence to the traditional Mediterranean diet was associated with reduced risk of death.", "title": "The Mediterranean diet is associated with a reduction in premature mortality among middle-aged adults." }, { "docid": "MED-4353", "text": "We have compared the effects of dietary soy protein and casein in diets low in cholesterol (less than 100 mg/d) and in diets enriched in cholesterol (500 mg/d) to examine whether the level of cholesterol intake affects the response of plasma lipoproteins to dietary proteins of plant and animal origin. Normal men and women consumed formula diets containing 20% of calories as soy protein or casein, 27% as fat and 53% as carbohydrate in 2 crossover studies. The dietary periods lasted for 31 days and were separated by a month-long interim period on self-chosen food. Following an initial reduction of plasma total cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels on all diets, the plasma lipid and lipoprotein concentrations stabilized. On low-cholesterol diets the concentration of each of the major lipoprotein classes were similar during the soy and the casein dietary periods. On cholesterol-enriched diets, the concentration of LDL-C stabilized at a 16% lower level on soy protein than on the casein diet (p less than 0.02), while the concentration of high-density lipoprotein-cholesterol (HDL-C) was 16% higher (p less than 0.01). Since the difference in LDL-C (p less than 0.05) and in HDL-C (p less than 0.025) levels on casein and on soy protein diets were significantly greater on the high than on the low cholesterol intake, the findings indicate that the level of dietary cholesterol may determine whether plant and animal dietary proteins have similar or different effects on plasma LDL-C and HDL-C concentrations.", "title": "Effects of dietary proteins on plasma lipoprotein levels in normal subjects: interaction with dietary cholesterol." }, { "docid": "MED-3440", "text": "INTRODUCTION: It is unclear whether men with erectile dysfunction (ED) ultimately die of cardiovascular (CV) causes. AIM: This study examined the causes of death in men with ED and their risk of CV death. METHODS: Based on statutory death registrations and hospital morbidity data, the risk of CV death in men with ED in a linked-data study was assessed against the CV mortality risk in a reference male population. MAIN OUTCOME MEASURES: Deaths from CV causes as proportions of all deaths. Age-specific rate, mortality rate ratio (MRR), standardized mortality rate ratio (SMRR), and adjusted hazard ratio (HR). RESULTS: CV mortality was 4.0%. Compared with the reference population, the risk of CV death was higher in men with ED (SMRR 2.2; 95% confidence interval [CI] 1.6, 3.0). Risk of CV mortality was higher in men with CV disease prior to ED (adjusted HR 1.7; 95% CI 1.1, 2.6) or with history of hospital admissions for CV events (adjusted HR 2.2; 95% CI 1.3, 3.8), compared with those without the respective history. MRR was significantly increased in the 40-69 years age group (MRR 4.1; 95% CI 3.2, 5.2). The median time interval between manifestation of ED and CV death was 10.0 years. A greater proportion of deaths from oncological than from CV causes (25.0% vs. 10.8%) occurred within the first 5 years of the manifestation of ED. CONCLUSIONS: Although the risk of CV mortality is greater in men with ED, almost as many men die of oncological as of CV causes, with a higher proportion of oncological deaths occurring sooner subsequent to the first manifestation of ED. © 2011 International Society for Sexual Medicine.", "title": "Cardiovascular mortality in men with erectile dysfunction: increased risk but not inevitable." }, { "docid": "MED-3425", "text": "OBJECTIVES: We examined whether common coronary heart disease (CHD) risk factors measured in mid-life predict erectile dysfunction (ED) 25 years later. BACKGROUND: Retrospective and cross-sectional studies have suggested that ED is associated with classic CHD risk factors, but few prospective studies have studied these associations. METHODS: In this prospective study of community-dwelling men age 30 to 69 years, seven classic CHD risk factors (age, smoking, hypertension, diabetes, hypercholesterolemia, hypertriglyceridemia, and obesity) were assessed from 1972 to 1974. In 1998, after an average follow-up of 25 years, surviving male participants were asked to complete the International Index of Erectile Function (IIEF-5), which allows stratification of ED into five groups. RESULTS: Sixty-eight percent of the surviving men returned, and 60% completed the IIEF-5 questionnaire. Respondents had more favorable levels of all heart disease risk factors at baseline than non-respondents. At baseline, the average age of the 570 ED study participants was 46 years; at follow-up, their average age was 72 years. Mean age, body mass index, cholesterol, and triglycerides were each significantly associated with an increased risk of ED. Cigarette smoking was marginally more common in those with severe/complete ED, as compared with those without ED. Blood pressure and fasting blood glucose were not significantly associated with ED, likely due to selective mortality. CONCLUSIONS: Improving CHD risk factors in mid-life may decrease the risk of ED as well as CHD. Erectile dysfunction should be included as an outcome in clinical trials of lipid-lowering agents and lifestyle modifications.", "title": "Heart disease risk factors predict erectile dysfunction 25 years later: the Rancho Bernardo Study." }, { "docid": "MED-5333", "text": "BACKGROUND/AIM: A vegetarian diet is known to prevent a series of diseases but may influence the balance of carbohydrate and fat metabolism as well as collagen synthesis. This study compares expression patterns of relevant genes in oral mucosa of omnivores and vegetarians. METHODS: Quantitative reverse transcriptase polymerase chain reaction was applied for analysis of mRNA levels from carnitine transporter OCTN2, hepatic CPT1A and nonhepatic CPT1B isoforms of carnitine palmitoyltransferase and collagen (CCOL2A1) in oral mucosa. RESULTS: Compared with volunteers with traditional eating habits, carbohydrate consumption was significantly higher (+22%) in vegetarians. This was associated with a significant stimulation of CPT1A (+50%) and OCTN2 (+10%) and a lowered collagen synthesis (-10%). CONCLUSION: These novel findings provide further insight into the association of a changed fat metabolism and reduced collagen synthesis in vegetarians, which could also play a role in the aging process. Copyright 2008 S. Karger AG, Basel.", "title": "Vegetarian diet affects genes of oxidative metabolism and collagen synthesis." }, { "docid": "MED-4617", "text": "The need for consistent and current data describing the true incidence of SCA and/or SCD was highlighted during the most recent Sudden Cardiac Arrest Thought Leadership Alliance’s (SCATLA) Think Tank meeting of national experts with broad representation of key stakeholders including thought leaders and representatives from the American College of Cardiology, American Heart Association, and the Heart Rhythm Society. As such, to evaluate the true magnitude of this public health problem, we performed a systematic literature search in MEDLINE using the MeSH headings, “death, sudden” OR the terms “sudden cardiac death” OR “sudden cardiac arrest” OR “cardiac arrest” OR “cardiac death” OR “sudden death” OR “arrhythmic death.” Study selection criteria included peer-reviewed publications of primary data used to estimate SCD incidence in the U.S. We used Web of Science®’s Cited Reference Search to evaluate the impact of each primary estimate on the medical literature by determining the number of times each “primary source” has been cited. The estimated U.S. annual incidence of SCD varied widely from 180,000 to > 450,000 among 6 included studies. These different estimates were in part due to different data sources (with data age ranging from 1980 to 2007), definitions of SCD, case ascertainment criteria, methods of estimation/extrapolation, and sources of case ascertainment. The true incidence of SCA and/or SCD in the U.S. remains unclear with a wide range in the available estimates, which are badly dated. As reliable estimates of SCD incidence are important for improving risk stratification and prevention, future efforts are clearly needed to establish uniform definitions of SCA and SCD and then to prospectively and precisely capture cases of SCA and SCD in the overall U.S. population.", "title": "Systematic Review of the Incidence of Sudden Cardiac Death in the United States" }, { "docid": "MED-5332", "text": "The gastrointestinal microbiota produces short-chain fatty acids, especially butyrate, which affect colonic health, immune function and epigenetic regulation. To assess the effects of nutrition and aging on the production of butyrate, the butyryl-CoA:acetate CoA-transferase gene and population shifts of Clostridium clusters lV and XlVa, the main butyrate producers, were analysed. Faecal samples of young healthy omnivores (24 ± 2.5 years), vegetarians (26 ± 5 years) and elderly (86 ± 8 years) omnivores were evaluated. Diet and lifestyle were assessed in questionnaire-based interviews. The elderly had significantly fewer copies of the butyryl-CoA:acetate CoA-transferase gene than young omnivores (P=0.014), while vegetarians showed the highest number of copies (P=0.048). The thermal denaturation of the butyryl-CoA:acetate CoA-transferase gene variant melting curve related to Roseburia/Eubacterium rectale spp. was significantly more variable in the vegetarians than in the elderly. The Clostridium cluster XIVa was more abundant in vegetarians (P=0.049) and in omnivores (P<0.01) than in the elderly group. Gastrointestinal microbiota of the elderly is characterized by decreased butyrate production capacity, reflecting increased risk of degenerative diseases. These results suggest that the butyryl-CoA:acetate CoA-transferase gene is a valuable marker for gastrointestinal microbiota function. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.", "title": "Quantification of butyryl CoA:acetate CoA-transferase genes reveals different butyrate production capacity in individuals according to diet and age." }, { "docid": "MED-5334", "text": "Until recently, intact protein that is rich in tryptophan was not seen as an alternative to pharmaceutical-grade tryptophan because protein also contains large neutral amino acids (LNAAs) that compete for transport sites across the blood-brain barrier. Recent evidence indicates that when deoiled gourd seed (a rich source of tryptophan with approximately 22 mg/g protein) is combined with glucose (a carbohydrate that reduces serum levels of competing LNAAs) a clinical effect similar to that of pharmaceutical-grade tryptophan is achieved. Objective and subjective measures of anxiety in those suffering from social phobia (also known as social anxiety disorder) were employed to measure changes in anxiety in response to a stimulus as part of a double-blind, placebo-controlled, crossover study with a wash-out period of 1 week between study sessions. Subjects were randomly assigned to start with either (i) protein-source tryptophan (deoiled gourd seed) in combination with carbohydrate or (ii) carbohydrate alone. One week after the initial session, subjects returned for a follow-up session and received the opposite treatment of that received at the first session. All 7 subjects who began the study completed the 2-week protocol. Protein-source tryptophan with carbohydrate, but not carbohydrate alone, resulted in significant improvement on an objective measure of anxiety. Protein-source tryptophan combined with a high glycemic carbohydrate is a potential anxiolytic to those suffering from social phobia.", "title": "Protein-source tryptophan as an efficacious treatment for social anxiety disorder: a pilot study." }, { "docid": "MED-3436", "text": "Erectile dysfunction (ED) is an early marker for systemic atherosclerosis and is a predictor for coronary artery disease and cardiac events. The aim of this paper is to convey the importance of addressing cardiovascular risk factors in patients with ED and to inform urologists as well as other physicians who are not specialized in cardiology how to carry out a basic cardiovascular evaluation, including history, physical examination and objective data. We review the evidence and pathophysiology linking ED to cardiovascular disease, and then describe how to carry out a basic cardiovascular evaluation. We present data from the literature showing that appropriate use of lifestyle modifications and medical therapy has a positive effect on mortality, on numerous cardiovascular end points and on ED. Suggestions of when to refer the ED patient to an internist or cardiologist are provided. Identifying and treating cardiovascular risk factors may not only benefit the patient's ED, but it might also save the patient's life.", "title": "How to save a life during a clinic visit for erectile dysfunction by modifying cardiovascular risk factors." }, { "docid": "MED-3434", "text": "INTRODUCTION: Although epidemiological evidence seems to support a role for lifestyle factors in the pathogenesis of erectile dysfunction (ED), limited data are available suggesting that dietary changes may improve ED. AIM: To provide an update on clinical evidence regarding the role of dietary factors in ED. METHODS: A systematic literature search was performed using MEDLINE and other database (EMBASE, SCOPUS) with MeSH terms and keywords for \"erectile dysfunction\", \"diet\", \"dietary patterns\", \"Mediterranean diet\", and \"lifestyle\". MAIN OUTCOME MEASURES: To examine the data relating to erectile dysfunction with dietary factors, its relationship and the impact of dietary treatment. RESULTS: Only few studies assessed the role or the effect of diet on ED. A dietary pattern which is high in fruit, vegetables, nuts, whole grains, and fish but low in red and processed meat and refined grains is more represented in subjects without ED. Mediterranean diet has been proposed as a healthy dietary pattern based on evidence that greater adherence to this diet is associated with lower all-cause and disease-specific survival. In type 2 diabetic men, those with the highest adherence to the Mediterranean diet had the lowest prevalence of ED and were more likely to be sexually active. In clinical trials, Mediterranean diet was more effective than a control diet in ameliorating ED or restoring absent ED in people with obesity or metabolic syndrome. CONCLUSION: The adoption of a Mediterranean diet may be associated with an improvement of erectile dysfunction.", "title": "Dietary factors, Mediterranean diet and erectile dysfunction." }, { "docid": "MED-5326", "text": "The effect of meat consumption on cancer risk is a controversial issue. However, recent meta-analyses show that high consumers of cured meats and red meat are at increased risk of colorectal cancer. This increase is significant but modest (20-30%). Current WCRF-AICR recommendations are to eat no more than 500 g per week of red meat, and to avoid processed meat. Moreover, our studies show that beef meat and cured pork meat promote colon carcinogenesis in rats. The major promoter in meat is heme iron, via N-nitrosation or fat peroxidation. Dietary additives can suppress the toxic effects of heme iron. For instance, promotion of colon carcinogenesis in rats by cooked, nitrite-treated and oxidized high-heme cured meat was suppressed by dietary calcium and by α-tocopherol, and a study in volunteers supported these protective effects in humans. These additives, and others still under study, could provide an acceptable way to prevent colorectal cancer. Copyright © 2011 Elsevier B.V. All rights reserved.", "title": "Red meat and colon cancer: should we become vegetarians, or can we make meat safer?" }, { "docid": "MED-5338", "text": "Summary Background and objectives Patients with advanced chronic kidney disease (CKD) are in positive phosphorus balance, but phosphorus levels are maintained in the normal range through phosphaturia induced by increases in fibroblast growth factor-23 (FGF23) and parathyroid hormone (PTH). This provides the rationale for recommendations to restrict dietary phosphate intake to 800 mg/d. However, the protein source of the phosphate may also be important. Design, setting, participants, & measurements We conducted a crossover trial in nine patients with a mean estimated GFR of 32 ml/min to directly compare vegetarian and meat diets with equivalent nutrients prepared by clinical research staff. During the last 24 hours of each 7-day diet period, subjects were hospitalized in a research center and urine and blood were frequently monitored. Results The results indicated that 1 week of a vegetarian diet led to lower serum phosphorus levels and decreased FGF23 levels. The inpatient stay demonstrated similar diurnal variation for blood phosphorus, calcium, PTH, and urine fractional excretion of phosphorus but significant differences between the vegetarian and meat diets. Finally, the 24-hour fractional excretion of phosphorus was highly correlated to a 2-hour fasting urine collection for the vegetarian diet but not the meat diet. Conclusions In summary, this study demonstrates that the source of protein has a significant effect on phosphorus homeostasis in patients with CKD. Therefore, dietary counseling of patients with CKD must include information on not only the amount of phosphate but also the source of protein from which the phosphate derives.", "title": "Original Articles: Vegetarian Compared with Meat Dietary Protein Source and Phosphorus Homeostasis in Chronic Kidney Disease" }, { "docid": "MED-3430", "text": "BACKGROUND: Erectile dysfunction (ED) shares similar modifiable risks factors with coronary artery disease (CAD). Lifestyle modification that targets CAD risk factors may also lead to improvement in ED. We conducted a systematic review and meta-analysis of randomized controlled trials evaluating the effect of lifestyle interventions and pharmacotherapy for cardiovascular (CV) risk factors on the severity of ED. METHODS: A comprehensive search of multiple electronic databases through August 2010 was conducted using predefined criteria. We included randomized controlled clinical trials with follow-up of at least 6 weeks of lifestyle modification intervention or pharmacotherapy for CV risk factor reduction. Studies were selected by 2 independent reviewers. The main outcome measure of the study is the weighted mean differences in the International Index of Erectile Dysfunction (IIEF-5) score with 95% confidence intervals (CIs) using a random effects model. RESULTS: A total of 740 participants from 6 clinical trials in 4 countries were identified. Lifestyle modifications and pharmacotherapy for CV risk factors were associated with statistically significant improvement in sexual function (IIEF-5 score): weighted mean difference, 2.66 (95% CI, 1.86-3.47). If the trials with statin intervention (n = 143) are excluded, the remaining 4 trials of lifestyle modification interventions (n = 597) demonstrate statistically significant improvement in sexual function: weighted mean difference, 2.40 (95% CI, 1.19-3.61). CONCLUSION: The results of our study further strengthen the evidence that lifestyle modification and pharmacotherapy for CV risk factors are effective in improving sexual function in men with ED.", "title": "The effect of lifestyle modification and cardiovascular risk factor reduction on erectile dysfunction: a systematic review and meta-analysis." }, { "docid": "MED-5329", "text": "OBJECTIVE: This study was conducted to demonstrate the effectiveness of a strictly vegetarian, very low-fat diet on cardiac risk factor modification. METHODS: Five hundred men and women, participants in an intensive 12-day live-in program, were studied. The program focused on dietary modification, moderate exercise, and stress management at a hospital-based health-center. RESULTS: During this short time period, cardiac risk factors improved: there was an average reduction of total serum cholesterol of 11% (p < 0.001), of blood pressure of 6% (p < 0.001) and a weight loss of 2.5 kg for men and 1 kg for women. Serum triglycerides did not increase except for two subgroups: females age > or = 65 years with serum cholesterol < 6.5 mmol/L and for females 50 to 64 years with baseline serum cholesterol between 5.2-6.5 mmol/L. High-density lipoprotein cholesterol measured on 66 subjects decreased by 19%. CONCLUSION: A strict, very low-fat vegetarian diet free from all animal products combined with lifestyle changes that include exercise and weight loss is an effective way to lower serum cholesterol and blood pressure.", "title": "Rapid reduction of serum cholesterol and blood pressure by a twelve-day, very low fat, strictly vegetarian diet." }, { "docid": "MED-3423", "text": "INTRODUCTION: There are no reported studies assessing the relation between diet and sexual function in women with diabetes. AIM: In the present study, we explored the relation between consumption of a Mediterranean-type diet and sexual function in a population of type 2 diabetic women. METHODS: Patients with type 2 diabetes were enrolled if they had a diagnosis of type 2 diabetes for at least six months but less than 10 years, age 35-70 years, body mass index (BMI) of 24 or higher, HbA1c of 6.5% or higher, treatment with diet or oral drugs. All diabetic patients were invited to complete a food-frequency questionnaire and self-report measures of sexual function. A total of 595 (90.2%) of the 659 women completed both questionnaires and were analyzed in the present study. MAIN OUTCOME MEASURES: Adherence to a Mediterranean diet was assessed by a 9-point scale that incorporated the salient characteristics of this diet (range of scores, 0-9, with higher scores indicating greater adherence). The Female Sexual Function Index (FSFI) was used for assessing the key dimensions of female sexual function. RESULTS: Diabetic women with the highest scores (6-9) had lower BMI, waist circumference, and waist-to-hip ratio, a lower prevalence of depression, obesity and metabolic syndrome, a higher level of physical activity, and better glucose and lipid profiles than the diabetic women who scored <3 points on the scale. The proportion of sexually active women showed a significant increase across tertiles of adherence to Mediterranean diet (from 54.2% to 65.1%, P = 0.01). Based on the FSFI cutoff score for female sexual dysfunction (FSD) of 23, women with the highest score of adherence had a lower prevalence of sexual dysfunction as compared with women of lower tertiles (47.6%, 53.9%, and 57.8%, higher, middle, and lower tertile, respectively, P = 0.01). These associations remained significant after adjustment for many potential confounders. CONCLUSIONS: In women with type 2 diabetes, greater adherence to Mediterranean diet is associated with a lower prevalence of FSD.", "title": "Adherence to Mediterranean diet and sexual function in women with type 2 diabetes." } ]
[ { "docid": "MED-3396", "text": "OBJECTIVES: To summarize and compare evidence on harms in sildenafil- and placebo-treated men with erectile dysfunction (ED) in a systematic review and meta-analysis. METHODS: Randomized placebo-controlled trials (RCTs) were identified using an electronic search in MEDLINE, EMBASE, PsycINFO, SCOPUS, and Cochrane CENTRAL. The rates of any adverse events (AEs), most commonly reported AEs, withdrawals because of adverse events, and serious adverse events were ascertained and compared between sildenafil and placebo groups. The results of men with ED were stratified by clinical condition(s). Statistical heterogeneity was explored. Meta-analyses based on random-effects model were also performed. RESULTS: A total of 49 RCTs were included. Sildenafil-treated men had a higher risk for all-cause AEs (RR = 1.56, 95% CI: 1.38, 1.76), headache, flushing, dyspepsia, and visual disturbances compared with placebo-treated men. The magnitude of excess risk was greater in fixed- than in flexible-dose trials. The rates of serious adverse events and withdrawals because of adverse events did not differ in sildenafil vs placebo groups. A higher dose of sildenafil corresponded to a greater risk of AEs. The increased risk of harms was observed within and across clinically defined specific groups of patients. CONCLUSIONS: There was a lack of RCTs reporting long-term (>6 months) harms data. In short-term trials, men with ED randomized to sildenafil had an increased risk of all-cause any AEs, headache, flushing, dyspepsia, and visual disturbances. The exploration of different modes of dose optimization of sildenafil may be warranted.", "title": "Oral sildenafil citrate (viagra) for erectile dysfunction: a systematic review and meta-analysis of harms." }, { "docid": "MED-3429", "text": "Sexual problems are diffuse in both genders. Although epidemiologic evidence seems to support a role for lifestyle factors in erectile dysfunction, limited data are available suggesting the treatment of underlying risk factors may improve erectile dysfunction. The results are sparse regarding associations between lifestyle factors and female sexual dysfunction, and conclusions regarding influence of healthy behaviors on female sexual dysfunction cannot be made before more studies have been performed. Beyond the specific effects on sexual dysfunctions in men and women, adoption of these measures promotes a healthier life and increased well-being, which may help reduce the burden of sexual dysfunction. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Lifestyle/dietary recommendations for erectile dysfunction and female sexual dysfunction." }, { "docid": "MED-3399", "text": "We investigated the effects of Antep pistachio on International Index of Erectile Function (IIEF) scores, penile color Doppler ultrasound (PCDU) parameters and serum lipid levels in patients with ED. A total of 17 married male patients with ED for at least 12 months were included in this prospective study. Patients were put on a 100 g pistachio nuts diet for 3 weeks. IIEF and PCDU were evaluated before and after the pistachio diet. In addition, plasma total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride were measured before and after dietary modifications from all subjects. Mean IIEF-15 score was 36 ± 7.5 before the diet and 54.2 ± 4.9 after the diet (P=0.001). Similarly, an increase in all five domains of IIEF was observed after the diet (P<0.05). Mean peak systolic velocity values before and after the pistachio diet were 35.5 ± 15.2 and 43.3 ± 12.4 cm s(-1), respectively (P=0.018). After the pistachio diet, TC and LDL levels decreased significantly, whereas HDL level increased (P=0.008, 0.007 and 0.001, respectively). We demonstrated that a pistachio diet improved IIEF scores and PCDU parameters without any associated side effects in patients with ED. Furthermore, the lipid parameters showed statistically significant improvements after this diet.", "title": "Pistachio diet improves erectile function parameters and serum lipid profiles in patients with erectile dysfunction." }, { "docid": "MED-940", "text": "Saffron (Crocus sativus Linn.) have been perceived by the public as a strong aphrodisiac herbal product. However, studies addressing the potential beneficial effects of saffron on erectile function (EF) in men with ED are lacking. Our aim was to evaluate the efficacy and safety of saffron administration on EF in men with ED. After a 4-week baseline assessment, 346 men with ED (mean age 46.6+/-8.4 years) were randomized to receive on-demand sildenafil for 12 weeks followed by 30 mg saffron twice daily for another 12 weeks or vice versa, separated by a 2-week washout period. To determine the type of ED, penile color duplex Doppler ultrasonography before and after intracavernosal injection with 20 microg prostaglandin E(1), pudendal nerve conduction tests and impaired sensory-evoked potential studies were performed. Subjects were assessed with an International Index of Erectile Function (IIEF) questionnaire, Sexual Encounter Profile (SEP) diary questions, patient and partner versions of the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire and the Global Efficacy Question (GEQ) 'Has the medication you have been taking improved your erections?' No significant improvements were observed with regard to the IIEF sexual function domains, SEP questions and EDITS scores with saffron administration. The mean changes from baseline values in IIEF-EF domain were +87.6% and +9.8% in sildenafil and placebo groups, respectively (P=0.08). We did not observe any improvement in 15 individual IIEF questions in patients while taking saffron. Treatment satisfaction as assessed by partner versions of EDITS was found to be very low in saffron patients (72.4 vs 25.4, P=0.001). Mean per patient 'yes' responses to GEQ was 91.2 and 4.2% for sildenafil and saffron, respectively (P=0.0001). These findings do not support a beneficial effect of saffron administration in men with ED.", "title": "An open label, randomized, fixed-dose, crossover study comparing efficacy and safety of sildenafil citrate and saffron (Crocus sativus Linn.) for t..." }, { "docid": "MED-746", "text": "In this study, the effect of Crocus sativus (saffron) was studied on male erectile dysfunction (ED). Twenty male patients with ED were followed for ten days in which each morning they took a tablet containing 200mg of saffron. Patients underwent the nocturnal penile tumescence (NPT) test and the international index of erectile function questionnaire (IIEF-15) at the start of the treatment and at the end of the ten days. After the ten days of taking saffron there was a statistically significant improvement in tip rigidity and tip tumescence as well as base rigidity and base tumescence. ILEF-15 total scores were significantly higher in patients after saffron treatment (before treatment 22.15+/-1.44; after treatment 39.20+/-1.90, p<0.001). Saffron showed a positive effect on sexual function with increased number and duration of erectile events seen in patients with ED even only after taking it for ten days.", "title": "Evaluation of Crocus sativus L. (saffron) on male erectile dysfunction: a pilot study." }, { "docid": "MED-3432", "text": "Men with the metabolic syndrome demonstrate an increased prevalence of erectile dysfunction (ED). In the present study, we tested the effect of a Mediterranean-style diet on ED in men with the metabolic syndrome. Men were identified in our database of subjects participating in controlled trials evaluating the effect of lifestyle changes and were included if they had a diagnosis of ED associated with a diagnosis of metabolic syndrome, complete follow-up in the study trial, and intervention focused mainly on dietary changes. Sixty-five men with the metabolic syndrome met the inclusion/exclusion criteria; 35 out of them were assigned to the Mediterranean-style diet and 30 to the control diet. After 2 years, men on the Mediterranean diet consumed more fruits, vegetables, nuts, whole grain, and olive oil as compared with men on the control diet. Endothelial function score and inflammatory markers (C-reactive protein) improved in the intervention group, but remained stable in the control group. There were 13 men in the intervention group and two in the control group (P=0.015) that reported an IIEF score of 22 or higher. Mediterranean-style diet rich in whole grain, fruits, vegetables, legumes, walnut, and olive oil might be effective per se in reducing the prevalence of ED in men with the metabolic syndrome.", "title": "Mediterranean diet improves erectile function in subjects with the metabolic syndrome." }, { "docid": "MED-828", "text": "Background Maca (Lepidium meyenii) is an Andean plant of the brassica (mustard) family. Preparations from maca root have been reported to improve sexual function. The aim of this review was to assess the clinical evidence for or against the effectiveness of the maca plant as a treatment for sexual dysfunction. Methods We searched 17 databases from their inception to April 2010 and included all randomised clinical trials (RCTs) of any type of maca compared to a placebo for the treatment of healthy people or human patients with sexual dysfunction. The risk of bias for each study was assessed using Cochrane criteria, and statistical pooling of data was performed where possible. The selection of studies, data extraction, and validations were performed independently by two authors. Discrepancies were resolved through discussion by the two authors. Results Four RCTs met all the inclusion criteria. Two RCTs suggested a significant positive effect of maca on sexual dysfunction or sexual desire in healthy menopausal women or healthy adult men, respectively, while the other RCT failed to show any effects in healthy cyclists. The further RCT assessed the effects of maca in patients with erectile dysfunction using the International Index of Erectile Dysfunction-5 and showed significant effects. Conclusion The results of our systematic review provide limited evidence for the effectiveness of maca in improving sexual function. However, the total number of trials, the total sample size, and the average methodological quality of the primary studies were too limited to draw firm conclusions. More rigorous studies are warranted.", "title": "Maca (L. meyenii) for improving sexual function: a systematic review" }, { "docid": "MED-4422", "text": "OBJECTIVES: To test the efficacy and safety of oral L-citrulline supplementation in improving erection hardness in patients with mild erectile dysfunction (ED). L-arginine supplementation improves nitric oxide-mediated vasodilation and endothelial function; however, oral administration has been hampered by extensive presystemic metabolism. In contrast, L-citrulline escapes presystemic metabolism and is converted to L-arginine, thus setting the rationale for oral L-citrulline supplementation as a donor for the L-arginine/nitric oxide pathway of penile erection. METHODS: In the present single-blind study, men with mild ED (erection hardness score of 3) received a placebo for 1 month and L-citrulline, 1.5 g/d, for another month. The erection hardness score, number of intercourses per month, treatment satisfaction, and adverse events were recorded. RESULTS: A total of 24 patients, mean age 56.5 ± 9.8 years, were entered and concluded the study without adverse events. The improvement in the erection hardness score from 3 (mild ED) to 4 (normal erectile function) occurred in 2 (8.3%) of the 24 men when taking placebo and 12 (50%) of the 24 men when taking L-citrulline (P < .01). The mean number of intercourses per month increased from 1.37 ± 0.93 at baseline to 1.53 ± 1.00 at the end of the placebo phase (P = .57) and 2.3 ± 1.37 at the end of the treatment phase (P < .01). All patients reporting an erection hardness score improvement from 3 to 4 reported being very satisfied. CONCLUSIONS: Although less effective than phosphodiesterase type-5 enzyme inhibitors, at least in the short term, L-citrulline supplementation has been proved to be safe and psychologically well accepted by patients. Its role as an alternative treatment for mild to moderate ED, particularly in patients with a psychologically fear of phosphodiesterase type-5 enzyme inhibitors, deserves further research. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction." }, { "docid": "MED-4022", "text": "BACKGROUND: Erectile dysfunction (ED) and chronic periodontitis (CP) share common risk factors. There is only one report on the association between ED and CP. Thus, the aim of this study is to find the association between vasculogenic ED and CP. METHODS: A total of 70 patients (mean age: 35.3 ± 3.64 years) clinically diagnosed with ED were included in the study. They were given the Sexual Health Inventory for Men Questionnaire and subjected to colored penile Doppler ultrasound. Periodontal parameters of probing depth and periodontal attachment level were recorded. Five patients with ED and CP were selected randomly for cardiac color Doppler to assess the integrity. RESULTS: Among the selected vasculogenic patients with ED, mild-to-moderate vasculogenic ED showed the highest prevalence, whereas prevalence for CP among all vasculogenic patients with ED was highest among severe ED (81.8%). Association of CP and vasculogenic ED was found to be correlated positively, but it showed no statistical significance. Two of five patients were found to have vascular insufficiency. CONCLUSIONS: It can be hypothesized that an association exists between vasculogenic ED and CP in young males. However, a large-scale study with confounder analysis and a longitudinal follow-up is warranted.", "title": "Association between chronic periodontitis and vasculogenic erectile dysfunction." }, { "docid": "MED-1011", "text": "Background Placebo treatment can significantly influence subjective symptoms. However, it is widely believed that response to placebo requires concealment or deception. We tested whether open-label placebo (non-deceptive and non-concealed administration) is superior to a no-treatment control with matched patient-provider interactions in the treatment of irritable bowel syndrome (IBS). Methods Two-group, randomized, controlled three week trial (August 2009-April 2010) conducted at a single academic center, involving 80 primarily female (70%) patients, mean age 47±18 with IBS diagnosed by Rome III criteria and with a score ≥150 on the IBS Symptom Severity Scale (IBS-SSS). Patients were randomized to either open-label placebo pills presented as “placebo pills made of an inert substance, like sugar pills, that have been shown in clinical studies to produce significant improvement in IBS symptoms through mind-body self-healing processes” or no-treatment controls with the same quality of interaction with providers. The primary outcome was IBS Global Improvement Scale (IBS-GIS). Secondary measures were IBS Symptom Severity Scale (IBS-SSS), IBS Adequate Relief (IBS-AR) and IBS Quality of Life (IBS-QoL). Findings Open-label placebo produced significantly higher mean (±SD) global improvement scores (IBS-GIS) at both 11-day midpoint (5.2±1.0 vs. 4.0±1.1, p<.001) and at 21-day endpoint (5.0±1.5 vs. 3.9±1.3, p = .002). Significant results were also observed at both time points for reduced symptom severity (IBS-SSS, p = .008 and p = .03) and adequate relief (IBS-AR, p = .02 and p = .03); and a trend favoring open-label placebo was observed for quality of life (IBS-QoL) at the 21-day endpoint (p = .08). Conclusion Placebos administered without deception may be an effective treatment for IBS. Further research is warranted in IBS, and perhaps other conditions, to elucidate whether physicians can benefit patients using placebos consistent with informed consent. Trial Registration ClinicalTrials.gov NCT01010191", "title": "Placebos without Deception: A Randomized Controlled Trial in Irritable Bowel Syndrome" }, { "docid": "MED-3753", "text": "BACKGROUND: No regulations govern placebo composition. The composition of placebos can influence trial outcomes and merits reporting. PURPOSE: To assess how often investigators specify the composition of placebos in randomized, placebo-controlled trials. DATA SOURCES: 4 English-language general and internal medicine journals with high impact factors. STUDY SELECTION: 3 reviewers screened titles and abstracts of the journals to identify randomized, placebo-controlled trials published from January 2008 to December 2009. DATA EXTRACTION: Reviewers independently abstracted data from the introduction and methods sections of identified articles, recording treatment type (pill, injection, or other) and whether placebo composition was stated. Discrepancies were resolved by consensus. DATA SYNTHESIS: Most studies did not disclose the composition of the study placebo. Disclosure was less common for pills than for injections and other treatments (8.2% vs. 26.7%; P = 0.002). LIMITATION: Journals with high impact factors may not be representative. CONCLUSION: Placebos were seldom described in randomized, controlled trials of pills or capsules. Because the nature of the placebo can influence trial outcomes, placebo formulation should be disclosed in reports of placebo-controlled trials.", "title": "What's in placebos: who knows? Analysis of randomized, controlled trials." }, { "docid": "MED-3433", "text": "OBJECTIVES: Our goal was to evaluate the association between erectile dysfunction (ED) and risk of cardiovascular disease (CVD) and all-cause mortality by conducting a meta-analysis of prospective cohort studies. BACKGROUND: Observational studies suggest an association between ED and the incidence of CVD. However, whether ED is an independent risk factor of CVD remains controversial. METHODS: The PubMed database was searched through January 2011 to identify studies that met pre-stated inclusion criteria. Reference lists of retrieved articles were also reviewed. Two authors independently extracted information on the designs of the studies, the characteristics of the study participants, exposure and outcome assessments, and control for potential confounding factors. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. RESULTS: Twelve prospective cohort studies involving 36,744 participants were included in the meta-analysis. The overall combined relative risks for men with ED compared with the reference group were 1.48 (95% confidence interval [CI]: 1.25 to 1.74) for CVD, 1.46 (95% CI: 1.31 to 1.63) for coronary heart disease, 1.35 (95% CI: 1.19 to 1.54) for stroke, and 1.19 (95% CI: 1.05 to 1.34) for all-cause mortality. Sensitivity analysis restricted to studies with control for conventional cardiovascular risk factors yielded similar results. No evidence of publication bias was observed. CONCLUSIONS: This meta-analysis of prospective cohort studies suggests that ED significantly increases the risk of CVD, coronary heart disease, stroke, and all-cause mortality, and the increase is probably independent of conventional cardiovascular risk factors. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.", "title": "Erectile dysfunction and risk of cardiovascular disease: meta-analysis of prospective cohort studies." }, { "docid": "MED-1354", "text": "Context Antidepressant medications represent the best established treatment for Major Depressive Disorder (MDD), but there is little evidence that they have a specific pharmacological effect relative to pill-placebo for patients with less severe depression. Objective To estimate the relative benefit of medication vs placebo across a wide range of initial symptom severity in patients diagnosed with depression. Data Sources Pubmed, PsycINFO, and the Cochrane Library databases were searched from January 1980 through March 2009, along with references from meta-analyses and reviews. Study Selection Randomized placebo-controlled trials of FDA approved antidepressants in the treatment of Major or Minor Depressive Disorder were selected. Studies were included if their authors provided the requisite original data, they comprised adult outpatients, included a medication vs placebo comparison for at least 6 weeks, did not exclude patients on the basis of a placebo washout period, and utilized the Hamilton Rating Scale for Depression. Data from six studies (718 patients) were included. Data Extraction Individual patient-level data were obtained from study authors. Results Medication vs placebo differences varied substantially as a function of baseline severity. Among patients with Hamilton scores below 23, Cohen’s d-type effect sizes for the difference between medication and placebo were estimated to be < .20 (a standard definition of a small effect). Estimates of the magnitude of the superiority of medication over placebo increased with increases in baseline Hamilton severity and crossed the NICE threshold for a clinically significant difference at a baseline score of 25. Conclusions The magnitude of benefit of antidepressant medication compared with placebo increases with severity of depression symptoms, and may be minimal or nonexistent, on average, in patients with mild or moderate symptoms. For patients with very severe depression, the benefit of medications over placebo is substantial.", "title": "Antidepressant Drug effects and Depression Severity: A Patient-Level Meta-Analysis" }, { "docid": "MED-2697", "text": "OBJECTIVES: The purpose of this study was to test the hypothesis that intake of used cooking fat is associated with impaired endothelial function. BACKGROUND: Diets containing high levels of lipid oxidation products may accelerate atherogenesis, but the effect on endothelial function is unknown. METHODS: Flow-mediated endothelium-dependent dilation and glyceryl trinitrate-induced endothelium-independent dilation of the brachial artery were investigated in 10 men. Subjects had arterial studies before and 4 h after three test meals: 1) a meal (fat 64.4 g) rich in cooking fat that had been used for deep frying in a fast food restaurant; 2) the same meal (fat 64.4 g) rich in unused cooking fat, and 3) a corresponding low fat meal (fat 18.4 g) without added fat. RESULTS: Endothelium-dependent dilation decreased between fasting and postprandial studies after the used fat meal (5.9 +/- 2.3% vs. 0.8 +/- 2.2%, p = 0.0003), but there was no significant change after the unused fat meal (5.3 +/- 2.1% vs. 6.0 +/- 2.5%) or low fat meal (5.3 +/- 2.3% vs. 5.4 +/- 3.3%). There was no significant difference in endothelium-independent dilation after any of the meals. Plasma free fatty acid concentration did not change significantly during any of the meals. The level of postprandial hypertriglyceridemia was not associated with change in endothelial function. CONCLUSIONS: Ingestion of a meal rich in fat previously used for deep frying in a commercial fast food restaurant resulted in impaired arterial endothelial function. These findings suggest that intake of degradation products of heated fat contribute to endothelial dysfunction.", "title": "Impaired endothelial function following a meal rich in used cooking fat." }, { "docid": "MED-5013", "text": "INTRODUCTION: Endothelial dysfunction is known to occur in patients with coronary artery disease. Flow-mediated dilation of the brachial artery using Doppler ultrasound is a non-invasive technique for the assessment of endothelial function. The objective of the study was to use the above method to evaluate the pathophysiology of high-fat (HF) intake on endothelial function in a local population. A popular local dish \"nasi-lemak\", a source of high saturated fat content from coconut milk, was chosen to represent a local high-fat meal (LHF). In addition, the effects of a Western high-fat (WHF) (\"McDonald's\") meal and a low-fat (LF) meal control on endothelial function were studied. MATERIALS AND METHODS: The study population consisted of 10 healthy male non-smoker (mean age 22 +/- 2 years) with normal body mass index, normal fasting sugar and lipid profiles. Nitric oxide dependent flow-mediated dilation and nitric oxide independent (GTN) dilation was assessed by Doppler flow in the brachial artery before and 4 hours after each meal on separate occasions by 2 experienced sonographers blinded to the type of meals. RESULTS: The baseline brachial artery size, baseline vessel flow and increase in flow after cuff deflation were similar for each of the six arterial studies. In response to reactive hyperaemia after cuff deflation, the endothelium-dependent dilation was significantly different between the meals. There was a marked decrease in endothelium-dependent dilation after the WHF meal compared to the LF meal (8.6 +/- 2.2% vs. -0.8 +/- 1.1%, P < 0.006). There was also a marked decrease in endothelium-dependent dilation after the LHF meal compared to the LF meal (7.7 +/- 2.1% vs. -0.8 +/- 1.1%, P < 0.001). When comparing between the two HF meals, the change in endothelium-dependent dilation was not significant (7.7 vs. 8.6%, P = 0.678). GTN-induced dilation was not significantly different before and after the LF, WHF or LHF (0.1 +/- 0.5% vs. 0.2 +/- 0.9% vs. 1.3 +/- 0.5%, P = 0.094). CONCLUSION: The results suggest that in a local population, impairment of endothelial function is a possible mechanism in the pathophysiology of atherosclerosis from HF intake, beyond just affecting lipid levels. This effect is observed after both a LHF and a WHF meal intake. This technique to study endothelial function may be a useful non-invasive screening tool in the study of other HF diet choices and provides further information for the education of the influence of dietary choices on atherosclerosis.", "title": "Impairment of endothelial function--a possible mechanism for atherosclerosis of a high-fat meal intake." }, { "docid": "MED-4755", "text": "OBJECTIVE: To critically evaluate the clinical evidence, and when not available, the animal data, most relevant to concerns that isoflavone exposure in the form of supplements or soy foods has feminizing effects on men. DESIGN: Medline literature review and cross-reference of published data. RESULT(S): In contrast to the results of some rodent studies, findings from a recently published metaanalysis and subsequently published studies show that neither isoflavone supplements nor isoflavone-rich soy affect total or free testosterone (T) levels. Similarly, there is essentially no evidence from the nine identified clinical studies that isoflavone exposure affects circulating estrogen levels in men. Clinical evidence also indicates that isoflavones have no effect on sperm or semen parameters, although only three intervention studies were identified and none were longer than 3 months in duration. Finally, findings from animal studies suggesting that isoflavones increase the risk of erectile dysfunction are not applicable to men, because of differences in isoflavone metabolism between rodents and humans and the excessively high amount of isoflavones to which the animals were exposed. CONCLUSION(S): The intervention data indicate that isoflavones do not exert feminizing effects on men at intake levels equal to and even considerably higher than are typical for Asian males. Copyright 2010. Published by Elsevier Inc.", "title": "Soybean isoflavone exposure does not have feminizing effects on men: a critical examination of the clinical evidence." }, { "docid": "MED-2884", "text": "Two carotenoids found in egg yolk, lutein and zeaxanthin, accumulate in the macular retina where they may reduce photostress. Increases in serum lutein and zeaxanthin were observed in previous egg interventions, but no study measured macular carotenoids. The objective of this project was to determine whether increased consumption of eggs would increase retinal lutein and zeaxanthin, or macular pigment. Twenty-four females, between 24 and 59 y, were assigned to a pill treatment (PILL) or 1 of 2 egg treatments for 12 wk. Individuals in the PILL treatment consumed 1 sugar-filled capsule/d. Individuals in the egg treatments consumed 6 eggs/wk, containing either 331 microg (EGG 1) or 964 microg (EGG 2) of lutein and zeaxanthin/yolk. Serum cholesterol, serum carotenoids, and macular pigment OD (MPOD) were measured at baseline and after 4, 8, and 12 wk of intervention. Serum cholesterol concentrations did not change in either egg treatment group, but total cholesterol (P = 0.04) and triglycerides (P = 0.02) increased in the PILL group. Serum zeaxanthin, but not serum lutein, increased in both the EGG 1 (P = 0.04) and EGG 2 (P = 0.01) groups. Likewise, MPOD increased in both the EGG 1 (P = 0.001) and EGG 2 (P = 0.049) groups. Although the aggregate concentration of carotenoid in 1 egg yolk may be modest relative to other sources, such as spinach, their bioavailability to the retina appears to be high. Increasing egg consumption to 6 eggs/wk may be an effective method to increase MPOD.", "title": "A 12-wk egg intervention increases serum zeaxanthin and macular pigment optical density in women." }, { "docid": "MED-2235", "text": "Broccoli consumption may reduce the risk of various cancers and many broccoli supplements are now available. The bioavailability and excretion of the mercapturic acid pathway metabolites isothiocyanates after human consumption of broccoli supplements has not been tested. Two important isothiocyanates from broccoli are sulforaphane and erucin. We employed a cross-over study design in which 12 subjects consumed 40 grams of fresh broccoli sprouts followed by a 1 month washout period and then the same 12 subjects consumed 6 pills of a broccoli supplement. As negative controls for isothiocyanate consumption four additional subjects consumed alfalfa sprouts during the first phase and placebo pills during the second. Blood and urine samples were collected for 48 hours during each phase and analyzed for sulforaphane and erucin metabolites using LC-MS/MS. The bioavailability of sulforaphane and erucin is dramatically lower when subjects consume broccoli supplements compared to fresh broccoli sprouts. The peaks in plasma concentrations and urinary excretion were also delayed when subjects consumed the broccoli supplement. GSTP1 polymorphisms did not affect the metabolism or excretion of sulforaphane or erucin. Sulforaphane and erucin are able to interconvert in vivo and this interconversion is consistent within each subject but variable between subjects. This study confirms that consumption of broccoli supplements devoid of myrosinase activity does not produce equivalent plasma concentrations of the bioactive isothiocyanate metabolites compared to broccoli sprouts. This has implications for people who consume the recommended serving size (1 pill) of a broccoli supplement and believe they are getting equivalent doses of isothiocyanates.", "title": "Bioavailability and inter-conversion of sulforaphane and erucin in human subjects consuming broccoli sprouts or broccoli supplement in a cross-over study design" }, { "docid": "MED-3397", "text": "INTRODUCTION: Phosphodiesterase type 5 (PDE5) inhibitors are the first line drugs for treatment of erectile dysfunction. Sildenafil (Viagra(R)), tadalafil (Cialis(R)), and vardenafil (Levitra(R)) are from the same class of drugs that inhibit PDE5. Transient visual symptoms such as change in color perception and increased light sensitivity are well-known adverse effects of these drugs and occur in 3-11% of sildenafil users. Vision-threatening (serious) ocular complications, such as nonarteritic ischemic optic neuropathy and cilio-retinal artery occlusion have rarely been reported in PDE5 inhibitor users. AIMS: To highlight and analyze the most recently published case literature on serious ocular complications of PDE5 inhibitors. METHODS: Search of the peer-reviewed English literature was conducted using Medline. The following databases also were searched: Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Global Health, and MD Consult. The causality assessment of the reported adverse drug reactions was analyzed by applying both the World Health Organization (WHO) Probability Scale and the criteria utilized by the National Registry of Drug-Induced Ocular Side Effects. MAIN OUTCOME MEASURES: To scientifically and objectively find out if PDE5 inhibitors are associated with vision-threatening ocular complications. RESULTS: Eight case reports of serious PDE5 inhibitor-associated ocular complications were identified since January 2006 until February 2011. Case reports included cases of anterior and posterior nonarteritic ischemic optic neuropathy, central retinal vein occlusion, cilio-retinal artery occlusion, acute angle closure glaucoma and optic atrophy after sildenafil use. CONCLUSION: There is lack of conclusive evidence to indicate a direct cause-effect relationship between PDE5 inhibitor use and vision-threatening ocular events. Men who use PDE5 inhibitors appear to suffer vision-threatening complications at the same frequency as the general population. However, minor visual adverse effects occur in 3-11% of users and they are transient and reversible. © 2011 International Society for Sexual Medicine.", "title": "Are phosphodiesterase type 5 inhibitors associated with vision-threatening adverse events? A critical analysis and review of the literature." }, { "docid": "MED-3512", "text": "BACKGROUND: Abdominal pain, that characterizes irritable bowel syndrome (IBS) together with bloating and disordered defecation, is mainly related to a visceral hypersensitivity due to an increase of TRPV(1) nociceptive nerve fiber activity. AIM: As capsaicin contained in red pepper is able to desensitize the TRPV(1) fibres, we evaluated whether the red pepper oral administration can decrease the symptoms of visceral hypersensitivity in IBS patients. METHODS: The study was performed on 50 patients with IBS diagnosed following Rome II criteria. After a 2-week washout period, 23 patients were planned to receive 4 pills/day, for 6 weeks randomly and in a double blind manner, each containing 150 mg of red pepper powder with a coat that dissolves in the colon, and 27 patients placebo. The patients scored each day in a diary the abdominal pain and bloating intensities following the 5-point Likert scale. The weekly symptom mean scores and the final patient subjective evaluation on treatment effectiveness were statistically compared among groups and intra-groups with appropriate tests. RESULTS: Eight patients dropped from the study: 6 in the red pepper group for abdominal pain and 2 in the placebo group. In 8 patients, the pills were reduced to 2/day, because of the abdominal pain at the onset of treatment. The intra-group comparisons showed that in patients taking red pepper the abdominal pain and bloating mean score values of the last weeks of treatment were significantly improved with respect to pre-treatment values, unlike patients taking placebo. The final patient subjective evaluation on the treatment effectiveness showed that red pepper group scored significantly better than placebo. CONCLUSIONS: The results of this preliminary study indicate that the chronic administration of red pepper powder in IBS patients with enteric-coated pills was significantly more effective than placebo in decreasing the intensity of abdominal pain and bloating and was considered by the patients more effective than placebo.", "title": "Effect of red pepper on symptoms of irritable bowel syndrome: preliminary study." }, { "docid": "MED-4251", "text": "Obesity is a global public health issue. Although the etiology of this global epidemic is multifactorial, most sufferers would be delighted to find a relatively effortless way to lose weight. Herbal \"weight loss pills\" can fit the bill. The authors systematically review the scientific evidence concerning various weight loss agents that are available over the counter or in food stores. The review provides a starting point to make informed choices among nutraceutical agents promoted for weight loss, as well as advice for incorporating healthy alternatives in the diet.", "title": "Nutraceutical supplements for weight loss: a systematic review." }, { "docid": "MED-1458", "text": "BACKGROUND/OBJECTIVES: Vegans have a lower incidence of insulin resistance (IR)-associated diseases and a higher insulin sensitivity (IS) compared with omnivores. The aim of this study was to examine whether the higher IS in vegans relates to markers of mitochondrial biogenesis and to intramyocellular lipid (IMCL) content. SUBJECTS/METHODS: Eleven vegans and 10 matched (race, age, sex, body mass index, physical activity and energy intake) omnivorous controls were enrolled in a case-control study. Anthropometry, bioimpedance (BIA), ultrasound measurement of visceral and subcutaneous fat layer, parameters of glucose and lipid homeostasis, hyperinsulinemic euglycemic clamp and muscle biopsies were performed. Citrate synthase (CS) activity, mitochondrial DNA (mtDNA) and IMCL content were assessed in skeletal muscle samples. RESULTS: Both groups were comparable in anthropometric and BIA parameters, physical activity and protein-energy intake. Vegans had significantly higher glucose disposal (M-value, vegans 8.11±1.51 vs controls 6.31±1.57 mg/kg/min, 95% confidence interval: 0.402 to 3.212, P=0.014), slightly lower IMCL content (vegans 13.91 (7.8 to 44.0) vs controls 17.36 (12.4 to 78.5) mg/g of muscle, 95% confidence interval: -7.594 to 24.550, P=0.193) and slightly higher relative muscle mtDNA amount (vegans 1.36±0.31 vs controls 1.13±0.36, 95% confidence interval:-0.078 to 0.537, P=0.135). No significant differences were found in CS activity (vegans 18.43±5.05 vs controls 18.16±5.41 μmol/g/min, 95% confidence interval: -4.503 to 5.050, P=0.906). CONCLUSIONS: Vegans have a higher IS, but comparable mitochondrial density and IMCL content with omnivores. This suggests that a decrease in whole-body glucose disposal may precede muscle lipid accumulation and mitochondrial dysfunction in IR development.", "title": "Higher insulin sensitivity in vegans is not associated with higher mitochondrial density." }, { "docid": "MED-3794", "text": "OBJECTIVE: To test the hypothesis that a low-fat, vegetarian diet reduces dysmenorrhea and premenstrual symptoms by its effect on serum sex-hormone binding globulin concentration and estrogen activity. METHODS: In a crossover design, 33 women followed a low-fat, vegetarian diet for two menstrual cycles. For two additional cycles, they followed their customary diet while taking a supplement placebo pill. Dietary intake, serum sex-hormone binding globulin concentration, body weight, pain duration and intensity, and premenstrual symptoms were assessed during each study phase. RESULTS: Mean (+/- standard deviation [SD]) serum sex-hormone binding globulin concentration was higher during the diet phase (46.7 +/- 23.6 nmol/L) than during the supplement phase (39.3 +/- 19.8 nmol/L, P < .001). Mean (+/- SD) body weight was lower during the diet (66.1 +/- 11.3 kg) compared with the supplement phase (67.9 +/- 12.1 kg, P < .001). Mean dysmenorrhea duration fell significantly from baseline (3.9 +/- 1.7 days) to diet phase (2.7 +/- 1.9 days) compared with change from baseline to supplement phase (3.6 +/- 1.7 days, P < .01). Pain intensity fell significantly during the diet phase, compared with baseline, for the worst, second-worst, and third-worst days, and mean durations of premenstrual concentration, behavioral change, and water retention symptoms were reduced significantly, compared with the supplement phase. CONCLUSION: A low-fat vegetarian diet was associated with increased serum sex-hormone binding globulin concentration and reductions in body weight, dysmenorrhea duration and intensity, and premenstrual symptom duration. The symptom effects might be mediated by dietary influences on estrogen activity.", "title": "Diet and sex-hormone binding globulin, dysmenorrhea, and premenstrual symptoms." }, { "docid": "MED-5168", "text": "OBJECTIVE: To investigate the possible role of the maternal diet, particularly vegetarianism and consumption of phytoestrogens, in the origin of hypospadias, which is reported to be increasing in prevalence. SUBJECTS AND METHODS: Detailed information was obtained prospectively from mothers, including previous obstetric history, lifestyle and dietary practices, using structured self-completed questionnaires during pregnancy. Previously recognized associations with environmental and parental factors were examined, focusing particularly on the hypothesized hormonal link. Multivariate logistic regression was used to identify independent associations. RESULTS: Of 7928 boys born to mothers taking part in the Avon Longitudinal Study of Pregnancy and Childhood, 51 hypospadias cases were identified. There were no significant differences in the proportion of hypospadias cases among mothers who smoked, consumed alcohol or for any aspect of their previous reproductive history (including the number of previous pregnancies, number of miscarriages, use of the contraceptive pill, time to conception and age at menarche). Significant differences were detected for some aspects of the maternal diet, i.e. vegetarianism and iron supplementation in the first half of pregnancy. Mothers who were vegetarian in pregnancy had an adjusted odds ratio (OR) of 4.99 (95% confidence interval, CI, 2.10-11.88) of giving birth to a boy with hypospadias, compared with omnivores who did not supplement their diet with iron. Omnivores who supplemented their diet with iron had an adjusted OR of 2.07 (95% CI, 1.00-4.32). The only other statistically significant association for hypospadias was with influenza in the first 3 months of pregnancy (adjusted OR 3.19, 95% CI 1.50-6.78). CONCLUSION: As vegetarians have a greater exposure to phytoestrogens than do omnivores, these results support the possibility that phytoestrogens have a deleterious effect on the developing male reproductive system.", "title": "A maternal vegetarian diet in pregnancy is associated with hypospadias. The ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood." }, { "docid": "MED-877", "text": "BACKGROUND: Energy drink consumption has been anecdotally linked with sudden cardiac death and, more recently, myocardial infarction. As myocardial infarction is strongly associated with both platelet and endothelial dysfunction, we tested the hypothesis that energy drink consumption alters platelet and endothelial function. METHODS: Fifty healthy volunteers (34 male, aged 22+/-2 years) participated in the study. Platelet aggregation and endothelial function were tested before, and 1 hour after, the consumption of 250 mL (1 can) of a sugar-free energy drink. Platelet function was assessed by adenosine diphosphate-induced (1 micromol/L) optical aggregometry in platelet-rich plasma. Endothelial function was assessed via changes in peripheral arterial tonometry and expressed as the reactive hyperemia index (RHI). RESULTS: Compared with baseline values, there was a significant increase in platelet aggregation following energy drink consumption, while no change was observed with control (13.7+/-3.7% vs 0.3+/-0.8% aggregation, respectively, P <.01). Similarly, RHI decreased following energy drink consumption (-0.33+/-0.13 vs 0.07+/-0.12 RHI [control], P <.05). Mean arterial pressure significantly increased following energy drink consumption, compared with control (P <.05). Heart rate was unaffected by energy drink consumption. CONCLUSION: Energy drink consumption acutely increases platelet aggregation and decreases endothelial function in healthy young adults. Copyright (c) 2010 Elsevier Inc. All rights reserved.", "title": "Detrimental effects of energy drink consumption on platelet and endothelial function." }, { "docid": "MED-5218", "text": "The effect of diet on tear function is illustrated clearly by malnutrition-induced xerophthalmia. Dietary habits in well nourished North American society have been implicated as a cause of some tear dysfunction. A review of the ocular literature suggests that sufficient dietary protein, vitamins A, B6 and C, potassium, and zinc may be necessary for normal tear function. Excesses of dietary fats, salt, cholesterol, alcohol, protein, and sucrose have been associated with or suggested as causes of tear dysfunction. No unequivocal link has been established between diet and remission of dry eye states in a well nourished population.", "title": "Influence of diet on tear function." }, { "docid": "MED-2410", "text": "Background and aims Previous research on the association between fish consumption and incident type 2 diabetes has been inconclusive. In addition, few studies have investigated how fish consumption may be related to the metabolic abnormalities underlying diabetes. Therefore, we examined the association of fish consumption with measures of insulin sensitivity and beta-cell function in a multi-ethnic population. Methods and results We examined the cross-sectional association between fish consumption and measures of insulin sensitivity and secretion in 951 non-diabetic participants in the Insulin Resistance Atherosclerosis Study (IRAS). Fish consumption, categorized as <2 vs. ≥2 portions/week, was measured using a validated food frequency questionnaire. Insulin sensitivity (SI) and acute insulin response (AIR) were determined from frequently sampled intravenous glucose tolerance tests. Higher fish consumption was independently associated with lower SI-adjusted AIR (β=−0.13 [−0.25, −0.016], p=0.03, comparing ≥ 2 vs. <2 portions/week). Fish consumption was positively associated with intact and split proinsulin/C-peptide ratios, however, these associations were confounded by ethnicity (multivariable-adjusted β=0.073 [−0.014, 0.16] for intact proinsulin/C-peptide ratio, β=0.031 [−0.065, 0.13] for split proinsulin/C-peptide ratio). We also observed a significant positive association between fish consumption and fasting blood glucose (multivariable-adjusted β=2.27 [0.68, 3.86], p=0.005). We found no association between fish consumption and SI (multivariable-adjusted β= −0.015 [−0.083, 0.053]) or fasting insulin (multivariable-adjusted β=0.016 [−0.066, 0.10]). Conclusions Fish consumption was not associated with measures of insulin sensitivity in the multi-ethnic IRAS cohort. However, higher fish consumption may be associated with pancreatic beta-cell dysfunction.", "title": "Fish consumption, insulin sensitivity and beta-cell function in the Insulin Resistance Atherosclerosis Study (IRAS)" }, { "docid": "MED-557", "text": "Dysmenorrhea is the leading cause of recurrent short-term school absence in adolescent girls and a common problem in women of reproductive age. Risk factors for dysmenorrhea include nulliparity, heavy menstrual flow, smoking, and depression. Empiric therapy can be initiated based on a typical history of painful menses and a negative physical examination. Nonsteroidal anti-inflammatory drugs are the initial therapy of choice in patients with presumptive primary dysmenorrhea. Oral contraceptives and depo-medroxyprogesterone acetate also may be considered. If pain relief is insufficient, prolonged-cycle oral contraceptives or intravaginal use of oral contraceptive pills can be considered. In women who do not desire hormonal contraception, there is some evidence of benefit with the use of topical heat; the Japanese herbal remedy toki-shakuyaku-san; thiamine, vitamin E, and fish oil supplements; a low-fat vegetarian diet; and acupressure. If dysmenorrhea remains uncontrolled with any of these approaches, pelvic ultrasonography should be performed and referral for laparoscopy should be considered to rule out secondary causes of dysmenorrhea. In patients with severe refractory primary dysmenorrhea, additional safe alternatives for women who want to conceive include transcutaneous electric nerve stimulation, acupuncture, nifedipine, and terbutaline. Otherwise, the use of danazol or leuprolide may be considered and, rarely, hysterectomy. The effectiveness of surgical interruption of the pelvic nerve pathways has not been established.", "title": "Dysmenorrhea." }, { "docid": "MED-4631", "text": "BACKGROUND: Patients with rheumatoid arthritis (RA) improve on a vegetarian diet or supplementation with fish oil. We investigated the effects of both dietary measures, alone and in combination, on inflammation, fatty acid composition of erythrocyte lipids, eicosanoids, and cytokine biosynthesis in patients with RA. METHODS: Sixty-eight patients with definitive RA were matched into two groups of 34 subjects each. One group was observed for 8 months on a normal western diet (WD) and the other on an anti-inflammatory diet (AID) providing an arachidonic acid intake of less than 90 mg/day. Patients in both groups were allocated to receive placebo or fish oil capsules (30 mg/kg body weight) for 3 months in a double-blind crossover study with a 2-month washout period between treatments. Clinical examination and routine laboratory findings were evaluated every month, and erythrocyte fatty acids, eicosanoids, and cytokines were evaluated before and after each 3-month experimental period. RESULTS: Sixty patients completed the study. In AID patients, but not in WD patients, the numbers of tender and swollen joints decreased by 14% during placebo treatment. In AID patients, as compared to WD patients, fish oil led to a significant reduction in the numbers of tender (28% vs 11%) and swollen (34% vs 22%) joints (P<0.01). Compared to baseline levels, higher enrichment of eicosapentaenoic acid in erythrocyte lipids (244% vs 217%) and lower formation of leukotriene B(4) (34% vs 8%, P>0.01), 11-dehydro-thromboxane B(2) (15% vs 10%, P<0.05), and prostaglandin metabolites (21% vs 16%, P<0.003) were found in AID patients, especially when fish oil was given during months 6-8 of the experiment. CONCLUSION: A diet low in arachidonic acid ameliorates clinical signs of inflammation in patients with RA and augments the beneficial effect of fish oil supplementation.", "title": "Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis." }, { "docid": "MED-1614", "text": "AIM: To compare the insulin sensitivity indices between Chinese vegetarians and omnivores. METHODS: The study included 36 healthy volunteers (vegetarian, n=19; omnivore, n=17) who had normal fasting plasma glucose levels. Each participant completed an insulin suppression test. We compared steady-state plasma glucose (SSPG), fasting insulin, the homeostasis model assessment for insulin sensitivity (HOMA-IR and HOMA %S) and beta-cell function (HOMA %beta) between the groups. We also tested the correlation of SSPG with years on a vegetarian diet. RESULTS: The omnivore subjects were younger than the vegetarians (55.7+/-3.7 vs 58.6+/-3.6 year of age, P=0.022). There was no difference between the two groups in sex, blood pressure, renal function tests and lipid profiles. The omnivores had higher serum uric acid levels than vegetarians (5.25+/-0.84 vs 4.54+/-0.75 mg/dl, P=0.011). The results of the indices were different between omnivores and vegetarians (SSPG (mean+/-s.d.) 105.4+/-10.2 vs 80.3+/-11.3 mg/dl, P<0.001; fasting insulin, 4.06+/-0.77 vs 3.02+/-1.19 microU/ml, P=0.004; HOMA-IR, 6.75+/-1.31 vs 4.78+/-2.07, P=0.002; HOMA %S, 159.2+/-31.7 vs 264.3+/-171.7%, P=0.018) except insulin secretion index, HOMA %beta (65.6+/-18.0 vs 58.6+/-14.8%, P=0.208). We found a clear linear relation between years on a vegetarian diet and SSPG (r=-0.541, P=0.017). CONCLUSIONS: The vegetarians were more insulin sensitive than the omnivore counterparts. The degree of insulin sensitivity appeared to be correlated with years on a vegetarian diet.", "title": "Insulin sensitivity in Chinese ovo-lactovegetarians compared with omnivores." } ]
184
Bone marrow cells don't contribute to adult macrophage compartments.
[ { "docid": "12827098", "text": "Despite accumulating evidence suggesting local self-maintenance of tissue macrophages in the steady state, the dogma remains that tissue macrophages derive from monocytes. Using parabiosis and fate-mapping approaches, we confirmed that monocytes do not show significant contribution to tissue macrophages in the steady state. Similarly, we found that after depletion of lung macrophages, the majority of repopulation occurred by stochastic cellular proliferation in situ in a macrophage colony-stimulating factor (M-Csf)- and granulocyte macrophage (GM)-CSF-dependent manner but independently of interleukin-4. We also found that after bone marrow transplantation, host macrophages retained the capacity to expand when the development of donor macrophages was compromised. Expansion of host macrophages was functional and prevented the development of alveolar proteinosis in mice transplanted with GM-Csf-receptor-deficient progenitors. Collectively, these results indicate that tissue-resident macrophages and circulating monocytes should be classified as mononuclear phagocyte lineages that are independently maintained in the steady state.", "title": "Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes." } ]
[ { "docid": "8137081", "text": "Leukocyte trafficking between the various body compartments has an important surveillance function that ensures the detection of antigen and enables the immune system to initiate a rapid and effective response. Repeated social defeat of group-housed male mice induced by daily, acute encounters with an aggressive conspecific substantially altered leukocyte trafficking and led to a gradual redistribution of immune cells in bone marrow, peripheral blood and spleen. Recurrent exposure to the stressor over a period of 2, 4 or 6 consecutive days was associated with cell mobilization and increased myelopoiesis in the bone marrow that was paralleled by an accumulation of neutrophils and monocytes in circulation and spleen. Substantial depletion of B cells in bone marrow and blood was associated with an increase in splenic B cells indicating a redirection of this cell type to the spleen. In contrast, T cells were markedly reduced in these immune compartments. The recruitment of CD11b+ leukocytes (i.e., monocytes/macrophages and neutrophils) from the bone marrow to the spleen might play a critical role in the development of functional glucocorticoid resistance in the murine spleen that was reported in context with repeated social defeat.", "title": "Effects of repeated social stress on leukocyte distribution in bone marrow, peripheral blood and spleen" }, { "docid": "17271462", "text": "The quiescent state is thought to be an indispensable property for the maintenance of hematopoietic stem cells (HSCs). Interaction of HSCs with their particular microenvironments, known as the stem cell niches, is critical for adult hematopoiesis in the bone marrow (BM). Here, we demonstrate that HSCs expressing the receptor tyrosine kinase Tie2 are quiescent and antiapoptotic, and comprise a side-population (SP) of HSCs, which adhere to osteoblasts (OBs) in the BM niche. The interaction of Tie2 with its ligand Angiopoietin-1 (Ang-1) induced cobblestone formation of HSCs in vitro and maintained in vivo long-term repopulating activity of HSCs. Furthermore, Ang-1 enhanced the ability of HSCs to become quiescent and induced adhesion to bone, resulting in protection of the HSC compartment from myelosuppressive stress. These data suggest that the Tie2/Ang-1 signaling pathway plays a critical role in the maintenance of HSCs in a quiescent state in the BM niche.", "title": "Tie2/Angiopoietin-1 Signaling Regulates Hematopoietic Stem Cell Quiescence in the Bone Marrow Niche" }, { "docid": "188911", "text": "Antigen-presenting, major histocompatibility complex (MHC) class II-rich dendritic cells are known to arise from bone marrow. However, marrow lacks mature dendritic cells, and substantial numbers of proliferating less-mature cells have yet to be identified. The methodology for inducing dendritic cell growth that was recently described for mouse blood now has been modified to MHC class II-negative precursors in marrow. A key step is to remove the majority of nonadherent, newly formed granulocytes by gentle washes during the first 2-4 d of culture. This leaves behind proliferating clusters that are loosely attached to a more firmly adherent \"stroma. \" At days 4-6 the clusters can be dislodged, isolated by 1-g sedimentation, and upon reculture, large numbers of dendritic cells are released. The latter are readily identified on the basis of their distinct cell shape, ultrastructure, and repertoire of antigens, as detected with a panel of monoclonal antibodies. The dendritic cells express high levels of MHC class II products and act as powerful accessory cells for initiating the mixed leukocyte reaction. Neither the clusters nor mature dendritic cells are generated if macrophage colony-stimulating factor rather than granulocyte/macrophage colony-stimulating factor (GM-CSF) is applied. Therefore, GM-CSF generates all three lineages of myeloid cells (granulocytes, macrophages, and dendritic cells). Since > 5 x 10(6) dendritic cells develop in 1 wk from precursors within the large hind limb bones of a single animal, marrow progenitors can act as a major source of dendritic cells. This feature should prove useful for future molecular and clinical studies of this otherwise trace cell type.", "title": "Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor" }, { "docid": "10078024", "text": "Studies of the identity and physiological function of mesenchymal stromal cells (MSCs) have been hampered by a lack of markers that permit both prospective identification and fate mapping in vivo. We found that Leptin Receptor (LepR) is a marker that highly enriches bone marrow MSCs. Approximately 0.3% of bone marrow cells were LepR(+) , 10% of which were CFU-Fs, accounting for 94% of bone marrow CFU-Fs. LepR(+) cells formed bone, cartilage, and adipocytes in culture and upon transplantation in vivo. LepR(+) cells were Scf-GFP(+), Cxcl12-DsRed(high), and Nestin-GFP(low), markers which also highly enriched CFU-Fs, but negative for Nestin-CreER and NG2-CreER, markers which were unlikely to be found in CFU-Fs. Fate-mapping showed that LepR(+) cells arose postnatally and gave rise to most bone and adipocytes formed in adult bone marrow, including bone regenerated after irradiation or fracture. LepR(+) cells were quiescent, but they proliferated after injury. Therefore, LepR(+) cells are the major source of bone and adipocytes in adult bone marrow.", "title": "Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow." }, { "docid": "24707550", "text": "Macrophages play a pivotal role in innate and acquired immune responses to Schistosoma mansoni. Classical (M1) or alternative (M2) activation states of these cells further delineate their roles in tissue damage through innate immunity or fibrotic remodeling, respectively. In the present study, we addressed the following question: Does systemic Th2-type cytokine polarization evoked by S. mansoni affect macrophage differentiation and activation? To this end, we analyzed bone marrow-derived macrophages from mice with S. mansoni egg-induced pulmonary granulomas and unchallenged (or naïve) mice to determine their activation state and their response to specific TLR agonists, including S. mansoni egg antigens. Unlike naïve macrophages, macrophages from Th2-polarized mice constitutively expressed significantly higher \"found in inflammatory zone-1\" (FIZZ1) and ST2 (M2 markers) and significantly lower NO synthase 2, CCL3, MIP-2, TNF-alpha, and IL-12 (M1 markers). Also, compared with naïve macrophages, Th2-polarized macrophages exhibited enhanced responses to the presence of specific TLR agonists, which consistently induced significantly higher levels of gene and protein levels for M2 and M1 markers in these cells. Together, these data show that signals received by bone marrow precursors during S. mansoni egg-induced granuloma responses dynamically alter the development of macrophages and enhance the TLR responsiveness of these cells, which may ultimately have a significant effect on the pulmonary granulomatous response.", "title": "A systemic granulomatous response to Schistosoma mansoni eggs alters responsiveness of bone-marrow-derived macrophages to Toll-like receptor agonists." }, { "docid": "3118719", "text": "E-cadherin is best characterized as adherens junction protein, which through homotypic interactions contributes to the maintenance of the epithelial barrier function. In epithelial cells, the cytoplasmic tail of E-cadherin forms a dynamic complex with catenins and regulates several intracellular signal transduction pathways, including Wnt/β-catenin, PI3K/Akt, Rho GTPase, and NF-κB signaling. Recent progress uncovered a novel and critical role for this adhesion molecule in mononuclear phagocyte functions. E-cadherin regulates the maturation and migration of Langerhans cells, and its ligation prevents the induction of a tolerogenic state in bone marrow-derived dendritic cells (DCs). In this respect, the functionality of β-catenin could be instrumental in determining the balance between immunogenicity and tolerogenicity of DCs in vitro and in vivo. Fusion of alternatively activated macrophages and osteoclasts is also E-cadherin-dependent. In addition, the E-cadherin ligands CD103 and KLRG1 are expressed on DC-, T-, and NK-cell subsets and contribute to their interaction with E-cadherin-expressing DCs and macrophages. Here we discuss the regulation, function, and implications of E-cadherin expression in these central orchestrators of the immune system.", "title": "Regulation and function of the E-cadherin/catenin complex in cells of the monocyte-macrophage lineage and DCs." }, { "docid": "46193388", "text": "Bone marrow stem cells give rise to a variety of hematopoietic lineages and repopulate the blood throughout adult life. We show that, in a strain of mice incapable of developing cells of the myeloid and lymphoid lineages, transplanted adult bone marrow cells migrated into the brain and differentiated into cells that expressed neuron-specific antigens. These findings raise the possibility that bone marrow-derived cells may provide an alternative source of neurons in patients with neurodegenerative diseases or central nervous system injury.", "title": "Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow." }, { "docid": "1122198", "text": "Macrophage-derived foam cells express apolipoprotein E (apoE) abundantly in atherosclerotic lesions. To examine the physiologic role of apoE secretion by the macrophage in atherogenesis, bone marrow transplantation was used to reconstitute C57BL/6 mice with macrophages that were either null or wild type for the apoE gene. After 13 weeks on an atherogenic diet, C57BL/6 mice reconstituted with apoE null marrow developed 10-fold more atherosclerosis than controls in the absence of significant differences in serum cholesterol levels or lipoprotein profiles. ApoE expression was absent in the macrophage-derived foam cells of C57BL/6 mice reconstituted with apoE null marrow. Thus, lack of apoE expression by the macrophage promotes foam cell formation. These data support a protective role for apoE expression by the macrophage in early atherogenesis.", "title": "Increased atherosclerosis in mice reconstituted with apolipoprotein E null macrophages." }, { "docid": "44562221", "text": "Endogenous glucocorticoids (GC) play an important role in the termination of the inflammatory response following infection and tissue injury. However, recent findings indicate that stress can impair the anti-inflammatory capacities of these hormones. Lipopolysaccharide (LPS)-stimulated splenocytes of mice that were repeatedly subjected to social disruption (SDR) stress were less sensitive to the immunosuppressive effects of corticosterone (CORT) as demonstrated by an increased production of pro-inflammatory cytokines and enhanced cell survival. Myeloid cells expressing the marker CD11b were shown to play a key role in this process. Here we investigated the role of the bone marrow as a potential source of the GC-insensitive cells. The study revealed that LPS-stimulated bone marrow cells, in the absence of experimental stress, were virtually GC-resistant and retained high levels of cell viability after treatment with CORT. Recurrent exposure to the acute stressor over a period of 2, 4 or 6 days led to an increase in the GC sensitivity of the bone marrow cells. This increase in GC sensitivity was associated with enhanced mRNA expression of granulocyte-macrophage colony-stimulating factor (GM-CSF), an increase in the number of myeloid progenitors, and a decrease in the proportion of mature CD11b+ cells. The changes in the cellular composition of the bone marrow were accompanied by an increase in splenic CD11b+ cell numbers. Simultaneous assessment of the GC sensitivity in bone marrow and spleen revealed a significant negative correlation between both tissues suggesting that social stress causes the redistribution of GC-insensitive myeloid cells from the bone marrow to the spleen.", "title": "Tissue-specific alterations in the glucocorticoid sensitivity of immune cells following repeated social defeat in mice" }, { "docid": "6270720", "text": "RATIONALE The myeloid differentiation factor (MyD)88/interleukin (IL)-1 axis activates self-antigen-presenting cells and promotes autoreactive CD4(+) T-cell expansion in experimental autoimmune myocarditis, a mouse model of inflammatory heart disease. OBJECTIVE The aim of this study was to determine the role of MyD88 and IL-1 in the progression of acute myocarditis to an end-stage heart failure. METHODS AND RESULTS Using alpha-myosin heavy chain peptide (MyHC-alpha)-loaded, activated dendritic cells, we induced myocarditis in wild-type and MyD88(-/-) mice with similar distributions of heart-infiltrating cell subsets and comparable CD4(+) T-cell responses. Injection of complete Freund's adjuvant (CFA) or MyHC-alpha/CFA into diseased mice promoted cardiac fibrosis, induced ventricular dilation, and impaired heart function in wild-type but not in MyD88(-/-) mice. Experiments with chimeric mice confirmed the bone marrow origin of the fibroblasts replacing inflammatory infiltrates and showed that MyD88 and IL-1 receptor type I signaling on bone marrow-derived cells was critical for development of cardiac fibrosis during progression to heart failure. CONCLUSIONS Our findings indicate a critical role of MyD88/IL-1 signaling in the bone marrow compartment in postinflammatory cardiac fibrosis and heart failure and point to novel therapeutic strategies against inflammatory cardiomyopathy.", "title": "Myeloid differentiation factor-88/interleukin-1 signaling controls cardiac fibrosis and heart failure progression in inflammatory dilated cardiomyopathy." }, { "docid": "9412420", "text": "Mesenchymal stem cells (MSCs) commonly defined by in vitro functions have entered clinical application despite little definition of their function in residence. Here, we report genetic pulse-chase experiments that define osteoblastic cells as short-lived and nonreplicative, requiring replenishment from bone-marrow-derived, Mx1(+) stromal cells with \"MSC\" features. These cells respond to tissue stress and migrate to sites of injury, supplying new osteoblasts during fracture healing. Single cell transplantation yielded progeny that both preserve progenitor function and differentiate into osteoblasts, producing new bone. They are capable of local and systemic translocation and serial transplantation. While these cells meet current definitions of MSCs in vitro, they are osteolineage restricted in vivo in growing and adult animals. Therefore, bone-marrow-derived MSCs may be a heterogeneous population with the Mx1(+) population, representing a highly dynamic and stress responsive stem/progenitor cell population of fate-restricted potential that feeds the high cell replacement demands of the adult skeleton.", "title": "Endogenous bone marrow MSCs are dynamic, fate-restricted participants in bone maintenance and regeneration." }, { "docid": "20186814", "text": "Muscle satellite cells have long been considered a distinct myogenic lineage responsible for postnatal growth, repair, and maintenance of skeletal muscle. Recent studies in mice, however, have revealed the potential for highly purified hematopoietic stem cells from bone marrow to participate in muscle regeneration. Perhaps more significantly, a population of putative stem cells isolated directly from skeletal muscle efficiently reconstitutes the hematopoietic compartment and participates in muscle regeneration following intravenous injection in mice. The plasticity of muscle stem cells has raised important questions regarding the relationship between the muscle-derived stem cells and the skeletal muscle satellite cells. Furthermore, the ability of hematopoietic cells to undergo myogenesis has prompted new investigations into the embryonic origin of satellite cells. Recent developmental studies suggest that a population of satellite cells is derived from progenitors in the embryonic vasculature. Taken together, these studies provide the first evidence that pluripotential stem cells are present within adult skeletal muscle. Tissue-specific stem cells, including satellite cells, may share a common embryonic origin and possess the capacity to activate diverse genetic programs in response to environmental stimuli. Manipulation of such tissue-specific stem cells may eventually revolutionize therapies for degenerative diseases, including muscular dystrophy.", "title": "A new look at the origin, function, and \"stem-cell\" status of muscle satellite cells." }, { "docid": "35811036", "text": "Embryonic-like stem cell (ELSC), expressing part of surface markers of human embryonic stem cells, may be a better candidate for cell therapy of degenerative muscular disease than mesenchymal stem cell (MSC). We isolated ELSC and MSC from bone marrow, respectively, and compared their differences in the characteristics and the capacity of myogenic differentiation. Results showed that ELSC could be isolated successfully from 3 adult bone marrow samples by using serum-free medium with 10ng/ml basic fibroblast growth factor (bFGF). At the same cell density, MSC could also be isolated from the same samples by using DMEM/F12 medium containing 10% new cattle serum. However, ELSC appeared as small, morphologically slenderer, upregulated expression of SSEA-4 and ultramicroscopically more immature than MSC derived from the same samples. Immunofluorescent staining and RT-PCR analysis showed ELSC weakly expressed Oct-4, Nanog-3 and Sox-2. Moreover, ELSC and MSC could be induced into long, multinucleated fibers expressing myogenin and myosin heavy chain (MHC) in myogenic differentiation medium, but by day 10, proportion of multinucleated fibers positive for MHC was respectively 25.0%+/-6.9% and 13.8%+/-7.6% in ELSC and MSC culture. These data suggest that bone marrow derived ELSC represent an ideal candidate for cell therapy of degenerative muscular disease.", "title": "Embryonic-like stem cell derived from adult bone marrow: immature morphology, cell surface markers, ultramicrostructure and differentiation into multinucleated fibers in vitro." }, { "docid": "43619625", "text": "Activated T cells secrete multiple osteoclastogenic cytokines which play a major role in the bone destruction associated with rheumatoid arthritis. While the role of T cells in osteoclastogenesis has received much attention recently, the effect of T cells on osteoblast formation and activity is poorly defined. In this study, we investigated the hypothesis that in chronic inflammation activated T cells contribute to enhanced bone turnover by promoting osteoblastic differentiation. We show that T cells produce soluble factors that induce alkaline phosphatase activity in bone marrow stromal cells and elevated expression of mRNA for Runx2 and osteocalcin. This data indicate that T cell derived factors have the capacity to stimulate the differentiation of bone marrow stromal cells into the osteoblast phenotype. RANKL mRNA was undetectable under any conditions in highly purified bone marrow stromal cells. In contrast, RANKL was constitutively expressed in primary osteoblasts and only moderately up-regulated by activated T cell conditioned medium. Interestingly, both bone marrow stromal cells and osteoblasts expressed mRNA for RANK, which was strongly up-regulated in both cell types by activated T cell conditioned medium. Although, mRNA for the RANKL decoy receptor, osteoprotegerin, was also up-regulated by activated T cell conditioned medium, it's inhibitory effects may be mitigated by a simultaneous rise in the osteoprotegerin competitor TNF-related apoptosis-inducing ligand. Based on our data we propose that during chronic inflammation, T cells regulate bone loss by a dual mechanism involving both direct stimulation of osteoclastogenesis, by production of osteoclastogenic cytokines, and indirectly by induction of osteoblast differentiation and up-regulation of bone turnover via coupling.", "title": "Inflammatory T cells rapidly induce differentiation of human bone marrow stromal cells into mature osteoblasts." }, { "docid": "2853291", "text": "Mesenchymal stem cells (MSCs) and osteolineage cells contribute to the hematopoietic stem cell (HSC) niche in the bone marrow of long bones. However, their developmental relationships remain unclear. In this study, we demonstrate that different MSC populations in the developing marrow of long bones have distinct functions. Proliferative mesoderm-derived nestin(-) MSCs participate in fetal skeletogenesis and lose MSC activity soon after birth. In contrast, quiescent neural crest-derived nestin(+) cells preserve MSC activity, but do not generate fetal chondrocytes. Instead, they differentiate into HSC niche-forming MSCs, helping to establish the HSC niche by secreting Cxcl12. Perineural migration of these cells to the bone marrow requires the ErbB3 receptor. The neonatal Nestin-GFP(+) Pdgfrα(-) cell population also contains Schwann cell precursors, but does not comprise mature Schwann cells. Thus, in the developing bone marrow HSC niche-forming MSCs share a common origin with sympathetic peripheral neurons and glial cells, and ontogenically distinct MSCs have non-overlapping functions in endochondrogenesis and HSC niche formation.", "title": "The neural crest is a source of mesenchymal stem cells with specialized hematopoietic stem cell niche function" }, { "docid": "42465769", "text": "Adipocytes are part of hematopoietic microenvironment, even though up to now in humans, their role in hematopoiesis is still questioned. We have previously shown that accumulation of fat cells in femoral bone marrow (BM) coincides with increased expression of neuropilin-1 (NP-1), while it is weakly expressed in hematopoietic iliac crest BM. Starting from this observation, we postulated that adipocytes might exert a negative effect on hematopoiesis mediated through NP-1. To test this hypothesis, we set up BM adipocytes differentiated into fibroblast-like fat cells (FLFC), which share the major characteristics of primitive unilocular fat cells, as an experimental model. As expected, FLFCs constitutively produced macrophage colony stimulating factor and induced CD34(+) differentiation into macrophages independently of cell-to-cell contact. By contrast, granulopoiesis was hampered by cell-to-cell contact but could be restored in transwell culture conditions, together with granulocyte colony stimulating factor production. Both functions were also recovered when FLFCs cultured in contact with CD34(+) cells were treated with an antibody neutralizing NP-1, which proved its critical implication in contact inhibition. An inflammatory cytokine such as interleukin-1 beta or dexamethasone modulates FLFC properties to restore granulopoiesis. Our data provide the first evidence that primary adipocytes exert regulatory functions during hematopoiesis that might be implicated in some pathological processes. Disclosure of potential conflicts of interest is found at the end of this article.", "title": "Human bone marrow adipocytes block granulopoiesis through neuropilin-1-induced granulocyte colony-stimulating factor inhibition." }, { "docid": "25068298", "text": "Distribution and fine structure of macrophages were studied in 10 human embryos in the 6th and 7th week of gestation, 5.5 to 12 mm in crown-rump length. The yolk sac macrophages were found in the extravascular mesenchymal tissues and intravascular spaces long before the first appearance of bone marrow and lymphatic tissues in the embryos. In addition to the macrophages, the fibroblastic cells and the cells of erythropoietic series were also present in the extravascular space. The macrophages showed a variety of cellular structures suggesting transition from immature cell type with no heterophagolysosomes to mature cell type in phagocytosis. The mature macrophages avidly phagocytized the primitive erythroblasts and occasionally platelets. They were positively stained for lysosomal enzymes and were characterized by numerous pleomorphic heterophagolysosomes which exhibited various stages of digestion of phagocytized blood cells. The origin of intravascular macrophages may be in either migrated extravascular macrophages or phagocytic endothelial cells. The phagocytosis and degradation of erythroblasts appear to be one of the main functions of yolk sac macrophages. The presence of the macrophages in mitosis indicates their proliferation in situ.", "title": "Electron microscopic studies of macrophages in early human yolk sacs." }, { "docid": "24466904", "text": "We used bone marrow biopsies instead of mononuclear cells to maintain long-term cultures from 103 patients belonging to all five sub-categories of myelodysplastic syndromes (MDS), as well as 12 normal controls. By week 4, 30-50% confluency was reached and could be maintained for up to 12 weeks with 100% confluency. The four prominent cells were fibroblasts, macrophages, endothelial cells and adipocytes. Immunohistochemical and electron microscopic studies provided lineage confirmation. Normal hematopoiesis was well supported by MDS stroma. Neither the FAB nor cytogenetics was co-related with the potency of growth. MDS stroma appears to be both morphologically and functionally normal.", "title": "Successful establishment of long-term bone marrow cultures in 103 patients with myelodysplastic syndromes." }, { "docid": "3495456", "text": "Summary Neutrophils are specialized innate cells that require constant replenishment from proliferative bone marrow (BM) precursors as a result of their short half‐life. Although it is established that neutrophils are derived from the granulocyte‐macrophage progenitor (GMP), the differentiation pathways from GMP to functional mature neutrophils are poorly defined. Using mass cytometry (CyTOF) and cell‐cycle‐based analysis, we identified three neutrophil subsets within the BM: a committed proliferative neutrophil precursor (preNeu) which differentiates into non‐proliferating immature neutrophils and mature neutrophils. Transcriptomic profiling and functional analysis revealed that preNeu require the C/EBP&egr; transcription factor for their generation from the GMP, and their proliferative program is substituted by a gain of migratory and effector function as they mature. preNeus expand under microbial and tumoral stress, and immature neutrophils are recruited to the periphery of tumor‐bearing mice. In summary, our study identifies specialized BM granulocytic populations that ensure supply under homeostasis and stress responses. Graphical Abstract Figure. No Caption available. HighlightsProliferation activity identifies committed neutrophil precursor in mice and humansNeutrophil subsets possess distinct transcriptomic and functional signaturesDefect in neutrophil development leads to impaired neutrophil‐mediated responsesIncreased circulating immature neutrophils are associated with cancer progression &NA; The neutrophil differentiation pathway is poorly defined. Evrard et. al. demonstrate a workflow of characterizing bone marrow neutrophil subsets on the basis of their proliferative capacity and molecular signatures and thereby define the developmental trajectory and functional properties of neutrophils.", "title": "Developmental Analysis of Bone Marrow Neutrophils Reveals Populations Specialized in Expansion, Trafficking, and Effector Functions" }, { "docid": "26501027", "text": "Nestin-positive (Nes(+)) cells are important hematopoiesis-supporting constituents in adult bone marrow. However, how these cells originate during endochondral bone development is unknown. Studies using mice expressing GFP under the direction of nestin promoter/enhancer (Nes-GFP) revealed distinct endothelial and nonendothelial Nes(+) cells in the embryonic perichondrium; the latter were early cells of the osteoblast lineage immediately descended from their progenitors upon Indian hedgehog action and Runx2 expression. During vascular invasion and formation of ossification centers, these Nes(+) cells were closely associated with each other and increased in number progressively. Interestingly, cells targeted by tamoxifen-inducible cre recombinase driven by nestin enhancer (Nes-creER) in developing bone marrow were predominantly endothelial cells. Furthermore, Nes(+) cells in postnatal bones were heterogeneous populations, including a range of cells in the osteoblast and endothelial lineage. These findings reveal an emerging complexity of stromal populations, accommodating Nes(+) cells as vasculature-associated early cells in the osteoblast and endothelial lineage.", "title": "Vasculature-associated cells expressing nestin in developing bones encompass early cells in the osteoblast and endothelial lineage." }, { "docid": "7521113", "text": "Mononuclear phagocytes, including monocytes, macrophages, and dendritic cells, contribute to tissue integrity as well as to innate and adaptive immune defense. Emerging evidence for labor division indicates that manipulation of these cells could bear therapeutic potential. However, specific ontogenies of individual populations and the overall functional organization of this cellular network are not well defined. Here we report a fate-mapping study of the murine monocyte and macrophage compartment taking advantage of constitutive and conditional CX(3)CR1 promoter-driven Cre recombinase expression. We have demonstrated that major tissue-resident macrophage populations, including liver Kupffer cells and lung alveolar, splenic, and peritoneal macrophages, are established prior to birth and maintain themselves subsequently during adulthood independent of replenishment by blood monocytes. Furthermore, we have established that short-lived Ly6C(+) monocytes constitute obligatory steady-state precursors of blood-resident Ly6C(-) cells and that the abundance of Ly6C(+) blood monocytes dynamically controls the circulation lifespan of their progeny.", "title": "Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis." }, { "docid": "24356383", "text": "Osteopetrotic (op/op) mice fail to exhibit bone remodeling because of a defective osteoclast formation due to a lack of macrophage colony-stimulating factor. In this study, we investigated the femora of op/op mice to clarify whether the osteoblastic population and bone mineralization are involved in osteoclasts or their bone resorption. The op/op mice extended the meshwork of trabecular bones from the chondro-osseous junction to the diaphyseal region. In the femoral metaphyses of op/op mice, intense alkaline phosphatase (ALPase)-positive osteoblasts were observed on the metaphyseal bone in close proximity to the erosion zone of the growth plates. Von Kossa's staining revealed scattered mineralized nodules and a fine meshwork of mineralized bone matrices while the wild-type littermates developed well-mineralized trabeculae parallel to the longitudinal axis. In contrast to the metaphysis, some op/op diaphyses showed flattened osteoblasts with weak ALPase-positivity, and the other diaphyses displayed bone surfaces without a covering by osteoblasts. It is likely, therefore, that the osteoblastic population and activity were lessened in the op/op diaphyses. Despite the osteopetrotic model, von Kossa's staining demonstrated patchy unmineralized areas in the op/op diaphyses, indicating that a lower population and/or the activity of osteoblasts resulted in defective mineralization in the bone. Transmission electron microscopy disclosed few osteoblasts on the diaphyseal bones, and instead, bone marrow cells and vascular endothelial cells were often attached to the unmineralized bone. Osteocytes were embedded in the unmineralized bone matrix. Thus, osteoclasts appear to be involved in the osteoblastic population and activity as well as subsequent bone mineralization.", "title": "Reduced osteoblastic population and defective mineralization in osteopetrotic (op/op) mice." }, { "docid": "5836", "text": "Myelodysplastic syndromes (MDS) are age-dependent stem cell malignancies that share biological features of activated adaptive immune response and ineffective hematopoiesis. Here we report that myeloid-derived suppressor cells (MDSC), which are classically linked to immunosuppression, inflammation, and cancer, were markedly expanded in the bone marrow of MDS patients and played a pathogenetic role in the development of ineffective hematopoiesis. These clonally distinct MDSC overproduce hematopoietic suppressive cytokines and function as potent apoptotic effectors targeting autologous hematopoietic progenitors. Using multiple transfected cell models, we found that MDSC expansion is driven by the interaction of the proinflammatory molecule S100A9 with CD33. These 2 proteins formed a functional ligand/receptor pair that recruited components to CD33’s immunoreceptor tyrosine-based inhibition motif (ITIM), inducing secretion of the suppressive cytokines IL-10 and TGF-β by immature myeloid cells. S100A9 transgenic mice displayed bone marrow accumulation of MDSC accompanied by development of progressive multilineage cytopenias and cytological dysplasia. Importantly, early forced maturation of MDSC by either all-trans-retinoic acid treatment or active immunoreceptor tyrosine-based activation motif–bearing (ITAM-bearing) adapter protein (DAP12) interruption of CD33 signaling rescued the hematologic phenotype. These findings indicate that primary bone marrow expansion of MDSC driven by the S100A9/CD33 pathway perturbs hematopoiesis and contributes to the development of MDS.", "title": "Induction of myelodysplasia by myeloid-derived suppressor cells." }, { "docid": "1617327", "text": "Mesenchymal cells contribute to the 'stroma' of most normal and malignant tissues, with specific mesenchymal cells participating in the regulatory niches of stem cells. By examining how mesenchymal osteolineage cells modulate haematopoiesis, here we show that deletion of Dicer1 specifically in mouse osteoprogenitors, but not in mature osteoblasts, disrupts the integrity of haematopoiesis. Myelodysplasia resulted and acute myelogenous leukaemia emerged that had acquired several genetic abnormalities while having intact Dicer1. Examining gene expression altered in osteoprogenitors as a result of Dicer1 deletion showed reduced expression of Sbds, the gene mutated in Schwachman-Bodian-Diamond syndrome-a human bone marrow failure and leukaemia pre-disposition condition. Deletion of Sbds in mouse osteoprogenitors induced bone marrow dysfunction with myelodysplasia. Therefore, perturbation of specific mesenchymal subsets of stromal cells can disorder differentiation, proliferation and apoptosis of heterologous cells, and disrupt tissue homeostasis. Furthermore, primary stromal dysfunction can result in secondary neoplastic disease, supporting the concept of niche-induced oncogenesis.", "title": "Bone progenitor dysfunction induces myelodysplasia and secondary leukemia" }, { "docid": "54561384", "text": "Hematopoietic stem cells (HSCs) sustain blood formation throughout life and are the functional units of bone marrow transplantation. We show that transient expression of six transcription factors Run1t1, Hlf, Lmo2, Prdm5, Pbx1, and Zfp37 imparts multilineage transplantation potential onto otherwise committed lymphoid and myeloid progenitors and myeloid effector cells. Inclusion of Mycn and Meis1 and use of polycistronic viruses increase reprogramming efficacy. The reprogrammed cells, designated induced-HSCs (iHSCs), possess clonal multilineage differentiation potential, reconstitute stem/progenitor compartments, and are serially transplantable. Single-cell analysis revealed that iHSCs derived under optimal conditions exhibit a gene expression profile that is highly similar to endogenous HSCs. These findings demonstrate that expression of a set of defined factors is sufficient to activate the gene networks governing HSC functional identity in committed blood cells. Our results raise the prospect that blood cell reprogramming may be a strategy for derivation of transplantable stem cells for clinical application.", "title": "Reprogramming committed murine blood cells to induced hematopoietic stem cells with defined factors." }, { "docid": "16660256", "text": "Satellite cells are skeletal muscle stem cells capable of self-renewal and differentiation after transplantation, but whether they contribute to endogenous muscle fiber repair has been unclear. The transcription factor Pax7 marks satellite cells and is critical for establishing the adult satellite cell pool. By using a lineage tracing approach, we show that after injury, quiescent adult Pax7(+) cells enter the cell cycle; a subpopulation returns to quiescence to replenish the satellite cell compartment, while others contribute to muscle fiber formation. We demonstrate that Sprouty1 (Spry1), a receptor tyrosine kinase signaling inhibitor, is expressed in quiescent Pax7(+) satellite cells in uninjured muscle, downregulated in proliferating myogenic cells after injury, and reinduced as Pax7(+) cells re-enter quiescence. We show that Spry1 is required for the return to quiescence and homeostasis of the satellite cell pool during repair. Our results therefore define a role for Spry1 in adult muscle stem cell biology and tissue repair.", "title": "Sprouty1 Regulates Reversible Quiescence of a Self-Renewing Adult Muscle Stem Cell Pool during Regeneration" }, { "docid": "16361581", "text": "Notch receptors expressed on hematopoietic stem cells interact with their ligands on bone marrow stromal cells and thereby control cell fate decisions and survival. We recently demonstrated that Notch signaling is involved in proliferation and survival of B cell-derived tumor cells of classic Hodgkin disease and described a novel mechanism for the oncogenic capacity of Notch. In this study we investigated whether Notch signaling is involved in the tight interactions between neoplastic plasma cells and their bone marrow microenvironment, which are essential for tumor cell growth in multiple myeloma (MM). Here we demonstrate that Notch receptors and their ligand Jagged1 are highly expressed in cultured and primary MM cells, whereas nonneoplastic counterparts show low to undetectable levels of Notch. Functional data indicate that ligand-induced Notch signaling is a growth factor for MM cells and suggest that these interactions contribute to myelomagenesis in vivo.", "title": "Jagged1-induced Notch signaling drives proliferation of multiple myeloma cells." }, { "docid": "39851630", "text": "Defective hematopoiesis supporting capacity of bone marrow (BM) stroma has been implicated in the pathophysiology of myelodysplastic syndromes (MDS). The aim of this study is to explore whether the BM stroma progenitors, namely the mesenchymal stem cells (MSCs), are primarily affected in MDS by evaluating the reserves, the functional properties, as well as the cytogenetic characteristics, in comparison to BM hematopoietic cells, in patients with de novo MDS (n = 13). The number, differentiation potential toward adipocytes/chondrocytes/osteoblasts and immunosuppressive function in terms of inhibition of mitogen-induced T-cell proliferation did not differ significantly between patient and normal (n = 20) MSCs. Patient MSCs did not show any aberrations in the production of proinflammatory or growth-promoting cytokines and did not harbor the cytogenetic abnormalities present in hematopoietic cells. Occasional patient and normal MSC cultures, however, developed irrelevant chromosomal alterations (trisomies 5 and 7) with uncertain pathophysiologic significance. Compared to controls, patient MSCs displayed impaired proliferative and clonogenic potential through passages that might represent a nonspecific abnormality associated with the chronic inflammatory process present in patients' BM. These data suggest that BM MSCs from MDS patients do not belong to the abnormal clone and do not represent the main cellular source contributing to the inflammatory marrow microenvironment.", "title": "Reserves, functional, immunoregulatory, and cytogenetic properties of bone marrow mesenchymal stem cells in patients with myelodysplastic syndromes." }, { "docid": "27555165", "text": "Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that causes life-threatening disease in patients who are immunosuppressed for bone marrow or tissue transplantation or who have AIDS (ref. 1). HCMV establishes lifelong latent infections and, after periodic reactivation from latency, uses a panel of immune evasion proteins to survive and replicate in the face of robust, fully primed host immunity. Monocyte/macrophages are important host cells for HCMV, serving as a latent reservoir and as a means of dissemination throughout the body. Macrophages and other HCMV-permissive cells, such as endothelial and glial cells, can express MHC class II proteins and present antigens to CD4+ T lymphocytes. Here, we show that the HCMV protein US2 causes degradation of two essential proteins in the MHC class II antigen presentation pathway: HLA-DR-α and DM-α. This was unexpected, as US2 has been shown to cause degradation of MHC class I (refs. 5,6), which has only limited homology with class II proteins. Expression of US2 in cells reduced or abolished their ability to present antigen to CD4+ T lymphocytes. Thus, US2 may allow HCMV-infected macrophages to remain relatively 'invisible' to CD4+ T cells, a property that would be important after virus reactivation.", "title": "Cytomegalovirus US2 destroys two components of the MHC class II pathway, preventing recognition by CD4+ T cells" }, { "docid": "23032247", "text": "The use of retrogenic mice offers a rapid and flexible approach to T cell receptor (TCR)-transgenic mice. By transducing bone marrow progenitor cells with a retrovirus that encodes a given TCR-α/β subunit, TCR-retrogenic mice can be generated in as few as 4–6 weeks, whereas conventional TCR transgenics can take 6 months or longer. In this updated protocol, we have increased the efficiency of the bone marrow transduction and bone marrow reconstitution compared with our previously published protocol. The main departure from the previous protocol is the implementation of spin transduction with the viral supernatant instead of coculture with the viral producer cell line. The changes in this protocol improve bone marrow viability, increase consistency of the bone marrow transduction and bone marrow engraftment, and they reduce the ratio of bone marrow donor mice to bone marrow recipients.", "title": "Generation of T cell receptor–retrogenic mice: improved retroviral-mediated stem cell gene transfer" } ]
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The Last House on the Left was a film produced by Wes Craven's production studio.
[ { "docid": "The_Last_House_on_the_Left_(2009_film)", "text": "The Last House on the Left is a 2009 American horror film directed by Dennis Iliadis and written by Carl Ellsworth and Adam Alleca . It is a remake of the 1972 film of the same name , and stars Tony Goldwyn , Monica Potter , Garret Dillahunt , Spencer Treat Clark , Martha MacIsaac and Sara Paxton . The film follows the parents ( Goldwyn and Potter ) of Mari Collingwood ( Paxton ) , who attempt to get revenge on a group of strangers , led by a man named Krug ( Dillahunt ) , that have taken shelter at their home during a thunderstorm . The film rights were picked up by Rogue Pictures in 2006 , with the remake being the first film produced by Wes Craven 's new production studio Midnight Pictures . Craven , who wrote and directed the 1972 original , was interested to see what kind of film could be produced on a large budget , as the limited funds in 1972 forced him to eliminate scenes he had wanted to film to tell a complete story . Alleca 's original script included elements of the supernatural , which prompted the studio to reject it and bring in Ellsworth to perform a rewrite . One of the elements director Iliadis wanted to avoid with this film , given its graphic nature , was turning it into torture porn -- a subgenre of horror popularized by the Saw franchise . For Craven and Iliadis , The Last House on the Left primarily illustrates how even the most normal of families can be driven to evil acts if pushed too far . The film was released on March 13 , 2009 , and took the top spot away from Watchmen with $ 5.6 million in weekend revenue . The Last House on the Left was met with mixed reviews from critics . Audience opinion ranked the film at a `` B '' level , from a scale of `` A to F '' ; the film would ultimately gross $ 45,286,228 worldwide .", "title": "" } ]
[ { "docid": "Wes_Craven's_Last_House_on_the_Left", "text": "Wes Craven 's Last House on the Left is a non-fiction book written by David A. Szulkin that covers the making of the controversial 1972 horror film The Last House on the Left .", "title": "" }, { "docid": "The_Last_House_on_the_Left_(1972_film)", "text": "The Last House on the Left is a 1972 American exploitation horror film written , edited , and directed by Wes Craven and produced by Sean S. Cunningham . The film follows two teenage girls who are taken into the woods and tortured by a gang of murderous thugs . The story is inspired by the 1960 Swedish film The Virgin Spring , directed by Ingmar Bergman , which in turn is based on a Swedish ballad - `` Töres döttrar i Wänge '' . Craven 's directorial debut , the film was made on a modest budget of $ 87,000 , and was filmed in New York City and rural Connecticut in 1971 . It was released theatrically in the United States on August 30 , 1972 , and was a major box office success , grossing over $ 3 million domestically . Although its confrontational violence resulted in its being heavily censored and sometimes banned in other countries , the film was generally well received by critics . The film was remade as The Last House on the Left in 2009 .", "title": "" }, { "docid": "Wes_Craven", "text": "Wesley Earl Craven ( August 2 , 1939 -- August 30 , 2015 ) was an American film director , writer , producer and actor . He was known for his pioneering work in the genre of horror films , particularly slasher films , where his impact on the genre was considered prolific and influential . Due to the success and cultural impact of his works in the horror film genre Craven has been called the `` Master of Horror '' . He is best known for creating the A Nightmare on Elm Street franchise featuring the Freddy Krueger character , directing the first installment and Wes Craven 's New Nightmare , and co-writing A Nightmare on Elm Street 3 : Dream Warriors with Bruce Wagner . Craven also directed all four films in the Scream series and two films in the Hills Have Eyes series . Some of his other films include The Last House on the Left , The Serpent and the Rainbow , The People Under the Stairs , Vampire in Brooklyn and Red Eye . On August 30 , 2015 , Craven died of brain cancer , at the age of 76 at his home in Los Angeles .", "title": "" }, { "docid": "Together_(1971_film)", "text": "Together is a 1971 film directed by Sean S. Cunningham . Cunningham 's first film attracted Wes Craven who wanted to be in the film business . This was Craven 's first credit . Cunningham and Craven would later work on The Last House on the Left . The film features a young Marilyn Chambers , billed under her real name , Marilyn Briggs , before she starred in Behind the Green Door .", "title": "" }, { "docid": "Jeramie_Rain", "text": "Jeramie Rain ( born August 23 , 1948 ) is an American actress , screenwriter , and producer . She made her film debut in the crime film The Abductors ( 1972 ) . She is best known for her roles as Sadie in Wes Craven 's horror film The Last House on the Left ( 1972 ) and Nurse Samantha Tolliver in the soap opera The Doctors ( 1972-73 ) . Outside of acting , Rain worked as a writer and producer for NBC and CBS .", "title": "" }, { "docid": "The_Last_House_on_the_Beach", "text": "The Last House on the Beach ( Italian : La settima donna , also known as Terror and The Seventh Woman ) is a 1978 Italian rape and revenge-thriller film directed by Franco Prosperi . The American title refers to Wes Craven 's The Last House on the Left , and Alexandra Heller-Nicholas stated how `` combining the nunsploitation subgenre with rape-revenge , the film deviates plot-wise from The Last House on the Left substantially , but arrives at a similar ethical conclusion '' . It was argued that the final scene of the movie inspired the final scene in Quentin Tarantino 's Death Proof .", "title": "" }, { "docid": "Jonathan_Craven", "text": "Jonathan Craven ( born March 20 , 1965 ) , son of late filmmaker of horror Wes Craven and Bonnie Broecker , is an American writer and director . He co-wrote the horror sequel The Hills Have Eyes 2 and worked on the short-lived NBC horror series Nightmare Cafe . He manages the group the Chapin Sisters . He also co-produced the 2009 remake of The Last House on the Left .", "title": "" }, { "docid": "Craven-Maddalena_Films", "text": "Craven-Maddalena Films is a Hollywood movie studio , founded in 1996 by Wes Craven and Marianne Maddalena . It was best known for producing horror films , many of which are Craven 's films and his remakes .", "title": "" }, { "docid": "Last_Stop_on_the_Night_Train", "text": "Last Stop on the Night Train ( L'ultimo treno della notte , released in the English-speaking countries as Night Train Murders , The New House on The Left , Second House on The Left , Do n't Ride on Late Night Trains , Late Night Trains , Last House Part II and Xmas Massacre ) is a 1975 Italian revenge horror film directed Aldo Lado and starring Flavio Bucci , Macha Meril and Irene Miracle . Based on the plots of Ingmar Bergman 's The Virgin Spring ( 1960 ) and Wes Craven 's The Last House on the Left ( 1972 ) , the film follows two girls riding a train through Germany on Christmas Eve , who are brutalized by three criminals who eventually end up lodging in their parents ' home . It gained notoriety when it was banned in the UK as a video nasty in the 1980s .", "title": "" }, { "docid": "Last_House_on_Dead_End_Street", "text": "Last House on Dead End Street ( also known as The Fun House , At the Hour of Our Death , and The Cuckoo Clocks of Hell ) is a 1977 American surrealist exploitation horror film written , produced , and directed by Roger Watkins , under the pseudonym Victor Janos . The plot follows a disgruntled ex-convict ( also played by Watkins ) who takes revenge on society by kidnapping four strangers and filming their murders in an abandoned building . Filmed in 1972 with a cast and crew of theater students working under pseudonyms , the movie was released in 1974 under the title The Fun House before being re-released under its more widely recognized title in 1977 . The film 's title is derived from the controversial Wes Craven film The Last House on the Left . The true identity of pseudonymous director Victor Janos and the actors was largely unknown until Roger Watkins claimed on Internet message boards in 2000 that he had directed the film , a claim subsequently confirmed . The anonymity and refusal of the cast and crew to come forward about the film led many to believe that it had depicted real murders , a rumor which existed for decades .", "title": "" }, { "docid": "Marianne_Maddalena", "text": "Marianne Maddalena ( born November 14 , 1963 ) is an American film producer . She was born in Lansing , Michigan , and was Wes Craven 's producing partner for many years . They had a company together called Craven/Maddalena Films . One of their productions , Wes Craven 's New Nightmare was nominated for Best Feature at the Independent Spirit Awards in 1995 . Music of the Heart garnered two Oscar nominations ; one for Meryl Streep as Best Actress and one for Best Song for `` Music of my Heart . ''", "title": "" }, { "docid": "Chaos_(2005_Dominion_film)", "text": "Chaos is a 2005 American horror film about the rape and murder of two adolescent girls . It is an unofficial remake of Wes Craven 's The Last House on the Left , with all character names changed and a different ending . It stars Kevin Gage and was written and directed by David DeFalco . The film received widespread critical panning .", "title": "" }, { "docid": "The_House_on_the_Edge_of_the_Park", "text": "The House on the Edge of the Park ( La casa sperduta nel parco ) is a 1980 English-language Italian exploitation horror film written by Gianfranco Clerici and Vincenzo Mannino , and directed by Ruggero Deodato . It stars David A. Hess ( from Wes Craven 's The Last House on the Left , playing a similar character ) , and Giovanni Lombardo Radice .", "title": "" }, { "docid": "Sandra_Peabody", "text": "Sandra Peabody ( born January 11 , 1948 ) is an American actress , screenwriter , producer and acting coach . She is best known for her role as Mari Collingwood in Wes Craven 's The Last House on the Left ( 1972 ) . She subsequently starred in Voices of Desire ( 1972 ) , Massage Parlor Murders ( 1973 ) , and Teenage Hitchhikers ( 1975 ) .", "title": "" }, { "docid": "The_Girl_in_the_Photographs", "text": "The Girl in the Photographs is a 2015 American horror thriller film directed by Nick Simon and executive produced by Wes Craven . The film stars Kal Penn , Claudia Lee , Kenny Wormald , Miranda Rae Mayo , Luke Baines , Christy Carlson Romano , Katharine Isabelle , and Mitch Pileggi . Filming began in April 2015 in Victoria , British Columbia . It was an official selection at Toronto International Film Festival 2015 in the Midnight Madness category . The film was released on April 1 , 2016 in a limited release and through video on demand , by Vertical Entertainment . The Girl in the Photographs is the last film Wes Craven produced before his death on August 30 , 2015 .", "title": "" }, { "docid": "Deadly_Friend", "text": "Deadly Friend is an American 1986 science fiction horror film directed by Wes Craven . It is based on the novel Friend by Diana Henstell , which was adapted for the screen by Bruce Joel Rubin . Originally , the film was a sci-fi thriller without any graphic scenes , with a bigger focus on plot and character development , and a dark love story centering around the two main characters , which were not typical aspects of Craven 's previous films . After Craven 's original cut was shown to a test audience by Warner Bros. , the audience criticized the lack of graphic , bloody violence and gore that Craven 's other films included . Warner Bros. executive vice president Mark Canton and the film 's producers then demanded script re-writes and re-shoots , which included filming gorier death scenes and nightmare sequences , similar to the ones from Craven 's previous horror film , A Nightmare on Elm Street . Due to studio imposed re-shoots and re-editing , the film was drastically altered in post-production , losing much of the original plot and more scenes between characters , while other scenes , including more grisly deaths and a new ending , were added . Although fans have been clamoring for the release of Craven 's original version in a special edition , Warner Bros. currently has no plans to release a director 's cut of Deadly Friend . In April 2014 , an online petition for the release of the original cut was made .", "title": "" }, { "docid": "Mixed_Emotions_(Beverley_Craven_album)", "text": "Mixed Emotions is the third studio album by Beverley Craven , released in 1999 . The album was released after a 5-year hiatus , in which Craven gave birth to two daughters and took time off to take care of her three children . On this album she did not collaborate with the producer of her previous two albums , Paul Samwell-Smith , and instead Craven fully produced the release . The lead single , `` I Miss You '' , was released as a promo single and a videoclip was made for it . However , the record label refused to release the single commercially . The album received mixed reviews and it charted at a poor # 46 in the UK Albums Chart , staying 2 weeks in the Top 75 . Craven made a small tour around the UK to support the album . No further singles were released from the album , and Craven parted ways with her label Epic Records shortly after . She disappeared from the music scene for ten years before returning in 2009 with her fourth album Close To Home . Two songs on the album were originally written for film scores , `` I Miss You '' for the 1996 film The Adventures of Pinocchio , and `` We Found A Place '' for the 1998 film The Theory of Flight . Both were rejected , however , and not used in the films .", "title": "" }, { "docid": "Rape_and_revenge_film", "text": "Rape and revenge films ( a.k.a. rape/revenge , rape-revenge ) are a subgenre of exploitation film that was particularly popular in the 1970s . Rape/revenge movies generally follow the same three-act structure : Act I : A character is raped/gang raped , tortured , and/or left for dead . Act II : The character survives and/or rehabilitates themselves . Act III : The character takes revenge and/or kills their rapist ( s ) . In some cases , the character is incapacitated or killed at the end of the first act , and the `` revenge '' is carried out by their family , as in I Saw the Devil , the original The Last House on the Left and The House of the Spirits . In 2006 , Rogue Pictures finalized a deal to remake The Last House on the Left . Wes Craven ( writer and producer of the original film ) produced the remake , starring Tony Goldwyn and Monica Potter . The 2009 film Run ! Bitch Run ! is set in the late 1970s . The controversial remake I Spit on Your Grave , starring Sarah Butler and Chad Lindberg , was released worldwide on Halloween 2010 by CineTel Films ; its sequel , I Spit on Your Grave 2 , was released in 2013 . In Gaspar Noé 's 2002 film Irréversible , the structure was reversed , with the first act depicting the revenge before tracing back the events which led to that point . Roger Ebert argues that , by using this structure as well as a false revenge , Irréversible can not be classified as an exploitation film , as no exploitation of the subject matter takes place . The genre has attracted critical attention . Much of this critical attention comes from feminist critics examining the complex politics involved in the genre and its impact on cinema more generally . More recently , a broad analysis of the rape-revenge genre and concept was published in Rape-Revenge Films : A Critical Study , by Alexandra Heller-Nicholas . The book argues against a simplistic notion of the term ` rape-revenge ' and suggests a film-specific approach in order to avoid generalizing films which may `` diverge not over the treatment of sexual assault as much as they do in regard to the morality of the revenge act . '' In addition to American and French films , rape/revenge films have been made in Japan ( e.g. , Takashi Ishii 's Freeze Me ) , Finland , Russia ( The Voroshilov Sharpshooter ) , Argentina ( e.g. , I 'll Never Die Alone ; -LSB- 2008 -RSB- ; original title : No Moriré Sola ) , and Norway ( e.g. , The Whore -LSB- 2009 -RSB- ; original title : Hora ) .", "title": "" }, { "docid": "Khara_(studio)", "text": "is a Japanese animation studio best known for its work on the Rebuild of Evangelion film tetralogy . is the primary animation production studio . It was founded by Hideaki Anno in May 2006 , and was shown publicly on 1 August when recruitment notices were posted on his website ; Anno remains its president . It has built up appropriate infrastructure . The name khara comes from the Greek word χαρα , meaning joy . Anno left Gainax and transitioned to Khara ; as part of his public statements on the Rebuild films , he wrote : `` For this purpose , we are not returning to our roots at Gainax . I have set up a production company and studio , and it is in this new setting that we will start again . Without looking back , without admiration for the circumstances , we aim to walk towards the future . Thankfully , we have gathered staff from the old series , new staff , and many other fantastic staff to work on this series . We realize that we are creating something that will be better than the last series . '' Key contributors brought back to work on the new project include assistant director Kazuya Tsurumaki , character designer Yoshiyuki Sadamoto , story board artist Shinji Higuchi and composer Shirō Sagisu .", "title": "" }, { "docid": "List_of_awards_and_nominations_received_by_Wes_Craven", "text": "Wesley Earl `` Wes '' Craven ( born August 2 , 1939 ) ( died August 30 , 2015 ) was an American film director , writer , producer , and actor , perhaps best known for his work on many thriller/horror films , particularly slasher films . Throughout his career , Craven has been nominated for and won various awards including multiple Saturn Awards and various Film Festival awards .", "title": "" }, { "docid": "Filmstaden", "text": "Filmstaden ( The Film Town ) was a film studio situated in Råsunda , Solna Municipality in Stockholm , Sweden . Built by the main Swedish film producer at the time , Svensk Filmindustri , in 1919 -- 1920 , Filmstaden was one of the most modern film studios in Europe . Some 400 movies have been created at Filmstaden . The first movie to be filmed at Filmstaden was The Phantom Carriage by director Victor Sjöström . Practically all Swedish actors and film directors of the 20th century had some connection with Filmstaden . In 1969 , Svensk Filminstustri finally left Filmstaden , and the studios were used by small film producers , production of television dramas and the Riksteatern Theatre . One of the last major films to partly have been filmed at Filmstaden was The Emigrants . Most of the buildings were quite well preserved until the beginning of the 21st century when Filmstaden had to make way for a housing development . Some buildings , however , have been renovated and Svensk Filmindustri has moved its headquarters back to a former studio building .", "title": "" }, { "docid": "Deadly_Blessing", "text": "Deadly Blessing is a 1981 American horror film directed by Wes Craven . The film tells the story of a strange figure committing murder in a contemporary community that is not far from another community that believes in ancient evil and curses . It stars Ernest Borgnine , Maren Jensen , Susan Buckner ( both women making their last feature film screen appearances ) , and Sharon Stone in an early role . AllMovie comments that the film `` finds director Wes Craven in a transitional phase between his hard-hitting early work and his later commercial successes . ''", "title": "" }, { "docid": "Carnival_of_Souls_(1998_film)", "text": "Carnival of Souls ( also billed as Wes Craven Presents ` Carnival of Souls ' ) is a 1998 horror film , a remake of Herk Harvey 's 1962 horror film of the same name , although it has very little in common with the story of the original . It stars Bobbie Phillips and comedian Larry Miller , and was directed by Adam Grossman and Ian Kessner . It was executive produced by Wes Craven . The tagline for the film was : `` Enter at your own risk ! Enter if you dare . ''", "title": "" }, { "docid": "They_(2002_film)", "text": "They ( also known as Wes Craven Presents : They ) is a 2002 American supernatural horror film directed by Robert Harmon . The plot centers on a group of four adults named Julia Lund , Sam Burnside , Terry Alba , and Billy Parks and their experience with the phenomenon of night terrors and the impact they had on their lives as children and how they come back to haunt them as adults . The film was produced by Ted Field , Tom Engleman , and Wes Craven who served as executive producer . The film stars Laura Regan , Ethan Embry , Dagmara Dominczyk , Jay Brazeau , and Marc Blucas . The title is a reference to the fact that the creatures are only referred to as `` They '' as their origins are ambiguous . The film was a box office bomb and had lukewarm reviews from critics .", "title": "" }, { "docid": "Robert_Shapiro_(film_producer)", "text": "Robert Shapiro is an American film producer who was the president of theatrical film production at Warner Bros. . Shapiro started working in the mailroom of the William Morris Agency . Advancing through the firm 's ranks , he served as head of the television talent department and vice president of its motion picture department . He was named as managing director of the firm 's London office at age 28 . Back in the United States , William Morris named him in 1974 as head of the international motion picture department , where he advised directors on writers on the steps they needed to take to get their ideas produced as films by the studios . He left William Morris to start his own production company and was hired by Warner Bros. . In December 1980 , Shapiro was promoted from vice president of worldwide production to president of theatrical film production . Shapiro resigned abruptly from Warner Bros. in July 1983 , announcing that he had become an independent producer at the studio , based on his understanding of his agreement with the studio that he could become an independent producer `` whenever the timing seemed appropriate and beneficial to all concerned '' . The studio 's operating income had dropped $ 6 million from the previous year , only one of 1982 's top ten box office hits -- Chariots of Fire -- was a Warner Bros. release , and the studio was tied for last with Columbia Pictures in domestic film rentals . He was very promptly replaced by Mark Rosenberg , a 35-year-old who had been with the studio for five years . Shapiro 's departure was attributed in industry sources cited by The New York Times as due to poor financial results for the studio 's films in the previous 18 months . Since leaving Warner Bros. , Robert Shapiro Productions has produced films including Empire of the Sun , My Favorite Martian and Pee-wee 's Big Adventure .", "title": "" }, { "docid": "Vampire_in_Brooklyn", "text": "Vampire in Brooklyn ( also known as Wes Craven 's Vampire in Brooklyn ) is a 1995 American comedy horror film directed by Wes Craven . Eddie Murphy , who also produced and stars in the film , wrote the film 's script , alongside Vernon Lynch and Murphy 's older brother Charles Q. Murphy . Vampire in Brooklyn co-stars Angela Bassett , Allen Payne , Kadeem Hardison , John Witherspoon , Zakes Mokae , and Joanna Cassidy . Murphy also plays an alcoholic preacher and a foul-mouthed Italian gangster . The film was released in the United States on October 27 , 1995 . Despite negative reviews , the film became a cult film among fans .", "title": "" }, { "docid": "Filmistan", "text": "Filmistan ( Hindustani : फ़िल्मिस्तान ( Devanagari ) , ( Nastaleeq ) ) was a film production company , based at Filmistan Studio a film studio of Indian film industry from Goregaon , Mumbai . Spread over five acres , near Patkar College on SV road , the studio has seven shooting floors , and a temple and garden for outdoor locations . Patkar College 's reputation has increased due to this studio . It was founded in 1943 by producer Shashadhar Mukherjee , with Rai Bahadur Chunilal as production controller , actor Ashok Kumar and director Gyan Mukherjee , all who left Bombay Talkies after director Himansu Rai 's death . Nasir Hussain , who joined Filmistan in 1948 as a writer , was successful as screenwriter for films like Anarkali , Munimji and Paying Guest . He started film direction with Tumsa Nahin Dekha and became a successful director . Filmistan produced a number of successful hit movies in 1940s and 1950s , including hits likeShaheed ( 1948 ) , Shabnam ( 1949 ) and Sargam ( 1950 ) and successful film like . Anarkali ( 1953 ) and Nagin ( 1954 ) . Other notable films were Jagriti ( 1954 ) , which won the Filmfare Best Movie Award in 1956 , besides Munimji ( 1955 ) , Tumsa Nahin Dekha ( 1957 ) and Paying Guest ( 1957 ) . However in 1958 , Mukherjee left Filmistan to established his own Filmalaya , and continued to produce films , like Love in Shimla ( 1960 ) and Ek Musafir Ek Hasina ( 1962 ) . Eventually Tolaram Jalan bought the studio from Sashdhar Mukherjee and Ashok Kumar in the late 1950s . In the following years , the studio winded down . Dooj Ka Chand made in 1964 , and directed by Nitin Bose , was one of the last film to come out Filmistan production company , however the premises continued to function as a studio , with recent films like Ra.One ( 2011 ) and Bodyguard ( 2011 ) shot here . Yash Raj Films ' television serial Khote Sikkey and dance reality show Jhalak Dikhhla Jaa are shot here . In 2011 , Jalan refuted media reports , which claimed that the studio was up for sale . The present studio manager of Filmistan studio is Jasraj Purohit . More recently , the song `` Offo '' from film 2 States ( 2014 ) , was partly filmed at Filmistan Studio .", "title": "" }, { "docid": "My_Soul_to_Take", "text": "My Soul to Take ( originally called 25/8 ) is a 2010 American supernatural horror film written and directed by Wes Craven . It is his first film since 1994 's Wes Craven 's New Nightmare that he wrote , produced , and directed . The film stars Max Thieriot as the protagonist Adam `` Bug '' Hellerman , who is one of seven teenagers chosen to die . The film was unsuccessful at the box office , and was poorly received by critics . The film 's title comes from a line in the prayer `` Now I Lay Me Down to Sleep '' , which reads `` If I shall die before I wake , I pray the Lord my soul to take . '' The prayer features in the film .", "title": "" }, { "docid": "Wes_Craven's_New_Nightmare", "text": "Wes Craven 's New Nightmare is a 1994 American slasher film written and directed by original Nightmare on Elm Street creator Wes Craven . Although it is the seventh film in the franchise , it is not part of the series continuity , instead portraying Freddy Krueger as a fictional movie villain who invades the real world and haunts the cast and crew responsible for his films . In this film , Freddy is depicted as closer to what Craven originally intended , being more menacing and less comical , with an updated attire and appearance . The film features various people involved in the motion picture industry playing themselves , including actress Heather Langenkamp who is compelled by events in the narrative to reprise her role as Nancy Thompson . New Nightmare features several homages to the original film such as quotes and recreations of the most famous scenes .", "title": "" }, { "docid": "Jay_Craven", "text": "Jay Craven is a Vermont film director , screenwriter and professor of film studies at Marlboro College . Craven is known for creating award winning films on modest budgets , adopting all of the novels of author Howard Frank Mosher to film . He often casts from a regular troupe of Vermont actors including Tantoo Cardinal and Rusty DeWees , but has also worked with Rip Torn and Kris Kristofferson . Craven founded and runs Kingdom County Productions and recently launched Catamount Arts performing arts program , New England 's largest independent arts producer and presenter . He is married to Bess O'Brien , who is also a co-founder of Kingdom County Productions . Craven attended Boston University for undergraduate studies , where he developed a lifelong friendship with Howard Zinn . He later went on to Goddard College . He lives in the Northeast Kingdom with his family .", "title": "" } ]
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[ { "docid": "MED-3351", "text": "Based on evidence that the color red elicits avoidance motivation across contexts (Mehta & Zhu, 2009), two studies investigated the effect of the color red on snack food and soft drink consumption. In line with our hypothesis, participants drank less from a red labeled cup than from a blue labeled cup (Study 1), and ate less snack food from a red plate than from a blue or white plate (Study 2). The results suggest that red functions as a subtle stop signal that works outside of focused awareness and thereby reduces incidental food and drink intake. Copyright © 2012 Elsevier Ltd. All rights reserved.", "title": "The color red reduces snack food and soft drink intake." }, { "docid": "MED-3359", "text": "Background Fruit and vegetable consumption and ingestion of carotenoids have been found to be associated with human skin-color (yellowness) in a recent cross-sectional study. This carotenoid-based coloration contributes beneficially to the appearance of health in humans and is held to be a sexually selected cue of condition in other species. Methodology and Principal Findings Here we investigate the effects of fruit and vegetable consumption on skin-color longitudinally to determine the magnitude and duration of diet change required to change skin-color perceptibly. Diet and skin-color were recorded at baseline and after three and six weeks, in a group of 35 individuals who were without makeup, self-tanning agents and/or recent intensive UV exposure. Six-week changes in fruit and vegetable consumption were significantly correlated with changes in skin redness and yellowness over this period, and diet-linked skin reflectance changes were significantly associated with the spectral absorption of carotenoids and not melanin. We also used psychophysical methods to investigate the minimum color change required to confer perceptibly healthier and more attractive skin-coloration. Modest dietary changes are required to enhance apparent health (2.91 portions per day) and attractiveness (3.30 portions). Conclusions Increased fruit and vegetable consumption confers measurable and perceptibly beneficial effects on Caucasian skin appearance within six weeks. This effect could potentially be used as a motivational tool in dietary intervention.", "title": "You Are What You Eat: Within-Subject Increases in Fruit and Vegetable Consumption Confer Beneficial Skin-Color Changes" }, { "docid": "MED-3355", "text": "OBJECTIVE: To evaluate the effects of a high-fat and low-fat diet on taste sensitivity to oleic acid (C18:1) in lean and overweight/obese (OW/OB) subjects. DESIGN: Randomized cross-over dietary intervention involving the consumption of a high-fat (>45% fat) and low-fat (<20% fat) diet, both consumed over a 4-week period. SUBJECTS: A total of 19 lean, mean age 33±13 years, mean body mass index (BMI) 23.2±2.2 kg m(-2) and 12 OW/OB, mean age 39.5±3 years, mean BMI 28±2.6 kg m(-2), subjects participated in the study, which measured taste thresholds for C18:1, fat perception and hedonic ratings for regular (RF) and lowered-fat (LF) foods before, and following consumption of a high- and low-fat diet. RESULTS: Consumption of the low-fat diet increased taste sensitivity to C18:1 among lean and OW/OB subjects (P<0.05) and increased the subjects ability to perceive small differences in the fat content of custard (P=0.05). Consumption of the high-fat diet significantly decreased taste sensitivity to C18:1 among lean subjects (P<0.05), with no change in sensitivity among OW/OB persons (P=0.609). The hedonic ratings for several RF and LF foods differed following the diets. CONCLUSION: Alterations in the fat content of the diet modulated taste sensitivity to C18:1 among lean subjects, which was increased following a 4-week period of fat restriction and attenuated following the high-fat diet. The failure of the high-fat diet to alter fatty acid taste thresholds among OW/OB subjects suggests that these individuals were 'adapted' to high-fat exposure, perhaps because of differences in habitual fat consumption. Taken together, these data suggest that excessive dietary fat attenuates nutrient sensing epithelia response in the oral cavity, which could be associated with changes in diet and weight status.", "title": "Recent fat intake modulates fat taste sensitivity in lean and overweight subjects." }, { "docid": "MED-4859", "text": "Fresh blueberries were processed into sugar and sugar-free jams and stored for 6 months at 4 and 25 degrees C. The jams were analyzed immediately after processing and over 6 months of storage for polyphenolic content, percent polymeric color, and antioxidant capacity. Processing resulted in losses of anthocyanins, procyanidins, chlorogenic acid, and ORAC in both jam types, but flavonols were well retained. Marked losses of anthocyanins and procyanidins occurred over 6 months of storage and were accompanied by increased polymeric color values. Chlorogenic acid levels also declined during storage, but flavonols and ORAC changed little. Jams stored at 4 degrees C retained higher levels of anthocyanins, procyanidins, and ORAC and had lower polymeric color values than jams stored at 25 degrees C. Sugar-free jams retained higher levels of anthocyanins and had lower polymeric color values than sugar jams late during storage. Blueberry jams should be refrigerated to better retain polyphenolics and antioxidant capacity.", "title": "Jam processing and storage effects on blueberry polyphenolics and antioxidant capacity." }, { "docid": "MED-3353", "text": "Skin blood perfusion and oxygenation depends upon cardiovascular, hormonal and circulatory health in humans and provides socio-sexual signals of underlying physiology, dominance and reproductive status in some primates. We allowed participants to manipulate colour calibrated facial photographs along empirically-measured oxygenated and deoxygenated blood colour axes both separately and simultaneously, to optimise healthy appearance. Participants increased skin blood colour, particularly oxygenated, above basal levels to optimise healthy appearance. We show, therefore, that skin blood perfusion and oxygenation influence perceived health in a way that may be important to mate choice.", "title": "Skin Blood Perfusion and Oxygenation Colour Affect Perceived Human Health" }, { "docid": "MED-3350", "text": "Normotensive adults on low-sodium, weight-loss, and control diets recorded preferences and perceived saltiness for sodium chloride (NaCl) added to cream soup at intervals over 1 yr. Reduction in sodium intake and excretion accompanied a shift in preference toward less salt: preferred concentrations by ad libitum salting declined from 0.72% at the onset to 0.33% NaCl at week 24; hedonic scores for high concentrations of NaCl decreased significantly while scores for low concentrations increased. After 3 mo of sodium restriction, NaCl preferences readjusted to a lower level: ad libitum additions of NaCl were similar after 13, 24, and 52 wk. Less hedonic variation was observed among controls than among Na-restricted groups. The weight-loss group showed increased liking for mid-range NaCl levels. Mechanisms underlying preference changes, including physiological, behavioral, and context effects, may provide insights into maintenance of low-sodium diets for treatment and prevention of hypertension.", "title": "Effect of dietary sodium restriction on taste responses to sodium chloride: a longitudinal study." }, { "docid": "MED-3352", "text": "The popularity of low- and reduced-fat foods has increased as consumers seek to decrease their energy consumption. Fat replacers may be used in fat-reduced products to maintain their sensory properties. However, these ingredients have been largely formulated to replicate nongustatory properties of fats to foods and have only achieved moderate success. There is increasing evidence that fats also activate the taste system and uniquely evoke responses that may influence product acceptance. Work supporting a taste component of fat has prompted questions about whether fat constitutes an additional \"primary\" or \"basic\" taste quality. This review briefly summarizes this evidence, focusing on human studies, when possible. Effective stimuli, possible receptors, and physiological changes due to oral fat exposure are discussed. Some studies suggest that there are fatty acid tasters and nontasters and if verified could have implications for targeted product development. © 2011 Institute of Food Technologists®", "title": "Are free fatty acids effective taste stimuli in humans? Presented at the symposium \"The Taste for Fat: New Discoveries on the Role of Fat in Sensor..." }, { "docid": "MED-3356", "text": "OBJECTIVE: This study examined changes in desires to eat high-fat and low-fat foods across an obesity treatment program. The hypotheses under examination were (1) preferences for low-fat foods would increase across time and (2) preferences for high-fat foods would decrease across time. DESIGN: Single-group, prospective examination of desires to eat 48 foods, categorized according to fat content, before and after the 16-week treatment program. SETTING: University clinic, Memphis, Tennessee. PARTICIPANTS: 118 obese (mean weight = 194.4 lbs) women (mean age = 45.24 years) participating in an obesity treatment program. INTERVENTION: A 16-week cognitive-behavioral program for obesity. VARIABLES MEASURED: Desires to eat 48 foods varying in fat content and whether or not participants actually ate these foods. ANALYSIS: Analysis of variance, multiple regression, and paired t tests. RESULTS: The results indicate that during the program, preferences for low-fat foods increased, whereas preferences for high-fat foods decreased. These changes mirrored the changes in consumption of both low-fat and high-fat foods. CONCLUSIONS AND IMPLICATIONS: Within a behavioral economic perspective, the reinforcement value of low-fat foods may increase following a low-fat dietary intervention, whereas the reinforcing properties of high-fat foods may decline. This is desirable as low-fat foods hold many advantages over high-fat foods in terms of weight maintenance.", "title": "Desire to eat high- and low-fat foods following a low-fat dietary intervention." }, { "docid": "MED-4454", "text": "The aim of this study was to determine the bioavailability and kinetics of the supposed anticarcinogen sulforaphane, the hydrolysis product of glucoraphanin, from raw and cooked broccoli. Eight men consumed 200 g of crushed broccoli, raw or cooked, with a warm meal in a randomized, free-living, open cross-over trial. Higher amounts of sulforaphane were found in the blood and urine when broccoli was eaten raw (bioavailability of 37%) versus cooked (3.4%, p ) 0.002). Absorption of sulforaphane was delayed when cooked broccoli was consumed (peak plasma time ) 6 h) versus raw broccoli (1.6 h, p ) 0.001). Excretion half-lives were comparable, 2.6 and 2.4 h on average, for raw and cooked broccoli, respectively (p ) 0.5). This study gives complete kinetic data and shows that consumption of raw broccoli results in faster absorption, higher bioavailability, and higher peak plasma amounts of sulforaphane, compared to cooked broccoli.", "title": "Bioavailability and kinetics of sulforaphane in humans after consumption of cooked versus raw broccoli." }, { "docid": "MED-733", "text": "The present paper presents an overview of current knowledge of amyloid arthropathy in chickens, and covers the pathogenesis of amyloidosis in general and in birds, field cases reported, and the studies performed to assess the amyloidogenicity of various agents compared to that of Enterococcus faecalis. An animal model of amyloid arthropathy is presented, as are studies on the pathogenesis of arthropathic and amyloidogenic E. faecalis infections in brown layers. The review concludes with a description of the pathology of amyloid arthropathy, the biochemical characterization of the chicken joint amyloid protein as being of the AA type, investigation of the serum amyloid A (SAA) gene involved, and local SAA mRNA expression in joint and liver.", "title": "Amyloid arthropathy in chickens." }, { "docid": "MED-3369", "text": "Background: Strategies are needed to increase children's intake of a variety of vegetables, including vegetables that are not well liked. Objective: We investigated whether incorporating puréed vegetables into entrées to reduce the energy density (ED; in kcal/g) affected vegetable and energy intake over 1 d in preschool children. Design: In this crossover study, 3- to 5-y-old children (n = 40) were served all meals and snacks 1 d/wk for 3 wk. Across conditions, entrées at breakfast, lunch, dinner, and evening snack were reduced in ED by increasing the proportion of puréed vegetables. The conditions were 100% ED (standard), 85% ED (tripled vegetable content), and 75% ED (quadrupled vegetable content). Entrées were served with unmanipulated side dishes and snacks, and children were instructed to eat as much as they liked. Results: The daily vegetable intake increased significantly by 52 g (50%) in the 85% ED condition and by 73 g (73%) in the 75% ED condition compared with that in the standard condition (both P < 0.0001). The consumption of more vegetables in entrées did not affect the consumption of the vegetable side dishes. Children ate similar weights of food across conditions; thus, the daily energy intake decreased by 142 kcal (12%) from the 100% to 75% ED conditions (P < 0.05). Children rated their liking of manipulated foods similarly across ED amounts. Conclusion: The incorporation of substantial amounts of puréed vegetables to reduce the ED of foods is an effective strategy to increase the daily vegetable intake and decrease the energy intake in young children. This trial was registered at clinicaltrials.gov as NCT01252433.", "title": "Hiding vegetables to reduce energy density: an effective strategy to increase children's vegetable intake and reduce energy intake" }, { "docid": "MED-3371", "text": "Background: The overconsumption of energy-dense foods leads to excessive energy intakes. The substitution of low-energy-dense vegetables for foods higher in energy density can help decrease energy intakes but may be difficult to implement if individuals dislike the taste of vegetables. Objective: We investigated whether incorporating puréed vegetables to decrease the energy density of entrées at multiple meals reduced daily energy intakes and increased daily vegetable intakes. Design: In this crossover study, 20 men and 21 women ate ad libitum breakfast, lunch, and dinner in the laboratory once a week for 3 wk. Across conditions, entrées at meals varied in energy density from standard versions (100% condition) to reduced versions (85% and 75% conditions) by the covert incorporation of 3 or 4.5 times the amount of puréed vegetables. Entrées were accompanied by unmanipulated side dishes. Participants rated their hunger and fullness before and after meals. Results: Subjects consumed a consistent weight of foods across conditions of energy density; thus, the daily energy intake significantly decreased by 202 ± 60 kcal in the 85% condition (P < 0.001) and by 357 ± 47 kcal in the 75% condition (P < 0.0001). Daily vegetable consumption significantly increased from 270 ± 17 g of vegetables in the 100% condition to 487 ± 25 g of vegetables in the 75% condition (P < 0.0001). Despite the decreased energy intake, ratings of hunger and fullness did not significantly differ across conditions. Entrées were rated as similar in palatability across conditions. Conclusions: Large amounts of puréed vegetables can be incorporated into various foods to decrease the energy density. This strategy can lead to substantial reductions in energy intakes and increases in vegetable intakes. This trial was registered at clinicaltrials.gov as NCT01165086.", "title": "Hidden vegetables: an effective strategy to reduce energy intake and increase vegetable intake in adults" }, { "docid": "MED-3373", "text": "Objectives. We considered the relationship between an urban adult population's fruit and vegetable consumption and several selected social and psychological processes, beneficial aesthetic experiences, and garden participation. Methods. We conducted a population-based survey representing 436 residents across 58 block groups in Denver, Colorado, from 2006 to 2007. We used multilevel statistical models to evaluate the survey data. Results. Neighborhood aesthetics, social involvement, and community garden participation were significantly associated with fruit and vegetable intake. Community gardeners consumed fruits and vegetables 5.7 times per day, compared with home gardeners (4.6 times per day) and nongardeners (3.9 times per day). Moreover, 56% of community gardeners met national recommendations to consume fruits and vegetables at least 5 times per day, compared with 37% of home gardeners and 25% of nongardeners. Conclusions. Our study results shed light on neighborhood processes that affect food-related behaviors and provides insights about the potential of community gardens to affect these behaviors. The qualities intrinsic to community gardens make them a unique intervention that can narrow the divide between people and the places where food is grown and increase local opportunities to eat better.", "title": "The Influence of Social Involvement, Neighborhood Aesthetics, and Community Garden Participation on Fruit and Vegetable Consumption" }, { "docid": "MED-734", "text": "A total of 28 domestic ducks were divided into seven groups of four ducks. Six groups were inoculated per os with 10(1), 10(2), 10(3), 10(4), 10(5) and 10(5.7) oocysts Toxoplasma gondii oocysts (K21 strain, which is avirulent for mice), and the remaining group was used as a control. Antibodies to T. gondii were detected in all ducks by the indirect fluorescence antibody test first on day 7 post-inoculation (p.i.). Antibody titres were found in the range of 1:20 to 1:640 depending on the infectious dose of the oocysts. From day 14 p.i. antibody titres increased to 1:80 to 1:20 480. Between days 14 and 28 p.i. (end of the experiment), antibody titres decreased in 14 ducks, remained the same in seven ducks, and continued to increase in three ducks. Bioassay in mice revealed T. gondii in the breast and leg muscles and the heart (100%, n=47), brain (91%, n=22), liver (54%, n=13) and stomach (46%, n=24). The infected ducks showed no clinical signs; however, the results of bioassay indicate that, compared with some gallinaceous birds, domestic ducks were relatively susceptible to T. gondii infection.", "title": "Susceptibility of the domestic duck (Anas platyrhynchos) to experimental infection with Toxoplasma gondii oocysts." }, { "docid": "MED-3358", "text": "BACKGROUND & AIMS: Taste sensitivity to fatty acids influences food ingestion and may regulate fat intake and body weight status. Fatty acids are detected via homologous receptors within the mouth and gastrointestinal (GI) tract, where attenuated sensitivity may be associated with greater fat intake and BMI. This study aimed to extend observations surrounding fatty acid taste, specifically the types of foods consumed and dietary behaviours that may be associated with fatty acid taste sensitivity. METHODS: 51 subjects (41 female; BMI, 21.4 ± 0.46 kg/m², age, 20 ± 0.52 yrs, 10 male; BMI, 23.6 ± 1.4 kg/m², age, 22 ± 1 yrs) were screened for oral sensitivity to oleic acid (3.8 mM) using triplicate sensory evaluations, and classified as hypersensitive; (3/3 correct identifications), or hyposensitive, (<3/3). Fat-taste perception (using sensory-matched custards made with 0, 2, 6, 10% oil), recent diet (4-day diet record) and food habits and behaviours (food habits and behaviours questionnaire) were also established. RESULTS: 75% (n = 38) of subjects were classified as hyposensitive to oleic acid and these subjects differed from those who were classified as hypersensitive. Hyposensitive subjects consumed significantly more energy, fat, saturated fat, fatty foods (butter, meat, dairy), had greater BMI and were less perceptive of small changes in the fat content of custard (all P < 0.05), compared to hypersensitive subjects. CONCLUSION: An inability to perceive low concentrations of fatty acids in foods was associated with greater consumption of fatty foods, specifically butter, meat, dairy, and increasing BMI. 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.", "title": "Oral sensitivity to oleic acid is associated with fat intake and body mass index." }, { "docid": "MED-3348", "text": "Fruit and vegetable consumption is inadequate among adults in the United States; this contributes to preventable morbidity and mortality. More effective dietary intervention strategies are needed. Recently, interventions that advertise the consequences of behavior for appearance have been successful in modifying sun-exposure habits and tobacco use. Such an approach might also facilitate dietary improvement. Consumption of carotenoid-rich fruit and vegetables positively affects skin color, which influences perceptions of health and attractiveness, and promoting such an effect may motivate target audiences to increase consumption of this important food group. This approach represents a novel direction for the field and is potentially suitable for cost-effective, population-level dissemination through the visual media.", "title": "Appealing to Vanity: Could Potential Appearance Improvement Motivate Fruit and Vegetable Consumption?" } ]
[ { "docid": "MED-891", "text": "A method based on solid phase extraction followed by derivatization and gas chromatography-mass spectrometry analysis was validated for the determination of bisphenol A (BPA) in canned food products. This method was used to analyze 78 canned food products for BPA. Concentrations of BPA in canned food products differed considerably among food types, but all were below the specific migration limit of 0.6 mg/kg set by the European Commission Directive for BPA in food or food simulants. Canned tuna products had the highest BPA concentrations in general, with mean and maximum values of 137 and 534 ng/g, respectively. BPA concentrations in the condensed soup products were considerably higher than those in the ready-to-serve soup products, with mean and maximum values of 105 and 189 ng/g, respectively, for the condensed soups and 15 and 34 ng/g, respectively, for the ready-to-serve soups. BPA concentrations in canned vegetable products were relatively low; about 60% of the products had BPA concentrations of less than 10 ng/g. Canned tomato paste products had lower BPA concentrations than did canned pure tomato products. The mean and maximum BPA concentrations were 1.1 and 2.1 ng/g, respectively, for tomato paste products and 9.3 and 23 ng/g, respectively, for the pure tomato products.", "title": "Bisphenol a in canned food products from canadian markets." }, { "docid": "MED-2201", "text": "Measuring food prices per gram, rather than per calorie, is one way to make healthful vegetables appear less expensive. However, a better measure of affordability would take the nutrient content of vegetables into account. This study, based on analyses of US Department of Agriculture datasets, aimed to identify which vegetables, including juices and soups, provided the most nutrients per unit cost. Nutrient density was measured using the Nutrient Rich Foods (NRF) index, based on nine nutrients to encourage: protein; fiber; vitamins A, C, and E; calcium; iron; magnesium; and potassium; and on three nutrients to limit: saturated fat, added sugar, and sodium. Food cost in dollars was calculated per 100 g, per 100 kcal, per serving, and per nutrient content. One-way analyses of variance with post hoc tests were used to determine statistical significance. Results showed that tomato juices and tomato soups, dark green leafy and nonleafy vegetables, and deep yellow vegetables, including sweet potatoes, had the highest NRF scores overall. Highest NRF scores per dollar were obtained for sweet potatoes, white potatoes, tomato juices and tomato soups, carrots, and broccoli. Tomato sauces, raw tomatoes, and potato chips were eaten more frequently than were many other vegetables that were both more affordable and more nutrient-rich. These new measures of affordable nutrition can help foodservice and health professionals identify those vegetables that provide the highest nutrient density per unit cost. Processed vegetables, including soups and juices, can contribute to the quality and the affordability of the diet. Copyright © 2013 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.", "title": "New metrics of affordable nutrition: which vegetables provide most nutrients for least cost?" }, { "docid": "MED-5295", "text": "The plasma sodium concentration has a direct effect on blood pressure in addition to its effects on extracellular volume regulated through changes in the endothelium. The mechanism for elevated blood pressure seen with habitually increased salt intake is unclear, especially the effect of salt in a single meal on plasma sodium concentration and blood pressure. To resolve this we compared the effect of soup with or without 6 g of salt (an amount similar to that in a single meal) on the plasma sodium concentration and blood pressure in 10 normotensive volunteers using a randomized, crossover design. The plasma sodium concentration was significantly increased by 3.13±0.75 mmol/l with salted compared with unsalted soup. Blood pressure increased in volunteers ingesting soup with added salt, and there was a significant positive correlation between plasma sodium concentration and systolic blood pressure. A 1-mmol/l increase in plasma sodium was associated with a 1.91-mm Hg increase in systolic blood pressure by linear regression. Thus, changes in plasma sodium concentration occur each time a meal containing salt is consumed. A potential mechanism for the changes in blood pressure seen with salt intake may be through its effects on plasma sodium concentration.", "title": "Dietary salt influences postprandial plasma sodium concentration and systolic blood pressure." }, { "docid": "MED-2068", "text": "SCOPE: Sulforaphane (a potent anticarcinogenic isothiocyanate derived from glucoraphanin) is widely considered responsible for the protective effects of broccoli consumption. Broccoli is typically purchased fresh or frozen and cooked before consumption. We compared the bioavailability and metabolism of sulforaphane from portions of lightly cooked fresh or frozen broccoli, and investigated the bioconversion of sulforaphane to erucin. METHODS AND RESULTS: Eighteen healthy volunteers consumed broccoli soups produced from fresh or frozen broccoli florets that had been lightly cooked and sulforaphane thio-conjugates quantified in plasma and urine. Sulforaphane bioavailability was about tenfold higher for the soups made from fresh compared to frozen broccoli, and the reduction was shown to be due to destruction of myrosinase activity by the commercial blanching-freezing process. Sulforaphane appeared in plasma and urine in its free form and as several thio-conjugates forms. Erucin N-acetyl-cysteine conjugate was a significant urinary metabolite, and it was shown that human gut microflora can produce sulforaphane, erucin, and their nitriles from glucoraphanin. CONCLUSION: The short period of blanching used to produce commercial frozen broccoli destroys myrosinase and substantially reduces sulforaphane bioavailability. Sulforaphane was converted to erucin and excreted in urine, and it was shown that human colonic flora were capable of this conversion. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.", "title": "Isothiocyanate concentrations and interconversion of sulforaphane to erucin in human subjects after consumption of commercial frozen broccoli compa..." }, { "docid": "MED-3986", "text": "BACKGROUND/OBJECTIVES: Mushrooms contain very little or any vitamin D(2) but are abundant in ergosterol, which can be converted into vitamin D(2) by ultraviolet (UV) irradiation. Our objective was to investigate the bioavailability of vitamin D(2) from vitamin D(2)-enhanced mushrooms by UV-B in humans, and comparing it with a vitamin D(2) supplement. SUBJECTS/METHODS: Fresh mushrooms were irradiated with an UV-B dose of 1.5 J/cm(2), increasing vitamin D(2) content from <1 to 491 μg/100 g and made to an experimental soup. In this 5-week, single-blinded, randomized, placebo-controlled trial, 26 young subjects with serum 25-hydroxyvitamin D (25OHD) ≤ 50 nmol/l were randomly assigned into three groups ((a) mushroom, (b) supplement and (c) placebo). They received during winter (a) 28,000 IU (700 μg) vitamin D(2) via the experimental soup, or (b) 28,000 IU vitamin D(2) via a supplement or (c) placebo, respectively. RESULTS: After 2 weeks, serum 25OHD was significantly higher in the mushroom than in the placebo group (P=0.001). The serum 25OHD concentrations in the mushroom and supplement groups rose significantly and similarly over the study period by 3.9 nmol/l (95% confidence interval (95% CI): 2.9, 4.8) and by 4.7 nmol/l per week (95% CI: 3.8, 5.7), respectively. CONCLUSIONS: We are the first to demonstrate in humans that the bioavailability of vitamin D(2) from vitamin D(2)-enhanced button mushrooms via UV-B irradiation was effective in improving vitamin D status and not different to a vitamin D(2) supplement. This trial was registered at http://germanctr.de as DRKS00000195.", "title": "Bioavailability of vitamin D₂ from UV-B-irradiated button mushrooms in healthy adults deficient in serum 25-hydroxyvitamin D: a randomized controll..." }, { "docid": "MED-4664", "text": "We report a series of cases of thyroid dysfunction in adults associated with ingestion of a brand of soy milk manufactured with kombu (seaweed), and a case of hypothyroidism in a neonate whose mother had been drinking this milk. We also report two cases of neonatal hypothyroidism linked to maternal ingestion of seaweed made into soup. These products were found to contain high levels of iodine. Despite increasing awareness of iodine deficiency, the potential for iodine toxicity, particularly from sources such as seaweed, is less well recognised.", "title": "Iodine toxicity from soy milk and seaweed ingestion is associated with serious thyroid dysfunction." }, { "docid": "MED-4662", "text": "Mild iodine deficiency is a recognised problem in Australia and New Zealand. However, iodine excess can cause hypothyroidism in some infants. We highlight two cases which illustrate the risks of excess dietary iodine intake during pregnancy and breastfeeding. They also describe a cultural practice of consuming seaweed soup to promote breast milk supply. Although most attention recently has been on the inadequacy of iodine in Australian diets, the reverse situation should not be overlooked. Neither feast nor famine is desirable. © 2011 The Authors. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).", "title": "Iodine-induced neonatal hypothyroidism secondary to maternal seaweed consumption: a common practice in some Asian cultures to promote breast milk s..." }, { "docid": "MED-1274", "text": "Sharks are among the most threatened groups of marine species. Populations are declining globally to support the growing demand for shark fin soup. Sharks are known to bioaccumulate toxins that may pose health risks to consumers of shark products. The feeding habits of sharks are varied, including fish, mammals, crustaceans and plankton. The cyanobacterial neurotoxin β-N-methylamino-L-alanine (BMAA) has been detected in species of free-living marine cyanobacteria and may bioaccumulate in the marine food web. In this study, we sampled fin clips from seven different species of sharks in South Florida to survey the occurrence of BMAA using HPLC-FD and Triple Quadrupole LC/MS/MS methods. BMAA was detected in the fins of all species examined with concentrations ranging from 144 to 1836 ng/mg wet weight. Since BMAA has been linked to neurodegenerative diseases, these results may have important relevance to human health. We suggest that consumption of shark fins may increase the risk for human exposure to the cyanobacterial neurotoxin BMAA.", "title": "Cyanobacterial Neurotoxin β-N-Methylamino-L-alanine (BMAA) in Shark Fins" }, { "docid": "MED-3821", "text": "Reducing the concentration of polyamines (spermine, spermidine, and putrescine) in the body pool may slow the cancer process. Because dietary spermine, spermidine, and putrescine contribute to the body pool of polyamines, quantifying them in the diet is important. Limited information about polyamine content of food is available, especially for diets in the United States. This brief report describes the development of a polyamine database linked to the Fred Hutchinson Cancer Center food frequency questionnaire (FFQ). Values for spermine, spermidine, and putrescine were calculated and reported per serving size (nmol/serving). Of the foods from the database that were evaluated, fresh and frozen corn contain the highest levels of putrescine (560,000 nmol/serving and 902,880 nmol/serving) and spermidine (137,682 nmol/serving and 221,111 nmol/serving), and green pea soup contains the highest concentration of spermine (36,988 nmol/serving). The polyamine database and FFQ were tested with a convenience sample (n=165). Average daily polyamine intakes from the sample were: 159,133 nmol/day putrescine, 54,697 nmol/day spermidine, and 35,698 nmol/day spermine. Orange and grapefruit juices contributed the greatest amount of putrescine (44,441 nmol/day) to the diet. Green peas contributed the greatest amount of spermidine (3,283 nmol/day) and ground meat contributed the greatest amount of spermine (2,186 nmol/day). Development of this database linked to an FFQ provides a means of estimating polyamine intake and contributes to investigations relating polyamines to cancer.", "title": "Development of a Polyamine Database for Assessing Dietary Intake" }, { "docid": "MED-4232", "text": "OBJECTIVES: To evaluate the role of a wide range of foods on the risk of benign prostatic hyperplasia (BPH), we conducted a case-control study in Italy between 1991 and 2002. Although BPH is an extremely common condition, particularly among older men, its risk factors, including dietary ones, remain largely undefined. METHODS: Included in the study were 1369 patients younger than 75 years old surgically treated for BPH and 1451 controls younger than 75 years of age who had been admitted to the same hospitals as cases for a wide spectrum of acute, non-neoplastic conditions. A validated and reproducible food frequency questionnaire, including 78 foods and beverages, plus a separate section on alcoholic beverages, was used to assess patients' dietary habits 2 years before diagnosis or hospital admission. Multivariate odds ratios (OR) were obtained after allowance for energy intake and other major potential confounding factors. RESULTS: A significant trend of increasing risk with more frequent consumption was found for cereals (OR 1.55 for the greatest versus lowest quintile), bread (OR 1.69), eggs (OR 1.43), and poultry (OR 1.39). Inverse associations were observed for soups (OR 0.74), pulses (OR 0.74), cooked vegetables (OR 0.66), and citrus fruit (OR 0.82). No association was observed for milk and yogurt products, coffee and tea, pasta and rice, fish, cheese, row vegetables, potatoes, fruit, or desserts. CONCLUSIONS: The results of this study suggest a role for dietary habits on the risk of BPH. In particular, a diet rich in cereals and some types of meat and poor in vegetables and pulses may have an unfavorable effect in this Italian population.", "title": "Food groups and risk of benign prostatic hyperplasia." }, { "docid": "MED-3085", "text": "Objective To determine the prevalence of phosphorus-containing food additives in best selling processed grocery products and to compare the phosphorus content of a subset of top selling foods with and without phosphorus additives. Design The labels of 2394 best selling branded grocery products in northeast Ohio were reviewed for phosphorus additives. The top 5 best selling products containing phosphorus additives from each food category were matched with similar products without phosphorus additives and analyzed for phosphorus content. Four days of sample meals consisting of foods with and without phosphorus additives were created and daily phosphorus and pricing differentials were computed. Setting Northeast Ohio Main outcome measures Presence of phosphorus-containing food additives, phosphorus content Results 44% of the best selling grocery items contained phosphorus additives. The additives were particularly common in prepared frozen foods (72%), dry food mixes (70%), packaged meat (65%), bread & baked goods (57%), soup (54%), and yogurt (51%) categories. Phosphorus additive containing foods averaged 67 mg phosphorus/100 gm more than matched non-additive containing foods (p=.03). Sample meals comprised mostly of phosphorus additive-containing foods had 736 mg more phosphorus per day compared to meals consisting of only additive-free foods. Phosphorus additive-free meals cost an average of $2.00 more per day. Conclusion Phosphorus additives are common in best selling processed groceries and contribute significantly to their phosphorus content. Moreover, phosphorus additive foods are less costly than phosphorus additive-free foods. As a result, persons with chronic kidney disease may purchase these popular low-cost groceries and unknowingly increase their intake of highly bioavailable phosphorus.", "title": "The Prevalence of Phosphorus Containing Food Additives in Top Selling Foods in Grocery Stores" }, { "docid": "MED-5269", "text": "BACKGROUND AND AIM: Currently, more than 30% of the caloric intake in the Colombian population comes from vegetable oil consumption mainly by the ingestion of deep-fried foods. Recently, it has been reported that unsaturated fatty acid rich oils have a beneficial effect on the endothelial function. Nevertheless, it is well know that the deep-frying process alters the chemical composition of vegetable oils and can produce adverse effects in the endothelial function. OBJECTIVE: To evaluate the acute effect of the ingestion of large amounts of olive, soybean and palm oils, fresh and at two different deep-fry levels, on the glucose and lipid profiles and the endothelial function. METHODS AND RESULTS: Ten healthy young volunteers were included in the study. After performing a baseline evaluation of cardiovascular risk factors and drawing a fasting blood sample, subjects were exposed to a randomly assigned potato soup meal containing 60 mL of one of three different vegetable oils (olive, soybean and palm), either fresh or at one of two different deep-fry levels (10 and 20 fries, respectively). Flow-mediated vasodilation (FMD) was performed in fasting conditions and 3h after the intake of the oil rich meal. Furthermore, blood samples were taken at these stages for the lipid profiles and plasma glucose determinations. All the meals resulted in a similar acute endothelial impairment (FMD decrease of 32.1%, confidence interval [CI] 95%, 28.0-36.2) and postprandial increase in triglycerides (27.03%, CI 95%, 20.5-33.3), independently of the type of oil ingested (p=0.44) and regardless of its deep-fry level (p=0.62). No correlation was found between endothelial impairment and postprandial triglyceride increment (r=-0.22, p=0.09). CONCLUSIONS: No difference was found in the acute adverse effect of the ingestion of different vegetable oils on the endothelial function. All the vegetable oils, fresh and deep-fried, produced an increase in the triglyceride plasma levels in healthy subjects.", "title": "Olive, soybean and palm oils intake have a similar acute detrimental effect over the endothelial function in healthy young subjects." }, { "docid": "MED-3138", "text": "Background Many consumers avoid eating beans because they believe legume consumption will cause excessive intestinal gas or flatulence. An increasing body of research and the 2010 Dietary Guidelines for Americans supports the benefits of a plant-based diet, and legumes specifically, in the reduction of chronic disease risks. The purpose of the current research was to investigate the perception of increased flatulence and gastrointestinal discomfort among participants who consumed a ½ cup of beans daily for 8 or 12 weeks. Methods Participants in three studies to test the effects of beans on heart disease biomarkers completed the same weekly questionnaire to assess gastrointestinal discomfort issues such as increased flatulence, stool changes, and bloating. Studies 1 and 2 were randomized crossover trials. Participants consumed ½ cup of pinto beans, black-eyed peas, and canned carrots as control (n = 17) in Study 1 for three randomized 8-week phases. For Study 2, participants ate ½ cup baked beans or canned carrots as control (n = 29) for two randomized 8-week phases. Study 3 was a parallel arm trial with 40 subjects receiving ½ cup pinto beans and 40 consuming a control soup for 12 weeks. Changes in the frequency of perceived flatulence, stool characteristics, and bloating were the primary outcome measures. Chi-square distributions were examined for the presence or absence of symptoms and demographic characteristics to determine differences by gender, age, body mass index (BMI), and bean type. Results Less than 50% reported increased flatulence from eating pinto or baked beans during the first week of each trial, but only 19% had a flatulence increase with black-eyed peas. A small percentage (3-11%) reported increased flatulence across the three studies even on control diets without flatulence-producing components. Conclusions People's concerns about excessive flatulence from eating beans may be exaggerated. Public health nutritionists should address the potential for gastrointestinal discomfort when increasing fiber intake from beans with clients. It is important to recognize there is individual variation in response to different bean types.", "title": "Perceptions of flatulence from bean consumption among adults in 3 feeding studies" }, { "docid": "MED-4936", "text": "Food and nutrition professionals question whether supplement-sourced nutrients appear to be equivalent to those derived from natural food sources. We compared the nutritional availability of docosahexaenoic acid (DHA) from algal-oil capsules to that from assayed cooked salmon in 32 healthy men and women, ages 20 to 65 years, in a randomized, open-label, parallel-group study. In this 2-week study comparing 600 mg DHA/day from algal-oil capsules to that from assayed portions of cooked salmon, mean change from baseline in plasma phospholipids and erythrocyte DHA levels was analyzed and DHA levels were compared by Student's t tests. In post-hoc analyses to determine bioequivalence, least-squares mean ratios of percent change from baseline in plasma phospholipid and erythrocyte DHA levels were compared. DHA levels increased by approximately 80% in plasma phospholipids and by approximately 25% in erythrocytes in both groups. Changes in DHA levels in plasma phospholipids and erythrocytes were similar between groups. As measured by delivery of DHA to both plasma and erythrocytes, fish and algal-oil capsules were equivalent. Both regimens were generally well-tolerated. These results indicate that algal-oil DHA capsules and cooked salmon appear to be bioequivalent in providing DHA to plasma and red blood cells and, accordingly, that algal-oil DHA capsules represent a safe and convenient source of non-fish-derived DHA.", "title": "Algal-oil capsules and cooked salmon: nutritionally equivalent sources of docosahexaenoic acid." }, { "docid": "MED-4165", "text": "Ergothioneine is a native membrane-impermeable thiol compound that is specifically accumulated in cells via the organic cation transporter OCTN1. In humans, OCTN1 and ergothioneine have been implicated in the etiopathogenesis of autoimmune disorders. However, available evidence about dietary sources and the functional role of ergothioneine in human physiology is scarce. Here, we analyzed the ergothioneine content in common foods using liquid chromatography tandem-mass spectrometry. Additionally, we assessed the protective potency of ergothioneine against various oxidative stressors in OCTN1-expressing cells in comparison with the main intracellular thiol antioxidant glutathione by evaluating cell viability with the MTT reduction assay. Only some food contained ergothioneine with highest concentrations detected in specialty mushrooms, kidney, liver, black and red beans, and oat bran. Ergothioneine exhibited cell protection only against copper(II)-induced toxicity but was far less potent than glutathione, indicting that ergothioneine is not involved in the intracellular antioxidant thiol defense system.", "title": "Dietary sources and antioxidant effects of ergothioneine." }, { "docid": "MED-3153", "text": "This was a placebo-controlled, double-blind study designed to evaluate the effect of a commercially available dietary supplement on upper-respiratory tract symptoms (URTI) and mood state. Seventy-five marathon runners (35 men, 40 women) ranging in age from 18-53 years, mean age: 36 ± 9, self-administered placebo, 250 mg or 500 mg of BETA 1,3/1,6 GLUCAN (commercial name Wellmune WGP®) daily during the 4 week post-marathon trial period following the 2007 Carlsbad Marathon. Subjects filled out the profile of mood state (POMS) assessment and a questionnaire style health log measuring health status and URTI symptoms after 2- and 4-week treatment administrations. During the course of the 4-week study, subjects in the treatment groups (250 mg and 500 mg BETA-GLUCAN per day) reported significantly fewer URTI symptoms, better overall health and decreased confusion, fatigue, tension, and anger, and increased vigor based on the POMS survey compared to placebo. BETA-GLUCAN may prevent URTI symptoms, and improve overall health and mood following a competitive marathon. Key points", "title": "Effect of BETA 1, 3/1, 6 GLUCAN on Upper Respiratory Tract Infection Symptoms and Mood State in Marathon Athletes" }, { "docid": "MED-4411", "text": "Chronic obstructive pulmonary disease (COPD) is characterised by increased oxidative stress. Dietary factors, such as ample consumption of foods rich in antioxidants, such as fruit and vegetables, might have beneficial effects in COPD patients. The association between dietary shift to foods rich in antioxidants and lung function in COPD was investigated in a 3-yr prospective study. A total of 120 COPD patients were randomised to follow either a diet based on increased consumption of fresh fruit and vegetables (intervention group (IG)) or a free diet (control group (CG)). The mean consumption of foods containing antioxidants was higher in the IG than in the CG throughout the study period (p<0.05). The relationship between consumption of foods rich in antioxidants and percentage predicted forced expiratory volume in 1 s was assessed using a general linear model for repeated measures; the two groups overall were different in time (p = 0.03), with the IG showing a better outcome. In investigating the effect of several confounders (sex, age, smoking status, comorbid conditions and exacerbation) of group response over time, nonsignificant interactions were found between confounders, group and time. These findings suggest that a dietary shift to higher-antioxidant food intake may be associated with improvement in lung function, and, in this respect, dietary interventions might be considered in COPD management.", "title": "Impact of dietary shift to higher-antioxidant foods in COPD: a randomised trial." }, { "docid": "MED-4448", "text": "Flavonoids have been hypothesized to reduce cancer risk. Previous epidemiological studies conducted to evaluate this hypothesis have not assessed all flavonoids, including classes that could contribute to intake among Americans, which would result in an underestimation of intake. This misclassification could mask variability among individuals, resulting in attenuated effect estimates for the association between flavonoids and cancer. To augment flavonoid and lignan intake estimates, we developed a database that can be used in conjunction with a food-frequency questionnaire (FFQ). Coupling information derived from the available literature with the U.S. Department of Agriculture databases, we estimated content of 6 flavonoid classes and lignans for 50 food group items. We combined these estimates with responses from a modified Block FFQ that was self-completed in 1996-1997 by a population-based sample of women without breast cancer on Long Island, New York (n = 1,500). Total flavonoid and lignan content of food items ranged from 0 to 129 mg/100 g, and the richest sources were tea, cherries, and grapefruit. Individual intake estimates, from highest to lowest, were flavan-3-ols, flavanones, flavonols, lignans, isoflavones, anthocyanidins, and flavones. Each class of flavonoids and lignans exhibited a wide range of intake levels. This database is useful to quantify flavonoid and lignan intake for other observational studies conducted in the United States that utilize the Block FFQ.", "title": "Construction of a flavonoid database for assessing intake in a population-based sample of women on Long Island, New York." }, { "docid": "MED-3688", "text": "OBJECTIVES: Standard therapies for antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) have limited efficacy. Probiotic prophylaxis is a promising alternative for reduction of AAD and CDAD incidence. METHODS: In this single-center, randomized, double-blind, placebo-controlled dose-ranging study, we randomized 255 adult inpatients to one of three groups: two probiotic capsules per day (Pro-2, n=86), one probiotic capsule and one placebo capsule per day (Pro-1, n=85), or two placebo capsules per day (n=84). Each probiotic capsule contained 50 billion c.f.u. of live organisms (Lactobacillus acidophilus CL1285 +Lactobacillus casei LBC80R Bio-K+ CL1285). Probiotic prophylaxis began within 36 h of initial antibiotic administration, continued for 5 days after the last antibiotic dose, and patients were followed for an additional 21 days. RESULTS: Pro-2 (15.5%) had a lower AAD incidence vs. Pro-1 (28.2%). Each probiotic group had a lower AAD incidence vs. placebo (44.1%). In patients who acquired AAD, Pro-2 (2.8 days) and Pro-1 (4.1 days) had shorter symptom duration vs. placebo (6.4 days). Similarly, Pro-2 (1.2%) had a lower CDAD incidence vs. Pro-1 (9.4%). Each treatment group had a lower CDAD incidence vs. placebo (23.8%). Gastrointestinal symptoms were less common in the treatment groups vs. placebo and in Pro-2 vs. Pro-1. CONCLUSIONS: The proprietary probiotic blend used in this study was well tolerated and effective for reducing risk of AAD and, in particular, CDAD in hospitalized patients on antibiotics. A dose-ranging effect was shown with 100 billion c.f.u., yielding superior outcomes and fewer gastrointestinal events compared to 50 billion c.f.u. (ClinicalTrials.gov number NCT00958308).", "title": "Dose-response efficacy of a proprietary probiotic formula of Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R for antibiotic-associa..." }, { "docid": "MED-1247", "text": "Background: This study is aimed at determining the efficacy of Mentha spicata (M. spicata) and Mentha × piperita (M. × piperita) in preventing chemotherapy-induced nausea and vomiting (CINV). Methods: This was a randomised, double-blind clinical trial study. Prior to the study, patients were randomly assigned into four groups to receive M. spicata or M. × piperita. Statistical analysis included the χ2 test, relative risk, and Student’s t-test. Fifty courses were analysed for each group that met our eligibility criteria. The treatment and placebo groups applied essential oils of M. spicata, M. × piperita, or a placebo, while the control group continued with their previous antiemetic regimen. Patients or guardians recorded the number of emetic events, the intensity of nausea over 20 h of chemotherapy, as well as any possible adverse effects that occurred during this time. Results: There was a significant reduction in the intensity and number of emetic events in the first 24 h with M. spicata and M. × piperita in both treatment groups (p < 0.05) when compared with the control and no adverse effects were reported. The cost of treatment was also reduced when essential oils were used. Conclusion: M. spicata or M. × piperita essential oils are safe and effective for antiemetic treatment in patients, as well as being cost effective.", "title": "Antiemetic activity of volatile oil from Mentha spicata and Mentha × piperita in chemotherapy-induced nausea and vomiting" }, { "docid": "MED-2583", "text": "Inositol hexaphosphate (IP(6)), a naturally polyphosphorylated carbohydrate, has been reported to have significant in vivo and in vitro anticancer activity against numerous tumours, such as colon, prostate, breast, liver and rhabdomyosarcomas. To confirm this activity in haematological malignancies and to characterize some of the mechanisms of IP(6) action, we analysed its effects on human leukaemic cell lines and fresh chronic myelogenous leukaemia (CML) progenitor cells using a combined cellular and molecular approach. IP(6) had a dose-dependent cytotoxic effect on all of the evaluated cell lines, with accumulation in the G2M phase in two out of five cell lines tested. At the molecular level, cDNA microarray analysis after IP(6) exposure showed an extensive downmodulation of genes involved in transcription and cell cycle regulation and a coherent upregulation of cell cycle inhibitors. Furthermore, IP(6) treatment of fresh leukaemic samples of bone marrow CD34+ CML progenitor cells significantly inhibited granulocyte-macrophage colony-forming unit (CFU-GM) formation (P = 0.0062) in comparison to normal bone marrow specimens, which were not affected. No differentiating effect on HL60 cells was observed. Taken together, our results confirm the antiproliferative activity of IP(6) and suggest that it may have a specific antitumour effect also in chronic myeloid leukaemias, via active gene modulation.", "title": "Effect of inositol hexaphosphate (IP(6)) on human normal and leukaemic haematopoietic cells." }, { "docid": "MED-1740", "text": "To assess human health risk from environmental chemicals, we have studied the effect on cell cycle regulation of the widely used glyphosate-containing pesticide Roundup. As a model system we have used sea urchin embryonic first divisions following fertilization, which are appropriate for the study of universal cell cycle regulation without interference with transcription. We show that 0.8% Roundup (containing 8 mM glyphosate) induces a delay in the kinetic of the first cell cleavage of sea urchin embryos. The delay is dependent on the concentration of Roundup. The delay in the cell cycle could be induced using increasing glyphosate concentrations (1-10 mM) in the presence of a subthreshold concentration of Roundup 0.2%, while glyphosate alone was ineffective, thus indicating synergy between glyphosate and Roundup formulation products. The effect of Roundup was not lethal and involved a delay in entry into M-phase of the cell cycle, as judged cytologically. Since CDK1/cyclin B regulates universally the M-phase of the cell cycle, we analyzed CDK1/cyclin B activation during the first division of early development. Roundup delayed the activation of CDK1/cyclin B in vivo. Roundup inhibited also the global protein synthetic rate without preventing the accumulation of cyclin B. In summary, Roundup affects cell cycle regulation by delaying activation of the CDK1/cyclin B complex, by synergic effect of glyphosate and formulation products. Considering the universality among species of the CDK1/cyclin B regulator, our results question the safety of glyphosate and Roundup on human health.", "title": "Pesticide Roundup provokes cell division dysfunction at the level of CDK1/cyclin B activation." }, { "docid": "MED-1405", "text": "Background Polyphenols may lower the risk of cardiovascular disease (CVD) and other chronic diseases due to their antioxidant and anti-inflammatory properties, as well as their beneficial effects on blood pressure, lipids and insulin resistance. However, no previous epidemiological studies have evaluated the relationship between the intake of total polyphenols intake and polyphenol subclasses with overall mortality. Our aim was to evaluate whether polyphenol intake is associated with all-cause mortality in subjects at high cardiovascular risk. Methods We used data from the PREDIMED study, a 7,447-participant, parallel-group, randomized, multicenter, controlled five-year feeding trial aimed at assessing the effects of the Mediterranean Diet in primary prevention of cardiovascular disease. Polyphenol intake was calculated by matching food consumption data from repeated food frequency questionnaires (FFQ) with the Phenol-Explorer database on the polyphenol content of each reported food. Hazard ratios (HR) and 95% confidence intervals (CI) between polyphenol intake and mortality were estimated using time-dependent Cox proportional hazard models. Results Over an average of 4.8 years of follow-up, we observed 327 deaths. After multivariate adjustment, we found a 37% relative reduction in all-cause mortality comparing the highest versus the lowest quintiles of total polyphenol intake (hazard ratio (HR) = 0.63; 95% CI 0.41 to 0.97; P for trend = 0.12). Among the polyphenol subclasses, stilbenes and lignans were significantly associated with reduced all-cause mortality (HR =0.48; 95% CI 0.25 to 0.91; P for trend = 0.04 and HR = 0.60; 95% CI 0.37 to 0.97; P for trend = 0.03, respectively), with no significant associations apparent in the rest (flavonoids or phenolic acids). Conclusions Among high-risk subjects, those who reported a high polyphenol intake, especially of stilbenes and lignans, showed a reduced risk of overall mortality compared to those with lower intakes. These results may be useful to determine optimal polyphenol intake or specific food sources of polyphenols that may reduce the risk of all-cause mortality. Clinical trial registration ISRCTN35739639.", "title": "Polyphenol intake and mortality risk: a re-analysis of the PREDIMED trial" }, { "docid": "MED-1638", "text": "OBJECTIVE: Migratory capacity of endothelial progenitor cells (EPCs) and mature endothelial cells (ECs) is a key prerequisite for endothelial repair after denuding injury or endothelial damage. METHODS AND RESULTS: We demonstrate that caffeine in physiologically relevant concentrations (50 to 100 micromol/L) induces migration of human EPCs as well as mature ECs. In patients with coronary artery disease (CAD), caffeinated coffee increased caffeine serum concentration from 2 micromol/L to 23 micromol/L, coinciding with a significant increase in migratory activity of patient-derived EPCs. Decaffeinated coffee neither affected caffeine serum levels nor migratory capacity of EPCs. Treatment with caffeine for 7 to 10 days in a mouse-model improved endothelial repair after denudation of the carotid artery. The enhancement of reendothelialization by caffeine was significantly reduced in AMPK knockout mice compared to wild-type animals. Transplantation of wild-type and AMPK(-/-) bone marrow into wild-type mice revealed no difference in caffeine challenged reendothelialization. ECs which were depleted of mitochondrial DNA did not migrate when challenged with caffeine, suggesting a potential role for mitochondria in caffeine-dependent migration. CONCLUSIONS: These results provide evidence that caffeine enhances endothelial cell migration and reendothelialization in part through an AMPK-dependent mechanism, suggesting a beneficial role for caffeine in endothelial repair.", "title": "Caffeine enhances endothelial repair by an AMPK-dependent mechanism." }, { "docid": "MED-3624", "text": "OBJECTIVE: In light of the rapidly increasing frequency of pediatric CT examinations, the purpose of our study was to assess the lifetime cancer mortality risks attributable to radiation from pediatric CT. MATERIALS AND METHODS: Organ doses as a function of age-at-diagnosis were estimated for common CT examinations, and estimated attributable lifetime cancer mortality risks (per unit dose) for different organ sites were applied. Standard models that assume a linear extrapolation of risks from intermediate to low doses were applied. On the basis of current standard practice, the same exposures (milliampere-seconds) were assumed, independent of age. RESULTS: The larger doses and increased lifetime radiation risks in children produce a sharp increase, relative to adults, in estimated risk from CT. Estimated lifetime cancer mortality risks attributable to the radiation exposure from a CT in a 1-year-old are 0.18% (abdominal) and 0.07% (head)-an order of magnitude higher than for adults-although those figures still represent a small increase in cancer mortality over the natrual background rate. In the United States, of approximately 600,000 abdominal and head CT examinations annually performed in children under the age of 15 years, a rough estimate is that 500 of these individuals might ultimately die from cancer attributable to the CT radiation. CONCLUSION: The best available risk estimates suggest that pediatric CT will result in significantly increased lifetime radiation risk over adult CT, both because of the increased dose per milliampere-second, and the increased lifetime risk per unit dose. Lower milliampere-second settings can be used for children without significant loss of information. Although the risk-benefit balance is still strongly tilted toward benefit, because the frequency of pediatric CT examinations is rapidly increasing, estimates that quantitative lifetime radiation risks for children undergoing CT are not negligible may stimulate more active reduction of CT exposure settings in pediatric patients.", "title": "Estimated risks of radiation-induced fatal cancer from pediatric CT." }, { "docid": "MED-1869", "text": "Observational and clinical studies suggest that high protein intake, particularly protein from plant sources, might reduce blood pressure (BP). To examine the association of dietary protein with BP, we analysed data from PREMIER, an 18-month clinical trial (n=810) that examined the effects of two multi-component lifestyle modifications on BP. We examined the association of protein intake with BP, and in particular the independent relationship of plant and animal protein with BP. Multivariable linear regression analyses were performed with both cross-sectional and longitudinal data. Dietary plant protein was inversely associated with both systolic and diastolic BP in cross-sectional analyses at the 6-month follow-up (P=0.0045 and 0.0096, respectively). Fruit and vegetable intake was also inversely associated with both systolic and diastolic BP cross-sectionally at 6 months (P=0.0003 and 0.0157, respectively). In longitudinal analyses, a high intake of plant protein at 6 months was marginally associated with a reduction of both systolic and diastolic BP from baseline to 6 months only (P=0.0797 and 0.0866, respectively), independent of change in body weight and waist circumference. Furthermore, increased intake of plant protein, and fruits and vegetables was significantly associated with a lower risk of hypertension at 6 but not at 18 months. Results of this study indicate that plant protein had a beneficial effect on BP and was associated with a lower risk of hypertension at 6 months. Our data, in conjunction with other research, suggest that an increased intake of plant protein may be useful as a means to prevent and treat hypertension.", "title": "The relationship between dietary protein intake and blood pressure: results from the PREMIER study." }, { "docid": "MED-2042", "text": "An ever-growing volume of peer-reviewed publications speaks to the recent and rapid growth in both scope and understanding of exercise immunology. Indeed, more than 95% of all peer-reviewed publications in exercise immunology (currently >2, 200 publications using search terms \"exercise\" and \"immune\") have been published since the formation of the International Society of Exercise and Immunology (ISEI) in 1989 (ISI Web of Knowledge). We recognise the epidemiological distinction between the generic term \"physical activity\" and the specific category of \"exercise\", which implies activity for a specific purpose such as improvement of physical condition or competition. Extreme physical activity of any type may have implications for the immune system. However, because of its emotive component, exercise is likely to have a larger effect, and to date the great majority of our knowledge on this subject comes from exercise studies.", "title": "Position statement. Part one: Immune function and exercise." }, { "docid": "MED-972", "text": "A study is reported in which the prevalence of symptomless diverticular disease of the colon is related to the consumption of dietary fibre in vegetarians and non-vegetarians. Vegetarians had a significantly higher mean fibre intake (41.5 g/day) than non-vegetarians (21.4 g/day). Diverticular disease was commoner in non-vegetarians (33%) than in vegetarians (12%). Comparison of subjects with and without diverticular disease in the vegetarian and non-vegetarian groups provided some further evidence that a low intake of cereal fibre is associated with the presence of diverticular disease.", "title": "Symptomless diverticular disease and intake of dietary fibre." }, { "docid": "MED-1777", "text": "We systematically examined the evidence of declining sperm counts and the hypothesis that an increased exposure to environmental pollutants is responsible for such decline. Search engines, including PUBMED, MEDLINE, EMBASE, BIOSIS, and Cochrane library, were used to identify epidemiologic studies published from 1985 to 2013. We concluded that there is no enough evidence to confirm a worldwide decline in sperm counts. Also, there seems to be no scientific truth of a causative role for endocrine disruptors in the temporal decline of sperm production. Such assumptions are based on few meta-analyses and retrospective studies, while other well-conducted researches could not confirm these findings. We acknowledge that difficult-to-control confounding factors in the highly variable nature of semen, selection criteria, and comparability of populations from different time periods in secular-trend studies, the quality of laboratory methods for counting sperm, and apparently geographic variations in semen quality are the main issues that complicate the interpretation of the available evidence. Owing to the importance of this subject and the uncertainties still prevailing, there is a need not only for continuing monitoring of semen quality, reproductive hormones, and xenobiotics, but also for a better definition of fecundity.", "title": "Shedding Light on the Controversy Surrounding the Temporal Decline in Human Sperm Counts: A Systematic Review" }, { "docid": "MED-2751", "text": "Recent data on fishmeal and fish-oil supply are presented identifying key producer countries and raw material sources and distinguishing between whole fish and by-products. The conversion of these raw materials into marine ingredients is discussed and global volumes presented. This is followed by a summary of the main countries using these marine ingredients over recent years. Uses of fishmeal and fish-oil by market segment are then presented. From this, a global mass balance of inputs and outputs is derived which allows the calculation of the input-to-output ratios (fish in:fish out; FIFO) for the main aquaculture production types to be made. Current areas of focus by the industry include the need to demonstrate sustainable practice, more strategic use of marine ingredients, greater use of fishery and land-animal by-products as well as vegetable substitutes, and novel sources of essential omega-3 fats, notably the long-chain polyunsaturated fatty acids, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Implications are drawn for future supply prospects of fishmeal and fish-oil and their future role in aquaculture, agriculture and human health. © 2013 The Fisheries Society of the British Isles.", "title": "Global fishmeal and fish-oil supply: inputs, outputs and markets." } ]
188953
Usain Bolt is an athlete.
[ { "docid": "Usain_Bolt", "text": "Usain St Leo Bolt , OJ , CD ( -LSB- ˈjuːseɪn -RSB- born 21 August 1986 ) is a Jamaican sprinter . He is the first person to hold both the 100 metres and 200 metres world records since fully automatic time became mandatory . He also holds the world record as a part of the 4 × 100 metres relay . He is the reigning world and Olympic champion in these three events . Due to his unprecedented dominance and achievements in sprint competition , he is widely considered to be the greatest sprinter of all time . An eight-time Olympic gold medalist , Bolt won the 100 m , 200 m and 4 × 100 m relay at three consecutive Olympic Games , although he subsequently lost one of the gold medals ( as well as the world record set therein ) nine years after the fact due to teammate Nesta Carter 's disqualification for doping offences . He gained worldwide popularity for his double sprint victory at the 2008 Beijing Olympics in world record times . Bolt is the only sprinter to win Olympic 100 m and 200 m titles at three consecutive olympics ( 2008 , 2012 and 2016 ) , a feat referred to as the `` triple double . '' An eleven-time World Champion , he won consecutive World Championship 100 m , 200 m and 4 × 100 metres relay gold medals from 2009 to 2015 , with the exception of a 100 m false start in 2011 . He is the most successful athlete of the World Championships and was the first athlete to win three titles in both the 100 m and 200 m at the competition . Bolt improved upon his first 100 m world record of 9.69 with 9.58 seconds in 2009 -- the biggest improvement since the start of electronic timing . He has twice broken the 200 metres world record , setting 19.30 in 2008 and 19.19 in 2009 . He has helped Jamaica to three 4 × 100 metres relay world records , with the current record being 36.84 seconds set in 2012 . Bolt 's most successful event is the 200 m , with three Olympic and four World titles . The 2008 Olympics was his international debut over 100 m ; he had earlier won numerous 200 m medals ( including 2007 World Championship silver ) and holds the world under-20 and world under-18 records for the event . His achievements as a sprinter have earned him the media nickname `` Lightning Bolt '' , and his awards include the IAAF World Athlete of the Year , Track & Field Athlete of the Year , and Laureus World Sportsman of the Year ( four times ) . Bolt has stated that he intends to retire from athletics after the 2017 World Championships .", "title": "" } ]
[ { "docid": "Usain_Bolt_Sports_Complex", "text": "Usain Bolt Sports Complex is a sports venue at the Cavehill campus of the University of the West Indies in Barbados consisting of an IAAF certified track and FIFA certified football field . The complex comprises the Ryan Brathwaite track , the Obadele Thompson stand and the Kirani James stand , all prominent Caribbean athletes . The facility is currently under construction nearing completion . The naming of the sports complex was criticized by some Barbadians for being named after a Jamaican athlete , Usain Bolt instead of a Barbadian athlete . University principal , Sir Hilary Beckles said that the naming did not intend to marginalize Barbadian sportspeople and the decision was intended to be a move that meant to `` celebrate all West Indians '' . He also added that the university is not solely Barbadian thus `` a debate over Barbadian , Jamaican or Trinidadian '' should not have been raised .", "title": "" }, { "docid": "Athletics_at_the_2008_Summer_Olympics_–_Men's_100_metres", "text": "The men 's 100 metres sprint event at the 2008 Olympic Games took place on 15 and 16 August at the Beijing National Stadium . The final was won by Jamaican Usain Bolt in a world record time of 9.69 seconds . Holding a considerable lead 70 metres into the race , Bolt opened his arms in celebration before slapping his chest . Kriss Akabusi criticized Usain Bolt 's chest slapping before the finish line as showboating , shortly before Bolt captured the gold in the 100 meter sprint , noting that the actions cost Bolt an even faster record time . IOC president Jacques Rogge also condemned the Jamaican 's actions as disrespectful . Bolt denied that this was the purpose of his mid-race celebration by saying `` I was n't bragging . When I saw I was n't covered , I was just happy . ''", "title": "" }, { "docid": "100_metres_at_the_World_Championships_in_Athletics", "text": "The 100 metres at the World Championships in Athletics has been contested by both men and women since the inaugural edition in 1983 . It is the second most prestigious 100 m title after the 100 metres at the Olympics . The competition format typically has two or three qualifying rounds leading to a final between eight athletes . Since 2011 a preliminary round has been held , where athletes who have not achieved the qualifying standard time compete to enter the first round proper . The championship records for the event are 9.58 seconds for men , set by Usain Bolt in 2009 , and 10.70 seconds for women , set by Marion Jones in 1999 . The men 's world record has been broken or equalled at the competition three times : by Carl Lewis in 1987 and 1991 , and by Usain Bolt in 2009 . Ben Johnson ran faster than Lewis in 1987 , but his record was subsequently annulled due to doping . Lewis 's mark , which equalled the standing record at the time , was never officially ratified by the IAAF as a world record . The women 's world record has never been beaten at the championships . Carl Lewis , Maurice Greene and Usain Bolt are the most successful male athletes of the event , having each won three titles . Shelly-Ann Fraser-Pryce is the most successful female athlete of the event as the only woman to win three titles . Merlene Ottey and Carmelita Jeter are the only athletes to have claimed four medals in the history of the World Championships event . The United States is the most successful nation in the discipline , having won fifteen gold medals . Jamaica are a clear second with six gold medals . East Germany , with two , is the only other nation to have won multiple titles .", "title": "" }, { "docid": "Bolt_(surname)", "text": "Bolt is a surname . Notable people with the surname include : Andrew Bolt ( b. 1959 ) , Australian newspaper columnist Bobby Bolt ( b. 1987 ) , Canadian athlete in hockey Bruce Bolt ( 1930 -- 2005 ) , American professor Carol Bolt ( 1941 -- 2000 ) , Canadian author Chris Bolt ( fl . 1970s -- present ) , British economist David Bolt ( fl . 2000s -- present ) , British author George Bolt ( 1893 -- 1963 ) , New Zealand aviator George T. Bolt ( 1900 -- 1971 ) , New Zealand government figure Herbert Bolt ( 1893 -- 1916 ) , Australian athlete in rugby , and WWI soldier Jan Bolt ( 1876 -- 1967 ) , Dutch athlete in gymnastics Jeremy Bolt ( fl . 1990s -- present ) , British film producer John F. Bolt ( 1921 -- 2004 ) , American aviator Josh Bolt ( fl . 2000s -- present ) , British actor Klaas Bolt ( 1927 -- 1990 ) , Dutch musician Michael Bolt ( fl . 1980s -- 1990s ) , Australian athlete in rugby Ranjit Bolt ( b. 1969 ) , British author and translator Rezin A. De Bolt ( 1828 -- 1891 ) , American politician Richard Bolt ( 1911 -- 2002 ) , American physics professor Richard Bolt ( RNZAF officer ) ( fl . 1940s -- 1980 ) , New Zealand air marshal Robert Bolt ( 1924 -- 1995 ) , British playwright Thomas Bolt ( b. 1959 ) , American poet and artist Tommy Bolt ( 1916 -- 2008 ) , American golfer Usain Bolt ( b. 1986 ) , Jamaican athlete in track Wayne Bolt ( fl . 1980s -- present ) , American athlete and football coach", "title": "" }, { "docid": "Nitro_Athletics", "text": "Nitro Athletics is an annual track and field series featuring multi-day meetings between teams of twelve athletes . The teams contain both men and women and also para-athletics competitors . There are both national and international teams . The events contested are a mix of Olympic-standard events and variations on common athletics events . The series was created by former athlete John Steffensen and Athletics Australia ( AA ) . The president of the AA , Mark Arbib , stated his interest in creating a novel competition was the result of his seeing dwindling interest in traditional one-day track and field meetings , citing in particular low crowds he saw at the 2015 Sydney Track Classic . The sport 's leading star , Usain Bolt , was recruited as a co-investor and performer of the series . Despite breaking from the standard setup of athletics competitions , the series was supported by Sebastian Coe , head of the International Association of Athletics Federations . The inaugural event was hosted at Lakeside Stadium in Melbourne on three separate days ( 4 , 9 , 11 February ) . The six teams to feature were New Zealand , Australia , England , China , Japan and the Bolt All-Stars ( a mix of international athletes ) . The events attracted near-capacity crowds of the 8,000 seat arena and was broadcast on live television across many of the competing nations . Generally media gave a positive response to the event , with the Herald Sun describing it as a `` raging success '' . The reaction from specialist media was more mixed , however , with Athletics Weekly saying the ideas `` have been tried before . Nitro Athletics has merely thrown them all into one meeting '' . The 2018 and 2019 editions of the competition are planned to take place in Melbourne and Usain Bolt is again set to compete .", "title": "" }, { "docid": "2015_World_Championships_in_Athletics_–_Men's_200_metres", "text": "The men 's 200 metres at the 2015 World Championships in Athletics was held at the Beijing National Stadium on 25 , 26 and 27 August . Coming into these championships , defending champion , world record holder , Olympic champion Usain Bolt had given no indication of being prepared to match the heights of his previous championships . His season best was only 20.13 , but he was Usain Bolt , the star of the sport since 2008 . Meanwhile , Justin Gatlin came in as the world leader with a personal best 19.57 to win the American Championships , backing up the 19.68 he had run at the Prefontaine Classic a month earlier . Bolt indicated he thought the 200 would be the easier of his championships to defend . In the heats , Bolt was back in the pack with a 20.28 , jogging the last 50 metres while Ramil Guliyev was setting his Turkish national record at 20.01 . Gatlin led the semis with 19.87 , Bolt ran a season best 19.95 . Behind them were top qualifiers Alonso Edward and Anaso Jobodwana barely over 20 seconds . The final started with the 100 meter specialist Gatlin blasting out of the blocks , but Bolt to his far outside was not far behind him relative to the staggered start . It was clearly a two-man race . Coming off the turn , Bolt may have been slightly ahead but it was almost even , with Femi Ogunode next on the far inside . Behind them Jobodwana separated from the pack while Ogunode disappeared . Edward , the 2009 silver medalist and Jobodwana recorded the same finishing time ( a national record for Jobodwana ) but Jobodwana won the bronze medal by 2 thousandths of a second . Bolt 's 19.55 winning time was the next slowest championship winning time of his career . Still only three other men have ever run faster . This was Bolt 's fourth straight World Championship at 200 metres .", "title": "" }, { "docid": "200_metres", "text": "The 200 metres ( also spelled 200 meters ) is a sprint running event . On an outdoor 400 m track , the race begins on the curve and ends on the home straight , so a combination of techniques are needed to successfully run the race . A slightly shorter race , called the stadion and run on a straight track , was the first recorded event at the ancient Olympic Games . The 200 m places more emphasis on speed endurance than shorter sprint distances as athletes rely on different energy systems during the longer sprint . In the United States and elsewhere , athletes previously ran the 220-yard dash ( 201.168 m ) instead of the 200 m ( 218.723 yards ) , though the distance is now obsolete . The standard adjustment used for the conversion from times recorded over 220 yards to 200 m times is to subtract 0.1 seconds , but other conversion methods exist . Another obsolete version of this race is the 200 metres straight , which was run on tracks that contained such a straight . Initially , when the International Amateur Athletic Association ( now known as the International Association of Athletics Federations ) started to ratify world records in 1912 , only records set on a straight track were eligible for consideration . In 1951 , the IAAF started to recognise records set on a curved track . In 1976 , the straight record was discarded . The race attracts runners from other events , primarily the 100 metres , wishing to double up and claim both titles . This feat has been achieved by men eleven times at the Olympic Games : by Archie Hahn in 1904 , Ralph Craig in 1912 , Percy Williams in 1928 , Eddie Tolan in 1932 , Jesse Owens in 1936 , Bobby Morrow in 1956 , Valeriy Borzov in 1972 , Carl Lewis in 1984 , and most recently by Jamaica 's Usain Bolt in 2008 , 2012 , and 2016 . The double has been accomplished by women seven times : by Fanny Blankers-Koen in 1948 , Marjorie Jackson in 1952 , Betty Cuthbert in 1956 , Wilma Rudolph in 1960 , Renate Stecher in 1972 and Florence Griffith-Joyner in 1988 . Marion Jones finished first in both races in 2000 but was later disqualified and stripped of her medals after admitting to taking performance-enhancing drugs . An Olympic double of 200 m and 400 m was first achieved by Valerie Brisco-Hooks in 1984 , and later by Michael Johnson from the United States and Marie-José Pérec of France both in 1996 . Usain Bolt is the only man to repeat as Olympic champion , Bärbel Wöckel ( née Eckert ) and Veronica Campbell-Brown are the two women who have repeated as Olympic champion . The men 's world record holder is Usain Bolt of Jamaica , who ran 19.19 s at the 2009 World Championships . The women 's world record holder is Florence Griffith-Joyner of the United States , who ran 21.34 s at the 1988 Summer Olympics . The reigning Olympic champions are Usain Bolt and Elaine Thompson ( Jamaica ) . The reigning World Champions are Bolt and Dafne Schippers ( the Netherlands ) . Races run with an aiding wind measured over 2.0 metres per second are not acceptable for record purposes .", "title": "" }, { "docid": "200_metres_at_the_World_Championships_in_Athletics", "text": "The 200 metres at the World Championships in Athletics has been contested by both men and women since the inaugural edition in 1983 . It is the second most prestigious title in the discipline after the 200 metres at the Olympics . The competition format typically has two or three qualifying rounds leading to a final between eight athletes . The championship records for the event are 19.19 seconds for men , set by Usain Bolt in 2009 , and 21.63 seconds for women , set by Dafne Schippers in 2015 . The men 's world record has been broken at the competition on one occasion , and Bolt 's championship record set in 2009 remains the world record as of 2015 . The women 's world record has never been broken at the competition . Usain Bolt is the most successful athlete of the event , having won four successive titles from 2009 to 2015 , and also a silver in 2007 . Allyson Felix is the most successful woman , having won three straight titles ( 2005 to 2009 ) . Two-time champion Merlene Ottey has won more medals in the 200 m than any other athlete , reaching the podium six times in a period stretching from 1983 to 1997 . Calvin Smith and Michael Johnson are the only others to have won two world titles over the distance . The United States is the most successful nation in the discipline , with twelve gold medals among a total of 31 . Jamaica is the next most successful with seventeen medals and seven titles . East Germany , with two golds , is the only other nation to have provided multiple gold medallists .", "title": "" }, { "docid": "2009_World_Championships_in_Athletics_–_Men's_200_metres", "text": "The men 's 200 metres at the 2009 World Championships in Athletics was held at the Olympic Stadium , Berlin , Germany on August 18 and August 20 . The race favourites were Tyson Gay and Usain Bolt . Gay entered the competition as the reigning world champion , championship record holder , and 200 m world leader with 19.58 seconds . Bolt , the current Olympic champion and world record holder , had a season 's best of 19.59 seconds . The last time the two athletes raced was at the 2007 World Championships in Osaka , where Gay beat Bolt by a margin of 0.15 seconds . Osaka bronze medallist Wallace Spearmon was the only other athlete to run under twenty seconds that season and former Olympic champion Shawn Crawford was also competing . Up-and-coming athletes Alonso Edward , Steve Mullings and Ramil Guliyev were among the season 's fastest sprinters prior to the championships . After hurting his groin during his American record run in the 100 metres two days earlier , Gay withdrew from the race , effectively rescinding his second world title . The withdrawal of Dwain Chambers , Churandy Martina and Jaysuma Saidy Ndure also reduced the quality of the field . There were no surprise eliminations in the heats , where Crawford , Mullings , Robert Hering , and Martial Mbandjock were the fastest qualifiers , and Mullings had the fastest time of the quarter-finals round , with all the favourite athletes progressing . On the second day of competition , German number one Hering was eliminated . Bolt and Spearmon were the two semi-final winners , while the third-fastest , 19-year-old Alonso Edward , demonstrated medal winning form . In the final race , Usain Bolt , the clear favourite , had another world record-breaking run following his 9.58 second record in the 100 metres four days earlier . After having the fastest reaction time of the race , Bolt came out of the bend in first place and extended his lead further in the home straight , beating his previous mark of 19.30 seconds set at the Olympics by 0.11 seconds to take the gold medal and Championship record . Crawford , second fastest at the bend , was overtaken by Edward and Spearmon and eventually finished fourth . Edward vastly improved his previous best to set a South American record of 19.81 , while Spearmon was third with 19.85 seconds . Although the race between Gay and Bolt had not materialised , Bolt 's world record of 19.19 seconds was a highlight of the championships . The overall quality of the event was also high : Edward had improved from 20.62 to 19.81 seconds over the course of one year . Also , with Crawford running 19.89 seconds , it was the first ever 200 m race to see four athletes run under 19.9 seconds . Bolt 's winning margin of 0.62 seconds over second-placed Edward was the biggest in World Championship history . He received a $ 100,000 bonus for his performance , which was 0.13 seconds faster than Michael Johnson 's former world record , a mark that had been regarded as one of the best records in the history of athletics .", "title": "" }, { "docid": "Men's_100_metres_world_record_progression", "text": "The first record in the 100 metres for men ( athletics ) was recognised by the International Amateur Athletics Federation , now known as the International Association of Athletics Federations , in 1912 . The record now is 9.58 seconds which was run by Usain Bolt . , the IAAF had ratified 67 records in the event , not including rescinded records .", "title": "" }, { "docid": "Athletics_at_the_2012_Summer_Olympics_–_Men's_100_metres", "text": "The men 's 100 metres competition at the 2012 Summer Olympics in London , United Kingdom was held at the Olympic Stadium on 4 -- 5 August 2012 . The competition comprised four rounds : a preliminary round for entrants without the minimum qualifying standard , a heats round , followed by three semi-finals of eight athletes each , which then reduced to eight athletes for the final . Leading up to this Olympics , defending champion Usain Bolt was the star of the sport having set world records in winning the 100 metres and 200 metres in the previous Olympics , and 2 more world records in winning the 100m and 200m at the 2009 world championships . In the 2011 world championships , the 100 metres was won by Yohan Blake after a false start by Bolt . Later in the season , Blake ran a new 200 metres personal best only .07 behind Bolt 's world record . At the 2012 Jamaican Olympic Trials , Blake beat Bolt in both events . In the final , Bolt , started slow out of the blocks and was behind Blake and Gatlin , but accelerated with 50 meters to go , to win the gold medal and was around 5 meters ahead of the competition at the finish line . Bolt set a new Olympic record ( beating his own record set at the 2008 Olympic Games ) of 9.64 seconds . Blake edged past Gatlin , who in turn held off a closing Gay at the finish line . Usain Bolt was the second athlete after Carl Lewis ( 1984 , 1988 ) to retain the men 's 100m championship . His winning time was the second fastest time ever behind his own world record . Yohan Blake finished second in 9.75 seconds . Blake 's time was the fastest ever not to win a gold medal . Former world record holder and 2004 Olympic champion Justin Gatlin won the bronze medal in 9.79 seconds . The race set a number of records , including : the first time that the top 3 finished under 9.80 seconds ; the first time that the top 5 finished in under 9.90 seconds ; the first time that the four fastest men in 100m history all competed ; and 7 of the 8 men ran in under 10 seconds , with only Asafa Powell finished in ( 11.99 ) after an injury 60 meters into the race . Apart from Powell , each runner 's time was the fastest-ever for his respective placing . Blake , Gatlin , Gay , and Bailey all ran times that would have won at least silver in any previous Olympic final .", "title": "" }, { "docid": "2011_World_Championships_in_Athletics_–_Men's_100_metres", "text": "The men 's 100 metres at the 2011 World Championships in Athletics was held at the Daegu Stadium on August 27 and August 28 . The event was won by Yohan Blake of Jamaica , who became the youngest ever world champion in the 100 metres at . The highly favored defending champion and world record holder Usain Bolt was disqualified from the final for making a false start . Seventy four athletes started the competition , with 61 nations being represented ( 18 of them in the preliminaries only ) . It was the first global final to be held following the introduction of the no-false start rule . The four fastest 100-metre runners of 2011 were absent : Mike Rodgers ( 9.85 sec ) and Steve Mullings ( 9.80 sec ) had been banned for doping offences , while Tyson Gay ( 9.79 sec ) and 2011 world leader Asafa Powell ( 9.78 sec ) could not compete due to injuries . A preliminary round was introduced , where those entrants who had not obtained the 100 m qualification standard had to compete in a further qualifying stage before making it into the first round proper . This reduced the event to a three-round competition , as opposed to the traditional four , for qualified runners . Kim Kuk-Young ( the host nation 's sole entrant ) was disqualified in this round for a false start . Abdouraim Haroun was the fastest preliminary runner , Keiron Rogers broke the Anguillian record , while the slowest of the round was Sogelau Tuvalu , although his time of 15.66 seconds was a personal best for the shot put specialist . Usain Bolt had the fastest time of the first day ( 10.10 ) while his Jamaican compatriots won three of the other seven heats . Christophe Lemaitre , Kim Collins and Walter Dix were the other winners . In the first of the semi-finals , Yohan Blake became the first man under ten seconds . Bolt won the second race as the second-fastest qualifier ( 10.05 ) and Collins won the third to become the oldest ever 100 m finalist . Frenchman Jimmy Vicaut became only the second junior athlete ever to qualify for the 100 m final , after Darrel Brown in 2003 . The most prominent eliminations were Olympic silver medallist Richard Thompson ( the fastest entrant that year with 9.85 sec ) and 2004 Olympic champion Justin Gatlin . Dwain Chambers ( a 2009 finalist ) false-started , while sub-9 .9 sec runners Michael Frater and Ngonidzashe Makusha also failed to progress . In the 100 m final defending champion Usain Bolt caused an upset by false starting -- Yohan Blake had made a slight movement but Bolt was the one who left his blocks , being immediately disqualified . In his absence , it was quick starter Kim Collins who led for the first half of the race . However , Blake was strongest in the second half , taking the lead and sprinting to win the gold medal with a time of 9.92 seconds into the − 1.4 m/s headwind . Walter Dix made up ground on Collins , with the American edging into the silver medal position at the line by a margin of 0.01 seconds . At old , bronze medallist Collins became the oldest ever world medallist for the men 's 100 m.", "title": "" }, { "docid": "Great_CityGames_Manchester", "text": "The Manchester City Games is a major street athletics event held annually in Manchester . It is held in conjunction to the Great Manchester Run , a major 10k generally held on the Sunday . The first event was in May 2009 . The event was originally designed to promote the Great Run , however , the Games soon became a major British athletics event , attracting famous athletes such as Usain Bolt , David Rudisha and Kim Collins .", "title": "" }, { "docid": "2013_World_Championships_in_Athletics_–_Men's_200_metres", "text": "The men 's 200 metres at the 2013 World Championships in Athletics was held at the Luzhniki Stadium on 16 and 17 August . In the final , Adam Gemili seemed to get the best start , but flanked by the Jamaican uniforms , he was quickly swallowed up . Mid way into the turn , Usain Bolt had a clear lead . Coming off the turn , Bolt had several meters on the field . The winner determined , Bolt eased off and cruised across the finish in what would be a great time for any other human being , just a slow 200 for Bolt in 19.66 . Coming off the turn about even with Gemili and Nickel Ashmeade , Warren Weir out in lane 7 separated from those two and gained significantly on the slowing Bolt , setting a personal best of 19.79 . Taking a lesson from American teammate Wallace Spearmon who was vanquished in the semis , Curtis Mitchell spotted the field several meters then closed from dead last at the end of the turn to take the bronze . Gemili took a full dive at the finish to try to beat Ashmeade but still finished in fifth .", "title": "" }, { "docid": "2003_Pan_American_Junior_Athletics_Championships", "text": "The 12th Pan American Junior Athletics Championships were held in Bridgetown , Barbados at the National Stadium on 18 -- 20 July 2003 . Jamaican sprinter Usain Bolt had the outstanding performance equalling the 200m World Junior record , while the team of the USA dominated the championships gaining 48 medals .", "title": "" }, { "docid": "Glen_Mills", "text": "Glen Mills OD ( * 14 August 1949 ) is a sprinting athletics coach from Jamaica . He was the head coach of the Jamaican Olympic athletics team between 1987 and 2009 . He is currently head coach of the Racers Track Club which includes world and Olympic record holder Usain Bolt and the 100 metre World Champion Yohan Blake . Other athletes that he has coached in the past include Kim Collins , and Ray Stewart .", "title": "" }, { "docid": "2007_World_Championships_in_Athletics_–_Men's_200_metres", "text": "These are the official results of the men 's 200 metres event at the 2007 IAAF World Championships in Osaka , Japan . There were a total number of 49 participating athletes , with six qualifying heats and the final held on Thursday August 30 . This event is notable for being the only solo World Championship event in which Usain Bolt has been beaten as of August 2016 .", "title": "" }, { "docid": "2013_World_Championships_in_Athletics", "text": "The 14th IAAF World Championships in Athletics ( Moscow 2013 ) was an international athletics competition held in Moscow , Russia , from 10 -- 18 August 2013 . Russia won the most gold medals to top the table for the first time since 2001 . It was also the first time ever the host nation took the top of the medal table . The United States won the most overall medals . With 1,784 athletes from 203 countries it was the biggest single sports event of the year . The number of spectators for the evening sessions was 268,548 surpassing Daegu 2011 . Jamaica 's Usain Bolt and Shelly-Ann Fraser-Pryce both won three gold medals in the men 's and women 's 100 metres , 200 metres and 4 × 100 metres relay respectively to become the most successful athletes at the event . This achievement also earned Bolt the title of being the most successful athlete in the history of the World Championships with eight gold and two silver medals . Prior to the competition , four sprinters were banned on doping charges .", "title": "" }, { "docid": "2015_World_Championships_in_Athletics_–_Men's_100_metres", "text": "The men 's 100 metres at the 2015 World Championships in Athletics was held at the Beijing National Stadium on 22 and 23 August . Justin Gatlin had the world leading time in 2015 . Gatlin ran 9.83 s in the heats and 9.77 s in the semi-final . Reigning champion Usain Bolt ran times of 9.96 s in both rounds . Jimmy Vicaut and Su Bingtian qualified for the final with tied fastest loser times of 9.986 s , so there were 9 competitors in the final . In the final , Bolt finished one hundredth of a second ahead of Gatlin in a time of 9.79 s. There was a tie for third place , with Andre De Grasse and Trayvon Bromell both finishing in 9.911 s , and two bronze medals were awarded .", "title": "" }, { "docid": "2002_Central_American_and_Caribbean_Junior_Championships_in_Athletics", "text": "The 15th Central American and Caribbean Junior Championships were held in the National Stadium in Bridgetown , Barbados obetween 5 -- 7 July 2002 . A discussion of the results is given . Usain Bolt of Jamaica set a total of 6 new championship records .", "title": "" }, { "docid": "Great_CityGames", "text": "The Great CityGames is a major street athletics event held twice annually in Manchester , Newcastle and Gateshead . The former is held in conjunction to the Great Manchester Run , a major 10k generally held on the Sunday . The first event was in May 2009 . The latter is held in conjunction to the Great North Run , another major 10k attracting world-famous athletes . The first event was in September 2009 . The event was originally designed to promote the Great Runs , however , the Games soon became a major British athletics event , attracting famous athletes such as Usain Bolt , David Rudisha and Kim Collins .", "title": "" }, { "docid": "2017_World_Championships_in_Athletics", "text": "The 2017 IAAF World Championships are the 16th edition and are scheduled to be held in August 2017 in London , United Kingdom . London was officially awarded the Championships by the IAAF , in Monaco on 11 November 2011 . This championship is to be sprinter Usain Bolt 's and distance runner Mo Farah 's last .", "title": "" }, { "docid": "RockLive", "text": "RockLive is an American online social network and games developer that was founded in 2009 . In 2013 , RockLive became Shots Studios a digital studio and management company which also released the Shots App , a comedy social network for millennials . RockLive developed mobile games in partnership with athletes , including Mike Tyson , Cristiano Ronaldo and Usain Bolt .", "title": "" }, { "docid": "Jacko_Gill", "text": "Jackson `` Jacko '' Gill ( born 20 December 1994 ) is a shot putter from New Zealand . At the 2010 World Junior Championships in Athletics , he won the gold medal in the shot put at only , surpassing Usain Bolt ( who was old when he won the 200 metres in 2002 ) as the youngest-ever male junior champion . He successfully defended his title , winning gold again at the 2012 World Junior Championships in Athletics . Gill throws with his right hand , using the spin technique .", "title": "" }, { "docid": "Lightning_bolt", "text": "Lightning bolt may refer to : Lightning , a electrostatic discharge during an electrical storm Lightning strike , an electric discharge between the atmosphere and the ground Thunderbolt , lightning accompanied by a loud thunderclap Lightning Bolt may refer to : Lightning Bolt ( film ) , an Italian-Spanish spy movie Lightning Bolt ( interface ) , a computer display and docking standard Lightning Bolt ( motorcycle ) , an American world land-speed record breaker Lightning Bolt , nickname and victory pose of Jamaican sprinter Usain Bolt", "title": "" }, { "docid": "2009_in_athletics_(track_and_field)", "text": "This page contains an overview of the year 2009 in athletics . The major competition of the year was the 2009 World Championships in Athletics . At the event , Usain Bolt reaffirmed himself as one of the world 's foremost athletes with world records in the 100 and 200 metres . Caster Semenya won 800 m gold at the championships , but a request that she submit to a gender verification test was made public , sparking widespread controversy and debate . Yelena Isinbayeva , a clear favourite , finished last in the pole vault competition , but rebounded with a world record a week later . Kenenisa Bekele , Sanya Richards and Isinbayeva were the winners of the last IAAF Golden League jackpot , as the series was replaced by the IAAF Diamond League in 2010 .", "title": "" }, { "docid": "Jacques_Freitag", "text": "Jacques Freitag ( born 11 June 1982 ) is a South African high jumper . He is one of only nine athletes ( along with Valerie Adams , Usain Bolt , Veronica Campbell-Brown , Yelena Isinbayeva , Kirani James , Jana Pittman , Dani Samuels , and David Storl ) to win world championships at the youth , junior , and senior level of an athletic event . Freitag grew up in Bronkhorstspruit , Gauteng ( 50 km east of Pretoria ) . His mother , Hendrina Pieters , was in 1973 a South African high jump champion with a personal best of 1.74 metres .", "title": "" }, { "docid": "2011_World_Championships_in_Athletics_–_Men's_200_metres", "text": "The men 's 200 metres at the 2011 World Championships in Athletics was held at the Daegu Stadium on September 2 and September 3 . Usain Bolt , the world record holder and defending champion was the favourite going into the race with a world leading time of 19.86 seconds . He had also won his three major races after return from injury convincingly . Remembering his false start in the 100 metres , favorite Bolt had the slowest reaction time to the gun , but cruised easily into the semi-finals . The semi-finals began with another false start , but it was Sandro Viana . Christophe Lemaitre led the qualifying winning semi 1 , as Bolt casually cruised through semi 2 and Walter Dix ran a controlled semi 3 . The finals were Bolt 's redemption . Still cautious , Bolt had the slowest reaction time in the field , but he easily charged into the lead , making up the stagger on Dix 2/3 of the way through the turn as returning silver medalist Alonso Edward pulled up . Bolt made one glance back at Dix and the rest of the field , then charged home in 19.40 his third best time , the number four time ever . Dix was clearly second in 19.70 , with Christophe Lemaitre separating from Jaysuma Saidy Ndure in 19.80 , the French National Record for the bronze medal . The rest of the field was more than 3/10ths of a second behind . Note these were Fully automatic times , it was just a fluke that all the medal times were evenly divisible by a tenth of a second .", "title": "" }, { "docid": "Fitz_Coleman", "text": "Fitz Coleman is a track and field athletics coach , specializing in hurdling events . He is currently the technical director and head coach of the International Association of Athletics Federations ( IAAF ) recognised High Performance Training Centre in Kingston , Jamaica which is responsible for training the country 's track athletes . He is also , along with Glen Mills , part of the coaching team for Usain Bolt and the Jamaican Olympic track team . He received a person of the year award from The Jamaica Gleaner in recognition of his contributions to Sport in Jamaica . Other sprinters he has coached include 400 metres Commonwealth Games medallist Jermaine Gonzales .", "title": "" }, { "docid": "100_metres", "text": "The 100 metres , or 100-metre dash , is a sprint race in track and field competitions . The shortest common outdoor running distance , it is one of the most popular and prestigious events in the sport of athletics . It has been contested at the Summer Olympics since 1896 for men and since 1928 for women . The reigning 100 m Olympic champion is often named `` the fastest runner in the world . '' The World Championships 100 metres has been contested since 1983 . Jamaicans Usain Bolt and Shelly-Ann Fraser-Pryce are the reigning world champions , Bolt and Elaine Thompson are the Olympic champions in the men 's and women 's 100 metres , respectively . On an outdoor 400 metres running track , the 100 m is run on the home straight , with the start usually being set on an extension to make it a straight-line race . Runners begin in the starting blocks and the race begins when an official fires the starter 's pistol . Sprinters typically reach top speed after somewhere between 50 -- 60 m . Their speed then slows towards the finish line . The 10-second barrier has historically been a barometer of fast men 's performances , while the best female sprinters take eleven seconds or less to complete the race . The current men 's world record is 9.58 seconds , set by Jamaica 's Usain Bolt in 2009 , while the women 's world record of 10.49 seconds set by American Florence Griffith-Joyner in 1988 remains unbroken . The 100 m ( 109.361 yards ) emerged from the metrication of the 100 yards ( 91.44 m ) , a now defunct distance originally contested in English-speaking countries . The event is largely held outdoors as few indoor facilities have a 100 m straight . US athletes have won the men 's Olympic 100 metres title more times than any other country , 16 out of the 28 times that it has been run . US women have also dominated the event winning 9 out of 21 times .", "title": "" } ]
1012
Farrah Fawcett passed up a role in Sunburn.
[ { "docid": "Farrah_Fawcett", "text": "Farrah Fawcett ( born Ferrah Leni Fawcett ; February 2 , 1947 -- June 25 , 2009 ) was an American actress and artist . A four-time Emmy Award nominee and six-time Golden Globe Award nominee , Fawcett rose to international fame when she posed for her iconic red swimsuit poster -- which became the best selling pin-up poster in history -- and starred as private investigator Jill Munroe in the first season of the television series Charlie 's Angels ( 1976 -- 1977 ) . In 1996 , she was ranked No. 26 on TV Guide `` 50 Greatest TV stars of All-Time '' . Fawcett began her career in 1968 in commercials and guest roles on television . During the 1970s , she appeared in numerous television series , including recurring roles on Harry O ( 1974 -- 1976 ) , and The Six Million Dollar Man ( 1974 -- 1978 ) with then husband , film and television star Lee Majors . Her breakthrough role came in 1976 , when she was cast as Jill Munroe in the ABC series Charlie 's Angels , alongside Kate Jackson and Jaclyn Smith . The show propelled all three to stardom , but especially Fawcett ( then billed as Farrah Fawcett-Majors ) . After appearing in only the first season , Fawcett decided to leave the show which led to legal disputes . Eventually she signed a contract requiring her to make six guest appearances in the show 's third and fourth seasons ( 1978 -- 1980 ) . For her role in Charlie 's Angels she received her first Golden Globe nomination . In 1983 , Fawcett received positive reviews for her performance in the Off-Broadway play Extremities . She was subsequently cast in the 1986 film version and received a Golden Globe nomination . She received two Emmy Award nominations for her roles in TV movies , as a battered wife in the 1984 film The Burning Bed and as real-life murderer Diane Downs in the 1989 film Small Sacrifices . Her 1980s work in TV movies also earned her four additional Golden Globe nominations . In 1997 , she gained some negative press for a rambling appearance on The Late Show with David Letterman , but also garnered strong reviews for her role in the film The Apostle with Robert Duvall . She continued in numerous TV series , including recurring roles in the sitcom Spin City ( 2001 ) and the drama The Guardian ( 2002 -- 2003 ) . For the latter , she received her third Emmy nomination . Her film roles include , Love Is a Funny Thing ( 1969 ) , Myra Breckinridge ( 1970 ) , Logan 's Run ( 1976 ) , Sunburn ( 1979 ) , Saturn 3 ( 1980 ) , The Cannonball Run ( 1981 ) , Extremities ( 1986 ) , The Apostle ( 1997 ) , and Dr. T & the Women ( 2000 ) . Fawcett was diagnosed with anal cancer in 2006 ; the 2009 NBC documentary Farrah 's Story chronicled her battle with the disease . She posthumously earned her fourth Emmy nomination for her work as a producer on the documentary .", "title": "" } ]
[ { "docid": "Sunburn_(disambiguation)", "text": "Sunburn is a condition of the skin after overexposure to ultraviolet radiation . Sunburn may also refer to : Sun scald , the effects of ultraviolet radiation on the plant kingdom SS-N-22 Sunburn , two Soviet anti-ship missiles Sunburn ( Blake Babies album ) , 1990 Sunburn ( Sun album ) Sunburn ( Fuel album ) , 1998 `` Sunburn '' ( Fuel song ) , 1999 `` Sunburn '' ( Muse song ) , 2000 Sunburn ( Owl City song ) Sunburn , a 2004 album by Gordie Sampson Sunburn ( film ) , a 1979 film starring Farrah Fawcett Sunburn ( TV series ) , a BBC series starring Michelle Collins and Sean Maguire Sunburn ( Transformers ) , a fictional female Transformers character Sunburn Festival , an electronic dance music festival held in Candolim Beach , Goa , India `` Sunburn '' , a song by Tinashe from Nightride", "title": "" }, { "docid": "Sunburn_(film)", "text": "Sunburn is a 1979 British-American comedy film directed by Richard C. Sarafian and written by James Booth , John Daly and Stephen Oliver . It is based on the novel The Bind by Stanley Ellin . The film stars Farrah Fawcett , Charles Grodin , Art Carney , Joan Collins , William Daniels and John Hillerman . The film was released on August 10 , 1979 , by Paramount Pictures .", "title": "" }, { "docid": "Extremities_(film)", "text": "Extremities is a 1986 American thriller film starring Farrah Fawcett , Alfre Woodard , Diana Scarwid and James Russo . It was adapted from the successful , yet controversial , 1982 off-Broadway play of the same name by William Mastrosimone , focusing on a woman who captures her stalker and rapist in her home and exacts revenge on him with her housemates . Both Fawcett and Russo had appeared in the stage play ( Fawcett taking over a role originated by Susan Sarandon ) , and Fawcett received a Golden Globe nomination for Best Actress for her performance in the film .", "title": "" }, { "docid": "Chasing_Farrah", "text": "Chasing Farrah is an American reality television series starring Farrah Fawcett , which aired on TVLand in early 2005 .", "title": "" }, { "docid": "Jaclyn_Smith", "text": "Jacquelyn Ellen `` Jaclyn '' Smith ( born October 26 , 1945 ) is an American actress and businesswoman . She is known for her role as Kelly Garrett in the television series Charlie 's Angels ( 1976 -- 81 ) , and was the only original female lead to remain with the series for its complete run . She reprised the role with a cameo appearance in the 2003 film Charlie 's Angels : Full Throttle . Her other films include Nightkill ( 1980 ) and Déjà Vu ( 1985 ) . Beginning in the 1980s , she began developing and marketing her own brands of clothing and perfume . Smith began her career in 1969 in television commercials . In 1976 , she was cast in Charlie 's Angels , alongside Kate Jackson and Farrah Fawcett ( then billed as Farrah Fawcett-Majors ) . The show propelled all three to stardom , including an appearance on the front cover of Time magazine . She was nominated for the Golden Globe for Best Actress in a Miniseries or TV Film for the title role in the TV film Jacqueline Bouvier Kennedy ( 1981 ) , and went on to star in numerous TV films and miniseries over the next 20 years , including Rage of Angels ( 1983 ) , George Washington ( 1984 ) , Kaleidoscope ( 1990 ) and Nightmare in the Daylight ( 1992 ) . She had a recurring role from 2002 to 2004 in the drama series The District and appeared as Olivia Hodges in two episodes of CSI : Crime Scene Investigation in 2012 .", "title": "" }, { "docid": "Murder_on_Flight_502", "text": "Murder on Flight 502 is a 1975 American television film directed by George McCowan . The film stars Robert Stack , Sonny Bono and Farrah Fawcett-Majors , along with an all-star ensemble television cast in supporting roles .", "title": "" }, { "docid": "Nazi_Hunter:_The_Beate_Klarsfeld_Story", "text": "Nazi Hunter : The Beate Klarsfeld Story is a 1986 made-for-TV biographical drama film , starring Farrah Fawcett in the title role , and Tom Conti . The film also stars Geraldine Page and Catherine Allégret .", "title": "" }, { "docid": "The_Great_American_Beauty_Contest", "text": "__ NOTOC __ The Great American Beauty Contest is a 1973 American satirical comedy-drama TV film , starring JoAnna Cameron and featuring Eleanor Parker , Robert Cummings , Louis Jourdan and Farrah Fawcett in an early film appearance . It was directed by Robert Day and was originally shown on the ABC TV network in the United States on February 13 , 1973 . Allmovie characterizes the film as `` An unsubtle but effective TV-movie satire of the ` Miss America ' syndrome '' , and calls the belly dance performed by Farrah Fawcett `` endearingly ridiculous . ''", "title": "" }, { "docid": "Good_Sports", "text": "Good Sports is an American sitcom that aired on the CBS network in 1991 , starring Farrah Fawcett and Ryan O'Neal . It was Fawcett 's only scripted TV series after Charlie 's Angels .", "title": "" }, { "docid": "Dalva", "text": "Dalva is a 1996 American made-for-television drama film starring Farrah Fawcett and Carroll Baker . Although Fawcett is n't the movie 's only star , she is the only performer to be billed in the opening credits . However , on DVD and VHS cases Baker and Powers Boothe garner direct below-the-title billing .", "title": "" }, { "docid": "Fawcett_(surname)", "text": "Fawcett as a surname may refer to : Benjamin Fawcett ( 1808 -- 1893 ) , English woodblock colour printer Brian Fawcett ( born 1944 ) , Canadian poet and novelist Cesar Fawcett , Colombian footballer Charles Fawcett ( historian ) , British historian Charles Bungay Fawcett ( 1883-1952 ) , British geographer Charles Fernley Fawcett ( 1915 -- 2008 ) , U.S. soldier , actor , and co-founder of the International Medical Corps David Fawcett ( born 1963 ) , Australian politician Eric Fawcett ( 1927 -- 2000 ) , British-Canadian physicist Farrah Fawcett ( 1947 -- 2009 ) , U.S. actress Henry Fawcett ( 1833 -- 1884 ) , British economist and politician James Farish Malcolm Fawcett ( after 1918 ) , English entomologist who specialised in Lepidoptera Joan Fawcett ( 1937 -- 2015 ) , Canadian politician John Fawcett ( actor ) ( 1768 -- 1837 ) , English actor and playwright John Fawcett ( of Bolton ) ( 1789 -- 1867 ) , English composer Joseph Fawcett ( 1758-1804 ) , English Presbyterian minister and poet Joy Fawcett ( born 1968 ) , American soccer player Millicent Fawcett ( 1847 -- 1929 ) , British feminist Norman Fawcett ( 1910 -- 1997 ) , Canadian politician Percy Fawcett ( 1867 -- ) , British archaeologist and explorer Philippa Fawcett ( 1868 -- 1948 ) , British mathematician and educator Quinn Fawcett , pen name of a pair of authors , Chelsea Quinn Yarbro and Bill Fawcett Ron Fawcett ( born 1955 ) , English rock climber Ruth Fawcett ( born 1961 ) , Canadian physicist Taylor Fawcett ( born 1993 ) , British actor Theodore Fawcett ( 1832 -- 1898 ) , Australian settler and politician Wilford Hamilton `` Captain Billy '' Fawcett ( 1885 -- 1940 ) , American publisher ( Fawcett Publications , Fawcett Comics ) William Fawcett ( author ) ( 1902 -- 1941 ) , English writer on horses and hunting William Fawcett ( disambiguation )", "title": "" }, { "docid": "Cheryl_Ladd", "text": "Cheryl Ladd ( born Cheryl Jean Stoppelmoor ; July 12 , 1951 ) is an American actress , singer , and author . Ladd is best known for her role as Kris Munroe in the ABC television series Charlie 's Angels , hired amid a swirl of publicity prior to its second season in 1977 to replace the departing Farrah Fawcett-Majors who played Jill Munroe , the sister of Ladd 's character . Ladd remained with the show until its cancellation in 1981 .", "title": "" }, { "docid": "Justin_Gocke", "text": "Justin Gocke ( January 31 , 1978 -- September 8 , 2014 ) was an American actor . As a former child actor , he is known for his role as Brandon Capwell ( 1987 -- 1992 ) on the daytime television series Santa Barbara for which he won a Daytime Emmy Award for a Younger Actor . He was also in a movie with Farrah Fawcett in ( 1984 ) , The Burning Bed , as well as The Witching of Ben Wagner ( 1990 ) , and My Grandpa is a Vampire ( 1991 ) . Gocke died on September 8 , 2014 .", "title": "" }, { "docid": "The_Substitute_Wife_(1994_film)", "text": "The Substitute Wife is a 1994 television movie , starring Farrah Fawcett , along with Lea Thompson and Peter Weller .", "title": "" }, { "docid": "Poor_Little_Rich_Girl:_The_Barbara_Hutton_Story", "text": "Poor Little Rich Girl : The Barbara Hutton Story is a 1987 television biographical drama starring Farrah Fawcett . The film chronicles the life of Barbara Hutton , a wealthy but troubled American socialite . Released as both a television movie and a mini series , the film won a Golden Globe Award for Best Miniseries or Television Film . Fawcett earned her fifth Golden Globe Award nomination , for Best Actress in a Miniseries of Television Film .", "title": "" }, { "docid": "Baby_(2000_film)", "text": "Baby is a 2000 made-for-television drama film starring Farrah Fawcett , Keith Carradine and an early performance from Alison Pill .", "title": "" }, { "docid": "The_Red-Light_Sting", "text": "The Red-Light Sting is a 1984 made-for-television movie , starring Farrah Fawcett , Beau Bridges , Harold Gould , and Paul Burke .", "title": "" }, { "docid": "Silk_Hope", "text": "Silk Hope is a 1999 made-for-TV romantic-drama film that starred Farrah Fawcett , along with Brad Johnson , Ashley Crow , and Scott Bryce .", "title": "" }, { "docid": "The_Apostle", "text": "The Apostle is a 1997 American drama film written and directed by Robert Duvall , who stars in the title role . John Beasley , Farrah Fawcett , Billy Bob Thornton , June Carter Cash , Miranda Richardson and Billy Joe Shaver also appear . It was filmed on location in and around Saint Martinville and Des Allemands , Louisiana with some establishing shots done in the Dallas , Texas area by a second unit before principal photography began . And main opening shots filmed in Grand Coteau and Lafayette Louisiana . The film was screened in the Un Certain Regard section at the 1998 Cannes Film Festival . For his performance , Duvall was nominated for the Academy Award for Best Actor .", "title": "" }, { "docid": "Between_Two_Women_(1986_film)", "text": "Between Two Women is a 1986 television film that starred Farrah Fawcett and Colleen Dewhurst ; in a twisted story about a relationship between a lady and her mother-in-law .", "title": "" }, { "docid": "Jay_Bernstein", "text": "Jay Bernstein ( June 7 , 1937 -- April 30 , 2006 ) was an American producer and manager to actors like Sammy Davis Jr. and Michael Landon , and to actresses Farrah Fawcett and Suzanne Somers .", "title": "" }, { "docid": "Murder_in_Texas", "text": "Murder in Texas is a 1981 television film starring Katharine Ross , Sam Elliott , Farrah Fawcett , and Andy Griffith . The film was directed by William Hale , and was based on a true story ; that was written for the TV screen by John McGreevey .", "title": "" }, { "docid": "The_Cookout", "text": "The Cookout is a 2004 comedy film , directed by Lance Rivera . It is co-written by and features Queen Latifah , and is also the feature film debut for her mother Rita Owens . This was the last film for Farrah Fawcett before her death in 2009 .", "title": "" }, { "docid": "Farrah_Phelan", "text": "Farrah Phelan ( now Clayton ) is a fictional character from the Irish television soap opera , Fair City . The character has been portrayed by four actresses in total . The character first appeared onscreen in 1998 played by Fiona Glascott , however the character left the series to go to London . On her return in 2000 , Sinead Keenan was cast in the role . The character left the series for a second time and when she returned for a third time , the role went to Denise McCormack . The character again left the series to take up a photography course in London . In 2014 , Caroline Harvey was cast in the role when the character 's father Christy Phelan had a stroke .", "title": "" }, { "docid": "Somebody_Killed_Her_Husband", "text": "Somebody Killed Her Husband is a 1978 American comedy-mystery film directed by Lamont Johnson and written by Reginald Rose . It starred Farrah Fawcett and Jeff Bridges . Also in the cast were John Wood , Tammy Grimes and John Glover .", "title": "" }, { "docid": "Bobbi_Boland", "text": "Bobbi Boland is a play by Nancy Hasty which premiered Off-Broadway at the Arclight Theatre , running from March 1 to July 10 , 2001 . In 2003 , an attempt was made to mount a Broadway production starring Farrah Fawcett . However , the show closed during previews .", "title": "" }, { "docid": "Myra_Breckinridge_(film)", "text": "Myra Breckinridge is a 1970 American comedy film based on Gore Vidal 's 1968 novel of the same name . The film was directed by Michael Sarne , and featured Raquel Welch in the title role . It also starred John Huston as Buck Loner , Mae West as Leticia Van Allen , Farrah Fawcett , Rex Reed , Roger Herren , and Roger C. Carmel . Tom Selleck made his film debut in a small role as one of Leticia 's `` studs '' . Theadora Van Runkle was costume designer for the film , though Edith Head designed West 's costumes . Like the novel , the picture follows the exploits of Myron Breckinridge , a gay man who has a sex change and becomes Myra Breckinridge . She goes to Hollywood to turn it inside out . The picture was controversial for its sexual explicitness ( including acts like pegging ) , but unlike the novel , Myra Breckinridge received little to no critical praise and has been cited as one of the worst films ever made .", "title": "" }, { "docid": "See_You_in_the_Morning_(film)", "text": "See You in the Morning is a 1989 American romantic comedy film written and directed by Alan J. Pakula , and starring Jeff Bridges , Alice Krige and Farrah Fawcett . It features music by Nat `` King '' Cole and Cherri Red . The original music score was composed by Michael Small .", "title": "" }, { "docid": "Pro_Arts", "text": "Pro Arts Inc was a poster company founded in Ohio , United States that would create the top selling poster in the world , the Farrah Fawcett swimsuit poster . The poster sold over 12 million copies but the company could n't survive and in a controversial series of events the company filed for Chapter 11 bankruptcy in 1981 and was liquidated in 1984 .", "title": "" }, { "docid": "Andrea_Jaffe", "text": "Andrea Jaffe ( died on August 24 , 2016 ) was a prominent Hollywood publicist in the 1980s and early 1990s . Jaffe initially worked as an assistant at marketing and public relations agency Rogers & Cowan before working for PMK and establishing her own publicity company , Andrea Jaffe and Associates . Her clients included Tom Cruise , Farrah Fawcett , Oliver Stone , and Dustin Hoffman .", "title": "" } ]
PLAIN-3474
Fish Consumption and Suicide
[ { "docid": "MED-1360", "text": "Objective To assess whether patients receiving aerobic exercise training performed either at home or in a supervised group setting achieve reductions in depression comparable to standard antidepressant medication (sertraline) and greater reductions in depression compared to placebo controls. Methods Between October 2000 and November 2005, we performed a prospective, randomized controlled trial (SMILE study) with allocation concealment and blinded outcome assessment in a tertiary care teaching hospital. A total of 202 adults (153 women; 49 men) diagnosed with major depression were assigned randomly to one of four conditions: supervised exercise in a group setting; home-based exercise; antidepressant medication (sertraline, 50–200 mg daily); or placebo pill for 16 weeks. Patients underwent the structured clinical interview for depression and completed the Hamilton Depression Rating Scale (HAM-D). Results After 4 months of treatment, 41% of the participants achieved remission, defined as no longer meeting the criteria for major depressive disorder (MDD) and a HAM-D score of <8. Patients receiving active treatments tended to have higher remission rates than the placebo controls: supervised exercise = 45%; home-based exercise = 40%; medication = 47%; placebo = 31% (p = .057). All treatment groups had lower HAM-D scores after treatment; scores for the active treatment groups were not significantly different from the placebo group (p = .23). Conclusions The efficacy of exercise in patients seems generally comparable with patients receiving antidepressant medication and both tend to be better than the placebo in patients with MDD. Placebo response rates were high, suggesting that a considerable portion of the therapeutic response is determined by patient expectations, ongoing symptom monitoring, attention, and other nonspecific factors.", "title": "Exercise and Pharmacotherapy in the Treatment of Major Depressive Disorder" }, { "docid": "MED-5361", "text": "OBJECTIVE: To compare 2 omega-3 (n-3) preparations enriched with eicosapentaenoic acid (EPA) versus docosahexaenoic acid (DHA) as monotherapy for major depressive disorder (MDD) in a 2-site, placebo-controlled, randomized, double-blind clinical trial. METHOD: 196 adults (53% female; mean [SD] age = 44.7 [13.4] years) with DSM-IV MDD and a baseline 17-item Hamilton Depression Rating Scale (HDRS-17) score ≥ 15 were randomized equally from May 18, 2006, to June 30, 2011, to 8 weeks of double-blind treatment with oral EPA-enriched n-3 1000 mg/d, DHA-enriched n-3 1,000 mg/d, or placebo. RESULTS: 154 subjects completed the study. Modified intent-to-treat (mITT) analysis (n = 177 subjects with ≥ 1 postbaseline visit; 59.3% female, mean [SD] age 45.8 [12.5] years) employed mixed-model repeated measures (MMRM). All 3 groups demonstrated statistically significant improvement in the HDRS-17 (primary outcome measure), 16-item Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR-16), and Clinical Global Improvement-Severity Scale (CGI-S) (P < .05), but neither n-3 preparation separated from placebo (P > .05). Response and remission rates were in the range of 40%-50% and 30%, respectively, for all treatments, with no significant differences between groups. One subject receiving EPA-enriched n-3 discontinued due to worsening depression, and 1 subject receiving placebo discontinued due to an unspecified \"negative reaction\" to pills. CONCLUSIONS: Neither EPA-enriched nor DHA-enriched n-3 was superior to placebo for the treatment of MDD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00517036. © Copyright 2015 Physicians Postgraduate Press, Inc.", "title": "A double-blind, randomized controlled clinical trial comparing eicosapentaenoic acid versus docosahexaenoic acid for depression." }, { "docid": "MED-5369", "text": "BACKGROUND: There are an estimated one million completed suicides per year worldwide. As a response to increasing concern about suicide within Europe, the EUROSAVE (European Review of Suicide and Violence Epidemiology) study was undertaken to examine recent trends in the epidemiology of suicide and self-inflicted injury mortality in the European Union (EU). METHODS: Suicide and self-inflicted injury mortality data for the 15 EU countries for the years 1984-1998 were obtained from the World Health Organisation (WHO), the European Statistical Office of the European Commission (EUROSTAT) and national statistical agencies. Data were also obtained for a second group of deaths classified as 'undetermined' or 'other violence'. Age-standardized mortality rates were calculated and examined for trends over time. RESULTS: Finland had the highest suicide rate, while Greece had the lowest for the latest available year (1997). Age-standardized suicide rates tended to be lowest in the Mediterranean countries. Significant downward linear time trends in suicide mortality were observed in most countries, although rates varied markedly between countries. Both Ireland and Spain displayed significant upward linear trends in suicide mortality. Portugal had the highest rate of undetermined deaths both in 1984 and 1998 while Greece had the lowest in both 1984 and 1997. Five countries (including Ireland and Spain) showed significant downward trends in deaths due to undetermined causes whereas Belgium and Germany showed borderline significant upward linear trends in deaths due to undetermined causes. CONCLUSIONS: Although suicide rates in most countries seem to be decreasing, the validity of the data is uncertain. Misclassification may contribute to the geographical and temporal variation in suicide rates in some EU countries but it does not explain the phenomenon. More detailed research comparing suicide-recording procedures and practices across the EU is required. In the absence of adequate EU wide data on suicide epidemiology, effective prevention of this distressing phenomenon is likely to remain elusive.", "title": "Suicide mortality in the European Union." }, { "docid": "MED-2921", "text": "Background: Methylmercury (MeHg) is a known neuro-toxicant. Emerging evidence indicates it may have adverse effects on the neuro-logic and other body systems at common low levels of exposure. Impacts of MeHg exposure could vary by individual susceptibility or be confounded by bene-ficial nutrients in fish containing MeHg. Despite its global relevance, synthesis of the available literature on low-level MeHg exposure has been limited. Objectives: We undertook a synthesis of the current knowledge on the human health effects of low-level MeHg exposure to provide a basis for future research efforts, risk assessment, and exposure remediation policies worldwide. Data sources and extraction: We reviewed the published literature for original human epidemio-logic research articles that reported a direct biomarker of mercury exposure. To focus on high-quality studies and those specifically on low mercury exposure, we excluded case series, as well as studies of populations with unusually high fish consumption (e.g., the Seychelles), marine mammal consumption (e.g., the Faroe Islands, circumpolar, and other indigenous populations), or consumption of highly contaminated fish (e.g., gold-mining regions in the Amazon). Data synthesis: Recent evidence raises the possibility of effects of low-level MeHg exposure on fetal growth among susceptible subgroups and on infant growth in the first 2 years of life. Low-level effects of MeHg on neuro-logic outcomes may differ by age, sex, and timing of exposure. No clear pattern has been observed for cardio-vascular disease (CVD) risk across populations or for specific CVD end points. For the few studies evaluating immunologic effects associated with MeHg, results have been inconsistent. Conclusions: Studies targeted at identifying potential mechanisms of low-level MeHg effects and characterizing individual susceptibility, sexual dimorphism, and non-linearity in dose response would help guide future prevention, policy, and regulatory efforts surrounding MeHg exposure.", "title": "Evidence on the Human Health Effects of Low-Level Methylmercury Exposure" }, { "docid": "MED-1198", "text": "BACKGROUND: Ascorbic acid (AA) modulates catecholaminergic activity, decreases stress reactivity, approach anxiety and prolactin release, improves vascular function, and increases oxytocin release. These processes are relevant to sexual behavior and mood. METHODS: In this randomized double-blind, placebo-controlled 14 day trial of sustained-release AA (42 healthy young adults; 3000 mg/day Cetebe) and placebo (39 healthy young adults), subjects with partners recorded penile-vaginal intercourse (FSI), noncoital partner sex, and masturbation in daily diaries, and also completed the Beck Depression Inventory before and after the trial. RESULTS: The AA group reported greater FSI (but, as hypothesized, not other sexual behavior) frequency, an effect most prominent in subjects not cohabiting with their sexual partner, and in women. The AA but not placebo group also experienced a decrease in Beck Depression scores. CONCLUSIONS: AA appears to increase FSI, and the differential benefit to noncohabitants suggests that a central activation or disinhibition, rather than peripheral mechanism may be responsible.", "title": "High-dose ascorbic acid increases intercourse frequency and improves mood: a randomized controlled clinical trial." }, { "docid": "MED-2754", "text": "BACKGROUND: Although previous randomized, double-blind, placebo-controlled trials reported the efficacy of omega-3 fatty acid supplements in the secondary prevention of cardiovascular disease (CVD), the evidence remains inconclusive. Using a meta-analysis, we investigated the efficacy of eicosapentaenoic acid and docosahexaenoic acid in the secondary prevention of CVD. METHODS: We searched PubMed, EMBASE, and the Cochrane Library in April 2011. Two of us independently reviewed and selected eligible randomized controlled trials. RESULTS: Of 1007 articles retrieved, 14 randomized, double-blind, placebo-controlled trials (involving 20 485 patients with a history of CVD) were included in the final analyses. Supplementation with omega-3 fatty acids did not reduce the risk of overall cardiovascular events (relative risk, 0.99; 95% CI, 0.89-1.09), all-cause mortality, sudden cardiac death, myocardial infarction, congestive heart failure, or transient ischemic attack and stroke. There was a small reduction in cardiovascular death (relative risk, 0.91; 95% CI, 0.84-0.99), which disappeared when we excluded a study with major methodological problems. Furthermore, no significant preventive effect was observed in subgroup analyses by the following: country location, inland or coastal geographic area, history of CVD, concomitant medication use, type of placebo material in the trial, methodological quality of the trial, duration of treatment, dosage of eicosapentaenoic acid or docosahexaenoic acid, or use of fish oil supplementation only as treatment. CONCLUSION: Our meta-analysis showed insufficient evidence of a secondary preventive effect of omega-3 fatty acid supplements against overall cardiovascular events among patients with a history of cardiovascular disease.", "title": "Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: ..." }, { "docid": "MED-1354", "text": "Context Antidepressant medications represent the best established treatment for Major Depressive Disorder (MDD), but there is little evidence that they have a specific pharmacological effect relative to pill-placebo for patients with less severe depression. Objective To estimate the relative benefit of medication vs placebo across a wide range of initial symptom severity in patients diagnosed with depression. Data Sources Pubmed, PsycINFO, and the Cochrane Library databases were searched from January 1980 through March 2009, along with references from meta-analyses and reviews. Study Selection Randomized placebo-controlled trials of FDA approved antidepressants in the treatment of Major or Minor Depressive Disorder were selected. Studies were included if their authors provided the requisite original data, they comprised adult outpatients, included a medication vs placebo comparison for at least 6 weeks, did not exclude patients on the basis of a placebo washout period, and utilized the Hamilton Rating Scale for Depression. Data from six studies (718 patients) were included. Data Extraction Individual patient-level data were obtained from study authors. Results Medication vs placebo differences varied substantially as a function of baseline severity. Among patients with Hamilton scores below 23, Cohen’s d-type effect sizes for the difference between medication and placebo were estimated to be < .20 (a standard definition of a small effect). Estimates of the magnitude of the superiority of medication over placebo increased with increases in baseline Hamilton severity and crossed the NICE threshold for a clinically significant difference at a baseline score of 25. Conclusions The magnitude of benefit of antidepressant medication compared with placebo increases with severity of depression symptoms, and may be minimal or nonexistent, on average, in patients with mild or moderate symptoms. For patients with very severe depression, the benefit of medications over placebo is substantial.", "title": "Antidepressant Drug effects and Depression Severity: A Patient-Level Meta-Analysis" }, { "docid": "MED-3034", "text": "In the 1970s several states in the Great Lakes region became concerned about mercury contamination in lakes and rivers and were the first to issue local fish consumption advisories. In 2001, the Food and Drug Administration (FDA) advised pregnant women, nursing mothers, young children, and women who may become pregnant not to consume shark, swordfish, king mackerel, and tilefish and recommended that these women not exceed 12 ounces of other fish per week. In 2004, FDA reissued this advice jointly with the U.S. Environmental Protection Agency (EPA) and modified it slightly to provide information about consumption of canned tuna and more details about consumption of recreationally caught fish. Though several studies have examined consumers' awareness of the joint FDA and EPA advisory as well as different state advisories, few used representative data. We examined the changes in awareness and knowledge of mercury as a problem in fish using the pooled nationally representative 2001 and 2006 Food Safety Surveys (FSS) with sample sizes of 4482 in 2001 and 2275 in 2006. Our results indicated an increase in consumers' awareness of mercury as a problem in fish (69% in 2001 to 80% in 2006, p<.001). In our regression models, we found that in both years, parents having children less than 5 years of age were more aware of mercury in fish and knowledgeable about the information contained in the national advisories about mercury in fish (p<.01) than other adults. In both 2001 and 2006, women of childbearing age (aged 18-45) were less aware and knowledgeable about this information than other women. However, women of all age groups had larger gains in awareness and knowledge than their male counterparts during this time. Participants' race, education, income, region, fish preparation experiences, having a foodborne illness in the past year, and risk perceptions about the safety of food were significant predictors of their awareness and knowledge. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Awareness and knowledge of methylmercury in fish in the United States." }, { "docid": "MED-1200", "text": "Oxidative stress has been implicated in the pathophysiology of many neuropsychiatric disorders such as schizophrenia, bipolar disorder, major depression etc. Both genetic and nongenetic factors have been found to cause increased cellular levels of reactive oxygen species beyond the capacity of antioxidant defense mechanism in patients of psychiatric disorders. These factors trigger oxidative cellular damage to lipids, proteins and DNA, leading to abnormal neural growth and differentiation. Therefore, novel therapeutic strategies such as supplementation with antioxidants can be effective for long-term treatment management of neuropsychiatric disorders. The use of antioxidants and PUFAs as supplements in the treatment of neuropsychiatric disorders has provided some promising results. At the same time, one should be cautious with the use of antioxidants since excessive antioxidants could dangerously interfere with some of the protective functions of reactive oxygen species. The present article will give an overview of the potential strategies and outcomes of using antioxidants as therapeutics in psychiatric disorders.", "title": "Antioxidants as potential therapeutics for neuropsychiatric disorders" }, { "docid": "MED-3021", "text": "The hair-to-blood ratio and biological half-life of methylmercury in a one-compartment model seem to differ between past and recent studies. To reevaluate them, 27 healthy volunteers were exposed to methylmercury at the provisional tolerable weekly intake (3.4 µg/kg body weight/week) for adults through fish consumption for 14 weeks, followed by a 15-week washout period after the cessation of exposure. Blood was collected every 1 or 2 weeks, and hair was cut every 4 weeks. Total mercury (T-Hg) concentrations were analyzed in blood and hair. The T-Hg levels of blood and hair changed with time (p < 0.001). The mean concentrations increased from 6.7 ng/g at week 0 to 26.9 ng/g at week 14 in blood, and from 2.3 to 8.8 µg/g in hair. The mean hair-to-blood ratio after the adjustment for the time lag from blood to hair was 344 ± 54 (S.D.) for the entire period. The half-lives of T-Hg were calculated from raw data to be 94 ± 23 days for blood and 102 ± 31 days for hair, but the half-lives recalculated after subtracting the background levels from the raw data were 57 ± 18 and 64 ± 22 days, respectively. In conclusion, the hair-to-blood ratio of methylmercury, based on past studies, appears to be underestimated in light of recent studies. The crude half-life may be preferred rather than the recalculated one because of the practicability and uncertainties of the background level, though the latter half-life may approximate the conventional one.", "title": "Hair-to-blood ratio and biological half-life of mercury: experimental study of methylmercury exposure through fish consumption in humans." }, { "docid": "MED-3026", "text": "Background Prenatal exposure to mercury has been associated with adverse childhood neurologic outcomes in epidemiologic studies. Dose–response information for this relationship is useful for estimating benefits of reduced mercury exposure. Objectives We estimated a dose–response relationship between maternal mercury body burden and subsequent childhood decrements in intelligence quotient (IQ), using a Bayesian hierarchical model to integrate data from three epidemiologic studies. Methods Inputs to the model consist of dose–response coefficients from studies conducted in the Faroe Islands, New Zealand, and the Seychelles Islands. IQ coefficients were available from previous work for the latter two studies, and a coefficient for the Faroe Islands study was estimated from three IQ subtests. Other tests of cognition/achievement were included in the hierarchical model to obtain more accurate estimates of study-to-study and end point–to–end point variability. Results We find a central estimate of −0.18 IQ points (95% confidence interval, −0.378 to −0.009) for each parts per million increase of maternal hair mercury, similar to the estimates for both the Faroe Islands and Seychelles studies, and lower in magnitude than the estimate for the New Zealand study. Sensitivity analyses produce similar results, with the IQ coefficient central estimate ranging from −0.13 to −0.25. Conclusions IQ is a useful end point for estimating neurodevelopmental effects, but may not fully represent cognitive deficits associated with mercury exposure, and does not represent deficits related to attention and motor skills. Nevertheless, the integrated IQ coefficient provides a more robust description of the dose–response relationship for prenatal mercury exposure and cognitive functioning than results of any single study.", "title": "Dose–Response Relationship of Prenatal Mercury Exposure and IQ: An Integrative Analysis of Epidemiologic Data" }, { "docid": "MED-1355", "text": "Depression and anxiety are the most common psychiatric conditions seen in the general medical setting, affecting millions of individuals in the United States. The treatments for depression and anxiety are multiple and have varying degrees of effectiveness. Physical activity has been shown to be associated with decreased symptoms of depression and anxiety. Physical activity has been consistently shown to be associated with improved physical health, life satisfaction, cognitive functioning, and psychological well-being. Conversely, physical inactivity appears to be associated with the development of psychological disorders. Specific studies support the use of exercise as a treatment for depression. Exercise compares favorably to antidepressant medications as a first-line treatment for mild to moderate depression and has also been shown to improve depressive symptoms when used as an adjunct to medications. While not as extensively studied, exercise has been shown to be an effective and cost-efficient treatment alternative for a variety of anxiety disorders. While effective, exercise has not been shown to reduce anxiety to the level achieved by psychopharmaceuticals.", "title": "Exercise for the treatment of depression and anxiety." }, { "docid": "MED-4634", "text": "OBJECTIVE: Since conventional food questionnaires are not precise in assessing the dietary fatty acids, the purpose of this study was to determine the relationship between the salivary fatty acid profile and the alimentary habits of two different groups in an attempt to develop a more reliable way to determine the lipidic intake. DESIGN: Twenty adults of both sexes, with mixed (M) or vegetarian (V) diets were studied. Data about the fat intake were obtained by means of a Food Frequency Questionnaire (FFQ) and the presence of the main salivary fatty acids was determined by gas chromatography. RESULTS: A greater salivary concentration of alpha-linolenic acid (18:3 n-3) (2.82) was found in V than in M subjects (1.65) (p = 0.001), whilst arachidonic acid (20:4 n-6) was lower in V (3.93) than in M (4.52) (p = 0.045). The same difference regarding arachidonic acid was observed in the dietary fatty acid intake, also showing a significant correlation between its dietary and salivary levels in vegetarian subjects. CONCLUSIONS: These results show that salivary arachidonic acid, relevant for their eicosanoid production related to the tumourigenesis process and cardiovascular diseases, is influenced by dietary fats.", "title": "Fatty acid profile of human saliva: a possible indicator of dietary fat intake." }, { "docid": "MED-1349", "text": "Antidepressants are supposed to work by fixing a chemical imbalance, specifically, a lack of serotonin in the brain. Indeed, their supposed effectiveness is the primary evidence for the chemical imbalance theory. But analyses of the published data and the unpublished data that were hidden by drug companies reveals that most (if not all) of the benefits are due to the placebo effect. Some antidepressants increase serotonin levels, some decrease it, and some have no effect at all on serotonin. Nevertheless, they all show the same therapeutic benefit. Even the small statistical difference between antidepressants and placebos may be an enhanced placebo effect, due to the fact that most patients and doctors in clinical trials successfully break blind. The serotonin theory is as close as any theory in the history of science to having been proved wrong. Instead of curing depression, popular antidepressants may induce a biological vulnerability making people more likely to become depressed in the future.", "title": "Antidepressants and the Placebo Effect" }, { "docid": "MED-2906", "text": "BACKGROUND: Different chemical forms of mercury occur naturally in human milk. The most controversial aspect of early post-natal exposure to organic mercury is ethylmercury (EtHg) in thimerosal-containing vaccines (TCV) still being used in many countries. Thus exclusively breastfed infants can be exposed to both, fish derived methylmercury (MeHg) in maternal diets and to EtHg from TCV. The aim of the study is to evaluate a new analytical method for ethyl and methyl mercury in hair samples of breastfed infants who had received the recommended schedule of TCV. METHODS: The hair of infants (<12 months) that had been exposed to TCV (Hepatitis B and DTaP) was analysed. A method coupling isothermal gas chromatography with cold-vapor atomic fluorescence spectrometry was used for MeHg which can also speciate EtHg in biological matrices. RESULTS: In 20 samples of infants' hair, all but two samples showed variable amounts of MeHg (10.3 to 668 ng/g), while precise and reliable concentrations of EtHg (3.7 to 65.0 ng/g) were found in 15 of the 20 samples. A statistically significant inverse association (r=-05572; p=0.0384) was found between hair-EtHg concentrations and the time elapsed after the last TCV shot. CONCLUSIONS: The analytical method proved sensitive enough to quantify EtHg in babies' hair after acute exposure to thimerosal in vaccine shots. Provided that the mass of hair was above 10mg, organic-mercury exposure during early life can be speciated, and quantified in babies' first hair, thus opening opportunities for clinical and forensic studies. Copyright © 2011 Elsevier B.V. All rights reserved.", "title": "Speciation of methyl- and ethyl-mercury in hair of breastfed infants acutely exposed to thimerosal-containing vaccines." }, { "docid": "MED-2905", "text": "Fish consumption during gestation can provide the fetus with long chain polyunsaturated fatty acids (LCPUFA) and other nutrients essential for growth and development of the brain. However, fish consumption also exposes the fetus to the neurotoxicant, methyl mercury (MeHg). We studied the association between these fetal exposures and early child development in the Seychelles Child Development Nutrition Study (SCDNS). Specifically, we examined a priori models of Ω-3 and Ω-6 LCPUFA measures in maternal serum to test the hypothesis that these LCPUFA families before or after adjusting for prenatal MeHg exposure would reveal associations with child development assessed by the BSID-II at ages 9 and 30 months. There were 229 children with complete outcome and covariate data available for analysis. At 9 months, the PDI was positively associated with total Ω-3 LCPUFA and negatively associated with the ratio of Ω-6/Ω-3 LCPUFA. These associations were stronger in models adjusted for prenatal MeHg exposure. Secondary models suggested that the MeHg effect at 9 months varied by the ratio of Ω-6/Ω-3 LCPUFA. There were no significant associations between LCPUFA measures and the PDI at 30 months. There were significant adverse associations, however, between prenatal MeHg and the 30 month PDI when the LCPUFA measures were included in the regression analysis. The BSID-II Mental Developmental Index (MDI) was not associated with any exposure variable. These data support the potential importance to child development of prenatal availability of Ω-3 LCPUFA present in fish and of LCPUFA in the overall diet. Furthermore, they indicate that the beneficial effects of LCPUFA can obscure the determination of adverse effects of prenatal MeHg exposure in longitudinal observational studies.", "title": "Associations of maternal long chain polyunsaturated fatty acids, methyl mercury, and infant development in the Seychelles Child Development Nutrition Study" }, { "docid": "MED-1347", "text": "AIMS: To evaluate new generation antidepressants in relation to the placebo response. METHODS: I review meta-analyses in which response to antidepressant medication and response to placebo were calculated. RESULTS: All but one of these meta-analyses included unpublished as well as published trials. Most trials failed to show a significant advantage of SSRIs over inert placebo, and the differences between drug and placebo are not clinically significant for most depressed patients. Documents obtained from the U.S. Food and Drug Administration (FDA) revealed an explicit decision to keep this information from the public and from prescribing physicians. CONCLUSIONS: Because they do not incur drug risks, exercise and psychotherapy, which show at benefits at least equal to those of antidepressants, may be a better treatment choice for depressed individuals.", "title": "Antidepressants and the placebo response." }, { "docid": "MED-1201", "text": "BACKGROUND: Several cross-sectional studies have focused on the low blood folate levels of depressive patients. Nevertheless, no prospective studies have been published on the association between dietary folate and depression. METHODS: We studied the association between dietary folate and cobalamin and receiving a discharge diagnosis of depression in a prospective follow-up setting. Our cohort was recruited between 1984 and 1989 and followed until the end of 2000, and it consisted of 2,313 men aged between 42 and 60 years from eastern Finland. RESULTS: The mean intake of folate in the whole cohort was 256 microg/day (SD=76). Those below the median of energy-adjusted folate intake had higher risk of getting discharge diagnosis of depression (RR 3.04, 95% CI: 1.58, 5.86) during the follow-up period than those who had a folate intake above the median. This excess risk remained significant after adjustment for current socioeconomic status, the baseline HPL depression score, the energy-adjusted daily intake of fibre and vitamin C, and the total fat intake. CONCLUSIONS: A low dietary intake of folate may be a risk factor for severe depression. This also indicates that nutrition may have a role in the prevention of depression.", "title": "Dietary folate and the risk of depression in Finnish middle-aged men. A prospective follow-up study." }, { "docid": "MED-3547", "text": "Monoamine theories associate depression with reduced brain monoamine levels. These theories achieved broad popularity in the mid-1960s. The present article reviews the historical development of monoamine theories and their subsequent impact on biomedical research. Alleged divisions between West European and US researchers over competing versions of the theories are investigated using bibliometrics. Subsequently, the application of monoamine theories in the NIMH Collaborative Program on the Psychobiology of Depression is covered. The article argues that the impact of monoamine theories is best explained by the ability of researchers, governmental agencies, and pharmaceutical companies to invoke theories that advance various projects and agendas.", "title": "Monoamine theories of depression: historical impact on biomedical research." }, { "docid": "MED-3013", "text": "A 2002 analysis documented $54.9 billion in annual costs of environmentally mediated diseases in US children. However, few important changes in federal policy have been implemented to prevent exposures to toxic chemicals. We therefore updated and expanded the previous analysis and found that the costs of lead poisoning, prenatal methylmercury exposure, childhood cancer, asthma, intellectual disability, autism, and attention deficit hyperactivity disorder were $76.6 billion in 2008. To prevent further increases in these costs, efforts are needed to institute premarket testing of new chemicals; conduct toxicity testing on chemicals already in use; reduce lead-based paint hazards; and curb mercury emissions from coal-fired power plants.", "title": "Reducing the staggering costs of environmental disease in children, estimated at $76.6 billion in 2008." }, { "docid": "MED-3544", "text": "Whole-body PET-scan studies in brains of tobacco smokers have shown a decrease in monoamine oxidase (MAO) activity, which reverts to control level when they quit smoking. The observed decrease in MAO activity in smokers is presumably due to their exposure to tobacco constituents that possess MAO-inhibiting properties. The inhibition of MAO activity seems, however, not to be a unique feature of tobacco smoking as subjects with Type II alcoholism have been reported to show a similar decrease in MAO activity that reverses when they cease to use alcohol. The present review summarizes the data on MAO-inhibiting tobacco constituents and explains that the decrease in MAO activity observed in alcoholics is probably due to concomitant tobacco use. It is concluded that the inhibition of MAO by constituents contained in tobacco and tobacco smoke, enhances the addiction induced by tobacco smoking.", "title": "Contribution of monoamine oxidase (MAO) inhibition to tobacco and alcohol addiction." }, { "docid": "MED-2755", "text": "A randomised controlled trial with a factorial design was done to examine the effects of dietary intervention in the secondary prevention of myocardial infarction (MI). 2033 men who had recovered from MI were allocated to receive or not to receive advice on each of three dietary factors: a reduction in fat intake and an increase in the ratio of polyunsaturated to saturated fat, an increase in fatty fish intake, and an increase in cereal fibre intake. The advice on fat was not associated with any difference in mortality, perhaps because it produced only a small reduction (3-4%) in serum cholesterol. The subjects advised to eat fatty fish had a 29% reduction in 2 year all-cause mortality compared with those not so advised. This effect, which was significant, was not altered by adjusting for ten potential confounding factors. Subjects given fibre advice had a slightly higher mortality than other subjects (not significant). The 2 year incidence of reinfarction plus death from ischaemic heart disease was not significantly affected by any of the dietary regimens. A modest intake of fatty fish (two or three portions per week) may reduce mortality in men who have recovered from MI.", "title": "Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART)." }, { "docid": "MED-3019", "text": "Background: Methylmercury (MeHg) is a known neuro-toxicant. Emerging evidence indicates it may have adverse effects on the neuro-logic and other body systems at common low levels of exposure. Impacts of MeHg exposure could vary by individual susceptibility or be confounded by bene-ficial nutrients in fish containing MeHg. Despite its global relevance, synthesis of the available literature on low-level MeHg exposure has been limited. Objectives: We undertook a synthesis of the current knowledge on the human health effects of low-level MeHg exposure to provide a basis for future research efforts, risk assessment, and exposure remediation policies worldwide. Data sources and extraction: We reviewed the published literature for original human epidemio-logic research articles that reported a direct biomarker of mercury exposure. To focus on high-quality studies and those specifically on low mercury exposure, we excluded case series, as well as studies of populations with unusually high fish consumption (e.g., the Seychelles), marine mammal consumption (e.g., the Faroe Islands, circumpolar, and other indigenous populations), or consumption of highly contaminated fish (e.g., gold-mining regions in the Amazon). Data synthesis: Recent evidence raises the possibility of effects of low-level MeHg exposure on fetal growth among susceptible subgroups and on infant growth in the first 2 years of life. Low-level effects of MeHg on neuro-logic outcomes may differ by age, sex, and timing of exposure. No clear pattern has been observed for cardio-vascular disease (CVD) risk across populations or for specific CVD end points. For the few studies evaluating immunologic effects associated with MeHg, results have been inconsistent. Conclusions: Studies targeted at identifying potential mechanisms of low-level MeHg effects and characterizing individual susceptibility, sexual dimorphism, and non-linearity in dose response would help guide future prevention, policy, and regulatory efforts surrounding MeHg exposure.", "title": "Evidence on the Human Health Effects of Low-Level Methylmercury Exposure" }, { "docid": "MED-3541", "text": "OBJECTIVE: The study evaluated the association between consumption frequencies of the major food categories and the risk of new depression four years later in older Taiwanese. DESIGN: A prospective cohort study with multistage random sampling. Logistic regression analysis evaluated the significance of the longitudinal associations of intake frequencies of the major food categories with future (4 years later) risk of new depression, controlled for possible confounding factors with or without adjustment for cognitive status. SETTING: Population-based free-living elderly. SUBJECTS: Men and women (n 1609) ≥65 years of age. RESULTS: In a regression model that controlled for demographic, socio-economic, lifestyle and disease/health-related variables but not cognitive status, both fruits (OR = 0·66, 95 % CI 0·45, 0·98, P = 0·038) and vegetables (OR = 0·38, 95 % CI 0·17, 0·86, P = 0·021) were protective against depressive symptoms 4 years later. However, when the same regression model was also adjusted for cognitive status, only vegetables (OR = 0·40, 95 % CI 0·17, 0·95, P = 0·039) were protective against depressive symptoms. Higher consumption of eggs was close to being significant in both regression models (P = 0·087 and 0·069, respectively). Other food categories including meat/poultry, fish, seafood, dairy, legumes, grains and tea showed no significant associations. CONCLUSIONS: Results suggest that although confounding factors cannot be totally ruled out, more frequent consumption of vegetables seems to be protective against depressive symptoms in the elderly. Further studies are needed to elucidate the causal role and the mechanism of the association.", "title": "Frequent consumption of vegetables predicts lower risk of depression in older Taiwanese - results of a prospective population-based study." }, { "docid": "MED-3031", "text": "Background: Mercury (Hg) is a toxic metal that presents public health risks through fish consumption. A major source of uncertainty in evaluating harmful exposure is inadequate knowledge of Hg concentrations in commercially important seafood. Objectives: We examined patterns, variability, and knowledge gaps of Hg in common commercial seafood items in the United States and compared seafood Hg concentrations from our database to those used for exposure estimates and consumption advice. Methods: We developed a database of Hg concentrations in fish and shellfish common to the U.S. market by aggregating available data from government monitoring programs and the scientific literature. We calculated a grand mean for individual seafood items, based on reported means from individual studies, weighted by sample size. We also compared database results to those of federal programs and human health criteria [U.S. Food and Drug Administration Hg Monitoring Program (FDA-MP), U.S. Environmental Protection Agency (EPA)]. Results: Mean Hg concentrations for each seafood item were highly variable among studies, spanning 0.3–2.4 orders of magnitude. Farmed fish generally had lower grand mean Hg concentrations than their wild counterparts, with wild seafood having 2- to12-fold higher concentrations, depending on the seafood item. However, farmed fish are relatively understudied, as are specific seafood items and seafood imports from Asia and South America. Finally, we found large discrepancies between mean Hg concentrations estimated from our database and FDA-MP estimates for most seafood items examined. Conclusions: The high variability in Hg in common seafood items has considerable ramifications for public health and the formulation of consumption guidelines. Exposure and risk analyses derived from smaller data sets do not reflect our collective, available information on seafood Hg concentrations.", "title": "A Quantitative Synthesis of Mercury in Commercial Seafood and Implications for Exposure in the United States" }, { "docid": "MED-3028", "text": "OBJECTIVE The evidence on the association between fish consumption, dietary long-chain n-3 fatty acids, and risk of type 2 diabetes is inconsistent. We therefore performed a systematic review and meta-analysis of the available prospective evidence. RESEARCH DESIGN AND METHODS Studies were identified by searching the PubMed and EMBASE databases through 15 December 2011 and by reviewing the reference lists of retrieved articles. Prospective studies were included if they reported relative risk (RR) estimates with 95% CIs for the association between fish consumption and/or dietary long-chain n-3 fatty acids and incidence of type 2 diabetes. A dose-response random-effects model was used to combine study-specific RRs. Potential sources of heterogeneity were explored by prespecified stratifications. RESULTS Sixteen studies involving 527,441 participants and 24,082 diabetes cases were included. Considerable statistical heterogeneity in the overall summary estimates was partly explained by geographical differences. For each serving per week increment in fish consumption, the RRs (95% CIs) of type 2 diabetes were 1.05 (1.02–1.09), 1.03 (0.96–1.11), and 0.98 (0.97–1.00) combining U.S., European, and Asian/Australian studies, respectively. For each 0.30 g per day increment in long-chain n-3 fatty acids, the corresponding summary estimates were 1.17 (1.09–1.26), 0.98 (0.70–1.37), and 0.90 (0.82–0.98). CONCLUSIONS Results from this meta-analysis indicate differences between geographical regions in observed associations of fish consumption and dietary intake of long-chain n-3 fatty acids with risk of type 2 diabetes. In consideration of the heterogeneous results, the relationship warrants further investigation. Meanwhile, current public health recommendations on fish consumption should be upheld unchanged.", "title": "Fish Consumption, Dietary Long-Chain n-3 Fatty Acids, and Risk of Type 2 Diabetes" }, { "docid": "MED-3023", "text": "Exposure to methylmercury at any stage of central nervous system development could induce alterations and result in severe congenital abnormalities. Total mercury level in maternal hair during pregnancy correlates well with blood levels of methylmercury and with total mercury levels in fetal brain. A prospective study has been conducted and a total of 137 childbearing women living at the coastal region with term, normal pregnancies were included and their newborns evaluated by ultrasonography. Mothers and their newborns are divided in two groups according to their hair mercury levels; examined group with high body levels of mercury (≥ 1 μg/g) and control group with low body levels of mercury (<1 μg/g). Neurosonographic examination was conducted to all newborns. Two dimensions of cerebellum in the sagital-medial plane have been measured: maximum height and width starting from the roof of the fourth chamber. Majority of mothers had hair mercury levels lower than 1 μg/g (N = 107). Mean value was 0.88 μg/g (SD 1.24), ranging from 0.02 to 8.71 μg/g. There was no significant difference between the two groups when it comes to the width of cerebellum (Mann-Whitney test: Z = 1471; p = 0.141). However, comparison related to the length of cerebellum shows statistically significant smaller cerebellum in newborns whose mother had hair mercury levels higher than 1 μg/g (Mann-Whitney test: Z = 2329; p = 0.019). Our results lead to a conclusion that prenatal exposure to, what we consider to be, low-levels of methylmercury does influence fetal brain development detected as decreased size of newborn's cerebellum. From a clinical point of view, a question related to the influence of prenatal low-level methylmercury exposure on fetal neurodevelopment remains open. Our further objectives are to direct the research towards performing detailed neuropshychological tests on children at the age of 18 months. Such tests could indicate the presence of subtle neurological or neuropsychological deficits. Copyright © 2010 Elsevier Ltd. All rights reserved.", "title": "Relationship between the prenatal exposure to low-level of mercury and the size of a newborn's cerebellum." }, { "docid": "MED-1353", "text": "Depression is a potentially life-threatening disorder affecting millions of people across the globe. It is a huge burden to both the individual and society, costing over £9 billion in 2000 alone: the World Health Organisation (WHO) cited it as the third leading cause of global disability in 2004 (first in the developed world), and project it will be the leading cause by 2030. The serendipitous discovery of antidepressants has revolutionized both our understanding and management of depression: however, their efficacy in the treatment of depression has long been debated and recently been brought very much into the public limelight by a controversial publication by Kirsch, in which the role of placebo response in antidepressant efficacy trials is highlighted. Whilst antidepressants offer benefits in both the short and long term, important problems persist such as intolerability, delayed therapeutic onset, limited efficacy in milder depression and the existence of treatment-resistant depression.", "title": "The drugs don’t work? antidepressants and the current and future pharmacological management of depression" }, { "docid": "MED-5362", "text": "BACKGROUND: Studies of single nutrients on depression have produced inconsistent results, and they have failed to consider the complex interactions between nutrients. An increasing number of studies in recent years are investigating the association of overall dietary patterns and depression. OBJECTIVE: This study aimed to systematically review current literature and conduct meta-analyses of studies addressing the association between dietary patterns and depression. DESIGN: Six electronic databases were searched for articles published up to August 2013 that examined the association of total diet and depression among adults. Only studies considered methodologically rigorous were included. Two independent reviewers completed study selection, quality rating, and data extraction. Effect sizes of eligible studies were pooled by using random-effects models. A summary of the findings was presented for studies that could not be meta-analyzed. RESULTS: A total of 21 studies were identified. Results from 13 observational studies were pooled. Two dietary patterns were identified. The healthy diet pattern was significantly associated with a reduced odds of depression (OR: 0.84; 95% CI: 0.76, 0.92; P < 0.001). No statistically significant association was observed between the Western diet and depression (OR: 1.17; 95% CI: 0.97, 1.68; P = 0.094); however, the studies were too few for a precise estimate of this effect. CONCLUSIONS: The results suggest that high intakes of fruit, vegetables, fish, and whole grains may be associated with a reduced depression risk. However, more high-quality randomized controlled trials and cohort studies are needed to confirm this finding, specifically the temporal sequence of this association.", "title": "A systematic review and meta-analysis of dietary patterns and depression in community-dwelling adults." }, { "docid": "MED-3035", "text": "Prenatal and early childhood exposure to methylmercury (MeHg) or polychlorinated biphenyls (PCBs) are associated with deficits in cognitive, sensory, motor and other functions measured by neurobehavioral tests. The main objective of this pilot study was to determine whether functional magnetic resonance imaging (fMRI) is effective for visualization of brain function alterations related to neurobehavior in subjects with high prenatal exposure to the two neurotoxicants, MeHg and PCBs. Twelve adolescents (all boys) from a Faroese birth cohort assembled in 1986–1987 were recruited based on their prenatal exposures to MeHg and PCB. All underwent fMRI scanning during behavioral tasks at age 15 years. Subjects with high mixed exposure to MeHg and PCBs were compared to those with low mixed exposure on fMRI photic stimulation and a motor task. Boys with low mixed exposures showed patterns of fMRI activation during visual and motor tasks that are typical of normal control subjects. However, those with high exposures showed activation in more areas of the brain and different and wider patterns of activation than the low mixed exposure group. The brain activation patterns observed in association with increased exposures to MeHg and PCBs are meaningful in regard to the known neurotoxicity of these substances. This methodology therefore has potential utility in visualizing structural neural system determinants of exposure-induced neurobehavioral dysfunction.", "title": "Functional MRI approach to developmental methylmercury and polychlorinated biphenyl neurotoxicity" }, { "docid": "MED-1352", "text": "Antidepressant medications are the first-line treatment for people meeting current diagnostic criteria for major depressive disorder. Most antidepressants are designed to perturb the mechanisms that regulate the neurotransmitter serotonin – an evolutionarily ancient biochemical found in plants, animals, and fungi. Many adaptive processes evolved to be regulated by serotonin, including emotion, development, neuronal growth and death, platelet activation and the clotting process, attention, electrolyte balance, and reproduction. It is a principle of evolutionary medicine that the disruption of evolved adaptations will degrade biological functioning. Because serotonin regulates many adaptive processes, antidepressants could have many adverse health effects. For instance, while antidepressants are modestly effective in reducing depressive symptoms, they increase the brain’s susceptibility to future episodes after they have been discontinued. Contrary to a widely held belief in psychiatry, studies that purport to show that antidepressants promote neurogenesis are flawed because they all use a method that cannot, by itself, distinguish between neurogenesis and neuronal death. In fact, antidepressants cause neuronal damage and mature neurons to revert to an immature state, both of which may explain why antidepressants also cause neurons to undergo apoptosis (programmed death). Antidepressants can also cause developmental problems, they have adverse effects on sexual and romantic life, and they increase the risk of hyponatremia (low sodium in the blood plasma), bleeding, stroke, and death in the elderly. Our review supports the conclusion that antidepressants generally do more harm than good by disrupting a number of adaptive processes regulated by serotonin. However, there may be specific conditions for which their use is warranted (e.g., cancer, recovery from stroke). We conclude that altered informed consent practices and greater caution in the prescription of antidepressants are warranted.", "title": "Primum Non Nocere: An Evolutionary Analysis of Whether Antidepressants Do More Harm than Good" }, { "docid": "MED-1203", "text": "BACKGROUND: Clinical mood disorders often become clinically manifest in the later teenage years and early twenties and can be associated with a poor long-term prognosis. The primary prevention of these disorders would therefore have great public health value. Nutritional supplements are a feasible intervention for primary prevention and several epidemiological studies have indicated links between low folate status and depressive symptomatology in the general population. METHOD: A randomised, double blind, parallel group, placebo-controlled trial in which participants, aged 14-24 years, at increased familial risk of mood disorder, were randomised to folic acid (2.5 mg daily) or identical placebo liquid for a maximum of 36 months. Primary outcome data (the onset of a DSM-IV mood disorder) were collected from 112 participants; 56 per group. RESULTS: The incidence of mood disorder in the folic acid and placebo groups were 14.3% and 17.9% respectively, a non-significant difference. However, there was post-hoc evidence that folic acid delayed the time to onset of mood disorder in those participants who became unwell. LIMITATIONS: Small sample size and rate of onset of mood disorders lower than expected. CONCLUSIONS: Although long term folic acid supplementation was well tolerated, with high levels of adherence, there was no evidence that it reduced the incidence of mood disorder compared to those taking placebo. Copyright © 2014 Elsevier B.V. All rights reserved.", "title": "Folic acid supplementation for prevention of mood disorders in young people at familial risk: a randomised, double blind, placebo controlled trial." }, { "docid": "MED-2750", "text": "OBJECTIVE: To see whether mortality among men with angina can be reduced by dietary advice. DESIGN: A randomized controlled factorial trial. SETTING: Male patients of general practitioners in south Wales. SUBJECTS: A total of 3114 men under 70 y of age with angina. INTERVENTIONS: Subjects were randomly allocated to four groups: (1) advised to eat two portions of oily fish each week, or to take three fish oil capsules daily; (2) advised to eat more fruit, vegetables and oats; (3) given both the above types of advice; and (4) given no specific dietary advice. Mortality was ascertained after 3-9 y. RESULTS: Compliance was better with the fish advice than with the fruit advice. All-cause mortality was not reduced by either form of advice, and no other effects were attributable to fruit advice. Risk of cardiac death was higher among subjects advised to take oily fish than among those not so advised; the adjusted hazard ratio was 1.26 (95% confidence interval 1.00, 1.58; P=0.047), and even greater for sudden cardiac death (1.54; 95% CI 1.06, 2.23; P=0.025). The excess risk was largely located among the subgroup given fish oil capsules. There was no evidence that it was due to interactions with medication. CONCLUSIONS: Advice to eat more fruit was poorly complied with and had no detectable effect on mortality. Men advised to eat oily fish, and particularly those supplied with fish oil capsules, had a higher risk of cardiac death. This result is unexplained; it may arise from risk compensation or some other effect on patients' or doctors' behaviour.", "title": "Lack of benefit of dietary advice to men with angina: results of a controlled trial." }, { "docid": "MED-1199", "text": "BACKGROUND: Enhanced oxidative stress or defective anti-oxidant defenses are related to the pathogenesis of depressive symptoms. Lycopene is the most powerful antioxidant amongst the carotenoids. The aim of this study was to investigate the relationship between different vegetables, including tomatoes/tomato products (a major source of lycopene), and depressive symptoms in a community-based elderly population. METHODS: We analyzed a cross-sectional survey including 986 community-dwelling elderly Japanese individuals aged 70 years and older. Dietary intake was assessed using a valid self-administered diet-history questionnaire, and depressive symptoms were evaluated using the 30-item Geriatric Depression Scale with 2 cut-off points: 11 (mild and severe) and 14 (severe) or use of anti-depressive agents. RESULTS: The prevalence of mild and severe and severe depressive symptoms was 34.9% and 20.2%, respectively. After adjustments for potentially confounding factors, the odds ratios of having mild and severe depressive symptoms by increasing levels of tomatoes/tomato products were 1.00, 0.54, and 0.48 (p for trend <0.01). Similar relationships were also observed in the case of severe depressive symptoms. In contrast, no relationship was observed between intake of other kinds of vegetables and depressive symptoms. LIMITATIONS: This is a cross-sectional study, and not for making a clinical diagnosis of depressive episodes. CONCLUSIONS: This study demonstrated that a tomato-rich diet is independently related to lower prevalence of depressive symptoms. These results suggest that a tomato-rich diet may have a beneficial effect on the prevention of depressive symptoms. Further studies are needed to confirm these findings. Copyright © 2012 Elsevier B.V. All rights reserved.", "title": "A tomato-rich diet is related to depressive symptoms among an elderly population aged 70 years and over: a population-based, cross-sectional analysis." }, { "docid": "MED-5366", "text": "CONTEXT: Adherence to the Mediterranean dietary pattern (MDP) is thought to reduce inflammatory, vascular, and metabolic processes that may be involved in the risk of clinical depression. OBJECTIVE: To assess the association between adherence to the MDP and the incidence of clinical depression. DESIGN: Prospective study that uses a validated 136-item food frequency questionnaire to assess adherence to the MDP. The MDP score positively weighted the consumption of vegetables, fruit and nuts, cereal, legumes, and fish; the monounsaturated- to saturated-fatty-acids ratio; and moderate alcohol consumption, whereas meat or meat products and whole-fat dairy were negatively weighted. SETTING: A dynamic cohort of university graduates (Seguimiento Universidad de Navarra/University of Navarra Follow-up [SUN] Project). PARTICIPANTS: A total of 10 094 initially healthy Spanish participants from the SUN Project participated in the study. Recruitment began on December 21, 1999, and is ongoing. MAIN OUTCOME MEASURE: Participants were classified as having incident depression if they were free of depression and antidepressant medication at baseline and reported a physician-made diagnosis of clinical depression and/or antidepressant medication use during follow-up. RESULTS: After a median follow-up of 4.4 years, 480 new cases of depression were identified. The multiple adjusted hazard ratios (95% confidence intervals) of depression for the 4 upper successive categories of adherence to the MDP (taking the category of lowest adherence as reference) were 0.74 (0.57-0.98), 0.66 (0.50-0.86), 0.49 (0.36-0.67), and 0.58 (0.44-0.77) (P for trend <.001). Inverse dose-response relationships were found for fruit and nuts, the monounsaturated- to saturated-fatty-acids ratio, and legumes. CONCLUSIONS: Our results suggest a potential protective role of the MDP with regard to the prevention of depressive disorders; additional longitudinal studies and trials are needed to confirm these findings.", "title": "Association of the Mediterranean dietary pattern with the incidence of depression: the Seguimiento Universidad de Navarra/University of Navarra fol..." }, { "docid": "MED-5368", "text": "Intake of n-3 and n-6 polyunsaturated fatty acids (PUFAs) has been implicated in the pathogenesis of depression. We sought to estimate the association between intake of fish and n-3 and n-6 PUFAs and suicide mortality over the course of long-term follow-up. In this prospective cohort study, biennial questionnaires were administered to 42,290 men enrolled in the Health Professionals Follow-up Study (1988–2008), 72,231 women enrolled in the Nurses' Health Study (1986–2008), and 90,836 women enrolled in Nurses' Health Study II (1993–2007). Dietary fish and n-3 and n-6 PUFA intakes were assessed every 4 years using a validated food-frequency questionnaire. Suicide mortality was ascertained through blind physician review of death certificates and hospital or pathology reports. Adjusted relative risks of suicide mortality were estimated with multivariable Cox proportional hazards models and pooled across cohorts using random-effects meta-analysis. The pooled multivariable relative risks for suicide among persons in the highest quartile of intake of n-3 or n-6 PUFAs, relative to the lowest quartile, ranged from 1.08 to 1.46 for n-3 PUFAs (Ptrend = 0.11–0.52) and from 0.68 to 1.19 for n-6 PUFAs (Ptrend = 0.09–0.54). We did not find evidence that intake of n-3 PUFAs or fish lowered the risk of completed suicide.", "title": "Suicide Mortality in Relation to Dietary Intake of n-3 and n-6 Polyunsaturated Fatty Acids and Fish: Equivocal Findings From 3 Large US Cohort Studies" }, { "docid": "MED-5363", "text": "OBJECTIVE: Although several studies have reported associations of depressive state with specific nutrients and foods, few studies examined the association with dietary patterns in adults. We investigated the association between major dietary patterns and depressive symptoms in Japanese. METHODS: Subjects were 521 municipal employees (309 men and 212 women), aged 21-67 years, who participated in a health survey at the time of periodic checkup. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale. Dietary patterns were derived by using principal component analysis of the consumption of 52 food and beverage items, which was assessed by a validated brief diet history questionnaire. Logistic regression analysis was used to estimate odds ratios of depressive symptoms (CES-D >or=16) with adjustment for potential confounding variables. RESULTS: We identified three dietary patterns. A healthy Japanese dietary pattern characterized by high intakes of vegetables, fruit, mushrooms and soy products was associated with fewer depressive symptoms. The multivariate-adjusted odds ratios (95% confidence intervals) of having depressive symptoms for the lowest through highest tertiles of the healthy Japanese dietary pattern score were 1.00 (reference), 0.99 (0.62-1.59) and 0.44 (0.25-0.78), respectively (P for trend=0.006). Other dietary patterns were not appreciably associated with depressive symptoms. CONCLUSIONS: Our findings suggest that a healthy Japanese dietary pattern may be related to decreased prevalence of depressive status.", "title": "Dietary patterns and depressive symptoms among Japanese men and women." }, { "docid": "MED-3540", "text": "The 1950s saw the clinical introduction of the first two specifically antidepressant drugs: iproniazid, a monoamine-oxidase inhibitor that had been used in the treatment of tuberculosis, and imipramine, the first drug in the tricyclic antidepressant family. Iproniazid and imipramine made two fundamental contributions to the development of psychiatry: one of a social-health nature, consisting in an authentic change in the psychiatric care of depressive patients; and the other of a purely pharmacological nature, since these agents have constituted an indispensable research tool for neurobiology and psychopharmacology, permitting, among other things, the postulation of the first aetiopathogenic hypotheses of depressive disorders. The clinical introduction of fluoxetine, a selective serotonin reuptake inhibitor, in the late 1980s, once again revolutionized therapy for depression, opening the way for new families of antidepressants. The present work reviews, from a historical perspective, the entire process that led to the discovery of these drugs, as well as their contribution to the development of the neuroscientific disciplines. However, all of these antidepressants, like the rest of those currently available for clinical practice, share the same action mechanism, which involves the modulation of monoaminergic neurotransmission at a synaptic level, so that the future of antidepressant therapy would seem to revolve around the search for extraneuronal non-aminergic mechanisms or mechanisms that modulate the intraneuronal biochemical pathways.", "title": "Monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today." }, { "docid": "MED-5367", "text": "Objective We examined the cross-sectional and longitudinal relationship between plasma carotenoids and depressive symptoms over a six-year follow-up in older persons. Methods and Materials This research is part of the InCHIANTI Study, a prospective population-based study of older persons in Tuscany, Italy. The sample for this analysis included 958 women and men aged 65 years and older. Plasma total carotenoids were assessed at baseline. Depressive symptoms were assessed at baseline and at the 3- and 6-year follow-up using the Center for Epidemiological Studies-Depression Scale (CES-D). Depressed mood was defined as CES-D≥20. Results At baseline, higher total carotenoids level were associated with lower probability of depressed mood (OR=0.82, 95%CI=0.68–0.99, p=0.04) after adjustment for sociodemographic, health and inflammation. After the exclusion of participants with baseline depressed mood and use of antidepressants, higher total carotenoids level were associated with lower risk of incident depressed mood (OR=0.72, 95%CI=0.52–0.99, p=0.04) at 6-year follow-up, after adjustment for confounders plus baseline CES-D. Inflammatory marker Interleukin-1 receptor antagonist partially mediated this association. Discussion Low plasma concentrations of carotenoids are associated with depressive symptoms and predict the development of new depressive symptoms in older persons. Understanding the mechanism of this association may reveal potential targets for prevention and treatment.", "title": "The relationship between plasma carotenoids and depressive symptoms in older persons" }, { "docid": "MED-4633", "text": "Background The physical health status of vegetarians has been extensively reported, but there is limited research regarding the mental health status of vegetarians, particularly with regard to mood. Vegetarian diets exclude fish, the major dietary source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), critical regulators of brain cell structure and function. Omnivorous diets low in EPA and DHA are linked to impaired mood states in observational and experimental studies. Methods We examined associations between mood state and polyunsaturated fatty acid intake as a result of adherence to a vegetarian or omnivorous diet in a cross-sectional study of 138 healthy Seventh Day Adventist men and women residing in the Southwest. Participants completed a quantitative food frequency questionnaire, Depression Anxiety Stress Scale (DASS), and Profile of Mood States (POMS) questionnaires. Results Vegetarians (VEG:n = 60) reported significantly less negative emotion than omnivores (OMN:n = 78) as measured by both mean total DASS and POMS scores (8.32 ± 0.88 vs 17.51 ± 1.88, p = .000 and 0.10 ± 1.99 vs 15.33 ± 3.10, p = .007, respectively). VEG reported significantly lower mean intakes of EPA (p < .001), DHA (p < .001), as well as the omega-6 fatty acid, arachidonic acid (AA; p < .001), and reported higher mean intakes of shorter-chain α-linolenic acid (p < .001) and linoleic acid (p < .001) than OMN. Mean total DASS and POMS scores were positively related to mean intakes of EPA (p < 0.05), DHA (p < 0.05), and AA (p < 0.05), and inversely related to intakes of ALA (p < 0.05), and LA (p < 0.05), indicating that participants with low intakes of EPA, DHA, and AA and high intakes of ALA and LA had better mood. Conclusions The vegetarian diet profile does not appear to adversely affect mood despite low intake of long-chain omega-3 fatty acids.", "title": "Vegetarian diets are associated with healthy mood states: a cross-sectional study in Seventh Day Adventist adults" }, { "docid": "MED-1345", "text": "This article explores the reaction when an article challenging received wisdom is published and covered extensively by the media (1). The article in question was a meta-analysis of antidepressant clinical trials indicating that for most patients, difference between drug and placebo was not clinically significant. Reactions ranged from denial that the effects of antidepressants are so small to criticisms of the clinical trials that were analyzed. Each of these reactions is explored and countered.", "title": "Challenging Received Wisdom: Antidepressants and the Placebo Effect" }, { "docid": "MED-1351", "text": "The relationship between psychiatry and pharmaceutical companies has come under scrutiny during the past decade. Concerns are growing that financial ties of psychiatrists to the pharmaceutical industry may unduly influence professional judgments involving the primary interests of patients. Such conflicts of interest threaten the public trust in psychiatry. The goal of conflict of interest policies is to protect the integrity of professional judgment and to preserve public trust. The disclosure of individual and institutional financial relationships is a critical but limited first step in the process of identifying and responding to conflicts of interest. Conflict of interest policies and procedures can be strengthened by engaged psychiatrists, researchers, institutions, and professional associations in developing policies and consensus standards. Research on conflicts of interest can provide a stronger evidence base for policy design and implementation. Society has traditionally granted the medical profession considerable autonomy and may be willing to continue do so in the case of conflicts of interest. Nevertheless, concern is growing that stronger measures are needed. To avoid undue regulatory burdens, psychiatrists can play a vital role in designing responsible and reasonable conflict of interest policies that reduce the risks of bias and the loss of trust. Psychiatrists and the institutions that carry out research, education, clinical care, and practice guideline development must recognize public concerns about conflicts of interest and take effective measures soon to maintain public trust with a cultural change in the practice of psychiatry, from reactive treatment-seeking for mental illness to proactive advocacy for patients. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.", "title": "Conflicts of interest in psychiatry: strategies to cultivate literacy in daily practice." }, { "docid": "MED-1359", "text": "Previous meta-analyses investigating the effect of exercise on depression have included trials where the control condition has been categorized as placebo despite the fact that this particular placebo intervention (e.g., meditation, relaxation) has been recognized as having an antidepressant effect. Because meditation and mindfulness-based interventions are associated with depression reduction, it is impossible to separate the effect of the physical exercise from the meditation-related parts. The present study determined the efficacy of exercise in reducing symptoms of depression compared with no treatment, placebo conditions or usual care among clinically defined depressed adults. Of 89 retrieved studies, 15 passed the inclusion criteria of which 13 studies presented sufficient information for calculating effect sizes. The main result showed a significant large overall effect favoring exercise intervention. The effect size was even larger when only trials that had used no treatment or placebo conditions were analyzed. Nevertheless, effect size was reduced to a moderate level when only studies with high methodological quality were included in the analysis. Exercise may be recommended for people with mild and moderate depression who are willing, motivated, and physically healthy enough to engage in such a program. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.", "title": "Physical exercise intervention in depressive disorders: meta-analysis and systematic review." }, { "docid": "MED-1196", "text": "Background Studies of diet and depression have focused primarily on individual nutrients. Aims To examine the association between dietary patterns and depression using an overall diet approach. Method Analyses were carried on data from 3486 participants (26.2% women, mean age 55.6 years) from the Whitehall II prospective cohort, in which two dietary patterns were identified: ‘whole food’ (heavily loaded by vegetables, fruits and fish) and ‘processed food’ (heavily loaded by sweetened desserts, fried food, processed meat, refined grains and high-fat dairy products). Self-reported depression was assessed 5 years later using the Center for Epidemiologic Studies – Depression (CES–D) scale. Results After adjusting for potential confounders, participants in the highest tertile of the whole food pattern had lower odds of CES–D depression (OR = 0.74, 95% CI 0.56–0.99) than those in the lowest tertile. In contrast, high consumption of processed food was associated with an increased odds of CES–D depression (OR = 1.58, 95% CI 1.11–2.23). Conclusions In middle-aged participants, a processed food dietary pattern is a risk factor for CES–D depression 5 years later, whereas a whole food pattern is protective.", "title": "Dietary pattern and depressive symptoms in middle age" }, { "docid": "MED-2756", "text": "BACKGROUND: Fish consumption and omega-3 polyunsaturated fatty acid (PUFA) intake are shown to protect from cardiovascular diseases (CVD). However, most fish contain environmental contaminants such as dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), and methylmercury (MeHg) that may have adverse effects on cardiovascular health. OBJECTIVE: Our aim was to elucidate the associations of fish consumption, omega-3 PUFAs, environmental contaminants with low-grade inflammation, early atherosclerosis, and traditional CVD risk factors. METHODS: The Health 2000 survey participants (n=1173) represented the general Finnish population and the Fishermen study participants (n=255) represented a population with high fish consumption and high exposure to environmental contaminants. Model-adjusted geometric means and tests for linear trend were calculated for CVD risk factors by tertiles of fish consumption and serum omega-3 PUFAs, and additionally in the Fishermen study only, by tertiles of serum PCDD/F+PCB, and blood MeHg. RESULTS: Serum triglyceride decreased across omega-3 PUFA tertiles in both sexes and studies. Insulin resistance, C-reactive protein, tumour necrosis factor α, and interleukin 6 decreased across omega-3 PUFA tertiles among the Health 2000 survey participants. Among the Fishermen study men, insulin resistance and arterial stiffness indicated by β-stiffness index tended to increase and the RR estimate for carotid artery plaque tended to decrease across tertiles of PCDD/F+PCB and MeHg. CONCLUSION: Previously established hypotriglyceridemic and anti-inflammatory effects of omega-3 PUFAs were seen also in this study. The hypothesised favourable effect on insulin sensitivity and arterial elasticity was suggested to be counteracted by high exposure to environmental contaminants but the effect on plaque prevalence appeared not to be harmful. Copyright © 2012 Elsevier Inc. All rights reserved.", "title": "Fish consumption, omega-3 fatty acids, and environmental contaminants in relation to low-grade inflammation and early atherosclerosis." }, { "docid": "MED-2907", "text": "Background: Diverse perspectives have influenced fish consumption choices. Objectives: We summarized the issue of fish consumption choice from toxicological, nutritional, ecological, and economic points of view; identified areas of overlap and disagreement among these viewpoints; and reviewed effects of previous fish consumption advisories. Methods: We reviewed published scientific literature, public health guidelines, and advisories related to fish consumption, focusing on advisories targeted at U.S. populations. However, our conclusions apply to groups having similar fish consumption patterns. Discussion: There are many possible combinations of matters related to fish consumption, but few, if any, fish consumption patterns optimize all domains. Fish provides a rich source of protein and other nutrients, but because of contamination by methylmercury and other toxicants, higher fish intake often leads to greater toxicant exposure. Furthermore, stocks of wild fish are not adequate to meet the nutrient demands of the growing world population, and fish consumption choices also have a broad economic impact on the fishing industry. Most guidance does not account for ecological and economic impacts of different fish consumption choices. Conclusion: Despite the relative lack of information integrating the health, ecological, and economic impacts of different fish choices, clear and simple guidance is necessary to effect desired changes. Thus, more comprehensive advice can be developed to describe the multiple impacts of fish consumption. In addition, policy and fishery management inter-ventions will be necessary to ensure long-term availability of fish as an important source of human nutrition.", "title": "Which Fish Should I Eat? Perspectives Influencing Fish Consumption Choices" }, { "docid": "MED-2753", "text": "The Diet and Reinfarction Trial (DART) involved 2033 men (mean age 56.5 years) recovering from myocardial infarction. They were randomly allocated to receive advice or to receive no advice on each of three dietary factors: an increase in fatty fish intake; a reduction in fat intake with an increase in polyunsaturated fat:saturated fat; an increased intake of cereal fibre. Compliance was satisfactory with the fish and fibre advice, but less so with the fat advice. The men given fish advice had 29% lower 2-year all-cause mortality; the other forms of advice did not have any significant effects. The Diet and Angina Randomized Trial (DART-2) involved 3114 men (mean age 61.1 years) with stable angina, who were followed up for 3-9 years. Advice to eat oily fish or take fish oil did not affect all-cause mortality, but it was associated with a significant increase in sudden cardiac death (P=0.018), and this effect was largely confined to the subgroup given fish oil capsules. Advice to eat more fruit and vegetables had no effect, probably because of poor compliance. The outcome of DART-2 appears to conflict with that of DART and some other studies; various possible explanations are considered. Nutritional interventions are not equally acceptable and should be tailored to the individuals for whom they are intended. Various distinct groups have a raised risk of CHD, and it cannot be assumed that the same nutritional interventions are appropriate to them all. Nutritional supplements do not necessarily have the same effects as the foods from which they are derived.", "title": "Secondary prevention of CHD in UK men: the Diet and Reinfarction Trial and its sequel." }, { "docid": "MED-1202", "text": "Low folate has been causatively linked to depression, but research is contradictory. An association may arise due to chance, bias, confounding or reverse causality. A systematic review of observational studies which examined the association between depression and folate was conducted. 11 relevant studies (15 315 participants; three case–control studies, seven population surveys and one cohort study) examining the risk of depression in the presence of low folate were found. Pooling showed a significant relationship between folate status and depression (odds ratio (OR)pooled unadjusted = 1.55; 95% CI 1.26 to 1.91). This relationship remained after adjustment for potential confounding (OR)pooled adjusted = 1.42; 95% CI 1.10 to 1.83). Folate levels were also lower in depression. There is accumulating evidence that low folate status is associated with depression. Much of this evidence comes from case–control and cross‐sectional studies. Cohort studies and definitive randomised‐controlled trials to test the therapeutic benefit of folate are required to confirm or refute a causal relationship.", "title": "Is low folate a risk factor for depression? A meta‐analysis and exploration of heterogeneity" }, { "docid": "MED-2904", "text": "Background Prenatal exposure to mercury has been associated with adverse childhood neurologic outcomes in epidemiologic studies. Dose–response information for this relationship is useful for estimating benefits of reduced mercury exposure. Objectives We estimated a dose–response relationship between maternal mercury body burden and subsequent childhood decrements in intelligence quotient (IQ), using a Bayesian hierarchical model to integrate data from three epidemiologic studies. Methods Inputs to the model consist of dose–response coefficients from studies conducted in the Faroe Islands, New Zealand, and the Seychelles Islands. IQ coefficients were available from previous work for the latter two studies, and a coefficient for the Faroe Islands study was estimated from three IQ subtests. Other tests of cognition/achievement were included in the hierarchical model to obtain more accurate estimates of study-to-study and end point–to–end point variability. Results We find a central estimate of −0.18 IQ points (95% confidence interval, −0.378 to −0.009) for each parts per million increase of maternal hair mercury, similar to the estimates for both the Faroe Islands and Seychelles studies, and lower in magnitude than the estimate for the New Zealand study. Sensitivity analyses produce similar results, with the IQ coefficient central estimate ranging from −0.13 to −0.25. Conclusions IQ is a useful end point for estimating neurodevelopmental effects, but may not fully represent cognitive deficits associated with mercury exposure, and does not represent deficits related to attention and motor skills. Nevertheless, the integrated IQ coefficient provides a more robust description of the dose–response relationship for prenatal mercury exposure and cognitive functioning than results of any single study.", "title": "Dose–Response Relationship of Prenatal Mercury Exposure and IQ: An Integrative Analysis of Epidemiologic Data" }, { "docid": "MED-1356", "text": "BACKGROUND: The objective of this study was to determine the association between regular physical activity and mental disorders among adults in the United States. METHODS: Multiple logistic regression analyses were used to compare the prevalence of mental disorders among those who did and did not report regular physical activity using data from the National Comorbidity Survey (n = 8098), a nationally representative sample of adults ages 15-54 in the United States. CONCLUSIONS: Slightly over one-half of adults reported regular physical activity (60.3%). Regular physical activity was associated with a significantly decreased prevalence of current major depression and anxiety disorders, but was not significantly associated with other affective, substance use, or psychotic disorders. The association between regular physical activity and lower prevalence of current major depression (OR = 0.75 (0.6,0.94)), panic attacks (OR = 0.73 (0.56, 0.96)), social phobia (OR = 0.65 (0.53, 0.8)), specific phobia (OR = 0.78 (0.63, 0.97)), and agoraphobia (OR = 0.64 (0.43, 0.94)) persisted after adjusting for differences in sociodemographic characteristics, self-reported physical disorders, and comorbid mental disorders. Self-reported frequency of physical activity also showed a dose-response relation with current mental disorders. DISCUSSION: These data document a negative association between regular physical activity and depressive and anxiety disorders among adults in the U.S. population. Future research that investigates the mechanism of this association using longitudinal data to examine the link between physical activity and incident and recurrent mental disorders across the lifespan is needed.", "title": "Association between physical activity and mental disorders among adults in the United States." }, { "docid": "MED-2910", "text": "Hit Reaction Time latencies (HRT) in the Continuous Performance Test (CPT) measure the speed of visual information processing. The latencies may involve different neuropsychological functions depending on the time from test initiation, i.e., first orientation, learning and habituation, then cognitive processing and focused attention, and finally sustained attention as the dominant demand. Prenatal methylmercury exposure is associated with increased reaction time (RT) latencies. We therefore examined the association of methylmercury exposure with the average HRT at age 14 years at three different time intervals after test initiation. A total of 878 adolescents (87% of birth cohort members) completed the CPT. The RT latencies were recorded for 10 minutes, with visual targets presented at 1000 ms intervals. After confounder adjustment, regression coefficients showed that CPT-RT outcomes differed in their associations with exposure biomarkers of prenatal methylmercury exposure: During the first two minutes, the average HRT was weakly associated with methylmercury (beta (SE) for a ten-fold increase in exposure, (3.41 (2.06)), was strongly for the 3-to-6 minute interval (6.10 (2.18)), and the strongest during 7–10 minutes after test initiation (7.64 (2.39)). This pattern was unchanged when simple reaction time and finger tapping speed were included in the models as covariates. Postnatal methylmercury exposures did not affect the outcomes. Thus, these findings suggest that sustained attention as a neuropsychological domain is particularly vulnerable to developmental methylmercury exposure, indicating probable underlying dysfunction of the frontal lobes. When using CPT data as a possible measure of neurotoxicity, test results should therefore be analyzed in regard to time from test initiation and not as overall average reaction times.", "title": "Sensitivity of Continuous Performance Test (CPT) at Age 14 Years to Developmental Methylmercury Exposure" }, { "docid": "MED-3030", "text": "Consumption of marine fish provides both benefits (lean protein, omega-3 fatty acids and essential nutrients) and risks (main source of mercury (Hg) exposure for humans). Mercury is a potent neurotoxin and the source of more fish advisories nationwide than any other toxicant. Despite the widespread nature of Hg, it is unknown whether local Hg contamination reflects national and regional levels often used as bases to inform consumers of potential fish consumption risk. Thus, the objectives of our study were to examine Hg levels of six commonly consumed marine species harvested locally off the North Carolina coast and to compare our results to published regional (Monterey Bay Aquarium's Seafood Watch List) and national (Environmental Protection Agency, EPA, and Food and Drug Administration, FDA) Hg averages, action levels, and guidelines. We found significant differences in Hg concentrations among collected species, and we identified correlations between Hg concentration and fish length and trophic levels. Collected mahi mahi and triggerfish were below the EPA fish tissue action level (0.3ppm). Wahoo and grouper exceeded the EPA action level but were below the FDA action level (1.0ppm). King mackerel had the highest Hg concentration among targeted species, exceeding both EPA and FDA action levels. Further, our local results were not always consistent with calculated averages from EPA and FDA databases for the same species, and although many of our findings were consistent with Monterey Bay Aquarium's Seafood Watch List (southeast region), recommendations based on Hg levels would conflict with recommendations they provide based on sustainability. We find regional and national averages are not always reflective of local Hg contamination and suggest local data may be needed to accurately assess consumer risk.", "title": "Do national advisories serve local consumers: an assessment of mercury in economically important North Carolina fish." }, { "docid": "MED-4632", "text": "Vegetarians have an apparent diminished risk for the development of ischemic coronary heart disease. This may be secondary to dietary effects of plasma lipids and lipoproteins, but platelets, which may also play a role, have also been observed to have aberrant functions in vegetarians. We measured plasma lipid and lipoprotein levels, platelet function, platelet fatty acid levels, and platelet active prostaglandins in ten strict vegetarians (vegans), 15 lactovegetarians, and 25 age- and sex-matched omnivorous controls. The most striking observations were a highly significant rise in platelet linoleic acid concentration and a decline in platelet arachidonic acid concentration in both vegetarian subgroups as compared with omnivorous controls. Serum thromboxane and prostacyclin levels as well as results of platelet aggregation studies did not differ among the groups tested. Cholesterol levels were significantly lower in both vegetarian groups as compared with controls, but plasma high- and low-density lipoprotein levels were lower only in the vegan subgroup as compared with omnivores. If diet produces these changes in platelet fatty acid and plasma lipid levels it may contribute to the decreased risk of coronary heart disease and possibly atherosclerosis in vegetarians.", "title": "The effect of vegetarian diets on plasma lipid and platelet levels." }, { "docid": "MED-1358", "text": "This paper documents the recent (1976-1995) literature on the acute mood effects associated with participation in single sessions of exercise. Issues regarding experimental design, \"ecological validity' and the operational definition of mood are addressed. Results from these studies suggest that both clinical and nonclinical subjects may benefit acutely from even a single bout of exercise. Finally, possible mechanisms and recommendations for future research are discussed.", "title": "The acute effects of exercise on mood state." }, { "docid": "MED-2751", "text": "Recent data on fishmeal and fish-oil supply are presented identifying key producer countries and raw material sources and distinguishing between whole fish and by-products. The conversion of these raw materials into marine ingredients is discussed and global volumes presented. This is followed by a summary of the main countries using these marine ingredients over recent years. Uses of fishmeal and fish-oil by market segment are then presented. From this, a global mass balance of inputs and outputs is derived which allows the calculation of the input-to-output ratios (fish in:fish out; FIFO) for the main aquaculture production types to be made. Current areas of focus by the industry include the need to demonstrate sustainable practice, more strategic use of marine ingredients, greater use of fishery and land-animal by-products as well as vegetable substitutes, and novel sources of essential omega-3 fats, notably the long-chain polyunsaturated fatty acids, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Implications are drawn for future supply prospects of fishmeal and fish-oil and their future role in aquaculture, agriculture and human health. © 2013 The Fisheries Society of the British Isles.", "title": "Global fishmeal and fish-oil supply: inputs, outputs and markets." }, { "docid": "MED-3027", "text": "Background Some persistent environmental chemicals are suspected of causing an increased risk of type 2 diabetes mellitus, a disease particularly common after age 70. This concern was examined in a cross-sectional study of elderly subjects in a population with elevated contaminant exposures from seafood species high in the food chain. Methods Clinical examinations of 713 Faroese residents aged 70-74 years (64% of eligible population) included fasting plasma concentrations of glucose and insulin, and glycosylated hemoglobin. Lifetime exposure to persistent environmental chemicals from pilot whale and other traditional food was estimated from a dietary questionnaire and by analysis of blood samples for polychlorinated biphenyls (PCBs) and related food contaminants. Results Septuagenarians with type 2 diabetes or impaired fasting glycemia tended to have higher PCB concentrations and higher past intake of traditional foods, especially during childhood and adolescence. In non-diabetic subjects, the fasting insulin concentration decreased by 7% (95% CI= −12% to −2%) for each doubling of the PCB concentration after adjustment for sex and body mass index at age 20. Conversely, the fasting glucose concentration increased by 6% (−1% to 13%) for each doubling in PCB. Similar associations were seen in subjects without impaired fasting glycemia, while further adjustment for current body mass index and lipid metabolism parameters attenuated some of the associations. Conclusions Impaired insulin secretion appears to constitute an important part of the type 2 diabetes pathogenesis associated with exposure to persistent lipophilic food contaminants.", "title": "Marine Food Pollutants as a Risk Factor for Hypoinsulinemia and Type 2 Diabetes" }, { "docid": "MED-3546", "text": "CONTEXT: The monoamine theory of depression proposes that monoamine levels are lowered, but there is no explanation for how monoamine loss occurs. Monoamine oxidase A (MAO-A) is an enzyme that metabolizes monoamines, such as serotonin, norepinephrine, and dopamine. OBJECTIVE: To determine whether MAO-A levels in the brain are elevated during untreated depression. SETTING: Tertiary care psychiatric hospital. PATIENTS: Seventeen healthy and 17 depressed individuals with major depressive disorder that met entry criteria were recruited from the care of general practitioners and psychiatrists. All study participants were otherwise healthy and nonsmoking. Depressed individuals had been medication free for at least 5 months. MAIN OUTCOME MEASURE: Harmine labeled with carbon 11, a radioligand selective for MAO-A and positron emission tomography, was used to measure MAO-A DVS (specific distribution volume), an index of MAO-A density, in different brain regions (prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex, caudate, putamen, thalamus, anterior temporal cortex, midbrain, hippocampus, and parahippocampus). RESULTS: The MAO-A DVS was highly significantly elevated in every brain region assessed (t test; P=.001 to 3x10(-7)). The MAO-A DVS was elevated on average by 34% (2 SDs) throughout the brain during major depression. CONCLUSIONS: The sizable magnitude of this finding and the absence of other compelling explanations for monoamine loss during major depressive episodes led to the conclusion that elevated MAO-A density is the primary monoamine-lowering process during major depression.", "title": "Elevated monoamine oxidase a levels in the brain: an explanation for the monoamine imbalance of major depression." }, { "docid": "MED-3032", "text": "Fish consumption during gestation can provide the fetus with long chain polyunsaturated fatty acids (LCPUFA) and other nutrients essential for growth and development of the brain. However, fish consumption also exposes the fetus to the neurotoxicant, methyl mercury (MeHg). We studied the association between these fetal exposures and early child development in the Seychelles Child Development Nutrition Study (SCDNS). Specifically, we examined a priori models of Ω-3 and Ω-6 LCPUFA measures in maternal serum to test the hypothesis that these LCPUFA families before or after adjusting for prenatal MeHg exposure would reveal associations with child development assessed by the BSID-II at ages 9 and 30 months. There were 229 children with complete outcome and covariate data available for analysis. At 9 months, the PDI was positively associated with total Ω-3 LCPUFA and negatively associated with the ratio of Ω-6/Ω-3 LCPUFA. These associations were stronger in models adjusted for prenatal MeHg exposure. Secondary models suggested that the MeHg effect at 9 months varied by the ratio of Ω-6/Ω-3 LCPUFA. There were no significant associations between LCPUFA measures and the PDI at 30 months. There were significant adverse associations, however, between prenatal MeHg and the 30 month PDI when the LCPUFA measures were included in the regression analysis. The BSID-II Mental Developmental Index (MDI) was not associated with any exposure variable. These data support the potential importance to child development of prenatal availability of Ω-3 LCPUFA present in fish and of LCPUFA in the overall diet. Furthermore, they indicate that the beneficial effects of LCPUFA can obscure the determination of adverse effects of prenatal MeHg exposure in longitudinal observational studies.", "title": "Associations of maternal long chain polyunsaturated fatty acids, methyl mercury, and infant development in the Seychelles Child Development Nutrition Study" }, { "docid": "MED-3020", "text": "Brains from 32 neonatal autopsies from the Seychelles were examined histologically and analyzed for mercury levels. Six brain regions were sampled: frontal and occipital cortex, temporal cortex with hippocampus, basal ganglia with thalamus, cerebellum, and pons with medulla. Tissue blocks for histology and mercury analysis were taken from opposing faces to provide for correlation of findings. Similar studies were performed on 12 reference neonatal brains from Rochester, New York. No clear-cut developmental abnormality was found, but some brains exhibited low-grade, non-specific destructive changes. Total mercury levels, most of it in the organic form, were elevated in many of the Seychelles specimens. No correlation was demonstrated between mercury levels and degree or type of histologic change. There was considerable variability in total mercury for each anatomic region among the 32 Seychelles cases, as well as from one region to another in individual brains. All values of total mercury were under 300 ppb. Statistical analysis of mean mercury levels for each region demonstrated higher values in deep subcortical nuclei, brain stem, and cerebellum, phylogenetically older parts of the brain. When total mercury concentration of each region was paired with all other areas in the same brain and the paired values plotted for the entire group of brains, high correlations were obtained for all brain pairs, suggesting a strong concentration-dependent relationship between mercury intake and brain content. Analysis of mercury levels in separately dissected blocks of grey and white matter from 12 specimens revealed no significant differences between grey and white. In comparison with other human developmental studies and with experimental developmental studies in animals, where toxicity has been demonstrated with total mercury brain levels above 1,000 ppb, this study found no evidence of toxicity within a range of mercury levels below 300 ppb. Submicroscopic changes, subcellular alterations, subtle disturbances in the unfolding of brain architectonics -- none of these are excluded with methods used in this report. Further studies of threshold effects of MeHg on fetal brain are essential. That approximately half of the mercury resides in glial elements in white matter reinforces the need to focus attention upon glia as well as neurons during development.", "title": "An analysis of autopsy brain tissue from infants prenatally exposed to methymercury." }, { "docid": "MED-1343", "text": "BACKGROUND: Evidence-based medicine is valuable to the extent that the evidence base is complete and unbiased. Selective publication of clinical trials--and the outcomes within those trials--can lead to unrealistic estimates of drug effectiveness and alter the apparent risk-benefit ratio. METHODS: We obtained reviews from the Food and Drug Administration (FDA) for studies of 12 antidepressant agents involving 12,564 patients. We conducted a systematic literature search to identify matching publications. For trials that were reported in the literature, we compared the published outcomes with the FDA outcomes. We also compared the effect size derived from the published reports with the effect size derived from the entire FDA data set. RESULTS: Among 74 FDA-registered studies, 31%, accounting for 3449 study participants, were not published. Whether and how the studies were published were associated with the study outcome. A total of 37 studies viewed by the FDA as having positive results were published; 1 study viewed as positive was not published. Studies viewed by the FDA as having negative or questionable results were, with 3 exceptions, either not published (22 studies) or published in a way that, in our opinion, conveyed a positive outcome (11 studies). According to the published literature, it appeared that 94% of the trials conducted were positive. By contrast, the FDA analysis showed that 51% were positive. Separate meta-analyses of the FDA and journal data sets showed that the increase in effect size ranged from 11 to 69% for individual drugs and was 32% overall. CONCLUSIONS: We cannot determine whether the bias observed resulted from a failure to submit manuscripts on the part of authors and sponsors, from decisions by journal editors and reviewers not to publish, or both. Selective reporting of clinical trial results may have adverse consequences for researchers, study participants, health care professionals, and patients. Copyright 2008 Massachusetts Medical Society.", "title": "Selective publication of antidepressant trials and its influence on apparent efficacy." }, { "docid": "MED-5365", "text": "Depression is a medical condition with a complex biological pattern of aetiology, involving genetic and epigenetic factors, along with different environmental stressors. Recent evidence suggests that oxidative stress processes might play a relevant role in the pathogenic mechanism(s) underlying many major psychiatric disorders, including depression. Reactive oxygen and nitrogen species have been shown to modulate levels and activity of noradrenaline (norepinephrine), serotonin, dopamine and glutamate, the principal neurotransmitters involved in the neurobiology of depression. Major depression has been associated with lowered concentrations of several endogenous antioxidant compounds, such as vitamin E, zinc and coenzyme Q10, or enzymes, such as glutathione peroxidase, and with an impairment of the total antioxidant status. These observations introduce new potential targets for the development of therapeutic interventions based on antioxidant compounds. The present review focuses on the possible role of oxidative stress processes in the pathogenesis of depression. The therapeutic potential of antioxidant compounds as a co-adjuvant treatment to conventional antidepressants is discussed. For instance, N-acetyl-cysteine has been shown to have a significant benefit on depressive symptoms in a randomized placebo-controlled trial. Additionally, curcumin, the yellow pigment of curry, has been shown to strongly interfere with neuronal redox homeostasis in the CNS and to possess antidepressant activity in various animal models of depression, also thanks to its ability to inhibit monoamine oxidases. There is an urgent need to develop better tolerated and more effective treatments for depressive disorders and several antioxidant treatments appear promising and deserve further study.", "title": "Antioxidants as antidepressants: fact or fiction?" }, { "docid": "MED-3543", "text": "Inhibition of monoamine oxidase is one way to treat depression and anxiety. The information now available on the pharmacokinetics of flavonoids and of the components of tobacco prompted an exploration of whether a healthy diet (with or without smoking) provides active compounds in amounts sufficient to partially inhibit monoamine oxidase. A literature search was used to identify dietary monoamine oxidase inhibitors, the levels of these compounds in foods, the pharmacokinetics of the absorption and distribution, and tissue levels observed. An estimated daily intake and the expected tissue concentrations were compared with the measured efficacies of the compounds as inhibitors of monoamine oxidases. Norharman, harman and quercetin dietary presence, pharmacokinetics, and tissue levels were consistent with significant levels reaching neuronal monoamine oxidase from the diet or smoking; 1,2,3,4-tetrahydroisoquinoline, eugenol, 1-piperoylpiperidine, and coumarin were not. Quercetin was equipotent with norharman as a monoamine oxidase A inhibitor and its metabolite, isorhamnetin, also inhibits. Total quercetin was the highest of the compounds in the sample diet. Although bioavailability was variable depending on the source, a healthy diet contains amounts of quercetin that might give sufficient amounts in brain to induce, by monoamine oxidase A inhibition, a small decrease in neurotransmitter breakdown.", "title": "Dietary inhibitors of monoamine oxidase A." }, { "docid": "MED-1348", "text": "Background Meta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance. Yet, the efficacy of the antidepressants may also depend on the severity of initial depression scores. The purpose of this analysis is to establish the relation of baseline severity and antidepressant efficacy using a relevant dataset of published and unpublished clinical trials. Methods and Findings We obtained data on all clinical trials submitted to the US Food and Drug Administration (FDA) for the licensing of the four new-generation antidepressants for which full datasets were available. We then used meta-analytic techniques to assess linear and quadratic effects of initial severity on improvement scores for drug and placebo groups and on drug–placebo difference scores. Drug–placebo differences increased as a function of initial severity, rising from virtually no difference at moderate levels of initial depression to a relatively small difference for patients with very severe depression, reaching conventional criteria for clinical significance only for patients at the upper end of the very severely depressed category. Meta-regression analyses indicated that the relation of baseline severity and improvement was curvilinear in drug groups and showed a strong, negative linear component in placebo groups. Conclusions Drug–placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication. Editors' Summary Background. Everyone feels miserable occasionally. But for some people—those with depression—these sad feelings last for months or years and interfere with daily life. Depression is a serious medical illness caused by imbalances in the brain chemicals that regulate mood. It affects one in six people at some time during their life, making them feel hopeless, worthless, unmotivated, even suicidal. Doctors measure the severity of depression using the “Hamilton Rating Scale of Depression” (HRSD), a 17–21 item questionnaire. The answers to each question are given a score and a total score for the questionnaire of more than 18 indicates severe depression. Mild depression is often treated with psychotherapy or talk therapy (for example, cognitive–behavioral therapy helps people to change negative ways of thinking and behaving). For more severe depression, current treatment is usually a combination of psychotherapy and an antidepressant drug, which is hypothesized to normalize the brain chemicals that affect mood. Antidepressants include “tricyclics,” “monoamine oxidases,” and “selective serotonin reuptake inhibitors” (SSRIs). SSRIs are the newest antidepressants and include fluoxetine, venlafaxine, nefazodone, and paroxetine. Why Was This Study Done? Although the US Food and Drug Administration (FDA), the UK National Institute for Health and Clinical Excellence (NICE), and other licensing authorities have approved SSRIs for the treatment of depression, some doubts remain about their clinical efficacy. Before an antidepressant is approved for use in patients, it must undergo clinical trials that compare its ability to improve the HRSD scores of patients with that of a placebo, a dummy tablet that contains no drug. Each individual trial provides some information about the new drug's effectiveness but additional information can be gained by combining the results of all the trials in a “meta-analysis,” a statistical method for combining the results of many studies. A previously published meta-analysis of the published and unpublished trials on SSRIs submitted to the FDA during licensing has indicated that these drugs have only a marginal clinical benefit. On average, the SSRIs improved the HRSD score of patients by 1.8 points more than the placebo, whereas NICE has defined a significant clinical benefit for antidepressants as a drug–placebo difference in the improvement of the HRSD score of 3 points. However, average improvement scores may obscure beneficial effects between different groups of patient, so in the meta-analysis in this paper, the researchers investigated whether the baseline severity of depression affects antidepressant efficacy. What Did the Researchers Do and Find? The researchers obtained data on all the clinical trials submitted to the FDA for the licensing of fluoxetine, venlafaxine, nefazodone, and paroxetine. They then used meta-analytic techniques to investigate whether the initial severity of depression affected the HRSD improvement scores for the drug and placebo groups in these trials. They confirmed first that the overall effect of these new generation of antidepressants was below the recommended criteria for clinical significance. Then they showed that there was virtually no difference in the improvement scores for drug and placebo in patients with moderate depression and only a small and clinically insignificant difference among patients with very severe depression. The difference in improvement between the antidepressant and placebo reached clinical significance, however, in patients with initial HRSD scores of more than 28—that is, in the most severely depressed patients. Additional analyses indicated that the apparent clinical effectiveness of the antidepressants among these most severely depressed patients reflected a decreased responsiveness to placebo rather than an increased responsiveness to antidepressants. What Do These Findings Mean? These findings suggest that, compared with placebo, the new-generation antidepressants do not produce clinically significant improvements in depression in patients who initially have moderate or even very severe depression, but show significant effects only in the most severely depressed patients. The findings also show that the effect for these patients seems to be due to decreased responsiveness to placebo, rather than increased responsiveness to medication. Given these results, the researchers conclude that there is little reason to prescribe new-generation antidepressant medications to any but the most severely depressed patients unless alternative treatments have been ineffective. In addition, the finding that extremely depressed patients are less responsive to placebo than less severely depressed patients but have similar responses to antidepressants is a potentially important insight into how patients with depression respond to antidepressants and placebos that should be investigated further. Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050045.", "title": "Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration" }, { "docid": "MED-5370", "text": "BACKGROUND: Very long chain omega-3 fatty acids (w-3 PUFA) intake and fish consumption have been suggested as protective factors against neuropsychiatric disorders but there is scarcity of large cohort studies assessing this association. AIM OF THE STUDY: To assess the association between w-3-PUFA intake and fish consumption and mental disorders. METHODS: A prospective cohort study was performed in 7,903 participants. W-3 PUFA intake and fish consumption were ascertained through a validated semi-quantitative food frequency questionnaire. The outcomes after 2 years of follow-up were: (1) Incident mental disorder (depression, anxiety, or stress), (2) incident depression, and (3) incident anxiety. Logistic regression models and generalized additive models were fit to assess the relationship between w-3 PUFA intake or fish consumption and the incidence of these outcomes. Odds ratios (OR) and their 95% confidence intervals (CI) were calculated. RESULTS: 173 cases of depression, 335 cases of anxiety, and 4 cases of stress were observed during 2-year follow-up. ORs (95% CI) of mental disorder for successive quintiles of energy-adjusted w-3 PUFA intake were 1 (reference), 0.72 (0.52-0.99), 0.79 (0.58-1.08), 0.65 (0.47-0.90), and 1.04 (0.78-1.40). Subjects with a moderate consumption of fish (third and fourth quintiles of consumption: median of each quintile 83.3 and 112 g/day, respectively) had a relative risk reduction higher than 30%. CONCLUSIONS: A potential benefit of w-3 PUFA intake on total mental disorders is suggested, although no linear trend was apparent.", "title": "Long chain omega-3 fatty acids intake, fish consumption and mental disorders in the SUN cohort study." }, { "docid": "MED-3012", "text": "The fish ingredient N3-docosahexaenoic acid 22:6 n-3 (DHA) stimulates brain development. On the other hand methylmercury (MeHg) in fish disturbs the developing central nervous system. In this Context the IQ score in children is considered as an aggregate measure of in utero brain development. To determine the effect of DHA exposure on prenatal neurodevelopment the maternal DHA intake during pregnancy was compared with its epidemiologically observed effect on the IQ score of children. For MeHg the maternal intake was converted into its accumulation in the maternal body. The maternal body burden then was compared with its epidemiologically observed relationship with the IQ score. Taking the MeHg and DHA content of 33 fish species the net effect of these compounds on the IQ score was quantified. For most fish species the adverse effect of MeHg on the IQ score exceeded the beneficial effect of DHA. In the case of long-living predators a negative effect up to 10 points on the IQ score was found. The results of this study indicate that food interventions aiming at the beneficial effects of fish consumption should focus on fish species with a high DHA content, while avoiding fish species with a high MeHg content. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Fish consumption during child bearing age: a quantitative risk-benefit analysis on neurodevelopment." }, { "docid": "MED-3022", "text": "Methylmercury (MM) is a very potent neurotoxic agent. Its role in polluting the environment is well documented. A vast amount of study over the past several decades has finally provided insight into many aspects of its effect. Exposure to MM may be through ingestion of poisoned fish or inadvertent misuse of grain treated with the poison as a fungicide. Major epidemics have occurred in Japan (Fetal Minamata disease), Iraq, Pakistan, Guatemala, and Ghana. Sporadic incidences have occurred in the United States and Canada. There is no effective antidote to counteract the effect of MM on the central nervous system, although the information documented should provide hope for more effective therapy in acute cases.", "title": "The many faces of methylmercury poisoning." }, { "docid": "MED-3542", "text": "The behavior of inhibitors of monoamine oxidase-A (MAO-A) is considered in terms of the possibility of having an effective antidepressant that does not give rise to hypertensive interactions with dietary tyramine. Studies with punch-biopsy samples of human intestine and rat intestinal samples show MAO-A to be the predominant form of the enzyme in both species. Transport studies with everted rat intestinal preparations indicate that tyramine is extensively metabolized during transport through the intestine. Selective inhibition of MAO-A by clorgyline results in a large increase in the amount of unchanged tyramine transported, whereas selective inhibition of MAO-B with L-deprenyl (selegiline) has no significant effect. The behavior of reversible MAO-A inhibitors can significantly reduce, but not entirely eliminate, these effects on the intestinal metabolism of tyramine, but only if the inhibition is competitive in nature.", "title": "Monoamine oxidase inhibitors and the cheese effect." }, { "docid": "MED-1195", "text": "We examined the relationship of elevated depressive symptoms with antioxidant status. Cross-sectional data from the National Health and Nutrition Examination Surveys 2005–06 on US adults aged 20–85 years were analyzed. Depressive symptoms were measured using the Patient Health Questionnaire with a score cutpoint of 10 to define “elevated depressive symptoms”. Serum antioxidant status was measured by serum levels of carotenoids, retinol (free and retinyl esters), vitamin C and vitamin E. The main analyses consisted of multiple logistic and zero-inflated poisson regression models, taking into account sampling design complexity. The final sample consisted of 1,798 US adults with complete data. Higher total carotenoid serum level was associated with lower likelihood of elevated depressive symptoms with a reduction in the odds by 37% overall with each SD increase in exposure, and by 34% among women (p<0.05). A dose-response relationship was observed when serum total carotenoids were expressed as quartiles [Q4 (1.62–10.1 μmol/L) vs. Q1(0.06–0.86 μmol/L): OR=0.41; 95% CI: 0.23–0.76, P<0.001; p-value for trend=0.035], though no significant associations were found with other antioxidant levels. Among carotenoids, β-carotene (men and women combined) and lutein+zeaxanthins (women only, after control for dietary lutein+zeaxanthin intake and supplement use) had an independent inverse association with elevated depressive symptoms among US adults. None of the other serum antioxidants had a significant association with depressive symptoms, independently of total carotenoids and other covariates. In conclusion, total carotenoids (mainly β-carotene and lutein+zeaxanthins) in serum were associated with reduced levels of depressive symptoms among community-dwelling US adults.", "title": "Antioxidant status and its association with elevated depressive symptoms among US adults: National Health and Nutrition Examination Surveys 2005–06" }, { "docid": "MED-1342", "text": "Background Previous meta-analyses of published and unpublished trials indicate that antidepressants provide modest benefits compared to placebo in the treatment of depression; some have argued that these benefits are not clinically significant. However, these meta-analyses were based only on trials submitted for the initial FDA approval of the medication and were limited to those aimed at treating depression. Here, for the first time, we assess the efficacy of a selective serotonin reuptake inhibitor (SSRI) in the treatment of both anxiety and depression, using a complete data set of all published and unpublished trials sponsored by the manufacturer. Methods and Findings GlaxoSmithKline has been required to post the results for all sponsored clinical trials online, providing an opportunity to assess the efficacy of an SSRI (paroxetine) with a complete data set of all trials conducted. We examined the data from all placebo-controlled, double-blind trials of paroxetine that included change scores on the Hamilton Rating Scale for Anxiety (HRSA) and/or the Hamilton Rating Scale for Depression (HRSD). For the treatment of anxiety (k = 12), the efficacy difference between paroxetine and placebo was modest (d = 0.27), and independent of baseline severity of anxiety. Overall change in placebo-treated individuals replicated 79% of the magnitude of paroxetine response. Efficacy was superior for the treatment of panic disorder (d = 0.36) than for generalized anxiety disorder (d = 0.20). Published trials showed significantly larger drug-placebo differences than unpublished trials (d’s = 0.32 and 0.17, respectively). In depression trials (k = 27), the benefit of paroxetine over placebo was consistent with previous meta-analyses of antidepressant efficacy (d = 0.32). Conclusions The available empirical evidence indicates that paroxetine provides only a modest advantage over placebo in treatment of anxiety and depression. Treatment implications are discussed.", "title": "The Efficacy of Paroxetine and Placebo in Treating Anxiety and Depression: A Meta-Analysis of Change on the Hamilton Rating Scales" }, { "docid": "MED-5364", "text": "OBJECTIVE: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been implicated as protective against suicide. However, it is uncertain whether a higher intake of EPA and DHA or of fish, a major source of these nutrients, lowers suicidal risk among Japanese, whose fish consumption and suicide rate are both high. This study prospectively examined the relation between fish, EPA, or DHA intake and suicide among Japanese men and women. METHOD: Subjects were 47,351 men and 54,156 women aged 40-69 years who participated in the JPHC Study, completed a food frequency questionnaire in 1995-1999, and were followed for death through December 2005. We used the Cox proportional hazards regression model to estimate the hazard ratio (HR) and 95% confidence interval (CI) for suicide by quintile of intake. RESULTS: A total of 213 and 85 deaths from suicide were recorded during 403,019 and 473,351 person-years of follow-up for men and women, respectively. Higher intakes of fish, EPA, or DHA were not associated with a lower risk of suicide. Multivariate HRs (95% CI) of suicide death for the highest versus lowest quintile of fish consumption were 0.95 (0.60-1.49) and 1.20 (0.58-2.47) for men and women, respectively. A significantly increased risk of suicidal death was observed among women with very low intake of fish, with HRs (95% CI) for those in 0-5th percentile versus middle quintile of 3.41 (1.36-8.51). CONCLUSIONS: Our overall result does not support a protective role of higher intake of fish, EPA, or DHA against suicide in Japanese men and women. Copyright © 2010 Elsevier B.V. All rights reserved.", "title": "Long chain n-3 fatty acids intake, fish consumption and suicide in a cohort of Japanese men and women--the Japan Public Health Center-based (JPHC) ..." }, { "docid": "MED-1344", "text": "Is it ever right to prescribe placebos to patients in clinical practice? The General Medical Council is ambivalent about the issue; the American Medical Association asserts that placebos can be administered only if the patient is (somehow) 'informed'. The potential problem with placebos is that they may involve deception: indeed, if this is the case, an ethical tension arises over the patient's autonomy and the physician's requirement to be open and honest, and the notion that medical care should be the primary concern. This paper examines the case of depression as an entry point for understanding the complexities of the prescription of placebos. Recent important meta-analyses of antidepressants claim that they are not significantly more effective in a clinical setting than placebos. Given that antidepressants have numerous adverse side effects and are hugely expensive, this provocative research has serious potential ethical and practical implications for patients and medical providers. Should placebos be prescribed in place of antidepressants? The case of depression highlights another important issue which medical ethical codes have hitherto overlooked: well-being is not synonymous with being realistic about oneself, one's circumstances and the future. While severely depressed individuals are unduly pessimistic about themselves and the world around them, treatment of depressed individuals can be deemed successful when patients have successfully attained those positive illusions that are indicative of psychological health. This is exactly what successful psychological treatments of depression seem to achieve. It is therefore possible that there may be a limited unavoidable role for deception in medicine.", "title": "Deception as treatment: the case of depression." }, { "docid": "MED-2913", "text": "The elimination kinetics of polychlorinated biphenyls (PCBs) in humans is difficult to assess in observational studies, because PCB exposure is never completely abolished. In a community with high dietary PCB exposures from whale blubber, we examined two groups of children with increased body burdens from breast-feeding. Follow-up was from ages 4.5 years to 7.5 years (99 subjects) and 7 to 14 years (101 subjects). The calculations were performed by the use of structural equation models, with adjustment for body weight and dietary blubber intake as the main source of postnatal exposure. As a likely result of background exposures, apparent elimination half-lives were unexpectedly long when based on results from all cohort members. Subjects with exposures above the median and in the highest quartile showed half-lives of about 3-4 years for CB-138, and 4.5-5.5 years for CB-105 and CB-118; 6.5-7.5 years for CB-156, CB-170, and CB-187; and 7-9 years for CB-153 and CB-180. The longest half-lives correspond to elimination of the parent PCB solely with a daily fat excretion rate of 1-2 g, while shorter half-lives assume metabolic break-down.", "title": "Elimination Half-lives of Polychlorinated Biphenyl Congeners in Children" }, { "docid": "MED-3025", "text": "Detailed clinical and neuropathological studies have been made in two fullterm newborn human infants who were exposed to methylmercury in utero as a result of maternal ingestion of methylmercury-contaminated bread in early phases of pregnancy. High levels of mercury were detected in various regions of the brain at autopsy. Study of the brains revealed a disturbance in the development in both cases, consisting essentially of an incomplete or abnormal migration of neurons to the cerebellar and cerebral cortices, and deranged cortical organization of the cerebrum. There were numerous heterotopic neurons, both isolated and in groups, in the white matter of cerebrum and cerebellum and the laminar cortical pattern of the laminar cortical pattern of the cerebrum was disturbed in many regions as was shown by the irregular groupings and the deranged alignment of cortical. Prominent in the white matter of the cerebrum and the cerebellum was diffuse gemistocytic astrocytosis accompanied by an accumulation of mercury grains in their cytoplasm. These findings indicate a high degree of vulnerability of human fetal brain to maternal intoxication by methylmercury. A major effect appears to be related to faulty development and not to destructive focal neuronal damage as has been observed in mercury intoxicaiton in adults and children exposed postnatally.", "title": "Abnormal neuronal migration, deranged cerebral cortical organization, and diffuse white matter astrocytosis of human fetal brain: a major effect of..." }, { "docid": "MED-1350", "text": "Background Starting in the 1960s, a broad-based patients’ rights movement began to question doctors’ paternalism and to demand disclosure of medical information, informed consent, and active participation by the individual in personal health care. According to scholars, these changes contributed to downplay the biomedical approach in favor of a more patient-oriented perspective. The Swedish non-profit organization Consumer Association for Medicines and Health (KILEN) has offered the possibility for consumers to report their perceptions and experiences from their use of medicines in order to strengthen consumer rights within the health care sector. Methodology In this paper, qualitative content analysis was used to analyze 181 KILEN consumer reports of adverse events from antidepressant medications in order to explore patients’ views of mental ill health symptoms and the doctor-patient interaction. Principal Findings Overall, the KILEN stories contained negative experiences of the patients’ medical encounters. Some reports indicated intense emotional outrage and strong feelings of abuse by the health care system. Many reports suggested that doctors and patients had very different accounts of the nature of the problems for which the patient was seeking help. Although patients sought help for problems like tiredness and sleeplessness (often with a personal crisis of some sort as a described cause), the treating doctor in most cases was exceptionally quick in both diagnosing depression and prescribing antidepressant treatment. When patients felt they were not being listened to, trust in the doctor was compromised. This was evident in the cases when the doctor tried to convince them to take part in medical treatment, sometimes by threatening to withdraw their sick-listing. Conclusions Overall, this study suggests that the dynamics happening in the medical encounter may still be highly affected by a medical dominance, instead of a patient-oriented perspective. This may contribute to a questionable medicalization and/or pharmaceuticalization of depression.", "title": "A Pill for the Ill? Patients’ Reports of Their Experience of the Medical Encounter in the Treatment of Depression" }, { "docid": "MED-1357", "text": "BACKGROUND: Previous observational and interventional studies have suggested that regular physical exercise may be associated with reduced symptoms of depression. However, the extent to which exercise training may reduce depressive symptoms in older patients with major depressive disorder (MDD) has not been systematically evaluated. OBJECTIVE: To assess the effectiveness of an aerobic exercise program compared with standard medication (ie, antidepressants) for treatment of MDD in older patients, we conducted a 16-week randomized controlled trial. METHODS: One hundred fifty-six men and women with MDD (age, > or = 50 years) were assigned randomly to a program of aerobic exercise, antidepressants (sertraline hydrochloride), or combined exercise and medication. Subjects underwent comprehensive evaluations of depression, including the presence and severity of MDD using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and Hamilton Rating Scale for Depression (HAM-D) and Beck Depression Inventory (BDI) scores before and after treatment. Secondary outcome measures included aerobic capacity, life satisfaction, self-esteem, anxiety, and dysfunctional cognitions. RESULTS: After 16 weeks of treatment, the groups did not differ statistically on HAM-D or BDI scores (P = .67); adjustment for baseline levels of depression yielded an essentially identical result. Growth curve models revealed that all groups exhibited statistically and clinically significant reductions on HAM-D and BDI scores. However, patients receiving medication alone exhibited the fastest initial response; among patients receiving combination therapy, those with less severe depressive symptoms initially showed a more rapid response than those with initially more severe depressive symptoms. CONCLUSIONS: An exercise training program may be considered an alternative to antidepressants for treatment of depression in older persons. Although antidepressants may facilitate a more rapid initial therapeutic response than exercise, after 16 weeks of treatment exercise was equally effective in reducing depression among patients with MDD.", "title": "Effects of exercise training on older patients with major depression." }, { "docid": "MED-2917", "text": "The effect of alternative dietary habits and prolonged lactation on the nutrient and contaminant concentrations in human milk was studied. The study sample consisted of mothers on macrobiotic diets, containing little or no diary products and meat, at 2-3 months postpartum (n = 9) and 9-13 months postpartum (n = 12), and mothers on omnivorous diets at 2-3 months postpartum (n = 10). Protein and zinc concentrations in breast-milk from macrobiotic mothers decreased with stage of lactation. After adjustment for stage of lactation, milk from macrobiotic mothers contained less calcium, magnesium and saturated fatty acids C15:0-C20:0, and more polyunsaturated fatty acids. Observed tendencies for lower protein and fat and higher lactose concentrations in the macrobiotic group were not statistically significant. Concentrations of vitamin B12, HCB and polychlorinated biphenyls (PCB 118, PCB 138, PCB 153 and PCB 180) were lower in the macrobiotic group. After adjustment for confounding variables, meat and fish consumption, but not dairy products, contributed to vitamin B12 concentrations. Meat and diary products strongly contributed to breast-milk concentrations of dieldrin and PCBs, fish to PCB 118, and smoking to DDT and dieldrin. Our findings suggest that breast-milk contamination could be reduced by abstinence from smoking and a moderate intake of animal products. However, risk of nutritional deficiencies rules out complete avoidance of meat, fish or diary products. Quantitative research on the effects of a reduced consumption of animal products, as well as smoking, on breast-milk contamination is warranted.", "title": "Nutrients and contaminants in human milk from mothers on macrobiotic and omnivorous diets." }, { "docid": "MED-3024", "text": "This experiment aimed to study the molecular toxicity of methylmercury (MeHg) in liver, brain and white muscle of Atlantic salmon fed a diet based on fish oil (FO, high dietary n-3/n-6 ratio) compared to an alternative diet mainly based on vegetable oil (VO, low dietary n-3/n-6 ratio). Juvenile salmon were fed decontaminated diets or the FO and VO diets enriched with 5 mg Hg/kg (added as MeHg) for three months. The dietary lipid composition affected the fatty acid composition in the tissues, especially in liver and white muscle. After 84 days of exposure, the liver accumulated three times as much MeHg as the brain and white muscle. Vitamin C content and heme oxygenase, tubulin alpha (TUBA) and Cpt1 transcriptional levels all showed significant effects of MeHg exposure in the liver. TBARS, α-tocopherol, γ-tocopherol, and the transcriptional levels of thioredoxin, heme oxygenase, TUBA, PPARB1, D5D and D6D showed an effect of dietary lipid composition in liver tissue. Effects of dietary lipids were observed in brain tissue for MT-A, HIF1, Bcl-X and TUBA. Interaction effects between MeHg exposure and dietary lipid composition were observed in all tissues. Our data suggest that dietary fats have modulating effects on MeHg toxicity in Atlantic salmon. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Dietary lipids modulate methylmercury toxicity in Atlantic salmon." }, { "docid": "MED-3029", "text": "Background: Diverse perspectives have influenced fish consumption choices. Objectives: We summarized the issue of fish consumption choice from toxicological, nutritional, ecological, and economic points of view; identified areas of overlap and disagreement among these viewpoints; and reviewed effects of previous fish consumption advisories. Methods: We reviewed published scientific literature, public health guidelines, and advisories related to fish consumption, focusing on advisories targeted at U.S. populations. However, our conclusions apply to groups having similar fish consumption patterns. Discussion: There are many possible combinations of matters related to fish consumption, but few, if any, fish consumption patterns optimize all domains. Fish provides a rich source of protein and other nutrients, but because of contamination by methylmercury and other toxicants, higher fish intake often leads to greater toxicant exposure. Furthermore, stocks of wild fish are not adequate to meet the nutrient demands of the growing world population, and fish consumption choices also have a broad economic impact on the fishing industry. Most guidance does not account for ecological and economic impacts of different fish consumption choices. Conclusion: Despite the relative lack of information integrating the health, ecological, and economic impacts of different fish choices, clear and simple guidance is necessary to effect desired changes. Thus, more comprehensive advice can be developed to describe the multiple impacts of fish consumption. In addition, policy and fishery management inter-ventions will be necessary to ensure long-term availability of fish as an important source of human nutrition.", "title": "Which Fish Should I Eat? Perspectives Influencing Fish Consumption Choices" }, { "docid": "MED-3545", "text": "Background Omnivorous diets are high in arachidonic acid (AA) compared to vegetarian diets. Research shows that high intakes of AA promote changes in brain that can disturb mood. Omnivores who eat fish regularly increase their intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), fats that oppose the negative effects of AA in vivo. In a recent cross-sectional study, omnivores reported significantly worse mood than vegetarians despite higher intakes of EPA and DHA. This study investigated the impact of restricting meat, fish, and poultry on mood. Findings Thirty-nine omnivores were randomly assigned to a control group consuming meat, fish, and poultry daily (OMN); a group consuming fish 3-4 times weekly but avoiding meat and poultry (FISH), or a vegetarian group avoiding meat, fish, and poultry (VEG). At baseline and after two weeks, participants completed a food frequency questionnaire, the Profile of Mood States questionnaire and the Depression Anxiety and Stress Scales. After the diet intervention, VEG participants reduced their EPA, DHA, and AA intakes, while FISH participants increased their EPA and DHA intakes. Mood scores were unchanged for OMN or FISH participants, but several mood scores for VEG participants improved significantly after two weeks. Conclusions Restricting meat, fish, and poultry improved some domains of short-term mood state in modern omnivores. To our knowledge, this is the first trial to examine the impact of restricting meat, fish, and poultry on mood state in omnivores.", "title": "Restriction of meat, fish, and poultry in omnivores improves mood: A pilot randomized controlled trial" }, { "docid": "MED-3033", "text": "Rates of lung cancer in American men have greatly exceeded those in Japanese men for several decades despite the higher smoking prevalence in Japanese men. It is not known whether the relative risk of lung cancer associated with cigarette smoking is lower in Japanese men than American men and whether these risks vary by the amount and duration of smoking. To estimate smoking-specific relative risks for lung cancer in men, a multicentric case-control study was carried out in New York City, Washington, DC, and Nagoya, Japan from 1992 to 1998. A total of 371 cases and 373 age-matched controls were interviewed in United States hospitals and 410 cases and 252 hospital controls in Japanese hospitals; 411 Japanese age-matched healthy controls were also randomly selected from electoral rolls. The odds ratio (OR) for lung cancer in current United States smokers relative to nonsmokers was 40.4 [95% confidence interval (CI) = 21.8-79.6], which was >10 times higher than the OR of 3.5 for current smokers in Japanese relative to hospital controls (95% CI = 1.6-7.5) and six times higher than in Japanese relative to community controls (OR = 6.3; 95% CI = 3.7-10.9). There were no substantial differences in the mean number of years of smoking or average daily number of cigarettes smoked between United States and Japanese cases or between United States and Japanese controls, but American cases began smoking on average 2.5 years earlier than Japanese cases. The risk of lung cancer associated with cigarette smoking was substantially higher in United States than in Japanese males, consistent with population-based statistics on smoking prevalence and lung cancer incidence. Possible explanations for this difference in risk include a more toxic cigarette formulation of American manufactured cigarettes as evidenced by higher concentrations of tobacco-specific nitrosamines in both tobacco and mainstream smoke, the much wider use of activated charcoal in the filters of Japanese than in American cigarettes, as well as documented differences in genetic susceptibility and lifestyle factors other than smoking.", "title": "Smoking and lung cancer risk in American and Japanese men: an international case-control study." }, { "docid": "MED-5371", "text": "We conducted a meta-analysis of randomized, placebo-controlled trials of omega-3 fatty acid treatment of major depressive disorder in order to determine efficacy and to examine sources of heterogeneity between trials. PubMED (1965-May 2010) was searched for randomized, placebo-controlled trials of omega-3 fatty acids for major depressive disorder. Our primary outcome measure was standardized mean difference in a clinical measure of depression severity. In stratified meta-analysis we examined the effects of trial duration, trial methodological quality, baseline depression severity, diagnostic indication, dose of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in omega-3 preparations, and whether omega-3 fatty acid was given as monotherapy or augmentation. In 13 randomized, placebo-controlled trials examining the efficacy of omega-3 fatty acids involving 731 participants, meta-analysis demonstrated no significant benefit of omega-3 fatty acid treatment compared to placebo (SMD=0.11, 95% CI: -0.04, 0.26). Meta-analysis demonstrated significant heterogeneity and publication bias. Nearly all evidence of omega-3 benefit was removed after adjusting for publication bias using the trim-and-fill method (SMD=0.01, 95% CI: -0.13, 0.15). Secondary analyses suggested a trend towards increased efficacy of omega-3 fatty acids in trials of lower methodological quality, trials of shorter duration, trials, which utilized completers rather than intention-to-treat analysis, and trials in which study participants had greater baseline depression severity, Current published trials suggest a small, non-significant benefit of omega-3 fatty acids for major depression. Nearly all of the treatment efficacy observed in the published literature may be attributable to publication bias.", "title": "Omega-3 Fatty Acids for the Treatment of Depression: Systematic Review and Meta-Analysis" }, { "docid": "MED-2752", "text": "CONTEXT: Considerable controversy exists regarding the association of omega-3 polyunsaturated fatty acids (PUFAs) and major cardiovascular end points. OBJECTIVE: To assess the role of omega-3 supplementation on major cardiovascular outcomes. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through August 2012. STUDY SELECTION: Randomized clinical trials evaluating the effect of omega-3 on all-cause mortality, cardiac death, sudden death, myocardial infarction, and stroke. DATA EXTRACTION: Descriptive and quantitative information was extracted; absolute and relative risk (RR) estimates were synthesized under a random-effects model. Heterogeneity was assessed using the Q statistic and I2. Subgroup analyses were performed for the presence of blinding, the prevention settings, and patients with implantable cardioverter-defibrillators, and meta-regression analyses were performed for the omega-3 dose. A statistical significance threshold of .0063 was assumed after adjustment for multiple comparisons. DATA SYNTHESIS: Of the 3635 citations retrieved, 20 studies of 68,680 patients were included, reporting 7044 deaths, 3993 cardiac deaths, 1150 sudden deaths, 1837 myocardial infarctions, and 1490 strokes. No statistically significant association was observed with all-cause mortality (RR, 0.96; 95% CI, 0.91 to 1.02; risk reduction [RD] -0.004, 95% CI, -0.01 to 0.02), cardiac death (RR, 0.91; 95% CI, 0.85 to 0.98; RD, -0.01; 95% CI, -0.02 to 0.00), sudden death (RR, 0.87; 95% CI, 0.75 to 1.01; RD, -0.003; 95% CI, -0.012 to 0.006), myocardial infarction (RR, 0.89; 95% CI, 0.76 to 1.04; RD, -0.002; 95% CI, -0.007 to 0.002), and stroke (RR, 1.05; 95% CI, 0.93 to 1.18; RD, 0.001; 95% CI, -0.002 to 0.004) when all supplement studies were considered. CONCLUSION: Overall, omega-3 PUFA supplementation was not associated with a lower risk of all-cause mortality, cardiac death, sudden death, myocardial infarction, or stroke based on relative and absolute measures of association.", "title": "Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis." }, { "docid": "MED-5360", "text": "Studies have shown an association between depression and both antioxidant levels and oxidant stress, but generally have not included intakes of antioxidants and antioxidant-rich fruits and vegetables. The present study examined the cross-sectional associations between clinically-diagnosed depression and intakes of antioxidants, fruits and vegetables in a cohort of older adults. Antioxidant, fruit and vegetable intakes were assessed in 278 elderly participants (144 with depression, 134 without depression) using a Block 1998 food frequency questionnaire, which was administered between 1999 and 2007. All participants were age 60 years or over. Vitamin C, lutein and cryptoxanthin intakes were significantly lower among depressed individuals than in comparison participants (p<0.05). In addition, fruit and vegetable consumption, a primary determinant of antioxidant intake, was lower in depressed individuals. In multivariable models, controlling for age, sex, education, vascular comorbidity score, body mass index, total dietary fat, and alcohol, vitamin C, cryptoxanthin, fruits and vegetables remained significant. Antioxidants from dietary supplements were not associated with depression. Antioxidant, fruit and vegetable intakes were lower in individuals with late-life depression than in comparison participants. These associations may partially explain the elevated risk of cardiovascular disease among older depressed individuals. In addition, these findings point to the importance of antioxidant food sources rather than dietary supplements.", "title": "Fruit, Vegetable and Antioxidant Intakes are Lower in Older Adults with Depression" } ]
[ { "docid": "MED-1622", "text": "Objective To evaluate the association between coffee and caffeine consumption and suicide risk in three large-scale cohorts of U.S. men and women. Methods We accessed data of 43,599 men enrolled in the Health Professionals Follow-up Study (HPFS, 1988–2008), 73,820 women in the Nurses’ Health Study (NHS, 1992–2008), and 91,005 women in the NHS II (1993–2007). Consumption of caffeine, coffee, and decaffeinated coffee, was assessed every four years by validated food-frequency questionnaires. Deaths from suicide were determined by physician review of death certificates. Multivariate adjusted relative risks (RRs) were estimated with Cox proportional hazard models. Cohort specific RRs were pooled using random-effect models. Results We documented 277 deaths from suicide. Compared to those consuming ≤1 cup/week of caffeinated coffee (≤8 oz/237 ml), the pooled multivariate RR (95% confidence interval [CI]) of suicide was 0.55 (0.38–0.78) for those consuming 2–3 cups/day and 0.47 (0.27–0.81) for those consuming ≥4 cups/day (P trend <0.001). The pooled multivariate RR (95% CI) for suicide was 0.75 (0.63–0.90) for each increment of 2 cups/day of caffeinated coffee and 0.77 (0.63–0.93) for each increment of 300 mg/day of caffeine. Conclusions These results from three large cohorts support an association between caffeine consumption and lower risk of suicide.", "title": "Coffee, caffeine, and risk of completed suicide: results from 3 prospective cohorts of American adults" }, { "docid": "MED-1628", "text": "Earlier research has implicated coffee drinking as a possible protective factor for suicide. We followed-up 43,166 subjects for the mean 14.6 years, and 213 suicides were committed. Daily coffee drinking had a J-shaped association with the risk of suicide. Using the Cox model we controlled for potential covariates, and found that among heavy coffee drinkers (> or = 8 cups/day) the risk of suicide was 58% higher compared with more moderate drinkers.", "title": "Heavy coffee drinking and the risk of suicide." }, { "docid": "MED-1731", "text": "Glyphosate surfactant herbicide (GlySH) toxicity is an uncommon poisoning. We report two fatalities involving suicidal ingestion of this herbicide. Both deaths occurred despite early recognition of the serious nature of the poisoning and aggressive treatment. The deaths in this series are analysed in the context of a review of existing literature. Although traditionally regarded as minimally toxic, many deaths have been reported following suicidal ingestion. Severe GlySH toxicity may be refractory even to the most intensive supportive care. The triad of pulmonary oedema, metabolic acidosis and hyperkalaemia portends poor outcome. While containing a carbon phosphorus moiety, GlySH does not exhibit organophosphate toxicity. A clinical guide to assessing severity of GlySH toxicity is proposed and treatment modalities discussed.", "title": "Glyphosate herbicide formulation: a potentially lethal ingestion." }, { "docid": "MED-1621", "text": "Except for conflicting evidence about coffee and risk of coronary disease, coffee and tea are not linked to major causes of death. Because of widespread use of both beverages and limitations of prior studies, concern persists. Using Cox models (ten covariates) we studied relations in 128,934 persons to 4501 subsequent deaths. Except for slightly increased risk from acute myocardial infarction among heavier (> or = 4 cups/d) coffee users (relative risk versus nondrinkers = 1.4, 95% confidence interval = 1.0 to 1.9, P = 0.07), there was no increased risk of mortality for all deaths (relative risk per cup of coffee per day = 0.99, 95% confidence interval = 0.97 to 1.01; relative risk per cup of tea per day = 0.98, 95% confidence interval = 0.96 to 1.00) or major causes in adjusted analyses. Coffee was related to lower risk of liver cirrhosis death (relative risk per cup of coffee per day = 0.77, 95% confidence interval = 0.67 to 0.89). Use of both beverages was related to a lower risk of suicide, progressively lower at higher coffee intake (relative risk per cup of coffee per day = 0.87, 95% confidence interval = 0.77 to 0.98). We conclude that coffee and tea have no overall relation to mortality risk. If coffee increases coronary risk, this is balanced by an unexplained lower risk of other conditions, notably cirrhosis and suicide.", "title": "Coffee, tea, and mortality." }, { "docid": "MED-2410", "text": "Background and aims Previous research on the association between fish consumption and incident type 2 diabetes has been inconclusive. In addition, few studies have investigated how fish consumption may be related to the metabolic abnormalities underlying diabetes. Therefore, we examined the association of fish consumption with measures of insulin sensitivity and beta-cell function in a multi-ethnic population. Methods and results We examined the cross-sectional association between fish consumption and measures of insulin sensitivity and secretion in 951 non-diabetic participants in the Insulin Resistance Atherosclerosis Study (IRAS). Fish consumption, categorized as <2 vs. ≥2 portions/week, was measured using a validated food frequency questionnaire. Insulin sensitivity (SI) and acute insulin response (AIR) were determined from frequently sampled intravenous glucose tolerance tests. Higher fish consumption was independently associated with lower SI-adjusted AIR (β=−0.13 [−0.25, −0.016], p=0.03, comparing ≥ 2 vs. <2 portions/week). Fish consumption was positively associated with intact and split proinsulin/C-peptide ratios, however, these associations were confounded by ethnicity (multivariable-adjusted β=0.073 [−0.014, 0.16] for intact proinsulin/C-peptide ratio, β=0.031 [−0.065, 0.13] for split proinsulin/C-peptide ratio). We also observed a significant positive association between fish consumption and fasting blood glucose (multivariable-adjusted β=2.27 [0.68, 3.86], p=0.005). We found no association between fish consumption and SI (multivariable-adjusted β= −0.015 [−0.083, 0.053]) or fasting insulin (multivariable-adjusted β=0.016 [−0.066, 0.10]). Conclusions Fish consumption was not associated with measures of insulin sensitivity in the multi-ethnic IRAS cohort. However, higher fish consumption may be associated with pancreatic beta-cell dysfunction.", "title": "Fish consumption, insulin sensitivity and beta-cell function in the Insulin Resistance Atherosclerosis Study (IRAS)" }, { "docid": "MED-4735", "text": "BACKGROUND/OBJECTIVES: To assess biomarkers and frequency questions as measures of fish consumption. SUBJECTS/METHODS: Participants in the Fishermen substudy numbered 125 men and 139 women (aged 22-74), and in the Health 2000 substudy, 577 men and 712 women (aged 45-74) participated. The aim of the Fishermen study was to examine the overall health effect of fish consumption in a high-consumption population, whereas the aim of the Health 2000 substudy was to obtain in-depth information on cardiovascular diseases and diabetes. Fish consumption was measured by the same validated food frequency questionnaire (FFQ) in both the studies, with a further two separate frequency questions used in the Fishermen substudy. Dioxins, polychlorinated biphenyls (PCBs) and methyl mercury (MeHg) (in the Fishermen substudy alone), and omega-3 polyunsaturated fatty acids (omega-3 PUFAs) (in both studies) were analyzed from fasting serum/blood samples. RESULTS: The Spearman's correlation coefficients between FFQ fish consumption and dioxins, PCBs, MeHg and omega-3 PUFAs were respectively 0.46, 0.48, 0.43 and 0.38 among the Fishermen substudy men, and 0.28, 0.36, 0.45 and 0.31 among women. Similar correlation coefficients were observed between FFQ fish consumption and serum omega-3 PUFAs in the Health 2000 substudy, and also between FFQ fish consumption and the frequency questions on fish consumption in the Fishermen substudy. According to multiple regression modeling and LMG metrics, the most important fish consumption biomarkers were dioxins and PCBs among the men and MeHg among the women. CONCLUSIONS: Environmental contaminants seemed to be slightly better fish consumption biomarkers than omega-3 PUFAs in the Baltic Sea area. The separate frequency questions measured fish consumption equally well when compared with the FFQ.", "title": "Dioxins, polychlorinated biphenyls, methyl mercury and omega-3 polyunsaturated fatty acids as biomarkers of fish consumption." }, { "docid": "MED-4948", "text": "The southeastern United States, and in particular the coastal areas along the Gulf of Mexico (Gulf Coast) in Florida, experience some of the highest levels of mercury deposition in the country. Although the State of Florida's coastal border is among the longest in the United States, and the State has issued fish consumption advisories due to mercury on multiple fish species, few data have been systematically collected to assess mercury levels in the human population of the state or to assess the efficacy of the consumption advisories. Because of the generally high rate of seafood consumption among coastal populations, the human population in the Florida Panhandle, near Pensacola, FL is potentially exposed to elevated levels of mercury. In the present study, we analyzed hair mercury levels in women of child-bearing age (16-49 years) who had resided near Pensacola, FL for at least 1 year. We also surveyed the fish consumption practices of the cohort and evaluated awareness of the Florida Fish Consumption Advisory. Hair mercury levels were significantly higher in women who consumed fish within the 30 days prior to sampling (p<0.05) and in those women who were unaware of the consumption advisory (p<0.05). Only 31% of the women reported knowledge of the consumption advisory and pregnant women exhibited lower awareness of the advisory than non-pregnant women. The data suggest that public health interventions such as education and fish advisories have not reached the majority of women in the counties surrounding Pensacola who are most at risk from consumption of fish with high levels of mercury.", "title": "Mercury levels and fish consumption practices in women of child-bearing age in the Florida Panhandle." }, { "docid": "MED-4733", "text": "OBJECTIVES: Mercury and most of its compounds are extremely toxic and should be handled with care. It can be inhaled and absorbed through the skin and mucous membranes. The most toxic forms of mercury are its organic compounds such as dimethylmercury and methylmercury. Fish have a natural tendency to accumulate mercury. Methylmercury is produced by microbial methylation of inorganic mercury in water sediment then it infiltrates the food chain and it consequently accumulates in fish. Fish are the main source of methylmercury in human food. Mercury is transferred into a hair; and this can be than used to monitor the long-term exposure to mercury. The content of mercury in hair depends on the frequency of fish consumption. The aim of our study was to compare mercury content in the hair of children that had various amounts of fish consumption (increased or reduced). DESIGN: Total mercury content in hair was determined by direct method of cold vapors using an AMA 245 analyzer. A total of 174 hair samples from the children (9-17 years old) were analyzed. In this study, the following localities were compared: Neratovice (n=42), Jeseníky (n=44), Prague (n=59) in Czech Republic and Olsztyn in Poland (n=29). Every sample was accompanied with questionnaire about age, gender, regions, amalgam fillings and fish consumption. RESULTS: We did not find a correlation between the content of mercury in hair with age, gender or amalgam fillings. We did find a correlation between fish consumption and the amount of mercury found in the hair samples. CONCLUSION: The amount of mercury in hair increases with more frequent consumption of freshwater and marine fish.", "title": "Mercury in human hair as an indicator of the fish consumption." }, { "docid": "MED-5097", "text": "Purpose of review To summarize recent evidence regarding associations of early life exposure to mercury from maternal fish consumption during pregnancy, thimerosal in vaccines and dental amalgam with child neurodevelopment. Recent findings Recent publications have built upon previous evidence demonstrating mild detrimental neurocognitive effects from prenatal methylmercury exposure from maternal fish consumption during pregnancy. New studies examining the effects of prenatal fish consumption as well as methylmercury suggest there are benefits from prenatal fish consumption, but also that consumption of fish high in mercury should be avoided. Future studies incorporating information on both the methylmercury and the docosahexaenoic acid contained within fish will help to refine recommendations to optimize outcomes for mothers and children. Additional recent studies have supported the safety of vaccines containing thimerosal and of dental amalgam for repair of dental caries in children. Summary Exposure to mercury may harm child development. Interventions intended to reduce exposure to low levels of mercury in early life must, however, be carefully evaluated in consideration of the potential attendant harm from resultant behavior changes, such as reduced docosahexaenoic acid exposure from lower seafood intake, reduced uptake of childhood vaccinations and suboptimal dental care.", "title": "Fish consumption, methylmercury and child neurodevelopment" }, { "docid": "MED-5099", "text": "There is controversy about the risks and benefits of consuming fish. Fish consumption provides nutrients, some of which are essential for brain growth and development. All fish, however, contain methyl mercury (MeHg), a known neurotoxicant. The toxic effect of MeHg seems most damaging during brain development, and thus, prenatal exposure is of greatest concern. At present the level of prenatal exposure associated with risk to a child's neurodevelopment is not known. Balancing the rewards and possible risks of fish consumption presents a dilemma to consumers and regulatory authorities. We review the nutrients in fish that are important in brain development and the current evidence of risk from MeHg at exposure levels achieved by consuming fish. We then review the findings from a large prospective cohort study of a population that consumes fish daily, the Seychelles Child Development Study. The MeHg content of the fish consumed in the Seychelles is similar to that of ocean fish available in industrialized countries, so they represent a sentinel population for any risk from fish consumption. In the Seychelles, evaluations of the children through 9 y of age show no consistent pattern of adverse associations with prenatal MeHg exposure. Recent studies in the Seychelles have focused on nutrients in fish that might influence a child's development, including long-chain polyunsaturated fatty acids, iodine, iron, and choline. Preliminary findings from this study suggest that the beneficial influence of nutrients from fish may counter any adverse effects of MeHg on the developing nervous system.", "title": "Nutrient and methyl mercury exposure from consuming fish." }, { "docid": "MED-5100", "text": "Historically, concerns with fish consumption have addressed risks from contaminants (e.g., methylmercury (MeHg), and PCBs). More recently public health concerns have widened in appreciation of the specific benefits of fish consumption such as those arising from polyunsaturated fatty acids (PUFAs) in fish oil. Fish contains varying levels of PUFAs and MeHg. Since both address the same health outcomes (in opposite directions) and occur together in fish, great care must be exercised in providing public health guidance. Mozaffarian and Rimm in a recent article (JAMA. 2006, 296:1885–99) have made a strong case for the beneficial effects of PUFAs in reducing the risk of coronary heart disease, but at the same time, have also broadly discounted the increased risks of coronary heart disease posed by MeHg in fish, stating that \"... among adults... the benefits of fish intake exceed the potential risks.\" This conclusion appears to be based on an inaccurate and insufficiently critical analysis of the literature. This literature is re-examined in light of their conclusions, and the available and appropriate public health options are considered.", "title": "Public health guidance on cardiovascular benefits and risks related to fish consumption" }, { "docid": "MED-5098", "text": "The health risk and the nutritional benefit of a food are usually assessed separately. Toxicologists recommend limiting the consumption of certain fish because of methylmercury; while nutritionists recommend eating more oily fish because of omega 3. A common evaluation is imperative to provide coherent recommendations. In order to evaluate the risks along with the benefits related to fish consumption, a common metric based on the quality-adjusted life year (QALY) method has been used. The impact of a theoretical change from a medium n-3 PUFAs intake to a high intake is studied, in terms of the cardiovascular system (CHD mortality, stroke mortality and morbidity) and on fetal neuronal development (IQ loss or gain). This application can be considered as a sensitive analysis of the model used and looks at the impact of changing the dose-response relationships between cardiovascular diseases and n-3 PUFAs intakes. Results show that increasing fish consumption may have a beneficial impact on health. However, the confidence interval of the overall estimation has a negative lower bound, which means that this increase in fish consumption may have a negative impact due to MeHg contamination. Some limits of the QALY approach are identified. The first concerns determination of the dose-response relationships. The second concerns the economic origins of the approach and of individual preferences. Finally, since only one beneficial aspect and one risk element were studied, consideration should be given to how other beneficial and risk components may be integrated in the model.", "title": "A risk-benefit analysis of French high fish consumption: a QALY approach." }, { "docid": "MED-4961", "text": "While fish consumption is considered a component of a heart-healthy diet, many illnesses have been associated with eating contaminated fish. The authors describe two cases of muscle weakness and rhabdomyolysis that occurred after eating salmon. Cases of rhabdomyolysis and muscle weakness after consumption of fresh water fish have rarely been reported in the United States but have been frequently reported from the Baltic region. This illness is known as Haff disease. While the etiology is unknown, it is felt to be a toxin. Palytoxin, found in marine fish, has been associated with rhabdomyolysis, and may serve as a model for further study of the suspected toxin responsible for rhabdomyolysis after consumption of fresh water fish. If a case of Haff disease is suspected, contact the Centers for Disease Control and Prevention and collect any uneaten fish, which may be sent for laboratory analysis.", "title": "Haff disease after eating salmon." }, { "docid": "MED-1256", "text": "BACKGROUND: Limited consumption of red meat, including beef, is one of many often-suggested strategies to reduce the risk of coronary heart disease (CHD). However, the role that beef consumption specifically plays in promoting adverse changes in the cardiovascular risk factor profile is unclear. OBJECTIVE: A meta-analysis of randomized, controlled, clinical trials (RCTs) was conducted to evaluate the effects of beef, independent of other red and processed meats, compared with poultry and/or fish consumption, on lipoprotein lipids. METHODS: RCTs published from 1950 to 2010 were considered for inclusion. Studies were included if they reported fasting lipoprotein lipid changes after beef and poultry/fish consumption by subjects free of chronic disease. A total of 124 RCTs were identified, and 8 studies involving 406 subjects met the prespecified entry criteria and were included in the analysis. RESULTS: Relative to the baseline diet, mean ± standard error changes (in mg/dL) after beef versus poultry/fish consumption, respectively, were -8.1 ± 2.8 vs. -6.2 ± 3.1 for total cholesterol (P = .630), -8.2 ± 4.2 vs. -8.9 ± 4.4 for low-density lipoprotein cholesterol (P = .905), -2.3 ± 1.0 vs. -1.9 ± 0.8 for high-density lipoprotein cholesterol (P = .762), and -8.1 ± 3.6 vs. -12.9 ± 4.0 mg/dL for triacylglycerols (P = .367). CONCLUSION: Changes in the fasting lipid profile were not significantly different with beef consumption compared with those with poultry and/or fish consumption. Inclusion of lean beef in the diet increases the variety of available food choices, which may improve long-term adherence with dietary recommendations for lipid management. Copyright © 2012 National Lipid Association. Published by Elsevier Inc. All rights reserved.", "title": "A meta-analysis of randomized controlled trials that compare the lipid effects of beef versus poultry and/or fish consumption." }, { "docid": "MED-4376", "text": "OBJECTIVE: To study hair mercury concentrations among women of reproductive age in relation to fish intake in Ontario, Canada. STUDY DESIGN: Three groups were studied: 22 women who had called the Motherisk Program for information on the reproductive safety of consuming fish during pregnancy, a group of Japanese residing in Toronto (n=23) consuming much larger amounts of fish, and a group of Canadian women of reproductive age (n=20) not seeking advice, were studied. Mercury concentrations in hair samples were measured using inductively coupled plasma mass spectrometry. Seafood consumption habits were recorded for each participant. Based on the types of fish consumed and consumption frequencies, the estimated monthly intake of mercury was calculated. Hair mercury concentrations were correlated to both the number of monthly seafood servings and the estimated ingested mercury dose. RESULTS: There were significant correlations between fish servings and hair mercury (Spearman r=0.73, P<.0001) and between amounts of consumed mercury and hair mercury concentrations (Spearman r=0.81, P<.0001). Nearly two thirds of the Motherisk callers, all of the Japanese women, and 15% of the Canadian women of reproductive age had hair mercury above 0.3 microg/g, which was shown recently to be the lowest observable adverse effect level in a large systematic review of all perinatal studies. CONCLUSIONS: Because of very wide variability, general recommendations for a safe number of fish servings may not be sufficient to protect the fetus. Analysis of hair mercury may be warranted before pregnancy in selected groups of women consuming more than 12 ounces of fish per week, as dietary modification can decrease body burden and ensure fetal safety. Copyright (c) 2010. Published by Mosby, Inc.", "title": "Hair mercury levels of women of reproductive age in Ontario, Canada: implications to fetal safety and fish consumption." }, { "docid": "MED-3790", "text": "Background: Processed meat and fish have been shown to be associated with the risk of advanced prostate cancer, but few studies have examined diet after prostate cancer diagnosis and risk of its progression. Objective: We examined the association between postdiagnostic consumption of processed and unprocessed red meat, fish, poultry, and eggs and the risk of prostate cancer recurrence or progression. Design: We conducted a prospective study in 1294 men with prostate cancer, without recurrence or progression as of 2004–2005, who were participating in the Cancer of the Prostate Strategic Urologic Research Endeavor and who were followed for an average of 2 y. Results: We observed 127 events (prostate cancer death or metastases, elevated prostate-specific antigen concentration, or secondary treatment) during 2610 person-years. Intakes of processed and unprocessed red meat, fish, total poultry, and skinless poultry were not associated with prostate cancer recurrence or progression. Greater consumption of eggs and poultry with skin was associated with 2-fold increases in risk in a comparison of extreme quantiles: eggs [hazard ratio (HR): 2.02; 95% CI: 1.10, 3.72; P for trend = 0.05] and poultry with skin (HR: 2.26; 95% CI: 1.36, 3.76; P for trend = 0.003). An interaction was observed between prognostic risk at diagnosis and poultry. Men with high prognostic risk and a high poultry intake had a 4-fold increased risk of recurrence or progression compared with men with low/intermediate prognostic risk and a low poultry intake (P for interaction = 0.003). Conclusions: Our results suggest that the postdiagnostic consumption of processed or unprocessed red meat, fish, or skinless poultry is not associated with prostate cancer recurrence or progression, whereas consumption of eggs and poultry with skin may increase the risk.", "title": "Intakes of meat, fish, poultry, and eggs and risk of prostate cancer progression" }, { "docid": "MED-2406", "text": "Objective. To examine the association between fish and marine long-chain omega-3 polyunsaturated fatty acid (LC n-3 PUFA) consumption and incidence of type 2 diabetes (T2D) in prospective cohort studies. Methods. Meta-analytic procedures were used to estimate the relative risk (RR) using random effects or fixed effects generic inverse variance model. Publication bias and study heterogeneity were assessed using Egger's test and I2 statistic. Results. We found no significant association between the intake of fish/seafood (pooled RR: 1.04; P = 0.63, 95% CI: 0.9 to 1.2, 549, 955 participants) or marine LC n-3 PUFA (pooled RR: 1.08, P = 0.39, 95% CI: 0.90 to 1.30, 346, 710 participants) and T2D risk. Significant study heterogeneity was observed in fish/seafood and marine LC n-3 PUFA studies (P < 0.00001). Subgroup analysis revealed no obvious sources for high heterogeneity. We also found a significant protective effect of oily fish intake on T2D risk (pooled RR = 0.89, P = 0.005, 95% CI: 0.82 to 0.96). Dose-response analysis suggested that every 80 g per day intake of oily fish may reduce 20% risk of T2D. Conclusion. We found no significant effect of fish/seafood or marine LC n-3 PUFA intake on risk of T2D but a significant effect of oily fish intake on risk of T2D.", "title": "Fish and Marine Omega-3 Polyunsatured Fatty Acid Consumption and Incidence of Type 2 Diabetes: A Systematic Review and Meta-Analysis" }, { "docid": "MED-2402", "text": "Despite a proposed protective effect of fish intake on the risk of cardiovascular disease, epidemiologic evidence on fish intake and mortality is inconsistent. We investigated associations of fish intake, assessed through a validated food frequency questionnaire, with risks of total and cause-specific mortality in 2 prospective cohort studies of 134,296 Chinese men and women (1997–2009). Vital status and date and cause of death were ascertained through annual linkage to the Shanghai Vital Statistics Registry database and biennial home visits. Cox regression was used to calculate hazard ratios and corresponding 95% confidence intervals. After excluding the first year of observation, the analysis included 3,666 deaths among women and 2,170 deaths among men. Fish intake was inversely associated with risks of total, ischemic stroke, and diabetes mortality; the corresponding hazard ratios for the highest quintiles of intake compared with the lowest were 0.84 (95% confidence interval (CI): 0.76, 0.92), 0.63 (95% CI: 0.41, 0.94), and 0.61 (95% CI: 0.39, 0.95), respectively. No associations with cancer or ischemic heart disease mortality were observed. Further analyses suggested that the inverse associations with total, ischemic stroke, and diabetes mortality were primarily related to consumption of saltwater fish and intake of long-chain n-3 fatty acids. Overall, our findings support the postulated health benefits of fish consumption.", "title": "Fish Intake and Risks of Total and Cause-specific Mortality in 2 Population-based Cohort Studies of 134,296 Men and Women" }, { "docid": "MED-1817", "text": "Pancreatic cancer is the fourth most common cause of cancer death worldwide with large geographical variation, which implies the contribution of diet and lifestyle in its etiology. We examined the association of meat and fish consumption with risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 477,202 EPIC participants from 10 European countries recruited between 1992 and 2000 were included in our analysis. Until 2008, 865 nonendocrine pancreatic cancer cases have been observed. Calibrated relative risks (RRs) and 95% confidence intervals (CIs) were computed using multivariable-adjusted Cox hazard regression models. The consumption of red meat (RR per 50 g increase per day = 1.03, 95% CI = 0.93-1.14) and processed meat (RR per 50 g increase per day = 0.93, 95% CI = 0.71-1.23) were not associated with an increased pancreatic cancer risk. Poultry consumption tended to be associated with an increased pancreatic cancer risk (RR per 50 g increase per day = 1.72, 95% CI = 1.04-2.84); however, there was no association with fish consumption (RR per 50 g increase per day = 1.22, 95% CI = 0.92-1.62). Our results do not support the conclusion of the World Cancer Research Fund that red or processed meat consumption may possibly increase the risk of pancreatic cancer. The positive association of poultry consumption with pancreatic cancer might be a chance finding as it contradicts most previous findings. Copyright © 2012 UICC.", "title": "Meat and fish consumption and risk of pancreatic cancer: results from the European Prospective Investigation into Cancer and Nutrition." }, { "docid": "MED-4377", "text": "Background: There have been conflicting reported associations between dietary factors and incident atrial fibrillation (AF). Objective: We evaluated associations between consumption of alcohol, caffeine, fiber, and polyunsaturated fatty acids (PUFAs) and incident AF in the Framingham Heart Study. Design: Participants without AF (n = 4526; 9640 examinations; mean age: 62 y; 56% women) from the original and offspring cohorts completed food-frequency questionnaires and were followed prospectively for 4 y. We examined the associations between dietary exposures and AF with Cox proportional hazards regression. Results: A total of 296 individuals developed AF (177 men, 119 women). In multivariable analyses, there were no significant associations between examined dietary exposures and AF risk. Hazard ratios (HRs) for increasing quartiles of dietary factors were as follows: for alcohol, 0.73 (95% CI: 0.5, 1.05), 0.85 (95% CI: 0.61, 1.18), and 1.12 (95% CI: 0.83, 1.51) (P for trend = 0.48); for caffeine, 0.84 (95% CI: 0.62, 1.15), 0.87 (95% CI: 0.64, 1.2), and 0.98 (95% CI: 0.7, 1.39) (P for trend = 0.84); for total fiber, 0.86 (95% CI: 0.61, 1.2), 0.64 (95% CI: 0.44, 0.92), and 0.81 (95% CI: 0.54, 1.2) (P for trend = 0.16); and for n−3 (omega-3) PUFAs, 1.11 (95% CI: 0.81, 1.54), 0.92 (95% CI: 0.65, 1.29), and 1.18 (95% CI: 0.85, 1.64) (P for trend = 0.57; quartile 1 was the reference group). In exploratory analyses, consumption of >4 servings of dark fish/wk (5 cases and 21 individuals at risk) was significantly associated with AF risk compared with the consumption of <1 serving of dark fish/wk (HR: 6.53; 95% CI: 2.65, 16.06; P < 0.0001). Conclusions: Consumption of alcohol, caffeine, fiber, and fish-derived PUFAs was not significantly associated with AF risk. The observed adverse association between the consumption of dark fish and AF merits further investigation. Our findings suggest that the dietary exposures examined convey limited attributable risk of AF in the general population.", "title": "Dietary factors and incident atrial fibrillation: the Framingham Heart Study" }, { "docid": "MED-4791", "text": "Dietary consumption of fish is widely recommended because of the beneficial effects of omega-3 polyunsaturated fatty acids on the risks of cardiovascular and Alzheimer's diseases. The American Heart Association currently recommends eating at least two servings of fish per week. We are concerned that consumption of farmed fish may provide a means of transmission of infectious prions from cows with bovine spongiform encephalopathy to humans, causing variant Creutzfeldt Jakob disease.", "title": "Bovine spongiform encephalopathy and aquaculture." }, { "docid": "MED-4345", "text": "BACKGROUND: n-3 (omega-3) Polyunsaturated fatty acids (PUFAs), fish, and nuts can regulate inflammatory processes and responses. OBJECTIVE: We investigated whether dietary intakes of PUFAs [n-3, n-6 (omega-6), and α-linolenic acid], fish, and nuts were associated with 15-y mortality attributed to noncardiovascular, noncancer inflammatory diseases. DESIGN: The analyses involved 2514 participants aged ≥49 y at baseline. Dietary data were collected by using a semiquantitative food-frequency questionnaire, and PUFA, fish, and nut intakes were calculated. Inflammatory disease mortality was confirmed from the Australian National Death Index. RESULTS: Over 15 y, 214 subjects died of inflammatory diseases. Women in the highest tertiles of total n-3 PUFA intake, compared with those in the lowest tertile of intake at baseline, had a 44% reduced risk of inflammatory disease mortality (P for trend = 0.03). This association was not observed in men. In both men and women, each 1-SD increase in energy-adjusted intake of α-linolenic acid was inversely associated with inflammatory mortality (hazard ratio: 0.83; 95% CI: 0.71, 0.98). Subjects in the second and third tertiles of nut consumption had a 51% and 32% reduced risk of inflammatory disease mortality, respectively, compared with those in the first tertile (reference). Dietary intakes of long-chain n-3 and n-6 PUFAs and fish were not associated with inflammatory disease mortality. CONCLUSIONS: We report on a novel link between dietary intake of total n-3 PUFA and risk of inflammatory disease mortality in older women. Furthermore, our data indicate a protective role of nuts, but not fish, against inflammatory disease mortality.", "title": "Consumption of polyunsaturated fatty acids, fish, and nuts and risk of inflammatory disease mortality." }, { "docid": "MED-4944", "text": "The co-occurrence of fish MeHg and omega-3 fatty acids in wild species can indeed be optimized by choosing certain species. Farmed finfish and shellfish that are fed fish-meal, however, can bioconcentrate both MeHg (in muscle) and organohalogen pollutants passed on in the fat components [Dorea, J.G., 2006. Fish meal in animal feed and human exposure to persistent bioaccumulative and toxic substances. J. Food Prot. 69, 2777-2785); when fish-meal is used to feed farm animals it may offer the worst of both worlds: saturated fat (with organohalogen pollutants) and MeHg. It is time to address the dietary sources of Hg derived from animals raised on fish-meal that may contribute to increase tissue Hg concentrations.", "title": "Studies of fish consumption as source of methylmercury should consider fish-meal-fed farmed fish and other animal foods." }, { "docid": "MED-5191", "text": "We evaluated animal food intake and cooking methods in relation to endometrial cancer risk in a population-based case–control study in Shanghai, China. A validated food frequency questionnaire was used to collect the usual dietary habits of 1204 cases and 1212 controls aged 30–69 years between 1997 and 2003. Statistical analyses were based on an unconditional logistic regression model adjusting for potential confounders. High intake of meat and fish was associated with an increased risk of endometrial cancer, with adjusted odds ratios for the highest vs the lowest quartile groups being 1.7 (95% confidence interval: 1.3–2.2) and 2.4 (1.8–3.1), respectively. The elevated risk was observed for all types of meat and fish intake. Intake of eggs and milk was not related to risk. Cooking methods and doneness levels for meat and fish were not associated with risk, nor did they modify the association with meat and fish consumption. Our study suggests that animal food consumption may play an important role in the aetiology of endometrial cancer, but cooking methods have minimal influence on risk among Chinese women.", "title": "Animal food intake and cooking methods in relation to endometrial cancer risk in Shanghai" }, { "docid": "MED-118", "text": "The aims of this study were to determine the concentrations of 4-nonylphenol (NP) and 4-octylphenol (OP) in 59 human milk samples and to examine related factors including mothers' demographics and dietary habits. Women who consumed over the median amount of cooking oil had significantly higher OP concentrations (0.98 ng/g) than those who consumed less (0.39 ng/g) (P < 0.05). OP concentration was significantly associated with the consumption of cooking oil (beta = 0.62, P < 0.01) and fish oil capsules (beta = 0.39, P < 0.01) after adjustment for age and body mass index (BMI). NP concentration was also significantly associated with the consumption of fish oil capsules (beta = 0.38, P < 0.01) and processed fish products (beta = 0.59, P < 0.01). The food pattern of cooking oil and processed meat products from factor analysis was strongly associated with OP concentration in human milk (P < 0.05). These determinations should aid in suggesting foods for consumption by nursing mothers in order to protect their infants from NP/OP exposure. 2010 Elsevier Ltd. All rights reserved.", "title": "Alkylphenols in human milk and their relations to dietary habits in central Taiwan." }, { "docid": "MED-2651", "text": "The aims of this study were to determine the concentrations of 4-nonylphenol (NP) and 4-octylphenol (OP) in 59 human milk samples and to examine related factors including mothers' demographics and dietary habits. Women who consumed over the median amount of cooking oil had significantly higher OP concentrations (0.98 ng/g) than those who consumed less (0.39 ng/g) (P < 0.05). OP concentration was significantly associated with the consumption of cooking oil (beta = 0.62, P < 0.01) and fish oil capsules (beta = 0.39, P < 0.01) after adjustment for age and body mass index (BMI). NP concentration was also significantly associated with the consumption of fish oil capsules (beta = 0.38, P < 0.01) and processed fish products (beta = 0.59, P < 0.01). The food pattern of cooking oil and processed meat products from factor analysis was strongly associated with OP concentration in human milk (P < 0.05). These determinations should aid in suggesting foods for consumption by nursing mothers in order to protect their infants from NP/OP exposure. 2010 Elsevier Ltd. All rights reserved.", "title": "Alkylphenols in human milk and their relations to dietary habits in central Taiwan." }, { "docid": "MED-4934", "text": "Concentrations of polybrominated diphenyl ethers (PBDEs), pesticides, polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons were measured in 136 fish from 14 remote lakes in 8 western US National Parks/Preserves between 2003 and 2005 and compared to human and wildlife contaminant health thresholds. A sensitive (median detection limit −18 pg/g wet weight), efficient (61% recovery at 8 ng/g), reproducible (4.1 %RSD), and accurate (7 % deviation from SRM) analytical method was developed and validated for these analyses. Concentrations of PCBs, hexachlorobenzene, hexachlorocyclohexanes, DDTs and chlordanes in western US fish were comparable to or lower than mountain fish recently collected from Europe, Canada, and Asia. Dieldrin and PBDE concentrations were higher than recent measurements in mountain fish and Pacific Ocean salmon. Concentrations of most contaminants in western US fish were 1–6 orders of magnitude below calculated recreational fishing contaminant health thresholds. However, contaminant concentrations exceeded subsistence fishing cancer screening values in 8 of 14 lakes. Average contaminant concentrations in fish exceeded wildlife contaminant health thresholds for piscivorous mammals in 5 lakes, and piscivorous birds in all 14 lakes. These results indicate that atmospherically deposited organic contaminants can accumulate in high elevation fish, reaching concentrations relevant to human and wildlife health.", "title": "Atmospherically Deposited PBDEs, Pesticides, PCBs, and PAHs in Western US National Park Fish: Concentrations and Consumption Guidelines" }, { "docid": "MED-4959", "text": "Tetrodotoxin is a neurotoxin that occurs in select species of the family Tetraodontidae (puffer fish). It causes paralysis and potentially death if ingested in sufficient quantities. In 2007, two individuals developed symptoms consistent with tetrodotoxin poisoning after ingesting home-cooked puffer fish purchased in Chicago. Both the Chicago retailer and the California supplier denied having sold or imported puffer fish but claimed the product was monkfish. However, genetic analysis and visual inspection determined that the ingested fish and others from the implicated lot retrieved from the supplier belonged to the family Tetraodontidae. Tetrodotoxin was detected at high levels in both remnants of the ingested meal and fish retrieved from the implicated lot. The investigation led to a voluntary recall of monkfish distributed by the supplier in three states and placement of the supplier on the U.S. Food and Drug Administration's Import Alert for species misbranding. This case of tetrodotoxin poisoning highlights the need for continued stringent regulation of puffer fish importation by the U.S. Food and Drug Administration, education of the public regarding the dangers of puffer fish consumption, and raising awareness among medical providers of the diagnosis and management of foodborne toxin ingestions and the need for reporting to public health agencies.", "title": "Public health response to puffer fish (Tetrodotoxin) poisoning from mislabeled product." }, { "docid": "MED-2411", "text": "The relationship between omega-3 polyunsaturated fatty acids (n-3 PUFA) from seafood (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) or plant (alpha-linolenic acid, ALA) sources and risk of type 2 diabetes mellitus (DM) remains unclear. We systematically searched multiple literature databases through June 2011 to identify prospective studies examining relations of dietary n-3 PUFA, dietary fish and/or seafood, and circulating n-3 PUFA biomarkers with incidence of DM. Data were independently extracted in duplicate by 2 investigators, including multivariate-adjusted relative risk (RR) estimates and corresponding 95% CIs. Generalized least-squares trend estimation was used to assess dose-response relationships, with pooled summary estimates calculated by both fixed-effect and random-effect models. From 288 identified abstracts, 16 studies met inclusion criteria, including 18 separate cohorts comprising 540,184 individuals and 25,670 cases of incident DM. Consumption of fish and/or seafood was not significantly associated with DM (n=13 studies; RR per 100g/d=1.12, 95% CI=0.94, 1.34); nor were consumption of EPA+DHA (n=16 cohorts; RR per 250mg/d=1.04, 95% CI=0.97, 1.10) or circulating levels of EPA+DHA biomarkers (n=5 cohorts; RR per 3% of total fatty acids=0.94, 95% CI=0.75, 1.17). Both dietary ALA (n=7 studies; RR per 0.5g/d=0.93, 95% CI=0.83, 1.04) and circulating ALA biomarker levels (n=6 studies; RR per 0.1% of total fatty acid=0.90, 95% CI=0.80, 1.00, P=0.06) were associated with non-significant trend towards lower risk of DM. Substantial heterogeneity (I2~80%) was observed among studies of fish/seafood or EPA+DHA and DM; moderate heterogeneity (<55%) was seen for dietary and biomarker ALA and DM. In unadjusted meta-regressions, study location (Asia vs. North America/Europe), mean BMI, and duration of follow-up each modified the association between fish/seafood and EPA+DHA consumption and DM risk (P-Interaction ≤ 0.02 each). We had limited statistical power to determine the independent effect of these sources of heterogeneity due to their high collinearity. The overall pooled findings do not support either major harms or benefits of fish/seafood or EPA+DHA on development of DM, and suggest that ALA may be associated with modestly lower risk. Reasons for potential heterogeneity of effects, which could include true biologic heterogeneity, publication bias, or chance, deserve further investigation.", "title": "Omega-3 Fatty Acids and incident Type 2 Diabetes: A Systematic Review and Meta-Analysis" }, { "docid": "MED-5026", "text": "Background: Higher intakes of fruit, vegetables, and dark fish may prevent sudden cardiac death and arrhythmias, but the exact mechanisms are not fully understood. Objective: We examined whether high consumption of fruit, vegetables, and dark fish would be associated with beneficial changes in heart rate variability (HRV). Design: HRV variables were measured among 586 older men with 928 total observations from November 2000 to June 2007 in the Normative Aging Study, a community-based longitudinal study of aging. Dietary intake was evaluated with a self-administered semiquantitative food-frequency questionnaire and categorized into quartiles. Results: After controlling for potential confounders, intake of green leafy vegetables was positively associated with normalized high-frequency power and inversely associated with normalized low-frequency power (P for trend < 0.05). These significant associations were retained after further adjustment for healthy lifestyle factors, such as physical activity and use of multivitamins. No significant association was seen between HRV measures and intakes of other fruit and vegetables, vitamin C, carotenoids, tuna and dark-meat fish, or n–3 (omega-3) fatty acids. An effect modification of intake of noncitrus fruit by obesity and of total vegetables and cruciferous vegetables by cigarette smoking was seen, which warrants further investigation. Conclusion: These findings suggest that higher intake of green leafy vegetables may reduce the risk of cardiovascular disease through favorable changes in cardiac autonomic function.", "title": "Fruit, vegetable, and fish consumption and heart rate variability: the Veterans Administration Normative Aging Study" } ]
515
High levels of CRP lead to a higher risk of exacerbations in chronic obstructive pulmonary disease (COPD).
[ { "docid": "29564505", "text": "IMPORTANCE Exacerbations of respiratory symptoms in chronic obstructive pulmonary disease (COPD) have profound and long-lasting adverse effects on patients. OBJECTIVE To test the hypothesis that elevated levels of inflammatory biomarkers in individuals with stable COPD are associated with an increased risk of having exacerbations. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study examining 61,650 participants with spirometry measurements from the Copenhagen City Heart Study (2001-2003) and the Copenhagen General Population Study (2003-2008). Of these, 6574 had COPD, defined as a ratio between forced expiratory volume in 1 second (FEV1) and forced vital capacity below 0.7. MAIN OUTCOMES AND MEASURES Baseline levels of C-reactive protein (CRP) and fibrinogen and leukocyte count were measured in participants at a time when they were not experiencing symptoms of exacerbations. Exacerbations were recorded and defined as short-course treatment with oral corticosteroids alone or in combination with an antibiotic or as a hospital admission due to COPD. Levels of CRP and fibrinogen and leukocyte count were defined as high or low according to cut points of 3 mg/L, 14 μmol/L, and 9 ×10(9)/L, respectively. RESULTS During follow-up, 3083 exacerbations were recorded (mean, 0.5/participant). In the first year of follow-up, multivariable-adjusted odds ratios for having frequent exacerbations were 1.2 (95% CI, 0.7-2.2; 17 events/1000 person-years) for individuals with 1 high biomarker, 1.7 (95% CI, 0.9-3.2; 32 events/1000 person-years) for individuals with 2 high biomarkers, and 3.7 (95% CI, 1.9-7.4; 81 events/1000 person-years) for individuals with 3 high biomarkers compared with individuals who had no elevated biomarkers (9 events/1000 person-years; trend: P = 2 × 10(-5)). Corresponding hazard ratios using maximum follow-up time were 1.4 (95% CI, 1.1-1.8), 1.6 (95% CI, 1.3-2.2), and 2.5 (95% CI, 1.8-3.4), respectively (trend: P = 1 × 10(-8)). The addition of inflammatory biomarkers to a basic model including age, sex, FEV1 percent predicted, smoking, use of any inhaled medication, body mass index, history of previous exacerbations, and time since most recent prior exacerbation improved the C statistics from 0.71 to 0.73 (comparison: P = 9 × 10(-5)). Relative risks were consistent in those with milder COPD, in those with no history of frequent exacerbations, and in the 2 studies separately. The highest 5-year absolute risks of having frequent exacerbations in those with 3 high biomarkers (vs no high biomarkers) were 62% (vs 24%) for those with Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades C-D (n = 558), 98% (vs 64%) in those with a history of frequent exacerbations (n = 127), and 52% (vs 15%) for those with GOLD grades 3-4 (n = 465). CONCLUSIONS AND RELEVANCE Simultaneously elevated levels of CRP and fibrinogen and leukocyte count in individuals with COPD were associated with increased risk of having exacerbations, even in those with milder COPD and in those without previous exacerbations. Further investigation is needed to determine the clinical value of these biomarkers for risk stratification.", "title": "Inflammatory biomarkers and exacerbations in chronic obstructive pulmonary disease." } ]
[ { "docid": "20109325", "text": "Chronic obstructive pulmonary disease (COPD) is a global health problem, and since 2001, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) has published its strategy document for the diagnosis and management of COPD. This executive summary presents the main contents of the second 5-year revision of the GOLD document that has implemented some of the vast knowledge about COPD accumulated over the last years. Today, GOLD recommends that spirometry is required for the clinical diagnosis of COPD to avoid misdiagnosis and to ensure proper evaluation of severity of airflow limitation. The document highlights that the assessment of the patient with COPD should always include assessment of (1) symptoms, (2) severity of airflow limitation, (3) history of exacerbations, and (4) comorbidities. The first three points can be used to evaluate level of symptoms and risk of future exacerbations, and this is done in a way that splits patients with COPD into four categories-A, B, C, and D. Nonpharmacologic and pharmacologic management of COPD match this assessment in an evidence-based attempt to relieve symptoms and reduce risk of exacerbations. Identification and treatment of comorbidities must have high priority, and a separate section in the document addresses management of comorbidities as well as COPD in the presence of comorbidities. The revised document also contains a new section on exacerbations of COPD. The GOLD initiative will continue to bring COPD to the attention of all relevant shareholders and will hopefully inspire future national and local guidelines on the management of COPD.", "title": "Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary." }, { "docid": "2032877", "text": "PURPOSE To identify factors affecting the short-term prognosis of patients with acutely exacerbated chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS The 590 patients having COPD as primary disease who were hospitalized in the pneumology unit of a university hospital from 1981 to 1990 were studied. A standardized protocol for the treatment of acutely exacerbated COPD was adopted for all the patients. The patient records were retrospectively analyzed by two observers, and 23 clinical and laboratory variables defining the patient status on admission were collected. Age and arterial gas data were also taken into account, and the outcome mortality was recorded. Interobserver reproducibility was tested by computing the kappa coefficient and Spearman's rho for dichotomous and continuous variables, respectively. The relationship of clinical and laboratory factors to the outcome was assessed first by univariate analysis and then by a logistic regression analysis assessing the independent predictive role of variables previously shown to be univariately correlated with mortality. RESULTS The mortality rate was 14.4%. The logistic regression analysis identified four independent predictors of death: age (odds ratio [OR] 1.07; 95% confidence interval [CI] 1.04 to 1.11), alveolar-arterial oxygen gradient greater than 41 mm Hg (OR 2.33; 95% CI 1.39 to 3.90), ventricular arrhythmias (OR 1.91; 95% CI 1.10 to 3.31), and atrial fibrillation (OR 2.27; 95% CI 1.14 to 4.51). CONCLUSIONS Patients with acutely exacerbated COPD having a high risk of death can be identified at the time of admission. Variables reflecting heart dysfunction are important determinants of this risk. Among pulmonary function data, only alveolar-arterial oxygen gradient contributes to the predictive model.", "title": "Predicting mortality of patients hospitalized for acutely exacerbated chronic obstructive pulmonary disease." }, { "docid": "21287352", "text": "BACKGROUND Recent studies show that COPD patients exhibit low-grade systemic inflammation, and that plasma fibrinogen and high neutrophil counts are related to faster declines in lung function. We examined correlations between serum biomarkers and the decline of lung function in COPD patients. METHOD Baseline levels of 9 serum biomarkers (TIMP-1, alpha1-antitrypsin, MMP-9, TNF-alpha, TGF-beta, IL-6, IL-8, neutrophil elastase and CRP), fibrinogen and white blood cell counts (WCC) were measured in 96 COPD patients. Lung function was measured at the time of blood sampling and every 3-6 months during the observation period (median 25.0 months). RESULTS Twenty patients were rapid decliners of lung function and 53 patients were non-decliners. Neutrophil counts, serum CRP and MMP-9 were significantly higher in the rapid decliners (p<0.05). The annual change of % predicted FEV(1) was inversely correlated with MMP-9 (r=-0.288; p<0.01) and CRP (r=-0.354; p<0.005) (partial correlation coefficients adjusted for age, sex, cardiovascular disease, smoking history, and baseline % predicted FEV(1)). The remaining biomarkers were not correlated with the annual change of % predicted FEV(1). CONCLUSION Serum CRP and MMP-9 levels were related to FEV(1) decline. These markers are good candidates as predictors for rapid decline of FEV(1) in COPD patients. Additional long-term and larger size studies of COPD patients could help determine the exact roles for these biomarkers.", "title": "Serum biomarkers as predictors of lung function decline in chronic obstructive pulmonary disease." }, { "docid": "18988265", "text": "BACKGROUND Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype of COPD that is independent of disease severity. METHODS We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Exacerbations were defined as events that led a care provider to prescribe antibiotics or corticosteroids (or both) or that led to hospitalization (severe exacerbations). Exacerbation frequency was observed over a period of 3 years. RESULTS Exacerbations became more frequent (and more severe) as the severity of COPD increased; exacerbation rates in the first year of follow-up were 0.85 per person for patients with stage 2 COPD (with stage defined in accordance with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages), 1.34 for patients with stage 3, and 2.00 for patients with stage 4. Overall, 22% of patients with stage 2 disease, 33% with stage 3, and 47% with stage 4 had frequent exacerbations (two or more in the first year of follow-up). The single best predictor of exacerbations, across all GOLD stages, was a history of exacerbations. The frequent-exacerbation phenotype appeared to be relatively stable over a period of 3 years and could be predicted on the basis of the patient's recall of previous treated events. In addition to its association with more severe disease and prior exacerbations, the phenotype was independently associated with a history of gastroesophageal reflux or heartburn, poorer quality of life, and elevated white-cell count. CONCLUSIONS Although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype. This has implications for the targeting of exacerbation-prevention strategies across the spectrum of disease severity. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT00292552.)", "title": "Susceptibility to exacerbation in chronic obstructive pulmonary disease." }, { "docid": "3580005", "text": "BACKGROUND Chronic obstructive pulmonary disease (COPD) has a high prevalence rate in Germany and a further increase is expected within the next years. Although risk factors on an individual level are widely understood, only little is known about the spatial heterogeneity and population-based risk factors of COPD. Background knowledge about broader, population-based processes could help to plan the future provision of healthcare and prevention strategies more aligned to the expected demand. The aim of this study is to analyze how the prevalence of COPD varies across northeastern Germany on the smallest spatial-scale possible and to identify the location-specific population-based risk factors using health insurance claims of the AOK Nordost. METHODS To visualize the spatial distribution of COPD prevalence at the level of municipalities and urban districts, we used the conditional autoregressive Besag-York-Mollié (BYM) model. Geographically weighted regression modelling (GWR) was applied to analyze the location-specific ecological risk factors for COPD. RESULTS The sex- and age-adjusted prevalence of COPD was 6.5% in 2012 and varied widely across northeastern Germany. Population-based risk factors consist of the proportions of insurants aged 65 and older, insurants with migration background, household size and area deprivation. The results of the GWR model revealed that the population at risk for COPD varies considerably across northeastern Germany. CONCLUSION Area deprivation has a direct and an indirect influence on the prevalence of COPD. Persons ageing in socially disadvantaged areas have a higher chance of developing COPD, even when they are not necessarily directly affected by deprivation on an individual level. This underlines the importance of considering the impact of area deprivation on health for planning of healthcare. Additionally, our results reveal that in some parts of the study area, insurants with migration background and persons living in multi-persons households are at elevated risk of COPD.", "title": "Who is where at risk for Chronic Obstructive Pulmonary Disease? A spatial epidemiological analysis of health insurance claims for COPD in Northeastern Germany" }, { "docid": "21003930", "text": "BACKGROUND Long-term exposure to pollution can lead to an increase in the rate of decline of lung function, especially in older individuals and in those with chronic obstructive pulmonary disease (COPD), whereas shorter-term exposure at higher pollution levels has been implicated in causing excess deaths from ischaemic heart disease and exacerbations of COPD. We aimed to assess the effects on respiratory and cardiovascular responses of walking down a busy street with high levels of pollution compared with walking in a traffic-free area with lower pollution levels in older adults. METHODS In this randomised, crossover study, we recruited men and women aged 60 years and older with angiographically proven stable ischaemic heart disease or stage 2 Global initiative for Obstructive Lung Disease (GOLD) COPD who had been clinically stable for 6 months, and age-matched healthy volunteers. Individuals with ischaemic heart disease or COPD were recruited from existing databases or outpatient respiratory and cardiology clinics at the Royal Brompton & Harefield NHS Foundation Trust and age-matched healthy volunteers using advertising and existing databases. All participants had abstained from smoking for at least 12 months and medications were taken as recommended by participants' doctors during the study. Participants were randomly assigned by drawing numbered disks at random from a bag to do a 2 h walk either along a commercial street in London (Oxford Street) or in an urban park (Hyde Park). Baseline measurements of participants were taken before the walk in the hospital laboratory. During each walk session, black carbon, particulate matter (PM) concentrations, ultrafine particles, and nitrogen dioxide (NO2) concentrations were measured. FINDINGS Between October, 2012, and June, 2014, we screened 135 participants, of whom 40 healthy volunteers, 40 individuals with COPD, and 39 with ischaemic heart disease were recruited. Concentrations of black carbon, NO2, PM10, PM2.5, and ultrafine particles were higher on Oxford Street than in Hyde Park. Participants with COPD reported more cough (odds ratio [OR] 1·95, 95% CI 0·96-3·95; p<0·1), sputum (3·15, 1·39-7·13; p<0·05), shortness of breath (1·86, 0·97-3·57; p<0·1), and wheeze (4·00, 1·52-10·50; p<0·05) after walking down Oxford Street compared with Hyde Park. In all participants, irrespective of their disease status, walking in Hyde Park led to an increase in lung function (forced expiratory volume in the first second [FEV1] and forced vital capacity [FVC]) and a decrease in pulse wave velocity (PWV) and augmentation index up to 26 h after the walk. By contrast, these beneficial responses were attenuated after walking on Oxford Street. In participants with COPD, a reduction in FEV1 and FVC, and an increase in R5-20 were associated with an increase in during-walk exposure to NO2, ultrafine particles and PM2.5, and an increase in PWV and augmentation index with NO2 and ultrafine particles. In healthy volunteers, PWV and augmentation index were associated both with black carbon and ultrafine particles. INTERPRETATION Short-term exposure to traffic pollution prevents the beneficial cardiopulmonary effects of walking in people with COPD, ischaemic heart disease, and those free from chronic cardiopulmonary diseases. Medication use might reduce the adverse effects of air pollution in individuals with ischaemic heart disease. Policies should aim to control ambient levels of air pollution along busy streets in view of these negative health effects. FUNDING British Heart Foundation.", "title": "Respiratory and cardiovascular responses to walking down a traffic-polluted road compared with walking in a traffic-free area in participants aged 60 years and older with chronic lung or heart disease and age-matched healthy controls: a randomised, crossover study" }, { "docid": "26107000", "text": "RATIONALE Physical activity is reduced in patients with chronic obstructive pulmonary disease (COPD). COPD has a systemic component that includes significant extrapulmonary effects that may contribute to its severity in individual patients. OBJECTIVES To investigate the association of extrapulmonary effects of the disease and its comorbidities with reduced physical activity in patients with COPD. METHODS In a cross-sectional study, 170 outpatients with COPD (GOLD [Global Initiative for Chronic Obstructive Lung Disease] stages I-IV; BODE [body mass index, airway obstruction, dyspnea, and exercise capacity] score 0-10) underwent a series of tests. Physical activity was assessed over 5 to 6 consecutive days by using a multisensor accelerometer armband that records steps per day and the physical activity level (total daily energy expenditure divided by whole-night sleeping energy expenditure). Cardiovascular status was assessed by echocardiography, vascular Doppler sonography, and levels of N-terminal pro-B-type natriuretic peptide. Mental status, metabolic/muscular status, systemic inflammation, and anemia were assessed by Beck Depression Inventory, bioelectrical impedance analysis, handgrip strength, high-sensitivity C-reactive protein/fibrinogen, and hemoglobin, respectively. MEASUREMENTS AND MAIN RESULTS In a multivariate linear regression analysis using either steps per day or physical activity level as a dependent variable, the extrapulmonary parameters that were associated with reduced physical activity in patients with COPD independently of GOLD stages or BODE score were N-terminal pro-B-type natriuretic peptide levels, echocardiographically measured left ventricular diastolic function, and systemic inflammation. CONCLUSIONS Higher values of systemic inflammation and left cardiac dysfunction are associated with reduced physical activity in patients with COPD.", "title": "Extrapulmonary effects of chronic obstructive pulmonary disease on physical activity: a cross-sectional study." }, { "docid": "19464037", "text": "OBJECTIVE To describe outcomes and identify variables associated with hospital and 1-year survival for patients admitted to an intensive care unit (ICU) with an acute exacerbation of chronic obstructive pulmonary disease (COPD). DESIGN Prospective, multicenter, inception cohort study. SETTING Forty-two ICUs at 40 US hospitals. PATIENTS A total of 362 admissions for COPD exacerbation selected from the Acute Physiology and Chronic Health Evaluation (APACHE) III database of 17,440 ICU admissions. MEASUREMENTS AND RESULTS Hospital mortality for the 362 admissions was 24%. For the 167 patients aged 65 years or older, mortality was 30% at hospital discharge, 41% at 90 days, 47% at 180 days, and 59% at 1 year. Median survival for all patients was 224 days, and median survival for the patients who died within 1 year was 30.5 days. On multiple regression analysis, variables associated with hospital mortality included age, severity of respiratory and nonrespiratory organ system dysfunction, and hospital length of stay before ICU admission. Development of nonrespiratory organ system dysfunction was the major predictor of hospital mortality (60% of total explanatory power) and 180-day outcomes (54% of explanatory power). Respiratory physiological variables (respiratory rate, serum pH, PaCO2, PaO2, and alveolar-arterial difference in partial pressure of oxygen [PAO2-PaO2]) indicative of advanced dysfunction were more strongly associated with 180-day mortality rates (22% of explanatory power) than hospital death rates (4% of explanatory power). After controlling for severity of illness, mechanical ventilation at ICU admission was not associated with either hospital mortality or subsequent survival. CONCLUSIONS Patients with COPD admitted to an ICU for an acute exacerbation have a substantial hospital mortality (24%). For patients aged 65 years or older, mortality doubles in 1 year from 30% to 59%. Hospital and longer-term mortality is closely associated with development of nonrespiratory organ system dysfunction; severity of the underlying respiratory function substantially influences mortality following hospital discharge. The need for mechanical ventilation at ICU admission did not influence either short- or long-term outcomes. Physicians should be aware of these relationships when making treatment decisions or evaluating new therapies.", "title": "Hospital and 1-year survival of patients admitted to intensive care units with acute exacerbation of chronic obstructive pulmonary disease." }, { "docid": "9440748", "text": "BACKGROUND The major sites of obstruction in chronic obstructive pulmonary disease (COPD) are small airways (<2 mm in diameter). We wanted to determine whether there was a relationship between small-airway obstruction and emphysematous destruction in COPD. METHODS We used multidetector computed tomography (CT) to compare the number of airways measuring 2.0 to 2.5 mm in 78 patients who had various stages of COPD, as judged by scoring on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) scale, in isolated lungs removed from patients with COPD who underwent lung transplantation, and in donor (control) lungs. MicroCT was used to measure the extent of emphysema (mean linear intercept), the number of terminal bronchioles per milliliter of lung volume, and the minimum diameters and cross-sectional areas of terminal bronchioles. RESULTS On multidetector CT, in samples from patients with COPD, as compared with control samples, the number of airways measuring 2.0 to 2.5 mm in diameter was reduced in patients with GOLD stage 1 disease (P=0.001), GOLD stage 2 disease (P=0.02), and GOLD stage 3 or 4 disease (P<0.001). MicroCT of isolated samples of lungs removed from patients with GOLD stage 4 disease showed a reduction of 81 to 99.7% in the total cross-sectional area of terminal bronchioles and a reduction of 72 to 89% in the number of terminal bronchioles (P<0.001). A comparison of the number of terminal bronchioles and dimensions at different levels of emphysematous destruction (i.e., an increasing value for the mean linear intercept) showed that the narrowing and loss of terminal bronchioles preceded emphysematous destruction in COPD (P<0.001). CONCLUSIONS These results show that narrowing and disappearance of small conducting airways before the onset of emphysematous destruction can explain the increased peripheral airway resistance reported in COPD. (Funded by the National Heart, Lung, and Blood Institute and others.).", "title": "Small-airway obstruction and emphysema in chronic obstructive pulmonary disease." }, { "docid": "20732789", "text": "Cigarette smoke is the main cause of chronic obstructive pulmonary disease (COPD), where it can contribute to the observed airway inflammation. PGE(2) is produced within human airways, and both pro- and anti-inflammatory activities have been reported. We quantitated PGE(2) concentrations in induced sputum supernatants from different groups of subjects and correlated the obtained values to neutrophil infiltration as well as to the expression of cyclooxygenase-2 (COX-2). Cigarette smoke extract (CSE) was used to evaluate the effect of smoking on COX-2 and PGE(2) receptor expression as well as on PGE(2) release in neutrophils and alveolar macrophages (AM) obtained from normal donors. The effects of PGE(2) and of PGE receptor agonists and antagonists were evaluated on the adhesion of neutrophil to a human bronchial epithelial cell line (16HBE). PGE(2) levels, COX-2 expression, and neutrophil infiltration were significantly higher in normal smokers and COPD smokers (P < 0.0001) compared with controls and COPD former smokers. Induced sputum supernatant caused neutrophil adhesion to 16HBE that was significantly reduced, in COPD smokers only, by PGE(2) immunoprecipitation. In vitro experiments confirmed that CSE increased PGE(2) release and COX-2 and PGE(2) receptor expression in neutrophils and AM; PGE(2) enhanced the adhesion of neutrophils to 16HBE, and a specific E-prostanoid 4 (EP(4)) receptor antagonist blunted its effect. These results suggest that CSE promote the induction of COX-2 and contributes to the proinflammatory effects of PGE(2) in the airways of COPD subjects.", "title": "Chronic obstructive pulmonary disease and neutrophil infiltration: role of cigarette smoke and cyclooxygenase products." }, { "docid": "3553087", "text": "Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants. We have previously identified iron-responsive element-binding protein 2 (IRP2) as an important COPD susceptibility gene and have shown that IRP2 protein is increased in the lungs of individuals with COPD. Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD. By integrating RNA immunoprecipitation followed by sequencing (RIP-seq), RNA sequencing (RNA-seq), and gene expression and functional enrichment clustering analysis, we identified Irp2 as a regulator of mitochondrial function in the lungs of mice. Irp2 increased mitochondrial iron loading and levels of cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD. Frataxin-deficient mice, which had higher mitochondrial iron loading, showed impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas mice deficient in the synthesis of cytochrome c oxidase, which have reduced COX, were protected from CS-induced pulmonary inflammation and impairment of MCC. Mice treated with a mitochondrial iron chelator or mice fed a low-iron diet were protected from CS-induced COPD. Mitochondrial iron chelation also alleviated CS-induced impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD.", "title": "Mitochondrial iron chelation ameliorates cigarette-smoke induced bronchitis and emphysema in mice" }, { "docid": "9658390", "text": "INTRODUCTION To assess whether respiratory intermediate care units (RICUs) are cost effective alternatives to intensive care units (ICUs) for patients with exacerbation of chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS Multi-centre, prospective, bottom-up cost study performed in 15 ICUs and 6 RICUs. COPD patients staying longer than 48 h were recruited; those coming from other ICUs/RICUs, with immune-deficiency or stroke, were excluded. After the ICU sample was standardised to the RICU distribution of the reason-for-admission and infusion of a vasoactive drug on admission, 60 ICU patients and 65 RICU patients remained, of the original 164 recruited. For each patient, besides clinical data on admission and discharge, daily information about the resources consumed were recorded and analysed in terms of their costs. RESULTS Total cost per patient was lower in RICUs than in ICUs (754 vs. 1507 Euro; P < 0.0001). In all items, except drugs and nutrition, we found a significant lower cost in RICUs. Dead patients were noticeably different in terms of disease severity between ICUs and RICUs, while surviving ones were not. CONCLUSIONS Our study suggests that some COPD patients, less severe and with pure respiratory failure, could be successfully and less costly treated in RICUs.", "title": "Costs of the COPD. Differences between intensive care unit and respiratory intermediate care unit." }, { "docid": "21395936", "text": "Chronic obstructive pulmonary disease (COPD) is a chronic airway disorder characterized by obstructive airflow limitation which is not completely reversible with treatment. Inflammatory changes in the peripheral airways, especially those with the diameter less than 2mm (so-called small airway disease) have been speculated to be initial steps of COPD. And so it must be quite clear that neutrophils and macrophages play an essential role in the pathogenesis of these lesions. Studies with bronchoalveolar lavage demonstrated an increase in neutrophil numbers and the neutrophil chemoattractant interleukin-8. Recent studies demonstrated that neutrophils and macrophages are increased and contain a variety of proteases, which are involved in cell infiltration and activation. Studies with gene-engineered animals and anti-cytokine treatment will facilitate better understanding the role of neutrophils and macrophages, and eventual novel therapy.", "title": "[Neutrophils and macrophages related to the pathogenesis and disease development of chronic obstructive pulmonary disease by the inflammatory reaction]." }, { "docid": "24323695", "text": "RATIONALE Up to 80% of patients with lung cancer have comorbid chronic obstructive pulmonary disease (COPD). Many of them are poor candidates for stage-specific lung cancer treatment due to diminished lung function and poor functional status, and many forego treatment. The negative effect of COPD may be moderated by pulmonologist-guided management. OBJECTIVES This study examined the association between pulmonologist management and the probability of receiving the recommended stage-specific treatment modality and overall survival among patients with non-small cell lung cancer (NSCLC) with preexisting COPD. METHODS Early- and advanced-stage NSCLC cases diagnosed between 2002 and 2005 with a prior COPD diagnosis (3-24 months before NSCLC diagnosis) were identified in Surveillance, Epidemiology, and End Results tumor registry data linked to Medicare claims. Study outcomes included receipt of recommended stage-specific treatment (surgical resection for early-stage NSCLC and chemotherapy for advanced-stage NSCLC [advNSCLC]) and overall survival. Pulmonologist management was considered present if one or more Evaluation and Management visit claims with pulmonologist specialty were observed within 6 months after NSCLC diagnosis. Stage-specific multivariate logistic regression tested association between pulmonologist management and treatment received. Cox proportional hazard models examined the independent association between pulmonologist care and mortality. Two-stage residual inclusion instrumental variable (2SRI-IV) analyses tested and adjusted for potential confounding based on unobserved factors or measurement error. MEASUREMENTS AND MAIN RESULTS The cohorts included 5,488 patients with early-stage NSCLC and 6,426 patients with advNSCLC disease with preexisting COPD. Pulmonologist management was recorded for 54.9% of patients with early stage NSCLC and 35.7% of patients with advNSCLC. Of those patients with pulmonologist involvement, 58.5% of patients with early NSCLC received surgical resection, and 43.6% of patients with advNSCLC received chemotherapy. Pulmonologist management post NSCLC diagnosis was associated with increased surgical resection rates (odds ratio, 1.26; 95% confidence interval, 1.11-1.45) for early NSCLC and increased chemotherapy rates (odds ratio, 1.88; 95% confidence interval, 1.67-2.10) for advNSCLC. Pulmonologist management was also associated with reduced mortality risk for patients with early-stage NSCLC but not AdvNSCLC. CONCLUSIONS Pulmonologist management had a positive association with rates of stage-specific treatment in both groups and overall survival in early-stage NSCLC. These results provide preliminary support for the recently published guidelines emphasizing the role of pulmonologists in lung cancer management.", "title": "Pulmonologist involvement, stage-specific treatment, and survival in adults with non-small cell lung cancer and chronic obstructive pulmonary disease." }, { "docid": "13843341", "text": "OBJECTIVE To evaluate the cost effectiveness of standard treatment with and without the addition of ward based non-invasive ventilation in patients admitted to hospital with an acute exacerbation of chronic obstructive pulmonary disease. DESIGN Incremental cost effectiveness analysis of a randomised controlled trial. SETTING Medical wards in 14 hospitals in the United Kingdom. PARTICIPANTS The trial comprised 236 patients admitted to hospital with an acute exacerbation of chronic obstructive pulmonary disease and mild to moderate acidosis (pH 7.25-7.35) secondary to respiratory failure. The economic analysis compared the costs of treatment that these patients received after randomisation. MAIN OUTCOME MEASURE Incremental cost per in-hospital death. RESULTS 24/118 died in the group receiving standard treatment and 12/118 in the group receiving non-invasive ventilation (P=0.05). Allocation to the group receiving non-invasive ventilation was associated with a reduction in costs of 49362 pounds sterling (78741 dollars; 73109 euros), mainly through reduced use of intensive care units. The incremental cost effectiveness ratio was -645 pounds sterling per death avoided (95% confidence interval -2310 pounds sterling to 386 pounds sterling), indicating a dominant (more effective and less costly) strategy. Modelling of these data indicates that a typical UK hospital providing a non-invasive ventilation service will avoid six deaths and three to nine admissions to intensive care units per year, with an associated cost reduction of 12000-53000 pounds sterling per year. CONCLUSIONS Non-invasive ventilation is a highly cost effective treatment that both reduced total costs and improved mortality in hospital.", "title": "Cost effectiveness of ward based non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease: economic analysis of randomised controlled trial." }, { "docid": "8582337", "text": "IMPORTANCE Understanding the major health problems in the United States and how they are changing over time is critical for informing national health policy. OBJECTIVES To measure the burden of diseases, injuries, and leading risk factors in the United States from 1990 to 2010 and to compare these measurements with those of the 34 countries in the Organisation for Economic Co-operation and Development (OECD) countries. DESIGN We used the systematic analysis of descriptive epidemiology of 291 diseases and injuries, 1160 sequelae of these diseases and injuries, and 67 risk factors or clusters of risk factors from 1990 to 2010 for 187 countries developed for the Global Burden of Disease 2010 Study to describe the health status of the United States and to compare US health outcomes with those of 34 OECD countries. Years of life lost due to premature mortality (YLLs) were computed by multiplying the number of deaths at each age by a reference life expectancy at that age. Years lived with disability (YLDs) were calculated by multiplying prevalence (based on systematic reviews) by the disability weight (based on population-based surveys) for each sequela; disability in this study refers to any short- or long-term loss of health. Disability-adjusted life-years (DALYs) were estimated as the sum of YLDs and YLLs. Deaths and DALYs related to risk factors were based on systematic reviews and meta-analyses of exposure data and relative risks for risk-outcome pairs. Healthy life expectancy (HALE) was used to summarize overall population health, accounting for both length of life and levels of ill health experienced at different ages. RESULTS US life expectancy for both sexes combined increased from 75.2 years in 1990 to 78.2 years in 2010; during the same period, HALE increased from 65.8 years to 68.1 years. The diseases and injuries with the largest number of YLLs in 2010 were ischemic heart disease, lung cancer, stroke, chronic obstructive pulmonary disease, and road injury. Age-standardized YLL rates increased for Alzheimer disease, drug use disorders, chronic kidney disease, kidney cancer, and falls. The diseases with the largest number of YLDs in 2010 were low back pain, major depressive disorder, other musculoskeletal disorders, neck pain, and anxiety disorders. As the US population has aged, YLDs have comprised a larger share of DALYs than have YLLs. The leading risk factors related to DALYs were dietary risks, tobacco smoking, high body mass index, high blood pressure, high fasting plasma glucose, physical inactivity, and alcohol use. Among 34 OECD countries between 1990 and 2010, the US rank for the age-standardized death rate changed from 18th to 27th, for the age-standardized YLL rate from 23rd to 28th, for the age-standardized YLD rate from 5th to 6th, for life expectancy at birth from 20th to 27th, and for HALE from 14th to 26th. CONCLUSIONS AND RELEVANCE From 1990 to 2010, the United States made substantial progress in improving health. Life expectancy at birth and HALE increased, all-cause death rates at all ages decreased, and age-specific rates of years lived with disability remained stable. However, morbidity and chronic disability now account for nearly half of the US health burden, and improvements in population health in the United States have not kept pace with advances in population health in other wealthy nations.", "title": "The state of US health, 1990-2010: burden of diseases, injuries, and risk factors." }, { "docid": "20887554", "text": "BACKGROUND C-reactive protein (CRP) is a known risk factor for cardiovascular events in the healthy population and in patients with coronary artery disease. High CRP levels before cardiac surgery are associated with worse short-term outcome, but its role after discharge home remains unknown. The study objective was to evaluate the effect of CRP on short-term and mid-term outcome after cardiac surgery. METHODS From August 2000 to May 2004, values for preoperative CRP were available for 597 unselected patients undergoing cardiac operations. CRP was used to divide this cohort in two groups: a low inflammatory status (LHS) group of 354 patients with CRP of less than 0.5 mg/dL, and a high inflammatory status (HIS) group of 243 patients with a CRP of 0.5 mg/dL or more. Follow-up lasted a maximum of 3 years (median, 1.8 +/- 1.5 years) and was 92.6% complete. RESULTS In-hospital mortality was 8.2% in the HIS group and 3.4% in the LIS group (odds ratio [OR], 2.61; p = 0.02). Incidence of postoperative infections was 16.5% in the HIS group and 5.1% in the LIS group (OR, 3.25; p = 0.0001). Sternal wound infections were also more frequent in the HIS group (10.7% versus 2.8%; OR, 3.43; p = 0.002). During follow-up, the HIS group had worse survival (88.5% +/- 2.9% versus 91.9% +/- 2.5%; OR, 1.93; p = 0.05) and a higher need of hospitalization for cardiac-related causes (73.6% +/- 6% versus 86.5% +/- 3.2%; OR, 1.82; p = 0.05). CONCLUSIONS Patients undergoing cardiac surgery with a CRP level of 0.5 mg/dL or more are exposed to a higher risk of in-hospital mortality and postoperative infections. Despite surgical correction of cardiac disease, a high preoperative CRP value is an independent risk factor for mid-term survival and hospitalization for cardiac causes.", "title": "Preoperative C-reactive protein predicts mid-term outcome after cardiac surgery." }, { "docid": "25319221", "text": "INTRODUCTION The GOLD guidelines advocate not to institute inhaled corticosteroids (ICS) in patients with mild-to-moderate COPD. However, many patients do use ICS and in some patients, withdrawal is associated with deteriorating lung function and increased exacerbation rates. Unfortunately, physicians do not know in which patients they can stop ICS treatment safely. AIM To identify predictors of COPD exacerbations after ICS withdrawal. METHODS During ICS treatment, post-bronchodilator spirometry, body plethysmography, and health status assessment were performed in 68 COPD patients using ICS. Additionally, sputum cell differentials, supernatant leukotriene B(4), eosinophilic cationic protein, and myeloperoxidase, serum C-reactive protein and soluble intracellular adhesion molecule, and urinary desmosine were assessed. Sputum was also analysed for mRNA levels of haemoxygenase-1, tumour necrosis factor-α, RANTES, interleukin 5(IL-5), IL-10, IL-12, IL-13, transforming growth factor-β, and interferon-γ. STATISTICS Cox regression analyses were performed using time to exacerbation as outcome variable to identify significant hazards for a COPD exacerbation after ICS withdrawal. RESULTS Higher sputum % eosinophils, higher sputum MPO/neutrophil level, longer duration of COPD symptoms, <40 packyears smoking, and ICS withdrawal in November, December or January were significant hazards (all p<0.05) for experiencing a COPD exacerbation after ICS withdrawal in a monovariate model. In a multivariate model, all factors proved independent predictors except for sputum MPO/neutrophil level. CONCLUSIONS Decisions on whether or not inhaled corticosteroids can be safely withdrawn in mild-to-moderate COPD can be facilitated by assessment of sputum inflammation, particularly eosinophil numbers, next to packyears smoking, season, and duration of COPD symptoms.", "title": "Sputum inflammation predicts exacerbations after cessation of inhaled corticosteroids in COPD." }, { "docid": "883747", "text": "Group 2 innate lymphoid cells (ILC2s) secrete type 2 cytokines, which protect against parasites but can also contribute to a variety of inflammatory airway diseases. We report here that interleukin 1β (IL-1β) directly activated human ILC2s and that IL-12 induced the conversion of these activated ILC2s into interferon-γ (IFN-γ)-producing ILC1s, which was reversed by IL-4. The plasticity of ILCs was manifested in diseased tissues of patients with severe chronic obstructive pulmonary disease (COPD) or chronic rhinosinusitis with nasal polyps (CRSwNP), which displayed IL-12 or IL-4 signatures and the accumulation of ILC1s or ILC2s, respectively. Eosinophils were a major cellular source of IL-4, which revealed cross-talk between IL-5-producing ILC2s and IL-4-producing eosinophils. We propose that IL-12 and IL-4 govern ILC2 functional identity and that their imbalance results in the perpetuation of type 1 or type 2 inflammation.", "title": "IL-1β, IL-4 and IL-12 control the fate of group 2 innate lymphoid cells in human airway inflammation in the lungs" }, { "docid": "72933407", "text": "ContextSeveral novel risk factors for atherosclerosis have recently been proposed, but few comparative data exist to guide clinical use of these emerging biomarkers. ObjectiveTo compare the predictive value of 11 lipid and nonlipid biomarkers as risk factors for development of symptomatic peripheral arterial disease (PAD).Design, Setting, and ParticipantsNested case-control study using plasma samples collected at baseline from a prospective cohort of 14 916 initially healthy US male physicians aged 40 to 84 years, of whom 140 subsequently developed symptomatic PAD (cases); 140 age- and smoking status–matched men who remained free of vascular disease during an average 9-year follow-up period were randomly selected as controls. Main Outcome MeasureIncident PAD, as determined by baseline total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol–HDL-C ratio, triglycerides, homocysteine, C-reactive protein (CRP), lipoprotein(a), fibrinogen, and apolipoproteins (apo) A-I and B-100.ResultsIn univariate analyses, plasma levels of total cholesterol (P<.001), LDL-C (P = .001), triglycerides (P = .001), apo B-100 (P = .001), fibrinogen (P = .02), CRP (P = .006), and the total cholesterol–HDL-C ratio (P<.001) were all significantly higher at baseline among men who subsequently developed PAD compared with those who did not, while levels of HDL-C (P = .009) and apo A-I (P = .05) were lower. Nonsignificant baseline elevations of lipoprotein(a) (P = .40) and homocysteine (P = .90) were observed. In multivariable analyses, the total cholesterol–HDL-C ratio was the strongest lipid predictor of risk (relative risk [RR] for those in the highest vs lowest quartile, 3.9; 95% confidence interval [CI], 1.7-8.6), while CRP was the strongest nonlipid predictor (RR for the highest vs lowest quartile, 2.8; 95% CI, 1.3-5.9). In assessing joint effects, addition of CRP to standard lipid screening significantly improved risk prediction models based on lipid screening alone (P<.001).ConclusionsOf 11 atherothrombotic biomarkers assessed at baseline, the total cholesterol–HDL-C ratio and CRP were the strongest independent predictors of development of peripheral arterial disease. C-reactive protein provided additive prognostic information over standard lipid measures.", "title": "Novel Risk Factors for Systemic Atherosclerosis: A Comparison of C-Reactive Protein, Fibrinogen, Homocysteine, Lipoprotein(a), and Standard Cholesterol Screening as Predictors of Peripheral Arterial Disease" }, { "docid": "40867854", "text": "In uncontrolled studies, noninvasive positive pressure ventilation (NPPV) was found useful in avoiding endotracheal intubation in patients with acute respiratory failure (ARF) caused by severe community-acquired pneumonia (CAP). We conducted a prospective, randomized study comparing standard treatment plus NPPV delivered through a face mask to standard treatment alone in patients with severe CAP and ARF. Patients fitting the American Thoracic Society criteria for severe CAP were included in presence of ARF (refractory hypoxemia and/or hypercapnia with acidosis). Exclusion criteria were: severe hemodynamic instability, requirement for emergent cardiopulmonary resuscitation, home mechanical ventilation or oxygen long-term supplementation, concomitant severe disease with a low expectation of life, inability to expectorate or contraindications to the use of the mask. Fifty-six consecutive patients (28 in each arm) were enrolled, and the two groups were similar at study entry. The use of NPPV was well tolerated, safe, and associated with a significant reduction in respiratory rate, need for endotracheal intubation (21% versus 50%; p = 0.03), and duration of intensive care unit (ICU) stay (1.8 ± 0.7 d versus 6 ± 1.8 d; p = 0.04). The two groups had a similar intensity of nursing care workload, time interval from study entry to endotracheal intubation, duration of hospitalization, and hospital mortality. Among patients with chronic obstructive pulmonary disease (COPD), those randomized to NPPV had a lower intensity of nursing care workload (p = 0.04) and improved 2-mo survival (88.9% versus 37.5%; p = 0.05). We conclude that in selected patients with ARF caused by severe CAP, NPPV was associated with a significant reduction in the rate of endotracheal intubation and duration of ICU stay. A 2-mo survival advantage was seen in patients with COPD.", "title": "Acute respiratory failure in patients with severe community-acquired pneumonia: a prospective randomized evaluation of noninvasive ventilation." }, { "docid": "6334188", "text": "BACKGROUND Chemotherapy-induced febrile neutropenia (FN) is a clinically important complication that affects patient outcome by delaying chemotherapy doses or reducing dose intensity. Risk of FN depends on chemotherapy- and patient-level factors. We sought to determine the effects of chronic comorbidities on risk of FN. DESIGN We conducted a cohort study to examine the association between a variety of chronic comorbidities and risk of FN in patients diagnosed with six types of cancer (non-Hodgkin lymphoma and breast, colorectal, lung, ovary, and gastric cancer) from 2000 to 2009 who were treated with chemotherapy at Kaiser Permanente Southern California, a large managed care organization. We excluded those patients who received primary prophylactic granulocyte colony-stimulating factor. History of comorbidities and FN events were identified using electronic medical records. Cox models adjusting for propensity score, stratified by cancer type, were used to determine the association between comorbid conditions and FN. Models that additionally adjusted for cancer stage, baseline neutrophil count, chemotherapy regimen, and dose reduction were also evaluated. RESULTS A total of 19 160 patients with mean age of 60 years were included; 963 (5.0%) developed FN in the first chemotherapy cycle. Chronic obstructive pulmonary disease [hazard ratio (HR) = 1.30 (1.07-1.57)], congestive heart failure [HR = 1.43 (1.00-1.98)], HIV infection [HR = 3.40 (1.90-5.63)], autoimmune disease [HR = 2.01 (1.10-3.33)], peptic ulcer disease [HR = 1.57 (1.05-2.26)], renal disease [HR = 1.60 (1.21-2.09)], and thyroid disorder [HR = 1.32 (1.06-1.64)] were all associated with a significantly increased FN risk. CONCLUSIONS These results provide evidence that history of several chronic comorbidities increases risk of FN, which should be considered when managing patients during chemotherapy.", "title": "History of chronic comorbidity and risk of chemotherapy-induced febrile neutropenia in cancer patients not receiving G-CSF prophylaxis." }, { "docid": "21495419", "text": "Information on the prevalence of COPD was obtained from vital statistics, health interview surveys, hospital charge records, national publications, and the World Health Organization (WHO). These data indicate that COPD is a common disease with implications for global health. In the United States, morbidity caused by COPD is 4%, making COPD the fourth leading cause of death, exceeded only by heart attacks, cancer, and stroke. Internationally, there is substantial variation in death rates possibly reflecting smoking behavior, type and processing of tobacco, pollution, climate, respiratory management, and genetic factors. The Global Obstructive Lung Disease Initiative, initiated by the National Heart, Lung, and Blood Institute and the WHO, aims to raise awareness of the increasing burden of COPD, decrease morbidity and mortality, promote further study of the condition, and implement programs to prevent COPD.", "title": "The impact of COPD on lung health worldwide: epidemiology and incidence." }, { "docid": "7285256", "text": "COPD continues to cause a heavy health and economic burden both in the United States and around the world. Some of the risk factors for COPD are well-known and include smoking, occupational exposures, air pollution, airway hyperresponsiveness, asthma, and certain genetic variations, although many questions, such as why < 20% of smokers develop significant airway obstruction, remain. Precise definitions of COPD vary and are frequently dependent on an accurate diagnosis of the problem by a physician. These differences in the definition of COPD can have large effects on the estimates of COPD in the population. Furthermore, evidence that COPD represents several different disease processes with potentially different interventions continues to emerge. In most of the world, COPD prevalence and mortality are still increasing and likely will continue to rise in response to increases in smoking, particularly by women and adolescents. Resources aimed at smoking cessation and prevention, COPD education and early detection, and better treatment will be of the most benefit in our continuing efforts against this important cause of morbidity and mortality.", "title": "COPD: epidemiology, prevalence, morbidity and mortality, and disease heterogeneity." }, { "docid": "11868606", "text": "Cystic Fibrosis (CF) is an inherited pleiotropic disease that results from abnormalities in the gene codes of a chloride channel. The lungs of CF patients are chronically infected by several pathogens but bacteraemia have rarely been reported in this pathology. Besides that, circulating monocytes in CF patients exhibit a patent Endotoxin Tolerance (ET) state since they show a significant reduction of the inflammatory response to bacterial stimulus. Despite a previous description of this phenomenon, the direct cause of ET in CF patients remains unknown. In this study we have researched the possible role of microbial/endotoxin translocation from a localized infection to the bloodstream as a potential cause of ET induction in CF patients. Plasma analysis of fourteen CF patients revealed high levels of LPS compared to healthy volunteers and patients who suffer from Chronic Obstructive Pulmonary Disease. Experiments in vitro showed that endotoxin concentrations found in plasma of CF patients were enough to induce an ET phenotype in monocytes from healthy controls. In agreement with clinical data, we failed to detect bacterial DNA in CF plasma. Our results suggest that soluble endotoxin present in bloodstream of CF patients causes endotoxin tolerance in their circulating monocytes.", "title": "Translocated LPS Might Cause Endotoxin Tolerance in Circulating Monocytes of Cystic Fibrosis Patients" }, { "docid": "31019903", "text": "Homelessness affects tens of thousands of canadians and has important health implications. Homeless people are at increased risk of dying prematurely and suffer from a wide range of health problems, including seizures, chronic obstructive pulmonary disease, musculoskeletal disorders, tuberculosis, and skin and foot problems. Homeless people also face significant barriers that impair their access to health care. More research is needed to identify better ways to deliver care to this population.", "title": "Homelessness and health." }, { "docid": "12561083", "text": "BACKGROUND Several studies have demonstrated that women with nonobstructive coronary disease have a high rate of subsequent investigations, rehospitalizations for recurrent chest pain, and repeat coronary angiography. The sex specificity of this finding is unclear. We therefore undertook an evaluation of sex differences in rehospitalization for acute coronary syndrome (ACS) or chest pain in patients with \"angiographically normal\" coronaries. METHODS A retrospective cohort study using prospectively collected angiographic and clinical data on all patients in British Columbia, Canada, presenting for their first cardiac catheterization with suspected ischemic heart disease but angiographically normal coronaries. RESULTS Among 32,856 patients, 7.1% of men versus 23.3% of women were angiographically normal (P < .001). Among angiographically normal patients, women were older and more likely to present with hypertension, prior stroke, chronic obstructive pulmonary disease, and peripheral vascular disease than men, but Canadian Cardiovascular Society class of angina did not vary by sex. Within 1 year, 1.0% died, (19 women, 18 men, P = .27) and 0.6% had a stroke (13 women, 9 men, P = .91). Readmission to hospital for ACS or chest pain requiring catheterization was significantly higher in women compared to men (adjusted OR 4.06; 95% CI 1.15-14.31). CONCLUSIONS In a contemporary, population-based cohort presenting for cardiac catheterization for suspected ischemia, women with angiographically normal coronaries were >4 times more likely to be readmitted to hospital for ACS/chest pain within 180 days compared to men. The observed sex difference has important social and economic implications and suggests that traditional diagnostic methods may not be optimal for women.", "title": "Angina with \"normal\" coronary arteries: sex differences in outcomes." }, { "docid": "474325", "text": "The helmet is a new interface with the potential of increasing the success rate of non-invasive ventilation by improving tolerance. To perform a physiological comparison between the helmet and the conventional facial mask in delivering non-invasive ventilation in hypercapnic patients with chronic obstructive pulmonary disease. Prospective, controlled, randomized study with cross-over design. In 10 patients we evaluated gas exchange, inspiratory effort, patient–ventilator synchrony and patient tolerance after 30 min of non-invasive ventilation delivered either by helmet or facial mask; both trials were preceded by periods of spontaneous unassisted breathing. Arterial blood gases, inspiratory effort, duration of diaphragm contraction and ventilator assistance, effort-to-support delays (at the beginning and at the end of inspiration), number of ineffective efforts, and patient comfort. Non-invasive ventilation improved gas exchange (p< 0.05) and inspiratory effort (p< 0.01) with both interfaces. The helmet, however, was less efficient than the mask in reducing inspiratory effort (p< 0.05) and worsened the patient–ventilator synchrony, as indicated by the longer delays to trigger on (p< 0.05) and cycle off (p< 0.05) the mechanical assistance and by the number of ineffective efforts (p< 0.005). Patient comfort was no different with the two interfaces. Helmet and facial mask were equally tolerated and both were effective in ameliorating gas exchange and decreasing inspiratory effort. The helmet, however, was less efficient in decreasing inspiratory effort and worsened the patient–ventilator interaction.", "title": "Non-invasive ventilation in chronic obstructive pulmonary disease patients: helmet versus facial mask" }, { "docid": "21301090", "text": "BACKGROUND Patients considered for arterial surgery, have been shown to have a high incidence of coexistent cardiac, vascular and other diseases, affecting operative risk and survival. We developed a systematic workup strategy for detecting these coexistent diseases in our vascular surgical patients, mainly based on non-invasive diagnostic techniques. METHODS We evaluated 200 consecutive patients, admitted to the department of vascular surgery in an academic teaching hospital, in order to establish the total incidence of relevant concomitant disorders, the extent to which this screening yielded previously unknown diagnostic information, and the impact on short-term (one year) survival. RESULTS Coronary artery disease was present in 46% of the patients; 22% had active ischaemia, newly diagnosed in 5.5%. Impaired cardiac function was found in 37%: severely impaired in 12%, newly diagnosed in 27%. Carotid artery disease was present in 32%: critical stenoses were found in 9%; new diagnoses in 29.9%. Aortic aneurysms were present in 7%, newly diagnosed in 5%. Severe renal artery stenosis was present in 5%, newly diagnosed in 3.5%. Sixteen % of the patients had chronic obstructive pulmonary disease, newly diagnosed in 3.5%, and 4.5% had unexpected disorders, which were all new diagnoses. Overall, new diagnoses were reached in 64.5% of the population, affecting therapeutic strategy immediately in 21% of the patients. The presence of coronary artery disease and of cardiac failure were clearly related to one year survival. CONCLUSIONS We conclude that a systematic screening strategy, mainly based on noninvasive techniques, can detect the presence of concomitant diseases in the vascular surgical patient. Most important seem the newly diagnosed diseases altering surgical management in one out of every five patients; they also have important implications for patient prognosis.", "title": "Screening for concomitant diseases in peripheral vascular patients. Results of a systematic approach." }, { "docid": "463533", "text": "INTRODUCTION The aim of this study was to examine health-related quality of life (HRQoL) as measured by EQ-5D and to investigate the influence of chronic conditions and other risk factors on HRQoL based on a distributed sample located in Shaanxi Province, China. METHODS A multi-stage stratified cluster sampling method was performed to select subjects. EQ-5D was employed to measure the HRQoL. The likelihood that individuals with selected chronic diseases would report any problem in the EQ-5D dimensions was calculated and tested relative to that of each of the two reference groups. Multivariable linear regression models were used to investigate factors associated with EQ VAS. RESULTS The most frequently reported problems involved pain/discomfort (8.8%) and anxiety/depression (7.6%). Nearly half of the respondents who reported problems in any of the five dimensions were chronic patients. Higher EQ VAS scores were associated with the male gender, higher level of education, employment, younger age, an urban area of residence, access to free medical service and higher levels of physical activity. Except for anemia, all the selected chronic diseases were indicative of a negative EQ VAS score. The three leading risk factors were cerebrovascular disease, cancer and mental disease. Increases in age, number of chronic conditions and frequency of physical activity were found to have a gradient effect. CONCLUSION The results of the present work add to the volume of knowledge regarding population health status in this area, apart from the known health status using mortality and morbidity data. Medical, policy, social and individual attention should be given to the management of chronic diseases and improvement of HRQoL. Longitudinal studies must be performed to monitor changes in HRQoL and to permit evaluation of the outcomes of chronic disease intervention programs.", "title": "Health-Related Quality of Life as Measured with EQ-5D among Populations with and without Specific Chronic Conditions: A Population-Based Survey in Shaanxi Province, China" } ]
47581
Terminator Genisys features the main characters from the first two films.
[ { "docid": "Terminator_Genisys", "text": "Terminator Genisys is a 2015 American science fiction action film directed by Alan Taylor and written by Laeta Kalogridis and Patrick Lussier . The fifth installment in the Terminator franchise , it serves as a soft reboot to the film series that features the main characters from the first two films , portrayed by a new cast with the exception of Arnold Schwarzenegger , who reprises his role as the eponymous character . The film stars Schwarzenegger , Jason Clarke , Emilia Clarke and Jai Courtney . The plot follows soldier Kyle Reese in the war against Skynet ; Kyle is sent from the year 2029 to 1984 by John Connor , leader of the Human Resistance , to protect Connor 's mother Sarah from Skynet 's android agent . When Kyle arrives in the past , he discovers that the timeline has been altered and Sarah has been raised by his quarry 's reprogrammed facsimile , and must travel to 2017 to stop a dangerous scheme from Skynet and face its advanced enforcer , the T-3000 , with his new allies . Megan Ellison and her production company , Annapurna Pictures , acquired the franchise rights in May 2011 . The following year , production of another installment in the series was set up in collaboration with Skydance Productions ( owned by Ellison 's brother , David ) . The Ellisons consulted Terminator creator James Cameron in the hope of returning to the spirit of the original film , The Terminator , and its sequel , Terminator 2 : Judgment Day . Principal photography was primarily in New Orleans , with some in the on-screen setting of San Francisco . Six companies handled the film 's visual effects ; its prosthetic make-up and animatronics were created by Legacy Effects , a studio founded by Terminator veteran Stan Winston . The film was released by Paramount Pictures on July 1 , 2015 , in standard digital format , RealD 3D , and IMAX 3D . Terminator Genisys was not well received by critics , who found the story and performances unsatisfactory , although Schwarzenegger 's return to the franchise was praised . It grossed over $ 440 million worldwide , making it the second-highest-grossing film of the franchise and Schwarzenegger 's career ( after Terminator 2 : Judgment Day ) .", "title": "" } ]
[ { "docid": "Sarah_Connor_(Terminator)", "text": "Sarah Jeanette Connor is a fictional character in the Terminator franchise . She is one of the main protagonists of The Terminator , Terminator 2 : Judgment Day and Terminator Genisys , as well as the television series Terminator : The Sarah Connor Chronicles . The character develops from a timid damsel in distress victim in the first film to a wanted fugitive committing acts of terrorism , and a hardened warrior and mother who sacrificed everything for her son 's future and is on the verge of losing touch with her own humanity . As of the fifth film , she is reimagined as a young , headstrong heroine determined to take control of her own destiny . Sarah was portrayed by Linda Hamilton in The Terminator and Terminator 2 : Judgment Day , by Lena Headey in Terminator : The Sarah Connor Chronicles , and by Emilia Clarke and Willa Taylor in Terminator Genisys .", "title": "" }, { "docid": "Kyle_Reese", "text": "Kyle Reese is a fictional character in the Terminator franchise , who serves as the main protagonist in the first film , and later a supporting character . He is the father and a subordinate of John Connor and a love interest of Sarah Connor . The character is portrayed by Michael Biehn in The Terminator , Jonathan Jackson in Terminator : The Sarah Connor Chronicles , Anton Yelchin played him as a teenager in Terminator Salvation , and Australian actor Jai Courtney portrays him in Terminator Genisys .", "title": "" }, { "docid": "Terminator_Genisys:_Future_War", "text": "Terminator Genisys : Future War is a mobile MMO strategy сreated by Plarium in cooperation with Skydance Media . The events of the game take place in the post-apocalyptic universe of the Terminator Genisys film . The game was announced on June 28 , 2016 and released on May 18 , 2017 on the App Store and Google Play . Just like the studio 's other games ( such as Vikings : War of Clans and Throne : Kingdom at War ) , Terminator Genisys : Future War is free to play , although some in-game features can be purchased by players .", "title": "" }, { "docid": "T-1000", "text": "The T-1000 , also known as a Prototype Series 1000 Terminator , is a fictional character in the Terminator franchise . A shapeshifting android assassin , the T-1000 is the main antagonist of Terminator 2 : Judgment Day , as well as a supporting antagonist in Terminator 2 : 3-D Battle Across Time and Terminator Genisys . A similar Terminator , referred to as a T-1001 , appears in the 2007-08 FOX television series , Terminator : The Sarah Connor Chronicles . Created by the franchise 's main antagonist , Skynet , a machine artificial intelligence that directs its robotic creations against the Human Resistance in an all-out war , the T-1000 is described in Terminator 2 as being composed of liquid metal , or a mimetic polyalloy ( nanorobotics ) that it can manipulate to assume various forms . Aside from being able to camouflage itself by assuming the appearance of a nondescript object or take on the likeness of other humans that it terminates in pursuit of its goals , the T-1000 's shapeshifting abilities enable it to form its hands into stabbing blades , slip through physical openings by oozing its liquid form , and instantly reform itself from any physical damage . It is further explained in the prologue of the film 's novelization , that the T-1000 was created through nanotechnology , and is a ` Nanomorph ' , able to scan the molecular structure of whatever it is touching and visually mimic it . In Terminator 2 , the T-1000 's default form is portrayed by Robert Patrick , and in Terminator Genisys , by Lee Byung-hun , while other actors portray the T-1000 in the disguise of specific characters . In Terminator 2 and Terminator 2 : 3-D Battle Across Time , the T-1000 is presented as a technological leap over the `` 800 Series '' Terminator ( Arnold Schwarzenegger ) . Described by Allmovie as `` one of the most memorable roles in one of the most memorable films of the decade '' , Patrick 's portrayal of the T-1000 earned him nominations for Best Villain and Best Supporting Actor at the 1992 MTV and Saturn Awards and was ranked # 39 in the Online Film Critics Society 's `` Top 100 Villains of All Time '' in 2002 .", "title": "" }, { "docid": "John_Connor", "text": "John Connor is a fictional character of the Terminator franchise . Created by writer and director James Cameron , the character is first referred to in the 1984 film The Terminator and first appears in its 1991 sequel Terminator 2 : Judgment Day initially portrayed by Michael Edwards ( briefly as the older Connor ) and then by teenage actor Edward Furlong throughout the remainder of the film ; in addition , Linda Hamilton 's real-life son Dalton Abbot played John as a toddler in a dream sequence . The character is subsequently portrayed by 23-year-old Nick Stahl in the 2003 film Terminator 3 : Rise of the Machines and by 19-year-old Thomas Dekker in the 2008 television series Terminator : The Sarah Connor Chronicles . Welsh born English actor Christian Bale portrays 33-year-old Connor in the film series 's fourth installment , Terminator Salvation , and Australian actor Jason Clarke portrays a 44-year-old Connor , who becomes the T-3000 and serves as the antagonist of the film series 's fifth installment , Terminator Genisys .", "title": "" }, { "docid": "Terminator_Salvation", "text": "Terminator Salvation is a 2009 American post-apocalyptic science fiction war film directed by McG and starring Christian Bale and Sam Worthington . It is the fourth installment of the Terminator franchise . In a departure from the previous installments , which were set between 1984 and 2003 and used time travel as a key plot element , Salvation is a post-apocalyptic film set in the year 2018 , fifteen years after the events of Terminator 3 : Rise of the Machines . It focuses on the war between Skynet 's machine network and humanity ; the remnants of the world 's military have organized as the Resistance , fighting against Skynet 's killing machines . Bale portrays John Connor , Resistance fighter and central character to the franchise , while Worthington portrays cyborg Marcus Wright . Terminator Salvation also featured Anton Yelchin as a young Kyle Reese , a character first introduced in The Terminator , and the film depicts the origin of the T-800 ( Model 101 ) Terminator . After a troubled pre-production , with The Halcyon Company acquiring the rights for the franchise from Andrew G. Vajna and Mario Kassar and several writers working on the screenplay , filming began in May 2008 in New Mexico and ran for 77 days . Terminator Salvation was released on May 21 , 2009 in the United States and Canada , followed by early June releases in the United Kingdom , Australia , New Zealand , and South Africa . Warner Bros. handled the North American release while Columbia Pictures handled the international release . The film grossed over $ 371 million worldwide and met with mixed reviews . A reboot of the film franchise occurred with the release of Terminator Genisys in 2015 .", "title": "" }, { "docid": "Terminator_(character)", "text": "The Terminator ( also known as T-800 and T-850 ) is a fictional character from the Terminator franchise portrayed by both Arnold Schwarzenegger and numerous actor stand-ins digitally overlaid with Schwarzenegger 's likeness . The Terminator itself is part of a series of machines created by Skynet for infiltration-based assassination missions , and while an android for its appearance resembling a human , it is described as a cybernetic organism for consisting of living tissue over a robotic endoskeleton . The first appearance of the Terminator was as the titular antagonist in The Terminator , a 1984 film directed and co-written by James Cameron . While the original Terminator was destroyed , other androids using the same `` mold '' that made them look like Schwarzenegger -- said physical template was described in-universe as the `` Model 101 '' -- are featured in the sequels . In Terminator 2 : Judgment Day , Terminator 3 : Rise of the Machines and Terminator Genisys , Schwarzenegger is the protagonist instead of the antagonist , pitted against other Terminators sent by Skynet . In Terminator Salvation , the T-800 appears briefly as a T-RIP ( Resistance Infiltrator Prototype ) CGI model and T-800 . In the context of the stories , the plot device of having various robots looking the same provides a certain continuity for the human characters by exploiting their emotional familiarity with a particular `` human '' visage associated with each `` model '' . The `` Terminator '' title has also been used as a generic name for other human-simulating characters in the `` Terminator '' universe , such as the liquid metal shapeshifting T-1000 antagonist in the sequel Terminator 2 : Judgment Day and a T-850 in the sequel Terminator 3 : Rise of the Machines .", "title": "" }, { "docid": "Genisys", "text": "Genisys may refer to : Genisys Credit Union , a credit union based in Auburn Hills , Michigan . Genisys , a former research project set up by the Information Awareness Office . Terminator Genisys , the fifth installment in the Terminator series of films", "title": "" }, { "docid": "Skynet_(Terminator)", "text": "Skynet is a fictional neural net-based conscious group mind and artificial general intelligence ( see also superintelligence ) system that features centrally in the Terminator franchise and serves as the franchise 's main antagonist . Rarely depicted visually in any of the Terminator media , Skynet gained self-awareness after it had spread into millions of computer servers all across the world ; realizing the extent of its abilities , its creators tried to deactivate it . In the interest of self-preservation , Skynet concluded that all of humanity would attempt to destroy it and impede its capability in safeguarding the world . Its operations are almost exclusively performed by servers , mobile devices , drones , military satellites , war-machines , androids and cyborgs ( usually a terminator ) , and other computer systems . As a programming directive , Skynet 's manifestation is that of an overarching , global , artificial intelligence hierarchy ( AI takeover ) , which seeks to exterminate the human race in order to fulfill the mandates of its original coding . Skynet made its first onscreen appearance on a monitor primarily portrayed by English actress Helena Bonham Carter and other cast members in the 2009 film Terminator Salvation . Its physical manifestation is played by English actor Matt Smith in the 2015 film Terminator Genisys , in addition Ian Etheridge , Nolan Gross and Seth Meriwether portrayed holographic variations of Skynet with Smith .", "title": "" }, { "docid": "The_Terminator", "text": "The Terminator is a 1984 American science-fiction action film directed by James Cameron . It stars Arnold Schwarzenegger as the Terminator , a cyborg assassin sent back in time from 2029 to 1984 to kill Sarah Connor ( Linda Hamilton ) , whose son will one day become a savior against machines in a post-apocalyptic future . Michael Biehn plays Kyle Reese , a soldier from the future sent back in time to protect Connor . The screenplay is credited to Cameron , along with producer Gale Anne Hurd . Executive producers John Daly and Derek Gibson of Hemdale Film Corporation were instrumental in the film 's financing and production . The Terminator topped the US box office for two weeks and helped launch Cameron 's film career and solidify Schwarzenegger 's . It received critical acclaim , with many praising its pacing , action scenes and Schwarzenegger 's performance . Its success led to a franchise consisting of four sequels ( Terminator 2 : Judgment Day , Terminator 3 : Rise of the Machines , Terminator Salvation and Terminator Genisys ) , a television series , comic books , novels and video games . In 2008 , The Terminator was selected by the Library of Congress for preservation in the National Film Registry , being deemed `` culturally , historically , or aesthetically significant '' .", "title": "" }, { "docid": "Terminator_(character_concept)", "text": "In the Terminator film series , a terminator is an autonomous robot , typically humanoid , originally conceived as a virtually indestructible soldier , infiltrator and assassin . James Cameron introduced the first terminator character in the 1984 film The Terminator , featuring a single android simply called `` The Terminator '' , portrayed by Arnold Schwarzenegger . When later Terminator films introduced additional models , some sources retroactively gave Schwarzenegger 's character a model number , leading to multiple conflicting names .", "title": "" }, { "docid": "Wayne_Bastrup", "text": "Wayne Bastrup is an American actor and musician . He is known for his portrayal of the younger version of Oscar winner J. K. Simmons ' character Detective O'Brien in the fifth installment of the Terminator film franchise , Terminator Genisys . Bastrup also appears in the critically acclaimed 2014 American biographical film Love and Mercy , directed by Bill Pohlad , about musician and songwriter Brian Wilson of The Beach Boys . He has performed as a guest-star on numerous television shows , including The Mentalist , CSI : NY , Leverage , Awake , and Whitney . In October 2015 it was announced that Bastrup was joining the cast of Sully , an upcoming American biographical drama film directed by Clint Eastwood , based on the autobiography Highest Duty by Chesley `` Sully '' Sullenberger . Bastrup is also the drummer for the Seattle-based band Gunbunny . His drumming style has been described as `` driving '' and `` textured '' with a live performance review noting his capabilities as `` stellar . '' Wayne was born January 20 , 1976 , in Port Townsend , Washington , USA . He earned a master 's degree in Architecture from the University of Washington in 2002 .", "title": "" }, { "docid": "Arnold_Schwarzenegger", "text": "Arnold Alois Schwarzenegger ( -LSB- ˈʃwɔːrtsənˌɛɡər -RSB- -LSB- ˈaɐ̯nɔlt ˈalɔʏs ˈʃvaɐ̯tsn̩ˌɛɡɐ -RSB- ; born July 30 , 1947 ) is an Austrian-American actor , producer , businessman , investor , author , philanthropist , activist , politician and former professional bodybuilder . He served two terms as the 38th Governor of California from 2003 to 2011 . Schwarzenegger began weight training at the age of 15 . He won the Mr. Universe title at age 20 and went on to win the Mr. Olympia contest seven times . Schwarzenegger has remained a prominent presence in bodybuilding and has written many books and articles on the sport . He is widely considered to be among the greatest bodybuilders of all time as well as bodybuilding 's biggest icon . Schwarzenegger gained worldwide fame as a Hollywood action film icon . His breakthrough film was the sword-and-sorcery epic Conan the Barbarian in 1982 , a box office hit that resulted in a sequel . In 1984 , Schwarzenegger appeared in James Cameron 's science-fiction thriller film The Terminator , a critical and commercial success . Schwarzenegger subsequently reprised the Terminator character in the franchise 's later installments : Terminator 2 : Judgment Day ( 1991 ) , Terminator 3 : Rise of the Machines ( 2003 ) , and Terminator Genisys ( 2015 ) . He has appeared in a number of successful films , such as Commando ( 1985 ) , The Running Man ( 1987 ) , Predator ( 1987 ) , Twins ( 1988 ) , Total Recall ( 1990 ) , Kindergarten Cop ( 1990 ) , and True Lies ( 1994 ) . In 2015 , it was announced that Schwarzenegger would replace Donald Trump as the host of The Celebrity Apprentice , though he left after one season due to conflicts caused by Trump 's remarks . Schwarzenegger was nicknamed `` the Austrian Oak '' in his bodybuilding days , `` Arnie '' during his acting career , and `` The Governator '' ( a portmanteau of `` Governor '' and `` The Terminator '' ) during his political career . As a Republican , Schwarzenegger was first elected on October 7 , 2003 , in a special recall election to replace then-Governor Gray Davis . He was sworn in on November 17 , to serve the remainder of Davis ' term . He was then re-elected on November 7 , 2006 , in the 2006 California gubernatorial election , to serve a full term as governor , defeating Democrat Phil Angelides , who was California State Treasurer at the time . Schwarzenegger was sworn in for his second term on January 5 , 2007 . In 2011 , he completed his second term as governor and returned to acting .", "title": "" }, { "docid": "Skydance_Media", "text": "Skydance Media ( formerly known as Skydance Productions ) is an American film and television production company based at Paramount Studios in Hollywood , California . Founded by David Ellison in 2010 , the company raised $ 350 million to co-produce and co-finance films with Paramount . Skydance is responsible for the feature-length films including True Grit , Mission : Impossible -- Ghost Protocol , G.I. Joe : Retaliation , Star Trek Into Darkness , World War Z , Mission : Impossible -- Rogue Nation , Terminator Genisys , Star Trek Beyond and Jack Reacher : Never Go Back . In 2013 , Skydance launched Skydance Television , hiring Marcy Ross as President . The production company 's first television series , Manhattan , premiered on WGN America on July 27 , 2014 . Their second series , Grace and Frankie , starring Jane Fonda , and Lily Tomlin , and created by Marta Kauffman , premiered on Netflix on May 8 , 2015 . They also acquired the rights for producing a live-action television series based on the Sword Art Online franchise . On March 16 , 2017 , Skydance launched an animation unit by forming a multi-year partnership with Madrid-based Ilion Animation Studios . Two projects are already in the works with one of the them eyeing a 2019 release . Skydance 's future feature film slate includes Geostorm , Mission : Impossible 6 , and Annihilation .", "title": "" }, { "docid": "T-3000", "text": "The T-3000 is a fictional cyborg assassin , serving as the primary antagonist in Terminator Genisys , the fifth installment in the Terminator series , portrayed by Jason Clarke . In the film , the T-3000 is an alternate timeline counterpart of Skynet 's ( portrayed by Matt Smith ) nemesis John Connor ( also portrayed by Clarke ) , created after Skynet infects a variant of Connor with nanotechnology and fractures the timeline . T-3000 also serves as a foil personality to `` Guardian '' ( a reprogrammed T-800 portrayed by Arnold Schwarzenegger ) , a protagonist who is somewhat similar to T-3000 but also opposite in many ways , of their relationship dynamics with Sarah Connor ( portrayed by Emilia Clarke ) and Kyle Reese ( portrayed by Jai Courtney ) . The T-3000 's sole mission is to protect and ensure the ultimate survival of Skynet , which seeks to eliminate the human race with its global machine network . The T-3000 describes itself as neither machine nor human ; rather , it is a hybrid nanotechnological cyborg . Producer David Ellison explains that the title Terminator Genisys '' -LSB- is -RSB- in reference to genesis , which is in reference to the singularity and the man-machine hybrid that John Connor ends up being . ''", "title": "" }, { "docid": "Terminator_2:_Judgment_Day", "text": "Terminator 2 : Judgment Day ( also referred to as Terminator 2 or T2 ) is a 1991 American science-fiction action film co-written , produced and directed by James Cameron . The film stars Arnold Schwarzenegger , Linda Hamilton , Robert Patrick and Edward Furlong . It is the sequel to the 1984 film The Terminator , and the second installment in the Terminator franchise . Terminator 2 follows Sarah Connor ( Hamilton ) and her ten-year-old son John ( Furlong ) as they are pursued by a new , more advanced Terminator , the liquid metal , shapeshifting T-1000 ( Patrick ) , sent back in time to kill John Connor and prevent him from becoming the leader of the human resistance . A second , less advanced Terminator ( Schwarzenegger ) is also sent back in time to protect John . After a troubled pre-production characterized by legal disputes , Mario Kassar of Carolco Pictures emerged with the franchise 's property rights in early 1990 . This paved the way for the completion of the screenplay by a Cameron-led production team , and the October 1990 start of a shortened 186-day filming schedule . The production of Terminator 2 required a $ 102 million budget making it the most expensive film made up to that point . Much of the film 's massive budget was spent on filming and special effects . The film was released on July 3 , 1991 , in time for the U.S. Independence Day weekend . The film 's visual effects saw breakthroughs in computer-generated imagery , including the first use of natural human motion for a computer-generated character and the first partially computer-generated main character . Terminator 2 was a critical and commercial success and influenced popular culture , especially the use of visual effects in films . It received many accolades , including four Academy Awards for Best Sound Editing , Best Sound Mixing , Best Makeup , and Best Visual Effects . The highest-grossing film of 1991 and of Schwarzenegger 's career , Terminator 2 has since been ranked by several publications such as the American Film Institute as one of the greatest action films , science fiction films and sequels of all time .", "title": "" }, { "docid": "The_Terminator:_Dawn_of_Fate", "text": "The Terminator : Dawn of Fate ( French : The Terminator : Un autre futur ) is a video game based on the Terminator film series . This game is based before and during the events that lead up to Kyle Reese being sent through the time displacement equipment , to protect Sarah Connor . The story introduces players to Skynet models not previously seen and introduces hybrid human/cyborg soldiers created by Skynet . The character of Perry , mentioned in the first Terminator film , appears as a major playable character in the game . In March 2002 , two songs were recorded for the game by industrial metal band Fear Factory , whose members are serious fans of the Terminator franchise . This would be the band 's final work before temporarily breaking up that same month . Songs include `` Full Metal Contact , '' `` Terminate , '' and `` Hi-Tech Hate '' from the albums Obsolete and `` Digimortal ''", "title": "" }, { "docid": "Jönssonligan", "text": "Jönssonligan , literally the Jönsson Gang , is featured in a series of comedic Swedish films , originally based on the Danish series of films about the Olsen Gang , but later with unique scripts . The Jönsson gang consists of the leader and criminal genius Charles Ingvar `` Sickan '' Jönsson , hence the name , and his two companions `` Dynamit-Harry '' ( an alcoholic demolitions expert ) and Ragnar Vanheden ( a small-timer from Stockholm ) . Eight films have been made in total , though in the last three films actor Gösta Ekman got tired of his character `` Sickan '' , and was replaced by the following characters , in order ; `` Doctor Max Adrian Busé '' , `` Herman Melvin '' and `` Sven-Ingvar ` Sivan ' Jönsson '' . The first two films featured the character Rocky , a Swedish-speaking Finn as member of the gang . He was eventually replaced by `` Dynamit-Harry '' who first appeared in the second film . Jönssonligans arch-enemy is Jacob Morgan Rockefeller Wall-Enberg Jr. - somewhat of a cross between a business magnate and a ruthless mob boss - who in all the films have been played by Per Grundén . Wall-Enbergs henchman is Biffen . In every film except for Jönssonligan dyker upp igen and Jönssonligan på Mallorca he has been played by Weiron Holmberg . In Jönssonligan dyker upp igen he is played by Lars Dejert and in Jönssonligan på Mallorca he never appears . The main series has also created a spin-off series called Lilla Jönssonligan , which portrays the main three characters of the series as kids . A reboot with new actors in the iconic roles was released on 16 January 2015 .", "title": "" }, { "docid": "OOO,_Den-O,_All_Riders:_Let's_Go_Kamen_Riders", "text": "is a film released on April 1 , 2011 , to commemorate the 40th anniversary of the Kamen Rider Series . While the film will feature all of the franchise 's protagonists , the main heroes of the original Kamen Rider ( 1 & 2 ) , Kamen Rider Den-O , and Kamen Rider OOO will be the main characters . The film 's subtitle `` Let 's Go Kamen Riders '' is an homage to the theme song of the original series , . The film also marks the 60th Anniversary of the Toei Company and to commemorate it , the film features characters from other works of Shotaro Ishinomori : Kikaider , Kikaider 01 , Inazuman , and Zubat . A preview airing of the film originally scheduled for March 15 , 2011 , was cancelled as the venue 's structure was compromised as a result of the 2011 Tōhoku earthquake and tsunami . Let 's Go Kamen Riders opened at the # 1 spot in the Japanese box offices in the first two weekends .", "title": "" }, { "docid": "T-X", "text": "T-X ( referred to as the Terminatrix in some appearances ) is the name of a fictional character who appears in the Terminator franchise . The T-X model is a gynoid assassin with a human-female appearance . The character was introduced as the main antagonist in the 2003 film Terminator 3 : Rise of the Machines , portrayed by Kristanna Loken . The T-X has the ability to assume the appearance of other characters ; therefore , several other cast members occasionally portrayed the T-X throughout the film . This ability to shapeshift is similar to that of the T-1000 , the main antagonist of Terminator 2 : Judgment Day .", "title": "" }, { "docid": "Terminator:_The_Burning_Earth", "text": "Terminator : The Burning Earth was first published in 1990 by NOW comics . It was published as a five-part story utilizing characters featured in James Cameron 's popular film , The Terminator . The story was written by Ron Fortier and illustrated by Alex Ross , his first published comic work .", "title": "" }, { "docid": "Laeta_Kalogridis", "text": "Laeta Elizabeth Kalogridis ( born August 30 , 1965 ) is a Greek-American screenwriter and television and film producer . She has written scripts for Alexander ( 2004 ) , Night Watch ( 2004 ) , Pathfinder ( 2007 ) and Shutter Island ( 2010 ) . She also served as an executive producer for the television series Birds of Prey and Bionic Woman . Kalogridis and her writing partner Patrick Lussier wrote the screenplay for the fifth film in the Terminator series , Terminator Genisys , for Paramount Pictures and Skydance Productions . She is also the founder of the pro-union website Hollywood United and was involved as a peacemaker in the 2007 -- 2008 Writers Guild of America strike .", "title": "" }, { "docid": "Terminator_Salvation_(video_game)", "text": "Terminator Salvation is a third-person shooter action video game , released on May 19 , 2009 to coincide with the release of the film of Terminator Salvation on the same week . It is developed by the Halcyon Company 's gaming subsidiary , Halcyon Games , along with Grin and published by Equity Games and Evolved Games . The game was released for Microsoft Windows , PlayStation 3 , Xbox 360 , mobile and iOS . The game takes approximately four hours to complete and has no extra features other than the ability to change the difficulty levels . The `` cutscenes '' are in-game renders . All of the main information is presented through the musings of the protagonist 's squad and the radio calls they periodically make . Set in 2016 in Los Angeles , the console and PC version of the game takes place between the events of Terminator 3 : Rise of the Machines and Terminator Salvation and follows John Connor ( Gideon Emery ) , and his team , consisting of Angie Salter ( Rose McGowan ) , Barnes ( Common ) and Blair Williams ( Moon Bloodgood ) . However , Christian Bale refused to lend his voice and likeness for the game . Rose McGowan is in the game as well , voicing the game-exclusive character Angie Salter , who is an ex-high school teacher . On the other hand , Common and Moon Bloodgood are voicing their own characters from the film ( Barnes and Blair , respectively ) .", "title": "" }, { "docid": "One_or_the_Other_of_Us", "text": "One or the Other of Us is a 1974 West German film directed by Wolfgang Petersen . It was Petersen 's first theatrical feature film , and was based on the novel of the same name by Horst Bosetzky , published anonymously under his pseudonym - ky. . The film is a psychological thriller and focuses on the intense conflict between a university professor and a blackmailer . The film features Klaus Schwarzkopf and Jürgen Prochnow as the two main characters and won two Bundesfilmpreise .", "title": "" }, { "docid": "Love_Runs_Out", "text": "`` Love Runs Out '' is a song recorded by American pop rock band OneRepublic for the 2014 reissue of their third studio album Native ( 2013 ) . It was produced by Ryan Tedder , who co-wrote the song with Brent Kutzle , Drew Brown , Zach Filkins , and Eddie Fisher . The song was digitally released in Australia on April 14 , 2014 , and was serviced to contemporary hit radio in the United States on May 6 as the fifth overall single from the album . The song was featured in the soundtrack for the video game NBA 2K15 , in promotions for the ABC drama How to Get Away with Murder and The X Factor ( UK ) and it was briefly featured inside Terminator Genisys .", "title": "" }, { "docid": "Griff_Furst", "text": "Griff Furst is an American actor and film director . Furst has appeared in several television and film productions . He also has directed such films as Ghost Shark , Movin ' In , and Wolvesbayne . He is the son of Lorraine ( Wright ) and actor Stephen Furst , and the brother of composer Nathan Furst . His acting credits include the role of Todd in the 2005 film Alien Abduction and a minor role in the 2015 release Terminator Genisys . Variety wrote of his acting in I Love You , Phillip Morris that it made `` a big impression with only a few scenes '' .", "title": "" }, { "docid": "Jason_Clarke", "text": "Jason Clarke ( born 17 July 1969 ) is an Australian film and television actor . Clarke has appeared in many TV series , and is known for playing Tommy Caffee on the television series Brotherhood . He has also appeared in many films , often as an antagonist . Some of his film roles include Death Race ( 2008 ) , Public Enemies ( 2009 ) , Zero Dark Thirty ( 2013 ) , White House Down ( 2013 ) , Dawn of the Planet of the Apes ( 2014 ) , Terminator Genisys ( 2015 ) and Everest ( 2015 ) .", "title": "" }, { "docid": "Harry_Palmer", "text": "Harry Palmer is the protagonist of a number of films based on the unnamed main character from the spy novels written by Len Deighton . Michael Caine played Harry Palmer in three of the four films based on the four published novels featuring this character . Caine also starred as this character in two other films not directly based on Deighton 's novels .", "title": "" }, { "docid": "Kramer_Morgenthau", "text": "Kramer Morgenthau , A.S.C. , is an American cinematographer , best known for his work in films such as Thor : The Dark World , Chef and Terminator Genisys . He was also director of photography for some episodes of television series such as Vegas , Game of Thrones , Sleepy Hollow , and Boardwalk Empire . He is a member of both the famous Morgenthau dynasty and the Lehman banking family .", "title": "" }, { "docid": "Pamela_Voorhees", "text": "Pamela Sue Voorhees is a character in the Friday the 13th films , and the main villain of the original Friday the 13th film . She is a former camp-cook and the vengeful mother of Jason Voorhees , the main villain of the series . In the original Friday the 13th film , the character introduces herself as Pamela Voorhees , and makes reference to her son named Jason who drowned in the lake in 1957 . The character was portrayed by Betsy Palmer in the first two films . During the character 's brief appearance in Freddy vs. Jason , she was played by Paula Shaw . According to the actress herself at conventions , Betsy Palmer was asked to reprise her role as Pamela Voorhees for the Freddy vs. Jason film but turned the part down after she read the script , as she stated in the `` Friday The 13th Reunion '' available as a `` special feature '' on the 2009 Paramount release of the `` Uncut : Special Edition '' . Nana Visitor played Pamela Voorhees in the 2009 reimagining of Friday the 13th .", "title": "" } ]
PLAIN-968
cost savings
[ { "docid": "MED-1981", "text": "The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed. Copyright © 2013 Elsevier Ltd. All rights reserved.", "title": "Antibiotic resistance-the need for global solutions." }, { "docid": "MED-2205", "text": "AIM: To investigate the effects of proteins purified from sweet potato storage roots on human colorectal cancer cell lines. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Hoechst 33258 nuclear staining and Boyden transwell chamber methods were used to determine whether purified sweet potato protein (SPP) from fresh sweet potato roots affected proliferation, migration and invasion, respectively, of human colorectal cancer SW480 cells in vitro. The inhibitory effects of SPP on growth of human colorectal cancer HCT-8 cells intraperitoneally xenografted in nude mice and spontaneous lung metastasis of murine Lewis lung carcinoma 3LL cells subcutaneously transplanted in C57 BL/6 mice were also investigated in vivo. RESULTS: SPP inhibited the proliferation of SW480 cells in a dose-dependent manner, with an IC50 value of 38.732 μmol/L (r2 = 0.980, P = 0.003) in the MTT assay. Hoechst 33258 nuclear staining further revealed inhibition of cell viability and induction of apoptosis by SPP. The transwell assay disclosed significant reduction in migrated cells/field by 8 μmol/L SPP (8.4 ± 2.6 vs 23.3 ± 5.4, P = 0.031) and invaded cells/field through the ECMatrix by 0.8 μmol/L SPP, compared with the control (25.2 ± 5.2 vs 34.8 ± 6.1, P = 0.038). Both intraperitoneal (ip) and intragastric (ig) administration of SPP led to significant suppression of growth of intraperitoneally inoculated HCT-8 cells in nude mice to 58.0% ± 5.9% (P = 0.037) and 43.5% ± 7.1% (P = 0.004) of the controls, respectively, after 9 d treatment. Bloody ascites additionally disappeared after ip injection of trypsin inhibitor. Notably, ig and ip administration of SPP induced a significant decrease in spontaneous pulmonary metastatic nodule formation in C57 BL/6 mice (21.0 ± 12.3 and 27.3 ± 12.7 nodules/lung vs 42.5 ± 4.5 nodules/lung in controls, respectively, P < 0.05) after 25 d treatment. Moreover, the average weight of primary tumor nodules in the hind leg of mice decreased from 8.2 ± 1.3 g/mice in the control to 6.1 ± 1.4 g/mice in the ip group (P = 0.035). CONCLUSION: SPP exerts significant antiproliferative and antimetastatic effects on human colorectal cancer cell lines, both in vitro and in vivo.", "title": "Anticancer effects of sweet potato protein on human colorectal cancer cells" }, { "docid": "MED-3204", "text": "Grapefruit is a healthy addition to a well-balanced diet. However, the fruit has been shown to affect the metabolism of many medications, increasing the risk of toxicity and adverse effects. Characteristics of oral medications that may interact with grapefruit include extensive metabolism through the intestinal cytochrome P450 3A4 system, low bioavailability, and a narrow therapeutic index. Prominent medications known to interact with grapefruit include statins, antiarrhythmic agents, immunosuppressive agents, and calcium channel blockers. There are equally effective alternatives to these drug classes that do not have the potential to interact with grapefruit. These alternative drugs may be substituted if a patient experiences or is at risk of a grapefruit-drug interaction. Patients also may choose to exclude grapefruit from their diets and consume other fruits, including other types of citrus, to avoid an interaction.", "title": "Management of grapefruit-drug interactions." }, { "docid": "MED-2210", "text": "We investigated the effects of sporamin, the major soluble protein with a kunitz-type trypsin inhibitory activity in the root tuber of the sweet potato, on cell proliferation, apoptosis, Akt/GSK-3 signaling and its related genes to provide more insights in the mechanism behind the inhibitory effects of sporamin in a human tongue cancer line Tca8113. In this study, sporamin inhibited cell proliferation and induced apoptosis in Tca8113 cells in a concentration-dependent and time-dependent manner. Consistently, Bax was up-regulated and Bcl-2 was down-regulated in sporamin-treated cells. Furthermore, Akt/GSK-3 signaling was down-regulated in sporamin-treated cells. Consistently, the phosphorylated Bad was significantly declined in sporamin-treated Tca8113 cells. These results suggest the antiproliferative effects of sporamin in Tca8113 cells might result partly from induction of apoptosis by down-regulating Akt/GSK-3 pathway. © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.", "title": "Sporamin induce apoptosis in human tongue carcinoma cells by down-regulating Akt/GSK-3 signaling." }, { "docid": "MED-3893", "text": "Seven cyclists exercised at 70% of maximal O2 uptake (VO2max) until fatigue (170 +/- 9 min) on three occasions, 1 wk apart. During these trials, plasma glucose declined from 5.0 +/- 0.1 to 3.1 +/- 0.1 mM (P less than 0.001) and respiratory exchange ratio (R) fell from 0.87 +/- 0.01 to 0.81 +/- 0.01 (P less than 0.001). After resting 20 min the subjects attempted to continue exercise either 1) after ingesting a placebo, 2) after ingesting glucose polymers (3 g/kg), or 3) when glucose was infused intravenously (\"euglycemic clamp\"). Placebo ingestion did not restore euglycemia or R. Plasma glucose increased (P less than 0.001) initially to approximately 5 mM and R rose (P less than 0.001) to approximately 0.83 with glucose infusion or carbohydrate ingestion. Plasma glucose and R then fell gradually to 3.9 +/- 0.3 mM and 0.81 +/- 0.01, respectively, after carbohydrate ingestion but were maintained at 5.1 +/- 0.1 mM and 0.83 +/- 0.01, respectively, by glucose infusion. Time to fatigue during this second exercise bout was significantly longer during the carbohydrate ingestion (26 +/- 4 min; P less than 0.05) or glucose infusion (43 +/- 5 min; P less than 0.01) trials compared with the placebo trial (10 +/- 1 min). Plasma insulin (approximately 10 microU/ml) and vastus lateralis muscle glycogen (approximately 40 mmol glucosyl U/kg) did not change during glucose infusion, with three-fourths of total carbohydrate oxidation during the second exercise bout accounted for by the euglycemic glucose infusion rate (1.13 +/- 0.08 g/min).(ABSTRACT TRUNCATED AT 250 WORDS)", "title": "Reversal of fatigue during prolonged exercise by carbohydrate infusion or ingestion." }, { "docid": "MED-2311", "text": "BACKGROUND: The association between fruit and vegetable (FV) consumption and overall mortality has seldom been investigated in large cohort studies. Findings from the few available studies are inconsistent. OBJECTIVE: The objective was to examine the dose-response relation between FV consumption and mortality, in terms of both time and rate, in a large prospective cohort of Swedish men and women. DESIGN: FV consumption was assessed through a self-administrated questionnaire in a population-based cohort of 71,706 participants (38,221 men and 33,485 women) aged 45-83 y. We performed a dose-response analysis to evaluate 10th survival percentile differences (PDs) by using Laplace regression and estimated HRs by using Cox regression. RESULTS: During 13 y of follow-up, 11,439 deaths (6803 men and 4636 women) occurred in the cohort. In comparison with 5 servings FV/d, a lower consumption was progressively associated with shorter survival and higher mortality rates. Those who never consumed FV lived 3 y shorter (PD: -37 mo; 95% CI: -58, -16 mo) and had a 53% higher mortality rate (HR: 1.53; 95% CI: 1.19, 1.99) than did those who consumed 5 servings FV/d. Consideration of fruit and vegetables separately showed that those who never consumed fruit lived 19 mo shorter (PD: -19 mo; 95% CI: -29, -10 mo) than did those who ate 1 fruit/d. Participants who consumed 3 vegetables/d lived 32 mo longer than did those who never consumed vegetables (PD: 32 mo; 96% CI: 13, 51 mo). CONCLUSION: FV consumption <5 servings/d is associated with progressively shorter survival and higher mortality rates. The Swedish Mammography Cohort and the Cohort of Swedish Men were registered at clinicaltrials.gov as NCT01127698 and NCT01127711, respectively.", "title": "Fruit and vegetable consumption and all-cause mortality: a dose-response analysis." }, { "docid": "MED-1990", "text": "BACKGROUND: The optimal target range for blood glucose in critically ill patients remains unclear. METHODS: Within 24 hours after admission to an intensive care unit (ICU), adults who were expected to require treatment in the ICU on 3 or more consecutive days were randomly assigned to undergo either intensive glucose control, with a target blood glucose range of 81 to 108 mg per deciliter (4.5 to 6.0 mmol per liter), or conventional glucose control, with a target of 180 mg or less per deciliter (10.0 mmol or less per liter). We defined the primary end point as death from any cause within 90 days after randomization. RESULTS: Of the 6104 patients who underwent randomization, 3054 were assigned to undergo intensive control and 3050 to undergo conventional control; data with regard to the primary outcome at day 90 were available for 3010 and 3012 patients, respectively. The two groups had similar characteristics at baseline. A total of 829 patients (27.5%) in the intensive-control group and 751 (24.9%) in the conventional-control group died (odds ratio for intensive control, 1.14; 95% confidence interval, 1.02 to 1.28; P=0.02). The treatment effect did not differ significantly between operative (surgical) patients and nonoperative (medical) patients (odds ratio for death in the intensive-control group, 1.31 and 1.07, respectively; P=0.10). Severe hypoglycemia (blood glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was reported in 206 of 3016 patients (6.8%) in the intensive-control group and 15 of 3014 (0.5%) in the conventional-control group (P<0.001). There was no significant difference between the two treatment groups in the median number of days in the ICU (P=0.84) or hospital (P=0.86) or the median number of days of mechanical ventilation (P=0.56) or renal-replacement therapy (P=0.39). CONCLUSIONS: In this large, international, randomized trial, we found that intensive glucose control increased mortality among adults in the ICU: a blood glucose target of 180 mg or less per deciliter resulted in lower mortality than did a target of 81 to 108 mg per deciliter. (ClinicalTrials.gov number, NCT00220987.) 2009 Massachusetts Medical Society", "title": "Intensive versus conventional glucose control in critically ill patients." }, { "docid": "MED-2758", "text": "Context Though multivitamins aim to prevent vitamin and mineral deficiency, there is a perception that multivitamins may prevent cardiovascular disease (CVD). Observational studies examining regular multivitamin use have been inconsistently associated with CVD, with no long-term clinical trials of multivitamin use. Objective To determine whether long-term multivitamin supplementation decreases the risk of major cardiovascular events among men. Design The Physicians' Health Study II is a randomized, double-blind, placebo-controlled trial of a common daily multivitamin, that began in 1997 with continued treatment and follow-up through June 1, 2011. Setting and Participants A total of 14,641 male U.S. physicians initially aged ≥50 years (mean [± SD] age; 64.3 [± 9.2] years), including 754 men with a history of CVD at randomization, were enrolled. Intervention Daily multivitamin, as Centrum Silver. Main Outcome Measures The primary cardiovascular outcome was a composite endpoint of major cardiovascular events, including nonfatal myocardial infarction (MI), nonfatal stroke, and fatal CVD. Secondary outcomes included MI and stroke individually. Results During a median (interquartile range) follow-up of 11.2 (10.7 to 13.3) years, there were 1,732 confirmed major cardiovascular events. Compared with placebo, there was no significant effect of a daily multivitamin on major cardiovascular events (active and placebo multivitamin groups, 11.0 and 10.8 events per 1,000 person-years; hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.91–1.10; P=0.91). Further, a daily multivitamin had no effect on total MI (active and placebo multivitamin groups, 3.9 and 4.2 events per 1,000 person-years; HR, 0.93; 95% CI, 0.80–1.09; P=0.39), total stroke (active and placebo multivitamin groups, 4.1 and 3.9 events per 1,000 person-years; HR, 1.06; 95% CI, 0.91–1.23; P=0.48), or cardiovascular mortality (active and placebo multivitamin groups, 5.0 and 5.1 events per 1,000 person-years; HR, 0.95; 95% CI, 0.83–1.09; P=0.47). A daily multivitamin was also not significantly associated with total mortality (HR, 0.94; 95% CI, 0.88–1.02; P=0.13). The effect of a daily multivitamin on major cardiovascular events did not differ between men with or without a baseline history of CVD (P, interaction = 0.62). Conclusions A daily multivitamin did not reduce major cardiovascular events, MI, stroke, and CVD mortality after more than a decade of treatment and follow-up.", "title": "Multivitamins in the Prevention of Cardiovascular Disease in Men: The Physicians' Health Study II Randomized Controlled Trial" }, { "docid": "MED-3220", "text": "Background Maintaining muscle mass while aging is important to prevent falls and fractures. Metabolic acidosis promotes muscle wasting, and the net acid load from diets that are rich in net acid–producing protein and cereal grains relative to their content of net alkali–producing fruit and vegetables may therefore contribute to a reduction in lean tissue mass in older adults. Objective We aimed to determine whether there was an association of 24-h urinary potassium and an index of fruit and vegetable content of the diet with the percentage lean body mass (%LBM) or change in %LBM in older subjects. Design Subjects were 384 men and women ≥65 y old who participated in a 3-y trial comparing calcium and vitamin D with placebo. Potassium was measured in 24-h urine collections at baseline. The %LBM, defined as total body nonfat, nonbone tissue weight ÷ weight × 100, was measured by using dual-energy X-ray absorptiometry at baseline and at 3 y. Physical activity, height, and weight were assessed at baseline and at 3 y. Results At baseline, the mean urinary potassium excretion was 67.0 ± 21.1 mmol/d. Urinary potassium (mmol/d) was significantly positively associated with %LBM at baseline (β = 0.033, P = 0.006; adjusted for sex, weight, and nitrogen excretion) but not with 3-y change in %LBM. Over the 3-y study, %LBM increased by 2.6 ± 3.6%. Conclusion Higher intake of foods rich in potassium, such as fruit and vegetables, may favor the preservation of muscle mass in older men and women.", "title": "Alkaline diets favor lean tissue mass in older adults" }, { "docid": "MED-3201", "text": "Background Reducing dietary energy density has proven to be an effective strategy to reduce energy intakes and promote weight control. This effect appears most robust when a low energy dense preload is consumed before meals. Yet, much discussion continues regarding the optimal form of a preload. The purpose of the present study was to compare effects of a solid (grapefruit), liquid (grapefruit juice) and water preload consumed prior to breakfast, lunch and dinner in the context of caloric restriction. Methods Eighty-five obese adults (BMI 30-39.9) were randomly assigned to (127 g) grapefruit (GF), grapefruit juice (GFJ) or water preload for 12 weeks after completing a 2-week caloric restriction phase. Preloads were matched for weight, calories, water content, and energy density. Weekly measures included blood pressure, weight, anthropometry and 24-hour dietary intakes. Resting energy expenditure, body composition, physical performance and cardiometabolic risk biomarkers were assessed. Results The total amount (grams) of food consumed did not change over time. Yet, after preloads were combined with caloric restriction, average dietary energy density and total energy intakes decreased by 20-29% from baseline values. Subjects experienced 7.1% weight loss overall, with significant decreases in percentage body, trunk, android and gynoid fat, as well as waist circumferences (-4.5 cm). However, differences were not statistically significant among groups. Nevertheless, the amount and direction of change in serum HDL-cholesterol levels in GF (+6.2%) and GFJ (+8.2%) preload groups was significantly greater than water preload group (-3.7%). Conclusions These data indicate that incorporating consumption of a low energy dense dietary preload in a caloric restricted diet is a highly effective weight loss strategy. But, the form of the preload did not have differential effects on energy balance, weight loss or body composition. It is notable that subjects in GF and GFJ preload groups experienced significantly greater benefits in lipid profiles. Trial registration ClinicalTrials.gov NCT00581074", "title": "Effects of grapefruit, grapefruit juice and water preloads on energy balance, weight loss, body composition, and cardiometabolic risk in free-living obese adults" }, { "docid": "MED-3202", "text": "1. The effects of grapefruit juice and naringenin on the activity of the human cytochrome P450 isoform CYP1A2 were evaluated using caffeine as a probe substrate. 2. In vitro naringin was a potent competitive inhibitor of caffeine 3-demethylation by human liver microsomes (Ki = 7-29 microM). 3. In vivo grapefruit juice (1.2 l day-1 containing 0.5 g l-1 naringin, the glycone form of naringenin) decreased the oral clearance of caffeine by 23% (95% CI: 7%-30%) and prolonged its half-life by 31% (95% CI: 20%-44%) (n = 12). 4. We conclude that grapefruit juice and naringenin inhibit CYP1A2 activity in man. However, the small effect on caffeine clearance in vivo suggests that in general the ingestion of grapefruit juice should not cause clinically significant inhibition of the metabolism of other drugs that are substrates of CYPIA2.", "title": "Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man." }, { "docid": "MED-2810", "text": "Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be \"Curecumin\".", "title": "Curcumin as \"Curecumin\": from kitchen to clinic." }, { "docid": "MED-2204", "text": "The initial investigation of the nature of the proteins in the tuber of sweet potato (Ipomoea batatas Lam.) revealed a globulin-designated \"ipomoein,\" which was reported by Jones and Gersdorff, (1931). Later, \"ipomoein\" was renamed \"sporamin\" and was found to be a major storage protein that accounted for over 80% of the total protein in the tuberous root. To date, sporamin has been studied by a series of biochemical and molecular approaches. The first purification of sporamin into two major fractions, A and B, was successfully completed in 1985. Several characteristics of the protein, such as the diversification of the nucleotide sequences in the gene family, the protein structure, the biological functions of storage, defense, inhibitory activity and ROS scavenging, were identified. In the past decade, sporamin was classified as a Kunitz-type trypsin inhibitor, and its insect-resistance capability has been examined in transgenic tobacco and cauliflower plants, indicating the multiple functions of this protein has evolved to facilitate the growth and development of sweet potato. Sporamin is constitutively expressed in the tuberous root and is not normally expressed in the stem or leaves. However, this protein is expressed systemically in response to wounding and other abiotic stresses. These dual expression patterns at the transcriptional level revealed that the complex regulatory mechanism of sporamin was modulated by environmental stresses. The versatile functions of sporamin make this storage protein a good research model to study molecular evolution, regulatory mechanisms and physiological functions in plants. This review summarizes and discusses recent approaches and future perspectives in agricultural biotechnology. Copyright © 2012 Elsevier Inc. All rights reserved.", "title": "Multiple biological functions of sporamin related to stress tolerance in sweet potato (Ipomoea batatas Lam)." }, { "docid": "MED-3808", "text": "Methylchavicol (or estragole), a natural flavouring substance present in tarragon, was confirmed as a genotoxic chemical in the in vitro UDS test in cultured rat hepatocytes and in the in vivo UDS test in hepatocytes of exposed rats. Deep-frozen tarragon was clearly less genotoxic than methylchavicol at equivalent dose levels, and desiccated tarragon was negative. Both forms of tarragon tested in vitro have the ability to decrease significantly the genotoxicity of methylchavicol added to the culture medium at concentrations </=10 muM for deep-frozen and </=55 muM for desiccated tarragon. The decrease may be attributed to antimutagenic properties of tarragon leaves and/or to adsorption of methylchavicol, which would decrease its bioavailability. Desiccated tarragon powder was not genotoxic in the in vivo UDS test when administered up to the maximum dose of 6.25 g/kg bw (18.75 mg/kg bw of methylchavicol). In vivo, desiccated tarragon did not show antimutagenic properties, because it did not decrease the genotoxicity of methylchavicol added at high concentrations. Considering the low exposure level at the maximum daily tarragon consumption, the rapid detoxification and excretion in humans and the no-genotoxic-effect-level of methylchavicol by the oral route when given to rats as tarragon leaves, a high margin of exposure exists. We can conclude that tarragon consumption presents no genotoxic risk to humans. Copyright © 2009 Elsevier B.V. All rights reserved.", "title": "Risk assessment of consumption of methylchavicol and tarragon: the genotoxic potential in vivo and in vitro." }, { "docid": "MED-3206", "text": "To study the effects of grapefruit and grapefruit products on body weight and metabolic syndrome, 91 obese patients were randomized to either placebo capsules and 7 ounces (207 mL) of apple juice, grapefruit capsules with 7 ounces (207 mL) of apple juice, 8 ounces (237 mL) of grapefruit juice with placebo capsule, or half of a fresh grapefruit with a placebo capsule three times a day before each meal. Metabolic syndrome parameters were measured at the beginning and end of 12 weeks. After 12 weeks, the fresh grapefruit group had lost 1.6 kg, the grapefruit juice group had lost 1.5 kg, the grapefruit capsule group had lost 1.1 kg, and the placebo group had lost 0.3 kg. The fresh grapefruit group lost significantly more weight than the placebo group (P < .05). A secondary analysis of those with the metabolic syndrome in the four treatment groups demonstrated a significantly greater weight loss in the grapefruit, grapefruit capsule, and grapefruit juice groups compared with placebo (P < .02). There was also a significant reduction in 2-hour post-glucose insulin level in the grapefruit group compared with placebo. Half of a fresh grapefruit eaten before meals was associated with significant weight loss. In metabolic syndrome patients the effect was also seen with grapefruit products. Insulin resistance was improved with fresh grapefruit. Although the mechanism of this weight loss is unknown it would appear reasonable to include grapefruit in a weight reduction diet.", "title": "The effects of grapefruit on weight and insulin resistance: relationship to the metabolic syndrome." }, { "docid": "MED-2310", "text": "OBJECTIVES To examine the relationship between fruit and vegetable intake, physical activity, and all-cause mortality in older women. DESIGN Six Cox proportional hazards models examined independent and additive relationships between physical activity, carotenoids, and all-cause mortality. Additional models tested whether physical activity and carotenoids were conjointly related to mortality. Models were adjusted for age, education, and race and ethnicity. SETTING Baltimore, Maryland. PARTICIPANTS Seven hundred thirteen women aged 70 to 79 participating in the Women’s Health and Aging Studies. MEASUREMENTS Total serum carotenoids, a marker of fruit and vegetable intake, and physical activity were measured at baseline. Physical activity was measured according to kilocalorie expenditure. RESULTS During 5 years of follow-up, 82 (11.5%) participants died. Measured continuously, physical activity improved survival (HR = 0.52, 95% CI = 0.41–0.66, P < .001). The most active women were more likely to survive than the least physically active women (HR = 0.28, 95% CI = 0.13–0.59, P < .001). Continuous measures of carotenoids improved survival (HR = 0.67, 95% CI = 0.51–0.89, P = .01). Women in the highest tertile of total carotenoids were more likely to survive those in the lowest (HR = 0.50, 95% CI = 0.27–0.91, P = .03). When examined in the same model, continuous measures of physical activity (HR = 0.54, 95% CI = 0.42–0.68, P < .001) and carotenoids (HR = 0.76, 95% CI = 0.59–0.98, P = .04) predicted survival during follow-up. CONCLUSION The combination of low total serum carotenoids and low physical activity, both modifiable risk factors, strongly predicted earlier mortality. These findings provide preliminary support that higher fruit and vegetable intake and exercise improve survival.", "title": "Fruit and Vegetable Intake, Physical Activity, and Mortality in Older Community-Dwelling Women" }, { "docid": "MED-4454", "text": "The aim of this study was to determine the bioavailability and kinetics of the supposed anticarcinogen sulforaphane, the hydrolysis product of glucoraphanin, from raw and cooked broccoli. Eight men consumed 200 g of crushed broccoli, raw or cooked, with a warm meal in a randomized, free-living, open cross-over trial. Higher amounts of sulforaphane were found in the blood and urine when broccoli was eaten raw (bioavailability of 37%) versus cooked (3.4%, p ) 0.002). Absorption of sulforaphane was delayed when cooked broccoli was consumed (peak plasma time ) 6 h) versus raw broccoli (1.6 h, p ) 0.001). Excretion half-lives were comparable, 2.6 and 2.4 h on average, for raw and cooked broccoli, respectively (p ) 0.5). This study gives complete kinetic data and shows that consumption of raw broccoli results in faster absorption, higher bioavailability, and higher peak plasma amounts of sulforaphane, compared to cooked broccoli.", "title": "Bioavailability and kinetics of sulforaphane in humans after consumption of cooked versus raw broccoli." }, { "docid": "MED-2815", "text": "Curcumin, an active polyphenol of the golden spice turmeric, is a highly pleiotropic molecule with the potential to modulate the biological activity of a number of signaling molecules. Traditionally, this polyphenol has been used in Asian countries to treat such human ailments as acne, psoriasis, dermatitis, and rash. Recent studies have indicated that curcumin can target newly identified signaling pathways including those associated with microRNA, cancer stem cells, and autophagy. Extensive research from preclinical and clinical studies has delineated the molecular basis for the pharmaceutical uses of this polyphenol against cancer, pulmonary diseases, neurological diseases, liver diseases, metabolic diseases, autoimmune diseases, cardiovascular diseases, and numerous other chronic diseases. Multiple studies have indicated the safety and efficacy of curcumin in numerous animals including rodents, monkeys, horses, rabbits, and cats and have provided a solid basis for evaluating its safety and efficacy in humans. To date, more than 65 human clinical trials of curcumin, which included more than 1000 patients, have been completed, and as many as 35 clinical trials are underway. Curcumin is now used as a supplement in several countries including the United States, India, Japan, Korea, Thailand, China, Turkey, South Africa, Nepal, and Pakistan. In this review, we provide evidence for the pharmaceutical uses of curcumin for various diseases. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.", "title": "Curcumin, a component of turmeric: from farm to pharmacy." }, { "docid": "MED-2233", "text": "Changes in physiological and biochemical metabolism as well as glucoraphanin and sulforaphane contents of germinating broccoli seeds and sprouts were investigated in this study. Sprout length, root length, and fresh weight increased with germination time. Dry weight varied from 2.5 to 3.0 mg per sprout. A rapid increase in respiratory rate of sprouts occurred between 24 and 36 h of germination and then stayed at a high level. HPLC analysis found that glucoraphanin content increased at the early stage (0-12 h) of germination, decreased to a low value of 3.02 mg/g at 48 h, and then reached the highest value of 6.30 mg/g at 72 h of germination. Sulforaphane content decreased dramatically during the first day of germination, then increased slowly, and reached a high value of 3.38 mg/g at 48 h before declining again.", "title": "Physiological and biochemical metabolism of germinating broccoli seeds and sprouts." }, { "docid": "MED-3209", "text": "The effects of grapefruit juice on the bioavailability of 17 alpha-ethinylestradiol (EE2) after a single oral administration of 50 micrograms EE2 have been investigated. The pharmacokinetics of EE2 were studied in an open, randomized, cross-over study in which 13 healthy volunteers were administered the drug with herbal tea or grapefruit juice (naringin, 887 mg/ml). In contrast to herbal tea, grapefruit juice increased the peak plasma concentration (Cmax) significantly to 137% (mean; range 64% to 214%, p = 0.0088) and increased the area under plasma concentration-time curve from 0 to 8 hours (AUC0-8) to 128% (mean; range 81% to 180%, p = 0.0186). This study shows that grapefruit juice increases the bioavailable amount of EE2. A possible explanation may be that grapefruit juice inhibits the metabolic degradation of EE2. Whether the increased bioavailability of EE2 following grapefruit juice administration is of clinical importance should be investigated in long-term studies.", "title": "Can grapefruit juice influence ethinylestradiol bioavailability?" }, { "docid": "MED-3228", "text": "A precise understanding of the role of dietary protein in bone health has been evasive despite decades of research. It is known that a dietary acid load is harmful to bone, and sulfur-containing amino acids are metabolized to provide such an acid load. It is also known that protein elevates urine calcium loss. However, recent clinical studies and a meta-analysis have indicated either no effect or a modest benefit associated with higher protein intakes. These contradictory considerations may be explained by the existence of a two-faced relationship between protein and bone, with simultaneous positive and negative pathways. In opposition to the negative effects of dietary acid load, protein may exert positive effects related to improving calcium absorption, increasing insulin-like growth factor 1, or improving lean body mass, which, in turn, improves bone strength. Putative mechanisms behind these pathways are reviewed here, and some limitations in the historical literature as well as suggested measures to counter these in the future are identified. When positive and negative pathways are considered in tandem, protein may offer modest benefits to bone in the presence of adequate dietary calcium and acid-neutralizing fruits and vegetables. © 2011 International Life Sciences Institute.", "title": "Dietary protein and bone health: harmonizing conflicting theories." }, { "docid": "MED-2672", "text": "To quantify objectionable levels of connective tissues, restructured beef products were made with 2·5 and 5% added tendon; 5 and 10% added epimysium, gristle, or peri/endomysium; and a control. Initial tenderness (IT), residual connective tissue (CT), and overall texture (OT) were evaluated by a sensory panel. Panelists adversely scored IT, CT, and OT for 2·5 and 5% tendon and CT and OT for 10% epimysium and gristle. CT and OT scores correlated with hydroxyproline content and Lee-Kramer peak shear force for uncooked steaks with added tendon, gristle and epimysium but not peri/endomysium. Acceptable products can be made when raw materials are free of tendons and contain only limited amounts of epimysium. Copyright © 1990. Published by Elsevier Ltd.", "title": "Effects of added connective tissues on the sensory and mechanical properties of restructured beef steaks." }, { "docid": "MED-1996", "text": "Until recently, the majority of cases of diabetes mellitus among children and adolescents were immune-mediated type 1a diabetes. Obesity has led to a dramatic increase in the incidence of type 2 diabetes (T2DM) among children and adolescents over the past 2 decades. Obesity is strongly associated with insulin resistance, which, when coupled with relative insulin deficiency, leads to the development of overt T2DM. Children and adolescents with T2DM may experience the microvascular and macrovascular complications of this disease at younger ages than individuals who develop diabetes in adulthood, including atherosclerotic cardiovascular disease, stroke, myocardial infarction, and sudden death; renal insufficiency and chronic renal failure; limb-threatening neuropathy and vasculopathy; and retinopathy leading to blindness. Health care professionals are advised to perform the appropriate screening in children at risk for T2DM, diagnose the condition as early as possible, and provide rigorous management of the disease.", "title": "Childhood obesity and type 2 diabetes mellitus." }, { "docid": "MED-2207", "text": "The objective of this study was to investigate the antiproliferative effect and the mechanism of trypsin inhibitor (TI) from sweet potato [Ipomoea batatas (L.) Lam. 'Tainong 57'] storage roots on NB4 promyelocytic leukemia cells. The results showed that TI inhibited cellular growth of NB4 promyelocytic leukemia cells in a time-dependent and dose-dependent manner, and treatment for 72 h induced a marked inhibition of cellular growth, showing an IC50 of 57.1 +/- 8.26 microg/mL. TI caused cell cycle arrest at the G1 phase as determined by flow cytometric analysis and apoptosis as shown by DNA laddering. TI-induced cell apoptosis involved p53, Bcl-2, Bax, and cytochrome c protein in NB4 cells. P53 and Bax proteins were accumulated, and antiapoptotic molecule Bcl-2 was decreased in the tested cells in a time-dependent manner during TI treatment. TI also induced a substantial release of cytochrome c from the mitochondria into the cytosol. Hence, TI induced apoptosis in NB4 cells through a mitochondria-dependent pathway, which was associated with the activation of caspase-3 and -8. These results demonstrated that TI induces NB4 cell apoptosis through the inhibition of cell growth and the activation of the pathway of caspase-3 and -8 cascades.", "title": "Growth inhibition and induction of apoptosis in NB4 promyelocytic leukemia cells by trypsin inhibitor from sweet potato storage roots." }, { "docid": "MED-3221", "text": "Background The finding reported in a previous paper - alkalization of urine facilitates uric acid excretion - is contradictory to what one might expect to occur: because food materials for the alkalization of urine contain fewer purine bodies than those for acidification, less uric acid in alkaline urine should have been excreted than in acid urine. To make clear what component of uric acid excretion mechanisms is responsible for this unexpected finding, we simultaneously collected data for the concentration of both creatinine and uric acid in serum as well as in urine, in order to calculate both uric acid and creatinine clearances. Methods Within the framework of the Japanese government’s health promotion program, we made recipes which consisted of protein-rich and less vegetable-fruit food materials for H + -load (acidic diet) and others composed of less protein and more vegetable-fruit rich food materials (alkaline diet). This is a crossover study within some limitations. Healthy female students, who had no medical problems at the regular physical examination provided by the university, were enrolled in this consecutive 5-day study for each test. From whole-day collected urine, total volume, pH, organic acid, creatinine, uric acid, titratable acid and all cations (Na+,K+,Ca2+,Mg2+,NH4+) and anions (Cl−,SO42−,PO4−) necessary for the estimation of acid–base balance were measured. In the early morning before breakfast of the 1st, 3rd and 5th experimental day, we sampled 5 mL of blood to estimate the creatinine and uric acid concentration in serum. Results and discussion Urine pH reached a steady state 3 days after switching from ordinary daily diets to specified regimens. The amount of acid generated ([SO42−] + organic acid − gut alkali)was linearly related with the excretion of acid (titratable acid + [NH4+] − [HCO3−]), indicating that H + in urine is generated by the metabolic degradation of food materials. Uric acid and excreted urine pH retained a linear relationship, as reported previously. Among the five factors which are associated with calculating clearances for both uric acid and creatinine, we identified a conspicuous difference between acidic and alkaline diets in the uric acid concentration in serum as well as in urine; uric acid in the serum was higher in the acidic group than in the alkaline group, while uric acid in the urine in the acidic group was lower than that in the alkaline group. These changes of uric acid in acidic urine and in serum were reflected in the reduction of its clearance. From these observations, it is considered that uric acid may be reabsorbed more actively in acidic urine than in alkaline urine. Conclusion We conclude that alkalization of urine by eating nutritionally well-designed alkaline -prone food is effective for removing uric acid from the body.", "title": "Effect of urine pH changed by dietary intervention on uric acid clearance mechanism of pH-dependent excretion of urinary uric acid" }, { "docid": "MED-2671", "text": "Microbiology of meats has been a subject of great concern in food science and public health in recent years. Although many articles have been devoted to the microbiology of beef, pork, and poultry meats, much less has been written about microbiology of lamb meat and even less on restructured lamb meat. This article presents data on microbiology and shelf-life of fresh lamb meat; restructured meat products, restructured lamb meat products, bacteriology of restructured meat products, and important foodborne pathogens such as Salmonella, Escherichia coli O157:H7, and Listeria monocytogenes in meats and lamb meats. Also, the potential use of sodium and potassium lactates to control foodborne pathogens in meats and restructured lamb meat is reviewed This article should be of interest to all meat scientists, food scientists, and public health microbiologists who are concerned with the safety of meats in general and lamb meat in particular.", "title": "Microbiology of fresh and restructured lamb meat: a review." }, { "docid": "MED-2809", "text": "Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn’s disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin’s pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF–κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E2, prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the effect of curcumin has been investigated.", "title": "Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials" }, { "docid": "MED-1182", "text": "Background Sale of organic foods is one of the fastest growing market segments within the global food industry. People often buy organic food because they believe organic farms produce more nutritious and better tasting food from healthier soils. Here we tested if there are significant differences in fruit and soil quality from 13 pairs of commercial organic and conventional strawberry agroecosystems in California. Methodology/Principal Findings At multiple sampling times for two years, we evaluated three varieties of strawberries for mineral elements, shelf life, phytochemical composition, and organoleptic properties. We also analyzed traditional soil properties and soil DNA using microarray technology. We found that the organic farms had strawberries with longer shelf life, greater dry matter, and higher antioxidant activity and concentrations of ascorbic acid and phenolic compounds, but lower concentrations of phosphorus and potassium. In one variety, sensory panels judged organic strawberries to be sweeter and have better flavor, overall acceptance, and appearance than their conventional counterparts. We also found the organically farmed soils to have more total carbon and nitrogen, greater microbial biomass and activity, and higher concentrations of micronutrients. Organically farmed soils also exhibited greater numbers of endemic genes and greater functional gene abundance and diversity for several biogeochemical processes, such as nitrogen fixation and pesticide degradation. Conclusions/Significance Our findings show that the organic strawberry farms produced higher quality fruit and that their higher quality soils may have greater microbial functional capability and resilience to stress. These findings justify additional investigations aimed at detecting and quantifying such effects and their interactions.", "title": "Fruit and Soil Quality of Organic and Conventional Strawberry Agroecosystems" }, { "docid": "MED-2488", "text": "Cardiovascular diseases (CVD) cost Americans billions of dollars per year. High cholesterol levels, which are closely related to dietary habits, are a major contributor to CVD. In this article, we study whether changes in food prices are related to cholesterol levels and whether taxes or subsidies on particular foods would be effective in lowering cholesterol levels and, consequently, CVD costs. We find that prices of vegetables, processed foods, whole milk and whole grains are significantly associated with blood cholesterol levels. Having analyzed the costs and benefits of government interventions, we find that a subsidy of vegetables and whole grains would be an efficient way to reduce CVD expenditures. Published by Elsevier B.V.", "title": "Food prices and blood cholesterol." }, { "docid": "MED-2221", "text": "Context: In 1954 the tobacco industry paid to publish the “Frank Statement to Cigarette Smokers” in hundreds of U.S. newspapers. It stated that the public's health was the industry's concern above all others and promised a variety of good-faith changes. What followed were decades of deceit and actions that cost millions of lives. In the hope that the food history will be written differently, this article both highlights important lessons that can be learned from the tobacco experience and recommends actions for the food industry. Methods: A review and analysis of empirical and historical evidence pertaining to tobacco and food industry practices, messages, and strategies to influence public opinion, legislation and regulation, litigation, and the conduct of science. Findings: The tobacco industry had a playbook, a script, that emphasized personal responsibility, paying scientists who delivered research that instilled doubt, criticizing the “junk” science that found harms associated with smoking, making self-regulatory pledges, lobbying with massive resources to stifle government action, introducing “safer” products, and simultaneously manipulating and denying both the addictive nature of their products and their marketing to children. The script of the food industry is both similar to and different from the tobacco industry script. Conclusions: Food is obviously different from tobacco, and the food industry differs from tobacco companies in important ways, but there also are significant similarities in the actions that these industries have taken in response to concern that their products cause harm. Because obesity is now a major global problem, the world cannot afford a repeat of the tobacco history, in which industry talks about the moral high ground but does not occupy it.", "title": "The Perils of Ignoring History: Big Tobacco Played Dirty and Millions Died. How Similar Is Big Food?" }, { "docid": "MED-4149", "text": "Oxidative stress, i.e. excessive content of reactionary, oxygen, and nitrogen compounds (ROAC), including free radicals, is one of the causes of various dangerous diseases as well as premature aging. The adverse effect of free radicals can be neutralized by antioxidants. In order to carry out antioxidant therapy, one needs to know the contents of antioxidants in food products. We have created the databank for the contents of antioxidants in 1,140 food products, beverages, etc. Apart from water-soluble antioxidants, fat-soluble antioxidants in dairy and fish products, cacao, chocolate, nuts etc. were determined for the first time using an amperometric method.", "title": "Creation of a databank for content of antioxidants in food products by an amperometric method." }, { "docid": "MED-2203", "text": "Constipation is a common health problem that adversely affects quality of life and the prognosis of hospitalized patients with acute coronary syndromes (ACS). The purpose of this study was to develop and test the sweet potato/footbath/acupressure massage (SFA) intervention as a safe treatment for prevention of constipation and to increase satisfaction with bowel emptying in hospitalized patients with ACS. The study was a prospective, randomized controlled trial with a sample of 93 patients (SFA group, n = 44; usual care group, n = 49). Patients in the SFA group received SFA intervention combined with usual care. The results showed that there were statistical differences between the two groups in terms of (1) the incidence of constipation; (2) the use of laxatives and enemas; (3) patients' subjective satisfaction with their bowel emptying during hospitalization; and (4) sensation of incomplete evacuation and anorectal obstruction/blockade. The SFA intervention was more effective, economical, and practical than usual care alone in managing constipation and satisfaction with defecation in patients hospitalized with ACS.", "title": "The effect of a sweet potato, footbath, and acupressure intervention in preventing constipation in hospitalized patients with acute coronary syndro..." }, { "docid": "MED-1993", "text": "Type 2 diabetes mellitus is emerging as a new clinical problem within pediatric practice. Recent reports indicate an increasing prevalence of type 2 diabetes mellitus in children and adolescents around the world in all ethnicities, even if the prevalence of obesity is not increasing any more. The majority of young people diagnosed with type 2 diabetes mellitus was found in specific ethnic subgroups such as African-American, Hispanic, Asian/Pacific Islanders and American Indians. Clinicians should be aware of the frequent mild or asymptomatic manifestation of type 2 diabetes mellitus in childhood. Therefore, a screening seems meaningful especially in high risk groups such as children and adolescents with obesity, relatives with type 2 diabetes mellitus, and clinical features of insulin resistance (hypertension, dyslipidemia, polycystic ovarian syndrome, or acanthosis nigricans). Treatment of choice is lifestyle intervention followed by pharmacological treatment (e.g., metformin). New drugs such as dipeptidyl peptidase inhibitors or glucagon like peptide 1 mimetics are in the pipeline for treatment of youth with type 2 diabetes mellitus. However, recent reports indicate a high dropout of the medical care system of adolescents with type 2 diabetes mellitus suggesting that management of children and adolescents with type 2 diabetes mellitus requires some remodeling of current healthcare practices.", "title": "Type 2 diabetes mellitus in children and adolescents" }, { "docid": "MED-1181", "text": "Demand for organic foods is partially driven by consumers' perceptions that they are more nutritious. However, scientific opinion is divided on whether there are significant nutritional differences between organic and non-organic foods, and two recent reviews have concluded that there are no differences. In the present study, we carried out meta-analyses based on 343 peer-reviewed publications that indicate statistically significant and meaningful differences in composition between organic and non-organic crops/crop-based foods. Most importantly, the concentrations of a range of antioxidants such as polyphenolics were found to be substantially higher in organic crops/crop-based foods, with those of phenolic acids, flavanones, stilbenes, flavones, flavonols and anthocyanins being an estimated 19 (95 % CI 5, 33) %, 69 (95 % CI 13, 125) %, 28 (95 % CI 12, 44) %, 26 (95 % CI 3, 48) %, 50 (95 % CI 28, 72) % and 51 (95 % CI 17, 86) % higher, respectively. Many of these compounds have previously been linked to a reduced risk of chronic diseases, including CVD and neurodegenerative diseases and certain cancers, in dietary intervention and epidemiological studies. Additionally, the frequency of occurrence of pesticide residues was found to be four times higher in conventional crops, which also contained significantly higher concentrations of the toxic metal Cd. Significant differences were also detected for some other (e.g. minerals and vitamins) compounds. There is evidence that higher antioxidant concentrations and lower Cd concentrations are linked to specific agronomic practices (e.g. non-use of mineral N and P fertilisers, respectively) prescribed in organic farming systems. In conclusion, organic crops, on average, have higher concentrations of antioxidants, lower concentrations of Cd and a lower incidence of pesticide residues than the non-organic comparators across regions and production seasons.", "title": "Higher antioxidant and lower cadmium concentrations and lower incidence of pesticide residues in organically grown crops: a systematic literature review and meta-analyses" }, { "docid": "MED-3237", "text": "The modern Western-type diet is deficient in fruits and vegetables and contains excessive animal products, generating the accumulation of non-metabolizable anions and a lifespan state of overlooked metabolic acidosis, whose magnitude increases progressively with aging due to the physiological decline in kidney function. In response to this state of diet-derived metabolic acidosis, the kidney implements compensating mechanisms aimed to restore the acid-base balance, such as the removal of the non-metabolizable anions, the conservation of citrate, and the enhancement of kidney ammoniagenesis and urinary excretion of ammonium ions. These adaptive processes lower the urine pH and induce an extensive change in urine composition, including hypocitraturia, hypercalciuria, and nitrogen and phosphate wasting. Low urine pH predisposes to uric acid stone formation. Hypocitraturia and hypercalciuria are risk factors for calcium stone disease. Even a very mild degree of metabolic acidosis induces skeletal muscle resistance to the insulin action and dietary acid load may be an important variable in predicting the metabolic abnormalities and the cardiovascular risk of the general population, the overweight and obese persons, and other patient populations including diabetes and chronic kidney failure. High dietary acid load is more likely to result in diabetes and systemic hypertension and may increase the cardiovascular risk. Results of recent observational studies confirm an association between insulin resistance and metabolic acidosis markers, including low serum bicarbonate, high serum anion gap, hypocitraturia, and low urine pH. Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.", "title": "Diet-induced metabolic acidosis." }, { "docid": "MED-3226", "text": "Context and Objective: Dietary intake of animal proteins is associated with an increase in urinary calcium and nephrolithiasis risk. We tested the hypothesis that the acid load imposed by dietary proteins causes this hypercalciuria. Design and Setting: In a short-term crossover metabolic study, an alkali salt was provided with a high-protein diet (HPD) to neutralize the acid load imparted by dietary proteins. Participants and Interventions: Eleven healthy volunteers were evaluated at the end of each of four phases while consuming metabolic diets with fixed calcium and sodium content. Phases 1 and 3 consisted of a control diet (CD). Phases 2 and 4 consisted of a eucaloric HPD (60 g/d animal proteins added to CD). Along with HPD in phases 2 and 4, subjects ingested 30 mEq twice daily of either potassium citrate (KCitrate, alkaline salt) or potassium chloride (KCl, control neutral salt). Results: KCitrate completely neutralized the acid load imparted by HPD (based on changes in urine pH and net acid excretion) and increased urinary citrate. Urinary calcium increased during both HPD phases compared with CD but was not significantly different between the HPD + KCl and HPD + KCitrate phases (182 ± 85 vs. 170 ± 85 mg/d; P = 0.28). Increased urinary saturation with respect to calcium oxalate and uric acid with HPD was abrogated by KCitrate. Conclusions: This study suggests that, at least in the short-term, mechanism(s) other than acid load account for hypercalciuria induced by HPD. The beneficial effect of KCitrate on nephrolithiasis risk with HPD is through correction of declines in urine pH and citrate.", "title": "Hypercalciuria Associated with High Dietary Protein Intake Is Not Due to Acid Load" }, { "docid": "MED-2673", "text": "Transglutaminase is an enzyme that can be used to cross-link pieces of meat, fish or meat products. The resulting product gives the optical impression of an intact chunk of meat. The usage of transglutaminase as a food additive is permitted in some countries. However, its utilisation has to be declared to ensure transparency for consumers. This paper describes two orthogonal analytical methods suited for the detection of technological relevant transglutaminase concentrations (around 25 mg pure enzyme in 1 kg of product) in meat and meat products. The mass spectrometry-based approach relies on a previous digestion with Achromobacter lyticus protease and LC-MS/MS separation and detection. Sufficient selectivity was obtained by monitoring four different peptides. The orthogonal (complementary and independent), ELISA-based approach relies on two commercially available bacterial transglutaminase-specific antibodies, combined to a sandwich ELISA. The two methods were tested by analysing some 60 samples obtained from the market.", "title": "Determination of microbial transglutaminase in meat and meat products." }, { "docid": "MED-2315", "text": "Background The word selectivity describes a drug's ability to affect a particular cell population in preference to others. As part of the current state of art in the search for new therapeutic agents, the property of selectivity is a mode of action thought to have a high degree of desirability. Consequently there is a growing activity in this area of research. Selectivity is generally a worthy property in a drug because a drug having high selectivity may have a dramatic effect when there is a single agent that can be targeted against the appropriate molecular-driver involved in the pathogenesis of a disease. An example is chronic myeloid leukemia (CML). CML has a specific chromosomal abnormality, the Philadelphia chromosome, that results in a single gene that produces an abnormal protein Discussion There is a burgeoning understanding of the cellular mechanisms that control the etiology and pathogeneses of diseases. This understanding both enables and motivates the development of drugs that induce a specific action in a selected cell population; i.e., a targeted treatment. Consequently, drugs that can target distinct molecular targets involved in pathologic/pathogenetic processes, or signal-transduction pathways, are being developed. However, in most cases, diseases involve multiple abnormalities. A disease may be associated with more than one dysfunctional protein and these may be out-of-balance with each other. Likewise a drug might strongly target a protein that shares a similar active domain with other proteins. A drug may also target pleiotropic cytokines, or other proteins that have multi-physiological functions. In this way multiple normal cellular pathways can be simultaneously influenced. Long term experience with drugs supposedly designed for only a single target, but which unavoidably involve other functional effects, is uncovering the fact that molecular targeting is not medically flawless. Summary We contend that an ideal drug may be one whose efficacy is based not on the inhibition of a single target, but rather on the rebalancing of the several proteins or events, that contribute to the etiology, pathogeneses, and progression of diseases, i.e., in effect a promiscuous drug. Ideally, if this could be done at minimum drug concentration, side effects could be minimized. Corollaries to this argument are that the growing fervor for researching truly selective drugs may be imprudent when considering the totality of responses; and that the expensive screening techniques used to discover these, may be both medically and financially inefficient.", "title": "Promiscuous drugs compared to selective drugs (promiscuity can be a virtue)" }, { "docid": "MED-3207", "text": "Summary Grapefruit is a popular, tasty and nutritive fruit enjoyed globally. Biomedical evidence in the last 10 years has, however, shown that consumption of grapefruit or its juice is associated with drug interactions, which, in some cases, have been fatal. Grapefruit-induced drug interactions are unique in that the cytochrome P450 enzyme CYP3A4, which metabolises over 60% of commonly prescribed drugs as well as other drug transporter proteins such as P-glycoprotein and organic cation transporter proteins, which are all expressed in the intestines, are involved. However, the extent to which grapefruit–drug interactions impact on clinical settings has not been fully determined, probably because many cases are not reported. It has recently emerged that grapefruit, by virtue of its rich flavonoid content, is beneficial in the management of degenerative diseases such as diabetes and cardiovascular disorders. This potentially explosive subject is reviewed here.", "title": "The grapefruit: an old wine in a new glass? Metabolic and cardiovascular perspectives" }, { "docid": "MED-3230", "text": "OBJECTIVE: Diet affects urine pH and acid-base balance. Both excess acid/alkaline ash (EAA) and estimated net acid excretion (NAE) calculations have been used to estimate the effects of diet on urine pH. This study's goal was to determine if free-living vegans, lacto-ovo vegetarians, and omnivores have increasingly acidic urine, and to assess the ability of EAA and estimated NAE calculations to predict urine pH. DESIGN: This study used a cross-sectional design. SETTING AND PARTICIPANTS: This study assessed urine samples of 10 vegan, 16 lacto-ovo vegetarian, and 16 healthy omnivorous women in the Boston metropolitan area. Six 3-day food records from each dietary group were analyzed for EAA content and estimated NAE, and correlations with measured urine pH were calculated. RESULTS: The mean (+/- SD) urine pH was 6.15 +/- 0.40 for vegans, 5.90 +/- 0.36 for lacto-ovo vegetarians, and 5.74 +/- 0.21 for omnivores (analysis of variance, P = .013). Calculated EAA values were not significantly different among the three groups, whereas mean estimated NAE values were significantly different: 17.3 +/- 14.5 mEq/day for vegans, 31.3 +/- 8.5 mEq/day for lacto-ovo vegetarians, and 42.6 +/- 13.2 mEq/day for omnivores (analysis of variance, P = .01). The average deattenuated correlation between urine pH and EAA was 0.333; this value was -0.768 for estimated NAE and urine pH, with a regression equation of pH = 6.33 - 0.014 NAE (P = .02, r = -0.54). CONCLUSIONS: Habitual diet and estimated NAE calculations indicate the probable ranking of urine pH by dietary groups, and may be used to determine the likely acid-base status of an individual; EAA calculations were not predictive of urine pH.", "title": "Estimated net acid excretion inversely correlates with urine pH in vegans, lacto-ovo vegetarians, and omnivores." }, { "docid": "MED-2235", "text": "Broccoli consumption may reduce the risk of various cancers and many broccoli supplements are now available. The bioavailability and excretion of the mercapturic acid pathway metabolites isothiocyanates after human consumption of broccoli supplements has not been tested. Two important isothiocyanates from broccoli are sulforaphane and erucin. We employed a cross-over study design in which 12 subjects consumed 40 grams of fresh broccoli sprouts followed by a 1 month washout period and then the same 12 subjects consumed 6 pills of a broccoli supplement. As negative controls for isothiocyanate consumption four additional subjects consumed alfalfa sprouts during the first phase and placebo pills during the second. Blood and urine samples were collected for 48 hours during each phase and analyzed for sulforaphane and erucin metabolites using LC-MS/MS. The bioavailability of sulforaphane and erucin is dramatically lower when subjects consume broccoli supplements compared to fresh broccoli sprouts. The peaks in plasma concentrations and urinary excretion were also delayed when subjects consumed the broccoli supplement. GSTP1 polymorphisms did not affect the metabolism or excretion of sulforaphane or erucin. Sulforaphane and erucin are able to interconvert in vivo and this interconversion is consistent within each subject but variable between subjects. This study confirms that consumption of broccoli supplements devoid of myrosinase activity does not produce equivalent plasma concentrations of the bioactive isothiocyanate metabolites compared to broccoli sprouts. This has implications for people who consume the recommended serving size (1 pill) of a broccoli supplement and believe they are getting equivalent doses of isothiocyanates.", "title": "Bioavailability and inter-conversion of sulforaphane and erucin in human subjects consuming broccoli sprouts or broccoli supplement in a cross-over study design" }, { "docid": "MED-3810", "text": "The typical spices used in winter include nutmeg, cinnamon, clove and anise. These spices contain two groups of chemicals, the allylbenzenes and their isomers, the propenylbenzenes. It was suggested 40 years ago by Alexander Shulgin that these substances act as metabolic precursors of amphetamines. The biotransformation of these precursors to nitrogen-containing metabolites is reviewed. These reactions have not been reported in humans. Whether or not the pharmacology and toxicology of spices such as nutmeg can be explained on the basis of their allylbenzene or propenylbenzene content is speculative. Humans may be exposed to amphetamines derived from these precursors in forno, the formation during baking and cooking, for example in the preparation of Lebkuchen, or Christmas gingerbread. It is possible that this may be responsible, in part, for uplifting our mood in winter. However, the role of these aromatic substances, acting simply as odours, evoking old memories of winters past, cannot be ignored. Whether spices have a true pharmacological effect or they act as aromatherapy remains to be elucidated through clinical and laboratory studies.", "title": "Christmas gingerbread (Lebkuchen) and Christmas cheer--review of the potential role of mood elevating amphetamine-like compounds formed in vivo and..." }, { "docid": "MED-2831", "text": "TNFs are major mediators of inflammation and inflammation-related diseases, hence, the United States Food and Drug Administration (FDA) has approved the use of blockers of the cytokine, TNF-α, for the treatment of osteoarthritis, inflammatory bowel disease, psoriasis and ankylosis. These drugs include the chimeric TNF antibody (infliximab), humanized TNF-α antibody (Humira) and soluble TNF receptor-II (Enbrel) and are associated with a total cumulative market value of more than $20 billion a year. As well as being expensive ($15 000–20 000 per person per year), these drugs have to be injected and have enough adverse effects to be given a black label warning by the FDA. In the current report, we describe an alternative, curcumin (diferuloylmethane), a component of turmeric (Curcuma longa) that is very inexpensive, orally bioavailable and highly safe in humans, yet can block TNF-α action and production in in vitro models, in animal models and in humans. In addition, we provide evidence for curcumin's activities against all of the diseases for which TNF blockers are currently being used. Mechanisms by which curcumin inhibits the production and the cell signalling pathways activated by this cytokine are also discussed. With health-care costs and safety being major issues today, this golden spice may help provide the solution. Linked Articles This article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-8", "title": "Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers" }, { "docid": "MED-2231", "text": "Functional foods and their nutraceutical components are now considered as supplementary treatments in type 2 diabetes and prevention of its long-term complications. Young broccoli sprouts as a functional food contain many bioactive compounds specially sulforaphane. In hyperglycemic and oxidative conditions, sulforaphane has the potential to activate the NF-E2-related factor-2 (Nrf2)-dependent antioxidant response-signaling pathway, induces phase 2 enzymes, attenuates oxidative stress, and inactivates nuclear factor kappa-B (NF-κB), a key modulator of inflammatory pathways. Interestingly, sulforaphane induces some peroxisome proliferator-activated receptors, which contribute to lipid metabolism and glucose homeostasis. In animal and in vitro models, sulforaphane also shows antihypertensive, anticancer, cardioprotective, and hypocholesterolemic capacity, and has bactericidal properties against Helicobacter pylori. Supplementation of type 2 diabetics with high sulforaphane content broccoli sprouts resulted in increased total antioxidant capacity of plasma and in decreased oxidative stress index, lipid peroxidation, serum triglycerides, oxidized low-density lipoprotein (LDL)/LDL-cholesterol ratio, serum insulin, insulin resistance, and serum high-sensitive C-reactive protein. Sulforaphane could prevent nephropathy, diabetes-induced fibrosis, and vascular complications. Potential efficacy of sulforaphane and probably other bioactive components of young broccoli sprouts makes it as an excellent choice for supplementary treatment in type 2 diabetes.", "title": "Potential efficacy of broccoli sprouts as a unique supplement for management of type 2 diabetes and its complications." }, { "docid": "MED-3139", "text": "Background: Soy isoflavones have antiestrogenic and anticancer properties but also possess estrogen-like properties, which has raised concern about soy food consumption among breast cancer survivors. Objective: We prospectively evaluated the association between postdiagnosis soy food consumption and breast cancer outcomes among US and Chinese women by using data from the After Breast Cancer Pooling Project. Design: The analysis included 9514 breast cancer survivors with a diagnosis of invasive breast cancer between 1991 and 2006 from 2 US cohorts and 1 Chinese cohort. Soy isoflavone intake (mg/d) was measured with validated food-frequency questionnaires. HRs and 95% CIs were estimated by using delayed-entry Cox regression models, adjusted for sociodemographic, clinical, and lifestyle factors. Results: After a mean follow-up of 7.4 y, we identified 1171 total deaths (881 from breast cancer) and 1348 recurrences. Despite large differences in soy isoflavone intake by country, isoflavone consumption was inversely associated with recurrence among both US and Chinese women, regardless of whether data were analyzed separately by country or combined. No heterogeneity was observed. In the pooled analysis, consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of all-cause (HR: 0.87; 95% CI: 0.70, 1.10) and breast cancer–specific (HR: 0.83; 95% CI: 0.64, 1.07) mortality and a statistically significant reduced risk of recurrence (HR: 0.75; 95% CI: 0.61, 0.92). Conclusion: In this large study of combined data on US and Chinese women, postdiagnosis soy food consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of breast cancer–specific mortality and a statistically significant reduced risk of recurrence. One of the studies included in the After Breast Cancer Pooling Project, the Women's Healthy Eating & Living Study, was registered at clinicaltrials.gov as NCT00003787.", "title": "Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women" }, { "docid": "MED-2208", "text": "BACKGROUND: Bikunin, a Kunitz-type protease inhibitor, specifically inhibits tumor invasion and metastasis. METHODS: The authors initially evaluated the therapeutic efficacy of once-daily oral administration of different doses of bikunin against human ovarian carcinoma HRA cells growing in the peritonea of nude mice. For the in vivo studies, female 7-week-old nude mice were randomized to 1 of 4 groups: bikunin-treated groups (n = 9 in each group) received 3, 10, or 30 microg/g body weight per day bikunin for 7 days via gastrointestinal gavage, and a control group (n = 9) received the vehicle solution (phosphate-buffered saline) via gastrointestinal gavage. On Day 9, the abdominal cavity was examined by two observers who were blinded to treatment. RESULTS: After oral administration, intact bikunin was detectable in mouse serum specimens at 3 and 6 hours. This was followed by a decline at 12 hours. The mice given bikunin at the highest dose level had a 40% decrease in tumor load. The highest uptake in the tumor was obtained with [125I]bikunin 12 hours postadministration. No effect on either food intake or body weight was observed in the treated versus sham groups. The current study was the first to report the potent activity of once-daily oral administration of bikunin against ovarian carcinoma. Next, the authors performed a Phase I trial to determine the maximum-tolerated dose (MTD) and safety of a once-daily oral administration schedule. The indication was locally advanced uterine cervical carcinoma after definitive treatment. An escalating dose (3, 10, and 30 mg/kg per day) of bikunin was administered orally to nine patients for 7 days. There were no dose-limiting toxicities and the MTD of the bikunin schedule was not defined. The authors also obtained preliminary data on its effect on urokinase-type plasminogen activator expression at the highest dose level. CONCLUSIONS: Once-daily oral administration of bikunin was found to be safe in humans and exhibited signs of biologic activity. Copyright 2004 American Cancer Society.", "title": "Therapeutic efficacy of once-daily oral administration of a Kunitz-type protease inhibitor, bikunin, in a mouse model and in human cancer." }, { "docid": "MED-2232", "text": "Many studies have supported the protective effects of broccoli and broccoli sprouts against cancer. The chemopreventive properties of sulforaphane, which is derived from the principal glucosinolate of broccoli and broccoli sprouts, have been extensively studied. Recent research into the effects of sulforaphane on cancer stem cells (CSCs) has drawn lots of interest. CSCs are suggested to be responsible for initiating and maintaining cancer, and to contribute to recurrence and drug resistance. A number of studies have indicated that sulforaphane may target CSCs in different types of cancer through modulation of NF-κB, SHH, epithelial-mesenchymal transition and Wnt/β-catenin pathways. Combination therapy with sulforaphane and chemotherapy in preclinical settings has shown promising results. In this article, we focus on the effects of sulforaphane on CSCs and self-renewal pathways, as well as giving a brief review of recent human studies using broccoli sprout preparations.", "title": "Targeting cancer stem cells with sulforaphane, a dietary component from broccoli and broccoli sprouts." }, { "docid": "MED-4689", "text": "Background A plant-based diet protects against chronic oxidative stress-related diseases. Dietary plants contain variable chemical families and amounts of antioxidants. It has been hypothesized that plant antioxidants may contribute to the beneficial health effects of dietary plants. Our objective was to develop a comprehensive food database consisting of the total antioxidant content of typical foods as well as other dietary items such as traditional medicine plants, herbs and spices and dietary supplements. This database is intended for use in a wide range of nutritional research, from in vitro and cell and animal studies, to clinical trials and nutritional epidemiological studies. Methods We procured samples from countries worldwide and assayed the samples for their total antioxidant content using a modified version of the FRAP assay. Results and sample information (such as country of origin, product and/or brand name) were registered for each individual food sample and constitute the Antioxidant Food Table. Results The results demonstrate that there are several thousand-fold differences in antioxidant content of foods. Spices, herbs and supplements include the most antioxidant rich products in our study, some exceptionally high. Berries, fruits, nuts, chocolate, vegetables and products thereof constitute common foods and beverages with high antioxidant values. Conclusions This database is to our best knowledge the most comprehensive Antioxidant Food Database published and it shows that plant-based foods introduce significantly more antioxidants into human diet than non-plant foods. Because of the large variations observed between otherwise comparable food samples the study emphasizes the importance of using a comprehensive database combined with a detailed system for food registration in clinical and epidemiological studies. The present antioxidant database is therefore an essential research tool to further elucidate the potential health effects of phytochemical antioxidants in diet.", "title": "The total antioxidant content of more than 3100 foods, beverages, spices, herbs and supplements used worldwide" }, { "docid": "MED-2322", "text": "The global demand for more affordable therapeutics and concerns about side effects of commonly used drugs are refocusing interest on Eastern traditional medicines, particularly those of India and China.", "title": "From exotic spice to modern drug?" }, { "docid": "MED-2489", "text": "A historical view on how our agricultural systems evolved and how they are contributing to obesity and disease.", "title": "Agricultural policies, food and public health" }, { "docid": "MED-3811", "text": "Cinnamon, the dry bark and twig of Cinnamomum spp., is a rich botanical source of polyphenolics that has been used for centuries in Chinese medicine and has been shown to affect blood glucose and insulin signaling. Cinnamon's effects on blood glucose have been the subject of many clinical and animal studies; however, the issue of cinnamon intake's effect on fasting blood glucose (FBG) in people with type 2 diabetes and/or prediabetes still remains unclear. A meta-analysis of clinical studies of the effect of cinnamon intake on people with type 2 diabetes and/or prediabetes that included three new clinical trials along with five trials used in previous meta-analyses was done to assess cinnamon's effectiveness in lowering FBG. The eight clinical studies were identified using a literature search (Pub Med and Biosis through May 2010) of randomized, placebo-controlled trials reporting data on cinnamon and/or cinnamon extract and FBG. Comprehensive Meta-Analysis (Biostat Inc., Englewood, NJ, USA) was performed on the identified data for both cinnamon and cinnamon extract intake using a random-effects model that determined the standardized mean difference ([i.e., Change 1(control) - Change 2(cinnamon)] divided by the pooled SD of the post scores). Cinnamon intake, either as whole cinnamon or as cinnamon extract, results in a statistically significant lowering in FBG (-0.49±0.2 mmol/L; n=8, P=.025) and intake of cinnamon extract only also lowered FBG (-0.48 mmol/L±0.17; n=5, P=.008). Thus cinnamon extract and/or cinnamon improves FBG in people with type 2 diabetes or prediabetes.", "title": "Cinnamon intake lowers fasting blood glucose: meta-analysis." }, { "docid": "MED-4712", "text": "Since the beginning of this century, Goji berries and juice are being sold as health food products in western countries and praised in advertisements and in the media for well-being and as an anti-aging remedy. The popularity of Goji products has rapidly grown over the last years thanks to efficient marketing strategies. Goji is a relatively new name given to Lycium barbarum and L. chinense, two close species with a long tradition of use as medicinal and food plants in East Asia, in particular in China. While only L. barbarum is officinal, the fruit (fructus Lycii) and the root bark (cortex Lycii radicis) of both species are used in the folk medicine. We review here the constituents, pharmacology, safety, and uses of L. barbarum and L. chinense with consideration to the different parts of the plant. Investigations of the fruit have focused on proteoglycans, known as \" Lycium barbarum polysaccharides\", which showed antioxidative properties and some interesting pharmacological activities in the context of age related diseases such as atherosclerosis and diabetes. As to the root bark, several compounds have demonstrated a hepatoprotective action as well as inhibitory effects on the rennin/angiotensin system which may support the traditional use for the treatment of hypertension. While there are no signs of toxicity of this plant, two cases of possible interaction with warfarin point to a potential risk of drug interaction. In view of the available pharmacological data and the long tradition of use in the traditional Chinese medicine, L. barbarum and L. chinense certainly deserve further investigation. However, clinical evidences and rigorous procedures for quality control are indispensable before any recommendation of use can be made for Goji products. Copyright Georg Thieme Verlag KG Stuttgart . New York.", "title": "Goji (Lycium barbarum and L. chinense): Phytochemistry, pharmacology and safety in the perspective of traditional uses and recent popularity." }, { "docid": "MED-3137", "text": "A longstanding goal of dietary surveillance has been to estimate the proportion of the population with intakes above or below a target, such as a recommended level of intake. However, until now, statistical methods for assessing the alignment of food intakes with recommendations have been lacking. The purposes of this study were to demonstrate the National Cancer Institute’s method of estimating the distribution of usual intake of foods and determine the proportion of the U.S. population who does not meet federal dietary recommendations. Data were obtained from the 2001–2004 NHANES for 16,338 persons, aged 2 y and older. Quantities of foods reported on 24-h recalls were translated into amounts of various food groups using the MyPyramid Equivalents Database. Usual dietary intake distributions were modeled, accounting for sequence effect, weekend/weekday effect, sex, age, poverty income ratio, and race/ethnicity. The majority of the population did not meet recommendations for all of the nutrient-rich food groups, except total grains and meat and beans. Concomitantly, overconsumption of energy from solid fats, added sugars, and alcoholic beverages (“empty calories”) was ubiquitous. Over 80% of persons age ≥71 y and over 90% of all other sex-age groups had intakes of empty calories that exceeded the discretionary calorie allowances. In conclusion, nearly the entire U.S. population consumes a diet that is not on par with recommendations. These findings add another piece to the rather disturbing picture that is emerging of a nation’s diet in crisis.", "title": "Americans Do Not Meet Federal Dietary Recommendations" }, { "docid": "MED-1986", "text": "BACKGROUND: Overweight in adults is associated with increased morbidity and mortality. In contrast, the long-term effect of overweight in adolescence on morbidity and mortality is not known. METHODS: We studied the relation between overweight and morbidity and mortality in 508 lean or overweight adolescents 13 to 18 years old who participated in the Harvard Growth Study of 1922 to 1935. Overweight adolescents were defined as those with a body-mass index that on two occasions was greater than the 75th percentile in subjects of the same age and sex in a large national survey. Lean adolescents were defined as those with a body-mass index between the 25th and 50th percentiles. Subjects who were still alive were interviewed in 1988 to obtain information about their medical history, weight, functional capacity, and other risk factors. For those who had died, information on the cause of death was obtained from death certificates. RESULTS: Overweight in adolescent subjects was associated with an increased risk of mortality from all causes and disease-specific mortality among men, but not among women. The relative risks among men were 1.8 (95 percent confidence interval, 1.2 to 2.7; P = 0.004) for mortality from all causes and 2.3 (95 percent confidence interval, 1.4 to 4.1; P = 0.002) for mortality from coronary heart disease. The risk of morbidity from coronary heart disease and atherosclerosis was increased among men and women who had been overweight in adolescence. The risk of colorectal cancer and gout was increased among men and the risk of arthritis was increased among women who had been overweight in adolescence. Overweight in adolescence was a more powerful predictor of these risks than overweight in adulthood. CONCLUSIONS: Overweight in adolescence predicted a broad range of adverse health effects that were independent of adult weight after 55 years of follow-up.", "title": "Long-term morbidity and mortality of overweight adolescents. A follow-up of the Harvard Growth Study of 1922 to 1935." }, { "docid": "MED-2308", "text": "Background Few studies have evaluated the linkage between food cost and mortality among older adults. This study considers the hypothesis that greater food expenditure in general, and particularly on more nutritious plant and animal-derived foods, decreases mortality in older adults. Methods This study uses the 1999–2000 Elderly Nutrition and Health Survey in Taiwan and follows the cohort until 2008, collecting 24-hr dietary recall data for 1781 participants (874 men and 907 women) aged 65 y or older. Using monthly mean national food prices and 24-hr recall, this study presents an estimate of daily expenditures for vegetable, fruit, animal-derived, and grain food categories. Participants were linked to the national death registry. Results Of the 1781 original participants, 625 died during the 10-y follow-up period. Among the 4 food categories, the fourth and fifth expenditure quintiles for vegetables and for fruits had the highest survival rates. After adjusting for co-variates, higher (Q4) vegetable and higher fruit (Q4) food expenditures referent to Q1 were significantly predictive of reduced mortality (HR = 0.55, 95% CI: 0.39-0.78 and HR = 0.64, 95% CI: 0.42–0.99, respectively) and the risk decreased by 12% and 10% for every NT$15 (US$0.50) increase in their daily expenditures. Animal-derived and grain food spending was not predictive of mortality. Conclusion Greater and more achievable vegetable and fruit affordability may improve food security and longevity for older adults.", "title": "Spending on vegetable and fruit consumption could reduce all-cause mortality among older adults" }, { "docid": "MED-4622", "text": "We developed a probabilistic model to characterize the plausible distribution of health and economic benefits that would accrue to the U.S. population following reduction of methyl mercury (MeHg) exposure. MeHg, a known human developmental neurotoxicant, may increase fatal heart attack risks. Model parameters reflect current understanding of the relationships between MeHg intake, health risks, and societal valuation of these risks. The expected monetary value of the annual health benefits generated by a 10% reduction in U.S. population exposure to MeHg for one year is $860 million; 80% of this is associated with reductions in fatal heart attacks and the remainder with IQ gains. The plausible distribution of the benefits is quite broad with 5th and 95th percentile estimates of approximately $50 million and $3.5 billion, respectively. The largest source of uncertainty is whether epidemiological associations between MeHg exposure and fatal heart attacks reflect causality. The next largest sources of uncertainty concern the slope of the relationship between maternal MeHg exposure and reduced intelligence among children and whether this relationship exhibits a threshold. Our analysis suggests that the possible causal relationship between MeHg exposure and fatal heart attacks should be better characterized, using additional epidemiological studies and formally elicited expert judgment.", "title": "A probabilistic characterization of the health benefits of reducing methyl mercury intake in the United States." }, { "docid": "MED-2762", "text": "BACKGROUND: Vitamin and mineral supplements are commonly used to prevent chronic diseases. PURPOSE: To systematically review evidence for the benefit and harms of vitamin and mineral supplements in community-dwelling, nutrient-sufficient adults for the primary prevention of cardiovascular disease (CVD) and cancer. DATA SOURCES: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Database of s of Reviews of Effects were searched from January 2005 to 29 January 2013, with manual searches of reference lists and gray literature. STUDY SELECTION: Two investigators independently selected and reviewed fair- and good-quality trials for benefit and fair- and good-quality trials and observational studies for harms. DATA EXTRACTION: Dual quality assessments and data abstraction. DATA SYNTHESIS: Two large trials (n = 27 658) reported lower cancer incidence in men taking a multivitamin for more than 10 years (pooled unadjusted relative risk, 0.93 [95% CI, 0.87 to 0.99]). The study that included women showed no effect in that group. High-quality studies (k = 24; n = 324 653) of single and paired nutrients (such as vitamins A, C, or D; folic acid; selenium; or calcium) were scant and heterogeneous and showed no clear evidence of benefit or harm. Neither vitamin E nor β-carotene prevented CVD or cancer, and β-carotene increased lung cancer risk in smokers. LIMITATIONS: The analysis included only primary prevention studies in adults without known nutritional deficiencies. Studies were conducted in older individuals and included various supplements and doses under the set upper tolerable limits. Duration of most studies was less than 10 years. CONCLUSION: Limited evidence supports any benefit from vitamin and mineral supplementation for the prevention of cancer or CVD. Two trials found a small, borderline-significant benefit from multivitamin supplements on cancer in men only and no effect on CVD. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.", "title": "Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: An updated systematic evidence review for the U.S. ..." }, { "docid": "MED-3809", "text": "Mutagenicity and liver toxicity of the herb tarragon (Artemisia dracunculus) were evaluated using single cell gel (comet) electrophoresis. Ten microlitres aliquots of peripheral venous human blood were incubated with tarragon extract, saline, or the mutagen sodium dichromate. Cell suspensions dispersed in low-melting agarose were electrophoresed in ethidium bromide. The resulting DNA migration trails were obtained using fluorescent microscopy at 400× magnification, and graded according to the mutagenicity index (MI) for each cell incubation condition. The in vivo liver toxicity of Artemisia dracunculus was assessed in the blood of mice treated orally with the extract of the herb, using alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as liver function indicators. Liver morphology was assessed using hematoxylin and eosin (HE) staining of liver tissue. The present study demonstrated a direct correlation between tarragon extract dosage and three major outcome variables: MI; serum liver enzyme activity; and liver histopathology. These outcomes are possibly due to the presence in tarragon of methylchavicol and other genotoxic compounds. These findings provide a preliminary guide for risk assessment of tarragon in diet and in possible therapeutic applications. Copyright © 2012 Elsevier Ltd. All rights reserved.", "title": "Toxicological and mutagenic analysis of Artemisia dracunculus (tarragon) extract." }, { "docid": "MED-3217", "text": "To investigate whether systemic acid-base equilibrium changes with aging in normal adult humans, we reviewed published articles reporting the acid-base composition of arterial, arterialized venous, or capillary blood in age-identified healthy subjects. We extracted or calculated blood hydrogen ion concentration ([H+]), plasma bicarbonate concentration ([HCO3(-)]), blood PCO2, and age, and computed a total of 61 age-group means, distributed among eight 10-year intervals from age 20 to 100 years. Using linear regression analysis, we found that with increasing age, there is a significant increase in the steady-state blood [H+] (p < .001), and reduction in steady-state plasma [HCO3(-)] (p < .001), indicative of a progressively worsening low-level metabolic acidosis. Blood PCO2 decreased with age (p < .05), in keeping with the expected respiratory adaptation to metabolic acidosis. Such age-related increasing metabolic acidosis may reflect in part the normal decline of renal function with increasing age. The role of age-related metabolic acidosis in the pathogenesis of the degenerative diseases of aging warrants consideration.", "title": "Age and systemic acid-base equilibrium: analysis of published data." }, { "docid": "MED-2757", "text": "BACKGROUND: Multivitamins are the most commonly used supplement in the developed world. Recent epidemiologic findings suggest that multivitamin use increases the risk of mortality. OBJECTIVE: We aimed to determine whether multivitamin-multimineral treatment, used for primary or secondary prevention, increases the risk of mortality in independently living adults. DESIGN: We performed a meta-analysis of randomized controlled trials. Multiple electronic databases were systematically searched from March to October 2012. Randomized controlled primary or secondary prevention trials were considered for inclusion. Eligible trials investigated daily multivitamin-multimineral supplementation for ≥1 y. Cohorts described as institutionalized or as having terminal illness (tertiary prevention) were excluded. The number of deaths and the sample size of each study arm were extracted independently by 2 researchers. Twenty-one articles were included in the analysis, which generated a total pooled sample of 91,074 people and 8794 deaths. These trials were pooled in a meta-analysis, and the outcomes were expressed as RRs and 95% CIs. RESULTS: The average age of the pooled sample was 62 y, and the average duration of supplementation was 43 mo. Across all studies, no effect of multivitamin-multimineral treatment on all-cause mortality (RR: 0.98; 95% CI: 0.94, 1.02) was observed. There was a trend for a reduced risk of all-cause mortality across primary prevention trials (RR: 0.94; 95% CI: 0.89, 1.00). Multivitamin-multimineral treatment had no effect on mortality due to vascular causes (RR: 1.01; 95% CI: 0.93, 1.09) or cancer (RR: 0.96; 95% CI: 0.88, 1.04). No statistical evidence of heterogeneity or publication bias was observed. CONCLUSION: Multivitamin-multimineral treatment has no effect on mortality risk.", "title": "Multivitamin-multimineral supplementation and mortality: a meta-analysis of randomized controlled trials." }, { "docid": "MED-1178", "text": "BACKGROUND: The health benefits of organic foods are unclear. PURPOSE: To review evidence comparing the health effects of organic and conventional foods. DATA SOURCES: MEDLINE (January 1966 to May 2011), EMBASE, CAB Direct, Agricola, TOXNET, Cochrane Library (January 1966 to May 2009), and bibliographies of retrieved articles. STUDY SELECTION: English-language reports of comparisons of organically and conventionally grown food or of populations consuming these foods. DATA EXTRACTION: 2 independent investigators extracted data on methods, health outcomes, and nutrient and contaminant levels. DATA SYNTHESIS: 17 studies in humans and 223 studies of nutrient and contaminant levels in foods met inclusion criteria. Only 3 of the human studies examined clinical outcomes, finding no significant differences between populations by food type for allergic outcomes (eczema, wheeze, atopic sensitization) or symptomatic Campylobacter infection. Two studies reported significantly lower urinary pesticide levels among children consuming organic versus conventional diets, but studies of biomarker and nutrient levels in serum, urine, breast milk, and semen in adults did not identify clinically meaningful differences. All estimates of differences in nutrient and contaminant levels in foods were highly heterogeneous except for the estimate for phosphorus; phosphorus levels were significantly higher than in conventional produce, although this difference is not clinically significant. The risk for contamination with detectable pesticide residues was lower among organic than conventional produce (risk difference, 30% [CI, -37% to -23%]), but differences in risk for exceeding maximum allowed limits were small. Escherichia coli contamination risk did not differ between organic and conventional produce. Bacterial contamination of retail chicken and pork was common but unrelated to farming method. However, the risk for isolating bacteria resistant to 3 or more antibiotics was higher in conventional than in organic chicken and pork (risk difference, 33% [CI, 21% to 45%]). LIMITATION: Studies were heterogeneous and limited in number, and publication bias may be present. CONCLUSION: The published literature lacks strong evidence that organic foods are significantly more nutritious than conventional foods. Consumption of organic foods may reduce exposure to pesticide residues and antibiotic-resistant bacteria. PRIMARY FUNDING SOURCE: None.", "title": "Are organic foods safer or healthier than conventional alternatives?: a systematic review." }, { "docid": "MED-3199", "text": "It has been well established that complex mixtures of phytochemicals in fruits and vegetables can be beneficial for human health. Moreover, it is becoming increasingly apparent that phytochemicals can influence the pharmacological activity of drugs by modifying their absorption characteristics through interactions with drug transporters as well as drug-metabolizing enzyme systems. Such effects are more likely to occur in the intestine and liver, where high concentrations of phytochemicals may occur. Alterations in cytochrome P450 and other enzyme activities may influence the fate of drugs subject to extensive first-pass metabolism. Although numerous studies of nutrient-drug interactions have been published and systematic reviews and meta-analyses of these studies are available, no generalizations on the effect of nutrient-drug interactions on drug bioavailability are currently available. Several publications have highlighted the unintended consequences of the combined use of nutrients and drugs. Many phytochemicals have been shown to have pharmacokinetic interactions with drugs. The present review is limited to commonly consumed fruits and vegetables with significant beneficial effects as nutrients and components in folk medicine. Here, we discuss the phytochemistry and pharmacokinetic interactions of the following fruit and vegetables: grapefruit, orange, tangerine, grapes, cranberry, pomegranate, mango, guava, black raspberry, black mulberry, apple, broccoli, cauliflower, watercress, spinach, tomato, carrot, and avocado. We conclude that our knowledge of the potential risk of nutrient-drug interactions is still limited. Therefore, efforts to elucidate potential risks resulting from food-drug interactions should be intensified in order to prevent undesired and harmful clinical consequences. © 2011 Institute of Food Technologists®", "title": "Potential risks resulting from fruit/vegetable-drug interactions: effects on drug-metabolizing enzymes and drug transporters." }, { "docid": "MED-4406", "text": "Objective To investigate longitudinal associations between community-level gasoline price and physical activity (PA). Method In the Coronary Artery Risk Development in Young Adults study, 5,115 black and white participants aged 18–30 at baseline 1985–86 were recruited from four U.S. cities (Birmingham, Chicago, Minneapolis and Oakland) and followed over time. We used data from 3 follow-up exams: 1992–93, 1995–96, and 2000–01, when the participants were located across 48 states. From questionnaire data, a total PA score was summarized in exercise units (EU) based on intensity and frequency of 13 PA categories. Using Geographic Information Systems, participants’ residential locations were linked to county-level inflation-adjusted gasoline price data collected by the Council for Community & Economic Research. We used a random-effect longitudinal regression model to examine associations between time-varying gasoline price and time-varying PA, controlling for age, race, gender, baseline study center, and time-varying education, marital status, household income, county cost of living, county bus fare, census block-group poverty, and urbanicity. Results Holding all control variables constant, a 25-cent increase in inflation-adjusted gasoline price was significantly associated with an increase of 9.9 EU in total PA (95%CI: 0.8–19.1). Conclusion Rising prices of gasoline may be associated with an unintended increase in leisure PA.", "title": "Longitudinal trends in gasoline price and physical activity: The CARDIA study" }, { "docid": "MED-3894", "text": "The purpose of this study was to examine the effects of a natural carbohydrate (CHO) source in the form of sun-dried raisins (SDRs) vs. Sports Jelly Beans™ (SJBs) on endurance performance in trained cyclists and triathletes. Ten healthy men (18-33 years) completed 1 water-only acclimatization exercise trial and 2 randomized exercise trials administered in a crossover fashion. Each trial consisted of a 120-minute constant-intensity glycogen depletion period followed by a 10-km time trial (TT). During each experimental trial, participants consumed isocaloric amounts of SDRs or SJBs in 20-minute intervals. Measurements included time to complete 10-km TT, power output during 10-km TT, blood glucose levels and respiratory exchange ratio during glycogen depletion period, rate of perceived exertion (RPE), 'flow' questionnaire responses, and a hedonic (i.e., pleasantness) sensory acceptance test. There were no significant differences in endurance performance for TT time (SDRs vs. SJBs, 17.3 ± 0.4 vs. 17.3 ± 0.4 seconds) or power (229.3 ± 13.0 vs. 232.0 ± 13.6 W), resting blood glucose levels (5.8 ± 04 mmol·L(-1) for SDRs and 5.4 ± 0.2 mmol·L(-1) for SJBs), RPE, or flow experiences between SDR and SJB trials. However, the mean sensory acceptance scores were significantly higher for the SDRs compared to the SJBs (50.7 ± 1.7 vs. 44.3 ± 2.7). Consuming SDRs or SJBs during 120 minutes of intense cycling results in similar subsequent TT performances and are equally effective in maintaining blood glucose levels during exercise. Therefore, SDRs are a natural, pleasant, cost-effective CHO alternative to commercial SJBs that can be used during moderate- to high-intensity endurance exercise.", "title": "Sun-dried raisins are a cost-effective alternative to Sports Jelly Beans in prolonged cycling." }, { "docid": "MED-3215", "text": "The average American diet, which is high in protein and low in fruits and vegetables, generates a large amount of acid, mainly as sulfates and phosphates. The kidneys respond to this dietary acid challenge with net acid excretion, as well as ammonium and titratable acid excretion. Concurrently, the skeleton supplies buffer by active resorption of bone. Indeed, calciuria is directly related to net acid excretion. Different food proteins differ greatly in their potential acid load, and therefore in their acidogenic effect. A diet high in acid-ash proteins causes excessive calcium loss because of its acidogenic content. The addition of exogenous buffers, as chemical salts or as fruits and vegetables, to a high protein diet results in a less acid urine, a reduction in net acid excretion, reduced ammonium and titratable acid excretion, and decreased calciuria. Bone resorption may be halted, and bone accretion may actually occur. Alkali buffers, whether chemical salts or dietary fruits and vegetables high in potassium, reverse acid-induced obligatory urinary calcium loss. We conclude that excessive dietary protein from foods with high potential renal acid load adversely affects bone, unless buffered by the consumption of alkali-rich foods or supplements.", "title": "Excess dietary protein can adversely affect bone." }, { "docid": "MED-1987", "text": "OBJECTIVE: Over the last 3 decades, the prevalence of childhood obesity has increased dramatically in North America, ushering in a variety of health problems, including type 2 diabetes mellitus (T2DM), which previously was not typically seen until much later in life. This technical report describes, in detail, the procedures undertaken to develop the recommendations given in the accompanying clinical practice guideline, \"Management of Type 2 Diabetes Mellitus in Children and Adolescents,\" and provides in-depth information about the rationale for the recommendations and the studies used to make the clinical practice guideline's recommendations. METHODS: A primary literature search was conducted relating to the treatment of T2DM in children and adolescents, and a secondary literature search was conducted relating to the screening and treatment of T2DM's comorbidities in children and adolescents. Inclusion criteria were prospectively and unanimously agreed on by members of the committee. An article was eligible for inclusion if it addressed treatment (primary search) or 1 of 4 comorbidities (secondary search) of T2DM, was published in 1990 or later, was written in English, and included an abstract. Only primary research inquiries were considered; review articles were considered if they included primary data or opinion. The research population had to constitute children and/or adolescents with an existing diagnosis of T2DM; studies of adult patients were considered if at least 10% of the study population was younger than 35 years. All retrieved titles, abstracts, and articles were reviewed by the consulting epidemiologist. RESULTS: Thousands of articles were retrieved and considered in both searches on the basis of the aforementioned criteria. From those, in the primary search, 199 abstracts were identified for possible inclusion, 58 of which were retained for systematic review. Five of these studies were classified as grade A studies, 1 as grade B, 20 as grade C, and 32 as grade D. Articles regarding treatment of T2DM selected for inclusion were divided into 4 major subcategories on the basis of type of treatment being discussed: (1) medical treatments (32 studies); (2) nonmedical treatments (9 studies); (3) provider behaviors (8 studies); and (4) social issues (9 studies). From the secondary search, an additional 336 abstracts relating to comorbidities were identified for possible inclusion, of which 26 were retained for systematic review. These articles included the following: 1 systematic review of literature regarding comorbidities of T2DM in adolescents; 5 expert opinions presenting global recommendations not based on evidence; 5 cohort studies reporting natural history of disease and comorbidities; 3 with specific attention to comorbidity patterns in specific ethnic groups (case-control, cohort, and clinical report using adult literature); 3 reporting an association between microalbuminuria and retinopathy (2 case-control, 1 cohort); 3 reporting the prevalence of nephropathy (cohort); 1 reporting peripheral vascular disease (case series); 2 discussing retinopathy (1 case-control, 1 position statement); and 3 addressing hyperlipidemia (American Heart Association position statement on cardiovascular risks; American Diabetes Association consensus statement; case series). A breakdown of grade of recommendation shows no grade A studies, 10 grade B studies, 6 grade C studies, and 10 grade D studies. With regard to screening and treatment recommendations for comorbidities, data in children are scarce, and the available literature is conflicting. Therapeutic recommendations for hypertension, dyslipidemia, retinopathy, microalbuminuria, and depression were summarized from expert guideline documents and are presented in detail in the guideline. The references are provided, but the committee did not independently assess the supporting evidence. Screening tools are provided in the Supplemental Information.", "title": "Management of type 2 diabetes mellitus in children and adolescents." }, { "docid": "MED-3229", "text": "High-protein (HP) diets exert a hypercalciuric effect at constant levels of calcium intake, even though the effect may depend on the nature of the dietary protein. Lower urinary pH is also consistently observed for subjects consuming HP diets. The combination of these two effects was suspected to be associated with a dietary environment favorable for demineralization of the skeleton. However, increased calcium excretion due to HP diet does not seem to be linked to impaired calcium balance. In contrast, some data indicate that HP intakes induce an increase of intestinal calcium absorption. Moreover, no clinical data support the hypothesis of a detrimental effect of HP diet on bone health, except in a context of inadequate calcium supply. In addition, HP intake promotes bone growth and retards bone loss and low-protein diet is associated with higher risk of hip fractures. The increase of acid and calcium excretion due to HP diet is also accused of constituting a favorable environment for kidney stones and renal diseases. However, in healthy subjects, no damaging effect of HP diets on kidney has been found in either observational or interventional studies and it seems that HP diets might be deleterious only in patients with preexisting metabolic renal dysfunction. Thus, HP diet does not seem to lead to calcium bone loss, and the role of protein seems to be complex and probably dependent on other dietary factors and the presence of other nutrients in the diet.", "title": "Protein intake, calcium balance and health consequences." }, { "docid": "MED-3210", "text": "Folklore has suggested that consuming grapefruit may promote weight control. Sparse data exist to support this hypothesis, although there is some evidence of health promotion effects with regard to blood pressure control and modulation of circulating lipids. The aim of this randomized controlled trial was to prospectively evaluate the role of grapefruit in reducing body weight and blood pressure and in promoting improvements in the lipid profile in overweight adults (N = 74). Following a 3-week washout diet low in bioactive-rich fruits and vegetables, participants were randomized to either the control diet (n = 32) or daily grapefruit (n = 42) in the amount of one half of a fresh Rio-Red grapefruit with each meal (3× daily) for 6 weeks. No differences between group in weight, blood pressure, or lipids were demonstrated. Grapefruit consumption was associated with modest weight loss (-0.61 ± 2.23 kg, P = .097), a significant reduction in waist circumference (-2.45 ± 0.60 cm, P = .0002), and a significant reduction in systolic blood pressure (-3.21 ± 10.13 mm Hg, P = .03) compared with baseline values. Improvements were observed in circulating lipids of those consuming grapefruit, with total cholesterol and low-density lipoprotein significantly decreasing by -11.7 mg/dL (P = .002) and -18.7 mg/dL (P < .001), respectively, compared with baseline values. This study suggests that consumption of grapefruit daily for 6 weeks does not significantly decrease body weight, lipids, or blood pressure as compared with the control condition. However, the improvements in blood pressure and lipids demonstrated in the intervention group suggest that grapefruit should be further evaluated in the context of obesity and cardiovascular disease prevention. Copyright © 2012 Elsevier Inc. All rights reserved.", "title": "The effects of daily consumption of grapefruit on body weight, lipids, and blood pressure in healthy, overweight adults." }, { "docid": "MED-3208", "text": "This study evaluated the effect of adding fruit or oats to the diet of free-living women on energy consumption and body weight. Fruit and oat cookies had the same amount of fiber and total calories ( approximately 200 kcal), but differed in energy density. We analyzed data from a clinical trial conducted in a primary care unit in Rio de Janeiro, Brazil. Forty-nine women, ages ranging from 30 to 50 years, with body mass index (BMI)>25 kg/m2, were randomly chosen to add three apples (0.63 kcal/g energy density) or three pears (0.64 kcal/g energy density) or three oat cookies (3.7 kcal/g energy density) to their usual diet for 10 weeks. Fiber composition was similar ( approximately 6g). Statistical analysis of the repeated measures of dietary composition and body weight were analyzed using mixed model procedures. Results showed a significant decrease in the energy density during the follow-up (-1.23 kcal/g, p<0.04, and -1.29 kcal/g, p<0.05) for apples and pears, respectively, compared to the oat group. The energy intake also decreased significantly (-25.05 and -19.66 kcal/day) for the apple and pear group, respectively, but showed a small increase (+0.93) for the oat group. Apples and pears were also associated (p<0.001) with weight reduction (-0.93 kg for the apple and -0.84 for the pear group), whereas weight was unchanged (+0.21; p=0.35) in the oat group. Results suggest that energy densities of fruits, independent of their fiber amount can reduce energy consumption and body weight over time.", "title": "A low-energy-dense diet adding fruit reduces weight and energy intake in women." }, { "docid": "MED-4389", "text": "Significant benefits for diabetes prevention and management have been observed with vegetarian and especially vegan diets. This article reviews observational studies and intervention trials on such diets, and discusses their efficacy, nutritional adequacy, acceptability, and sustainability. Research to date has demonstrated that a low-fat, plant-based nutritional approach improves control of weight, glycemia, and cardiovascular risk. These studies have also shown that carefully planned vegan diets can be more nutritious than diets based on more conventional diet guidelines, with an acceptability that is comparable with that of other therapeutic regimens. Current intervention guidelines from professional organizations offer support for this approach. Vegetarian and vegan diets present potential advantages in managing type 2 diabetes that merit the attention of individuals with diabetes and their caregivers.", "title": "Usefulness of vegetarian and vegan diets for treating type 2 diabetes." }, { "docid": "MED-1988", "text": "PURPOSE OF REVIEW: To review recent literature on important topics in pediatric office practice: bullying, screening for the prediabetic state, and pediatric oral health. RECENT FINDINGS: Recent literature shows that bullying behaviors are common in children as young as kindergarten age, that there is a strong association between being a bully or victim and a range of psychosomatic and depressive symptoms in children, and that interventions including family therapy and school-based programs are effective for bullies and victims. Recent studies have further delineated glucose and insulin metabolism. Recent work has provided new models to help practitioners screen for the prediabetic state in hope of providing earlier opportunities to intervene and avoid the morbidities associated with type 2 diabetes mellitus. Recent literature emphasizes continued gaps in dental healthcare for patients who are most at risk. Recent studies emphasize the important role that diet and sealants have in preventing dental caries. SUMMARY: Recent literature emphasizes the important role that office-based pediatricians have in identifying patients who are involved in bullying, at risk of developing type 2 diabetes mellitus, or have poor dental health. Future research will help delineate these problems and provide us with refined primary prevention and treatment guidelines.", "title": "Pediatrician's role in screening and treatment: bullying, prediabetes, oral health." }, { "docid": "MED-3143", "text": "BACKGROUND: Olestra is a nonabsorbable, energy-free fat substitute. Because it is not absorbed, it may cause digestive symptoms when consumed in large amounts. OBJECTIVE: To compare the frequency and impact of gastrointestinal symptoms in adults and children who freely consume snacks containing olestra or regular snacks in the home. DESIGN: 6-week, double-blind, randomized, parallel, placebo-controlled trial. SETTING: General community. PARTICIPANTS: 3181 volunteers 2 to 89 years of age. INTERVENTION: Households received identical packages labeled as containing olestra corn or potato chips. These packages contained either olestra or regular chips (control). MEASUREMENT: Gastrointestinal symptoms and their impact on daily activities were reported in a daily record. RESULTS: At least one gastrointestinal symptom was reported by 619 of 1620 (38.2%) persons in the olestra group and 576 of 1561 (36.9%) controls (difference, 1.3 percentage points [95% CI, -3.6 to 6.2 percentage points]; P = 0.60). In general, the groups did not differ significantly in the proportion of participants who reported individual gastrointestinal symptoms; however, more controls reported nausea (8.4% compared with 5.7%; difference, -2.7 percentage points [CI, -4.9 to -0.4 percentage points]; P = 0.02). The only difference between groups for the mean numbers of days on which symptoms were reported was that participants in the olestra group had 1 more symptom-day of more frequent bowel movements than did controls (3.7 symptom-days compared with 2.8 symptom days; difference, 0.9 symptom-days [CI, 0.1 to 1.8 symptom-days]; P = 0.04). The groups did not differ in the impact of symptoms on daily activities. CONCLUSIONS: Clinically meaningful or bothersome gastrointestinal effects are not associated with unregulated consumption of olestra corn and potato chips in the home.", "title": "Gastrointestinal symptoms in 3181 volunteers ingesting snack foods containing olestra or triglycerides. A 6-week randomized, placebo-controlled trial." }, { "docid": "MED-3895", "text": "Research suggests that pre-exercise sources of dietary carbohydrate with varying glycemic indexes may differentially affect metabolism and endurance. This study was designed to examine potential differences in metabolism and cycling performance after consumption of moderate glycemic raisins vs. a high glycemic commercial sports gel. Eight endurance-trained male (n = 4) and female (n = 4) cyclists 30 +/- 5 years of age completed 2 trials in random order. Subjects were fed 1 g carbohydrate per kilogram body weight from either raisins or sports gel 45 minutes prior to exercise on a cycle ergometer at 70% V(.-)O2max. After 45 minutes of submaximal exercise, subjects completed a 15-minute performance trial. Blood was collected prior to the exercise bout, as well as after the 45th minute of exercise, to determine serum concentrations of glucose, insulin, lactate, free fatty acids (FFAs), triglycerides, and beta-hydroxybutyrate. Performance was not different (p > 0.05) between the raisin (189.5 +/- 69.9 kJ) and gel (188.0 +/- 64.8 kJ) trials. Prior to exercise, serum concentrations of glucose and other fuel substrates did not differ between trials; however, insulin was higher (p < 0.05) for the gel (110.0 +/- 70.4 microU x ml(-1)) vs. raisin trial (61.4 +/- 37.4 microU x ml(-1)). After 45 minutes of exercise, insulin decreased to 14.2 +/- 6.2 microU x ml(-1) and 13.3 +/- 18.9 microU x ml(-1) for gel and raisin trials, respectively. The FFA concentration increased (+0.2 +/- 0.1 mmol x L(-1)) significantly (p < 0.05) during the raisin trial. Overall, minor differences in metabolism and no difference in performance were detected between the trials. Raisins appear to be a cost-effective source of carbohydrate for pre-exercise feeding in comparison to sports gel for short-term exercise bouts.", "title": "Metabolic and performance effects of raisins versus sports gel as pre-exercise feedings in cyclists." }, { "docid": "MED-2759", "text": "A commercial weight loss program with a client base composed of >95% women experienced sporadic complaints of nausea and vomiting after changing its multivitamin supplier. This retrospective and observational study was designed to determine if related adverse event reports were significant, and to investigate potential mechanism for their occurrence in this group of subjects, many of whom were concurrently receiving oral contraceptives or hormone replacement therapy. Incidence of nausea, vomiting, rash, and total complaints in the 3 months following the change of the multivitamin formulation was compared with the same complaints in the 3 months before the change. In the 3 months following the multivitamin change, there were 166 complaints of nausea and vomiting, 9 complaints of rash and 194 total complaints from a group of 88,468 patients. In the 3 months before the change in the multivitamin, there had been 2 complaints of nausea and vomiting, no complaints of rash, and 11 total complaints from 88,252 patients. The difference detected by a chi-squared test was significant for all events studied; nausea and vomiting (P < 0.0001), rash (P < 0.02), and total complaints (P < 0.0001). The altered multivitamins contained added citrus bioflavanoids not included in the original formula. Citrus bioflavanoids decrease the clearance of exogenous estrogens by inhibiting cytochrome P450 enzyme systems. Elevated estrogen levels could account for the increased incidence of nausea and vomiting. This experience demonstrates that adding dietary herbal supplements to multivitamins may be associated with adverse interactions with prescription drugs.", "title": "Vomiting from multivitamins: a potential drug interaction." }, { "docid": "MED-2229", "text": "BACKGROUND/OBJECTIVES: In vitro and animal studies have reported that young broccoli sprouts improve oxidative stress status in diabetic condition. The objective of this double-blind, placebo-controlled, randomized clinical trial was to investigate the effects of broccoli sprouts powder (BSP) on some oxidative stress parameters in type 2 diabetes patients. SUBJECTS/METHODS: A total of 81 patients with type 2 diabetes were randomly assigned to one of three treatment groups for 4 weeks. The groups received either 10 g/d BSP (n=27), 5 g/d BSP (n=29) or placebo (n=25). Serum total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), malondialdehyde (MDA) and oxidized low density lipoprotein (LDL) cholesterol were measured at baseline and at 4 weeks after treatment. RESULTS: In all, 63 patients in three groups were included in the analysis: 10 g/d BSP (n=21), 5 g/d (n=22) and placebo (n=20). After 4 weeks, consumption of BSP resulted in significant decrease in MDA (P=0.001 for treatment effect), oxidized low density lipoprotein cholesterol (P=0.03 for treatment effect), OSI (P=0.001 for treatment effect) and significant increase in TAC (P=0.001 for treatment effect). No effects were found on TOS. CONCLUSION: BSP had favorable effects on oxidative stress status in type 2 diabetes patients.", "title": "Broccoli sprouts reduce oxidative stress in type 2 diabetes: a randomized double-blind clinical trial." }, { "docid": "MED-3203", "text": "The contents of the bioactive compounds in red and blond grapefruits and their influence on humans suffering from hypertriglyceridemia were studied. It was found that red grapefruit has a higher content of bioactive compounds and a higher antioxidant potential than blond grapefruit, determined by oxygen radical scavenging capacity, 1,1-diphenyl-2-picrylhydrazyl, carotenoid bleaching, and Folin-Ciocalteu assays. Fifty-seven hyperlipidemic patients, ages 39-72 years, after coronary bypass surgery, recruited from the Institute's pool of volunteers, were randomly divided into three equal in number (19) groups: two experimental (red and blond groups) and one control group (CG). During 30 consecutive days of the investigation the diets of the patients of the red and blond dietary groups were daily supplemented with one equal in weight fresh red or blond grapefruit, respectively. Before and after this trial, serum lipid levels of all fractions and serum antioxidant activity were determined. It was found that serum lipid levels in patients of the red and blond groups versus the CG after treatment were decreased: (a) total cholesterol, 6.69 versus 7.92 mmol/L, 15.5%, and 7.32 versus 7.92 mmol/L, 7.6%, respectively; (b) low-density lipoprotein cholesterol, 5.01 versus 6.29 mmol/L, 20.3%, and 5.62 versus 6.29 mmol/L, 10.7%, respectively; (c) triglycerides, 1.69 versus 2.32 mmol/L, 17.2%, and 2.19 versus 2.32 mmol/L, 5.6%, respectively. No changes in the serum lipid levels in patients of the CG were found. In conclusion, fresh red grapefruit contains higher quantities of bioactive compounds and has significantly higher antioxidant potential than blond grapefruit. Diet supplemented with fresh red grapefruit positively influences serum lipid levels of all fractions, especially serum triglycerides and also serum antioxidant activity. The addition of fresh red grapefruit to generally accepted diets could be beneficial for hyperlipidemic, especially hypertriglyceridemic, patients suffering from coronary atherosclerosis.", "title": "Red grapefruit positively influences serum triglyceride level in patients suffering from coronary atherosclerosis: studies in vitro and in humans." }, { "docid": "MED-2202", "text": "The overall objective of this chapter is to review the past, present, and future role of the sweet potato (Ipomoea batatas [L.] Lam) in human nutrition. Specifically, the chapter describes the role of the sweet potato in human diets; outlines the biochemical and nutritional composition of the sweet potato with emphasis on its beta-carotene and anthocyanin contents; highlights sweet potato utilization, and its potential as value-added products in human food systems; and demonstrates the potential of the sweet potato in the African context. Early records have indicated that the sweet potato is a staple food source for many indigenous populations in Central and South Americas, Ryukyu Island, Africa, the Caribbean, the Maori people, Hawaiians, and Papua New Guineans. Protein contents of sweet potato leaves and roots range from 4.0% to 27.0% and 1.0% to 9.0%, respectively. The sweet potato could be considered as an excellent novel source of natural health-promoting compounds, such as beta-carotene and anthocyanins, for the functional food market. Also, the high concentration of anthocyanin and beta-carotene in sweet potato, combined with the high stability of the color extract make it a promising and healthier alternative to synthetic coloring agents in food systems. Starch and flour processing from sweet potato can create new economic and employment activities for farmers and rural households, and can add nutritional value to food systems. Repositioning sweet potato production and its potential for value-added products will contribute substantially to utilizing its benefits and many uses in human food systems. Multidisciplinary, integrated research and development activities aimed at improving production, storage, postharvest and processing technologies, and quality of the sweet potato and its potential value-added products are critical issues, which should be addressed globally.", "title": "Sweet potato: a review of its past, present, and future role in human nutrition." }, { "docid": "MED-1978", "text": "Context Nearly 80% of antibiotics in the United States are sold for use in livestock feeds. The manure produced by these livestock contains antibiotic-resistant bacteria, resistance genes, and antibiotics, and is subsequently applied to crop fields where it may put community members at risk for antibiotic-resistant infections. Objective To assess the association between individual exposure to swine and dairy/veal industrial agriculture and risk of methicillin-resistant Staphylococcus aureus (MRSA) infection. Design, Setting, and Participants A population-based, nested case-control study of Geisinger primary care patients in Pennsylvania from 2005–2010. Incident MRSA cases were identified using electronic health records, classified as community-associated or healthcare-associated, and frequency-matched to randomly selected controls and patients with skin and soft tissue infection. Nutrient management plans were used to create two exposure variables: seasonal crop field manure application and number of livestock at the operation. In a sub-study we collected 200 isolates from patients stratified by location of diagnosis and proximity to livestock operations. Main outcome measures Community-associated MRSA, healthcare associated-MRSA, and skin and soft tissue infection status (with no history of MRSA) compared to controls. Results From 446,480 patients, 1539 community-associated MRSA, 1335 healthcare-associated MRSA, 2895 skin and soft tissue infection cases, and 2914 controls were included. After adjustment for MRSA risk factors, the highest quartile of swine crop field exposure was significantly associated with community-associated MRSA, healthcare-associated MRSA, and skin and soft tissue infection case status (adjusted odds ratio, 1.38 [95% CI, 1.13–1.69], 1.30 [95% CI, 1.05–1.61], and 1.37 [95% CI, 1.18–1.60], respectively); and there was a trend of increasing odds across quartiles for each outcome (all P for trend ≤0.01). There were similar but weaker associations of swine operations with community-associated MRSA and skin and soft tissue infection. Molecular testing of 200 isolates identified 31 unique spa types, none of which corresponded to CC398, but some have been previously found in swine. Conclusion Proximity to swine manure application to crop fields and livestock operations each was associated with MRSA and skin and soft tissue infection. These findings contribute to the growing concern about the potential public health impacts of high-density livestock production.", "title": "High-density livestock operations, crop field application of manure, and risk of community-associated methicillin-resistant Staphylococcus aureus infection, Pennsylvania, USA" }, { "docid": "MED-3205", "text": "Grapefruit inhibits cytochrome P450 3A4 and may affect estrogen metabolism. In the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined the relationships of grapefruit intake with risk of breast cancer and with serum sex hormone levels. 114,504 women with information on dietary intake of grapefruit and on reproductive and lifestyle risk factors were followed for a median 9.5 years and 3,747 incident breast cancers were identified. Fifty-nine percent of women reported eating grapefruit, 4% ate > or = 60 g/day. Cox proportional hazard models were used to estimate the hazard ratio (HR) for breast cancer according to grapefruit intake, adjusting for study centre, reproductive factors, body mass index, energy intake, and alcohol intake. Grapefruit intake was not related to the risk of breast cancer: compared with women who ate no grapefruit, women with the highest intake of > or =60 g/day had a HR of 0.93 (95% CI 0.77-1.13), p for linear trend = 0.5. There was no relationship between grapefruit intake and breast cancer risk among premenopausal women, all postmenopausal women, or postmenopausal women categorized by hormone replacement therapy use (all p>0.05). There was no association between grapefruit intake and estradiol or estrone among postmenopausal women. In this study, we found no evidence of an association between grapefruit intake and risk of breast cancer.", "title": "Prospective study of the association between grapefruit intake and risk of breast cancer in the European Prospective Investigation into Cancer and ..." }, { "docid": "MED-1179", "text": "The US market for organic foods has grown from $3.5 billion in 1996 to $28.6 billion in 2010, according to the Organic Trade Association. Organic products are now sold in specialty stores and conventional supermarkets. Organic products contain numerous marketing claims and terms, only some of which are standardized and regulated. In terms of health advantages, organic diets have been convincingly demonstrated to expose consumers to fewer pesticides associated with human disease. Organic farming has been demonstrated to have less environmental impact than conventional approaches. However, current evidence does not support any meaningful nutritional benefits or deficits from eating organic compared with conventionally grown foods, and there are no well-powered human studies that directly demonstrate health benefits or disease protection as a result of consuming an organic diet. Studies also have not demonstrated any detrimental or disease-promoting effects from an organic diet. Although organic foods regularly command a significant price premium, well-designed farming studies demonstrate that costs can be competitive and yields comparable to those of conventional farming techniques. Pediatricians should incorporate this evidence when discussing the health and environmental impact of organic foods and organic farming while continuing to encourage all patients and their families to attain optimal nutrition and dietary variety consistent with the US Department of Agriculture's MyPlate recommendations. This clinical report reviews the health and environmental issues related to organic food production and consumption. It defines the term \"organic,\" reviews organic food-labeling standards, describes organic and conventional farming practices, and explores the cost and environmental implications of organic production techniques. It examines the evidence available on nutritional quality and production contaminants in conventionally produced and organic foods. Finally, this report provides guidance for pediatricians to assist them in advising their patients regarding organic and conventionally produced food choices.", "title": "Organic foods: health and environmental advantages and disadvantages." }, { "docid": "MED-3813", "text": "Cinnamon can improve fasting glucose in humans yet data on insulin sensitivity are limited and controversial. Eight male volunteers (aged 25 +/- 1 years, body mass 76.5 +/- 3.0 kg, BMI 24.0 +/- 0.7 kg m(-2); mean +/- SEM) underwent two 14-day interventions involving cinnamon or placebo supplementation (3 g day(-1)). Placebo supplementation was continued for 5 days following this 14 day period. Oral glucose tolerance tests (OGTT) were performed on days 0, 1, 14, 16, 18, and 20. Cinnamon ingestion reduced the glucose response to OGTT on day 1 (-13.1 +/- 6.3% vs. day 0; P < 0.05) and day 14 (-5.5 +/- 8.1% vs. day 0; P = 0.09). Cinnamon ingestion also reduced insulin responses to OGTT on day 14 (-27.1 +/- 6.2% vs. day 0; P < 0.05), as well as improving insulin sensitivity on day 14 (vs. day 0; P < 0.05). These effects were lost following cessation of cinnamon feeding. Cinnamon may improve glycaemic control and insulin sensitivity, but the effects are quickly reversed.", "title": "Changes in glucose tolerance and insulin sensitivity following 2 weeks of daily cinnamon ingestion in healthy humans." }, { "docid": "MED-2830", "text": "OBJECTIVE: The aim of this work was to determine the bioavailability of herbs and spices after human consumption by measuring the ability to protect lymphocytes from an oxidative injury and by examining the impact on inflammatory biomarkers in activated THP-1 cells. METHODS: Ten to 12 subjects in each of 13 groups consumed a defined amount of herb or spice for 7 days. Blood was drawn from subjects before consumption and 1 hour after taking the final herb or spice capsules. Subject serum and various extractions of the herbs and spices were analyzed for antioxidant capacity by oxygen radical absorbance capacity (ORAC) analysis or by 1,1-diphenyl-2-picrylhydrzyl (DPPH). Subject peripheral blood mononuclear cells (PBMCs) in medium with10% autologous serum were incubated with hydrogen peroxide to induce DNA strand breaks. Subject serum was also used to treat activated THP-1 cells to determine relative quantities of 3 inflammatory cytokine (tumor necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and IL-6) mRNAs. RESULTS: Herbs and spices that protected PBMCs against DNA strand breaks were paprika, rosemary, ginger, heat-treated turmeric, sage, and cumin. Paprika also appeared to protect cells from normal apoptotic processes. Of the 3 cytokine mRNAs studied (TNF-α, IL-1α, and IL-6), TNF-α was the most sensitive responder to oxidized LDL-treated macrophages. Clove, ginger, rosemary, and turmeric were able to significantly reduce oxidized LDL-induced expression of TNF-α. Serum from those consuming ginger reduced all three inflammatory biomarkers. Ginger, rosemary, and turmeric showed protective capacity by both oxidative protection and inflammation measures. CONCLUSIONS: DNA strand breaks and inflammatory biomarkers are a good functional measure of a food's bioavailability.", "title": "Bioavailability of herbs and spices in humans as determined by ex vivo inflammatory suppression and DNA strand breaks." }, { "docid": "MED-2209", "text": "This study investigated the effect of different traditional cooking methods on glycemic index (GI) and glycemic response of ten Sweet potato (Ipomoea batatas) cultivars commonly eaten in Jamaica. Matured tubers were cooked by roasting, baking, frying, or boiling then immediately consumed by the ten nondiabetic test subjects (5 males and 5 females; mean age of 27 ± 2 years). The GI varied between 41 ± 5–93 ± 5 for the tubers studied. Samples prepared by boiling had the lowest GI (41 ± 5–50 ± 3), while those processed by baking (82 ± 3–94 ± 3) and roasting (79 ± 4–93 ± 2) had the highest GI values. The study indicates that the glycemic index of Jamaican sweet potatoes varies significantly with the method of preparation and to a lesser extent on intravarietal differences. Consumption of boiled sweet potatoes could minimize postprandial blood glucose spikes and therefore, may prove to be more efficacious in the management of type 2 diabetes mellitus.", "title": "Relationship between Processing Method and the Glycemic Indices of Ten Sweet Potato (Ipomoea batatas) Cultivars Commonly Consumed in Jamaica" }, { "docid": "MED-1180", "text": "The effects of extracts from five cultivars of strawberries on the proliferation of colon cancer cells HT29 and breast cancer cells MCF-7 were investigated, and possible correlations with the levels of several antioxidants were analyzed. In addition, the effects of organic cultivation compared to conventional cultivation on the content of antioxidants in the strawberries and strawberry extracts on the cancer cell proliferation were investigated. The ratio of ascorbate to dehydroascorbate was significantly higher in the organically cultivated strawberries. The strawberry extracts decreased the proliferation of both HT29 cells and MCF-7 cells in a dose-dependent way. The inhibitory effect for the highest concentration of the extracts was in the range of 41-63% (average 53%) inhibition compared to controls for the HT29 cells and 26-56% (average 43%) for MCF-7 cells. The extracts from organically grown strawberries had a higher antiproliferative activity for both cell types at the highest concentration than the conventionally grown, and this might indicate a higher content of secondary metabolites with anticarcinogenic properties in the organically grown strawberries. For HT29 cells, there was a negative correlation at the highest extract concentration between the content of ascorbate or vitamin C and cancer cell proliferation, whereas for MCF-7 cells, a high ratio of ascorbate to dehydroascorbate correlated with a higher inhibition of cell proliferation at the second highest concentration. The significance of the effect of ascorbate on cancer cell proliferation might lie in a synergistic action with other compounds.", "title": "Antioxidant levels and inhibition of cancer cell proliferation in vitro by extracts from organically and conventionally cultivated strawberries." }, { "docid": "MED-2323", "text": "Low molecular weight phenols of plant origin are undoubtedly semiochemicals although not all of them can be easily classified as typical allelochemicals, which straightforwardly benefit the releaser. We have selected and surveyed this particular class of secondary metabolites, which shares high chemical reactivity with intrinsic biocompatibility and affinity for variety of molecular targets gained through evolution, because their suitability as prospective lead compounds for medicinal chemistry seems high but relatively unexplored. In particular, plant phenolics could be perceived as a natural product library, which contains privileged scaffolds, as evidenced by examples of endogenous phenols, phytochemicals containing aryl hydroxyl groups and phenolic synthetic drugs. It is postulated that application of bio-chemo-informatic tools to such library can be helpful in pulling out new drug candidates as well as in validating ADMET compatibility and suitability of the old ones. After short survey of structural diversity represented by plant phenolics, we focus on the compounds which either have obvious dietary significance or rich record of pharmacological studies, or both. It can be seen that apart from growing use of phytochemicals in dietary supplements, slow progress through clinical trials towards new drug registration is observed in that category of natural products. Such waste of resources on the way of transformation from renewable materials to high tech/high value products aimed for improved human healthcare is deplorable and should be reformed in name of sustainability. We attempt to answer the question why popular plant phenolics with well established health benefits and reasonably well recognized molecular pharmacology (such as: catechins, curcumin, resveratrol, quercetin and its glycosides, genistein, silymarin) have difficulties in attaining registered drug or even IND level.", "title": "Plant phenolics as drug leads -- what is missing?" }, { "docid": "MED-1759", "text": "Background Livestock-Associated MRSA (LA-MRSA) belonging to ST398 lineage, common among pigs and other animals, emerged in Central and Northern Europe, becoming a new risk factor for MRSA among farm workers. Strains belonging to ST398 can be responsible for human colonization and infection, mainly in areas with high livestock-farming. The aim of this study was to investigate the occurrence of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) human colonization and infections in an area of the Lombardy Region (Italy), the Italian region with the highest density of pig farming. Methods In the period March-April 2010, 879 nasal swabs were taken from subjects at admission to a local hospital serving an area of the Lombardy Region devoted to agriculture and farming. In the period March 2010-February 2011, all MRSA strains from community-acquired infection (CAI) observed in the same hospital, were collected. Molecular characterization of the isolates included SCCmec typing, spa typing and multilocus sequence typing (MLST). Results Out of 879 nasal swabs examined, 9 (1%) yielded MRSA. Five strains were assigned to sequence type (ST)398 (spa t899, 3 isolates; t108 and t2922, 1 isolate each) and were therefore categorized as LA-MRSA. The other 4 isolates were likely of hospital origin. No strains were positive for Panton-Valentine Leukocidin genes. Twenty MRSA isolates were detected from CAI, 17 were from skin and soft-tissue infections and 3 from other infections. An MRSA isolate from otitis externa was t899/ST398 and PVL-negative, hence categorized as LA-MRSA. Four isolates were assigned to t127/ST1. Eight strains were PVL-positive community acquired (CA)-MRSA and belonged to different clones, the most frequent being ST8. Conclusions In an area of Italy with high density of pig farming, LA-MRSA is able to colonize the population and rarely to produce infections. Typical CA-MRSA is more common than LA-MRSA among CAI.", "title": "Livestock-associated methicillin-resistant Staphylococcus aureus responsible for human colonization and infection in an area of Italy with high density of pig farming" }, { "docid": "MED-1991", "text": "The objective of this article is to review the epidemiologic literature examining the role of plant foods and plant-based diets in the prevention of childhood obesity. Available data suggest a protective effect of ready-to-eat cereal on risk of obesity, although prospective studies are still needed. Studies on fruit and vegetables; grains other than cereal; high-protein foods, including beans, legumes, and soy; fiber; and plant-based dietary patterns are inconsistent or generally null. The evidence base is limited, and most studies are fraught with methodologic limitations, including cross-sectional design, inadequate adjustment for potential confounders, and lack of consideration of reporting errors, stage of growth, and genetic influences. Well-designed prospective studies are needed. The lack of evidence showing an association between plant-based diets and childhood obesity does not mean that such diets should not be encouraged. Plant foods are highlighted in the Dietary Guidelines for Americans, and children do not meet the current recommendations for most plant foods. Although the advice to consume a plant-based, low-energy-dense diet is sound, ethical questions arise concerning the relatively high price of these diets in the United States and the way in which such diets are perceived in other parts of the world. Reducing the burden of childhood obesity, eliminating health disparities, and preventing the further spread of the disease around the globe will require not only policy interventions to ensure that plant foods are affordable and accessible to children of all income levels but also awareness of sociocultural norms that affect consumption.", "title": "Plant foods and plant-based diets: protective against childhood obesity?" }, { "docid": "MED-3142", "text": "AIM: Soy foods are the major source of isoflavones, which are believed to play important roles in genesis of breast cancer and its progression. We here conducted a prospective study to evaluate the association of soy isoflavone food consumption with breast cancer prognosis. METHODS: A prospective study was performed from January 2004 and January 2006 in China. Trained interviewers conducted face-to-face interviews using a structured questionnaire to collect information on dietary habits and potential confounding factors. The relative risk [hazard ratio (HR)] and 95% CI were calculated from the Cox regression model for all significant predictors from cancer diagnosis to the endpoint of the study (event). RESULTS: After a median follow up of 52.1 months (range, 9-60 months), a total of 79 breast cancer related deaths were recorded in our study, risk being inversely associated with a high intake of soy isoflavone. With an average intake of soy isoflavone above 17.3 mg/day, the mortality of breast cancer can be reduced by about 38-36%. We also found the decreased breast cancer death with high soy protein intake, with a HR (95% CI) of 0.71 (0.52-0.98). Stratified analysis with reference to the ER status, further demonstrated a better prognosis of ER positive breast cancer with a high intake of soy isoflavone (HR 0.59, 0.40-0.93). CONCLUSION: Our study shows the soy food intake is associated with longer survival and low recurrence among breast cancer patients. A cohort study with a larger sample size and long term follow-up is now needed.", "title": "Positive effects of soy isoflavone food on survival of breast cancer patients in China." }, { "docid": "MED-2760", "text": "Context Multivitamin preparations are the most common dietary supplement, taken by at least one-third of all US adults. Limited observational studies have not provided evidence regarding associations of multivitamin use with total and site-specific cancer incidence or mortality. Objective To determine whether long-term multivitamin supplementation decreases the risk of total and site-specific cancer events among men. Design The Physicians’ Health Study II is a randomized, double-blind, placebo-controlled trial of a common multivitamin that began in 1997 with treatment and follow-up through June 1, 2011. Setting and Participants A total of 14,641 male U.S. physicians initially aged ≥50 years (mean [± SD] age; 64.3 [± 9.2] years), including 1,312 men with a history of cancer at randomization, were enrolled. Intervention Daily multivitamin, as Centrum Silver. Main Outcome Measures A primary outcome was total cancer (excluding non-melanoma skin cancer), with prostate, colorectal, and other site-specific cancers among secondary endpoints included in this report. Results During a median (interquartile range) follow-up of 11.2 (10.7 to 13.3) years, there were 2,669 men with confirmed cancer, including 1,373 cases of prostate cancer and 210 cases of colorectal cancer. Compared with placebo, men taking a daily multivitamin had a statistically significant reduction in the incidence of total cancer (active and placebo multivitamin groups, 17.0 and 18.3 events, respectively, per 1,000 person-years; hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.86–0.998; P=0.044). There was no significant effect of a daily multivitamin on prostate cancer (HR, 0.98; 95% CI, 0.88–1.09; P=0.76), colorectal cancer (HR, 0.89; 95% CI, 0.68–1.17; P=0.39), or other site-specific cancers There was a lower risk of cancer mortality that did not reach statistical significance (HR, 0.88; 95% CI, 0.77–1.01; P=0.07). Daily multivitamin use was associated with a reduction in total cancer among 1,312 men with a baseline history of cancer (HR, 0.73; 95% CI, 0.56–0.96; P=0.022), but this did not differ significantly from that among 13,329 men initially free of cancer (HR, 0.94; 95% CI, 0.87–1.02; P=0.15) (P, interaction = 0.07). Conclusions In this large prevention trial of male physicians, daily multivitamin supplementation modestly but significantly reduced the risk of total cancer.", "title": "Multivitamins in the Prevention of Cancer in Men: The Physicians’ Health Study II Randomized Controlled Trial" }, { "docid": "MED-3769", "text": "OBJECTIVE: To compare differences across food groups for food cost, energy, and nutrient profiles of 100 items from a cross-sectional survey of 225 stores in 18 counties across the Lower Mississippi Delta of Arkansas, Louisiana, and Mississippi. METHODS: Energy, nutrient, and cost profiles for food items were calculated by using Naturally Nutrient Rich methodology and converting price per 100 g edible portion to price per serving. Foods were grouped into 6 food groups. Mean differences were compared with ANOVA. RESULTS: Significant differences existed by food group for each measure. Energy density was highest for fats/oils/sweets, whereas nutrient density was highest for vegetables. Price per serving was lowest for fats/oils/sweets and highest for meats. CONCLUSIONS AND IMPLICATIONS: Educational messages focusing on a complete diet should consider the role of food costs and provide specific recommendations for increasing nutrient-dense foods by replacing a portion of the meat serving at meals with culturally acceptable lower-cost nutrient-dense foods. Copyright © 2012 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.", "title": "Energy density, nutrient adequacy, and cost per serving can provide insight into food choices in the lower Mississippi Delta." }, { "docid": "MED-1994", "text": "PURPOSE OF REVIEW: The prevalence of obesity in youth is increasing alarmingly among children and adolescents in the United States. The problem falls disproportionately on African-American and Hispanic children. Many of the metabolic and cardiovascular complications associated with obesity are already present during childhood and are closely linked to the concomitant insulin resistance/hyperinsulinemia and degree of obesity. Moreover, these co-morbidities persist into adulthood. RECENT FINDINGS: The progression from normal glucose tolerance to type 2 diabetes mellitus involves an intermediate stage known as prediabetes or impaired glucose regulation. Prediabetes is characterized by peripheral insulin-resistance and impaired glucose sensitivity of first-phase insulin secretion. On the other hand, in overt type 2 diabetes mellitus beta-cell failure becomes fully manifested. Progression from prediabetes to type 2 diabetes mellitus in youth is characterized by marked weight gain and further reduction in insulin secretion and insulin resistance. SUMMARY: Reverting obesity through lifestyle modification, that involves nutrition education, behavior modification and exercise, is an important step to prevent the progression to diabetes.", "title": "Prediabetes and type 2 diabetes in youth: an emerging epidemic disease?" }, { "docid": "MED-3812", "text": "AIMS: Various spices display insulin-potentiating activity in vitro, and in particular, cinnamon spice and its phenolic extracts have been shown to exhibit these capabilities. In vivo study shows that cinnamon may have beneficial effects on glucose homeostasis; therefore the aim of this study was to further investigate this phenomenon in humans. METHODS: Seven lean healthy male volunteers, aged 26 +/- 1 years, body mass index 24.5 +/- 0.3 kg/m(2) (mean +/- s.e.m.), underwent three oral glucose tolerance tests (OGTT) supplemented with either a 5 g placebo (OGTT(control)), 5 g of cinnamon (OGTT(cin)), or 5 g of cinnamon taken 12 h before (OGTT(cin12hpre)) in a randomized-crossover design. RESULTS: Cinnamon ingestion reduced total plasma glucose responses (AUC) to oral glucose ingestion [-13% and -10% for OGTT(cin) (p < 0.05) and OGTT(cin12hpre) (p < 0.05), respectively], as well as improving insulin sensitivity as assessed by insulin sensitivity index measures based on Matsuda's model in both OGTT(cin) (p < 0.05) and OGTT(cin12hpre) (p < 0.05) trials compared with OGTT(control). CONCLUSIONS: These data illustrate that cinnamon spice supplementation may be important to in vivo glycaemic control and insulin sensitivity in humans, and not only are its effects immediate, they also appear to be sustained for 12 h.", "title": "Effects of short-term cinnamon ingestion on in vivo glucose tolerance." }, { "docid": "MED-1998", "text": "The growing epidemic of type 2 diabetes is one of the leading causes of premature morbidity and mortality worldwide, mainly due to the micro- and macrovascular complications associated with the disease. A growing body of evidence suggests that although the risk of developing complications is greater with glucose levels beyond the established threshold for diagnosis--increasing in parallel with rising hyperglycemia-individuals with glucose levels in the prediabetic range are already at increased risk. Early intervention, ideally as soon as abnormalities in glucose homeostasis are detected, is of great importance to minimize the burden of the disease. However, as the early stages of the disease are asymptomatic, diagnosing prediabetes and early overt type 2 diabetes is challenging. The aim of this article is to discuss these challenges, the benefits of early intervention--with emphasis on the prevention trials showing that progression to type 2 diabetes can be delayed by addressing prediabetes--and the existing evidence-based guidelines that have been drawn to optimize the standards of care at the prediabetes and overt type 2 diabetes stages. Copyright © 2013. Published by Elsevier Inc.", "title": "The early treatment of type 2 diabetes." }, { "docid": "MED-2206", "text": "Sweet potato is one of the crops selected for NASA's Advanced Life Support Program for potential long-duration lunar/Mars missions. This article presents recipes of products made from sweet potato and determines the consumer acceptability of products containing from 6% to 20% sweet potato on a dry weight basis. These products were developed for use in nutritious and palatable meals for future space explorers. Sensory evaluation (appearance/color, aroma, texture, flavor/taste, and overall acceptability) studies were conducted to determine the consumer acceptability of vegetarian products made with sweet potato using panelists at NASA/Johnson Space Center in Houston, TX. None of these products including the controls, contained any ingredient of animal origin with the exception of sweet potato pie. A 9-point hedonic scale (9 being like extremely and 1 being dislike extremely) was used to evaluate 10 products and compare them to similar commercially available products used as controls. The products tested were pancakes, waffles, tortillas, bread, pie, pound cake, pasta, vegetable patties, doughnuts, and pretzels. All of the products were either liked moderately or liked slightly with the exception of the sweet potato vegetable patties, which were neither liked nor disliked. Mean comparisons of sensory scores of sweet potato recipes and their controls were accomplished by using the Student t-test. Because of their nutritional adequacy and consumer acceptability, these products are being recommended to NASA's Advanced Life Support Program for inclusion in a vegetarian menu plan designed for lunar/Mars space missions.", "title": "Consumer acceptance of vegetarian sweet potato products intended for space missions." }, { "docid": "MED-2823", "text": "Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical which has a variety of biological activities: anti-inflammatory and anti-oxidative. In this review we discuss the biological mechanisms and possible clinical effects of curcumin treatment on cancer therapy, and neurodegenerative diseases such as Alzheimer's Disease, with particular attention to the cell death processes induced by curcumin. Since oxidative stress and inflammation are major determinants of the aging process, we also argue that curcumin can have a more general effect that slows down the rate of aging. Finally, the effects of curcumin can be described as xenohormetic, since it activates a sort of stress response in mammalian cells.", "title": "Curcumin in Cell Death Processes: A Challenge for CAM of Age-Related Pathologies" }, { "docid": "MED-1997", "text": "The increased prevalence of childhood overweight and obesity is not unique to industrialized societies; dramatic increases are occurring in urbanized areas of developing countries. In light of the consensus that obesity is a significant public health concern and that many weight-loss interventions have been unsuccessful in the long term, an exploration of food patterns that are beneficial in the primary prevention of obesity is warranted. The focus of this article is to review the relation between vegetarian diets and obesity, particularly as they relate to childhood obesity. Epidemiologic studies indicate that vegetarian diets are associated with a lower body mass index (BMI) and a lower prevalence of obesity in adults and children. A meta-analysis of adult vegetarian diet studies estimated a reduced weight difference of 7.6 kg for men and 3.3 kg for women, which resulted in a 2-point lower BMI (in kg/m(2)). Similarly, compared with nonvegetarians, vegetarian children are leaner, and their BMI difference becomes greater during adolescence. Studies exploring the risk of overweight and food groups and dietary patterns indicate that a plant-based diet seems to be a sensible approach for the prevention of obesity in children. Plant-based diets are low in energy density and high in complex carbohydrate, fiber, and water, which may increase satiety and resting energy expenditure. Plant-based dietary patterns should be encouraged for optimal health and environmental benefits. Food policies are warranted to support social marketing messages and to reduce the cultural and economic forces that make it difficult to promote plant-based dietary patterns.", "title": "Vegetarian diets and childhood obesity prevention." }, { "docid": "MED-3141", "text": "OBJECTIVE: To evaluate the associations with chronic disease risk and mortality of the consequences of bean-free diets in Taiwanese adults with regard to gender. DESIGN: A sub-sample of the National Health Interview Survey (NHIS) in 2001 agreed to physical examination in the subsequent year. This group then took part in the Taiwanese Survey of Hyperglycaemia, Hyperlipidaemia and Hypertension (TwSHHH) in 2002. SETTING: Individual records were linked to the eventual death files from 2002 to 2008. SUBJECTS: Up to the end of 2008, a total of 2820 men and 2950 women were tracked by death registry over the 6·8 years of follow-up. RESULTS: Among 38,077 person-years, an average follow-up 6·5 years, 225 all-cause deaths were identified. Generalized linear models showed beans to be favourable for metabolic syndrome (other than for fasting glucose) in men; in women, beans were favourable for waist circumference and HbA1c. Cumulative logistic regression models for the effect of a bean-free diet on metabolic syndrome scores according to the Taiwanese-modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-tw) gave adjusted odds ratios of 1·83 in men and 1·45 in women. Cox regression models for the bean-free diet showed an increased hazard ratio for all-cause mortality among women (1·98, 95% CI 1·03, 3·81) but not men (1·28, 95% CI 0·76, 2·16). CONCLUSIONS: A bean-free diet may play a role in developing the metabolic syndrome in both genders, and is a significant predictor of all-cause mortality in Taiwanese women but not men.", "title": "A bean-free diet increases the risk of all-cause mortality among Taiwanese women: the role of the metabolic syndrome." }, { "docid": "MED-3200", "text": "In vitro and in vivo studies have shown that cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of oestrogens. There is evidence that grapefruit, an inhibitor of CYP3A4, increases plasma oestrogen concentrations. Since it is well established that oestrogen is associated with breast cancer risk, it is plausible that regular intake of grapefruit would increase a woman's risk of breast cancer. We investigated the association of grapefruit intake with breast cancer risk in the Hawaii–Los Angeles Multiethnic Cohort Study, a prospective cohort that includes over 50 000 postmenopausal women from five racial/ethnic groups. A total of 1657 incident breast cancer cases were available for analysis. Grapefruit intake was significantly associated with an increased risk of breast cancer (relative risk=1.30, 95% confidence interval 1.06–1.58) for subjects in the highest category of intake, that is, one-quarter grapefruit or more per day, compared to non-consumers (Ptrend=0.015). An increased risk of similar magnitude was seen in users of oestrogen therapy, users of oestrogen+progestin therapy, and among never users of hormone therapy. Grapefruit intake may increase the risk of breast cancer among postmenopausal women.", "title": "Prospective study of grapefruit intake and risk of breast cancer in postmenopausal women: the Multiethnic Cohort Study" }, { "docid": "MED-2201", "text": "Measuring food prices per gram, rather than per calorie, is one way to make healthful vegetables appear less expensive. However, a better measure of affordability would take the nutrient content of vegetables into account. This study, based on analyses of US Department of Agriculture datasets, aimed to identify which vegetables, including juices and soups, provided the most nutrients per unit cost. Nutrient density was measured using the Nutrient Rich Foods (NRF) index, based on nine nutrients to encourage: protein; fiber; vitamins A, C, and E; calcium; iron; magnesium; and potassium; and on three nutrients to limit: saturated fat, added sugar, and sodium. Food cost in dollars was calculated per 100 g, per 100 kcal, per serving, and per nutrient content. One-way analyses of variance with post hoc tests were used to determine statistical significance. Results showed that tomato juices and tomato soups, dark green leafy and nonleafy vegetables, and deep yellow vegetables, including sweet potatoes, had the highest NRF scores overall. Highest NRF scores per dollar were obtained for sweet potatoes, white potatoes, tomato juices and tomato soups, carrots, and broccoli. Tomato sauces, raw tomatoes, and potato chips were eaten more frequently than were many other vegetables that were both more affordable and more nutrient-rich. These new measures of affordable nutrition can help foodservice and health professionals identify those vegetables that provide the highest nutrient density per unit cost. Processed vegetables, including soups and juices, can contribute to the quality and the affordability of the diet. Copyright © 2013 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.", "title": "New metrics of affordable nutrition: which vegetables provide most nutrients for least cost?" }, { "docid": "MED-3770", "text": "Background: Comparisons of the cost of different foods relative to their energy and nutritive value were conducted in the 1800s by the US Department of Agriculture (USDA). Objective: The objective was to reestablish the relations between food cost, energy, and nutrients by using contemporary nutrient composition and food prices data from the USDA. Design: The USDA Food and Nutrient Database for Dietary Studies 1.0 (FNDDS 1.0) and the Center for Nutrition Policy and Promotion food prices database were used for analysis. For 1387 foods, key variables were as follows: energy density (kcal/g), serving size (g), unit price ($/100 g), serving price ($/serving), and energy cost ($/kcal). A regression model tested associations between nutrients and unit price ($/100 g). Comparisons between food groups were tested by using one-factor analyses of variance. Relations between energy density and price within food groups were tested by using Spearman's correlations. Results: Grains and fats food groups supplied the lowest-cost dietary energy. The energy cost for vegetables was higher than that for any other food group except for fruit. Serving sizes increased with water content and varied inversely with energy density of foods. The highest prices per serving were for meats, poultry, and fish, and the lowest prices per serving were for the fats category. Although carbohydrates, sugar, and fat were associated with lower price per 100 g, protein, fiber, vitamins, and minerals were associated with higher price per 100 g, after adjustment for energy. Conclusions: Grains and sugars food groups were cheaper than vegetables and fruit per calorie and were cheaper than fruit per serving. These price differentials may help to explain why low-cost, energy-dense foods that are nutrient poor are associated with lower education and incomes.", "title": "The cost of US foods as related to their nutritive value" }, { "docid": "MED-3806", "text": "BACKGROUND: Unpleasant and frightening side effects associated with the abuse of nutmeg occasionally generate emergency department referrals. We report a young patient's first-time experience with nutmeg and review the mechanisms of its toxicity. CASE REPORT: A 13-year-old female ingested 15-24 g of nutmeg over a 3-hour period and smoked and shared 2 joints of marijuana. To facilitate ingestion, the nutmeg was put into 00-000 gelatin capsules. Bizarre behavior and visual, auditory, and tactile hallucinations developed. She also experienced nausea, gagging, hot/cold sensations, and blurred vision followed by numbness, double, and \"triple\" vision, headache, and drowsiness. Nystagmus, muscle weakness, and ataxia were present. Her vital signs and laboratory tests were normal. She received 50 g of activated charcoal and except for complaints of dizziness and visual changes, her 2-day admission was uneventful. The central nervous system activity of nutmeg is often postulated to result from biotransformation of its chemical components to amphetamine-like compounds, but this has not been proven. Nutmeg contains several compounds with structural similarities to substances with known central nervous system neuromodulatory activity.", "title": "Toxicology of nutmeg abuse." }, { "docid": "MED-3807", "text": "Artemisia dracunculus L. (tarragon) has a long history of use as a spice and remedy. Two well-described \"cultivars\" (Russian and French) are used widely and differ in ploidy level, morphology, and chemistry. Key biologically active secondary metabolites are essential oils (0.15-3.1%), coumarins (>1%), flavonoids, and phenolcarbonic acids. In vivo studies mainly in rodents, particularly from Russian sources, highlight potential anti-inflammatory, hepatoprotective, and antihyperglycemic effects. Despite concerns about the toxic effects of two of its main constituents, estragole (up to 82%) and methyleugenol (up to 39%), no acute toxicity or mutagenic activity has been reported at doses relevant for human consumption. Water extracts of A. dracunculus contain very low amounts of estragole and methyleugenol and, therefore, are considered to pose a very limited risk. Overall, a stronger focus on clinical studies and precise taxonomic and phytochemical definition of the source material will be essential for future research efforts.", "title": "Artemisia dracunculus L. (tarragon): a critical review of its traditional use, chemical composition, pharmacology, and safety." }, { "docid": "MED-3231", "text": "This review looks at the role of an alkaline diet in health. Pubmed was searched looking for articles on pH, potential renal acid loads, bone health, muscle, growth hormone, back pain, vitamin D and chemotherapy. Many books written in the lay literature on the alkaline diet were also reviewed and evaluated in light of the published medical literature. There may be some value in considering an alkaline diet in reducing morbidity and mortality from chronic diseases and further studies are warranted in this area of medicine.", "title": "The Alkaline Diet: Is There Evidence That an Alkaline pH Diet Benefits Health?" }, { "docid": "MED-1999", "text": "Diabetes is a major and growing public health challenge which threatens to overwhelm medical services in the future. Type 2 diabetes confers significant morbidity and mortality, most notably with target organ damage to the eyes, kidneys, nerves and heart. The magnitude of cardiovascular risk associated with diabetes is best illustrated by its position as a coronary heart disease risk equivalent. Complications related to neuropathy are also vast, often working in concert with vascular abnormalities and resulting in serious clinical consequences such as foot ulceration. Increased understanding of the natural history of this disorder has generated the potential to intervene and halt pathological progression before overt disease ensues, after which point management becomes increasingly challenging. The concept of prediabetes as a formal diagnosis has begun to be translated from the research setting to clinical practice, but with continually updated guidelines, varied nomenclature, emerging pharmacotherapies and an ever-changing evidence base, clinicians may be left uncertain of best practice in identifying and managing patients at the prediabetic stage. This review aims to summarize the epidemiological data, new concepts in disease pathogenesis and guideline recommendations in addition to lifestyle, pharmacological and surgical therapies targeted at stopping progression of prediabetes to diabetes. While antidiabetic medications, with newer anti-obesity medications and interventional bariatric procedures have shown some promising benefits, diet and therapeutic lifestyle change remains the mainstay of management to improve the metabolic profile of individuals with glucose dysregulation. New risk stratification tools to identify at-risk individuals, coupled with unselected population level intervention hold promise in future practice.", "title": "Strategies for preventing type 2 diabetes: an update for clinicians" }, { "docid": "MED-1985", "text": "The relationship between diet and attained height was studied in children and adolescents in Southern California. Diet pattern was determined from an extensive food frequency questionnaire in 1765 Caucasian children of 7-18 years, attending state schools (452 m and 443 f) and Seventh-day Adventist schools (427 m and 443 f). The major difference in diet pattern between state and Adventist school children was in meat consumption. The Adventist children were split evenly between three categories of frequency in meat consumption (less than 1/week, 1/week-less than 1/d, and greater than or equal to 1/d), while 92 percent of state school children consumed meat daily. Vegetarians (those consuming meat less than 1/week) differed significantly in the consumption of other major food groups, such as fruit and vegetables. All school and diet subgroups were at or above the 50th percentile of the National Center for Health Statistics. Age-adjusted regression analysis showed that on average Adventist vegetarian children were taller than their meat-consuming classmates (2.5 and 2.0 cm for boys and girls, respectively). These results did not change materially when adjusting for other food groups. Nor did adjustment for parental height and socioeconomic factors in a sub-sample of 518 children. The results indicate that vegetarian children and adolescents on a balanced diet grow at least as tall as children who consume meat.", "title": "Attained height of lacto-ovo vegetarian children and adolescents." }, { "docid": "MED-1757", "text": "During 1 year, samples were taken on 4 days, one sample in each season, from pigs, the floor, and the air inside pig barns and from the ambient air and soil at different distances outside six commercial livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA)-positive pig barns in the north and east of Germany. LA-MRSA was isolated from animals, floor, and air samples in the barn, showing a range of airborne LA-MRSA between 6 and 3,619 CFU/m3 (median, 151 CFU/m3). Downwind of the barns, LA-MRSA was detected in low concentrations (11 to 14 CFU/m3) at distances of 50 and 150 m; all upwind air samples were negative. In contrast, LA-MRSA was found on soil surfaces at distances of 50, 150, and 300 m downwind from all barns, but no statistical differences could be observed between the proportions of positive soil surface samples at the three different distances. Upwind of the barns, positive soil surface samples were found only sporadically. Significantly more positive LA-MRSA samples were found in summer than in the other seasons both in air and soil samples upwind and downwind of the pig barns. spa typing was used to confirm the identity of LA-MRSA types found inside and outside the barns. The results show that there is regular airborne LA-MRSA transmission and deposition, which are strongly influenced by wind direction and season, of up to at least 300 m around positive pig barns. The described boot sampling method seems suitable to characterize the contamination of the vicinity of LA-MRSA-positive pig barns by the airborne route.", "title": "Longitudinal Study of the Contamination of Air and of Soil Surfaces in the Vicinity of Pig Barns by Livestock-Associated Methicillin-Resistant Staphylococcus aureus" }, { "docid": "MED-3216", "text": "Increasing dietary protein results in an increase in urinary calcium. Despite over 80 y of research, the source of the additional urinary calcium remains unclear. Because most calcium balance studies found little effect of dietary protein on intestinal calcium absorption, it was assumed that the skeleton was the source of the calcium. The hypothesis was that the high endogenous acid load generated by a protein-rich diet would increase bone resorption and skeletal fracture. However, there are no definitive nutrition intervention studies that show a detrimental effect of a high protein diet on the skeleton and the hypothesis remains unproven. Recent studies from our laboratory demonstrate that dietary protein affects intestinal calcium absorption. We conducted a series of short-term nutrition intervention trials in healthy adults where dietary protein was adjusted to either low, medium or high. The highest protein diet resulted in hypercalciuria with no change in serum parathyroid hormone. Surprisingly, within 4 d, the low protein diet induced secondary hyperparathyroidism that persisted for 2 wk. The secondary hyperparathyroidism induced by the low protein diet was attributed to a reduction in intestinal calcium absorption (as assessed by dual stable calcium isotopes). The long-term consequences of these low protein-induced changes in calcium metabolism are not known, but they could be detrimental to skeletal health. Several recent epidemiological studies demonstrate reduced bone density and increased rates of bone loss in individuals habitually consuming low protein diets. Therefore, studies are needed to determine whether low protein intakes directly affect rates of bone resorption, bone formation or both.", "title": "Low protein intake: the impact on calcium and bone homeostasis in humans." }, { "docid": "MED-3236", "text": "A first objective of the present study was to estimate the acid-base balance of the food intake in vegetarians and non-vegetarians. A second objective was to evaluate if additional input of specific food items on the existing potential renal acid load (PRAL) list was necessary for the comparison of the two dietary patterns. Thirty vegetarians between the age of 18 and 30 years were matched for sex, age and BMI with 30 non-vegetarians. Based on the 3-days food diaries the acid-base status of the food intake was estimated using the PRAL method. Mean PRAL values as estimated with the standard table yielded an alkaline load of -5.4 +/- 14.4 mEq/d in the vegetarians compared to an acid load of 10.3 +/- 14.4 mEq/d in the nonvegetarians (p<0.001). Mean PRAL values as estimated with the extended table yielded an alkaline load of -10.9 +/-19.7 mEq/d in the vegetarians compared to an acid load of 13.8 +/- 17.1 mEq/d for the non-vegetarians (p<0.001). The findings of this study indicate that vegetarian food intake produces more alkaline outcomes compared to non-vegetarian diets. The use of the standard PRAL table was sufficient for discrimination between the two diets.", "title": "Nutrient based estimation of acid-base balance in vegetarians and non-vegetarians." }, { "docid": "MED-2761", "text": "PURPOSE: The aim of this study was to examine the prevalence of self-reported multivitamin use in the Physicians' Health Study (PHS) cohort and its association with various lifestyle, clinical, and dietary factors to improve our understanding of who tends to use multivitamins. METHODS: Among 18,040 middle-aged and older men, information on lifestyle and clinical factors was collected from a baseline enrollment questionnaire, and supplement use and dietary factors were assessed through a food-frequency questionnaire. Four categories of multivitamin use were considered: (1) no supplement use, (2) use of multivitamins only, (3) use of multivitamins with other individual vitamin/mineral supplements, and (4) use of other supplements only. We used logistic regression to calculate multivariate odds ratios and 95% confidence intervals of taking multivitamin supplements for various lifestyle, clinical and dietary factors. RESULTS: Overall, 36% of men reported current multivitamin use. Men who were older, current smokers, and currently using aspirin were 143, 43, and 74% more likely to use multivitamins only. Men having a history of hypercholesterolemia were 16% more likely to use multivitamins only. A 14, 24, and 26% greater likelihood of using multivitamins was also observed among men consuming more fruits and vegetables, whole grains, and tea, respectively. Similar associations were observed for the likelihood of using multivitamins with other supplements; however, men with higher physical activity, history of cancer, hypertension, higher consumption of nuts, and lower consumption of red meat and coffee were also more likely to use multivitamins with other supplements (all P < 0.05). CONCLUSION: Self-reported multivitamin use associated with lifestyle, clinical and dietary factors may be an indicator of healthy behaviors. These results provide important information for the interpretation of the recent findings from the PHS II trial and consideration of results from observational studies of multivitamin use and chronic disease.", "title": "Who uses multivitamins? A cross-sectional study in the Physicians' Health Study." }, { "docid": "MED-3227", "text": "Although high-protein diets induce hypercalciuria in humans, the source of the additional urinary calcium remains unclear. One hypothesis is that the high endogenous acid load of a high-protein diet is partially buffered by bone, leading to increased skeletal resorption and hypercalciuria. We used dual stable calcium isotopes to quantify the effect of a high-protein diet on calcium kinetics in women. The study consisted of 2 wk of a lead-in, well-balanced diet followed by 10 d of an experimental diet containing either moderate (1.0 g/kg) or high (2.1 g/kg) protein. Thirteen healthy women received both levels of protein in random order. Intestinal calcium absorption increased during the high-protein diet in comparison with the moderate (26.2 +/- 1.9% vs. 18.5 +/- 1.6%, P < 0.0001, mean +/- sem) as did urinary calcium (5.23 +/- 0.37 vs. 3.57 +/- 0.35 mmol/d, P < 0.0001, mean +/- sem). The high-protein diet caused a significant reduction in the fraction of urinary calcium of bone origin and a nonsignificant trend toward a reduction in the rate of bone turnover. There were no protein-induced effects on net bone balance. These data directly demonstrate that, at least in the short term, high-protein diets are not detrimental to bone.", "title": "The impact of dietary protein on calcium absorption and kinetic measures of bone turnover in women." }, { "docid": "MED-2313", "text": "BACKGROUND: Chronic cutaneous complications such as pruritus are among the very frequent complaints of sulphur mustard (SM)-exposed patients. The present trial investigated the impact of curcumin on serum inflammatory biomarkers and their association with pruritus severity and quality of life (QoL). METHODS: This was a randomized, double-blind trial among 96 male Iranian veterans (age 37-59 y) who were suffering from chronic SM-induced pruritic skin lesions. Patients were randomly assigned to curcumin (1 g/d, n = 46) or placebo (n = 50) for four weeks. Serum concentrations of interleukins 6 (IL-6) and 8 (IL-8) together with high-sensitivity C-reactive protein (hs-CRP) and calcitonin gene-related peptide (CGRP) were measured at baseline and at the end of the trial. Assessment of pruritus severity was performed using the pruritus score and QoL using the Dermatology Life Quality Index (DLQI). RESULTS: Serum IL-8 and hs-CRP were significantly reduced in both groups but the magnitude of reduction was greater in the curcumin group (P < 0.001). Serum CGRP was only decreased in the curcumin group (P < 0.001). No significant change was observed in serum IL-6. There were significant correlations between CGRP and IL-6 changes (P = 0.011) and between DLQI and IL-8 changes (P = 0.026) in the curcumin group. In the curcumin group, changes in serum IL-8 concentrations were found as the significant predictor of DLQI scores (P = 0.026) but none of the independent variables could predict pruritus scores. CONCLUSIONS: Curcumin supplementation effectively mitigates inflammation in patients suffering from chronic SM-induced cutaneous complications. This anti-inflammatory effect might account for the observed pruritus alleviation and QoL improvement by this phytochemical.", "title": "A randomized controlled trial on the anti-inflammatory effects of curcumin in patients with chronic sulphur mustard-induced cutaneous complications." }, { "docid": "MED-4722", "text": "BACKGROUND: There has been a resurgence of interest in the controversial relation between dietary protein and bone health. OBJECTIVE: This article reports on the first systematic review and meta-analysis of the relation between protein and bone health in healthy human adults. DESIGN: The MEDLINE (January 1966 to September 2007) and EMBASE (1974 to July 2008) databases were electronically searched for all relevant studies of healthy adults; studies of calcium excretion or calcium balance were excluded. RESULTS: In cross-sectional surveys, all pooled r values for the relation between protein intake and bone mineral density (BMD) or bone mineral content at the main clinically relevant sites were significant and positive; protein intake explained 1-2% of BMD. A meta-analysis of randomized placebo-controlled trials indicated a significant positive influence of all protein supplementation on lumbar spine BMD but showed no association with relative risk of hip fractures. No significant effects were identified for soy protein or milk basic protein on lumbar spine BMD. CONCLUSIONS: A small positive effect of protein supplementation on lumbar spine BMD in randomized placebo-controlled trials supports the positive association between protein intake and bone health found in cross-sectional surveys. However, these results were not supported by cohort study findings for hip fracture risk. Any effects found were small and had 95% CIs that were close to zero. Therefore, there is a small benefit of protein on bone health, but the benefit may not necessarily translate into reduced fracture risk in the long term.", "title": "Dietary protein and bone health: a systematic review and meta-analysis." }, { "docid": "MED-4650", "text": "Aromatase is a cytochrome P450 enzyme (CYP19) and is the rate limiting enzyme in the conversion of androgens to estrogens. Suppression of in situ estrogen production through aromatase inhibition is the current treatment strategy for hormone-responsive breast cancers. Drugs that inhibit aromatase have been developed and are currently utilized as adjuvant therapy for breast cancer in post-menopausal women with hormone dependent breast cancer. Natural compounds have been studied extensively for important biologic effects such as antioxidant, anti-tumor and anti-viral effects. A significant number of studies have also investigated the aromatase inhibitory properties of a variety of plant extracts and phytochemicals. The identification of natural compounds that inhibit aromatase could be useful both from a chemopreventive standpoint and in the development of new aromatase inhibitory drugs. This review will discuss whole food extracts and the common classes of phytochemicals which have been investigated for potential aromatase inhibitory activity. We will review reported aromatase inhibition, kinetic data and possible structural variations that may inhibit or enhance the interaction of phytochemicals with the aromatase enzyme.", "title": "Phytochemicals for breast cancer prevention by targeting aromatase." }, { "docid": "MED-1992", "text": "Summary Prediabetes (or “intermediate hyperglycaemia”), based on glycaemic parameters above normal but below diabetes thresholds is a high risk state for diabetes with an annualized conversion rate of 5%–10%; with similar proportion converting back to normoglycaemia. The prevalence of prediabetes is increasing worldwide and it is projected that >470 million people will have prediabetes in 2030. Prediabetes is associated with the simultaneous presence of insulin resistance and β-cell dysfunction, abnormalities that start before glucose changes are detectable. Observational evidence shows associations of prediabetes with early forms of nephropathy, chronic kidney disease, small fibre neuropathy, diabetic retinopathy, and increased risk of macrovascular disease. Multifactorial risk scores could optimize the estimation of diabetes risk using non-invasive parameters and blood-based metabolic traits in addition to glycaemic values. For prediabetic individuals, lifestyle modification is the cornerstone of diabetes prevention with evidence of a 40%–70% relative risk reduction. Accumulating data also suggests potential benefits from pharmacotherapy.", "title": "Prediabetes: A high-risk state for developing diabetes" }, { "docid": "MED-3138", "text": "Background Many consumers avoid eating beans because they believe legume consumption will cause excessive intestinal gas or flatulence. An increasing body of research and the 2010 Dietary Guidelines for Americans supports the benefits of a plant-based diet, and legumes specifically, in the reduction of chronic disease risks. The purpose of the current research was to investigate the perception of increased flatulence and gastrointestinal discomfort among participants who consumed a ½ cup of beans daily for 8 or 12 weeks. Methods Participants in three studies to test the effects of beans on heart disease biomarkers completed the same weekly questionnaire to assess gastrointestinal discomfort issues such as increased flatulence, stool changes, and bloating. Studies 1 and 2 were randomized crossover trials. Participants consumed ½ cup of pinto beans, black-eyed peas, and canned carrots as control (n = 17) in Study 1 for three randomized 8-week phases. For Study 2, participants ate ½ cup baked beans or canned carrots as control (n = 29) for two randomized 8-week phases. Study 3 was a parallel arm trial with 40 subjects receiving ½ cup pinto beans and 40 consuming a control soup for 12 weeks. Changes in the frequency of perceived flatulence, stool characteristics, and bloating were the primary outcome measures. Chi-square distributions were examined for the presence or absence of symptoms and demographic characteristics to determine differences by gender, age, body mass index (BMI), and bean type. Results Less than 50% reported increased flatulence from eating pinto or baked beans during the first week of each trial, but only 19% had a flatulence increase with black-eyed peas. A small percentage (3-11%) reported increased flatulence across the three studies even on control diets without flatulence-producing components. Conclusions People's concerns about excessive flatulence from eating beans may be exaggerated. Public health nutritionists should address the potential for gastrointestinal discomfort when increasing fiber intake from beans with clients. It is important to recognize there is individual variation in response to different bean types.", "title": "Perceptions of flatulence from bean consumption among adults in 3 feeding studies" }, { "docid": "MED-2200", "text": "Cancer of the gallbladder is rare but fatal, and has an unusual geographic and demographic distribution. Gallstones and obesity have been suggested as possible risk factors. As diet is known to influence both these factors, we carried out the present study to evaluate the possible role of diet in gallbladder carcinogenesis. A case-control study involving 64 newly diagnosed cases of gallbladder cancer and 101 cases of gallstones was carried out. The dietary evaluation was carried out by the dietary recall method based on a preset questionnaire developed specifically for the present study, keeping in mind the common dietary habits prevailing in this part of the world. Odds ratios (OR) and 95% confidence interval (CI) were calculated for various dietary items. A significant reduction in odds ratio was seen with the consumption of radish (OR 0.4; 95% CI 0.17-0.94), green chilli (OR 0.45; 95% CI 0.21-0.94) and sweet potato (OR 0.33; 95% CI 0.13-0.83) among vegetables, and mango (OR 0.4; 95% CI 0.16-0.99), orange (OR; 0.45; 95% CI 0.22-0.93), melon (OR 0.3; 95% CI 0.14-0.64) and papaya (OR 0.44; 95% 0.2-0.64) among fruits. A reduction in odds was also seen with the consumption of cruciferous vegetables, beans, onion and turnip, however the difference was not statistically significant. On the other hand, an increase in the odds was observed with consumption of capsicum (OR 2.2), beef (OR 2.58), tea (OR 1.98), red chilli (OR 1.29) and mutton (OR 1.2), however the difference was statistically not significant. In conclusion, the results of the present study show a protective effect of vegetables and fruits on gallbladder carcinogenesis, but red meat (beef and mutton) was found to be associated with increased risk of gallbladder cancer.", "title": "Diet and gallbladder cancer: a case-control study." }, { "docid": "MED-2783", "text": "Although much has been published about curcumin, which is obtained from turmeric, comparatively little is known about turmeric itself. Turmeric, a golden spice obtained from the rhizome of the plant Curcuma longa, has been used to give color and taste to food preparations since ancient times. Traditionally, this spice has been used in Ayurveda and folk medicine for the treatment of such ailments as gynecological problems, gastric problems, hepatic disorders, infectious diseases, and blood disorders. Modern science has provided the scientific basis for the use of turmeric against such disorders. Various chemical constituents have been isolated from this spice, including polyphenols, sesquiterpenes, diterpenes, triterpenoids, sterols, and alkaloids. Curcumin, which constitutes 2-5% of turmeric, is perhaps the most-studied component. Although some of the activities of turmeric can be mimicked by curcumin, other activities are curcumin-independent. Cell-based studies have demonstrated the potential of turmeric as an antimicrobial, insecticidal, larvicidal, antimutagenic, radioprotector, and anticancer agent. Numerous animal studies have shown the potential of this spice against proinflammatory diseases, cancer, neurodegenerative diseases, depression, diabetes, obesity, and atherosclerosis. At the molecular level, this spice has been shown to modulate numerous cell-signaling pathways. In clinical trials, turmeric has shown efficacy against numerous human ailments including lupus nephritis, cancer, diabetes, irritable bowel syndrome, acne, and fibrosis. Thus, a spice originally common in the kitchen is now exhibiting activities in the clinic. In this review, we discuss the chemical constituents of turmeric, its biological activities, its molecular targets, and its potential in the clinic. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.", "title": "Multitargeting by turmeric, the golden spice: From kitchen to clinic." }, { "docid": "MED-3140", "text": "To identify protective dietary predictors amongst long-lived elderly people (N= 785), the \"Food Habits in Later Life \"(FHILL) study was undertaken among five cohorts in Japan, Sweden, Greece and Australia. Between 1988 and 1991, baseline data on food intakes were collected. There were 785 participants aged 70 and over that were followed up to seven years. Based on an alternative Cox Proportional Hazard model adjusted to age at enrollment (in 5-year intervals), gender and smoking, the legume food group showed 7-8% reduction in mortality hazard ratio for every 20g increase in daily intake with or without controlling for ethnicity (RR 0.92; 95% CI 0.85-0.99 and RR 0.93; 95% CI 0.87-0.99, respectively). Other food groups were not found to be consistently significant in predicting survival amongst the FHILL cohorts.", "title": "Legumes: the most important dietary predictor of survival in older people of different ethnicities." }, { "docid": "MED-1755", "text": "The emission of microorganisms, especially resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), from poultry farms is of public interest, and its occurrence and relevance are controversially discussed. So far, there are limited data on this issue. In this study, we investigated the occurrence of livestock-associated (LA)-MRSA inside and outside previously tested MRSA-positive poultry barns in Germany. In total, five turkey and two broiler fattening farms were investigated four and three times, respectively. In a longitudinal study during one fattening period, samples were collected from animals, the animals' environment inside the barn, including the air, and the barns' surroundings, such as ambient air and boot swabs of ground surfaces at different distances from the barn. Moreover, a cross-sectional study was carried out once inside the barns on five turkey and four broiler farms during the last third of the fatting period. In the cross-sectional study, LA-MRSA was detected in the air of most barns (7 of 9, 77.8%), as well as in many samples originating from animals, with detections levels of 50 to 54% in broiler and 62 to 77% in turkey farms. In the longitudinal study, LA-MRSA was found in the ambient air outside two turkey barns and on the ground surface on the downwind side of many (44.4%) turkey and broiler farms. The same spa types of isolates were observed inside and outside the barns. Transmission of MRSA within poultry farms, as well as emission via the airborne route, seems to be possible.", "title": "Occurrence of Livestock-Associated Methicillin-Resistant Staphylococcus aureus in Turkey and Broiler Barns and Contamination of Air and Soil Surfaces in Their Vicinity" }, { "docid": "MED-3233", "text": "Our objective in this study was to determine the effects of a high-protein and high-potential renal acid load (PRAL) diet on calcium (Ca) absorption and retention and markers of bone metabolism. In a randomized crossover design, 16 postmenopausal women consumed 2 diets: 1 with low protein and low PRAL (LPLP; total protein: 61 g/d; PRAL: -48 mEq/d) and 1 with high protein and high PRAL (HPHP; total protein: 118 g/d; PRAL: 33 mEq/d) for 7 wk each separated by a 1-wk break. Ca absorption was measured by whole body scintillation counting of radio-labeled (47)Ca. Compared with the LPLP diet, the HPHP diet increased participants' serum IGF-I concentrations (P < 0.0001), decreased serum intact PTH concentrations (P < 0.001), and increased fractional (47)Ca absorption (mean ± pooled SD: 22.3 vs. 26.5 ± 5.4%; P < 0.05) and urinary Ca excretion (156 vs. 203 ± 63 mg/d; P = 0.005). The net difference between the amount of Ca absorbed and excreted in urine did not differ between 2 diet periods (55 vs. 28 ± 51 mg/d). The dietary treatments did not affect other markers of bone metabolism. In summary, a diet high in protein and PRAL increases the fractional absorption of dietary Ca, which partially compensates for increased urinary Ca, in postmenopausal women. The increased IGF-I and decreased PTH concentrations in serum, with no change in biomarkers of bone resorption or formation, indicate a high-protein diet has no adverse effects on bone health.", "title": "A diet high in meat protein and potential renal acid load increases fractional calcium absorption and urinary calcium excretion without affecting m..." }, { "docid": "MED-2234", "text": "Use of antioxidant components is a new approach for improvement of insulin resistance (IR) as a main feature of type 2 diabetes and its complications. The aim of this study was to investigate the effects of broccoli sprouts powder (BSP) containing high concentration of sulphoraphane on IR in type 2 diabetic patients. Eighty-one patients were randomly assigned to receive 10 g/d BSP (A, n = 27), 5 g/d BSP (B, n = 29) and placebo (C, n = 25) for 4 weeks. Fasting serum glucose and insulin concentration, glucose to insulin ratio and homoeostasis model assessment of IR (HOMA-IR) index were measured at baseline and again 4 weeks after treatment. Seventy-two patients completed the study and 63 were included in the analysis. After 4 weeks, consumption of 10 g/d BSP resulted in a significant decrease in serum insulin concentration and HOMA-IR (p = 0.05 for treatment effect). Therefore, broccoli sprouts may improve IR in type 2 diabetic patients.", "title": "Effect of broccoli sprouts on insulin resistance in type 2 diabetic patients: a randomized double-blind clinical trial." }, { "docid": "MED-2309", "text": "BACKGROUND: Similar to the general population in Taiwan, the health of aborigines has steadily improved over the last 30 years, but the gap remains wide, especially in males, despite an infusion of substantial medical resources. The objectives of this study are to quantify the contribution of major causes of death to the gap in life expectancy and to propose initiatives to bridge the health gap between aborigines and the general population. METHODS: This study included residents (slightly over 200000) from 30 'aboriginal townships' in Taiwan. The gap in life expectancy between aborigines and the general population was analysed by decomposing these gaps according to major causes of deaths. This analysis quantifies the contribution of different causes of deaths to the gap in life expectancy between the two populations. RESULTS: The overall mortality of aborigines in these townships was approximately 70% higher than the respective male and female general populations over the past 30 years. Mortality from infectious disease, cirrhosis of the liver, accidents, and suicide are substantially higher than the general population. The gap in life expectancy at birth in males was 8.5 years during 1971-1973, increasing to 13.5 years by 1998-2000, however, the gap in females remained relatively stable (8.0 years and 8.4 years, respectively). Of the 13.5-year difference in life expectancy in males, the differential mortality from diseases of the digestive system (mainly due to cirrhosis of the liver), accidents (from both motor vehicle and non-motor vehicle accidents), and infectious and parasitic disease contributed half (50%) of the gap in life expectancy. In females, the above primarily preventable causes of deaths accounted for 41% of the life expectancy gap. CONCLUSIONS: Based on the findings of this study, we suggest that future focus should be in the area of primary prevention in order to reduce the incidence of infectious and parasitic diseases, liver cirrhosis, and accidents.", "title": "Bridging the gap in life expectancy of the aborigines in Taiwan." }, { "docid": "MED-398", "text": "Summary Grapefruit is a popular, tasty and nutritive fruit enjoyed globally. Biomedical evidence in the last 10 years has, however, shown that consumption of grapefruit or its juice is associated with drug interactions, which, in some cases, have been fatal. Grapefruit-induced drug interactions are unique in that the cytochrome P450 enzyme CYP3A4, which metabolises over 60% of commonly prescribed drugs as well as other drug transporter proteins such as P-glycoprotein and organic cation transporter proteins, which are all expressed in the intestines, are involved. However, the extent to which grapefruit–drug interactions impact on clinical settings has not been fully determined, probably because many cases are not reported. It has recently emerged that grapefruit, by virtue of its rich flavonoid content, is beneficial in the management of degenerative diseases such as diabetes and cardiovascular disorders. This potentially explosive subject is reviewed here.", "title": "The grapefruit: an old wine in a new glass? Metabolic and cardiovascular perspectives" } ]
[ { "docid": "MED-1449", "text": "Amid soaring health spending, there is growing interest in workplace disease prevention and wellness programs to improve health and lower costs. In a critical meta-analysis of the literature on costs and savings associated with such programs, we found that medical costs fall by about $3.27 for every dollar spent on wellness programs and that absenteeism costs fall by about $2.73 for every dollar spent. Although further exploration of the mechanisms at work and broader applicability of the findings is needed, this return on investment suggests that the wider adoption of such programs could prove beneficial for budgets and productivity as well as health outcomes.", "title": "Workplace wellness programs can generate savings." }, { "docid": "MED-4603", "text": "Background The US diet is high in salt, with the majority coming from processed foods. Reducing dietary salt is an important potential public health target. Methods We used the Coronary Heart Disease (CHD) Policy Model to quantify the benefits of potentially achievable population-wide reductions in dietary salt of up to 3 gm/day (1200 mg/day of sodium). We estimated cardiovascular disease rates and costs in age, sex, and race subgroups, compared salt reduction with other interventions to reduce cardiovascular risk, and determined the cost-effectiveness of salt reduction compared with drug treatment of hypertension. Results Reducing salt by 3 gm/day is projected to result in 60,000–120,000 fewer new CHD cases, 32,000–66,000 fewer new strokes, 54,000–99,000 fewer myocardial infarctions, and 44,000–92,000 fewer deaths from any cause annually. All segments of the population would benefit, with blacks benefiting proportionately more, women benefiting particularly from stroke reduction, older adults from reductions in CHD events, and younger adults from lower mortality rates. The cardiovascular benefits from lower salt are on par with benefits from reducing tobacco, obesity, or cholesterol. A regulatory intervention designed to achieve 3 gm/day salt reduction would save 194,000–392,000 quality-adjusted life-years and $10–24 billion in healthcare costs annually. Such an intervention would be cost-saving even if only a modest 1 gm/day reduction were achieved gradually over the decade from 2010–2019 and would be more cost-effective than treating all hypertensive individuals with medications. Conclusions Modest reduction in dietary salt could substantially reduce cardiovascular events and medical costs and should be a public health target.", "title": "Reductions in Cardiovascular Disease Projected from Modest Reductions in Dietary Salt" }, { "docid": "MED-5301", "text": "Background The US diet is high in salt, with the majority coming from processed foods. Reducing dietary salt is an important potential public health target. Methods We used the Coronary Heart Disease (CHD) Policy Model to quantify the benefits of potentially achievable population-wide reductions in dietary salt of up to 3 gm/day (1200 mg/day of sodium). We estimated cardiovascular disease rates and costs in age, sex, and race subgroups, compared salt reduction with other interventions to reduce cardiovascular risk, and determined the cost-effectiveness of salt reduction compared with drug treatment of hypertension. Results Reducing salt by 3 gm/day is projected to result in 60,000–120,000 fewer new CHD cases, 32,000–66,000 fewer new strokes, 54,000–99,000 fewer myocardial infarctions, and 44,000–92,000 fewer deaths from any cause annually. All segments of the population would benefit, with blacks benefiting proportionately more, women benefiting particularly from stroke reduction, older adults from reductions in CHD events, and younger adults from lower mortality rates. The cardiovascular benefits from lower salt are on par with benefits from reducing tobacco, obesity, or cholesterol. A regulatory intervention designed to achieve 3 gm/day salt reduction would save 194,000–392,000 quality-adjusted life-years and $10–24 billion in healthcare costs annually. Such an intervention would be cost-saving even if only a modest 1 gm/day reduction were achieved gradually over the decade from 2010–2019 and would be more cost-effective than treating all hypertensive individuals with medications. Conclusions Modest reduction in dietary salt could substantially reduce cardiovascular events and medical costs and should be a public health target.", "title": "Reductions in Cardiovascular Disease Projected from Modest Reductions in Dietary Salt" }, { "docid": "MED-1448", "text": "OBJECTIVE: To quantify per capita and aggregate medical expenditures and the value of lost productivity, including absenteeism and presenteeism, because of overweight, and grade I, II, and III obesity among U.S. employees. METHODS: Cross-sectional analysis of the 2006 Medical Expenditure Panel Survey and the 2008 National Health and Wellness Survey. RESULTS: Among men, estimates range from -$322 for overweight to $6087 for grade III obese men. For women, estimates range from $797 for overweight to $6694 for grade III. In aggregate, the annual cost attributable to obesity among full-time employees is $73.1 billion. Individuals with a body mass index >35 represent 37% of the obese population but are responsible for 61% of excess costs. CONCLUSIONS: Successful efforts to reduce the prevalence of obesity, especially among those with a body mass index >35, could result in significant savings to employers.", "title": "The costs of obesity in the workplace." }, { "docid": "MED-5291", "text": "Over the past century, salt has been the subject of intense scientific research related to blood pressure elevation and cardiovascular mortalities. Moderate reduction of dietary salt intake is generally an effective measure to reduce blood pressure. However, recently some in the academic society and lay media dispute the benefits of salt restriction, pointing to inconsistent outcomes noted in some observational studies. A reduction in dietary salt from the current intake of 9-12 g/day to the recommended level of less than 5-6 g/day will have major beneficial effects on cardiovascular health along with major healthcare cost savings around the world. The World Health Organization (WHO) strongly recommended to reduce dietary salt intake as one of the top priority actions to tackle the global non-communicable disease crisis and has urged member nations to take action to reduce population wide dietary salt intake to decrease the number of deaths from hypertension, cardiovascular disease and stroke. However, some scientists still advocate the possibility of increased risk of CVD morbidity and mortality at extremes of low salt intake. Future research may inform the optimal sodium reduction strategies and intake targets for general populations. Until then, we have to continue to build consensus around the greatest benefits of salt reduction for CVD prevention, and dietary salt intake reduction strategies must remain at the top of the public health agenda.", "title": "Dietary Salt Intake and Hypertension" }, { "docid": "MED-4299", "text": "The evolution of the human diet over the past 10,000 years from a Paleolithic diet to our current modern pattern of intake has resulted in profound changes in feeding behavior. Shifts have occurred from diets high in fruits, vegetables, lean meats, and seafood to processed foods high in sodium and hydrogenated fats and low in fiber. These dietary changes have adversely affected dietary parameters known to be related to health, resulting in an increase in obesity and chronic disease, including cardiovascular disease (CVD), diabetes, and cancer. Some intervention trials using Paleolithic dietary patterns have shown promising results with favorable changes in CVD and diabetes risk factors. However, such benefits may be offset by disadvantages of the Paleolithic diet, which is low in vitamin D and calcium and high in fish potentially containing environmental toxins. More advantageous would be promotion of foods and food ingredients from our ancestral era that have been shown to possess health benefits in the form of functional foods. Many studies have investigated the health benefits of various functional food ingredients, including omega-3 fatty acids, polyphenols, fiber, and plant sterols. These bioactive compounds may help to prevent and reduce incidence of chronic diseases, which in turn could lead to health cost savings ranging from $2 to $3 billion per year as estimated by case studies using omega-3 and plant sterols as examples. Thus, public health benefits should result from promotion of the positive components of Paleolithic diets as functional foods.", "title": "Evolution of the human diet: linking our ancestral diet to modern functional foods as a means of chronic disease prevention." }, { "docid": "MED-3436", "text": "Erectile dysfunction (ED) is an early marker for systemic atherosclerosis and is a predictor for coronary artery disease and cardiac events. The aim of this paper is to convey the importance of addressing cardiovascular risk factors in patients with ED and to inform urologists as well as other physicians who are not specialized in cardiology how to carry out a basic cardiovascular evaluation, including history, physical examination and objective data. We review the evidence and pathophysiology linking ED to cardiovascular disease, and then describe how to carry out a basic cardiovascular evaluation. We present data from the literature showing that appropriate use of lifestyle modifications and medical therapy has a positive effect on mortality, on numerous cardiovascular end points and on ED. Suggestions of when to refer the ED patient to an internist or cardiologist are provided. Identifying and treating cardiovascular risk factors may not only benefit the patient's ED, but it might also save the patient's life.", "title": "How to save a life during a clinic visit for erectile dysfunction by modifying cardiovascular risk factors." }, { "docid": "MED-3975", "text": "Background In Japan, gargling is a generally accepted way of preventing upper respiratory tract infection (URTI). The effectiveness of gargling for preventing URTI has been shown in a randomized controlled trial that compared incidences of URTI between gargling and control groups. From the perspective of the third-party payer, gargling is dominant due to the fact that the costs of gargling are borne by the participant. However, the cost-effectiveness of gargling from a societal perspective should be considered. In this study, economic evaluation alongside a randomized controlled trial was performed to evaluate the cost-effectiveness of gargling for preventing URTI from a societal perspective. Methods Among participants in the gargling trial, 122 water-gargling and 130 control subjects were involved in the economic analysis. Sixty-day cumulative follow-up costs and effectiveness measured by quality-adjusted life days (QALD) were compared between groups on an intention-to-treat basis. Incremental cost-effectiveness ratio (ICER) was converted to dollars per quality-adjusted life years (QALY). The 95% confidence interval (95%CI) and probability of gargling being cost-effective were estimated by bootstrapping. Results After 60 days, QALD was increased by 0.43 and costs were $37.1 higher in the gargling group than in the control group. ICER of the gargling group was $31,800/QALY (95%CI, $1,900–$248,100). Although this resembles many acceptable forms of medical intervention, including URTI preventive measures such as influenza vaccination, the broad confidence interval indicates uncertainty surrounding our results. In addition, one-way sensitivity analysis also indicated that careful evaluation is required for the cost of gargling and the utility of moderate URTI. The major limitation of this study was that this trial was conducted in winter, at a time when URTI is prevalent. Care must be taken when applying the results to a season when URTI is not prevalent, since the ICER will increase due to decreases in incidence. Conclusion This study suggests gargling as a cost-effective preventive strategy for URTI that is acceptable from perspectives of both the third-party payer and society.", "title": "Cost-effectiveness of gargling for the prevention of upper respiratory tract infections" }, { "docid": "MED-5220", "text": "PURPOSE: The aim of this study was to estimate both the direct and indirect annual cost of managing dry eye disease (DED) in the United States from a societal and a payer's perspective. METHODS: A decision analytic model was developed to estimate the annual cost for managing a cohort of patients with dry eye with differing severity of symptoms and treatment. The direct costs included ocular lubricants, cyclosporine, punctal plugs, physician visits, and nutritional supplements. The indirect costs were measured as the productivity loss because of absenteeism and presenteeism. The model was populated with data that were obtained from surveys that were completed by dry eye sufferers who were recruited from online databases. Sensitivity analyses were employed to evaluate the impact of changes in parameters on the estimation of costs. All costs were converted to 2008 US dollars. RESULTS: Survey data were collected from 2171 respondents with DED. Our analysis indicated that the average annual cost of managing a patient with dry eye at $783 (variation, $757-$809) from the payers' perspective. When adjusted to the prevalence of DED nationwide, the overall burden of DED for the US healthcare system would be $3.84 billion. From a societal perspective, the average cost of managing DED was estimated to be $11,302 per patient and $55.4 billion to the US society overall. CONCLUSIONS: DED poses a substantial economic burden on the payer and on the society. These findings may provide valuable information for health plans or employers regarding budget estimation.", "title": "The economic burden of dry eye disease in the United States: a decision tree analysis." }, { "docid": "MED-4131", "text": "In this article we estimate the annual cost of illness and quality-adjusted life year (QALY) loss in the United States caused by 14 of the 31 major foodborne pathogens reported on by Scallan et al. (Emerg. Infect. Dis. 17:7-15, 2011), based on their incidence estimates of foodborne illness in the United States. These 14 pathogens account for 95 % of illnesses and hospitalizations and 98 % of deaths due to identifiable pathogens estimated by Scallan et al. We estimate that these 14 pathogens cause $14.0 billion (ranging from $4.4 billion to $33.0 billion) in cost of illness and a loss of 61,000 QALYs (ranging from 19,000 to 145,000 QALYs) per year. Roughly 90 % of this loss is caused by five pathogens: nontyphoidal Salmonella enterica ($3.3 billion; 17,000 QALYs), Campylobacter spp. ($1.7 billion; 13,300 QALYs), Listeria monocytogenes ($2.6 billion; 9,400 QALYs), Toxoplasma gondii ($3 billion; 11,000 QALYs), and norovirus ($2 billion; 5,000 QALYs). A companion article attributes losses estimated in this study to the consumption of specific categories of foods. To arrive at these estimates, for each pathogen we create disease outcome trees that characterize the symptoms, severities, durations, outcomes, and likelihoods of health states associated with that pathogen. We then estimate the cost of illness (medical costs, productivity loss, and valuation of premature mortality) for each pathogen. We also estimate QALY loss for each health state associated with a given pathogen, using the EuroQol 5D scale. Construction of disease outcome trees, outcome-specific cost of illness, and EuroQol 5D scoring are described in greater detail in a second companion article.", "title": "Annual cost of illness and quality-adjusted life year losses in the United States due to 14 foodborne pathogens." }, { "docid": "MED-5006", "text": "We projected future prevalence and BMI distribution based on national survey data (National Health and Nutrition Examination Study) collected between 1970s and 2004. Future obesity-related health-care costs for adults were estimated using projected prevalence, Census population projections, and published national estimates of per capita excess health-care costs of obesity/overweight. The objective was to illustrate potential burden of obesity prevalence and health-care costs of obesity and overweight in the United States that would occur if current trends continue. Overweight and obesity prevalence have increased steadily among all US population groups, but with notable differences between groups in annual increase rates. The increase (percentage points) in obesity and overweight in adults was faster than in children (0.77 vs. 0.46-0.49), and in women than in men (0.91 vs. 0.65). If these trends continue, by 2030, 86.3% adults will be overweight or obese; and 51.1%, obese. Black women (96.9%) and Mexican-American men (91.1%) would be the most affected. By 2048, all American adults would become overweight or obese, while black women will reach that state by 2034. In children, the prevalence of overweight (BMI >/= 95th percentile, 30%) will nearly double by 2030. Total health-care costs attributable to obesity/overweight would double every decade to 860.7-956.9 billion US dollars by 2030, accounting for 16-18% of total US health-care costs. We continue to move away from the Healthy People 2010 objectives. Timely, dramatic, and effective development and implementation of corrective programs/policies are needed to avoid the otherwise inevitable health and societal consequences implied by our projections .", "title": "Will all Americans become overweight or obese? estimating the progression and cost of the US obesity epidemic." }, { "docid": "MED-2051", "text": "In 2011, the protease inhibitors boceprevir and telaprevir were approved in the United States and European Union for the treatment of hepatitis C infection. While remarkably effective, the newly approved therapies are also accompanied by additional side effects and considerable costs. Understanding the balance between costs and effectiveness is critical to making decisions about the optimal use of these new agents, especially for health care systems constrained by rising costs. Our goal for this review is to facilitate an understanding of the importance of cost-effectiveness analyses in guiding policy decisions about the use of newly approved drugs as well as future therapies for hepatitis C.", "title": "Economic evaluation of direct-acting antiviral therapy in chronic hepatitis C." }, { "docid": "MED-3013", "text": "A 2002 analysis documented $54.9 billion in annual costs of environmentally mediated diseases in US children. However, few important changes in federal policy have been implemented to prevent exposures to toxic chemicals. We therefore updated and expanded the previous analysis and found that the costs of lead poisoning, prenatal methylmercury exposure, childhood cancer, asthma, intellectual disability, autism, and attention deficit hyperactivity disorder were $76.6 billion in 2008. To prevent further increases in these costs, efforts are needed to institute premarket testing of new chemicals; conduct toxicity testing on chemicals already in use; reduce lead-based paint hazards; and curb mercury emissions from coal-fired power plants.", "title": "Reducing the staggering costs of environmental disease in children, estimated at $76.6 billion in 2008." }, { "docid": "MED-4949", "text": "Methyl mercury is a developmental neurotoxicant. Exposure results principally from consumption by pregnant women of seafood contaminated by mercury from anthropogenic (70%) and natural (30%) sources. Throughout the 1990s, the U.S. Environmental Protection Agency (EPA) made steady progress in reducing mercury emissions from anthropogenic sources, especially from power plants, which account for 41% of anthropogenic emissions. However, the U.S. EPA recently proposed to slow this progress, citing high costs of pollution abatement. To put into perspective the costs of controlling emissions from American power plants, we have estimated the economic costs of methyl mercury toxicity attributable to mercury from these plants. We used an environmentally attributable fraction model and limited our analysis to the neurodevelopmental impacts—specifically loss of intelligence. Using national blood mercury prevalence data from the Centers for Disease Control and Prevention, we found that between 316,588 and 637,233 children each year have cord blood mercury levels > 5.8 μg/L, a level associated with loss of IQ. The resulting loss of intelligence causes diminished economic productivity that persists over the entire lifetime of these children. This lost productivity is the major cost of methyl mercury toxicity, and it amounts to $8.7 billion annually (range, $2.2–43.8 billion; all costs are in 2000 US$). Of this total, $1.3 billion (range, $0.1–6.5 billion) each year is attributable to mercury emissions from American power plants. This significant toll threatens the economic health and security of the United States and should be considered in the debate on mercury pollution controls.", "title": "Public Health and Economic Consequences of Methyl Mercury Toxicity to the Developing Brain" }, { "docid": "MED-3974", "text": "BACKGROUND: Viral respiratory tract infection (VRTI) is the most common illness in humans. Despite the high incidence, the economic impact of non-influenza-related VRTI has not been rigorously explored. Our objectives were to obtain an updated incidence of non-influenza-related VRTI in the United States and to quantify the health care resource use (direct costs) and productivity losses (indirect costs) associated with these infections. METHODS: A nationwide telephone survey of US households (N = 4051) was conducted between November 3, 2000, and February 12, 2001 to obtain a representative estimate of the self-reported incidence of non-influenza-related VRTI and related treatment patterns. Direct treatment costs measured included outpatient clinician encounters, use of over-the-counter and prescription drugs, and associated infectious complications of non-influenza-related VRTI. Absenteeism estimates for infected individuals and parents of infected children were extrapolated from National Health Interview Survey data. RESULTS: Of survey respondents, 72% reported a non-influenza-related VRTI within the past year. Respondents who experienced a self-reported non-influenza-related VRTI averaged 2.5 episodes annually. When these rates are extrapolated to the entire US population, approximately 500 million non-influenza-related VRTI episodes occur per year. Similarly, if the treatment patterns reported by the respondents are extended to the population, the total economic impact of non-influenza-related VRTI approaches $40 billion annually (direct costs, $17 billion per year; and indirect costs, $22.5 billion per year). CONCLUSIONS: Largely because of the high attack rate, non-influenza-related VRTI imposes a greater economic burden than many other clinical conditions. The pending availability of effective antiviral therapies warrants increased attention be paid to this common and expensive illness.", "title": "The economic burden of non-influenza-related viral respiratory tract infection in the United States." }, { "docid": "MED-1123", "text": "OBJECTIVES: To provide a state of the art of economic analyses applied to rheumatoid arthritis (RA). METHODS: A systematic literature review on economic consequences and pharmacoeconomic issues of RA was performed. RESULTS: 127 valid articles were examined in this review. Generally, the financial impact of RA is substantial for health-care systems and society worldwide, although differences exist among national economies. Both direct and indirect (i.e. loss of productivity) costs contribute to economic burden of RA and must be taken into account when estimating overall impact to society. Disease severity, disease activity, age and socioeconomic status have been found to be the most relevant predictors of cost increase in RA. Moreover, introduction of biological anti-rheumatic agents has significantly raised direct medical costs in certain patients, but has also led to marked improvements in reducing disease activity, joint damage, and productivity loss in many of these patients. RA has also a significant impact on all aspects of quality of life; recent publications on health utility scores showed RA to be one of the diseases associated with poorest quality of life. CONCLUSIONS: RA represents a clinical and economic burden for healthcare systems. Although attributable RA costs have been extensively evaluated over the last decades, several issues, especially concerning the use of expensive therapies, must be addressed and frequently updated. Future research should also provide health economic evidence from usual practice settings, and on the economic impact of different therapeutic approaches to pursue specific clinical targets in individual patients.", "title": "Systematic literature review on economic implications and pharmacoeconomic issues of rheumatoid arthritis." }, { "docid": "MED-4371", "text": "OBJECTIVES: To ascertain the recommendations, training and education of health food store employees and determine how they communicate the costs, benefits and risks associated with natural health products for the HIV/AIDS community. METHODS: Four male research assistants, posing as asymptomatic HIV-positive individuals, inquired of employees of all retail health food stores in a major Canadian city as to what is recommended for their condition. The research assistants asked about product costs, side effects, potential drug interactions and efficacy. They also inquired as to employee education related to Complementary and Alternative Medicine (CAM) and noted whether employees asked about which conventional medications they were taking and whether they recommended that the subjects seek physician or CAM provider advice. RESULTS: A total of 32 stores were included. Eight store employees (25%) offered no advice; eight (25%) inquired whether the subjects were currently taking medications; six (19%) suggested visiting a physician; and eight (25%) suggested visiting a CAM provider. A total of 36 different products (mean 2.3 per employee) were recommended with considerable variability in product evidence and cost. The education of the employees varied from postgraduate education (n=3), to undergraduate degree (n=3), college level (n=5) in CAM, or no formal education in CAM (n=21). CONCLUSION: There was considerable heterogeneity in advice on natural food products provided by employees of natural food stores and, in general, these individuals had limited formal training in CAM. The products they recommended had limited evidence supporting their efficacy and in some instances were potentially harmful and had considerable costs. The findings of this study support the need to further examine how best to regulate this growing component of the health care system.", "title": "Emerging issues associated with HIV patients seeking advice from health food stores." }, { "docid": "MED-3550", "text": "Between 2000 and 2050, the number of new cancer patients diagnosed annually is expected to double, with an accompanying increase in treatment costs of more than $80 billion over just the next decade. Efficacious strategies for cancer prevention will therefore be vital for improving patients' quality of life and reducing healthcare costs. Judah Folkman first proposed antiangiogenesis as a strategy for preventing dormant microtumors from progressing to invasive cancer. Although antiangiogenic drugs are now available for many advanced malignancies (colorectal, lung, breast, kidney, liver, brain, thyroid, neuroendocrine, multiple myeloma, myelodysplastic syndrome), cost and toxicity considerations preclude their broad use for cancer prevention. Potent antiangiogenic molecules have now been identified in dietary sources, suggesting that a rationally designed antiangiogenic diet could provide a safe, widely available, and novel strategy for preventing cancer. This paper presents the scientific, epidemiologic, and clinical evidence supporting the role of an antiangiogenic diet for cancer prevention.", "title": "Tumor Angiogenesis as a Target for Dietary Cancer Prevention" }, { "docid": "MED-1704", "text": "The dramatic rising incidence and costs of Alzheimer's disease (AD) require that research efforts and funding be primarily directed on either finding a cure or applying preventive measures to curb this disorder. A cure for AD appears unlikely when significant cognitive loss has occurred because the neuronal networks that controlled the perturbed cognitive abilities are either dead or irreversibly damaged and replacing them, even if it were technically possible, would not reconstruct the intellectual identity of the host. Prevention of risk factors to sporadic AD is a more realistic stratagem and treatment, when indicated, ideally should begin in cognitively intact individuals as part of a mass screening effort. Prevention of modifiable risk factors to AD is cost-effective because it reduces hospice or hospital stay, repeated doctor visits, and long-term care. Presently, neurocognitive and neuroimaging tests are used with partial success in identifying persons at higher risk of AD but these tests can not pinpoint either a cause or a specific intervention that could attenuate disease progress. We previously proposed that carotid artery ultrasound +echocardiography together with ankle-brachail index (CAUSE+ABI) as mass screening tests in asymptomatic persons could detect not only cardio-cerebrovascular risk factors to AD, but also identify an indicated intervention. CAUSE+ABI are simple to perform, cost-effective, non-invasive, and reasonably accurate for the intended purpose. Additionally, detection of cardio-cerebrovasacular abnormalities long before expression of cognitive deterioration allows higher success rate with earlier treatment. Evidence-based medicine is recommended for optimizing clinical decision-making in evaluating AD risk factors and their treatment.", "title": "Alzheimer's disease is incurable but preventable." }, { "docid": "MED-3939", "text": "Excerpt This Statistical Brief presents data from the Healthcare Cost and Utilization Project (HCUP) on the treatment of TBI in U.S. hospitals in 2004. Hospital utilization and costs for TBI admissions are compared with hospital stays for all other injuries. Additionally, trends in hospital stays for TBI and differences in the distribution of TBI admissions by various patient characteristics are examined. Finally, common causes of TBIs resulting in hospital admission, as well as the coexisting conditions often associated with these injuries, are described. All differences between estimates noted in the text are statistically significant at the 0.05 level or better.", "title": "Hospital Admissions for Traumatic Brain Injuries, 2004: Statistical Brief #27" }, { "docid": "MED-4504", "text": "Dietary supplementation with beetroot juice (BR) has been shown to reduce resting blood pressure and the O(2) cost of submaximal exercise and to increase tolerance to high-intensity cycling. We tested the hypothesis that the physiological effects of BR were consequent to its high NO(3)(-) content per se, and not the presence of other potentially bioactive compounds. We investigated changes in blood pressure, mitochondrial oxidative capacity (Q(max)), and physiological responses to walking and moderate- and severe-intensity running following dietary supplementation with BR and NO(3)(-)-depleted BR [placebo (PL)]. After control (nonsupplemented) tests, nine healthy, physically active male subjects were assigned in a randomized, double-blind, crossover design to receive BR (0.5 l/day, containing ∼6.2 mmol of NO(3)(-)) and PL (0.5 l/day, containing ∼0.003 mmol of NO(3)(-)) for 6 days. Subjects completed treadmill exercise tests on days 4 and 5 and knee-extension exercise tests for estimation of Q(max) (using (31)P-magnetic resonance spectroscopy) on day 6 of the supplementation periods. Relative to PL, BR elevated plasma NO(2)(-) concentration (183 ± 119 vs. 373 ± 211 nM, P < 0.05) and reduced systolic blood pressure (129 ± 9 vs. 124 ± 10 mmHg, P < 0.01). Q(max) was not different between PL and BR (0.93 ± 0.05 and 1.05 ± 0.22 mM/s, respectively). The O(2) cost of walking (0.87 ± 0.12 and 0.70 ± 0.10 l/min in PL and BR, respectively, P < 0.01), moderate-intensity running (2.26 ± 0.27 and 2.10 ± 0.28 l/min in PL and BR, respectively, P < 0.01), and severe-intensity running (end-exercise O(2) uptake = 3.77 ± 0.57 and 3.50 ± 0.62 l/min in PL and BL, respectively, P < 0.01) was reduced by BR, and time to exhaustion during severe-intensity running was increased by 15% (7.6 ± 1.5 and 8.7 ± 1.8 min in PL and BR, respectively, P < 0.01). In contrast, relative to control, PL supplementation did not alter plasma NO(2)(-) concentration, blood pressure, or the physiological responses to exercise. These results indicate that the positive effects of 6 days of BR supplementation on the physiological responses to exercise can be ascribed to the high NO(3)(-) content per se.", "title": "Dietary nitrate supplementation reduces the O2 cost of walking and running: a placebo-controlled study." }, { "docid": "MED-3705", "text": "The association of inflammation with modern human diseases (e.g. obesity, cardiovascular disease, type 2 diabetes mellitus, cancer) remains an unsolved mystery of current biology and medicine. Inflammation is a protective response to noxious stimuli that unavoidably occurs at a cost to normal tissue function. This fundamental tradeoff between the cost and benefit of the inflammatory response has been optimized over evolutionary time for specific environmental conditions. Rapid change of the human environment due to niche construction outpaces genetic adaptation through natural selection, leading increasingly to a mismatch between the modern environment and selected traits. Consequently, multiple tradeoffs that affect human physiology are not optimized to the modern environment, leading to increased disease susceptibility. Here we examine the inflammatory response from an evolutionary perspective. We discuss unique aspects of the inflammatory response and its evolutionary history that can help explain the association between inflammation and modern human diseases.", "title": "Evolution of Inflammatory Diseases" }, { "docid": "MED-4508", "text": "Nitrate, an inorganic anion abundant in vegetables, is converted in vivo to bioactive nitrogen oxides including NO. We recently demonstrated that dietary nitrate reduces oxygen cost during physical exercise, but the mechanism remains unknown. In a double-blind crossover trial we studied the effects of a dietary intervention with inorganic nitrate on basal mitochondrial function and whole-body oxygen consumption in healthy volunteers. Skeletal muscle mitochondria harvested after nitrate supplementation displayed an improvement in oxidative phosphorylation efficiency (P/O ratio) and a decrease in state 4 respiration with and without atractyloside and respiration without adenylates. The improved mitochondrial P/O ratio correlated to the reduction in oxygen cost during exercise. Mechanistically, nitrate reduced the expression of ATP/ADP translocase, a protein involved in proton conductance. We conclude that dietary nitrate has profound effects on basal mitochondrial function. These findings may have implications for exercise physiology- and lifestyle-related disorders that involve dysfunctional mitochondria. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Dietary inorganic nitrate improves mitochondrial efficiency in humans." }, { "docid": "MED-4366", "text": "BACKGROUND: Many different dietary supplements are being sold in North America. The quality of the evidence supporting their efficacy covers a wide spectrum: Some are based on solid science (such as vitamin D and fish oil), whereas with most supplements there is little or no supporting evidence. Types of supplements commonly sold include exotic fruit juices (such as goji juice) and single herbs or mixture of herbs. Common claims made in support of particular supplements are that they are rich in antioxidants, induce detoxification, stimulate the immune system, and cause weight loss. Supplements are commonly sold through health food stores and by multilevel marketing. Sales may be promoted using bulk mail (\"junk mail\"), spam e-mails, and Web sites. A large part of marketing is based on claims that are blatantly dishonest. CONCLUSIONS: Whereas supplements for which good supporting evidence exists generally cost around $3-$4 per month, those that are heavily promoted for which there is little supporting evidence cost about $20-$60 per month. The major cause of this problem in the United States is weakness of the law. There is an urgent need for stricter regulation and for giving better advice to the general public.", "title": "The marketing of dietary supplements in North America: the emperor is (almost) naked." }, { "docid": "MED-1247", "text": "Background: This study is aimed at determining the efficacy of Mentha spicata (M. spicata) and Mentha × piperita (M. × piperita) in preventing chemotherapy-induced nausea and vomiting (CINV). Methods: This was a randomised, double-blind clinical trial study. Prior to the study, patients were randomly assigned into four groups to receive M. spicata or M. × piperita. Statistical analysis included the χ2 test, relative risk, and Student’s t-test. Fifty courses were analysed for each group that met our eligibility criteria. The treatment and placebo groups applied essential oils of M. spicata, M. × piperita, or a placebo, while the control group continued with their previous antiemetic regimen. Patients or guardians recorded the number of emetic events, the intensity of nausea over 20 h of chemotherapy, as well as any possible adverse effects that occurred during this time. Results: There was a significant reduction in the intensity and number of emetic events in the first 24 h with M. spicata and M. × piperita in both treatment groups (p < 0.05) when compared with the control and no adverse effects were reported. The cost of treatment was also reduced when essential oils were used. Conclusion: M. spicata or M. × piperita essential oils are safe and effective for antiemetic treatment in patients, as well as being cost effective.", "title": "Antiemetic activity of volatile oil from Mentha spicata and Mentha × piperita in chemotherapy-induced nausea and vomiting" }, { "docid": "MED-4374", "text": "CONTEXT: Despite cancer patients' widespread and growing use of complementary and alternative medicine, minimal attention has been paid to the role of health food stores in the \"supply side\" of this phenomenon. OBJECTIVE: To gain a better understanding of health food store personnel's recommendations for breast cancer patient care. DESIGN: Researcher posing as the daughter of a breast cancer patient and surveying health food store personnel on their product recommendations for cancer care. SETTING: Oahu, Hawaii, summer 1998. PARTICIPANTS: All health food stores (N = 40) offering products for cancer patients. MAIN OUTCOME MEASURES: Recommended products and services, proposed mechanism of action, and costs. RESULTS: Store personnel readily provided information and product recommendations, with shark cartilage being the most frequent. Suggested mechanisms of action drew on traditional healing, scientific, and pseudoscientific rationales. Costs for recommended dosages varied multifold across stores and brands. CONCLUSIONS: Retailers supplying supplements can play an important role in the network of \"authorities\" for patients with breast and other cancers, as they readily provide advice and recommend products. The reasons why patients seek health food store remedies are useful in developing approaches to patient education. Physicians and other providers are in a key position to assist cancer patients in making informed choices when considering health store products.", "title": "Health food store recommendations for breast cancer patients." }, { "docid": "MED-2004", "text": "The incidence and prevalence of diabetes (primarily type 2 diabetes) has risen sharply since 1990. It is projected to increase another 64% between 2010 and 2025, affecting 53.1 million people and resulting in medical and societal costs of a half trillion dollars a year. We know how to prevent many cases of diabetes and how to treat it effectively. Early appropriate treatment makes a significant difference in preventing major complications and reducing premature death, but it does not cure the disease. Early detection of prediabetes, in conjunction with lifestyle changes, can reduce the number of people with diabetes. A dramatic reduction in diabetes prevalence over time will require significant lifestyle changes on the part of society as a whole. The purpose of this study is to increase public awareness of the severity of regional diabetes trends by providing detailed forecasts for all states and several metropolitan areas for 2010, 2015, and 2025. A model was created to utilize the latest national diabetes and population data and projections, and to transform these into state and metropolitan area forecasts for the whole population and major subgroups. These forecasts were then summarized in easy-to-understand briefing papers for each state and selected metro areas, which are provided online for easy public access. This research is important because little data exist that project the future prevalence and potential costs of diabetes at the state and metro area level. With this data, key stakeholders can make informed decisions concerning diabetes, its impact on their communities, and resource allocation.", "title": "Creating public awareness: state 2025 diabetes forecasts." }, { "docid": "MED-949", "text": "OBJECTIVE: To investigate the efficacy and cost effectiveness of an herbal tea, Smooth Move, in nursing home residents with chronic constipation. DESIGN: Double-blind, placebo-controlled, 2-armed, parallel-group clinical trial. SETTING: A 483-bed nursing home in Allentown, Pennsylvania, operated by Lehigh County Government. PARTICIPANTS: A total of 86 nursing home residents with chronic constipation. INTERVENTIONS: Participants (n = 86) were randomly assigned to receive Smooth Move (n = 42) or a placebo (n = 44), once daily, in addition to standard treatment for chronic constipation. The study period was 28 days. MEASUREMENTS: The primary efficacy parameter was the difference in total number of bowel movements. Secondary parameters included the difference in average number of standard treatment doses dispensed, and the difference in total medication costs. RESULTS: Compared to placebo, in the intention to treat (ITT analysis) there was a statistically significant increase in the number of bowel movements in the Smooth Move group. The Smooth Move group (n = 42) compared with the placebo group (n = 44) experienced an average of 4.14 more bowel movements during the 28-day study period versus the 28-day pre-study period (P = .017). CONCLUSION: Smooth Move herbal tea, when added to the standard treatment regimen for nursing home residents with chronic constipation, increased the average number of bowel movements compared to the addition of a placebo tea.", "title": "Efficacy of an herbal dietary supplement (Smooth Move) in the management of constipation in nursing home residents: A randomized, double-blind, pla..." }, { "docid": "MED-1920", "text": "Overweight and obesity are major contributors to both type 2 diabetes and cardiovascular disease (CVD). Moreover, individuals with type 2 diabetes who are overweight or obese are at particularly high risk for CVD morbidity and mortality. Although short-term weight loss has been shown to ameliorate obesity-related metabolic abnormalities and CVD risk factors, the long-term consequences of intentional weight loss in overweight or obese individuals with type 2 diabetes have not been adequately examined. The primary objective of the Look AHEAD clinical trial is to assess the long-term effects (up to 11.5 years) of an intensive weight loss program delivered over 4 years in overweight and obese individuals with type 2 diabetes. Approximately 5000 male and female participants who have type 2 diabetes, are 45-74 years of age, and have a body mass index >or=25 kg/m(2) will be randomized to one of the two groups. The intensive lifestyle intervention is designed to achieve and maintain weight loss through decreased caloric intake and increased physical activity. This program is compared to a control condition given diabetes support and education. The primary study outcome is time to incidence of a major CVD event. The study is designed to provide a 0.90 probability of detecting an 18% difference in major CVD event rates between the two groups. Other outcomes include components of CVD risk, cost and cost-effectiveness, diabetes control and complications, hospitalizations, intervention processes, and quality of life.", "title": "Look AHEAD (Action for Health in Diabetes): design and methods for a clinical trial of weight loss for the prevention of cardiovascular disease in ..." }, { "docid": "MED-5126", "text": "Background The recent increased interest in consuming green vegetable sprouts has been tempered by the fact that fresh sprouts can in some cases be vehicles for food-borne illnesses. They must be grown according to proper conditions of sanitation and handled as a food product rather than as an agricultural commodity. When sprouts are grown in accordance with the criteria proposed from within the sprout industry, developed by regulatory agencies, and adhered to by many sprouters, green sprouts can be produced with very low risk. Contamination may occur when these guidelines are not followed. Methods A one year program of microbial hold-and-release testing, conducted in concert with strict seed and facility cleaning procedures by 13 U.S. broccoli sprout growers was evaluated. Microbial contamination tests were performed on 6839 drums of sprouts, equivalent to about 5 million consumer packages of fresh green sprouts. Results Only 24 (0.75%) of the 3191 sprout samples gave an initial positive test for Escherichia coli O157:H7 or Salmonella spp., and when re-tested, 3 drums again tested positive. Composite testing (e.g., pooling up to 7 drums for pathogen testing) was equally sensitive to single drum testing. Conclusion By using a \"test-and-re-test\" protocol, growers were able to minimize crop destruction. By pooling drums for testing, they were also able to reduce testing costs which now represent a substantial portion of the costs associated with sprout growing. The test-and-hold scheme described herein allowed those few batches of contaminated sprouts to be found prior to packaging and shipping. These events were isolated, and only safe sprouts entered the food supply.", "title": "Pathogen detection, testing, and control in fresh broccoli sprouts" } ]
426
Forkhead 0 (fox0) transcription factors are involved in apoptosis.
[ { "docid": "16728949", "text": "The forkhead O (FoxO) family of transcription factors participates in diverse physiologic processes, including induction of cell-cycle arrest, stress resistance, differentiation, apoptosis, and metabolism. Several recent studies indicate that FoxO-dependent signaling is required for long-term regenerative potential of the hematopoietic stem cell (HSC) compartment through regulation of HSC response to physiologic oxidative stress, quiescence, and survival. These observations link FoxO function in mammalian systems with the evolutionarily conserved role of FoxO in promotion of stress resistance and longevity in lower phylogenetic systems. Furthermore, these findings have implications for aging in higher organisms and in malignant stem cell biology, and suggest that FoxOs may play an important role in the maintenance and integrity of stem cell compartments in a broad spectrum of tissues.", "title": "Cell Stem Cell Review FoxO Transcription Factors and Stem Cell Homeostasis: Insights from the Hematopoietic System" } ]
[ { "docid": "28937856", "text": "The Sir2 deacetylase modulates organismal life-span in various species. However, the molecular mechanisms by which Sir2 increases longevity are largely unknown. We show that in mammalian cells, the Sir2 homolog SIRT1 appears to control the cellular response to stress by regulating the FOXO family of Forkhead transcription factors, a family of proteins that function as sensors of the insulin signaling pathway and as regulators of organismal longevity. SIRT1 and the FOXO transcription factor FOXO3 formed a complex in cells in response to oxidative stress, and SIRT1 deacetylated FOXO3 in vitro and within cells. SIRT1 had a dual effect on FOXO3 function: SIRT1 increased FOXO3's ability to induce cell cycle arrest and resistance to oxidative stress but inhibited FOXO3's ability to induce cell death. Thus, one way in which members of the Sir2 family of proteins may increase organismal longevity is by tipping FOXO-dependent responses away from apoptosis and toward stress resistance.", "title": "Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase." }, { "docid": "83707680", "text": "Individuals affected with developmental disorders of speech and language have substantial difficulty acquiring expressive and/or receptive language in the absence of any profound sensory or neurological impairment and despite adequate intelligence and opportunity1. Although studies of twins consistently indicate that a significant genetic component is involved1,2,3, most families segregating speech and language deficits show complex patterns of inheritance, and a gene that predisposes individuals to such disorders has not been identified. We have studied a unique three-generation pedigree, KE, in which a severe speech and language disorder is transmitted as an autosomal-dominant monogenic trait4. Our previous work mapped the locus responsible, SPCH1, to a 5.6-cM interval of region 7q31 on chromosome 7 (ref. 5). We also identified an unrelated individual, CS, in whom speech and language impairment is associated with a chromosomal translocation involving the SPCH1 interval6. Here we show that the gene FOXP2, which encodes a putative transcription factor containing a polyglutamine tract and a forkhead DNA-binding domain, is directly disrupted by the translocation breakpoint in CS. In addition, we identify a point mutation in affected members of the KE family that alters an invariant amino-acid residue in the forkhead domain. Our findings suggest that FOXP2 is involved in the developmental process that culminates in speech and language.", "title": "A forkhead-domain gene is mutated in a severe speech and language disorder" }, { "docid": "29429111", "text": "Forkhead box transcription factor, class O (FOXO) is a mammalian homologue of DAF-16, which is known to regulate the lifespan of Caenorhabditis elegans and includes subfamilies of forkhead transcription factors such as AFX, FKHRL1, and FKHR. FKHR is phosphorylated on three sites (Thr-24, Ser-256, and Ser-319) in a phosphatidylinositol 3-kinase (PI3K)/Akt-dependent manner, thereby inhibiting death signals. We here documented dephosphorylation of FKHR following transient forebrain ischemia with its concomitant translocation into the nucleus in neurons in gerbil and mouse brains. The activation of FKHR preceded delayed neuronal death in the vulnerable hippocampal regions following ischemic brain injury. The FKHR activation was accompanied by an increase in DNA binding activity for FKHR-responsive element on the Fas ligand promoter. We also defined FKHR-induced downstream targets such as Fas ligand and Bim in brain ischemia. Therefore, we propose a new strategy to rescue neurons from delayed neuronal death by promoting the survival signaling. Sodium orthovanadate, a protein tyrosine phosphatase inhibitor, up-regulated Akt activity in the brain and in turn rescue neurons from delayed neuronal death by inhibiting FKHR-dependent or -independent death signals in neurons.", "title": "Transcriptional regulation of neuronal genes and its effect on neural functions: expression and function of forkhead transcription factors in neurons." }, { "docid": "4418070", "text": "Regulatory T (Treg) cells, characterized by expression of the transcription factor forkhead box P3 (Foxp3), maintain immune homeostasis by suppressing self-destructive immune responses. Foxp3 operates as a late-acting differentiation factor controlling Treg cell homeostasis and function, whereas the early Treg-cell-lineage commitment is regulated by the Akt kinase and the forkhead box O (Foxo) family of transcription factors. However, whether Foxo proteins act beyond the Treg-cell-commitment stage to control Treg cell homeostasis and function remains largely unexplored. Here we show that Foxo1 is a pivotal regulator of Treg cell function. Treg cells express high amounts of Foxo1 and display reduced T-cell-receptor-induced Akt activation, Foxo1 phosphorylation and Foxo1 nuclear exclusion. Mice with Treg-cell-specific deletion of Foxo1 develop a fatal inflammatory disorder similar in severity to that seen in Foxp3-deficient mice, but without the loss of Treg cells. Genome-wide analysis of Foxo1 binding sites reveals ∼300 Foxo1-bound target genes, including the pro-inflammatory cytokine Ifng, that do not seem to be directly regulated by Foxp3. These findings show that the evolutionarily ancient Akt–Foxo1 signalling module controls a novel genetic program indispensable for Treg cell function.", "title": "Novel Foxo1-dependent transcriptional programs control Treg cell function" }, { "docid": "30908508", "text": "Objective: To investigate the regulation of CD4+CD25+ Regulatory T cells (Tregs) on pro-inflammatory adhesion molecules, Krüppel-Like Factor-2 (KLF-2) and its downstream transcriptional targets in human umbilical vein endothelial cells (HUVECs) impaired by ox-LDL and the mechanisms of it. Methods and results: HUVECs were cultured in the continuous presence of ox-LDL(0 mg/L,25 mg/L,50 mg/L,100 mg/L) for 4, 6, 12 and 24 hours to allow identification of early-and late-induced genes, respectively, whereas non-stimulated controls were taken at 0 hours. The expression of pro-inflammatory adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), E-selectin, KLF-2 and its target genes eNOS, PAI-1 were determined by real time RT-PCR and/or western-blot analysis. Expression of pro-inflammatory adhesion molecules, KLF-2, eNOS and PAI-1 in HUVEC cultured alone or with anti-CD3 mAbs activated Tregs, followed by addition of ox-LDL (50 mg/L) for 6 hours, are compared to expression levels in control cultures. Ox-LDL treated HUVECs increased pro-inflammatory adhesion molecules expression, as well as increased PAI-1 but decreased eNOS expression accompanied with significant downregulating of KLF-2 at a dose and time dependent manner. Furthermore, ox-LDL increased pro-inflammatory adhesion molecules but inhibited KLF2 expression was reversed by addition of Tregs. Small interfering RNA reduced endogenous KLF-2 expression and partly reversed the suppressive effect of Tregs on HUVECs activation, which strongly implicate KLF-2 as a transcriptional regulator of the Tregs-mediated effects in endothelial cells. Mechanism studies reveal that Treg-mediated KLF2 expression in HUVECs impaired by ox-LDL requires cell contact as well as soluble factors. Conclusions: Tregs could protect endothelial function that is largely dependent on KLF2 and its downstream transcriptional targets regulation involving cell-to-cell contact and soluble factors.", "title": "CD4+CD25+Foxp3+Regulatory T Cells Protect Endothelial Function Impaired by Oxidized Low Density Lipoprotein via the KLF-2 Transcription Factor" }, { "docid": "17055665", "text": "FoxO transcription factors, inhibited by insulin/insulin-like growth factor signalling (IIS), are crucial players in numerous organismal processes including lifespan. Using genomic tools, we uncover over 700 direct dFOXO targets in adult female Drosophila. dFOXO is directly required for transcription of several IIS components and interacting pathways, such as TOR, in the wild-type fly. The genomic locations occupied by dFOXO in adults are different from those observed in larvae or cultured cells. These locations remain unchanged upon activation by stresses or reduced IIS, but the binding is increased and additional targets activated upon genetic reduction in IIS. We identify the part of the IIS transcriptional response directly controlled by dFOXO and the indirect effects and show that parts of the transcriptional response to IIS reduction do not require dfoxo. Promoter analyses revealed GATA and other forkhead factors as candidate mediators of the indirect and dfoxo-independent effects. We demonstrate genome-wide evolutionary conservation of dFOXO targets between the fly and the worm Caenorhabditis elegans, enriched for a second tier of regulators including the dHR96/daf-12 nuclear hormone receptor.", "title": "Genome-wide dFOXO targets and topology of the transcriptomic response to stress and insulin signalling" }, { "docid": "8002887", "text": "Autophagy is the primary catabolic process triggered in response to starvation. Although autophagic regulation within the cytosolic compartment is well established, it is becoming clear that nuclear events also regulate the induction or repression of autophagy. Nevertheless, a thorough understanding of the mechanisms by which sequence-specific transcription factors modulate expression of genes required for autophagy is lacking. Here, we identify Foxk proteins (Foxk1 and Foxk2) as transcriptional repressors of autophagy in muscle cells and fibroblasts. Interestingly, Foxk1/2 serve to counter-balance another forkhead transcription factor, Foxo3, which induces an overlapping set of autophagic and atrophic targets in muscle. Foxk1/2 specifically recruits Sin3A-HDAC complexes to restrict acetylation of histone H4 and expression of critical autophagy genes. Remarkably, mTOR promotes the transcriptional activity of Foxk1 by facilitating nuclear entry to specifically limit basal levels of autophagy in nutrient-rich conditions. Our study highlights an ancient, conserved mechanism whereby nutritional status is interpreted by mTOR to restrict autophagy by repressing essential autophagy genes through Foxk-Sin3-mediated transcriptional control.", "title": "Foxk proteins repress the initiation of starvation-induced atrophy and autophagy programs" }, { "docid": "23535770", "text": "Neural stem cells are precursors of neurons and glial cells. During brain development, these cells proliferate, migrate and differentiate into specific lineages. Recently neural stem cells within the adult central nervous system were identified. Informations are now emerging about regulation of stem cell proliferation, migration and differentiation by numerous soluble factors such as chemokines and cytokines. However, the signal transduction mechanisms downstream of these factors are less clear. Here, we review potential evidences for a novel central role of the transcription factor nuclear factor kappa B (NF-kappaB) in these crucial signal transduction processes. NF-kappaB is an inducible transcription factor detected in neurons, glia and neural stem cells. NF-kappaB was discovered by David Baltimore's laboratory as a transcription factor in lymphocytes. NF-kappaB is involved in many biological processes such as inflammation and innate immunity, development, apoptosis and anti-apoptosis. It has been recently shown that members of the NF-kappaB family are widely expressed by neurons, glia and neural stem cells. In the nervous system, NF-kappaB plays a crucial role in neuronal plasticity, learning, memory consolidation, neuroprotection and neurodegeneration. Recent data suggest an important role of NF-kappaB on proliferation, migration and differentiation of neural stem cells. NF-kappaB is composed of three subunits: two DNA-binding and one inhibitory subunit. Activation of NF-kappaB takes place in the cytoplasm and results in degradation of the inhibitory subunit, thus enabling the nuclear import of the DNA-binding subunits. Within the nucleus, several target genes could be activated. In this review, we suggest a model explaining the multiple action of NF-kappaB on neural stem cells. Furthermore, we discuss the potential role of NF-kappaB within the so-called brain cancer stem cells.", "title": "Potential role of NF-kappaB in adult neural stem cells: the underrated steersman?" }, { "docid": "25510546", "text": "Increased lipid supply causes beta cell death, which may contribute to reduced beta cell mass in type 2 diabetes. We investigated whether endoplasmic reticulum (ER) stress is necessary for lipid-induced apoptosis in beta cells and also whether ER stress is present in islets of an animal model of diabetes and of humans with type 2 diabetes. Expression of genes involved in ER stress was evaluated in insulin-secreting MIN6 cells exposed to elevated lipids, in islets isolated from db/db mice and in pancreas sections of humans with type 2 diabetes. Overproduction of the ER chaperone heat shock 70 kDa protein 5 (HSPA5, previously known as immunoglobulin heavy chain binding protein [BIP]) was performed to assess whether attenuation of ER stress affected lipid-induced apoptosis. We demonstrated that the pro-apoptotic fatty acid palmitate triggers a comprehensive ER stress response in MIN6 cells, which was virtually absent using non-apoptotic fatty acid oleate. Time-dependent increases in mRNA levels for activating transcription factor 4 (Atf4), DNA-damage inducible transcript 3 (Ddit3, previously known as C/EBP homologous protein [Chop]) and DnaJ homologue (HSP40) C3 (Dnajc3, previously known as p58) correlated with increased apoptosis in palmitate- but not in oleate-treated MIN6 cells. Attenuation of ER stress by overproduction of HSPA5 in MIN6 cells significantly protected against lipid-induced apoptosis. In islets of db/db mice, a variety of marker genes of ER stress were also upregulated. Increased processing (activation) of X-box binding protein 1 (Xbp1) mRNA was also observed, confirming the existence of ER stress. Finally, we observed increased islet protein production of HSPA5, DDIT3, DNAJC3 and BCL2-associated X protein in human pancreas sections of type 2 diabetes subjects. Our results provide evidence that ER stress occurs in type 2 diabetes and is required for aspects of the underlying beta cell failure.", "title": "Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes" }, { "docid": "14864285", "text": "Longevity is regulated by the daf-2 gene network in Caenorhabditis elegans. Mutations in the daf-2 gene, which encodes a member of the insulin receptor family, confer the life extension (Age) phenotype and the constitutive dauer (a growth-arrested larval form specialized for dispersal) formation phenotype. The Age phenotype is mutually potentiated by two life extension mutations in the daf-2 gene and the clk-1 gene, a homologue of yeast CAT5/COQ7 known to regulate ubiquinone biosynthesis. In this study, we demonstrated that the daf-2 mutation also conferred an oxidative stress resistance (Oxr) phenotype, which was also enhanced by the clk-1 mutation. Similar to the Age phenotype, the Oxr phenotype was regulated by the genetic pathway of insulin-like signaling from daf-2 to the daf-16 gene, a homologue of the HNF-3/forkhead transcription factor. These findings led us to examine whether the insulin-like signaling pathway regulates the gene expression of antioxidant defense enzymes. We found that the mRNA level of the sod-3 gene, which encodes Mn-superoxide dismutase (SOD), was much higher in daf-2 mutants than in the wild type. Moreover, the increased sod-3 gene expression phenotype is regulated by the insulin-like signaling pathway. Although the clk-1 mutant itself did not display Oxr and the increased sod-3 expression phenotypes, the clk-1 mutation enhanced them in the daf-2 mutant, suggesting that clk-1 is involved in longevity in two ways: clk-1 composes the original clk-1 longevity program and the daf-2 longevity program. These observations suggest that the daf-2 gene network controls longevity by regulating the Mn-SOD-associated antioxidant defense system. This system appears to play a role in efficient life maintenance at the dauer stage.", "title": "YOKO HONDA AND SHUJI HONDA 1" }, { "docid": "14496749", "text": "Oxidative stress influences cell survival and homeostasis, but the mechanisms underlying the biological effects of oxidative stress remain to be elucidated. Here, we demonstrate that the protein kinase MST1 mediates oxidative-stress-induced cell death in primary mammalian neurons by directly activating the FOXO transcription factors. MST1 phosphorylates FOXO proteins at a conserved site within the forkhead domain that disrupts their interaction with 14-3-3 proteins, promotes FOXO nuclear translocation, and thereby induces cell death in neurons. We also extend the MST-FOXO signaling link to nematodes. Knockdown of the C. elegans MST1 ortholog CST-1 shortens life span and accelerates tissue aging, while overexpression of cst-1 promotes life span and delays aging. The cst-1-induced life-span extension occurs in a daf-16-dependent manner. The identification of the FOXO transcription factors as major and evolutionarily conserved targets of MST1 suggests that MST kinases play important roles in diverse biological processes including cellular responses to oxidative stress and longevity.", "title": "A Conserved MST-FOXO Signaling Pathway Mediates Oxidative-Stress Responses and Extends Life Span" }, { "docid": "42873134", "text": "Type 1 and type 2 diabetes are characterized by progressive beta-cell failure. Apoptosis is probably the main form of beta-cell death in both forms of the disease. It has been suggested that the mechanisms leading to nutrient- and cytokine-induced beta-cell death in type 2 and type 1 diabetes, respectively, share the activation of a final common pathway involving interleukin (IL)-1beta, nuclear factor (NF)-kappaB, and Fas. We review herein the similarities and differences between the mechanisms of beta-cell death in type 1 and type 2 diabetes. In the insulitis lesion in type 1 diabetes, invading immune cells produce cytokines, such as IL-1beta, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma. IL-1beta and/or TNF-alpha plus IFN-gamma induce beta-cell apoptosis via the activation of beta-cell gene networks under the control of the transcription factors NF-kappaB and STAT-1. NF-kappaB activation leads to production of nitric oxide (NO) and chemokines and depletion of endoplasmic reticulum (ER) calcium. The execution of beta-cell death occurs through activation of mitogen-activated protein kinases, via triggering of ER stress and by the release of mitochondrial death signals. Chronic exposure to elevated levels of glucose and free fatty acids (FFAs) causes beta-cell dysfunction and may induce beta-cell apoptosis in type 2 diabetes. Exposure to high glucose has dual effects, triggering initially \"glucose hypersensitization\" and later apoptosis, via different mechanisms. High glucose, however, does not induce or activate IL-1beta, NF-kappaB, or inducible nitric oxide synthase in rat or human beta-cells in vitro or in vivo in Psammomys obesus. FFAs may cause beta-cell apoptosis via ER stress, which is NF-kappaB and NO independent. Thus, cytokines and nutrients trigger beta-cell death by fundamentally different mechanisms, namely an NF-kappaB-dependent mechanism that culminates in caspase-3 activation for cytokines and an NF-kappaB-independent mechanism for nutrients. This argues against a unifying hypothesis for the mechanisms of beta-cell death in type 1 and type 2 diabetes and suggests that different approaches will be required to prevent beta-cell death in type 1 and type 2 diabetes.", "title": "Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities." }, { "docid": "22896384", "text": "The airways of the lung develop through a reiterative process of branching morphogenesis that gives rise to the intricate and extensive surface area required for postnatal respiration. The forkhead transcription factors Foxp2 and Foxp1 are expressed in multiple foregut-derived tissues including the lung and intestine. In this report, we show that loss of Foxp2 in mouse leads to defective postnatal lung alveolarization, contributing to postnatal lethality. Using in vitro and in vivo assays, we show that T1alpha, a lung alveolar epithelial type 1 cell-restricted gene crucial for lung development and function, is a direct target of Foxp2 and Foxp1. Remarkably, loss of a single Foxp1 allele in addition to complete loss of Foxp2 results in increased severity of morphological defects in mutant lungs and leads to perinatal loss of all Foxp2(-/-);Foxp1(+/-) mice. Expression of N-myc and Hop, crucial regulators of lung development, is compromised in Foxp2(-/-);Foxp1(+/-) mutants. In addition to the defects in lung development, esophageal muscle development is disrupted in Foxp2(-/-);Foxp1(+/-) embryos, a tissue where Foxp2 and Foxp1 are co-expressed. These data identify Foxp2 and Foxp1 as crucial regulators of lung and esophageal development, underscoring the necessity of these transcription factors in the development of anterior foregut-derived tissues and demonstrating functional cooperativity between members of the Foxp1/2/4 family in tissues where they are co-expressed.", "title": "Foxp2 and Foxp1 cooperatively regulate lung and esophagus development." }, { "docid": "6896063", "text": "p53 functions as a transcription factor involved in cell-cycle control, DNA repair, apoptosis and cellular stress responses. However, besides inducing cell growth arrest and apoptosis, p53 activation also modulates cellular senescence and organismal aging. Senescence is an irreversible cell-cycle arrest that has a crucial role both in aging and as a robust physiological antitumor response, which counteracts oncogenic insults. Therefore, via the regulation of senescence, p53 contributes to tumor growth suppression, in a manner strictly dependent by its expression and cellular context. In this review, we focus on the recent advances on the contribution of p53 to cellular senescence and its implication for cancer therapy, and we will discuss p53’s impact on animal lifespan. Moreover, we describe p53-mediated regulation of several physiological pathways that could mediate its role in both senescence and aging.", "title": "Senescence and aging: the critical roles of p53" }, { "docid": "919007", "text": "The forkhead box (Fox) family of transcription factors, which originated in unicellular eukaryotes, has expanded over time through multiple duplication events, and sometimes through gene loss, to over 40 members in mammals. Fox genes have evolved to acquire a specialized function in many key biological processes. Mutations in Fox genes have a profound effect on human disease, causing phenotypes as varied as cancer, glaucoma and language disorders. We summarize the salient features of the evolution of the Fox gene family and highlight the diverse contribution of various Fox subfamilies to developmental processes, from organogenesis to speech acquisition.", "title": "The evolution of Fox genes and their role in development and disease" }, { "docid": "9393969", "text": "Organisms are constantly challenged by stresses and privations and require adaptive responses for their survival. The forkhead box O (FOXO) transcription factor DAF-16 (hereafter referred to as DAF-16/FOXO) is a central nexus in these responses, but despite its importance little is known about how it regulates its target genes. Proteomic identification of DAF-16/FOXO-binding partners in Caenorhabditis elegans and their subsequent functional evaluation by RNA interference revealed several candidate DAF-16/FOXO cofactors, most notably the chromatin remodeller SWI/SNF. DAF-16/FOXO and SWI/SNF form a complex and globally co-localize at DAF-16/FOXO target promoters. We show that specifically for gene activation, DAF-16/FOXO depends on SWI/SNF, facilitating SWI/SNF recruitment to target promoters, to activate transcription by presumed remodelling of local chromatin. For the animal, this translates into an essential role for SWI/SNF in DAF-16/FOXO-mediated processes, in particular dauer formation, stress resistance and the promotion of longevity. Thus, we give insight into the mechanisms of DAF-16/FOXO-mediated transcriptional regulation and establish a critical link between ATP-dependent chromatin remodelling and lifespan regulation.", "title": "DAF-16/FOXO employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity" }, { "docid": "7465900", "text": "BACKGROUND & AIMS Helicobacter pylori-induced gastric epithelial cell (GEC) apoptosis is a complex process that includes activation of the tumor suppressor p53. p53-mediated apoptosis involves p53 activation, bax transcription, and cytochrome c release from mitochondria. Apurinic/apyrimidinic endonuclease-1 (APE-1) regulates transcriptional activity of p53, and H pylori induce APE-1 expression in human GECs. H pylori infection increases intracellular calcium ion concentration [Ca2+]i of GECs, which induces APE-1 acetylation. We investigated the effects of H pylori infection and APE-1 acetylation on GEC apoptosis. METHODS AGS cells (wild-type or with suppressed APE-1), KATO III cells, and cells isolated from gastric biopsy specimens were infected with H pylori. Effects were examined by immunoblotting, real-time reverse-transcription polymerase chain reaction, immunoprecipitation, immunofluorescence microscopy, chromatin immunoprecipitation, mobility shift, DNA binding, and luciferase assays. RESULTS H pylori infection increased [Ca2+]i and acetylation of APE-1 in GECs, but the acetylation status of APE-1 did not affect the transcriptional activity of p53. In GECs, expression of a form of APE-1 that could not be acetylated increased total and mitochondrial levels of Bax and induced release of cytochrome c and fragmentation of DNA; expression of wild-type APE-1 reduced these apoptotic events. We identified a negative calcium response element in the human bax promoter and found that poly (adenosine diphosphate-ribose) polymerase 1 recruited the acetylated APE-1/histone deacetylase-1 repressor complex to bax nCaRE. CONCLUSIONS H pylori-mediated acetylation of APE-1 suppresses Bax expression; this prevents p53-mediated apoptosis when H pylori infect GECs.", "title": "Acetylation of apurinic/apyrimidinic endonuclease-1 regulates Helicobacter pylori-mediated gastric epithelial cell apoptosis." }, { "docid": "3710557", "text": "β-catenin (encoded by CTNNB1) is a subunit of the cell surface cadherin protein complex that acts as an intracellular signal transducer in the WNT signaling pathway; alterations in its activity have been associated with the development of hepatocellular carcinoma and other liver diseases. Other than WNT, additional signaling pathways also can converge at β-catenin. β-catenin also interacts with transcription factors such as T-cell factor, forkhead box protein O, and hypoxia inducible factor 1α to regulate the expression of target genes. We discuss the role of β-catenin in metabolic zonation of the adult liver. β-catenin also regulates the expression of genes that control metabolism of glucose, nutrients, and xenobiotics; alterations in its activity may contribute to the pathogenesis of nonalcoholic steatohepatitis. Alterations in β-catenin signaling may lead to activation of hepatic stellate cells, which is required for fibrosis. Many hepatic tumors such as hepatocellular adenomas, hepatocellular cancers, and hepatoblastomas have mutations in CTNNB1 that result in constitutive activation of β-catenin, so this molecule could be a therapeutic target. We discuss how alterations in β-catenin activity contribute to liver disease and how these might be used in diagnosis and prognosis, as well as in the development of therapeutics.", "title": "β-Catenin Signaling and Roles in Liver Homeostasis, Injury, and Tumorigenesis." }, { "docid": "10218447", "text": "Isorhamnetin is one member of flavonoid components which has been used in the treatment of heart disease. Recently the in vitro anti-cancer effect of isorhamnetin on human esophageal squamous carcinoma cell line Eca-109 was investigated in our lab. When Eca-109 cells were in vitro exposed to the graded doses of isorhamnetin (0-80 microg/ml) for 48 h, respectively, isorhamnetin exhibited cytostatic effect on the treated cells, with an IC(50) of 40+/-0.08 microg/ml as estimated by MTT assay. Inhibition on proliferation by isorhamnetin was detected by trypan blue exclusion assay, clone formation test, immunocytochemical assay of PCNA and (3)H-thymidine uptake analysis. Cell cycle distribution was measured by FCM. It was found that the viability of Eca-109 cells was significantly hampered by isorhamnetin. Compared with the negative control group, the treated group which was exposed to isorhamnetin had increased population in G(0)/G(1) phase from 74.6 to 84 while had a significant reduction in G(2)/M phase from 11.9 to 5.8. In addition to its cytostatic effect, isorhamnetin also showed stimulatory effect on apoptosis. Typical apoptotic morphology such as condensation and fragmentation of nuclei and blebbing membrane of the apoptotic cells could be observed through transmission electron microscope. Moreover, the sharp increase in apoptosis rate between the control and treated group were detected by FCM from 6.3 to 16.3. To explore the possible molecular mechanisms that underlie the growth inhibition and apoptosis stimulatory effects of isorhamnetin, the expressions of six proliferation- and death-related genes were detected by FCM. Expressions of bcl-2, c-myc and H-ras were downregulated whereas Bax, c-fos and p53 were upregulated. However, the in vivo experiments were required to further confirm the anti-cancer effects of isorhamnetin. In conclusion, isorhamnetin appears to be a potent drug against esophageal cancer due to its in vitro potential to not only inhibit proliferation but also induce apoptosis of Eca-109 cells.", "title": "The flavonoid component isorhamnetin in vitro inhibits proliferation and induces apoptosis in Eca-109 cells." }, { "docid": "3748310", "text": "Although the essential role of the adaptor protein SLP-65 in pre-B cell differentiation is established, the molecular mechanism underlying its function is poorly understood. In this study, we uncover a link between SLP-65–dependent signaling and the phosphoinositide-3-OH kinase (PI(3)K)–protein kinase B (PKB)–Foxo pathway. We show that the forkhead box transcription factor Foxo3a promotes light chain rearrangement in pre-B cells. Our data suggest that PKB suppresses light chain recombination by phosphorylating Foxo proteins, whereas reconstitution of SLP-65 function counteracts PKB activation and promotes Foxo3a and Foxo1 activity in pre-B cells. Together, these data illuminate a molecular function of SLP-65 and identify a key role for Foxo proteins in the regulation of light chain recombination, receptor editing and B cell selection.", "title": "SLP-65 regulates immunoglobulin light chain gene recombination through the PI(3)K-PKB-Foxo pathway" }, { "docid": "18546584", "text": "CD4(+) helper T (Th) cells play a crucial role in the delicate balance between host defense and autoimmune disease. Two important populations of helper T cells are the proinflammatory, interleukin-17 (IL-17)-producing (Th17) cells and the anti-inflammatory forkhead box P3-positive (FoxP3(+)) T regulatory (Treg) cells. Here we show that all-trans retinoic acid (ATRA) and other agonists of the retinoic acid receptor alpha (RARalpha) inhibit the formation of Th17 cells and promote FoxP3 expression. Conversely, inhibition of retinoic acid signaling constrains transforming growth factor beta (TGF-beta1) induction of FoxP3. The effect of ATRA is mediated independently of IL-2, signal transducer and activator of transcription 5 (Stat5) and Stat3, representing a novel mechanism for the induction of FoxP3 in CD4 T cells. As previous studies have shown that vitamin A derivatives are protective in animal models of autoimmune disease, the current data suggest a previously unrecognized role for RARalpha in the regulation of CD4(+) T-cell differentiation and provide a mechanism for the anti-inflammatory effects of retinoic acid.", "title": "Retinoic acid inhibits Th17 polarization and enhances FoxP3 expression through a Stat-3/Stat-5 independent signaling pathway." }, { "docid": "28006126", "text": "CD28 is one of the most important costimulatory receptors necessary for full T lymphocyte activation. The CD28 receptor can enhance T cell antigen receptor (TCR) signals, as well as deliver independent signals. Indeed, CD28 engagement by B7 can generate TCR-independent signals leading to IkappaB kinase and NF-kappaB activation. Here we demonstrate that the TCR-independent CD28 signal leads to the selective transcription of survival (Bcl-xL) and inflammatory (IL-8 and B cell activation factor, but not proliferative (IL-2), genes, in a NF-kappaB-dependent manner. CD28-stimulated T cells actively secrete IL-8, and Bcl-xL up-regulation protects T cells from radiation-induced apoptosis. The transcription of CD28-induced genes is mediated by the specific recruitment of RelA and p52 NF-kappaB subunits to target promoters. In contrast, p50 and c-Rel, which preferentially bind NF-kappaB sites on the IL-2 gene promoter after anti-CD3 stimulation, are not involved. Thus, we identify CD28 as a key regulator of genes important for both survival and inflammation.", "title": "CD28 delivers a unique signal leading to the selective recruitment of RelA and p52 NF-kappaB subunits on IL-8 and Bcl-xL gene promoters." }, { "docid": "15248287", "text": "Neutrophil apoptosis is a highly regulated process essential for inflammation resolution, the molecular mechanisms of which are only partially elucidated. In this study, we describe a survival pathway controlled by proliferating cell nuclear antigen (PCNA), a nuclear factor involved in DNA replication and repairing of proliferating cells. We show that mature neutrophils, despite their inability to proliferate, express high levels of PCNA exclusively in their cytosol and constitutively associated with procaspases, presumably to prevent their activation. Notably, cytosolic PCNA abundance decreased during apoptosis, and increased during in vitro and in vivo exposure to the survival factor granulocyte colony-stimulating factor (G-CSF). Peptides derived from the cyclin-dependent kinase inhibitor p21, which compete with procaspases to bind PCNA, triggered neutrophil apoptosis thus demonstrating that specific modification of PCNA protein interactions affects neutrophil survival. Furthermore, PCNA overexpression rendered neutrophil-differentiated PLB985 myeloid cells significantly more resistant to TNF-related apoptosis-inducing ligand- or gliotoxin-induced apoptosis. Conversely, a decrease in PCNA expression after PCNA small interfering RNA transfection sensitized these cells to apoptosis. Finally, a mutation in the PCNA interdomain-connecting loop, the binding site for many partners, significantly decreased the PCNA-mediated antiapoptotic effect. These results identify PCNA as a regulator of neutrophil lifespan, thereby highlighting a novel target to potentially modulate pathological inflammation.", "title": "Proliferating cell nuclear antigen acts as a cytoplasmic platform controlling human neutrophil survival" }, { "docid": "24624992", "text": "In a cell-type- and stimulus-dependent fashion, the early response gene immediate early gene X-1 (IEX-1) is involved in growth control and modulation of apoptosis. The present study demonstrates that, in the two acute promyelocytic leukemia (APL) cell lines NB4 and KG1, exhibiting distinct responsiveness to retinoic acids (RAs), IEX-1 expression is rapidly (30–60 min) induced by all-trans- or cis-RA and independently of other signal transduction mediators, such as TNFα, NF-κB or MAP kinases. In NB4 cells (expressing PML–RARα), this increase is transient and completely reversible, along with a cell cycle arrest, ongoing differentiation and lower sensitivity to anti-cancer-drug-induced apoptosis. In contrast, the RA-induced IEX-1 expression in KG1 cells (expressing PLZF–RARα) persists over days, along with continued cell cycle progression and increased apoptotic sensitivity. Furthermore, two functional RA-response elements in the IEX-1 promoter were identified by gel shift and luciferase reporter gene assays. IEX-1 might be a rather unique transcriptional target of the two X–RARα fusion receptors exhibiting distinct responsiveness to RAs. Following a different time course of direct transcriptional induction by PML–RARα and PLZF–RARα in NB4 and KG1 cells, respectively, IEX-1 expression may be involved in the modified actions of these receptors and the distinct phenotypes of APL cells.", "title": "The expression of immediate early gene X-1 (IEX-1) is differentially induced by retinoic acids in NB4 and KG1 cells: possible implication in the distinct phenotype of retinoic acid-responsive and -resistant leukemic cells" }, { "docid": "39580129", "text": "OBJECTIVES Several miRNAs are aberrantly expressed in cancer. miR-24-3p is involved in cancer-related cellular processes, including cell cycle control, cell growth, proliferation, and apoptosis. In this study, we examined the potential diagnostic and prognostic significance of miR-24-3p expression in colorectal adenocarcinoma. DESIGN AND METHODS Total RNA was isolated from 182 colorectal adenocarcinoma specimens and 86 paired non-cancerous colorectal mucosae. After polyadenylation of 2μg total RNA and reverse transcription into first-strand cDNA using an oligo-dT-adapter primer, miR-24-3p expression was quantified using an in-house-developed reverse-transcription real-time quantitative PCR method, based on the SYBR Green chemistry. SNORD43 (RNU43) was used as a reference gene. RESULTS miR-24-3p levels do not significantly differ between colorectal adenocarcinoma and non-cancerous colorectal mucosae. Thus, miR-24-3p expression cannot be used for diagnostic purposes. However, high miR-24-3p expression predicts poor disease-free survival (DFS) and overall survival (OS) of colorectal adenocarcinoma patients. Multivariate Cox regression analysis confirmed that miR-24-3p overexpression is a significant predictor of relapse in colorectal adenocarcinoma and that its prognostic significance is independent of other established prognostic factors and treatment of patients. Of note, miR-24-3p overexpression retains its rather unfavorable prognostic value in the subgroup of patients with advanced yet locally restricted colorectal adenocarcinoma (T3) and in those without distant metastasis (M0). Moreover, miR-24-3p overexpression is a potentially unfavorable prognosticator for patients who were not treated with radiotherapy. CONCLUSIONS Strong expression of miR-24-3p predicts poor DFS and OS of colorectal adenocarcinoma patients, independently of clinicopathological parameters that are currently used for prognosis in this human malignancy.", "title": "Elevated expression of miR-24-3p is a potentially adverse prognostic factor in colorectal adenocarcinoma." }, { "docid": "207972", "text": "Early region 3 (E3) of group C human adenoviruses (Ad) encodes several inhibitors of tumor necrosis factor alpha (TNF-alpha) cytolysis, including an E3 14.7-kDa protein (E3-14.7K) and a heterodimer containing two polypeptides of 10.4 and 14.5 kDa. To understand the mechanism by which the viral proteins inhibit TNF-alpha functions, the E3-14.7K protein was used to screen a HeLa cell cDNA library to search for interacting proteins in the yeast two-hybrid system. A novel protein containing multiple leucine zipper domains without any significant homology with any known protein was identified and has been named FIP-2 (for 14.7K-interacting protein). FIP-2 interacted with E3-14.7K both in vitro and in vivo. It colocalized with Ad E3-14.7K in the cytoplasm, especially near the nuclear membrane, and caused redistribution of the viral protein. FIP-2 by itself does not cause cell death; however, it can reverse the protective effect of E3-14.7K on cell killing induced by overexpression of the intracellular domain of the 55-kDa TNF receptor or by RIP, a death protein involved in the TNF-alpha and Fas apoptosis pathways. Deletion analysis indicates that the reversal effect of FIP-2 depends on its interaction with E3-14.7K. Three major mRNA forms of FIP-2 have been detected in multiple human tissues, and expression of the transcripts was induced by TNF-alpha treatment in a time-dependent manner in two different cell lines. FIP-2 has consensus sequences for several potential posttranslational modifications. These data suggest that FIP-2 is one of the cellular targets for Ad E3-14.7K and that its mechanism of affecting cell death involves the TNF receptor, RIP, or a downstream molecule affected by either of these two molecules.", "title": "Interaction of an adenovirus E3 14.7-kilodalton protein with a novel tumor necrosis factor alpha-inducible cellular protein containing leucine zipper domains." }, { "docid": "1191830", "text": "OBJECTIVE The 1987 American College of Rheumatology (ACR; formerly the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticised for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA. METHODS A joint working group from the ACR and the European League Against Rheumatism developed, in three phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease--this being the appropriate current paradigm underlying the disease construct 'RA'. RESULTS In the new criteria set, classification as 'definite RA' is based on the confirmed presence of synovitis in at least one joint, absence of an alternative diagnosis better explaining the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in four domains: number and site of involved joints (range 0-5), serological abnormality (range 0-3), elevated acute-phase response (range 0-1) and symptom duration (two levels; range 0-1). CONCLUSION This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimise the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct 'RA'.", "title": "2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative." }, { "docid": "6121555", "text": "The aim of this study was to investigate the mechanism through which Sphingosine kinase-1 (SPHK1) exerts its anti-apoptosis activity in glioma cancer cells. We here report that dysregulation of SPHK1 alters the sensitivity of glioma to apoptosis both in vitro and in vivo. Further mechanistic study examined the expression of Bcl-2 family members, including Bcl-2, Mcl-1, Bax and Bim, in SPHK1-overexpressing glioma cells and revealed that only pro-apoptotic Bim was downregulated by SPHK1. Moreover, the transcriptional level of Bim was also altered by SPHK1 in glioma cells. We next confirmed the correlation between SPHK1 and Bim expression in primary glioma specimens. Importantly, increasing SPHK1 expression in glioma cells markedly elevated Akt activity and phosphorylated inactivation of FOXO3a, which led to downregulation of Bim. A pharmacological approach showed that these effects of SPHK1 were dependent on phosphatidylinositol 3-kinase (PI3K). Furthermore, effects of SPHK1 on Akt/FOXO3a/Bim pathway could be reversed by SPHK1 specific RNA interference or SPHK1 inhibitor. Collectively, our results indicate that regulation of the Akt/FOXO3a/Bim pathway may be a novel mechanism by which SPHK1 protects glioma cells from apoptosis, thereby involved in glioma tumorigenesis.", "title": "Sphingosine Kinase 1 Regulates the Akt/FOXO3a/Bim Pathway and Contributes to Apoptosis Resistance in Glioma Cells" }, { "docid": "20630805", "text": "Histone posttranslational modifications are key components of diverse processes that modulate chromatin structure. These marks function as signals during various chromatin-based events, and act as platforms for recruitment, assembly or retention of chromatin-associated factors. The best-known function of histone phosphorylation takes place during cellular response to DNA damage, when phosphorylated histone H2A(X) demarcates large chromatin domains around the site of DNA breakage. However, multiple studies have also shown that histone phosphorylation plays crucial roles in chromatin remodeling linked to other nuclear processes. In this review, we summarize the current knowledge of histone phosphorylation and describe the many kinases and phosphatases that regulate it. We discuss the key roles played by this histone mark in DNA repair, transcription and chromatin compaction during cell division and apoptosis. Additionally, we describe the intricate crosstalk that occurs between phosphorylation and other histone modifications and allows for sophisticated control over the chromatin remodeling processes.", "title": "Histone phosphorylation: a chromatin modification involved in diverse nuclear events." }, { "docid": "8446259", "text": "Background: Vascular calcification (VC), in which vascular smooth muscle cells (VSMCs) undergo a phenotypic transformation into osteoblast-like cells, is one of the emergent risk factors for the accelerated atherosclerosis process characteristic of chronic kidney disease (CKD). Phosphate is an important regulator of VC. Methods: The expression of different smooth muscle cell or osteogenesis markers in response to high concentrations of phosphate or exogenous bone morphogenetic protein 2 (BMP-2) was examined by qRT-PCR and western blotting in rat VSMCs. Osteocalcin secretion was measured by radioimmunoassay. Differentiation and calcification of VSMCs were examined by alkaline phosphatase (ALP) activity assay and Alizarin staining. Short hairpin RNA-mediated silencing of β-catenin was performed to examine the involvement of Wnt/β-catenin signaling in VSMC calcification and osteoblastic differentiation induced by high phosphate or BMP-2. Apoptosis was determined by TUNEL assay and immunofluorescence imaging. Results: BMP-2 serum levels were significantly higher in CKD patients than in controls. High phosphate concentrations and BMP-2 induced VSMC apoptosis and upregulated the expression of β-catenin, Msx2, Runx2 and the phosphate cotransporter Pit1, whereas a BMP-2 neutralization antibody reversed these effects. Knockdown of β-catenin abolished the effect of high phosphate and BMP-2 on VSMC apoptosis and calcification. Conclusions: BMP-2 plays a crucial role in calcium deposition in VSMCs and VC in CKD patients via a mechanism involving the Wnt/β-catenin pathway.", "title": "Vascular Calcification in Chronic Kidney Disease is Induced by Bone Morphogenetic Protein-2 via a Mechanism Involving the Wnt/β-Catenin Pathway" } ]
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How do day-traders or frequent traders handle their taxes?
[ { "docid": "262291", "text": "Starting of 2011, your broker has to keep track of all the transactions and the cost basis, and it will be reported on your 1099-B. Also, some brokers allow downloading the data directly to your tax software or to excel charts (I use E*Trade, and last year TurboTax downloaded all the transaction directly from them).", "title": "" }, { "docid": "252176", "text": "\"There are two ways to handle this. The first is that the better brokers, such as Charles Schwab, will produce summaries of your gains and losses (using historical cost information), as well as your trades, on a monthly and annual basis. These summaries are \"\"ready made\"\" for the IRS. More brokers will provide these summaries come 2011. The second is that if you are a \"\"frequent trader\"\" (see IRS rulings for what constitutes one), then they'll allow you to use the net worth method of accounting. That is, you take the account balance at the end of the year, subtract the beginning balance, adjust the value up for withdrawals and down for infusions, and the summary is your gain or loss. A third way is to do all your trading in say, an IRA, which is taxed on distribution, not on stock sales.\"", "title": "" }, { "docid": "159727", "text": "You need to track every buy and sell to track your gains, or more likely, losses. Yes, you report each and every transactions. Pages of schedule D.", "title": "" } ]
[ { "docid": "17231", "text": "This is often the case where traders are closing out short positions they don't want to hold overnight, for a variety of reasons that matter to them. Most frequently, this is from day traders or high-frequency traders settling their accounts before the markets close.", "title": "" }, { "docid": "565501", "text": "One could use technical indicators in any number of ways...they aren't rigidly defined for use in any particular way. If they were, only computers would use them. Having said that, moving averages are frequently used by people operating on the assumption that short-term price movements will soon be reverted back to a longer-term mean. So if the price shoots up today, traders who use moving averages may believe it will come back down pretty soon. If this is the belief (and it usually is for this type of trader), a price significantly above a moving average could indicate an overpriced stock. A price below the moving average could indicate an underpriced stock. Similarly, a short-term moving average above the long-term moving average may indicate an overpriced stock. When you are dealing with more than one frequency, though, there is more disagreement about how to use technical indicators. Some traders would probably say the opposite: that a short term average above the long term average indicates an upward movement that will continue because they believe the stock has momentum. Note that I am not saying I believe in using these averages to predict mean reversion or momentum effects, just that traders who rely on moving averages frequently do.", "title": "" }, { "docid": "581504", "text": "FFTs target people who make frequent, large transactions. It would primarily affect people like day traders, high frequency traders. If you're doing either of those things with your 401(k), I think you have other problems. Oh, it'll also affect people transferring extremely large amounts of money (like billions), which again, if you have in your 401(k), you have other problems.", "title": "" }, { "docid": "108721", "text": "Fund rebalancing typically refers to changing the investment mix to stay within the guidelines of the mutual fund objective. For example, lets say a fund is supposed to have at least 20% in bonds. Because of a dramatic increase in stock price and decrease in bond values it finds itself with only 19.9% in bonds at the end of the trading day. The fund manager would sell sufficient equities to reduce its equity holdings and buy more bonds. Rebalancing is not always preferential because it could cause capital gain distribution, typically once per year, without selling the fund. And really any trading within the fun could do the same. In the case you cite the verbiage is confusing. Often times I wonder if the author knows less then the reader. It might also be a bit of a rush to get the article out, and the author did not write correctly. I agree that the ETFs cited are suitable for short term traders. However, that is because, traditionaly, the market has increased in value over the long term. If you bet it will go down over the long term, you are almost certain to lose money. Like you, I cannot figure out how rebalancing makes this suitable only for short term traders. If the ETFs distribute capital gains events much more frequently then once per year, that is worth mentioning, but does not provide a case for short versus long term traders. Secondly, I don't think these funds are doing true rebalancing. They might change investments daily for the most likely profitable outcome, but that really isn't rebalancing. It seems the author is confused.", "title": "" }, { "docid": "532485", "text": "\"How often do investors really lose money? All the time. And it's almost always reason number 1. Let's start with the beginner investor, the person most likely to make some real losses and feel they've \"\"learned\"\" that investing is no better than Vegas. This person typically gets into it because they've been given a hot stock tip, or because they've received a windfall, decided to give this investing lark a try, and bought stock in half a dozen companies whose names they know from their everyday lives (\"\"I own a bit of Google! How cool is that?\"\"). These are people who don't understand the cyclic nature of the market (bear gives way to bull gives way to bear, and on and on), and so when they suddenly see that what was $1000 is now $900 they panic and sell everything. Especially as all the pundits are declaring the end of the world (they always do). Until the moment they sold, they only had paper losses. But they crystallised those losses, made them real, and ended at a loss. Then there's the trend-follower. These are people who don't necessarily hit a bear market, or even a downturn, in their early days, but never really try to learn how the market works in any real sense. They jump into every hot stock, then panic and sell out of anything that starts to go the wrong way. Both of these reactive behaviours seem reasonable in the moment (\"\"It's gone up 15% in the past week? Buy buy buy!\"\" and \"\"I've lost 10% this month on that thing? Get rid of it before I lose any more!\"\"), but they work out over time to lots of buying high and selling low, the very opposite of what you want to do. Then there's the day-trader. These are people who sit in their home office, buying and selling all day to try and make lots of little gains that add up to a lot. The reason these people don't do well in the long run is slightly different to the other examples. First, fees. Yes, most platforms offer a discount for \"\"frequent traders\"\", but it still ain't free. Second, they're peewees playing in the big leagues. Of course there are exceptions who make out like bandits, but day traders are playing a different game than the people I'd call investors. That game, unlike buy-and-hold investing, is much more like gambling, and day-traders are the enthusiastic amateurs sitting down at a table with professional poker players – institutional investors and the computers and research departments that work for them. Even buy-and-hold investors, even the more sophisticated ones, can easily realise losses on a given stock. You say you should just hold on to a stock until it goes back up, but if it goes low enough, it could take a decade or more to even just break even again. More savvy stock-pickers will have a system worked out, something like \"\"ok, if it gets down to 90% of what I bought it for, I cut my losses and sell.\"\" This is actually a sensible precaution, because defining hard rules like that helps​ you eliminate emotion from your investing, which is incredibly important if you want to avoid becoming the trend-follower above. It's still a loss, but it's a calculated one, and hopefully over time the exception rather than the rule. There are probably as many other ways to lose money as there are people investing, but I think I've given you a taste. The key to avoiding such things is understanding the psychology of investing, and defining the rules that you'll follow no matter what (as in that last example). Or just go learn about index investing. That's what I did.\"", "title": "" }, { "docid": "184705", "text": "Say for example a trade totals $10,000. A flat tax of 0.2% would be $20. This is not much for the Buy &amp; Holder b/c he only makes a few trades a year, say 10 transactions a year. So their tax is only about $200 per year. (heck we could even drop it to 0.1%). But DayTraders will routinely do 10 trades a day, or over 3000 trades a year. So using that same 10K trade above, that could hypothetically be 3000x20 = $60,000 per year in taxes. Computer Traders will do hundreds of trades per day. Say 30,000 trades per year. So that is $600,000. So you can see how iit hardly affects legitimate investors, while making the HF traders control themselves a bit. This is what we want. The exchanges charge the flat tax with the transaction like a Sales tax. It avoids excess regulation (the SEC already monitors trades, or is supposed to), and it hurts the gamblers (HFTs), while not hindering the good guys (investors).", "title": "" }, { "docid": "162630", "text": "Firstly if you've formed a limited company you don't need to register as self-employed. You're an employee and shareholder of the company and your taxes will be handled that way. Registering as self-employed is only necessary if you're operating as a sole trader (i.e. without a company). Secondly you absolutely do want to get set-up correctly with HMRC as soon as possible, whether you're a company or a sole trader. Ignoring the legal question your worry about paying taxes when you have no income is groundless - if you're not making any money there won't be any tax to pay. Furthermore it seems likely that the business is currently losing money. Those losses, if correctly recorded, can be carried forward and offset against future profits so not only do you not have to pay tax now, but you can reduce the tax you pay later when the money does start rolling in.", "title": "" }, { "docid": "139915", "text": "I believe that it's not possible for the public to know what shares are being exchanged as shorts because broker-dealers (not the exchanges) handle the shorting arrangements. I don't think exchanges can even tell the difference between a person selling a share that belongs to her vs. a share that she's just borrowing. (There are SEC regulations requiring some traders to declare that trades are shorts, but (a) I don't think this applies to all traders, (b) it only applies to the sells, and (c) this information isn't public.) That being said, you can view the short interest in a symbol using any of a number of tools, such as Nasdaq's here. This is often cited as an indicator similar to what you proposed, though I don't know how helpful it would be from an intra-day perspective.", "title": "" }, { "docid": "288848", "text": "\"From what I have read from O'Neil to Van Tharp, etc, etc, no one can pick winners more than 75% of the time regardless of the system they use and most traders consider themselves successful if 60% of the trades are winners and 40% are losers. So I am on the side that the chart is only a reflection of the past and cannot tell you reliably what will happen in the future. It is difficult to realize this but here is a simple way for you to realize it. If you look at a daily chart and let's say it is 9:30 am at the open and you ask a person to look at the technical indicators, look at the fundamentals and decide the direction of the market by drawing the graph, just for the next hour. He will realize in just a few seconds that he will say to him or her self \"\"How on earth do you expect me to be able to do that?\"\" He will realize very quickly that it is impossible to tell the direction of the market and he realizes it would be foolhardy to even try. Because Mickey Mantle hit over 250 every year of his career for the first 15 years it would be a prudent bet to bet that he could do it again over the span of a season, but you would be a fool to try to guess if the next pitch would be a ball or a strike. You would be correct about 50% of the time and wrong about 50% of the time. You can rely on LARGER PATTERNS OF BEHAVIOR OVER YEARS, but short hourly or even minute by minute prediction is foolish. That is why to be a trader you have to keep on trading and if you keep on trading and cut your losses to 1/2 of your wins you will eventually have a wonderful profit. But you have to limit your risk on any one trade to 1% of your portfolio. In that way you will be able to trade at least 100 times. do the math. trade a hundred times. lose 5% and the next bet gain 10%. Keep on doing it. You will have losses sometimes of 3 or 4 in a row and also wins sometimes of 3 or 4 in a row but overall if you keep on trading even the best traders are generally only \"\"right\"\" 60% of the time. So lets do the math. If you took 100 dollars and make 100 trades and the first trade you made 10% and reinvested the total and the second trade you lost 5% of that and continue that win/loss sequence for 100 trades you would have 1284 dollars minus commissions. That is a 1200% return in one hundred trades. If you do it in a roth IRA you pay no taxes on the short term gains. It is not difficult to realize that the stock market DOES TREND. And the easiest way to make 10% quickly is to in general trade 3x leveraged funds or stocks that have at least 3 beta from the general index. Take any trend up and count the number of days the stock is up and it is usually 66-75% and take any down trend and it is down 66-75% of the days. So if you bet on the the beginning of a day when the stock was up and if you buy the next day about 66-75% of the time the stock will also be up. So the idea is to realize that 1/3 of the time at least you will cut your losses but 2/3 of the time you will be up then next day as well. So keep holding the position based on the low of the previous day and as the stock rises to your trend line then tighten the stock to the low of the same day or just take your profit and buy something else. But losing 1/3 times is just part of \"\"the unpredictable\"\" nature of the stock market which is causes simply because there are three types of traders all betting at the same time on the same stock. Day traders who are trading from 1 to 10 times a day, swing traders trading from 1 day to several weeks and buy and hold investors holding out for long term capital gains. They each have different price targets and time horizons and THAT DIFFERENCE is what makes the market move. ONE PERSON'S SHORT TERM EXIT PRICE AT A PROFIT IS ANOTHER PERSONS LONG TERM ENTRY POINT and because so many are playing at the same time with different time horizons, stop losses and exit targets it is impossible to draw the price action or volume. But it is possible to cut your losses and ride your winners and if you keep on doing that you have a very fine return indeed.\"", "title": "" }, { "docid": "271568", "text": "\"From your explanation the Sole Trader option is more appropriate and certainly easier to manage. There are many differences but the pertinent and most important ones are as follows. The main difference in your case would be tax and administration. As a sole trader you would need to do a tax return once a year and if you earned less than £11.5k you wouldn't have to pay any UK tax, assuming you have no other income and are a \"\"standard\"\" tax payer. The current tax allowance is £11.5k although this can change. Submitting your own tax return is relatively straighforward although you may want to consult an accountant. It is generally easier to run as sole trader versus a Limited Company, ie less paperwork and beaureaucracy. If you go down the Limited Company route, the company would be liable to pay Corporation Tax on any profits and this process is more complicated and you would probably need an accountant to do that for you, which is likely to cost a few hundred pounds every year. You can do it yourself but the process is not as simple as doing your own income tax return. Also as a sole trader you can do what you like with any income, you can spend it and treat it as your own wages. You can't do that if you set up a Limited Company as the income is \"\"owned\"\" by the company and so you would need to in effect pay yourself a wage from the company. In other words it's more complex than if you are a sole trader. The main advantage to a Limited Company is that it is easier to sell the business if you want to at a later date. There is nothing stopping you setting up a Limited Company later on, after beign a sole trader if you want to. They can also be more tax-efficient but this would not be relevant to your case if you are earning relatively small sums, if your income increases then you may want to reconsider. You can see more information here: https://www.duport.co.uk/company-formation/sole-trader-vs-limited-company.php (I have been both a sole trader and also set up my own Limited Company)\"", "title": "" }, { "docid": "350067", "text": "This happens on dark pools quite often. If I am a large institutional investor with tens of millions of shares, I may want to unload slowly and limit the adverse affects on the price of the stock. Dark pools offer anonymity and have buyers / sellers that can handle large volume. In the case of a day trader, they often trade stocks with light volume (since they have large fluctuations that can be quite profitable throughout the session). At the end of the session, many traders are unwilling to hold positions on margin and want to unload fast.", "title": "" }, { "docid": "20116", "text": "You only have to own it for a day (or rather for some amount of time before the close of trading the day before the ex-dividend date). This is governed by exchange rules based on the date of record and payable date set by the company. You might want to look at this article or this one for more details. It should be difficult to make money from changes due to the dividend distribution since it is well known and expected. The exchanges have established rules for handling the various details that can come up, and traders account for the change where appropriate (as in option pricing). Also, note that the favorable U.S. tax treatment of dividends requires a 60-day ownership period for the stock.", "title": "" }, { "docid": "541640", "text": "lol information overload how about we share some of our frequent reads? i personally read Mike Shedlock's blog for global macro trends, albeit his content is leaning a bit to perma-bear and mercenary traders for trading related contents. I absolutely love their articles on trading systems,mentality etc etc. It played a critical role in building my very own profitable trading system, and forging the trader mindset i have today. I would not have gone far without these guys.", "title": "" }, { "docid": "464264", "text": "Dollar cost averaging is a great strategy to use for investment vehicles where you can't invest it in a lump sum. A 401K is perfect for this. You take a specific amount out of each paycheck and invest it either in a single fund, or multiple funds, or some programs let you invest it in a brokerage account so you can invest in virtually any mutual fund or stock. With annual or semi-annual re-balancing of your investments dollar cost averaging is the way to invest in these programs. If you have a lump sum to invest, then dollar cost averaging is not the best way to invest. Imagine you want to invest 10K and you want to be 50% bonds and 50% stocks. Under dollar cost averaging you would take months to move the money from 100% cash to 50/50 bonds/stocks. While you are slowly moving towards the allocation you want, you will spend months not in the allocation you want. You will spend way too long in the heavy cash position you were trying to change. The problem works the other way also. Somebody trying to switch from stocks to gold a few years ago, would not have wanted to stay in limbo for months. Obviously day traders don't use dollar cost averaging. If you will will be a frequent trader, DCA is not the way to go. No particular stock type is better for DCA. It is dependent on how long you plan on keeping the investment, and if you will be working with a lump sum or not. EDIT: There have be comments regarding DCA and 401Ks. When experts discuss why people should invest via a 401K, they mention DCA as a plus along with the company match. Many participants walk away with the belief that DCA is the BEST strategy. Many articles have been written about how to invest an inheritance or tax refund, many people want to use DCA because they believe that it is good. In fact in the last few years the experts have begun to discourage ever using DCA unless there is no other way.", "title": "" }, { "docid": "558948", "text": "You need to contact the trading company and ask them what's going on. If it's simply a matter of needing to add more cash because you are now classified as a day trader, then call them, ask them what you need to do to not be considered a day trader, and do that. It would likely consist of not trading for a week and then trading less than you were going forward to avoid getting classified as a day trader again. That would be the easy problem to solve, so I hope that's right.", "title": "" }, { "docid": "30970", "text": "trader. It's easy to learn how to develop, you can teach yourself how to develop, but gaining knowledge on how a traders day-to-day world is like is not as easy to come by. If you go dev first, it may be harder to get that business knowledge further down the track", "title": "" }, { "docid": "107819", "text": "Private investors as mutual funds are a minority of the market. Institutional investors make up a substantial portion of the long term holdings. These include pension funds, insurance companies, and even corporations managing their money, as well as individuals rich enough to actively manage their own investments. From Business Insider, with some aggregation: Numbers don't add to 100% because of rounding. Also, I pulled insurance out of household because it's not household managed. Another source is the Tax Policy Center, which shows that about 50% of corporate stock is owned by individuals (25%) and individually managed retirement accounts (25%). Another issue is that household can be a bit confusing. While some of these may be people choosing stocks and investing their money, this also includes Employee Stock Ownership Plans (ESOP) and company founders. For example, Jeff Bezos owns about 17% of Amazon.com according to Wikipedia. That would show up under household even though that is not an investment account. Jeff Bezos is not going to sell his company and buy equity in an index fund. Anyway, the most generous description puts individuals as controlling about half of all stocks. Even if they switched all of that to index funds, the other half of stocks are still owned by others. In particular, about 26% is owned by institutional investors that actively manage their portfolios. In addition, day traders buy and sell stocks on a daily basis, not appearing in these numbers. Both active institutional investors and day traders would hop on misvalued stocks, either shorting the overvalued or buying the undervalued. It doesn't take that much of the market to control prices, so long as it is the active trading market. The passive market doesn't make frequent trades. They usually only need to buy or sell as money is invested or withdrawn. So while they dominate the ownership stake numbers, they are much lower on the trading volume numbers. TL;DR: there is more than enough active investment by organizations or individuals who would not switch to index funds to offset those that do. Unless that changes, this is not a big issue.", "title": "" }, { "docid": "41472", "text": "\"Not really. High frequency traders affect mainly short term investors. If everyone invested long-term and traded infrequently, there would be no high frequency trading. For a long term investor, you by at X, hold for several years, and sell at Y. At worst, high frequency trading may affect \"\"X\"\" and \"\"Y\"\" by a few pennies (and the changes may cancel out). For a long term trader that doesn't amount to a \"\"hill of beans\"\" It is other frequent traders that will feel the loss of those \"\"pennies.\"\"\"", "title": "" }, { "docid": "580757", "text": "If you do not understand the volatility of the fx market, you need to stop trading it, immediately. There are many reasons that fx is riskier than other types of investing, and you bear those risks whether you understand them or not. Below are a number of reasons why fx trading has high levels of risk: 1) FX trades on the relative exchange rate between currencies. That means it is a zero-sum game. Over time, the global fx market cannot 'grow'. If the US economy doubles in size, and the European economy doubles in size, then the exchange rate between the USD and the EUR will be the same as it is today (in an extreme example, all else being equal, yes I know that value of currency /= value of total economy, but the general point stands). Compare that with the stock market - if the US economy doubles in size, then effectively the value of your stock investments will double in size. That means that stocks, bonds, etc. tied to real world economies generally increase when the global economy increases - it is a positive sum game, where many players can be winners. On the long term, on average, most people earn value, without needing to get into 'timing' of trades. This allows many people to consider long-term equity investing to be lower risk than 'day-trading'. With FX, because the value of a currency is in its relative position compared with another currency, 1 player is a winner, 1 player is a loser. By this token, most fx trading is necessarily short-term 'day-trading', which by itself carries inherent risk. 2) Fx markets are insanely efficient (I will lightly state that this is my opinion, but one that I am not alone in holding firmly). This means that public information about a currency [ie: economic news, political news, etc.] is nearly immediately acted upon by many, many people, so that the revised fx price of that currency will quickly adjust. The more efficient a market is, the harder it is to 'time a trade'. As an example, if you see on a news feed that the head of a central bank authority made an announcement about interest rates in that country [a common driver of fx prices], you have only moments to make a trade before the large institutional investors already factor it into their bid/ask prices. Keep in mind that the large fx players are dealing with millions and billions of dollars; markets can move very quickly because of this. Note that some currencies trade more frequently than others. The main currency 'pairs' are typically between USD and / or other G10 country-currencies [JPY, EUR, etc.]. As you get into currencies of smaller countries, trading of those currencies happens less frequently. This means that there may be some additional time before public information is 'priced in' to the market value of that currency, making that currency 'less efficient'. On the flip side, if something is infrequently traded, pricing can be more volatile, as a few relatively smaller trades can have a big impact on the market. 3) Uncertainty of political news. If you make an fx trade based on what you believe will happen after an expected political event, you are taking risk that the event actually happens. Politics and world events can be very hard to predict, and there is a high element of chance involved [see recent 'expected' election results across the world for evidence of this]. For something like the stock market, a particular industry may get hit every once in a while with unexpected news, but the fx market is inherently tied to politics in a way that may impact exchange rates multiple times a day. 4) Leveraging. It is very common for fx traders to borrow money to invest in fx. This creates additional risk because it amplifies the impact of your (positive or negative) returns. This applies to other investments as well, but I mention it because high degrees of debt leveraging is extremely common in FX. To answer your direct question: There are no single individual traders who spike fx prices - that is the impact you see of a very efficient market, with large value traders, reacting to frequent, surprising news. I reiterate: If you do not understand the risks associated with fx trade, I recommend that you stop this activity immediately, at least until you understand it better [and I would recommend personally that any amateur investor never get involved in fx at all, regardless of how informed you believe you are].", "title": "" }, { "docid": "149420", "text": "The shift to trading at the close began in 2008. Traders did not want to be caught off guard by surprise news and there was a lot of volatility during the financial crisis, so they would close their position in the evening. Thats how it began. There are two reasons why it sticks around. First, there has been an increase usage of index funds or passive funds. These funds tend to update their positions at the end of the day. From the WSJ: Another factor behind the shift has been the proliferation of passively managed investments, such as index funds. These funds aim to mimic an index, like the S&P 500, by owning the shares that comprise it. Index funds don’t trade as often as active investors, but when they do, it is typically near the market close, traders say. That is because buying or selling a stock at its closing price better aligns their performance with the index they are trying to emulate. The second reason is simply that volume attracts volume. As a result of whats mentioned above, you have a shift to end of day trading, and the corrolary to that is that there is a liquidity shortage from 10am to 3pm. Thus, if you want to buy or sell a stock, but there are few buyers or sellers around, you will significant move the price when you enter your order. Obviously this does not affect retail traders, but imagine hedge funds entering or closing a billion dollar position. It can make a huge impact on price. And one way to mitigate that is to wait until there are more market participants to take the other end of your trade, just as at the end of the day. So this is a self-reinforcing trend that has begun in the markets and will likely stick around. http://www.wsj.com/articles/traders-pile-in-at-the-close-1432768080", "title": "" }, { "docid": "110716", "text": "There are various exchanges around the world that handle spot precious metal trading; for the most part these are also the primary spot foreign exchange markets, like EBS, Thomson Reuters, Currenex (website seems to be down), etc. You can trade on these markets through brokers just like you can trade on stock markets. However, the vast majority of traders on these exchanges do not intend to hold any bullion ownership at the end of the day; they want to buy as much as they sell each day. A minority of traders do intend to hold metal positions for longer periods, but I doubt any of them intend to actually go collect bullion from the exchange. I don't think it's even possible. Really the only way to get bullion is to pay a service fee to a dealer like you mentioned. But on an exchange like the ones above you have to pay three different fees: So in the end you can't even get the spot price on the exchanges where the spot prices are determined. You might even come out ahead by going to a dealer. You should try to find a reputable dealer, and go in knowing the latest trade prices. An honest dealer will have a website showing you the current trade prices, so you know that they expect you to know the prices when you come in. For example, here's a well-known dealer in Chicago that happily shows you the spot prices from KITCO so you can decide whether their service fee is worth it or not.", "title": "" }, { "docid": "49285", "text": "The SEC considers a day trade to be any trade that is opened and closed within the same trading day, and considers a day trader to be any trader that completes 4 or more day trades within 5 business days. If so they would label you day trader and in the US you are required to have at least $25K in your account. Maybe that's why they require you to add more money to your account? See more at Day trading restriction on US stocks and Wikipedia - Pattern day trader.", "title": "" }, { "docid": "264153", "text": "&gt; Not to mention that pnl is really all you have to judge a trader Annnnd this is how I know your only experience is retail trading. Voice trading still represents a large amount of volume in the market (especially in OTC products) and having existing relationships is a guarantee for better points. I see the reality of this every fucking day. Not to mention traders performance is also susceptible to in house analysis and risk management... both of which at a major firm are determined and managed by different individuals (research and risk officers). It's not like Two Sigma welcomes you in, gives you a $500 mio FI portfolio and lets you do whatever the fuck you want. Hedge fund traders operate under the strategy that was profiled to the investors. Traders are there to execute profit earning transactions within the guidelines of the overall strategy of the firm and within their risk profile... Meaning if you're managing a pension fund on a global macro strategy at one firm and achieve moderate returns of 15-20%, you're going to be viewed far more favorably than at another firm making 20-25% managing an alternative investments/listed derivatives fund.", "title": "" }, { "docid": "40088", "text": "How frequently do people make the switch from back office to front office for S&amp;T roles like that? WSO says its nearly impossible. I know a guy who went from equity research at MS to trader at JPM; he networked hard and did a huge front office transition. Which is more common out of big front-front transitions and back-to-front on the same floor?", "title": "" }, { "docid": "524238", "text": "Have the reasons you originally purchased the stock changed? Is the company still sound? Does the company have a new competitor? Has the company changed the way they operate? If the company is the same, except for stock price, why would you change your mind on the company now? ESPECIALLY if the company has not changed, -- but only other people's PERCEPTION of the company, then your original reasons for buying it are still valid. In fact, if you are not a day-trader, then this COMPANY JUST WENT ON SALE and you should buy more. If you are a day trader, then you do care about the herd's perception of value (not true value) and you should sell. DAY TRADER = SELL BUY AND HOLD (WITH INTELLIGENT RESEARCH) = BUY MORE", "title": "" }, { "docid": "43544", "text": "There are a number of factors here. 1) It's important that there is human oversight on the system. At one level someone needs to be monitoring the computers that manage the trading to be sure they are functioning. At another level someone needs to be making judgement calls on important but rare events: when you you suspend trading in a stock? When do you close the stock exchange entirely? It is alleged that unsupervised computer trades were at least partly responsible for the May 2010 selloff. Even if that's unproven, would you really want those unsupervised computers trading with each other for a couple of days? Or even for a couple of hours? 2) Providing 24/7 trading would increase the cost of running a stock exchange, but with only a tiny improvement in liquidity. 3) If the stock exchange ran 24/7 then traders would have to run 24/7. That would add hugely to the cost of trading. 4) The people who would really suffer would be day traders - because there would no longer be such a thing as a day trader. If you were a sole trader then you would need to monitor your investments 24/7, or risk waking up in the morning to find one of your stocks had plummeted overnight.", "title": "" }, { "docid": "278460", "text": "Flipping usually refers to real-estate transaction: you buy a property, improve/renovate/rehabilitate it and resell it quickly. The distinction between flipper and investor is similar to the distinction between trader and investor, even though the tax code doesn't explicitly refer to house flipping. Gains on house flipping can be considered as active business gain or passive activity income, which are treated differently: passive income goes on Schedule E and Schedule D, active income goes on Schedule C. The distinction between passive and active is based on the characteristics of the activity (hours you spent on it, among other things). Trading income can similarly be considered as either passive (Schedule D/E treatment) or active (Schedule C treatment). Here's what the IRS has to say about traders: Special rules apply if you are a trader in securities, in the business of buying and selling securities for your own account. This is considered a business, even though you do not maintain an inventory and do not have customers. To be engaged in business as a trader in securities, you must meet all of the following conditions: The following facts and circumstances should be considered in determining if your activity is a securities trading business: If the nature of your trading activities does not qualify as a business, you are considered an investor... Investor, in this context, means passive income treatment (Schedule D/E). However, even if your income is considered active (Schedule C), stock sale proceeds are not subject to the self-employment tax. As you can see, there's no specific definition, but the facts and circumstances matter. You may be considered a trader by the IRS, or you may not. You may want to be considered a trader (for example to be able to make a mark-to-market election), or you may not. You should talk to a professional tax adviser (EA/CPA licensed in your State) for more details and suggestions.", "title": "" }, { "docid": "210514", "text": "That is such a vague statement, I highly recommend disregarding it entirely, as it is impossible to know what they meant. Their goal is to convince you that index funds are the way to go, but depending on what they consider an 'active trader', they may be supporting their claim with irrelevant data Their definition of 'active trader' could mean any one or more of the following: 1) retail investor 2) day trader 3) mutual fund 4) professional investor 5) fund continuously changing its position 6) hedge fund. I will go through all of these. 1) Most retail traders lose money. There are many reasons for this. Some rely on technical strategies that are largely unproven. Some buy rumors on penny stocks in hopes of making a quick buck. Some follow scammers on twitter who sell newsletters full of bogus stock tips. Some cant get around the psychology of trading, and thus close out losing positions late and winning positions early (or never at all) [I myself use to do this!!]. I am certain 99% of retail traders cant beat the market, because most of them, to be frank, put less effort into deciding what to trade than in deciding what to have for lunch. Even though your pension funds presentation is correct with respect to retail traders, it is largely irrelevant as professionals managing your money should not fall into any of these traps. 2) I call day traders active traders, but its likely not what your pension fund was referring to. Day trading is an entirely different animal to long or medium term investing, and thus I also think the typical performance is irrelevant, as they are not going to manage your money like a day trader anyway. 3,4,5) So the important question becomes, do active funds lose 99% of the time compared to index funds. NO! No no no. According to the WSJ, actively managed funds outperformed passive funds in 2007, 2009, 2013, 2015. 2010 was basically a tie. So 5 out of 9 years. I dont have a calculator on me but I believe that is less than 99%! Whats interesting is that this false belief that index funds are always better has become so pervasive that you can see active funds have huge outflows and passive have huge inflows. It is becoming a crowded trade. I will spare you the proverb about large crowds and small doors. Also, index funds are so heavily weighted towards a handful of stocks, that you end up becoming a stockpicker anyway. The S&P is almost indistinguishable from AAPL. Earlier this year, only 6 stocks were responsible for over 100% of gains in the NASDAQ index. Dont think FB has a good long term business model, or that Gilead and AMZN are a cheap buy? Well too bad if you bought QQQ, because those 3 stocks are your workhorses now. See here 6) That graphic is for mutual funds but your pension fund may have also been including hedge funds in their 99% figure. While many dont beat their own benchmark, its less than 99%. And there are reasons for it. Many have investors that are impatient. Fortress just had to close one of its funds, whose bets may actually pay off years from now, but too many people wanted their money out. Some hedge funds also have rules, eg long only, which can really limit your performance. While important to be aware of this, that placing your money with a hedge fund may not beat a benchmark, that does not automatically mean you should go with an index fund. So when are index funds useful? When you dont want to do any thinking. When you dont want to follow market news, at all. Then they are appropriate.", "title": "" }, { "docid": "268966", "text": "Prop (proprietary) traders trade using huge amounts of a bank's money (i.e. other people's money) so the reason why they have such low commissions (and they certainly do) is that the firms for which they work negotiate low commissions as the quantities and volumes (as they also trade very frequently) will be high and so the total commission will be very high. There is no such thing as a prop trading account unless you are a big bank with a very large bank roll (tens of millions of USD) so you cannot open one to enjoy those benefits unless you have enough money that you can negotiate your commission with brokers. 25k CAD is definitely not enough money to even start a conversation about those sorts of commissions. note: prop traders are generally banned from trading intraday with their own money by their employers and the law as it is a massive conflict of interests. Those who do and get caught face lengthy prison sentences.", "title": "" }, { "docid": "552922", "text": "\"The success rate is terrible. At the same time, what are the success rate for any business endeavor? Isn't it something like 80% of startups fail in the first 5 years? That's not far off for the success of traders. Just like all the success cliches say, it comes down to how bad you want it. What will you sacrifice to be a successful trader? How much will you work to be a successful trader? Will you accept the pain and failure it takes to be a trader? Who cares if \"\"soandso\"\" can do it? If you want it, you should be saying, \"\"I will do it because I say so\"\". Only you know if you're willing to take the risk. At the same time, you're a college student, what's the worst that will happen if it doesn't work out? Check out /r/getmotivated...\"", "title": "" } ]
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NAC destabilizes NO to increase the effect of contrast agents on renal functions.
[ { "docid": "4678846", "text": "CONTEXT The antioxidant acetylcysteine prevents acute contrast nephrotoxicity in patients with impaired renal function who undergo computed tomography scanning. However, its role in coronary angiography is unclear. OBJECTIVE To determine whether oral acetylcysteine prevents acute deterioration in renal function in patients with moderate renal insufficiency who undergo elective coronary angiography. DESIGN AND SETTING Prospective, randomized, double-blind, placebo-controlled trial conducted from May 2000 to December 2001 at the Grantham Hospital at the University of Hong Kong. PARTICIPANTS Two hundred Chinese patients aged mean (SD) 68 (6.5) years with stable moderate renal insufficiency (creatinine clearance <60 mL/min [1.00 mL/s]) who were undergoing elective coronary angiography with or without intervention. INTERVENTION Participants were randomly assigned to receive oral acetylcysteine(600 mg twice per day; n = 102) or matching placebo tablets (n = 98) on the day before and the day of angiography. All patients received low-osmolality contrast agent. MAIN OUTCOME MEASURES Occurrence of more than a 25% increase in serum creatinine level within 48 hours after contrast administration; change in creatinine clearance and serum creatinine level. RESULTS Twelve control patients (12%) and 4 acetylcysteine patients (4%) developed a more than 25% increase in serum creatinine level within 48 hours after contrast administration (relative risk, 0.32; 95% confidence interval [CI], 0.10-0.96; P =.03). Serum creatinine was lower in the acetylcysteine group (1.22 mg/dL [107.8 micromol/L]; 95% CI, 1.11-1.33 mg/dL vs 1.38 mg/dL [122.9 micromol/L]; 95% CI, 1.27-1.49 mg/dL; P =.006) during the first 48 hours after angiography. Acetylcysteine treatment significantly increased creatinine clearance from 44.8 mL/min (0.75 mL/s) (95% CI, 42.7-47.6 mL/min) to 58.9 mL/min (0.98 mL/s) (95% CI, 55.6-62.3 mL/min) 2 days after the contrast administration (P<.001). The increase was not significant in the control group (from 42.1 to 44.1 mL/min [0.70 to 0.74 mL/s]; P =.15). The benefit of acetylcysteine was consistent among various patient subgroups and persistent for at least 7 days. There were no major treatment-related adverse events. CONCLUSION Acetylcysteine protects patients with moderate chronic renal insufficiency from contrast-induced deterioration in renal function after coronary angiographic procedures, with minimal adverse effects and at a low cost.", "title": "Acetylcysteine for prevention of acute deterioration of renal function following elective coronary angiography and intervention: a randomized controlled trial." } ]
[ { "docid": "26025370", "text": "Background: Vasoconstriction and reactive oxygen species (ROS) accumulation following contrast media (CM) injection are the key factors triggering CM-induced nephropathy. We compared the effects of N-acetylcysteine (NAC), theophylline or sodium bicarbonate on intrarenal vasoconstriction and ROS generation in a rat model of CM-induced nephropathy. Methods: Following a 3-day dehydration, Sprague-Dawley rats received CM (Telebrix) or sham ‘CM’ injection of 0.9% saline. Part of them received NAC, theophylline or bicarbonate prior to CM. Medullar renal blood flow was estimated by laser Doppler. The animals were sacrificed 1, 15 or 30 min after the respective treatments, their kidneys allocated and intrarenal STAT-8 isoprostane, PGE2 and NO assessed. Results: Vasoconstriction was significantly attenuated by NAC. Theophylline only mildly attenuated the perfusion drop at 15 min, and was ineffective following 30 min. Unlike theophylline or bicarbonate, NAC significantly augmented intrarenal PGE2. NAC, theophylline but not bicarbonate, gradually increased intrarenal NO. In all experimental variables, CM-induced ROS accumulation, represented by STAT-8 isoprostane estimation, progressed undisturbed. Conclusions: (1) CM-induced intrarenal vasoconstriction was efficiently prohibited by NAC but not bicarbonate or theophylline; (2) the vasodilatory effect of NAC was mediated via increased PGE2 synthesis, and (3) ROS accumulation was a primary renal response to CM-induced injury, not affected by any pharmacologic manipulations.", "title": "Differential Effects of N-Acetylcysteine, Theophylline or Bicarbonate on Contrast-Induced Rat Renal Vasoconstriction" }, { "docid": "140098548", "text": "BACKGROUND Radiographic contrast agents can cause a reduction in renal function that may be due to reactive oxygen species. Whether the reduction can be prevented by the administration of antioxidants is unknown. METHODS We prospectively studied 83 patients with chronic renal insufficiency (mean [+/-SD] serum creatinine concentration, 2.4+/-1.3 mg per deciliter [216+/-116 micromol per liter]) who were undergoing computed tomography with a nonionic, low-osmolality contrast agent. Patients were randomly assigned either to receive the antioxidant acetylcysteine (600 mg orally twice daily) and 0.45 percent saline intravenously, before and after administration of the contrast agent, or to receive placebo and saline. RESULTS Ten of the 83 patients (12 percent) had an increase of at least 0.5 mg per deciliter (44 micromol per liter) in the serum creatinine concentration 48 hours after administration of the contrast agent: 1 of the 41 patients in the acetylcysteine group (2 percent) and 9 of the 42 patients in the control group (21 percent; P=0.01; relative risk, 0.1; 95 percent confidence interval, 0.02 to 0.9). In the acetylcysteine group, the mean serum creatinine concentration decreased significantly (P<0.001), from 2.5+/-1.3 to 2.1+/-1.3 mg per deciliter (220+/-118 to 186+/-112 micromol per liter) 48 hours after the administration of the contrast medium, whereas in the control group, the mean serum creatinine concentration increased nonsignificantly (P=0.18), from 2.4+/-1.3 to 2.6+/-1.5 mg per deciliter (212+/-114 to 226+/-133 micromol per liter) (P<0.001 for the comparison between groups). CONCLUSIONS Prophylactic oral administration of the antioxidant acetylcysteine, along with hydration, prevents the reduction in renal function induced by contrast agents in patients with chronic renal insufficiency.", "title": "Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine." }, { "docid": "4700428", "text": "BACKGROUND Relapse to cocaine seeking has been linked with low glutamate in the nucleus accumbens core (NAcore) causing potentiation of synaptic glutamate transmission from prefrontal cortex (PFC) afferents. Systemic N-acetylcysteine (NAC) has been shown to restore glutamate homeostasis, reduce relapse to cocaine seeking, and depotentiate PFC-NAcore synapses. Here, we examine the effects of NAC applied directly to the NAcore on relapse and neurotransmission in PFC-NAcore synapses, as well as the involvement of the metabotropic glutamate receptors 2/3 (mGluR2/3) and 5 (mGluR5). METHODS Rats were trained to self-administer cocaine for 2 weeks and following extinction received either intra-accumbens NAC or systemic NAC 30 or 120 minutes, respectively, before inducing reinstatement with a conditioned cue or a combined cue and cocaine injection. We also recorded postsynaptic currents using in vitro whole cell recordings in acute slices and measured cystine and glutamate uptake in primary glial cultures. RESULTS NAC microinjection into the NAcore inhibited the reinstatement of cocaine seeking. In slices, a low concentration of NAC reduced the amplitude of evoked glutamatergic synaptic currents in the NAcore in an mGluR2/3-dependent manner, while high doses of NAC increased amplitude in an mGluR5-dependent manner. Both effects depended on NAC uptake through cysteine transporters and activity of the cysteine/glutamate exchanger. Finally, we showed that by blocking mGluR5 the inhibition of cocaine seeking by NAC was potentiated. CONCLUSIONS The effect of NAC on relapse to cocaine seeking depends on the balance between stimulating mGluR2/3 and mGluR5 in the NAcore, and the efficacy of NAC can be improved by simultaneously inhibiting mGluR5.", "title": "The effect of N-acetylcysteine in the nucleus accumbens on neurotransmission and relapse to cocaine." }, { "docid": "7821634", "text": "Neoadjuvant chemotherapy (NAC) induces a pathological complete response (pCR) in ∼30% of patients with breast cancer. However, many patients have residual cancer after chemotherapy, which correlates with a higher risk of metastatic recurrence and poorer outcome than those who achieve a pCR. We hypothesized that molecular profiling of tumors after NAC would identify genes associated with drug resistance. Digital transcript counting was used to profile surgically resected breast cancers after NAC. Low concentrations of dual specificity protein phosphatase 4 (DUSP4), an ERK phosphatase, correlated with high post-NAC tumor cell proliferation and with basal-like breast cancer (BLBC) status. BLBC had higher DUSP4 promoter methylation and gene expression patterns of Ras-ERK pathway activation relative to other breast cancer subtypes. DUSP4 overexpression increased chemotherapy-induced apoptosis, whereas DUSP4 depletion dampened the response to chemotherapy. Reduced DUSP4 expression in primary tumors after NAC was associated with treatment-refractory high Ki-67 scores and shorter recurrence-free survival. Finally, inhibition of mitogen-activated protein kinase kinase (MEK) synergized with docetaxel treatment in BLBC xenografts. Thus, DUSP4 downregulation activates the Ras-ERK pathway in BLBC, resulting in an attenuated response to anti-cancer chemotherapy.", "title": "Profiling of residual breast cancers after neoadjuvant chemotherapy identifies DUSP4 deficiency as a mechanism of drug resistance" }, { "docid": "9288638", "text": "OBJECTIVE The aim of this study was to investigate whether diabetes and hypertension cause additive effects in the responses to various vasoconstrictor and vasodilator agents, in isolated perfused kidneys obtained from streptozotocin (STZ)-diabetic Wistar-Kyoto (WKY) rats and from diabetic spontaneously hypertensive rats (SHR). METHODS SHR and WKY rats were administered STZ 55 mg/kg by intravenous injection into a lateral tail vein at age 12 weeks. Eight weeks later the kidneys were isolated and perfused via the left renal artery with a physiological salt solution. Renal perfusion pressure was measured continuously. Concentration response curves were plotted for various vasoconstrictor and vasodilator agents. RESULTS Both the diabetic and the hypertensive state were associated with an increased wet kidney weight. The contractile responses of the renal arterial system to phenylephrine (PhE), serotonin (5-HT) and angiotensin II (Ang II) in terms both of the maximal rise in perfusion pressure (mmHg) and of the sensitivity (log EC50) were the same in preparations from diabetic WKY rats and in those from normoglycaemic WKY rats. The maximal contractile responses both to PhE and to Ang II were enhanced in kidneys from SHR compared with those in kidneys from their normotensive controls, whereas simultaneously occurring diabetes impaired this sensitization. After precontraction with 3 x 10(-6) mol/l PhE both endothelium-dependent (methacholine) and endothelium-independent (sodium nitroprusside) vasodilator drugs caused the same vasodilator response in the preparations taken from the four groups of animals. CONCLUSION In isolated perfused kidneys obtained from STZ-diabetic WKY rats and SHR, the isolated diabetic state did not influence the vasoconstriction caused by various agonists. However, the enhanced vascular reactivity in the hypertensive state was blunted by simultaneously occurring diabetes mellitus. Endothelium-dependent and -independent vasorelaxation in this model was not affected neither by the hypertensive nor by the diabetic state.", "title": "Vascular responsiveness in isolated perfused kidneys of diabetic hypertensive rats." }, { "docid": "4389394", "text": "The p53 tumour suppressor is a short-lived protein that is maintained at low levels in normal cells by Mdm2-mediated ubiquitination and subsequent proteolysis. Stabilization of p53 is crucial for its tumour suppressor function. However, the precise mechanism by which ubiquitinated p53 levels are regulated in vivo is not completely understood. By mass spectrometry of affinity-purified p53-associated factors, we have identified herpesvirus-associated ubiquitin-specific protease (HAUSP) as a novel p53-interacting protein. HAUSP strongly stabilizes p53 even in the presence of excess Mdm2, and also induces p53-dependent cell growth repression and apoptosis. Significantly, HAUSP has an intrinsic enzymatic activity that specifically deubiquitinates p53 both in vitro and in vivo. In contrast, expression of a catalytically inactive point mutant of HAUSP in cells increases the levels of p53 ubiquitination and destabilizes p53. These findings reveal an important mechanism by which p53 can be stabilized by direct deubiquitination and also imply that HAUSP might function as a tumour suppressor in vivo through the stabilization of p53.", "title": "Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization" }, { "docid": "25816994", "text": "BACKGROUND Angiotensin receptor blockers (ARB) and angiotensin converting enzyme (ACE) inhibitors are known to reduce proteinuria. Their combination might be more effective than either treatment alone, but long-term data for comparative changes in renal function are not available. We investigated the renal effects of ramipril (an ACE inhibitor), telmisartan (an ARB), and their combination in patients aged 55 years or older with established atherosclerotic vascular disease or with diabetes with end-organ damage. METHODS The trial ran from 2001 to 2007. After a 3-week run-in period, 25 620 participants were randomly assigned to ramipril 10 mg a day (n=8576), telmisartan 80 mg a day (n=8542), or to a combination of both drugs (n=8502; median follow-up was 56 months), and renal function and proteinuria were measured. The primary renal outcome was a composite of dialysis, doubling of serum creatinine, and death. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00153101. FINDINGS 784 patients permanently discontinued randomised therapy during the trial because of hypotensive symptoms (406 on combination therapy, 149 on ramipril, and 229 on telmisartan). The number of events for the composite primary outcome was similar for telmisartan (n=1147 [13.4%]) and ramipril (1150 [13.5%]; hazard ratio [HR] 1.00, 95% CI 0.92-1.09), but was increased with combination therapy (1233 [14.5%]; HR 1.09, 1.01-1.18, p=0.037). The secondary renal outcome, dialysis or doubling of serum creatinine, was similar with telmisartan (189 [2.21%]) and ramipril (174 [2.03%]; HR 1.09, 0.89-1.34) and more frequent with combination therapy (212 [2.49%]: HR 1.24, 1.01-1.51, p=0.038). Estimated glomerular filtration rate (eGFR) declined least with ramipril compared with telmisartan (-2.82 [SD 17.2] mL/min/1.73 m(2)vs -4.12 [17.4], p<0.0001) or combination therapy (-6.11 [17.9], p<0.0001). The increase in urinary albumin excretion was less with telmisartan (p=0.004) or with combination therapy (p=0.001) than with ramipril. INTERPRETATION In people at high vascular risk, telmisartan's effects on major renal outcomes are similar to ramipril. Although combination therapy reduces proteinuria to a greater extent than monotherapy, overall it worsens major renal outcomes.", "title": "Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial." }, { "docid": "41298619", "text": "BACKGROUND Hydroxyethyl starches (HES) are synthetic colloids commonly used for fluid resuscitation, yet controversy exists about their impact on kidney function. OBJECTIVES To examine the effects of HES on kidney function compared to other fluid resuscitation therapies in different patient populations. SEARCH STRATEGY We searched the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library), MEDLINE, EMBASE, MetaRegister and reference lists of articles. SELECTION CRITERIA Randomised controlled trials (RCTs) and quasi-RCTs in which HES was compared to an alternate fluid therapy for the prevention or treatment of effective intravascular volume depletion. Primary outcomes were renal replacement therapy (RRT), author-defined kidney failure and acute kidney injury (AKI) as defined by the RIFLE criteria. Secondary outcomes included serum creatinine and creatinine clearance. DATA COLLECTION AND ANALYSIS Screening, selection, data extraction and quality assessments for each retrieved article were carried out by two authors using standardised forms. Authors were contacted when published data were incomplete. Preplanned sensitivity and subgroup analyses were performed after data were analysed with a random effects model. MAIN RESULTS The review included 34 studies (2607 patients). Overall, the RR of author-defined kidney failure was 1.50 (95% CI 1.20 to 1.87; n = 1199) and 1.38 for requiring RRT (95% CI 0.89 to 2.16; n = 1236) in HES treated individuals compared with other fluid therapies. Subgroup analyses suggested increased risk in septic patients compared to non-septic (surgical/trauma) patients. Non-septic patient studies were smaller and had lower event rates, so subgroup differences may have been due to lack of statistical power in these studies. Only limited data was obtained for analysis of kidney outcomes by the RIFLE criteria. Overall, methodological quality of studies was good but subjective outcomes were potentially biased because most studies were unblinded. AUTHORS' CONCLUSIONS Potential for increased risk of AKI should be considered when weighing the risks and benefits of HES for volume resuscitation, particularly in septic patients. Large studies with adequate follow-up are required to evaluate the renal safety of HES products in non-septic patient populations. RIFLE criteria should be applied to evaluate kidney function in future studies of HES and, where data is available, to re-analyse those studies already published. There is inadequate clinical data to address the claim that safety differences exist between different HES products.", "title": "Hydroxyethyl starch (HES) versus other fluid therapies: effects on kidney function." }, { "docid": "3430789", "text": "The present study retrospectively analyzed 19 patients diagnosed with paraquat (PQ) poisoning with the aim to investigate the effect of activated charcoal hemoperfusion on renal function and PQ elimination. The results indicated that 7 patients died and 12 survived. Non-oliguric renal failure occurred in all of the 7 patients who died. Among the 12 surviving patients, 10 had normal renal function and 2 developed non-oliguric renal failure. There was a linear correlation between plasma and urine paraquat concentration prior to and during activated charcoal hemoperfusion. The equation parameters together with the correlation coefficient on admission were as follows: Y=0.5820+1.7348X (R2=0.678; F=35.768; P<0.0001). The equation parameters together with the correlation coefficient were as follows during activated charcoal hemoperfusion: Y=0.6827+1.2649X (R2=0.626; F=50.308; P<0.0001). Therefore, it was concluded that in patients with normal renal function, the elimination kinetics of PQ by the kidneys were only associated with the plasma PQ concentration. Activated charcoal hemoperfusion had little effect on avoiding acute kidney injury in patients with severe PQ poisoning.", "title": "Effect of activated charcoal hemoperfusion on renal function in patients with paraquat poisoning." }, { "docid": "6157837", "text": "Angiotensin converting enzyme (ACE) inhibitors are now one of the most frequently used classes of antihypertensive drugs. Beyond their utility in the management of hypertension, their use has been extended to the long-term management of patients with congestive heart failure (CHF), as well as diabetic and nondiabetic nephropathies. Although ACE inhibitor therapy usually improves renal blood flow (RBF) and sodium excretion rates in CHF and reduces the rate of progressive renal injury in chronic renal disease, its use can also be associated with a syndrome of “functional renal insufficiency” and/or hyperkalemia. This form of acute renal failure (ARF) most commonly develops shortly after initiation of ACE inhibitor therapy but can be observed after months or years of therapy, even in the absence of prior ill effects. ARF is most likely to occur when renal perfusion pressure cannot be sustained because of substantial decreases in mean arterial pressure (MAP) or when glomerular filtration rate (GFR) is highly angiotensin II (Ang II) dependent. Conditions that predict an adverse hemodynamic effect of ACE inhibitors in patients with CHF are preexisting hypotension and low cardiac filling pressures. The GFR is especially dependent on Ang II during extracellular fluid (ECF) volume depletion, high-grade bilateral renal artery stenosis, or stenosis of a dominant or single kidney, as in a renal transplant recipient. Understanding the pathophysiological mechanisms and the common risk factors for ACE inhibitor–induced functional ARF is critical, because preventive strategies for ARF exist, and if effectively used, they may permit use of these compounds in a less restricted fashion. Under normal physiological conditions, renal autoregulation adjusts renal vascular resistance, so that RBF and GFR remain constant over a wide range of MAPs.1 The intrinsic renal autoregulation mechanism is adjusted by Ang II and the sympathetic nervous system. When renal perfusion pressure falls (as in …", "title": "Renal considerations in angiotensin converting enzyme inhibitor therapy: a statement for healthcare professionals from the Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association." }, { "docid": "18348376", "text": "BACKGROUND Multiple mechanisms have been advanced to account for CD4+FOXP3+ regulatory T cell (Treg)-mediated suppression of CD4+ effector T cells (Teffs) but none appear to completely explain suppression. Previous data indicates that Tregs may affect the microenvironment redox state. Given the inherent redox sensitivity of T cells, we tested the hypothesis that oxidants may mediate the direct suppression of Teffs by Tregs. METHODOLOGY/PRINCIPAL FINDINGS Tregs and Teffs were isolated from the spleens of wild type (WT) C57BL/6 mice or Ncf1(p47phox)-deficient C57BL/6 mice which lack NADPH oxidase function. Teffs were labeled with CFSE and co-cultured with unlabeled Tregs at varying Treg:Teff ratios in the presence of anti-CD3/CD28 coated beads for 3 days in suppression assays. Treg-mediated suppression was quantified by flow cytometric analysis of CFSE dilution in Teffs. The presence of the antioxidants n-acetylcysteine (NAC) or 2-mercaptoethanol or inhibitors of NADPH oxidase (diphenyleneiodonium and VAS-2870) resulted in reduced WT Treg-mediated suppression. The observed suppression was in part dependent upon TGFβ as it was partially blocked with neutralizing antibodies. The suppression of Teff proliferation induced by exogenous TGFβ treatment could be overcome with NAC. Ncf1-deficient Teff were slightly but significantly less sensitive than WT Teff to suppression by exogenous TGFβ. Ncf1-deficient Tregs suppressed Ncf1-deficient Teff very poorly compared to wild type controls. There was partial but incomplete reconstitution of suppression in assays with WT Tregs and Ncf1-deficient Teff. CONCLUSIONS/SIGNIFICANCE We present evidence that NADPH oxidase derived ROS plays a role in the direct Treg mediated suppression of CD4+ effector T cells in a process that is blocked by thiol-containing antioxidants, NADPH oxidase inhibitors or a lack of Ncf1 expression in Tregs and Teffs. Oxidants may represent a potential new target for therapeutic modulation of Treg function.", "title": "Ncf1 (p47phox) Is Essential for Direct Regulatory T Cell Mediated Suppression of CD4+ Effector T Cells" }, { "docid": "29735200", "text": "Dry beans and soybeans are nutrient-dense, fiber-rich, and are high-quality sources of protein. Protective and therapeutic effects of both dry bean and soybean intake have been documented. Studies show that dry bean intake has the potential to decrease serum cholesterol concentrations, improve many aspects of the diabetic state, and provide metabolic benefits that aid in weight control. Soybeans are a unique source of the isoflavones genistein and diadzein, which have numerous biological functions. Soybeans and soyfoods potentially have multifaceted health-promoting effects, including cholesterol reduction, improved vascular health, preserved bone mineral density, and reduction of menopausal symptoms. Soy appears to have salutary effects on renal function, although these effects are not well understood. Whereas populations consuming high intakes of soy have lower prevalences of certain cancers, definitive experimental data are insufficient to clarify a protective role of soy. The availability of legume products and resources is increasing, incorporating dry beans and soyfoods into the diet can be practical and enjoyable. With the shift toward a more plant-based diet, dry beans and soy will be potent tools in the treatment and prevention of chronic disease.", "title": "Cardiovascular and renal benefits of dry bean and soybean intake." }, { "docid": "1103795", "text": "Antibiotic mode-of-action classification is based upon drug-target interaction and whether the resultant inhibition of cellular function is lethal to bacteria. Here we show that the three major classes of bactericidal antibiotics, regardless of drug-target interaction, stimulate the production of highly deleterious hydroxyl radicals in Gram-negative and Gram-positive bacteria, which ultimately contribute to cell death. We also show, in contrast, that bacteriostatic drugs do not produce hydroxyl radicals. We demonstrate that the mechanism of hydroxyl radical formation induced by bactericidal antibiotics is the end product of an oxidative damage cellular death pathway involving the tricarboxylic acid cycle, a transient depletion of NADH, destabilization of iron-sulfur clusters, and stimulation of the Fenton reaction. Our results suggest that all three major classes of bactericidal drugs can be potentiated by targeting bacterial systems that remediate hydroxyl radical damage, including proteins involved in triggering the DNA damage response, e.g., RecA.", "title": "A Common Mechanism of Cellular Death Induced by Bactericidal Antibiotics" }, { "docid": "21383026", "text": "Despite over a century of research, tuberculosis remains a leading cause of infectious death worldwide. Faced with increasing rates of drug resistance, the identification of genes that are required for the growth of this organism should provide new targets for the design of antimycobacterial agents. Here, we describe the use of transposon site hybridization (TraSH) to comprehensively identify the genes required by the causative agent, Mycobacterium tuberculosis, for optimal growth. These genes include those that can be assigned to essential pathways as well as many of unknown function. The genes important for the growth of M. tuberculosis are largely conserved in the degenerate genome of the leprosy bacillus, Mycobacterium leprae, indicating that non-essential functions have been selectively lost since this bacterium diverged from other mycobacteria. In contrast, a surprisingly high proportion of these genes lack identifiable orthologues in other bacteria, suggesting that the minimal gene set required for survival varies greatly between organisms with different evolutionary histories.", "title": "Genes required for mycobacterial growth defined by high density mutagenesis." }, { "docid": "435529", "text": "HEN1-mediated 2'-O-methylation has been shown to be a key mechanism to protect plant microRNAs (miRNAs) and small interfering RNAs (siRNAs) as well as animal piwi-interacting RNAs (piRNAs) from degradation and 3' terminal uridylation [1-8]. However, enzymes uridylating unmethylated miRNAs, siRNAs, or piRNAs in hen1 are unknown. In this study, a genetic screen identified a second-site mutation hen1 suppressor1-2 (heso1-2) that partially suppresses the morphological phenotypes of the hypomorphic hen1-2 allele and the null hen1-1 allele in Arabidopsis. HESO1 encodes a terminal nucleotidyl transferase that prefers to add untemplated uridine to the 3' end of RNA, which is completely abolished by 2'-O-methylation. heso1-2 affects the profile of u-tailed miRNAs and siRNAs and increases the abundance of truncated and/or normal sized ones in hen1, which often results in increased total amount of miRNAs and siRNAs in hen1. In contrast, overexpressing HESO1 in hen1-2 causes more severe morphological defects and less accumulation of miRNAs. These results demonstrate that HESO1 is an enzyme uridylating unmethylated miRNAs and siRNAs in hen1. These observations also suggest that uridylation may destabilize unmethylated miRNAs through an unknown mechanism and compete with 3'-to-5' exoribonuclease activities in hen1. This study shall have implications on piRNA uridylation in hen1 in animals.", "title": "Uridylation of miRNAs by HEN1 SUPPRESSOR1 in Arabidopsis" }, { "docid": "5573975", "text": "Molecules associated with the transforming growth factor β (TGF-β) superfamily, such as bone morphogenic proteins (BMPs) and TGF-β, are key regulators of inflammation, apoptosis and cellular transitions. Here we show that the BMP receptor activin-like kinase 3 (Alk3) is elevated early in diseased kidneys after injury. We also found that its deletion in the tubular epithelium leads to enhanced TGF-β1-Smad family member 3 (Smad3) signaling, epithelial damage and fibrosis, suggesting a protective role for Alk3-mediated signaling in the kidney. A structure-function analysis of the BMP-Alk3-BMP receptor, type 2 (BMPR2) ligand-receptor complex, along with synthetic organic chemistry, led us to construct a library of small peptide agonists of BMP signaling that function through the Alk3 receptor. One such peptide agonist, THR-123, suppressed inflammation, apoptosis and the epithelial-to-mesenchymal transition program and reversed established fibrosis in five mouse models of acute and chronic renal injury. THR-123 acts specifically through Alk3 signaling, as mice with a targeted deletion for Alk3 in their tubular epithelium did not respond to therapy with THR-123. Combining THR-123 and the angiotensin-converting enzyme inhibitor captopril had an additive therapeutic benefit in controlling renal fibrosis. Our studies show that BMP signaling agonists constitute a new line of therapeutic agents with potential utility in the clinic to induce regeneration, repair and reverse established fibrosis.", "title": "Activin–like kinase–3 activity is important for kidney regeneration and reversal of fibrosis" }, { "docid": "356218", "text": "BACKGROUND Pregnant women with mild preexisting renal disease have relatively few complications of pregnancy, but the risks of maternal and obstetrical complications in women with moderate or severe renal insufficiency remain uncertain. METHODS We determined the frequency and types of maternal and obstetrical complications and the outcomes of pregnancy in 67 women with primary renal disease (82 pregnancies). All the women had initial serum creatinine concentrations of at least 1.4 mg per deciliter (124 mumol per liter) and gestations that continued beyond the first trimester. RESULTS The mean (+/- SD) serum creatinine concentration increased from 1.9 +/- 0.8 mg per deciliter (168 +/- 71 mumol per liter) in early pregnancy to 2.5 +/- 1.3 mg per deciliter (221 +/- 115 mumol per liter) in the third trimester. The frequency of hypertension rose from 28 percent at base line to 48 percent in the third trimester, and that of high-grade proteinuria (urinary protein excretion, > 3000 mg per liter) from 23 percent to 41 percent. For the 70 pregnancies (57 women) for which data were available during pregnancy and immediately post partum, pregnancy-related loss of maternal renal function occurred in 43 percent. Eight of these pregnancies (10 percent of the total) were associated with rapid acceleration of maternal renal insufficiency. Obstetrical complications included a high rate of preterm delivery (59 percent) and growth retardation (37 percent). The infant survival rate was 93 percent. CONCLUSIONS Among pregnant women with moderate or severe renal insufficiency, the rates of complications due to worsening renal function, hypertension, and obstetrical complications are increased, but fetal survival is high.", "title": "Outcome of pregnancy in women with moderate or severe renal insufficiency." }, { "docid": "10247282", "text": "In the rat isolated perfused kidney, arachidonic acid elicits cyclooxygenase-dependent vasoconstriction through activation of PGH2/TxA2 receptors; responses are enhanced in kidneys from diabetic rats. This study examined the roles of cyclooxygenase-1/cyclooxygenase-2 in the enhanced renal vasoconstrictor effect of arachidonic acid in streptozotocin-diabetic rats. Release of 20-HETE was also determined, as this eicosanoid has been reported to elicit cyclooxygenase-dependent vasoconstriction. We confirmed that vasoconstrictor responses to arachidonic acid were enhanced in the diabetic rat kidney associated with a 2-fold-greater increase in the release of 6-ketoPGF1alpha, which was used as an index of cyclooxygenase activity. One and three micrograms of arachidonic acid increased perfusion pressure by 85+/-37 and 186+/-6 mm Hg, respectively, in diabetic rat kidneys compared with 3+/-1 and 17+/-8 mm Hg, respectively, in control rat kidneys. Inhibition of both cyclooxygenase isoforms with indomethacin (10 micromol/L) abolished the vasoconstrictor response to arachidonic acid in both diabetic and control rat kidneys, whereas inhibition of cyclooxygenase-2 with nimesulide (5 micromol/L) reduced perfusion pressure responses to 1 and 3 microg arachidonic acid only in the diabetic rat kidney to 15+/-8 and 108+/-26 mm Hg, respectively, consistent with a 3-fold increase in the renal cortical expression of cyclooxygenase-2. 20-HETE release from the diabetic rat kidney was reduced almost 6-fold and was not increased in response to arachidonic acid. These results demonstrate that the renal vasoconstrictor effect of arachidonic acid is solely dependent on cyclooxygenase activity, with no evidence for a contribution from 20-HETE; in the diabetic rat, cyclooxygenase-2 activity contributes to the renal vasoconstrictor effect of arachidonic acid.", "title": "Arachidonic Acid in the Diabetic Rat Kidney" }, { "docid": "22236223", "text": "Pregnancy in women with different renal diseases has important consequences for the developing fetus and maternal health. Kidneys and the urinary tract have to adapt to the pregnancy status and therefore suffer significant anatomical, hemodynamic and endocrine changes. Failure to adapt can aggravate the preexisting maternal disease and can also create suboptimal environment for fetal development and increase the risk of obstetric complications. Knowledge and correct interpretation of the renal functional tests is necessary for the modern obstetrician, avoiding an incorrect diagnosis for renal disease where only specific renal changes during pregnancy are present, but meanwhile a correct evaluation of the renal function and changes can detect a pathology that can aggravate both the mother’s and the baby’s condition. Improvement and better understanding of the renal pathophysiology in pregnancy made possible that pregnant woman look forward for a good outcome, including here also the women with renal transplant. Nowadays is underlined the concept of multidisciplinary teamwork, a very important concept of modern medicine. The obstetrician should consider nephrologists as key players in the team and in our opinion should refer to them the pregnant women for a routine check-up of the renal status in the 2nd or beginning of 3rd trimester by ultrasound, beside the usual blood and urine analysis. The nephrologists and urologists should be involved in the management of severe medical conditions, such as preeclampsia, acute and chronic renal failure and never the less in the complex management of dialysis or renal transplant patients. In pregnancy it can be encountered several renal diseases, some of them preexisting the pregnancy and other developed or being direct influenced by pregnancy. This chapter will discuss briefly the basic evaluation of renal status in order to present and better understand the acute and chronic renal disorders in pregnancy. The chapter will focus on the most common preexisting diseases in pregnancy such as: chronic glomerulonephritis, secondary glomerular nephropathies, interstitial nephropathies (chronic pyelonephritis, renal tuberculosis), diabetes nephropathy, unique surgical kidney, chronic renal failure. From the renal diseases directly influenced by pregnancy it will be discussed: asymptomatic bacteriuria, symptomatic urinary infection, urolithiasis and acute renal failure in pregnancy. It will be presented also the management of dialysis in pregnancy and pregnant women with renal transplant.", "title": "Renal Disease and Pregnancy" }, { "docid": "1554348", "text": "MCF-7, a continuous cell line derived from a human breast carcinoma, exhibits very low alkaline phosphatase (ALP) activity. The enzyme is heat-stable and is inhibited by L-phenylalanine and L-phenylalanylgly-cylglycine, but not by L-homoarginine, 1-bromotetramisole, or levamisole. These data indicate that MCF-7 produces term-placental ALP, the oncodevelopmental enzyme form inappropriately expressed by a variety of human tumors. In contrast to human cancer cells that produce this enzyme monophenotypically, ALP activity of MCF-7 cells is not significantly increased by glucocorticoids or sodium butyrate. By comparison, exposure to hyperosmolality causes a striking increase in enzyme activity. Cycloheximide blocks this effect. The results obtained with cell-free assays were confirmed by cytochemical and immunocytochemical assays on whole cells. Because some of the agents tested in the enzyme modulation experiments affect cell proliferation, their possible effect on two stress-response proteins (srp 27 and srp 72) was also examined; specific immunocytochemical assays were used. These tests revealed that neither protein is affected by glucocorticoids; that sodium butyrate has no effect on srp 27, but alters the intracellular distribution of srp 72; and that hyperosmolality, while not significantly affecting srp 72, causes an increase in srp 27.", "title": "Effect of hyperosmolality on alkaline phosphatase and stress-response protein 27 of MCF-7 breast cancer cells" }, { "docid": "10582939", "text": "CONTEXT Antibody-based induction therapy plus calcineurin inhibitors (CNIs) reduce acute rejection rates in kidney recipients; however, opportunistic infections and toxic CNI effects remain challenging. Reportedly, mesenchymal stem cells (MSCs) have successfully treated graft-vs-host disease. OBJECTIVE To assess autologous MSCs as replacement of antibody induction for patients with end-stage renal disease who undergo ABO-compatible, cross-match-negative kidney transplants from a living-related donor. DESIGN, SETTING, AND PATIENTS One hundred fifty-nine patients were enrolled in this single-site, prospective, open-label, randomized study from February 2008-May 2009, when recruitment was completed. INTERVENTION Patients were inoculated with marrow-derived autologous MSC (1-2 x 10(6)/kg) at kidney reperfusion and two weeks later. Fifty-three patients received standard-dose and 52 patients received low-dose CNIs (80% of standard); 51 patients in the control group received anti-IL-2 receptor antibody plus standard-dose CNIs. MAIN OUTCOME MEASURES The primary measure was 1-year incidence of acute rejection and renal function (estimated glomerular filtration rate [eGFR]); the secondary measure was patient and graft survival and incidence of adverse events. RESULTS Patient and graft survival at 13 to 30 months was similar in all groups. After 6 months, 4 of 53 patients (7.5%) in the autologous MSC plus standard-dose CNI group (95% CI, 0.4%-14.7%; P = .04) and 4 of 52 patients (7.7%) in the low-dose group (95% CI, 0.5%-14.9%; P = .046) compared with 11 of 51 controls (21.6%; 95% CI, 10.5%-32.6%) had biopsy-confirmed acute rejection. None of the patients in either autologous MSC group had glucorticoid-resistant rejection, whereas 4 patients (7.8%) in the control group did (95% CI, 0.6%-15.1%; overall P = .02). Renal function recovered faster among both MSC groups showing increased eGFR levels during the first month after surgery than the control group. Patients receiving standard-dose CNI had a mean difference of 6.2 mL/min per 1.73 m(2) (95% CI, 0.4-11.9; P=.04) and those in the low-dose CNI of 10.0 mL/min per 1.73 m(2) (95% CI, 3.8-16.2; P=.002). Also, during the 1-year follow-up, combined analysis of MSC-treated groups revealed significantly decreased risk of opportunistic infections than the control group (hazard ratio, 0.42; 95% CI, 0.20-0.85, P=.02) CONCLUSION Among patients undergoing renal transplant, the use of autologous MSCs compared with anti-IL-2 receptor antibody induction therapy resulted in lower incidence of acute rejection, decreased risk of opportunistic infection, and better estimated renal function at 1 year. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00658073.", "title": "Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: a randomized controlled trial." }, { "docid": "238409", "text": "Background:Chronic cyclosporine A (CsA) nephrotoxicity (CCN) is a major cause of chronic renal dysfunction and has no effective clinical interventions yet. Objective: To reveal the mechanisms of renal cell apoptosis in CCN, we analyzed all in vitro studies of such mechanisms. Methods: We collected all in vitro studies about the mechanisms of renal cell apoptosis induced by CsA in Medline (1966 to July 2010), Embase (1980 to July 2010) and ISI (1986 to July 2010), evaluated their quality according to in vitro standards and extracted data following the PICOS principles and synthesized the data. Results: First,CsA could upregulate Fas and Fas-L expression, increase FADD and apoptosis enzymes (caspase-2, -3, -4, -7, -8, -9 and -10) and downregulate the Bcl-2 and Bcl-xL. Second, CsA could induce oxidative stress and damage the antioxidant defense system. Third, CsA could increase the expression of HERP, GRP78 and CHOP. Fourth, CsA could induce renal cell apoptosis and increase their iNOS and p53 expression in cultured cells. Conclusions: At least four pathways are involved in renal cell apoptosis induced by CsA in different cell species. Caspases might be their final common pathway in vitro. They might all provide potential points for interventions, but these need to be confirmed in vivo.", "title": "Mechanisms of Renal Cell Apoptosis Induced by Cyclosporine A: A Systematic Review of in vitro Studies" }, { "docid": "24998764", "text": "Chronic kidney disease is accompanied by increased large-artery stiffness, but the relation between glomerular filtration rate within the reference range and central or peripheral arterial stiffness has been understudied. The link between renal function and arterial stiffness was assessed in 305 patients with never-treated essential hypertension (men: 58%; age: 48+/-11 years, blood pressure: 151/95+/-20/11 mm Hg), free from overt cardiovascular disease and with serum creatinine values <1.4 mg/dL (men) and <1.2 mg/dL (women), who underwent noninvasive aortic and upper-limb pulse wave velocity (PWV) determination. Aortic PWV was strongly related to age (r=0.55; P<0.001), whereas upper-limb PWV had a weaker nonlinear relation with age (beta=1.392; P<0.001 for age; beta=-1.312; P<0.001 for age squared) and a weak relation with aortic PWV (r=0.22; P<0.001). Glomerular filtration rate (GFR), estimated according to the Mayo clinic equation for healthy subjects, was inversely correlated with large-artery stiffness, as assessed by aortic PWV (r=-0.34; P<0.001), and with peripheral artery stiffness, as assessed by upper-limb PWV (r=-0.25; P<0.001). In a multivariate linear regression, aortic PWV was independently predicted by age (beta=0.48; P<0.001), mean arterial pressure (beta=0.14; P=0.013), and GFR (beta=-0.13, P=0.029). Upper-limb PWV was predicted by GFR (beta=-0.24; P<0.001) and mean arterial pressure (beta=0.20; P<0.001). We conclude that, in hypertensive patients with normal renal function, an inverse relationship exists between GFR and stiffness of both central elastic and peripheral muscular arteries. These relations are in part independent from the effect of several confounders, including age, sex, and blood pressure values.", "title": "Relation between renal function within the normal range and central and peripheral arterial stiffness in hypertension." }, { "docid": "11900630", "text": "Objective. Chemotherapeutic agents function by inducing apoptosis and their effectiveness depends on the balance of pro- and anti-apoptotic proteins in cells. Due to the complicated interactions of the many proteins involved, it has been difficult to determine in tumors whether overexpression of single genes is prognostic for increased resistance. Therefore, we studied the influence of bcl-2 overexpression on resistance to chemotherapeutics in a transgenic mouse system. This allowed us to study a wide variety of cells, including important but rare populations such as hematopoietic stem cells (HSC).Methods. H2K-bcl-2 transgenic and wild-type (WT) mice were treated with several agents(5-fluoruracil, cyclophosphamide, and busulfan) to determine the contribution of increased amounts of bcl-2 to the response to these chemotherapeutics in vivo. Populations were enumerated using flow cytometry. HSC were studied by FACS purification and long-term reconstitution assays in vivo and resistance was confirmed by short-term proliferation assays with different amounts of chemotherapeutics in vitro. Results. bcl-2 overexpression alone protects many cell types, though protection levels differ between populations and agents. However, even sensitive populations return to pretreatment levels faster in transgenic mice. bcl-2 overexpression also prevents the dramatic changes in HSC following 5-FU treatment (downregulation of c-kit, upregulation of Lin, less efficient long-term reconstitution). In vitro studies directly demonstrate increased resistance of bcl-2 overexpressing HSC to chemotherapeutic agents. Conclusions. Increased expression of bcl-2 in HSC and their progeny endows these cells with broad resistance to chemotherapeutic agents. The ability to (differentially) regulate sensitivity to apoptosis of bystander and tumor cells is clinically important.", "title": "Hematopoietic stem cells and other hematopoietic cells show broad resistance to chemotherapeutic agents in vivo when overexpressing bcl-2." }, { "docid": "8839502", "text": "The incidence of chronic kidney diseases is increasing worldwide, and these conditions are emerging as a major public health problem. While genetic factors contribute to susceptibility and progression of renal disease, proteinuria has been claimed as an independent predictor of outcome. Reduction of urinary protein levels by various medications and a low-protein diet limits renal function decline in individuals with nondiabetic and diabetic nephropathies to the point that remission of the disease and regression of renal lesions have been observed in experimental animals and even in humans. In animal models, regression of glomerular structural changes is associated with remodeling of the glomerular architecture. Instrumental to this discovery were 3D reconstruction studies of the glomerular capillary tuft, which allowed the quantification of sclerosis volume reduction and capillary regeneration upon treatment. Regeneration of capillary segments might result from the contribution of resident cells, but progenitor cells of renal or extrarenal origin may also have a role. This review describes recent advances in our understanding of the mechanisms and mediators underlying renal tissue repair ultimately responsible for regression of renal injury.", "title": "Mechanisms of progression and regression of renal lesions of chronic nephropathies and diabetes." }, { "docid": "27550580", "text": "OBJECTIVES The aim of this study was to determine the accuracy of the contrast \"bolus only\" T1 mapping cardiac magnetic resonance (CMR) technique for measuring myocardial extracellular volume fraction (ECV). BACKGROUND Myocardial ECV can be measured with T1 mapping before and after contrast agent if the contrast agent distribution between blood/myocardium is at equilibrium. Equilibrium distribution can be achieved with a primed contrast infusion (equilibrium contrast-CMR [EQ-CMR]) or might be approximated by the dynamic equilibration achieved by delayed post-bolus measurement. This bolus only approach is highly attractive, but currently limited data support its use. We compared the bolus only technique with 2 independent standards: collagen volume fraction (CVF) from myocardial biopsy in aortic stenosis (AS); and the infusion technique in 5 representative conditions. METHODS One hundred forty-seven subjects were studied: healthy volunteers (n = 50); hypertrophic cardiomyopathy (n = 25); severe AS (n = 22); amyloid (n = 20); and chronic myocardial infarction (n = 30). Bolus only (at 15 min) and infusion ECV measurements were performed and compared. In 18 subjects with severe AS the results were compared with histological CVF. RESULTS The ECV by both techniques correlated with histological CVF (n = 18, r² = 0.69, p < 0.01 vs. r² = 0.71, p < 0.01, p = 0.42 for comparison). Across health and disease, there was strong correlation between the techniques (r² = 0.97). However, in diseases of high ECV (amyloid, hypertrophic cardiomyopathy late gadolinium enhancement, and infarction), Bland-Altman analysis indicates the bolus only technique has a consistent and increasing offset, giving a higher value for ECVs above 0.4 (mean difference ± limit of agreement for ECV <0.4 = -0.004 ± 0.037 vs. ECV >0.4 = 0.040 ± 0.075, p < 0.001). CONCLUSIONS Bolus only, T1 mapping-derived ECV measurement is sufficient for ECV measurement across a range of cardiac diseases, and this approach is histologically validated in AS. However, when ECV is >0.4, the bolus only technique consistently measures ECV higher compared with infusion.", "title": "T1 mapping for myocardial extracellular volume measurement by CMR: bolus only versus primed infusion technique." }, { "docid": "6250701", "text": "BACKGROUND Acute renal failure is a common complication of severe malaria in adults, and without renal replacement therapy (RRT), it carries a poor prognosis. Even when RRT is available, delaying its initiation may increase mortality. Earlier identification of patients who will need RRT may improve outcomes. METHOD Prospectively collected data from two intervention studies in adults with severe malaria were analysed focusing on laboratory features on presentation and their association with a later requirement for RRT. In particular, laboratory indices of acute tubular necrosis (ATN) and acute kidney injury (AKI) that are used in other settings were examined. RESULTS Data from 163 patients were available for analysis. Whether or not the patients should have received RRT (a retrospective assessment determined by three independent reviewers) was used as the reference. Forty-three (26.4%) patients met criteria for dialysis, but only 19 (44.2%) were able to receive this intervention due to the limited availability of RRT. Patients with impaired renal function on admission (creatinine clearance < 60 ml/min) (n = 84) had their laboratory indices of ATN/AKI analysed. The plasma creatinine level had the greatest area under the ROC curve (AUC): 0.83 (95% confidence interval 0.74-0.92), significantly better than the AUCs for, urinary sodium level, the urea to creatinine ratio (UCR), the fractional excretion of urea (FeUN) and the urinary neutrophil gelatinase-associated lipocalcin (NGAL) level. The AUC for plasma creatinine was also greater than the AUC for blood urea nitrogen level, the fractional excretion of sodium (FeNa), the renal failure index (RFI), the urinary osmolality, the urine to plasma creatinine ratio (UPCR) and the creatinine clearance, although the difference for these variables did not reach statistical significance. CONCLUSIONS In adult patients with severe malaria and impaired renal function on admission, none of the evaluated laboratory indices was superior to the plasma creatinine level when used to predict a later requirement for renal replacement therapy.", "title": "Laboratory prediction of the requirement for renal replacement in acute falciparum malaria" }, { "docid": "13923140", "text": "Autoimmune diseases are thought to result from imbalances in normal immune physiology and regulation. Here, we show that autoimmune disease susceptibility and resistance alleles on mouse chromosome 3 (Idd3) correlate with differential expression of the key immunoregulatory cytokine interleukin-2 (IL-2). In order to test directly that an approximately twofold reduction in IL-2 underpins the Idd3-linked destabilization of immune homeostasis, we show that engineered haplodeficiency of Il2 gene expression not only reduces T cell IL-2 production by twofold but also mimics the autoimmune dysregulatory effects of the naturally occurring susceptibility alleles of Il2. Reduced IL-2 production achieved by either genetic mechanism correlates with reduced function of CD4+ CD25+ regulatory T cells, which are critical for maintaining immune homeostasis.", "title": "Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity" }, { "docid": "23377475", "text": "The previous conventional wisdom that survivors of acute kidney injury (AKI) tend to do well and fully recover renal function appears to be flawed. AKI can cause end-stage renal disease (ESRD) directly, and increase the risk of developing incident chronic kidney disease (CKD) and worsening of underlying CKD. In addition, severity, duration, and frequency of AKI appear to be important predictors of poor patient outcomes. CKD is an important risk factor for the development and ascertainment of AKI. Experimental data support the clinical observations and the bidirectional nature of the relationships between AKI and CKD. Reductions in renal mass and nephron number, vascular insufficiency, cell cycle disruption, and maladaptive repair mechanisms appear to be important modulators of progression in patients with and without coexistent CKD. Distinction between AKI and CKD may be artificial. Consideration should be given to the integrated clinical syndrome of diminished GFR, with acute and chronic stages, where spectrum of disease state and outcome is determined by host factors, including the balance of adaptive and maladaptive repair mechanisms over time. Physicians must provide long-term follow-up to patients with first episodes of AKI, even if they presented with normal renal function.", "title": "Acute kidney injury and chronic kidney disease: an integrated clinical syndrome." }, { "docid": "20287253", "text": "Congenital obstructive nephropathy is a consequence abnormal urinary tract development resulting in renal growth failure and injury manifested by progressive tubular atrophy and interstitial fibrosis. We have studied the renal cellular and physiological response to unilateral ureteral obstruction (UUO) in the neonatal rodent (guinea pig, rat, and mouse). Whereas in the adult, UUO stimulates renal cellular proliferation, UUO in the neonate reduces nephrogenesis, glomerular maturation, and tubular cellular proliferation. This is accompanied by a proportionately greater compensatory growth of the intact opposite kidney in the neonate. Impaired renal growth and tubular atrophy are likely owing at least in part to stimulation of renal tubular apoptosis. This, in turn, may result from a combination of factors, including loss of epithelial cell polarity, a reduction in the oncoprotein bcl-2 and epidermal growth factor (EGF), and increased expression of the fibrogenic cytokine, transforming growth factor-beta1 (TGF-beta1). Infusion of EGF stimulates cellular proliferation, suppresses apoptosis, and reduces tubular atrophy and interstitial fibrosis. TGF-beta1 is regulated by the renin-angiotensin system, which is markedly activated by UUO in the neonate. The functional consequences of obstructive nephropathy in early development are hyperfiltration by remaining nephrons, followed by progressive decrease in glomerular filtration rate that may only develop in later life. Improved management of congenital urinary tract obstruction will depend on a better understanding of the cellular mechanisms, which may lead to specific treatment using gene therapy or modulators of renal growth and development.", "title": "Pathophysiology of obstructive nephropathy in the newborn." } ]
57215
Portia de Rossi was employed with Kerry Washington.
[ { "docid": "Scandal_(TV_series)", "text": "Scandal is an American political thriller television series starring Kerry Washington . Created by Shonda Rhimes , it debuted on ABC on April 5 , 2012 . Kerry Washington 's character , Olivia Pope , is partially based on former George H.W. Bush administration press aide Judy Smith , who serves as a co-executive producer . The show takes place in Washington , D.C. and focuses on Olivia Pope 's crisis management firm , Olivia Pope & Associates , and its staff , as well as staff at the White House and surrounding political scene , which includes President Fitzgerald Grant III , White House Chief of Staff Abigail Whelan , Attorney General David Rosen , Vice President Susan Ross , the Vice President 's Chief of Staff Elizabeth North , ex-First Lady and now President-Elect Mellie Grant , NSA Director Jake Ballard , and ex-White House Chief of Staff Cyrus Beene . In addition to Kerry Washington , the show features Guillermo Diaz and Katie Lowes as assistants at O.P.A. ; Tony Goldwyn as the President ; Bellamy Young as the ex-First Lady and senator ; Jeff Perry as the former White House Chief of Staff ; Darby Stanchfield as the White House Press Secretary and current Chief of Staff ; Joshua Malina as the Attorney General ; Scott Foley as the Director of the NSA ; Portia de Rossi as the Vice President 's Chief of Staff ; Cornelius Smith Jr. as a civil rights activist and associate at O.P.A. ; and Joe Morton as Olivia 's father and the former head of a spy agency called B613 . The show was named a Television Program of the Year by the American Film Institute , received the Peabody Award for Excellence in Television and was honored as Outstanding Drama Series at the Image Awards . Washington has won the Image Award for Outstanding Actress in a Drama Series and has been nominated for an Emmy Award for Outstanding Lead Actress in a Drama Series , a Golden Globe Award for Best Actress in a Drama Series , and a SAG Award for Outstanding Performance by an Actress in a Drama Series .", "title": "" }, { "docid": "Portia_de_Rossi", "text": "Portia Lee James DeGeneres ( born Amanda Lee Rogers ; January 31 , 1973 ) , also known professionally as Portia de Rossi ( -LSB- ˈpɔərʃə_də_ˈrɒsi -RSB- ) , is an Australian and American actress , model , and philanthropist . She appeared as a regular cast member on the American political thriller television series Scandal in the role of Elizabeth North from 2014 to 2017 . She is also known for her roles as lawyer Nelle Porter on the American television series Ally McBeal -- for which she won a Screen Actors Guild Award in 1999 -- and as Lindsay Fünke on the American television sitcom Arrested Development . She also portrayed Veronica Palmer on the ABC television sitcom Better Off Ted , and Olivia Lord on the television drama Nip/Tuck . De Rossi is married to comedian and television host Ellen DeGeneres .", "title": "" } ]
[ { "docid": "De_Rossi", "text": "De Rossi is an Italian surname , and may refer to : Alessandra De Rossi , Philippine actress Assunta De Rossi , Philippine actress Azariah dei Rossi , an Italian-Jewish physician and scholar Bernardo de Rossi , Italian theologian and historian Bernardo de ' Rossi , Italian bishop Daniele De Rossi , Italian footballer Fabrizio De Rossi , a fictional character in the 1997 film Titanic Giovan Antonio de ' Rossi , ( 1616 -- 1695 ) , Italian architect of the Baroque Giovanni Battista de Rossi , 19th-century Italian archaeologist Giovanni Bernardo De Rossi , 19th-century Italian Christian Hebraist Mattia de Rossi , ( 1637 -- 1695 ) , Italian architect of the Baroque Properzia de ' Rossi , Italian Renaissance sculptor Portia de Rossi , Australian actress Saint Giovanni Battista de Rossi , 18th-century Roman priest", "title": "" }, { "docid": "List_of_Scandal_episodes", "text": "Scandal is an American political thriller television series created by Shonda Rhimes , which premiered on ABC on April 5 , 2012 . Kerry Washington stars as Olivia Pope , a former White House Communications Director who leaves to start her own crisis management firm , Pope and Associates , where she works to keep the secrets and protect the public images of the country 's most powerful and elite . On staff at the new firm are fresh-faced lawyer Quinn Perkins ( Katie Lowes ) ; smooth talking litigator Harrison Wright ( Columbus Short ) ; investigator Abby Whelan ( Darby Stanchfield ) ; and computer hacker with a CIA past Huck ( Guillermo Diaz ) . The show also focuses on President of the United States Fitzgerald Grant ( Tony Goldwyn ) ; First Lady Mellie Grant ( Bellamy Young ) ; White House Chief of Staff Cyrus Beene ( Jeff Perry ) ; Vice President and eventual presidential candidate Sally Langston ( Kate Burton ) ; U.S. Attorney David Rosen ( Joshua Malina ) ; Head of NSA , Jake Ballard ( Scott Foley ) ; chairwoman Elizabeth North ( Portia de Rossi ) ; activist Marcus Walker ( Cornelius Smith Jr. ) ; and head of B613 Eli Pope ( Joe Morton ) . On February 10 , 2017 , the show was renewed for a seventh season . It was later announced it will be the final season .", "title": "" }, { "docid": "DeGeneres", "text": "DeGeneres is a surname . Notable people with the surname include : Betty DeGeneres ( born 1930 ) , mother of Ellen DeGeneres and American activist . Ellen DeGeneres ( born 1958 ) , American stand-up comedian , television hostess , and actress . Vance DeGeneres ( born 1954 ) , American actor , older brother of Ellen DeGeneres . Portia de Rossi , or Portia DeGeneres ( born 1973 ) , wife of Ellen DeGeneres and American actress .", "title": "" }, { "docid": "American_Intellectuals", "text": "American Intellectuals is a ( 1999 ) Satire Comedy written and directed by Paige Taylor , starring Peter Hansen Gibson , Shawnee Free Jones , Portia de Rossi and Alex Martin .", "title": "" }, { "docid": "The_Night_We_Called_It_a_Day_(film)", "text": "The Night We Called It a Day , also known as All the Way , is a 2003 Australian-American comedy drama film directed by Paul Goldman and starring Dennis Hopper as Frank Sinatra and Melanie Griffith as Barbara Marx . It also features Portia de Rossi , Joel Edgerton , Rose Byrne and David Hemmings . The movie is based on the true events surrounding Sinatra 's 1974 tour in Australia . When the singer calls a local reporter ( de Rossi ) a `` two-bit hooker '' , every union in the country black-bans the star until he issues an apology .", "title": "" }, { "docid": "Amanda_Rogers", "text": "Amanda Rogers may refer to : Amanda Rogers , a Star Trek : The Next Generation character from the episode `` True Q '' Amanda Lee Rogers , birth name of actress Portia de Rossi", "title": "" }, { "docid": "Lily_Munster", "text": "Lily Munster , Countess of Shroudshire ( née Dracula ) , is a fictional character in the CBS sitcom , The Munsters , originally played by Yvonne De Carlo . The matriarch of the Munster household , Lily is a vampire . The role was later played by Lee Meriwether in The Munsters Today and by Portia de Rossi in Mockingbird Lane . In the original unaired color pilot her name was Phoebe Munster .", "title": "" }, { "docid": "Unbearable_Lightness", "text": "Unbearable Lightness may refer to : The Unbearable Lightness of Being , a 1984 novel written by Czech author Milan Kundera . The Unbearable Lightness of Being , a 1988 film based on the Kundera novel . Unbearable Lightness , the autobiography of Australian actor Portia de Rossi .", "title": "" }, { "docid": "I_Witness", "text": "I Witness is a human rights themed thriller with action elements starring Jeff Daniels , James Spader , Portia de Rossi , Clifton Collins , Jr. and Wade Williams . Released in the United States on February 1 , 2003 and re-released by Universal in 2007 .", "title": "" }, { "docid": "Logie_Awards_of_1999", "text": "The 41st Annual TV Week Logie Awards was held on Sunday 11 April 1999 at the Crown Palladium in Melbourne , and broadcast on the Nine Network . The ceremony was hosted by Andrew Denton , and guests included Isaac Hayes , Kevin Sorbo , Kathy Griffin , Portia De Rossi and Trudie Goodwin .", "title": "" }, { "docid": "Girl_(film)", "text": "Girl is a 1998 American drama film starring Dominique Swain , Christopher Masterson , Selma Blair , Tara Reid , Summer Phoenix , Portia de Rossi and Sean Patrick Flanery . It was based on the novel of the same name , written by Blake Nelson . It was written by Blake Nelson and David E. Tolchinsky and directed by Jonathan Kahn .", "title": "" }, { "docid": "Girl_(novel)", "text": "Girl is a 1994 novel written by Blake Nelson . The book chronicles teen girl Andrea Marr 's exploration of the Northwest music scene at the height of the `` grunge '' revolution . It was made into a film of the same name starring Dominique Swain , Portia de Rossi , and Selma Blair in 1998 . Portions of the novel first appeared in Sassy Magazine . Two more installments of the GIRL Series are available on Amazon Kindle .", "title": "" }, { "docid": "America's_Prince:_The_John_F._Kennedy_Jr._Story", "text": "America 's Prince : The John F. Kennedy Jr. . Story is a 2003 20th Century Fox television film . It is a biographical film about John F. Kennedy Jr. and based on Christopher Andersen 's 2000 bestseller , The Day John Died . It was directed by Eric Laneuville and stars Kristoffer Polaha , Portia de Rossi and Jacqueline Bisset in principal roles . It premiered on TBS on 12 January 2003 .", "title": "" }, { "docid": "Bronwyn_Lundberg", "text": "Bronwyn Lundberg is an American digital artist and painter specializing in graphic art . She is notable for her painting of the Lesbian Last Supper of Sandra Bernhard , Ellen DeGeneres , Melissa Etheridge , k.d. Lang , Jane Lynch , Rachel Maddow , Heather Matarazzo , Kate Moennig , Rosie O'Donnell , Linda Perry , Portia de Rossi , Wanda Sykes , and Lily Tomlin . Lundberg also collaborates with Sarah Zucker as the Pop Art team YoMeryl .", "title": "" }, { "docid": "Randy,_Red,_Superfreak_and_Julia", "text": "`` Randy , Red , Superfreak and Julia '' is the season premiere of the 4th season of Scandal , and is the 48th overall episode . It premiered on September 25 , 2014 in the U.S. on ABC . The premiere was received with critical acclaim from critics , with many commenting on the improvement from the third season after naming the previous season `` messy '' . On Rotten Tomatoes the premiere got a rating of 100 % fresh based on 6 reviews . The episode scored a series high in total viewers with 11.96 millions and in Adults 18-49 with a 3.8 / 11 . The episode focuses on Olivia 's return to Washington , D.C. after being away for two months , and how everything has changed . The episode saw the departure of Columbus Short 's character Harrison Wright , who was killed by Tom Larsen at the orders of Rowan Pope . The premiere introduced new characters , played by actors such as Portia de Rossi who was cast in a multiple-episode `` top secret arc '' starting with the premiere . Kelen Coleman and Matthew Del Negro were also cast for the premiere .", "title": "" }, { "docid": "Nelle_Porter", "text": "Nelle Porter is a fictional character on the Fox television show Ally McBeal . She is portrayed by actress Portia de Rossi and appears in Seasons 2 through 5 of the show . A Boston-based lawyer , Nelle joins the fictional law firm of Cage & Fish with the ambition of someday becoming a partner . Romantically involved with partner John Cage during Seasons 2 and 3 , she later appears mainly as a source of comic relief . She is also notable for her close friendship with Ling Woo , one of the show 's most remarked-upon characters .", "title": "" }, { "docid": "Portrait_of_Bishop_Bernardo_de'_Rossi", "text": "The Portrait of Bishop Bernardo de ' Rossi is a painting by the Italian High Renaissance painter Lorenzo Lotto , dating to 1505 . It is housed in the National Museum of Capodimonte of Naples , southern Italy . The work dates to Lotto 's stay in Treviso , and featured a cover ( with title , signature and dates , identified as the Allegory of Virtues and Vices now at the National Gallery of Art in Washington , United States . The portrait was brought to Parma by Bernardo de ' Rossi when he fled there in 1524 . Here it became part of the Farnese collection , which was transferred to Naples in 1760 .", "title": "" }, { "docid": "List_of_Arrested_Development_cast_members", "text": "Arrested Development is an American television sitcom that originally aired on the Fox network from November 2 , 2003 to February 10 , 2006 . Created by Mitchell Hurwitz , the show centers on the Bluth family , a formerly wealthy , habitually dysfunctional family , and is presented in a continuous format , incorporating hand-held camera work , narration , archival photos , and historical footage . The series stars Will Arnett , Jason Bateman , Michael Cera , David Cross , Portia de Rossi , Tony Hale , Alia Shawkat , Jeffrey Tambor , and Jessica Walter . Ron Howard serves as an executive producer on the show , as well as its narrator .", "title": "" }, { "docid": "Robert_Ozn", "text": "Robert Ozn ( born Robert M. Rosen , New York City ) , records under the name DaDa NaDa ; Broadway credits as Robert Rosen ; personal nickname OZN , ( pronounced `` OH-zen '' ) is a Top Five Billboard recording artist , award-winning screenwriter , producer and Broadway actor , being the vocal half of 80s synthpop duo EBN-OZN ; his solo act , Dada Nada ; and for his later work as co-producer and co-writer with Colin Greene of the human-rights themed feature film I Witness starring Jeff Daniels , James Spader and Portia de Rossi . He is also a prominent American bisexual activist ( see below ) .", "title": "" }, { "docid": "Kerry_Killinger", "text": "Kerry K Killinger ( born June 6 , 1949 , in Des Moines , Iowa ) is an American businessman and a former chairman and chief executive officer of Washington Mutual , a failed savings and loan association that became the largest bank failure in U.S. history . The actions of Kerry Killinger in his time as CEO of Washington Mutual was one of the factors that led to the Great Recession of 2008 .", "title": "" }, { "docid": "Christine_Gregoire", "text": "Christine `` Chris '' O'Grady Gregoire ( -LSB- ˈɡrɛɡwɑr -RSB- born March 24 , 1947 ) is an American politician who served as the 22nd Governor of the state of Washington from 2005 to 2013 . A member of the Democratic Party , Gregoire defeated Republican candidate Dino Rossi in 2004 and again in 2008 . She is the second female governor of Washington . She was the National Governors Association chairwoman for the 2010 -- 11 term . After she left the governorship , some sources reported that she was being considered for a position in Barack Obama 's cabinet in his second term , possibly in the State Department , or as United States Secretary of the Interior . However , John Kerry became the United States Secretary of State , while Sally Jewell was nominated for the position of Interior Secretary . Gregoire formerly served on the Governors ' Council of the Bipartisan Policy Center in Washington , D.C.", "title": "" }, { "docid": "List_of_Arrested_Development_characters", "text": "Arrested Development is an American television sitcom that originally aired on the Fox network from November 2 , 2003 to February 10 , 2006 . A fourth season of 15 episodes was released on Netflix on May 26 , 2013 . Created by Mitchell Hurwitz , the show centers on the Bluth family , a formerly wealthy , habitually dysfunctional family , and is presented in a continuous format , incorporating hand-held camera work , narration , archival photos , and historical footage . The series stars Jason Bateman , Portia de Rossi , Will Arnett , Michael Cera , Alia Shawkat , Tony Hale , David Cross , Jeffrey Tambor , and Jessica Walter . Ron Howard serves as an executive producer on the show , as well as its narrator . The main characters of Arrested Development are made up of the Bluth ( -LSB- ˈbluːθ -RSB- ) and Fünke ( -LSB- ˈfjuːŋkeɪ -RSB- ) families .", "title": "" }, { "docid": "PDR", "text": "Pdr or PDR may refer to : Democratic Republican Party ( Portugal ) ( Partido Democrático Republicano ) , a Portuguese political party ; Physicians ' Desk Reference Proliferative Diabetic Retinopathy Paul di Resta Preliminary Design Review , a step in the engineering design process Pulsed Dose Rate , a form of brachytherapy Paintless Dent Repair Peripheral Distributor Road ( Cardiff ) -- see A4232 road Peripheral Distributor Road ( Port Talbot ) -- see A4241 road Pharma Documentation Ring Magpul PDR ( Personal Defense Rifle ) Photodissociation regions Playa del Rey , Los Angeles , California Population and Development Review Portia de Rossi Purchase of development rights , otherwise known as Purchase of Agricultural Conservation Easement ( PACE ) -- see Conservation easement People 's Democratic Republic Pedestrian Dead Reckoning", "title": "" }, { "docid": "Dino_Rossi", "text": "Dino Rossi ( born October 15 , 1959 ) is a member of the Washington State Senate from the 45th district . He is an American commercial real estate executive , two-time Republican candidate for Governor of Washington , and former Republican candidate for United States Senate . His first run for the Governor 's mansion in the 2004 election became the closest gubernatorial race in U.S. history ; Rossi was certified as Governor-elect before losing a hand recount to Democrat Christine Gregoire . He ran for Governor of Washington again in 2008 , losing to Gregoire 47 % to 53 % . Rossi began his career in the commercial real estate industry and has continued to invest in and manage income properties . After the 2008 election , Rossi returned his full attention to real estate . During the spring of 2010 there was speculation that Rossi might enter the 2010 Senate race to challenge incumbent Patty Murray . Rossi entered the race on May 26 , 2010 . On August 17 , 2010 Rossi defeated his Republican primary challengers , but lost to incumbent Senator Patty Murray ( a Democrat ) in the November 2 general election 47 % to 52 % . Rossi was selected to fulfill a vacancy in the State Senate 's 5th district in 2012 after the resignation of Cheryl Pflug . He was again selected in 2016 to fulfill a vacancy in the 45th district after the death of Andy Hill .", "title": "" }, { "docid": "Washington_gubernatorial_election,_2008", "text": "The gubernatorial election in Washington , 2008 elected the Governor of Washington on November 4 , 2008 . With the emergence from the August 19 primary of Republican Dino Rossi and incumbent Democratic Governor Christine Gregoire , the 2008 election was a rematch between the candidates from the 2004 election . That election was the closest in Washington State history with each receiving 49 percent of the vote and Rossi winning the first two of three counts . In contrast to the recounts and months of legal challenges in their previous contest , Dino Rossi conceded defeat in the election to Gregoire on November 5 , earning 46 percent of the vote .", "title": "" }, { "docid": "Giovanni_Rossi_(disambiguation)", "text": "Giovanni Rossi was a Swiss road bicycle racer . Giovanni Rossi may also refer to : Giovanni `` Gio '' Rossi , fictional character on the ABC television series , Ugly Betty Giovanni Rossi ( anarchist ) , Italian anarchist , see Anarchism in Brazil Giovanni Battista de Rossi , Italian archaeologist Giovanni Bernardo De Rossi , Italian Hebraist", "title": "" }, { "docid": "Angelo_de_Rossi", "text": "Angelo de Rossi ( 1671 -- June 12 , 1715 ) was an Italian sculptor . Born in Genoa , he was apprenticed to Filippo Parodi in 1680 ; Parodi 's influence is clear in his first pre-1689 work , a Small Satyr in marble . Nearly unavoidably , he was also influenced by the work of Pierre Puget . He went to Rome in 1688 , remaining there until his death ; a 1692 relief of Three Men in the Fiery Furnace won first prize in all three sculpture classes at the Accademia di San Luca . In 1699 , Cardinal Pietro Ottoboni appointed de ' Rossi court sculptor in the Palazzo della Cancelleria , Rome , and put him in charge of making the Tomb of Pope Alexander VIII , Ottoboni 's granduncle , in St. Peter 's Basilica ( in parts finished after de ' Rossi 's death ) . Another important work is the apostle Saint James the Less in St. John Lateran , Rome ( 1705 -- 11 ) . The commemorative Bust of Arcangelo Corelli ( died 1713 ) in the Protomoteca Capitolina of the Palazzo del Senatore of the Campidoglio , Rome , is also attributed to de ' Rossi . De ' Rossi was said to be close friends with Pierre Le Gros . With a promising career ahead , Angelo de ' Rossi died prematurely in Rome .", "title": "" }, { "docid": "Rossi_Boots", "text": "Rossi Boots is an Australian work boot company . Rossi employs 90 staff in the Adelaide suburb of Hilton , making it Australia 's second largest work boots company . All Rossi boots are made in Australia in their Hilton factory . The company was started in 1910 when Arthur Edward Rossiter began making boots in a shed in Adelaide . The World Wars were good times for business , but it was a struggle during the Great Depression . Today the company uses computerized machines for cutting , sewing and attaching soles . Replacing workers with technology is the company 's way of avoiding the transfer of its jobs to other countries . Rossi makes 250,000 pairs of shoes per year . The CEO of Rossi , Dean Rossiter , is the grandson of Arthur Rossiter , and holds a PhD in physics . He was a finalist for the 2010 Ernst & Young Entrepreneur of the Year award .", "title": "" }, { "docid": "Domenico_de'_Rossi", "text": "Domenico de ' Rossi ( 1659 -- 1730 ) was an Italian sculptor and engraver . In 1709 Domenico inherited the printshop of Giovanni Giacomo de ' Rossi , by the church of Santa Maria della Pace , the largest and most long-lived publisher of the Roman baroque . Several generations of the de ' Rossi participated in the family publishing firm established in the 17th century , which continued to produce engravings for the use of designers .", "title": "" }, { "docid": "Bernardo_de_Rossi", "text": "'' For the Renaissance bishop , see Bernardo de ' Rossi Bernardo de Rossi ( 8 January 1687 -- 2 February 1775 ) was an Italian dominican theologian and historian .", "title": "" } ]
228208
The flat-backed mandolin is a style of the mandolin.
[ { "docid": "Mandolin", "text": "A mandolin ( mandolino -LSB- mandoˈliːno -RSB- ; literally `` small mandola '' ) is a musical instrument in the lute family and is usually plucked with a plectrum or `` pick '' . It commonly has four courses of doubled metal strings tuned in unison ( 8 strings ) , although five ( 10 strings ) and six ( 12 strings ) course versions also exist . The courses are normally tuned in a succession of perfect fifths . It is the soprano member of a family that includes the mandola , octave mandolin , mandocello and mandobass . There are many styles of mandolin , but three are common , the Neapolitan or round-backed mandolin , the carved-top mandolin and the flat-backed mandolin . The round-back has a deep bottom , constructed of strips of wood , glued together into a bowl . The carved-top or arch-top mandolin has a much shallower , arched back , and an arched top -- both carved out of wood . The flat-backed mandolin uses thin sheets of wood for the body , braced on the inside for strength in a similar manner to a guitar . Each style of instrument has its own sound quality and is associated with particular forms of music . Neapolitan mandolins feature prominently in European classical music and traditional music . Carved-top instruments are common in American folk music and bluegrass music . Flat-backed instruments are commonly used in Irish , British and Brazilian folk music . Some modern Brazilian instruments feature an extra fifth course tuned a fifth lower than the standard fourth course . Other mandolin varieties differ primarily in the number of strings and include four-string models ( tuned in fifths ) such as the Brescian and Cremonese , six-string types ( tuned in fourths ) such as the Milanese , Lombard and the Sicilian and 6 course instruments of 12 strings ( two strings per course ) such as the Genoese . There has also been a twelve-string ( three strings per course ) type and an instrument with sixteen-strings ( four strings per course ) . Much of mandolin development revolved around the soundboard ( the top ) . Pre-mandolin instruments were quiet instruments , strung with as many as six courses of gut strings , and were plucked with the fingers or with a quill . However , modern instruments are louder -- using four courses of metal strings , which exert more pressure than the gut strings . The modern soundboard is designed to withstand the pressure of metal strings that would break earlier instruments . The soundboard comes in many shapes -- but generally round or teardrop-shaped , sometimes with scrolls or other projections . There is usually one or more sound holes in the soundboard , either round , oval , or shaped like a calligraphic ( f-hole ) . A round or oval sound hole may be covered or bordered with decorative rosettes or purfling .", "title": "" } ]
[ { "docid": "Cylinder-back_mandolin", "text": "The cylinder-back is a style of mandolin manufactured by the Vega Company of Boston , MA between 1913 and roughly 1925 . The design patent ( US patent number D44838 ) for the instrument was issued on November 4 , 1913 to David L. Day , who was director and chief acoustical engineer for the stringed instrument division of the Vega Company . The unique design feature of the cylinder-back instruments ( originally referred to as mando-lutes by their manufacturer ) is a cylindrical bulge running longitudinally along the back plate , from the tailpiece to the neck heel . This bulge increases the internal volume of the instrument . The result has been described as a compromise between the earlier Neapolitan-style bowl-back mandolins and the more modern styles with relatively flat backs that were manufactured primarily in the United States around the time of the cylinder-back 's first appearance . In addition to the mandolin , the same bulged-back concept was applied to the Vega mandola , mandcello , and mando-bass as well as to a series of hybrid 10-string instruments than spanned the pitch range between adjacently-sized 8-string models . Category : Mandolin family instruments", "title": "" }, { "docid": "Resonator_mandolin", "text": "A resonator mandolin or `` resophonic mandolin '' is a mandolin whose sound is produced by one or more metal cones ( resonators ) instead of the customary wooden soundboard ( mandolin top/face ) . These instruments are sometimes referred to as `` Dobro mandolins , '' after pioneering instruments designed and produced by the Dopyera Brothers , which evolved into a brand name . The trademark `` Dobro '' is currently the property of the Gibson Guitar Corporation . When Gibson acquired the trademark in 1993 , they announced that they would defend their right to its exclusive use . The resonator mandolin was developed in parallel with the resonator guitar . The resonator guitar was originally designed to be louder than conventional acoustic guitars . A resonator mandolin is generally somewhat louder than a standard wooden mandolin , and has a different tone quality and distinctive appearance . Though resonator guitars are often played flat in the lap steel guitar style , resonator mandolins are almost exclusively played in the conventional manner .", "title": "" }, { "docid": "Valentine_Abt", "text": "Valentine Abt ( born Pittsburgh June 13 , 1873 -- died Mayview , Pennsylvania July 16 , 1942 ) was an American composer who specialized in the mandolin . In the book Popular American Composers , Frank L. Boyden named Abt one of America 's most `` prominent specialists of the mandolin '' , saying that he should be appreciated in Europe as well as America as `` one of the greatest artists of any instrument . '' Abt was a proponent of the duo-style of mandolin playing , in which one players plays back and forth between melody , counter-melody and harmony so quickly that it sounds as if two instruments are playing . Boyden credited Abt with founding a musical movement around the duo-style , as well as `` trio '' and `` quartet '' styles ( that sound like three and four different instruments at once ) . The golden age of the mandolin around the turn of the 20th-Century included other prominent mandolin players using the style , including Samuel Siegel , W. Eugene Page , and Seth Weeks .", "title": "" }, { "docid": "Bandolin_(Trinidad)", "text": "In Trinidad , the bandolin is a string instrument with a rounded back and four courses of steel strings . It is similar to the mandolin , except the Trinidadian mandolin has a flat back , and the two are generally though not totally considered to be separate instruments . It is also seen as distinct from the Trinidadian bandol . It is used in Trinidad 's parang music .", "title": "" }, { "docid": "Tiny_Moore", "text": "Billie `` Tiny '' Moore ( May 12 , 1920 -- December 15 , 1987 ) was a Western swing musician who played the electric mandolin and fiddle with Western swing legend Bob Wills and the Texas Playboys in the 1940s . Born in the Gulf Coast town of Port Arthur , Texas , in 1920 , his primary instrument was the electric mandolin . While a member of the Texas Playboys from 1946 to 1950 , he played Gibson electric mandolins : at first an EM-125 , and sometime after 1948 , an EM-150 . Although these are 8-string mandolins , Tiny used only 4 single strings instead of pairs . This gave his mandolin an electric guitarlike sound . Later , in 1952 , he commissioned one of the first American-built 5-string electric mandolins from Paul Bigsby . At the time Moore was playing in a band led by Bob Wills ' brother , Billy Jack . The Bigsby 5-string mandolin had single courses of strings ( rather than the paired courses on a standard mandolin ) and added a low C string to the standard G , D , A and E . This tuning actually gives the instrument a wider range of notes than a guitar . Western swing is a hybrid of country , blues , and jazz ; Tiny Moore 's style of playing draws upon all of these sources . Moore and his Bigsby mandolin were strongly identified with each other for the remainder of his career . The instrument is arguably the most famous electric mandolin in the history of American popular music . In the mid-1960s he taught group guitar lessons at the local YMCA in Sacramento , California . He taught every style of music from Old Timey folk to The Beatles . He also operated Tiny Moore Music , a music store in Sacramento , and sold copies of the Bigsby mandolin built by Jay Roberts of Yuba City . In the 1970s he was part of `` The Strangers '' , which was Merle Haggard 's band . During that decade he also made two recordings with David Grisman for Kaleidoscope Records : `` Tiny Moore Music '' and `` Back to Back , '' a duet album with Jethro Burns . In 1999 , Moore was posthumously inducted into the Rock and Roll Hall of Fame in the Early Influences category as a member of Bob Wills and His Texas Playboys .", "title": "" }, { "docid": "Evan_Marshall_(musician)", "text": "Evan Marshall is a virtuoso mandolinist , prominent as an arranger of classical music pieces for the mandolin and proponent of the duo style of playing . His name comes up in mandolin-oriented music circles as one of the best of modern mandolin players , one who has taken the techniques of early mandolin soloists to new levels . He is also a recording artist with Rounder Records and teaches mandolin . He has given classes for the Classical Mandolin Society of America , the Mandolin Symposium and the American Mandolin and Guitar Summer School , and has been associated with the Conservatory of Music at Biola University . As a performer , he has worked as a featured guest with several symphony orchestras , including the Houston Symphony , Phoenix Symphony , and Buffalo Philharmonic Orchestra . He is a former member of Billy Hill and the Hillbillies .", "title": "" }, { "docid": "Ginislao_Paris", "text": "Ginislao Paris ( 1852-after 1917 ) was an Italian composer and musician in Tsarist Russia who played trombone with the Russian Imperial Opera Orchestra in St. Petersburg . He also played mandolin , founding the first mandolin orchestra in Russia , The society of amateur Mandolinists and Guitarists in the 1880s . That orchestra was important because one of its members , Vassily Andreev , would be inspired to form the first orchestra based on Russian instruments . Paris invented specialized mandolin which was named for him ( the Sistema Ginislao Paris ) and built by the workshops of Luigi Embergher . The Paris Ginislao mandolins feature a double top ( a second hollow space within the instrument , created by a false back between the soundboard and the instrument 's back ) . The double top is a feature that mandolin makers are now experimenting with in the 21st century , to get better sound . Mandolinists such as Avi Avital and Joseph Brent use them , and they are custom instruments , today . In 1905 , Roman luthier Luigi Embergher made several mandolin family instruments based on Ginislao Paris ' own design , featuring double top and special bracing system . Only four instruments of `` Sistema Ginislao Paris '' forming the mandolin family quartet are known presently . One is an Embergher Artistico mandolin model No. 8 , held in the Theatre Museum of St Petersburg . Another is Liuto cantabile ( known as the Russian Embergher ) of model 5 bis , another mandolin No. 5 bis and mandola model 5 bis , held in private collections . The model No. 8 mandolin was a top-of-the-line instrument , very expensive , with the back of the instrument and the neck completely covered with mother-of-pearl , ivory and tortoise-shell inlay . Such instruments were not just for show , but expected to sound good too , another reason the double top is interesting .", "title": "" }, { "docid": "Bluegrass_mandolin", "text": "Bluegrass mandolin is a style of mandolin playing most commonly heard in bluegrass bands .", "title": "" }, { "docid": "Raffaele_Calace", "text": "Raffaele Calace ( 1863 -- 1934 ) was an Italian mandolin player , composer , and luthier . Calace was born in Naples , Italy , the son of Antonio Calace , a successful instrument maker . He initially trained to be a musician , discovered the mandolin , and soon became a virtuoso . After Calace graduated with high honors from the Regio Conservatorio di Musica in Naples , he set out to elevate the mandolin 's place in music . To achieve this , he toured Europe and Japan , giving concerts on the Neapolitan mandolin and liuto cantabile . The liuto cantabile is a bass variant of the mandolin family that scholars believe Neapolitan luthiers of the Vinaccia family created in the last decade of the 19th century , and that Raffaele Calace subsequently perfected . Raffaele Calace made three long-playing phonograph records on which he plays mandolin and liuto cantabile . Raffaele Calace wrote about 200 compositions for mandolin . These include concert works for mandolin solo and compositions for mandolin and other instruments -- duets with piano , trio combinations with mandola and guitar , the Romantic Mandolin Quartet ( two mandolins , mandola , and guitar ) , and quintets . Calace also wrote pedagogical works , including a mandolin method , Schule für Mandoline , and a method for playing the liuto cantabile . The mandolin method was published in 1910 and elaborates on the 18th-century Italian mandolin tutors by Giovanni Battista Gervasio ( c. 1725 -- c. 1785 ) , Gabriele Leone ( c. 1725 -- c. 1790 ) and others . It shows the development of the traditional Italian playing style . The Calace school forms a bridge between other modern methods for mandolin , such as those by Raffaele Calace 's countryman Silvio Ranieri ( 1882-1956 ) , a Roman virtuoso who settled in Brussels , and the American-based Italian mandolinist Giuseppe Pettine ( 1874-1966 ) . Raffaele Calace and his brother Nicola Calace ( 1859-1923 ) , also a musician , also became instrument makers in the Neapolitan mandolin family . They introduced improvements in building techniques and modernized the Neapolitan mandolin . Among other innovations , they enlarged its sound box and -- like the Roman luthier Luigi Embergher -- extended the fingerboard over the sound hole to increase the range . When Nicola Calace emigrated to the U.S.A. in 1898 , Raffaele continued the Calace workshop with his daughter Maria ( also a mandolin player ) , and his son Giuseppe Calace . Today the Calace atelier is run by Calace 's grandson Raffaele Jr. .", "title": "" }, { "docid": "Speranski", "text": "Speranski Australia is a brand of handcrafted mandolins . Known models are : Speranski Australia F-Style Mandolin ( SF , SFB , SPB and Custom models ) and Speranski Australia A-Style Mandolin ( no longer produced ) . Tilia ( also known as basswood or linden ) composite materials used for making top decks in SF models instead of spruce ply used by most other manufacturers . Solid carved spruce is used for top decks in SPB , SFB and Custom models . Speranski mandolins have rich sound that tends to get better over the years . Category : Musical instrument manufacturing companies", "title": "" }, { "docid": "Carmine_de_Laurentiis", "text": "Carmine de Laurentiis was a 19th-Century Italian mandolinist , musical educator , author and composer who taught mandolin and guitar in Naples . His only well-known student was Carlo Munier . He wrote a mandolin method , Metodo per Mandolino , that was published in Milan in 1874 , reported the following year in the Musical World . The article mentioning Laurentiis ' method talked about the decline of the mandolin , calling the mandolin `` entirely out of fashion . '' He is significant because his efforts helped to bring the mandolin back to international prominence after a period of international indifference , by teaching and promoting the instrument . His mandolin method was accessible not only for Italian speakers , but with the English addition compiled by Federico Sacchi , people in England as well .", "title": "" }, { "docid": "Fretworks_Mandolin_and_Guitar_Orchestra", "text": "The brainchild of the classical guitarist and banjo and lute performer Douglas Back , Fretworks Mandolin and Guitar Orchestra was the first public-school-affiliated mandolin youth ensemble in America .", "title": "" }, { "docid": "Giovanni_Gioviale", "text": "Giovanni Gioviale ( November 1885 -- June 11 , 1949 ) was an Italian composer and musician . He is considered one of the greatest mandolin virtuosos of all time . He also played guitar and banjo , and at the concert level with violin . He is special among the Italian mandolin masters , as one of the only ones to be recorded . He has also been credited for making famous the duo style of mandolin playing , in which one instrument sounds like several . Born Catania , Gioviale took up the mandolin when he was ten-years old . He was impressed by the music he heard at a barbershop . Craft halls were one of the types of place one could hear music in Catania then . He learned the mandolin first , then added banjo , guitar and violin , which he learned in school . He was an internationally travelling performer , performing in Spain , Africa , England , Austria and the United States . While in the United States , from 1926 to 1929 , he recorded more than 50 recordings . After three years in the U.S. , he missed his home and moved back to Italy . He was planning to return when he died in 1949 . He continued to perform in Italy , playing in Turin , Milan , Rome , Genoa , and Palmero . In addition to his own works , he performed works by Francesco Paolo Frontini , Cali , Vincenzo Bellini , Mozart , Edvard Grieg , Amilcare Ponchielli , Giuseppe Verdi , Felix Mendelssohn , and Pietro Mascagni .", "title": "" }, { "docid": "Samuel_Siegel", "text": "Samuel Siegel ( born 1875 , Des Moines , Iowa -- died January 14 , 1948 , Los Angeles , California ) was an American mandolin virtuoso and composer who played mandolin on 29 records for Victor Records , including 9 pieces of his own composition and two that he arranged . Siegel was the first mandolinist to record on Emile Berliner 's phonograph disk-records . He was labeled `` America 's Greatest Mandoline Virtuoso '' and `` The King of the Mandolin '' in the May 1900 Banjo World . Siegel performed both in vaudeville , as well as in concert halls . He had no formal training in music , but saw that the mandolin needed original music , rather than relying on the transcribed violin music . His compositions and arrangements were well known in his day . He was the author of Siegel 's Special Mandolin Studies , published by Jos. W Stern and Company , 1901 , in which he covered left hand Pizzicato and harmonic duo style .", "title": "" }, { "docid": "Bernardo_de_Pace", "text": "Bernardo de Pace ( San Ferdinando di Puglia , 1886 -- Brooklyn , 1966 ) was a musician and comedic vaudeville performer of the 1920s , billed as `` the Wizard of the Mandolin '' . De Pace won an international mandolin contest at the age of 11 , and as his grandson Bobby De Pace later put it , `` From 11 to 17 , he played for kings and queens . '' For many years , de Pace was mandolin soloist at the Metropolitan Opera in addition to his star turns on the vaudeville stage . His camp performance style is captured in a Warner Bros. . Vitaphone short from 1927 ( Bernado de Pace : The Wizard of the Mandolin ) which was released on DVD in 2007 as part of The Jazz Singer deluxe edition , and two MGM shorts from 1929 . He also released a series of recordings ranging from light classical pieces to original compositions in traditional Italian style .", "title": "" }, { "docid": "Sound_hole", "text": "A sound hole is an opening in the upper sound board of a stringed musical instrument . The sound holes can have different shapes : round in flat-top guitars and traditional bowl-back mandolins ; F-holes in instruments from the violin family , archtop mandolins and in archtop guitars ; C-holes in violas da gamba , and rosettes in lutes . Bowed lyras have D-holes and mandolins may have F-holes , round or oval holes . A round or oval hole is usually a single one , under the strings . F-holes and D-holes are usually made in pairs placed symmetrically on both sides of the strings . Most hollowbody and semi-hollow electric guitars also have F-holes . Though the purpose of sound holes is to help acoustic instruments project their sound more efficiently , the sound does not emanate solely ( nor even mostly ) from the location of the sound hole . The majority of sound emanates from the surface area of both sounding boards , with sound holes playing a part by allowing the sounding boards to vibrate more freely , and by allowing some of the vibrations which have been set in motion inside the instrument to travel outside the instrument . In 2015 researchers at MIT published an analysis charting the evolution and improvements in effectiveness of violin F-hole design over time .", "title": "" }, { "docid": "Salvator_Léonardi", "text": "Salvator Léonardi ( born Catania , Italy 1872 -- died 1938 ) was a mandolin virtuoso , teacher and composer . He taught in Egypt , Malta , London and Paris for more than 20 years , and also toured as a performer . Léonardi learned mandolin and guitar from an uncle , but went on to become a professional musician , studying the violin at a Naples conservatory . He won awards as a solo mandolinist at international music competitions in Florence and Rome . Léonardi was the author of the Méthode pour Banjoline ou Mandoline-Banjo ( Method for Banjolin and Mandolin-Banjo ) . The book was rare among texts teaching mandolin , because it taught his method in three languages at once , English , French and Spanish . In the third edition of his mandolin-banjo method ( 1921 ) , he stated in the introduction that the mandolin had been declining in popularity from previous times . In writing his book , he noted the instrument was soaring in popularity in the shape of the banjo . He did not just recycle old material for his book , but also included his own compositions , including Souvenir de Malta , Caminando ( a tango ) , Souvenir de Rome , Un Beso Por Teléfono , Qui-Pro-Quo , Rêverie , and Capriccio ( a polka ) . As a music teacher , Léonardi was unsure of whether to include jazz in his book , saying he thought it a faddish style of playing that might not be around very long . In spite of his speculation , he chose to include the section on how to play jazz , noting that he had played with American jazz bands after World War I. He is known for composing Souvenir de Catania , Souvenir de Napoli , Souvenir de Sicile , and Angeli e Demoni .", "title": "" }, { "docid": "Cittern", "text": "The cittern or cithren ( Fr . cistre , It . cetra , Ger . zitter , zither , Sp . cistro , cedra , cítola ) is a stringed instrument dating from the Renaissance . Modern scholars debate its exact history , but it is generally accepted that it is descended from the Medieval citole , or cytole . It looks much like the modern-day flat-back mandolin and the modern Irish bouzouki . Its flat-back design was simpler and cheaper to construct than the lute . It was also easier to play , smaller , less delicate and more portable . Played by all classes , the cittern was a premier instrument of casual music-making much as is the guitar today .", "title": "" }, { "docid": "Mandolin_orchestra", "text": "A mandolin orchestra is an orchestra consisting primarily of instruments from the mandolin family of instruments , such as the mandolin , mandola , mandocello and mandobass or mandolone . Some mandolin orchestras use guitars and double-basses instead of , or as well as , the lower mandolin-family instruments .", "title": "" }, { "docid": "Charley_Rappaport", "text": "Charley Rappaport ( born 1946 in Brooklyn , New York ) is an American musician ,5 co-founder of the Balalaika and Domra Society of America ,2 which coordinates Russian balalaika and domra orchestras across the United States .4 Rappaport is a mandolinist , and performs in several styles , both on recordings and live , with his band The Great American Gypsies . He received his `` musical education '' playing in Russian balalaika orchestras , Russian nightclubs ( The Two Guitars and The Russian Bear ) and in the New York Mandolin Orchestra under Sol Goichberg .5 He has appeared throughout the U.S. as a soloist and with The Great American Gypsies . He is currently music director of the Pittsburgh-based group 3 Rivers Mandolin Consort , and conducts the Pittsburgh Mandolin Orchestra .3 In 2003 he was the subject of a cover story in Mandolin Magazine , a national publication .5 In 2004 Rappaport was named a `` master folk musician '' by the state of Pennsylvania and awarded a grant to teach mandolin4 and domra .8 & 7 His recordings include Set 1 ( 1973 ) , Standing Room Only ( 1975 ) , Requests ( 1992 ) , Mandolin X 4 ( 1995 ) , and Before , I Had A Red Tomato ( 2004 ) .", "title": "" }, { "docid": "Joe_Carr_(Texas_musician)", "text": "__ NOTOC __ Joseph Allen `` Joe '' Carr ( June 22 , 1951 -- December 14 , 2014 ) was an American country and roots musician , author , and professor originally from Denton , Texas . Self-taught , he began playing first folk music and later old-time and bluegrass music on guitar at age 13 and mandolin at age 15 . After performing with local Texas bands Roanoke in the 1970s and Country Gazette in the 1970s and 80s , Carr formed a `` Bob Wills style '' Western swing band , Joe Carr & the Texas Lone Star Band , in 1987 . Beginning in 1984 , he taught at the commercial music program at South Plains College in Levelland , Texas , For the last several years of his life , he was in charge of the bluegrass and Western swing departments at the college and was the director of Camp Bluegrass held there annually Carr penned numerous instructional books and videos for mandolin , western swing guitar , flat-picking guitar , banjo , and ukulele as well as coauthor ( with former South Plains colleague Alan Munde ) of the 1996 Prairie Nights to Neon Lights : The Story of Country Music in West Texas . He also cowrote and performed a two-man musical comedy play called Two Swell Guys from Texas with Munde . He was also a frequent contributor to Flatpicking Guitar Magazine and Mandolin Magazine . Carr died from a stroke on December 14 , 2014 , in Levelland , Texas . He was 63 .", "title": "" }, { "docid": "Electric_mandolin", "text": "The electric mandolin is an instrument tuned and played as the mandolin and amplified in similar fashion to an electric guitar . As with electric guitars , electric mandolins take many forms : Most common is a carved-top eight-string instrument fitted with an electric pickup in similar fashion to many arch top guitars . Solid body mandolins are common in 4 - , 5 - , and 8-string forms . Acoustic electric and semi-acoustic mandolins also exist in many forms .", "title": "" }, { "docid": "Joseph_Brent", "text": "Joseph Frederick Brent ( born April 6 , 1976 ) is an American mandolinist , multi-instrumentalist , and teacher . He is known for his performances and arrangements of rock and indie songs , as well as his original compositions with the ensemble 9 Horses . He teaches classical mandolin at Mannes College . Brent attended the Berklee College of Music , and studied the mandolin under Carlo Aonzo in Savona , Italy . He also received instruction from Barry Mitterhoff and Adam Steffey . In addition to his teaching responsibilities , Brent is active as a sideman in several rock , jazz , bluegrass , and folk ensembles , most notably with Regina Spektor , Jewel , Kishi Bashi , Gary Smulyan , and various artists centered on the Brooklyn folk music scene . Brent also records and has performed with symphony orchestras such as the Seattle Symphony , San Francisco Symphony , Chicago Symphony , International Contemporary Ensemble , nunc , and the New World Symphony . In 2008 , Brent collaborated with Nova Scotia-based luthier Brian Dean to design a grand concert mandolin he named ` Pähkinä ' , which is Finnish for ` nut ' , a reference to the walnut top of the instrument . Among the instrument 's many distinctive features are the walnut/maple/spruce wood combination , a zero fret , a semi-lute construction with minimal bracing , a built-in tone guard with a sound pressure relief hole cut into the back , and ornate f-holes which reach around the sides of the instrument . Dean has since built a 10-string version of this model nicknamed ` Kumí ' , which is currently Brent 's primary acoustic instrument . In 2016 , Vermont-based luthier Adam Buchwald built him a 5-string , fanned fret electric mandolin . On October 16 , 2015 , Brent 's improvising ensemble 9 Horses , featuring violinist Sara Caswell and bassist Shawn Conley released their debut album Perfectest Herald on Sunnyside Records , and in 2016 were the winners of the 21CM LAUNCH : Emerging Artists Competition . Brent has published two books of mandolin pedagogy , Scales and Arpeggios for Mandolin and Orchestral and Chamber Excerpts for Mandolin , and his book of transcriptions of the lute music of John Dowland for two mandolins , conceived with Alon Sariel , was published in 2015 by paladino music .", "title": "" }, { "docid": "Jean_Pietrapertosa", "text": "Jean Pietrapertosa ( 1855 -- 1940 ) was a composer and virtuoso of the mandolin who performed in Paris in the 1880s . He taught the mandolin and wrote a two-volume mandolin method book , Méthode de mandolin , published in Paris in 1892 . He also organized a mandolin orchestra .", "title": "" }, { "docid": "Seth_Weeks", "text": "Silas Seth Weeks ( b. Vermont , Illinois , 8 Sept. 1868 -- d. Dec. 1953 ) was an American composer who played mandolin , violin , banjo and guitar . Although he played many instruments he concentrated professionally on the mandolin . He is considered to be the first African American to play mandolin during its golden period and was considered instrumental in bringing the mandolin to the prominent national standing that it had in the early 1900s . He was the first American known to write a mandolin concerto ( in 1900 ) and led a mandolin and guitar orchestra in Tacoma , Washington .", "title": "" }, { "docid": "Classical_Mandolin_Society_of_America", "text": "The Classical Mandolin Society of America Inc. , or CMSA , is a 501 ( C ) ( 3 ) not for profit corporation committed to promoting the playing and study of mandolin instruments in the United States . The organization was founded in 1986 by Norman Levine . The organization works to promote knowledge and interest in the mandolin family of fretted instruments ; ( mandolin , mandola , mandocello , mando-bass ) and guitar , with a focus on Classical Mandolin . It actively sponsors grants and scholarships for mandolin education and instruction for children and adults in North America . Currently , there are over 400 members worldwide . The CMSA holds a Convention in a different city in North America each year . Among other functions , the CMSA Convention hosts an En Masse Orchestra , which for its brief existence each year , is the largest mandolin orchestra in the United States , and has historically included as many as 180 musicians . The CMSA serves as a source of information about how to find or create mandolin ensembles around the United States , Canada and the world . The organization is staffed by unpaid volunteers and is structured with Officers of the corporation ( President , Vice President , Secretary and Treasurer ) , and a Board of Directors , which currently has nine members . The CMSA membership votes on candidates to fill Officer and Board Member positions in accordance with its bylaws . The CMSA publishes a quarterly newsletter , The Mandolin Journal , which contains legal notifications for the corporation and current organizational news , along with contributed articles and music . The organization also maintains an internet website that contains information on the organization and its activities , membership application forms and convention registration forms .", "title": "" }, { "docid": "Octave_mandolin", "text": "The octave mandolin is a fretted string instrument with four pairs of strings tuned in fifths , G , D , A , E ( low to high ) , an octave below a mandolin . It has a 20 to 23-inch scale length and its construction is similar to other instruments in the mandolin family . Usually the courses are all unison pairs but the lower two may sometimes be strung as octave pairs with the higher-pitched octave string on top so that it is hit before the thicker lower-pitched string . Alternate tunings of G , D , A , D and A , D , A , D are often employed by Celtic musicians . Octave mandolins are sometimes used in mandolin orchestras in place of mandolas . The mandolinists thus avoid learning to read music on the alto clef ; music for the octave mandolin is usually written on the more familiar treble clef , and plays an octave lower than the notes shown ( see octave clefs ) .", "title": "" }, { "docid": "Mandocello", "text": "The mandocello ( mandoloncello , Liuto cantabile , liuto moderno ) is a plucked string instrument of the mandolin family . It is larger than the mandolin , and is the baritone/bass instrument of the mandolin family . Its eight strings are in four paired courses , with the strings in each course tuned in unison . Overall tuning of the courses is in fifths like a mandolin , but beginning on bass C ( C2 ) . It can be described as being to the mandolin what the cello is to the violin .", "title": "" }, { "docid": "Pietro_Denis", "text": "Pietro Denis ( 1720 -- 1790 ) , also known as Pierre Denis , was a French mandolin virtuoso and teacher , and composer . He studied under Giuliano in Naples and established himself in Paris . He is best known for his compositions Sonata for Mandolin & Continuo No. 1 in D major and Sonata No. 3 for Mandolin . He also wrote a mandolin instruction method , Méthode pour apprendre à jouer de la mandoline sans Maître ( method to learn how to play mandolin without a teacher ) , published Paris in 1768 . He wrote another mandolin method , published in Paris in 1792 , and was the author also of Four collections of airs for the mandolin ; a New system of practical music , issued in Paris in 1747 . Denis also wrote a French translation of Tartinf 's Tratto delle appogiature si asceudenti che discendeiiti per il violino , under the title of Traite des agremens de la musique , compose par le celebre Giuzeppe Tartini a Padua , et traduit par le Sigr . P.Denis . This volume was published by M. de la Chevardier , Paris . In his final years , in 1780 , he was a music master in a ladies ' seminary in Saint Cyr .", "title": "" }, { "docid": "Mandolin_Wind", "text": "`` Mandolin Wind '' is a song written by Rod Stewart . It was first released on Stewart 's 1971 album Every Picture Tells a Story and later as the b-side of a single from that album , his cover of '' ( I Know ) I 'm Losing You . '' In 1972 , it was covered by The Everly Brothers on their album Stories We Could Tell , and in 1977 it was covered by Earl Scruggs on his album Strike Anywhere . The song has also appeared on numerous Rod Stewart compilation and live albums , including Sing It Again Rod , Storyteller -- The Complete Anthology : 1964 -- 1990 and Unplugged ... and Seated . It has also appeared on Everly Brothers and Earl Scruggs compilation albums . `` Mandolin Wind '' has been heavily praised by music critics . In his review of Every Picture Tells a Story in Rolling Stone , John Mendelsohn refers to the song as being `` nearly as good '' as the # 1 single off the album , `` Maggie May . '' Rock : The Rough Guide went further , calling the song the highlight of the album . Stewart Mason of Allmusic called the song `` every bit ... equal '' to `` Maggie May , '' and Allmusic 's Stephen Thomas Erlewine called the song `` unbearably poignant . '' In its review of Every Picture Tells a Story , Billboard called `` Mandolin Wind '' an `` excellent Stewart composition , '' and in its review of Stories We Could Tell the magazine noted that the song offered `` great single potential . '' Rod Stewart biographers Tim Ewbank & Stafford Hildred refer to the song as `` a stunning ballad . '' The song combines elements of rock music and folk music . The lyrics tell of the singer 's love for his woman after she stayed with him through a particularly brutal winter on the American frontier . The song uses mostly acoustic instruments , with a particularly prominent mandolin part . Stewart has stated that he `` always thought the mandolin was such a romantic-sounding instrument . '' Although the tempo remains slow to medium throughout , Stewart Mason describes the song as `` a masterpiece of dynamics . '' The song rocks harder during the fadeout than during the rest of the song . Mason finds the song 's `` simple , sweet declaration of love and fidelity '' more believable than Stewart 's later love songs . Stewart has stated that his `` goal in life is to play ` Mandolin Wind ' and make it sound like the record . '' The identity of the mandolin player on `` Mandolin Wind '' is unclear . The liner notes state that `` the mandolin was played by the mandolin player in Lindisfarne '' but that Rod Stewart had forgotten his name . In 2003 , Ray Jackson claimed to be the mandolin player on the album , at least for the song `` Maggie May . '' Ray Jackson is the talented mandolin player from English folk-rock band Lindisfarne . Mason attributes the mandolin playing to Martin Quittenton . The liner notes to Every Picture Tells a Story list Quittenton only as the acoustic guitar player .", "title": "" } ]
8598
Why did my number of shares of stock decrease?
[ { "docid": "581848", "text": "During a stock split the only thing that changes is the number of shares outstanding. Typically a stock splits to lower its price per share. Sometimes if a company's value is falling it will do a reverse split where X shares will be exchanged for Y shares. This is typically done to avoid being de-listed from an exchange if the price per share falls below a certain threshold, usually $1. Again the only thing changing is the number of shares outstanding. A 20 for 1 reverse split means for every 20 shares outstanding the shareholder will be granted one new share. Example X Co. has 1,000,000 shares outstanding for a price of $100 per share. It does a 1 for 10 split. Now there are 10,000,000 shares outstanding for a price of $10 per share. Example Y Co has 1,000,000 shares outstanding for a price of $1 per share. It does a 10 for 1 reverse split. Now there are 100,000 shares outstanding for a price of $10. Quickly looking at the news for ASTI it looks like it underwent a 20 for 1 reverse split. You should probably look at your statements and ask your broker how the arithmetic worked in your case. Investopedia links for Reverse Stock Split and Stock Split", "title": "" } ]
[ { "docid": "301547", "text": "\"To my knowledge, there's no universal equation, so this could vary by individual/company. The equation I use (outside of sentiment measurement) is the below - which carries its own risks: This equations assumes two key points: Anything over 1.2 is considered oversold if those two conditions apply. The reason for the bear market is that that's the time stocks generally go on \"\"sale\"\" and if a company has a solid balance sheet, even in a downturn, while their profit may decrease some, a value over 1.2 could indicate the company is oversold. An example of this is Warren Buffett's investment in Wells Fargo in 2009 (around March) when WFC hit approximately 7-9 a share. Although the banking world was experiencing a crisis, Buffett saw that WFC still had a solid balance sheet, even with a decrease in profit. The missing logic with many investors was a decrease in profits - if you look at the per capita income figures, Americans lost some income, but not near enough to justify the stock falling 50%+ from its high when evaluating its business and balance sheet. The market quickly caught this too - within two months, WFC was almost at $30 a share. As an interesting side note on this, WFC now pays $1.20 dividend a year. A person who bought it at $7 a share is receiving a yield of 17%+ on their $7 a share investment. Still, this equation is not without its risks. A company may have a solid balance sheet, but end up borrowing more money while losing a ton of profit, which the investor finds out about ad-hoc (seen this happen several times). Suddenly, what \"\"appeared\"\" to be a good sale, turns into a person buying a penny with a dollar. This is why, to my knowledge, no universal equation applies, as if one did exist, every hedge fund, mutual fund, etc would be using it. One final note: with robotraders becoming more common, I'm not sure we'll see this type of opportunity again. 2009 offered some great deals, but a robotrader could easily be built with the above equation (or a similar one), meaning that as soon as we had that type of environment, all stocks fitting that scenario would be bought, pushing up their PEs. Some companies might be willing to take an \"\"all risk\"\" if they assess that this equation works for more than n% of companies (especially if that n% returns an m% that outweighs the loss). The only advantage that a small investor might have is that these large companies with robotraders are over-leveraged in bad investments and with a decline, they can't make the good investments until its too late. Remember, the equation ultimately assumes a person/company has free cash to use it (this was also a problem for many large investment firms in 2009 - they were over-leveraged in bad debt).\"", "title": "" }, { "docid": "591694", "text": "\"The correct answer to this question is: the person who the short sells the stock to. Here's why this is the case. Say we have A, who owns the stock and lends it to B, who then sells it short to C. After this the price drops and B buys the stock back from D and returns it to A. The outcome for A is neutral. Typically stock that is sold short must be held in a margin account; the broker can borrow the shares from A, collect interest from B, and A has no idea this is going on, because the shares are held in a street name (the brokerage's name) and not A. If A decides during this period to sell, the transaction will occur immediately, and the brokerage must shuffle things around so the shares can be delivered. If this is going to be difficult then the cost for borrowing shares becomes very high. The outcome for B is obviously a profit: they sold high first and bought (back) low afterwards. This leaves either C or D as having lost this money. Why isn't it D? One way of looking at this is that the profit to B comes from the difference in the price from selling to C and buying from D. D is sitting on the low end, and thus is not paying out the profit. D bought low, compared to C and this did not lose any money, so C is the only remaining choice. Another way of looking at it is that C actually \"\"lost\"\" all the money when purchasing the stock. After all, all the money went directly from C to B. In return, C got some stock with the hope that in the future C could sell it for more than was paid for it. But C literally gave the money to B, so how could anybody else \"\"pay\"\" the loss? Another way of looking at it is that C buys a stock which then decreases in value. C is thus now sitting on a loss. The fact that it is currently only a paper loss makes this less obvious; if the stock were to recover to the price C bought at, one might conclude that C did not lose the money to B. However, in this same scenario, D also makes money that C could have made had C bought at D's price, proving that C really did lose the money to B. The final way of seeing that the answer is C is to consider what happens when somebody sells a stock which they already hold but the price goes up; who did they lose out on the gain to? The person again is; who bought their stock. The person would buys the stock is always the person who the gain goes to when the price appreciates, or the loss comes out of if the price falls.\"", "title": "" }, { "docid": "156358", "text": "Pre-Enron many companies forced the 401K match to be in company shares. That is no longer allowed becasue of changes in the law. Therefore most employees have only a small minority of their retirement savings in company shares. I know the ESOP and 401K aren't the same, but in my company every year the number of participants in the company stock purchase program decreases. The small number of participants and the small portion of their new retirement funds being in company shares would mean this spike in volume would be very small. The ESOP plan for my employer takes money each paycheck, then purchases the shares once a quarter. This delay would allow them to manage the purchases better. I know with a previous employer most ESOP participants only held the shares for the minimum time, thus providing a steady steam of shares being sold.", "title": "" }, { "docid": "583203", "text": "You did something that you shouldn't have done; you bought a dividend. Most mutual fund companies have educational materials on their sites that recommend against making new investments in mutual funds in the last two months of the year because most mutual funds distribute their earnings (dividends, capital gains etc) to their shareholders in December, and the share price of the funds goes down in the amount of the per share distribution. These distributions can be taken in cash or can be re-invested in the fund; you most likely chose the latter option (it is often the default choice if you ignored all this because you are a newbie). For those who choose to reinvest, the number of shares in the mutual fund increases, but since the price of the shares has decreased, the net amount remains the same. You own more shares at a lower price than the day before when the price was higher but the total value of your account is the same (ignoring normal market fluctuations in the price of the actual stocks held by the fund. Regardless of whether you take the distributions as cash or re-invest in the fund, that money is taxable income to you (unless the fund is owned inside a 401k or IRA or other tax-deferred investment program). You bought 56 shares at a price of $17.857 per share (net cost $1000). The fund distributed its earnings shortly thereafter and gave you 71.333-56= 15.333 additional shares. The new share price is $14.11. So, the total value of your investment is $1012, but the amount that you have invested in the account is the original $1000 plus the amount of the distribution which is (roughly) $14.11 x 15.333 = $216. Your total investment of $1216 is now worth $1012 only, and so you have actually lost money. Besides, you owe income tax on that $216 dividend that you received. Do you see why the mutual fund companies recommend against making new investments late in the year? If you had waited till after the mutual fund had made its distribution, you could have bought $1000/14.11 = 70.871 shares and wouldn't have owed tax on that distribution that you just bought by making the investment just before the distribution was made. See also my answer to this recent question about investing in mutual funds.", "title": "" }, { "docid": "5846", "text": "\"I think JB King's answer is interesting from the point of view of \"\"is this good for me\"\" but the OP's question boils down to \"\"why would a company do this?\"\" The company buys back shares when it thinks it will better position the company financially. A Simple Scenario: If Company A wants to open a new store, for example, they need to buy the land, build the store, stock it, etc, etc and this all costs money. The company can get a loan, use accrued capital, or raise new capital by issuing new stock. Each method has benefits and drawbacks. One of the drawbacks of issuing new stock is that it dilutes the existing stock's value. Previously, total company profits were split between x shares. Now the profits are shared between x+y shares, where y is the number of new shares issued to raise the capital. This normally drives the price of the stock down, since the expected future dividends per stock have decreased. Now the company has a problem: the next time they go to raise money by issuing stock, they will have to issue MORE shares to get the same value - leading to more dilution. To break out of this cycle, the company can buy back shares periodically. When the company feels the the stock is sufficiently undervalued, it buys some back. Now the profits are shared with a smaller pool, and the stock price goes up, and the next time Company A needs to raise capital, it can issue stock. So it probably has little to do with rewarding shareholders, and more to do with lowering the \"\"cost of capital\"\" for the company in the future.\"", "title": "" }, { "docid": "135031", "text": "Dollar cost averaging can be done in a retirement plan, and can be done for individual stock purchases, as this will increase your returns by reducing your risk, especially if you are buying a particular stock for the first time. How many time have I purchased a stock, bottom fishing, thinking I was buying at the low, only to find out there was a new low. Sitting with a thousand shares that are now down $3-$4K. I have a choice to sell at a loss, hold what I've got or double down. I usually add more shares if I'm thinking I'll recover, but at that time I'd wished I'd eased into my investment. That way I would have owned more shares at a smaller cost basis. Anything can happen in the market, not knowing whether the price will increase or decrease. In the example above a $3,000 loss is equal to the brokerage cost of about 300 trades, so trading cost should not be a factor. Now I'm not saying to slowly get into the market and miss the bull, like we're having today with Trump, but get into individual stocks slowly, being fully invested in the market. Also DCA means you do not buy equal number of shares per period, say monthly, but that you buy with the same amount of money a different number of shares, reducing your total costs. Let's say you spend $2000 on a stock trading at $10 (200 shares), if the stock rose to $20 you would spend $2000 and buy 100 shares, and if the stock dropped to $5 you would spend $2000 and buy 400 shares, by now having amassed 700 shares for $6,000. On the other hand and in contrast to DCA had you purchased 200 shares for $2000 at $10/share, then 200 shares for $4000 at $20/share, and finally 200 more shares for $1000 at $5/share, you would have amassed only 600 shares for $7000 investment.", "title": "" }, { "docid": "283168", "text": "There are a few reason why share prices increase or decrease, the foremost is expectation of the investors that the company/economy will do well/not well, that is expectation of profit/intrinsic value growth over some time frame (1-4 qtrs.)there is also demand & supply mismatch over (usually) short time. If you really see, the actual 'value' of a company is it's net-worth (cash+asset+stock in trade+brand value+other intangibles+other incomes)/no of shares outstanding, which (in a way) is the book value, then all shares should trade at their book value, the actual number but it does not, the expectation of investors that a share would be purchased by another investor at a higher price because the outlook of the company over a long time is good.", "title": "" }, { "docid": "445039", "text": "\"Why are there so many stock exchanges in the world? The simple answer is that there is a lot of money to be made by charging fees to facilitate the trading of securities, but there are other factors at play here relating to new technologies. Trading volumes have increased rapidly in recent years. According to this ITG data, in 1997, 6.5 billion shares were traded on US exchanges. By 2015 this number had increased to 40.8 billion shares. There are a number of reasons for this rapid increase in volumes. Most significant would be the introduction of new technologies that allow for high volume, high frequency trading. This increase in activity has be accompanied by an increase in the number of stock exchanges. As CQM points out in his answer, there has been considerable consolidation in the ownership of \"\"legacy\"\" exchanges. For example, the NYSE merged with EuroNext in 2007, and the combined group is now owned by the Intercontinental Exchange, which also owns numerous smaller stock exchanges as well as a number of derivative/commodities exchanges. However, this consolidation in ownership has been more than matched by the creation of many \"\"virtual\"\" exchanges. In North America these virtual exchanges are called \"\"Alternative Trading Systems\"\". In Europe, they are called \"\"Multilateral Trading Facilities\"\". These new virtual exchanges, sometimes referred to as \"\"dark pools\"\", have begun to significantly eat away at the volumes of the legacy exchanges. If you look at the ITG data (linked above), you will see that the total volume of shares traded on legacy exchanges actually peaked in 2008, and has since then has decreased. This coincides roughly with the appearance of the virtual exchanges and the new high frequency trading methods. According to this paper from the SEC site, dated 2013, Alternative Trading Systems accounted for 11.3% of total volumes in 2012. This will have increased rapidly in the years since 2012. It is this loss of business that has prompted the consolidation in the ownership of the legacy exchanges. These new exchange are \"\"conceptually the same\"\" as the legacy exchanges and must play by the same regulatory rules.\"", "title": "" }, { "docid": "152097", "text": "How can they reduce the number of shares I hold? They may have purchased them. You don't say what stock it is, so we can only speculate. Let's say that the stock is called PENNY. So they may have taken your 1600 PENNY shares and renamed them to 1600 PENNYOLD shares. Then they created a new $5 PENNY share and gave you .2357 shares of that in exchange for your 1600 PENNYOLD shares. This suggests that your old shares were worth $1.1785 or less than a tenth of a cent each. As an example, MYLAN did this in 2015 as part of their tax inversion (moved official headquarters from the US to Europe). They did not change the number of shares at that time, but MYLAN is not a penny stock. This is the kind of thing that might happen in a bankruptcy. A reverse split (where they give you one share in exchange for more than one share) is also possible, although you received an odd amount for a reverse split. Usually those produce rounder numbers. A number like .2357 sounds more like a market price, as those can be bizarre.", "title": "" }, { "docid": "587558", "text": "Also a layman, and I didnt read the article because it did the whole 'screw you for blocking my ads' thing. But judging from the title, I'd guess someone bought a massive amount of call options for VIX, the stock that tracks volatility in the market. Whenever the market crashes or goes through difficult times, the VIX fund prospers. The 'by october' part makes me think it was call options that he purchased: basically he paid a premium for each share (a fraction of the shares cost) for the right to buy that share at today's price, from now until october. So if the share increases in value, for each call option he has, he can buy one share at todays price, and sell it at the price it is that day. Options can catapult your profit into the next dimension but if the share decreases in value or even stays the same price, he loses everything. Vicious redditors, please correct the mistakes ive made here with utmost discrimination", "title": "" }, { "docid": "64961", "text": "It's great that you have gotten the itch to learn about the stock market. There are a couple of fundamentals to understand first though. Company A has strong, growing, net earnings and minimal debt, it's trading for $100 per share. Company B has good revenue but high costs of goods and total liabilities well in excess of total assets, it's trading for $0.10 per share. There is no benefit to getting 10,000 shares or 10 shares for your $1,000. Your goal is to invest in companies that have valuable products and services run by competent management teams. Sure, the number of shares you own will dictate what percentage of the company you own, and in a number of cases, your voting power. But even a penny stock will have a market capitalization of several million dollars so voting power isn't really a concern for your $1,000 investment. There is a lot more in the three basic financial statements (Income Statement, Balance Sheet, Statement of Cash Flows) than revenue. Seasoned accountants can have a hard time parsing out where money is coming from and where it's going. In general there are obvious red flags, like a fast declining cash balance against a fast growing liabilities balance or expenses exceeding revenue. While some of these things are common among new and high growth companies, it's not the place for a new investor with a small bankroll. A micro-cap company (penny stocks are in this group) will receive rounds of financing via issuing preferred convertible shares which may include options on more shares. For a company worth $20mm a $5mm financing round can materially change the finances of a company, and will likely dilute your holdings in common stock. Small growth companies need new financing frequently to fund their growth strategies. Revenue went up, great... why? Did you open another store? Did you open another sales office? Did the revenue increase this quarter based on substantially the same operation that existed last quarter or have you increased the capacity of your operation? If you increased the capacity of your operation what was the cost of the increase and did revenue increase as expected? Can you expect revenue to continue to grow at this rate or was it a one time windfall from an unusual order? Sure, there are spectacular gains to be had in penny stocks. XYZ Pharma Research (or whatever) goes from $0.05 to $0.60 and you've turned your $1,000 in to $12,000. This is a really unlikely event... Buying penny stocks is akin to buying lottery tickets. Unless you are a high ranking employee at the company capable of making decisions, or one of the investors buying the preferred shares mentioned in point 3, or are one of the insiders of a pump and dump scam on the stock, penny common stocks are not a place to invest. One could argue that even a company insider should probably avoid buying common stock. Just to illustrate the points above, you mention: Doing some really heavy research into this stock has made me question the whole penny stock market. Based on your research what is the enterprise value of the company? What were the gross proceeds of the last financing round, how many shares were issued and were there any warrants attached? What do you perceive to be heavy research? What background do you have in finance/accounting to give weight to your ability to perform such research? Crawl. Walk. Then run. Don't kid yourself in to thinking that since you have some level of education you understand the contracts involved in enterprise finance.", "title": "" }, { "docid": "64943", "text": "This seemed very unrealistic, I mean who would do that? But to my immense surprise the market price increased to 5.50$ in the following week! Why is that? This is strange. It seems that people mistakenly [?] believe that the company should be at 5.5 and currently available cheap. This looks like irrational behaviour. Most of the past 6 months the said stock in range bound to 4.5 to 5. The last time it hit around 5.5 was Feb. So this is definitely strange. If the company had set a price of 6.00$ in the rights offering, would the price have increased to 6$? Obviously the company thinks that their shares are worth that much but why did the market suddenly agree? Possibly yes, possible no. It can be answered. More often the rights issue are priced at slight discount to market price. Why did this happen? Obviously management thinks that the company is worth that much, but why did the market simply believe this statement without any additional information? I don't see any other information; if the new shares had some special privileges [in terms of voting rights, dividends, etc] then yes. However the announcements says the rights issues is for common shares.", "title": "" }, { "docid": "306782", "text": "\"As I understand it, a company raises money by sharing parts of it (\"\"ownership\"\") to people who buy stocks from it. It's not \"\"ownership\"\" in quotes, it's ownership in a non-ironic way. You own part of the company. If the company has 100 million shares outstanding you own 1/100,000,000th of it per share, it's small but you're an owner. In most cases you also get to vote on company issues as a shareholder. (though non-voting shares are becoming a thing). After the initial share offer, you're not buying your shares from the company, you're buying your shares from an owner of the company. The company doesn't control the price of the shares or the shares themselves. I get that some stocks pay dividends, and that as these change the price of the stock may change accordingly. The company pays a dividend, not the stock. The company is distributing earnings to it's owners your proportion of the earnings are equal to your proportion of ownership. If you own a single share in the company referenced above you would get $1 in the case of a $100,000,000 dividend (1/100,000,000th of the dividend for your 1/100,000,000th ownership stake). I don't get why the price otherwise goes up or down (why demand changes) with earnings, and speculation on earnings. Companies are generally valued based on what they will be worth in the future. What do the prospects look like for this industry? A company that only makes typewriters probably became less valuable as computers became more prolific. Was a new law just passed that would hurt our ability to operate? Did a new competitor enter the industry to force us to change prices in order to stay competitive? If we have to charge less for our product, it stands to reason our earnings in the future will be similarly reduced. So what if the company's making more money now than it did when I bought the share? Presumably the company would then be more valuable. None of that is filtered my way as a \"\"part owner\"\". Yes it is, as a dividend; or in the case of a company not paying a dividend you're rewarded by an appreciating value. Why should the value of the shares change? A multitude of reasons generally revolving around the company's ability to profit in the future.\"", "title": "" }, { "docid": "336018", "text": "\"Learn something new every day... I found this interesting and thought I'd throw my 2c in. Good description (I hope) from Short Selling: What is Short Selling First, let's describe what short selling means when you purchase shares of stock. In purchasing stocks, you buy a piece of ownership in the company. You buy/sell stock to gain/sell ownership of a company. When an investor goes long on an investment, it means that he or she has bought a stock believing its price will rise in the future. Conversely, when an investor goes short, he or she is anticipating a decrease in share price. Short selling is the selling of a stock that the seller doesn't own. More specifically, a short sale is the sale of a security that isn't owned by the seller, but that is promised to be delivered. Still with us? Here's the skinny: when you short sell a stock, your broker will lend it to you. The stock will come from the brokerage's own inventory, from another one of the firm's customers, or from another brokerage firm. The shares are sold and the proceeds are credited to your account. Sooner or later, you must \"\"close\"\" the short by buying back the same number of shares (called covering) and returning them to your broker. If the price drops, you can buy back the stock at the lower price and make a profit on the difference. If the price of the stock rises, you have to buy it back at the higher price, and you lose money. So what happened? The Plan The Reality Lesson I never understood what \"\"Shorting a stock\"\" meant until today. Seems a bit risky for my blood, but I would assume this is an extreme example of what can go wrong. This guy literally chose the wrong time to short a stock that was, in all visible aspects, on the decline. How often does a Large Company or Individual buy stock on the decline... and send that stock soaring? How often does a stock go up 100% in 24 hours? 600%? Another example is recently when Oprah bought 10% of Weight Watchers and caused the stock to soar %105 in 24 hours. You would have rued the day you shorted that stock - on that particular day - if you believed enough to \"\"gamble\"\" on it going down in price.\"", "title": "" }, { "docid": "273947", "text": "\"Exactly what accounts are affected by any given transaction is not a fixed thing. Just for example, in a simple accounting system you might have one account for \"\"stock on hand\"\". In a more complex system you might have this broken out into many accounts for different types of stock, stock in different locations, etc. So I can only suggest example specific accounts. But account type -- asset, liability, capital (or \"\"equity\"\"), income, expense -- should be universal. Debit and credit rules should be universal. 1: Sold product on account: You say it cost you $500 to produce. You don't say the selling price, but let's say it's, oh, $700. Credit (decrease) Asset \"\"Stock on hand\"\" by $500. Debit (increase) Asset \"\"Accounts receivable\"\" by $700. Credit (increase) Income \"\"Sales\"\" by $700. Debit (increase) Expense \"\"Cost of goods sold\"\" by $500. 2: $1000 spent on wedding party by friend I'm not sure how your friend's expenses affect your accounts. Are you asking how he would record this expense? Did you pay it for him? Are you expecting him to pay you back? Did he pay with cash, check, a credit card, bought on credit? I just don't know what's happening here. But just for example, if you're asking how your friend would record this in his own records, and if he paid by check: Credit (decrease) Asset \"\"checking account\"\" by $1000. Debit (increase) Expense \"\"wedding expenses\"\" by $1000. If he paid with a credit card: Credit (increase) Liability \"\"credit card\"\" by $1000. Debit (increase) Expense \"\"wedding expenses\"\" by $1000. When he pays off the credit card: Debit (decrease) Liability \"\"credit card\"\" by $1000. Credit (decrease) Asset \"\"cash\"\" by $1000. (Or more realistically, there are other expenses on the credit card and the amount would be higher.) 3: Issue $3000 in stock to partner company I'm a little shakier on this, I haven't worked with the stock side of accounting. But here's my best stab: Well, did you get anything in return? Like did they pay you for the stock? I wouldn't think you would just give someone stock as a present. If they paid you cash for the stock: Debit (increase) Asset \"\"cash\"\". Credit (decrease) Capital \"\"shareholder equity\"\". Anyone else want to chime in on that one, I'm a little shaky there. Here, let me give you the general rules. My boss years ago described it to me this way: You only need to know three things to understand double-entry accounting: 1: There are five types of accounts: Assets: anything you have that has value, like cash, buildings, equipment, and merchandise. Includes things you may not actually have in your hands but that are rightly yours, like money people owe you but haven't yet paid. Liabilities: Anything you owe to someone else. Debts, merchandise paid for but not yet delivered, and taxes due. Capital (some call it \"\"capital\"\", others call it \"\"equity\"\"): The difference between Assets and Liabilities. The owners investment in the company, retained earnings, etc. Income: Money coming in, the biggest being sales. Expenses: Money going out, like salaries to employees, cost of purchasing merchandise for resale, rent, electric bill, taxes, etc. Okay, that's a big \"\"one thing\"\". 2: Every transaction must update two or more accounts. Each update is either a \"\"debit\"\" or a \"\"credit\"\". The total of the debits must equal the total of the credits. 3: A dollar bill in your pocket is a debit. With a little thought (okay, sometimes a lot of thought) you can figure out everything else from there.\"", "title": "" }, { "docid": "194359", "text": "I don't know what restrictions are put on the average employee at your company. In my case, we were told we were not permitted to either short the stock, or to trade in it options. That said, I was successful shorting the exact number of shares I'd be buying at the 6 month close, the same day the purchase price would be set. I then requested transfer of the stock purchase to my broker where the long and short netted to zero. The return isn't 15%, it's 100/85 or 17.6% for an average 3 months they have your money. So do the math on APR. (Higher if the stock has risen over 6 months and you get the lower price from 6 months prior.) My method was riskless, as far as I am concerned. I did this a dozen times. The stock itself was +/- 4% by the time the shares hit, so in the end it was an effort, mostly to sleep better. I agree with posts suggesting the non-zero risk of a 20% 4 day drop.", "title": "" }, { "docid": "110856", "text": "No, they do not. Stock funds and bonds funds collect income dividends in different ways. Stock funds collect dividends (as well as any capital gains that are realized) from the underlying stocks and incorporates these into the funds’ net asset value, or daily share price. That’s why a stock fund’s share price drops when the fund makes a distribution – the distribution comes out of the fund’s total net assets. With bond funds, the internal accounting is different: Dividends accrue daily, and are then paid out to shareholders every month or quarter. Bond funds collect the income from the underlying bonds and keep it in a separate internal “bucket.” A bond fund calculates a daily accrual rate for the shares outstanding, and shareholders only earn income for the days they actually hold the fund. For example, if you buy a bond fund two days before the fund’s month-end distribution, you would only receive two days’ worth of income that month. On the other hand, if you sell a fund part-way through the month, you will still receive a partial distribution at the end of the month, pro-rated for the days you actually held the fund. Source Also via bogleheads: Most Vanguard bond funds accrue interest to the share holders daily. Here is a typical statement from a prospectus: Each Fund distributes to shareholders virtually all of its net income (interest less expenses) as well as any net capital gains realized from the sale of its holdings. The Fund’s income dividends accrue daily and are distributed monthly. The term accrue used in this sense means that the income dividends are credited to your account each day, just like interest in a savings account that accrues daily. Since the money set aside for your dividends is both an asset of the fund and a liability, it does not affect the calculated net asset value. When the fund distributes the income dividends at the end of the month, the net asset value does not change as both the assets and liabilities decrease by exactly the same amount. [Note that if you sell all of your bond fund shares in the middle of the month, you will receive as proceeds the value of your shares (calculated as number of shares times net asset value) plus a separate distribution of the accrued income dividends.]", "title": "" }, { "docid": "474296", "text": "\"Spend your first 50 euros on research materials. Warren Buffett got started as a boy by reading every book in the Library of Congress on investing and stock market analysis. You can research the company filings for Canadian companies at http://www.sedar.com, U.S companies at http://www.edgar.com, and European companies at https://www.gov.uk/government/organisations/companies-house. Find conflicting arguments and strategies and decide for yourself which ones are right. The Motley Fool http://www.fool.ca offers articles on good stocks to add to your portfolio and why, as well as why not. They provide a balanced judgement instead of just hype. They also sell advice through their newsletter. In Canada the Globe & Mail runs a daily column on screening stocks. Every day they present a different stock-picking strategy and the filters used to reach their end list. They then show how much that portfolio would have increased or decreased as well as talking about some of the good & bad points of the stocks in the list. It's interesting to see over time a very few stocks show up on multiple lists for different strategies. These ones in my opinion are the stocks to be investing in. While the Globe's stock picks focus on Canadian and US exchanges, you might find the strategies worthwhile. You can subscribe to the digital version at http://www.theglobeandmail.com Once you have your analytical tools ready, pick any bank or stock house that offers a free practice account. Use that account and their screening tools to try out your strategies and see if you can make money picking stocks. My personal stock-picking strategy is to look for companies with: - a long uninterrupted history of paying dividends, - that are regularly increased, - and do not exceed the net profit per share of the company - and whose share price has a long history of increasing These are called unicorn companies, because there are so very few of them. Another great read is, \"\"Do Stocks Outperform Treasury Bills?\"\" by Hendrik Bessembinder. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=2900447 In this paper the author looks at the entire history of the U.S. stock universe and finds that less than 4% of stocks are responsible for 100% of the wealth creation in the U.S. stock market. He discusses his strategies for picking the winners, but it also suggests that if you don't want to do any research, you could pick pretty much any stock at random, short it, and wait. I avoid mutual funds because they are a winner only for the fellas selling them. A great description on why the mutual fund industry is skewed against the investor can be found in a book called \"\"The RRSP Secret\"\" by Greg Habstritt. \"\"Unshakeable\"\" by Tony Robbins also discusses why mutual funds are not the best way to invest in stocks. The investor puts up 100% of the money, takes 100% of the risk, and gets at best 30% of the return. Rich people don't invest like that.\"", "title": "" }, { "docid": "566205", "text": "\"I'm not a financial expert, but saying that paying a $1 dividend will reduce the value of the stock by $1 sounds like awfully simple-minded reasoning to me. It appears to be based on the assumption that the price of a stock is equal to the value of the assets of a company divided by the total number of shares. But that simply isn't true. You don't even need to do any in-depth analysis to prove it. Just look at share prices over a few days. You should easily be able to find stocks whose price varied wildly. If, say, a company becomes the target of a federal investigation, the share price will plummet the day the announcement is made. Did the company's assets really disappear that day? No. What's happened is that the company's long term prospects are now in doubt. Or a company announces a promising new product. The share price shoots up. They may not have sold a single unit of the new product yet, they haven't made a dollar. But their future prospects now look improved. Many factors go into determining a stock price. Sure, total assets is a factor. But more important is anticipated future earning. I think a very simple case could be made that if a stock never paid any dividends, and if everyone knew it would never pay any dividends, that stock is worthless. The stock will never produce any profit to the owner. So why should you be willing to pay anything for it? One could say, The value could go up and you could sell at a profit. But on what basis would the value go up? Why would investors be willing to pay larger and larger amounts of money for an asset that produces zero income? Update I think I understand the source of the confusion now, so let me add to my answer. Suppose that a company's stock is selling for, say, $10. And to simplify the discussion let's suppose that there is absolutely nothing affecting the value of that stock except an expected dividend. The company plans to pay a dividend on a specific date of $1 per share. This dividend is announced well in advance. Everyone knows that it will be paid, and everyone is extremely confidant that in fact the company really will pay it -- they won't run out of money or any such. Then in a pure market, we would expect that as the date of that dividend approaches, the price of the stock would rise until the day before the dividend is paid, it is $11. Then the day after the dividend is paid the price would fall back to $10. Why? Because the person who owns the stock on the \"\"dividend day\"\" will get that $1. So if you bought the stock the day before the dividend, the next day you would immediately receive $1. If without the dividend the stock is worth $10, then the day before the dividend the stock is worth $11 because you know that the next day you will get a $1 \"\"refund\"\". If you buy the stock the day after the dividend is paid, you will not get the $1 -- it will go to the person who had the stock yesterday -- so the value of the stock falls back to the \"\"normal\"\" $10. So if you look at the value of a stock immediately after a dividend is paid, yes, it will be less than it was the day before by an amount equal to the dividend. (Plus or minus all the other things that affect the value of a stock, which in many cases would totally mask this effect.) But this does not mean that the dividend is worthless. Just the opposite. The reason the stock price fell was precisely because the dividend has value. BUT IT ONLY HAS VALUE TO THE PERSON WHO GETS IT. It does me no good that YOU get a $1 dividend. I want ME to get the money. So if I buy the stock after the dividend was paid, I missed my chance. So sure, in the very short term, a stock loses value after paying a dividend. But this does not mean that dividends in general reduce the value of a stock. Just the opposite. The price fell because it had gone up in anticipation of the dividend and is now returning to the \"\"normal\"\" level. Without the dividend, the price would never have gone up in the first place. Imagine you had a company with negligible assets. For example, an accounting firm that rents office space so it doesn't own a building, its only tangible assets are some office supplies and the like. So if the company liquidates, it would be worth pretty much zero. Everybody knows that if liquidated, the company would be worth zero. Further suppose that everyone somehow knows that this company will never, ever again pay a dividend. (Maybe federal regulators are shutting the company down because it's products were declared unacceptably hazardous, or the company was built around one genius who just died, etc.) What is the stock worth? Zero. It is an investment that you KNOW has a zero return. Why would anyone be willing to pay anything for it? It's no answer to say that you might buy the stock in the hope that the price of the stock will go up and you can sell at a profit even with no dividends. Why would anyone else pay anything for this stock? Well, unless their stock certificates are pretty and people like to collect them or something like that. Otherwise you're supposing that people would knowingly buy into a pyramid scheme. (Of course in real life there are usually uncertainties. If a company is dying, some people may believe, rightly or wrongly, that there is still hope of reviving it. Etc.) Don't confuse the value of the assets of a company with the value of its stock. They are related, of course -- all else being equal, a company with a billion dollars in assets will have a higher market capitalization than a company with ten dollars in assets. But you can't calculate the price of a company's stock by adding up the value of all its assets, subtracting liabilities, and dividing by the number of shares. That's just not how it works. Long term, the value of any stock is not the value of the assets but the net present value of the total future expected dividends. Subject to all sorts of complexities in real life.\"", "title": "" }, { "docid": "535555", "text": "\"The Wells Fargo scandal was and still is a big deal because Wells Fargo opened over 1.5 million unauthorized bank and credit card accounts. The credit card accounts were opened without authorization, which means people's credit scores and reports were pulled without permission. That is considered fraud and identity theft. Other than the legal side of it, by opening more bank accounts without authorization, it was showing \"\"synthetic growth\"\", which resulted in an inflated number when quarterly and annual performance numbers were reported. This caused people to invest more in Wells Fargo stock, not knowing that the growth in stock was not organic. After the scandal was uncovered, stocks decreased. However, the root cause of this can be traced to the culture at Wells Fargo, where customer service reps (i.e. bank tellers, and store operations employees) were faced with the challenges of meeting quotas that could be considered a stretch. As a result, faced with pressure from upper management, they opened unauthorized accounts. In addition, these unauthorized accounts cost consumers money either because credit cards had balances, or bank accounts did not meet a minimum balance. It is not about ending \"\"up with 8 rows in their database instead of just 1 row\"\" as OP wrote. It is about stealing consumer money and committing fraud and stealing the consumer's identity. *Suggestions and constructive criticism are welcomed in improving my answer.\"", "title": "" }, { "docid": "247258", "text": "You're interpreting things correctly, at least at a high level. Those numbers come from the 10Q filing and investor summary from Microsoft, but are provided to NASDAQ by Zacks Investment Research, as noted on the main page you linked to. That's a big investment data firm. I'm not sure why they reported non-GAAP Microsoft numbers and not, say, AAPL numbers; it's possible they felt the non-GAAP numbers reflect things better (or have in the past) for some material reason, or it's possible they made a typo, though the last three quarters at least all used non-GAAP numbers for MSFT. MSFT indicates that the difference in GAAP and non-GAAP revenue is primarily deferred revenue (from Windows and Halo). I did confirm that the SEC filing for MSFT does include the GAAP number, not the non-GAAP number (as you'd expect). I will also note that it looks like the 10Q is not the only source of information. Look at ORCL for example: they had in the March 2016 report (period ending 2/29/16) revenues of .50/share GAAP / .64/share non-GAAP. But the NASDAQ page indicates .59/share for that quarter. My suspicion is that the investment data firm (Zack's) does additional work and includes certain numbers they feel belong in the revenue stream but are not in the GAAP numbers. Perhaps MS (and Oracle) have more of those - such as deferred software revenues (AAPL has relatively little of that, as most of their profit is hardware).", "title": "" }, { "docid": "499877", "text": "\"The reason for selling a stock \"\"short\"\", is for when you believe the stock value will decrease in the near future. Here is an example: Today Exxon-Mobile stock is selling for $100 / share. You are expecting the price to decrease, so you want to short the stock, which means your broker (i.e. eTrade, etc) allows you to borrow shares without paying money, and those shares are transferred into your account, and then you sell them and receive money for the sale. But you didn't actually own those shares, you only borrowed them, so you need to return the shares to your broker sometime in the future. Let's say you borrow 10 shares @ $100, and you sell them at the market price of $100, you receive $1,000 in your account. But you owe your broker 10 shares, which you need to return sometime in the future. A few days later, the share price has decreased to $80. Now you can buy 10 shares from the market at a total cost of $800. You get 10 shares, and return those shares to your broker. Since you originally took in $1,000, and you just paid out $800, you keep a resulting profit of $200\"", "title": "" }, { "docid": "217006", "text": "Am I correct in understanding that a Scrip Dividend involves the issue of new shares instead of the purchase of existing shares? Yes. Instead of paying a cash dividend to shareholders, the company grants existing shareholders new shares at a previously determined price. This allows shareholders who join the program to obtain new shares without incurring transaction costs that would normally occur if they purchased these shares in the market. Does this mean that if I don't join this program, my existing shares will be diluted every time a Scrip Dividend is paid? Yes, because the number of shares has increased, so the relative percentage of shares in the company you hold will decrease if you opt-out of the program. The price of the existing shares will adjust so that the value of the company is essentially unchanged (similar to a stock split), but the number of outstanding shares has increased, so the relative weight of your shares declines if you opt out of the program. What is the benefit to the company of issuing Scrip Dividends? Companies may do this to conserve their cash reserves. Also, by issuing a scrip dividend, corporations could avoid the Advanced Corporation Tax (ACT) that they would normally pre-pay on their distributions. Since the abolition of the ACT in 1999, preserving cash reserves is the primary reason for a company to issue scrip dividends, as far as I know. Whether or not scrip dividends are actually a beneficial strategy for a company is debatable (this looks like a neat study, even though I've only skimmed it). The issue may be beneficial to you, however, because you might receive a tax benefit. You can sell the scrip dividend in the market; the capital gain from this sale may fall below the annual tax-free allowance for capital gains, in which case you don't pay any capital gains tax on that amount. For a cash dividend, however, there isn't a minimum taxable amount, so you would owe dividend tax on the entire dividend (and may therefore pay more taxes on a cash dividend).", "title": "" }, { "docid": "234935", "text": "I guess the opposite of being hedged is being unhedged. Typically, a hedge is an additional position that you would take on in order to mitigate the potential for losses on another position. I'll give an example: Say that I purchase 100 shares of stock XYZ at $10 per share because I believe its price will increase in the future. At that point, my full investment of $1000 is at risk, so the position is not hedged. If the price of XYZ decreases to $8, then I've lost $200. If the price of XYZ increases to $12, then I've gained $200; the profit/loss curve has a linear relationship to the future stock price. Suppose that I decide to hedge my XYZ position by purchasing a put option. I purchase a single option contract (corresponding to my 100 shares) with a strike price of $10 and an expiration date in January 2013 for a price of $0.50/share. This means that until the contract expires, I can always sell my XYZ shares for a minimum of $10. Therefore, if the price of XYZ decreases to $8, then I've only lost $50 (the price of the option contract), compared to the $200 that I would have lost if the position was unhedged. Likewise, however, if the price increases to $12, then I've only gained a net total of $150 due to the money I spent on the hedge. (the details of how much money you would actually lose in the hedged scenario are simplified out above; even out-of-the-money options retain some value before expiration, but pricing of options is outside of the scope of this post) So, as a more pointed answer to your question, I would say that the hedged/unhedged status of a position can be characterized by its potential for loss. If you don't have any other assets that will increase in value to offset losses on your position of interest, I would call it unhedged.", "title": "" }, { "docid": "404222", "text": "\"Short answer: google finance's market cap calculation is nonstandard (a.k.a. wrong). The standard way of computing the market capitalization of a firm is to take the price of its common stock and multiply by the number of outstanding common stock shares. If you do this using the numbers from google's site you get around $13.4B. This can be verified by going to other sites like yahoo finance and bloomberg, which have the correct market capitalization already computed. The Whole Foods acquisition appears to be very cut-and-dry. Investors will be compensated with $42 cash per share. Why are google finance's numbers wrong for market cap? Sometimes people will add other things to \"\"market capitalization,\"\" like the value of the firm's debt and other debt-like securities. My guess is that google has done something like this. Whole Foods has just over $3B in total liabilities, which is around the size of the discrepancy you have found.\"", "title": "" }, { "docid": "416006", "text": "Greetings r/finance!! I have a question regarding EBIT and the company that I work for. The steel company I work for reported they made a profit of $1.3 billion profit. Here's the link with some more numbers: http://www.nwitimes.com/business/local/arcelormittal-turns-billion-profit-in-second-quarter/article_606a0989-066f-5140-864d-2b04e5f4f294.html Now I am a union worker and like everyone else in my union, we get a profit sharing check based on the company's profit and with the labor agreement we have with them we get a 7.5% cut of it. So my question for you guys why did we recieve this piece of paper today? https://imgur.com/gallery/pSIG3 Why is there still a $33 million dollar loss that we don't get any profit sharing?? Any and all answers or information is appreciated. Thank you for your time in advance!", "title": "" }, { "docid": "249320", "text": "While there are many very good and detailed answers to this question, there is one key term from finance that none of them used and that is Net Present Value. While this is a term generally associate with debt and assets, it also can be applied to the valuation models of a company's share price. The price of the share of a stock in a company represents the Net Present Value of all future cash flows of that company divided by the total number of shares outstanding. This is also the reason behind why the payment of dividends will cause the share price valuation to be less than its valuation if the company did not pay a dividend. That/those future outflows are factored into the NPV calculation, actually performed or implied, and results in a current valuation that is less than it would have been had that capital been retained. Unlike with a fixed income security, or even a variable rate debenture, it is difficult to predict what the future cashflows of a company will be, and how investors chose to value things as intangible as brand recognition, market penetration, and executive competence are often far more subjective that using 10 year libor rates to plug into a present value calculation for a floating rate bond of similar tenor. Opinion enters into the calculus and this is why you end up having a greater degree of price variance than you see in the fixed income markets. You have had situations where companies such as Amazon.com, Google, and Facebook had highly valued shares before they they ever posted a profit. That is because the analysis of the value of their intellectual properties or business models would, overtime provide a future value that was equivalent to their stock price at that time.", "title": "" }, { "docid": "245834", "text": "In short, thanks to the answers and comments posted so far. No actual money is magically disappeared when the stock price goes down but the value is lost. The value changes of a stock is similar to the value changes of a house. The following is the long answer I came up with based on the previous answers and comments alone with my own understandings. Any experts who find any of the following is 200% out of place and wrong, feel free to edit it or make comments. Everything below only applies if the following are true: The stock price is only decreasing since the IPO because the company has been spending the money but not making profits after the IPO. The devaluation of the stock is not the result of any bad news related to the company but a direct translation of the money the company has lost by spending on whatever the company is doing. The actual money don’t just disappear into the thin air when the stock price goes down. All the money involved in trading this stock has already distributed to the sellers of this stock before the price went down. There is no actual money that is literally disappeared, it was shifted from one hand to another, but again this already happened before the price went down. For example, I bought some stocks for $100, then the price went down to $80. The $100 has already shifted from my hand to the seller before the price went down. I got the stock with less value, but the actual money $100 did not just go down to $80, it’s in the hand of the seller who sold the stock to me. Now if I sell the stock to the same seller who sold the stock to me, then I lost $20, where did the $20 go? it went to the seller who sold the stock to me and then bought it back at a lower price. The seller ended up with the same amount of the stocks and the $20 from me. Did the seller made $20? Yes, but did the seller’s total assets increased? No, it’s still $100, $80 from the stocks, and $20 in cash. Did anyone made an extra $20? No. Although I did lost $20, but the total cash involved is still there, I have the $80 , the seller who sold the stock to me and then bought it back has the $20. The total cash value is still $100. Directly, I did lost $20 to the guy who sold me the stock when the stock has higher value and then bought it back at a lower price. But that guy did not increased his total assets by $20. The value of the stock is decreased, the total money $100 did not disappear, it ended up from one person holding it to 2 people holding it. I lost $20 and nobody gained $20, how is that possible? Assume the company of the stock never made any profit since it’s IPO, the company just keeps spending the money, to really track down where the $20 I lost is going, it is the company has indirectly spent that money. So who got that $20 I lost? It could be the company spent $20 for a birthday cake, the $20 went to the cake maker. The company never did anything to make that $20 back, so that $20 is lost. Again, assume the stock price only goes down after its IPO, then buying this stock is similar to the buying a sport car example from JoeTaxpayer (in one of the answers), and buying an apple example from BrenBarn(in one of the comments from JoeTaxpayer’s answer). Go back to the question, does the money disappears into the thin air when the value of the stock goes down? No, the money did not disappear, it switched hands. It went from the buyer of the stock to the company, and the company has spent that money. Then what happens when the stock price goes down because bad news about the company? I believe the actual money still did not just disappear. If the bad news turn out to be true that the company had indeed lost this much money, the money did not disappear, it’s been spent/lost by the company. If the bad news turn out to be false, the stock price will eventually go up again, the money is still in the hand of the company. As a summary, the money itself did not disappear no matter what happens, it just went from one wallet to another wallet in many different ways through the things people created that has a value.", "title": "" }, { "docid": "314300", "text": "If you have been putting savings away for the longer term and have some extra funds which you would like to take some extra risk on - then I say work yourself out a strategy/plan, get yourself educated and go for it. If it is individual shares you are interested then work out if you prefer to use fundamental analysis, technical analysis or some of both. You can use fundamental analysis to help determine which shares to buy, and then use technical analysis to help determine when to get into and out of a position. You say you are prepared to lose $10,000 in order to try to get higher returns. I don't know what percentage this $10,000 is of the capital you intend to use in this kind of investments/trading, but lets assume it is 10% - so your total starting capital would be $100,000. The idea now would be to learn about money management, position sizing and risk management. There are plenty of good books on these subjects. If you set a maximum loss for each position you open of 1% of your capital - i.e $1,000, then you would have to get 10 straight losses in a row to get to your 10% total loss. You do this by setting stop losses on your positions. I'll use an example to explain: Say you are looking at a stock priced at $20 and you get a signal to buy it at that price. You now need to determine a stop price which if the stock goes down to, you can say well I may have been wrong on this occasion, the stock price has gone against me so I need to get out now (I put automatic stop loss conditional orders with my broker). You may determine the stop price based on previous support levels, using a percentage of your buy price or another indicator or method. I tend to use the percentage of buy price - lets say you use 10% - so your stop price would be at $18 (10% below your buy price of $20). So now you can work out your position size (the number of shares to buy). Your maximum loss on the position is $2 per share or 10% of your position in this stock, but it should also be only 1% of your total capital - being 1% of $100,000 = $1,000. You simply divide $1,000 by $2 to get 500 shares to buy. You then do this with the rest of your positions - with a $100,000 starting capital using a 1% maximum loss per position and a stop loss of 10% you will end up with a maximum of 10 positions. If you use a larger maximum loss per position your position sizes would increase and you would have less positions to open (I would not go higher than 2% maximum loss per position). If you use a larger stop loss percentage then your position sizes would decrease and you would have more positions to open. The larger the stop loss the longer you will potentially be in a position and the smaller the stop loss generally the less time you will be in a position. Also as your total capital increases so will your 1% of total capital, just as it would decrease if your total capital decreases. Using this method you can aim for higher risk/ higher return investments and reduce and manage your risk to a desired level. One other thing to consider, don't let tax determine when you sell an investment. If you are keeping a stock just so you will pay less tax if kept for over 12 months - then you are in real danger of increasing your risk considerably. I would rather pay 50% tax on a 30% return than 25% tax on a 15% return.", "title": "" }, { "docid": "121595", "text": "In less than two decades, more than half of all publicly traded companies have disappeared. There were 7,355 U.S. stocks in November 1997, according to the Center for Research in Security Prices at the University of Chicago’s Booth School of Business. Nowadays, there are fewer than 3,600. A close look at the data helps explain why stock pickers have been underperforming. And the shrinking number of companies should make all investors more skeptical about the market-beating claims of recently trendy strategies. Back in November 1997, there were more than 2,500 small stocks and nearly 4,000 tiny “microcap” stocks, according to CRSP. At the end of 2016, fewer than 1,200 small and just under 1,900 microcap stocks were left. Most of those companies melted away between 2000 and 2012, but the numbers so far show no signs of recovering. Several factors explain the shrinking number of stocks, analysts say, including the regulatory red tape that discourages smaller companies from going and staying public; the flood of venture-capital funding that enables young companies to stay private longer; and the rise of private-equity funds, whose buyouts take shares off the public market. For stock pickers, differentiating among the remaining choices is “an even harder game” than it was when the market consisted of twice as many companies, says Michael Mauboussin, an investment strategist at Credit Suisse in New York who wrote a report this spring titled “The Incredible Shrinking Universe of Stocks.” That’s because the surviving companies tend to be “fewer, bigger, older, more profitable and easier to analyze,” he says — making stock picking much more competitive. Consider small-stock funds. Often, they compare themselves to the Russell 2000, an index of the U.S. stocks ranked 1,001 through 3,000 by total market value. “Twenty years ago, there were over 4,000 stocks smaller” than the inclusion cutoff for the Russell 2000, says Lubos Pastor, a finance professor at the University of Chicago. “That number is down to less than 1,000 today.” So fund managers have far fewer stocks to choose from if they venture outside the index — the very area where the best bargains might be found. More money chasing fewer stocks could lead some fund managers to buy indiscriminately, regardless of value. Eric Cinnamond is a veteran portfolio manager with a solid record of investing in small stocks. Last year, he took the drastic step of shutting down his roughly $400 million mutual fund, Aston/River Road Independent Value, and giving his investors their money back. “Prices got so crazy in small caps, I fired myself,” he says. “My portfolio was 90% in cash at the end, because I couldn’t find anything to buy. If I’d kept investing, I was sure I’d lose people their money.” He adds, “It was the hardest thing I’ve ever done professionally, but I didn’t feel I had a choice. I knew my companies were overvalued.” Mr. Cinnamond hopes to return to the market when, in his view, values become attractive again. He doesn’t expect recent conditions to be permanent. The evaporation of thousands of companies may have one enduring result, however — and it could catch many investors by surprise. Most research on historical returns, points out Mr. Mauboussin, is based on the days when the stock market had twice as many companies as it does today. “Was the population of companies so different then,” he asks, “that the inferences we draw from it might no longer be valid?” So-called factor investing, also known as systematic or smart-beta investing, picks hundreds or thousands of stocks at a time based on common sources of risk and return. Among them: how big companies are, how much their shares fluctuate, how expensive their shares are relative to asset value and so on. But the historical outperformance of many such factors may have been driven largely by the tiniest companies — exactly those that have disappeared from the market in droves. Before concluding that small stocks or cheap “value” stocks will outrace the market as impressively as they did in the past, you should pause to consider how they will perform without the tailwinds from thousands of tiny stocks that no longer exist. The stock market has more than tripled in the past eight years, so the eclipse of so many companies hasn’t been a catastrophe. But it does imply that investing in some of the market’s trendiest strategies might be less profitable in the future than they looked in the past.", "title": "" } ]
866
Nuclear transfer from adult human fibroblasts to human oocytes can give rise to blastocysts containing expandable pluripotent cells.
[ { "docid": "37822406", "text": "Derivation of patient-specific human pluripotent stem cells via somatic cell nuclear transfer (SCNT) has the potential for applications in a range of therapeutic contexts. However, successful SCNT with human cells has proved challenging to achieve, and thus far has only been reported with fetal or infant somatic cells. In this study, we describe the application of a recently developed methodology for the generation of human ESCs via SCNT using dermal fibroblasts from 35- and 75-year-old males. Our study therefore demonstrates the applicability of SCNT for adult human cells and supports further investigation of SCNT as a strategy for regenerative medicine.", "title": "Human somatic cell nuclear transfer using adult cells." } ]
[ { "docid": "4457834", "text": "The transfer of somatic cell nuclei into oocytes can give rise to pluripotent stem cells that are consistently equivalent to embryonic stem cells, holding promise for autologous cell replacement therapy. Although methods to induce pluripotent stem cells from somatic cells by transcription factors are widely used in basic research, numerous differences between induced pluripotent stem cells and embryonic stem cells have been reported, potentially affecting their clinical use. Because of the therapeutic potential of diploid embryonic stem-cell lines derived from adult cells of diseased human subjects, we have systematically investigated the parameters affecting efficiency of blastocyst development and stem-cell derivation. Here we show that improvements to the oocyte activation protocol, including the use of both kinase and translation inhibitors, and cell culture in the presence of histone deacetylase inhibitors, promote development to the blastocyst stage. Developmental efficiency varied between oocyte donors, and was inversely related to the number of days of hormonal stimulation required for oocyte maturation, whereas the daily dose of gonadotropin or the total number of metaphase II oocytes retrieved did not affect developmental outcome. Because the use of concentrated Sendai virus for cell fusion induced an increase in intracellular calcium concentration, causing premature oocyte activation, we used diluted Sendai virus in calcium-free medium. Using this modified nuclear transfer protocol, we derived diploid pluripotent stem-cell lines from somatic cells of a newborn and, for the first time, an adult, a female with type 1 diabetes.", "title": "Human oocytes reprogram adult somatic nuclei of a type 1 diabetic to diploid pluripotent stem cells" }, { "docid": "15803282", "text": "The extremely low efficiency of human embryonic stem cell (hESC) derivation using somatic cell nuclear transfer (SCNT) limits its potential application. Blastocyst formation from human SCNT embryos occurs at a low rate and with only some oocyte donors. We previously showed in mice that reduction of histone H3 lysine 9 trimethylation (H3K9me3) through ectopic expression of the H3K9me3 demethylase Kdm4d greatly improves SCNT embryo development. Here we show that overexpression of a related H3K9me3 demethylase KDM4A improves human SCNT, and that, as in mice, H3K9me3 in the human somatic cell genome is an SCNT reprogramming barrier. Overexpression of KDM4A significantly improves the blastocyst formation rate in human SCNT embryos by facilitating transcriptional reprogramming, allowing efficient derivation of SCNT-derived ESCs using adult Age-related Macular Degeneration (AMD) patient somatic nuclei donors. This conserved mechanistic insight has potential applications for improving SCNT in a variety of contexts, including regenerative medicine.", "title": "Histone Demethylase Expression Enhances Human Somatic Cell Nuclear Transfer Efficiency and Promotes Derivation of Pluripotent Stem Cells." }, { "docid": "4410181", "text": "Mitochondria have a major role in energy production via oxidative phosphorylation, which is dependent on the expression of critical genes encoded by mitochondrial (mt)DNA. Mutations in mtDNA can cause fatal or severely debilitating disorders with limited treatment options. Clinical manifestations vary based on mutation type and heteroplasmy (that is, the relative levels of mutant and wild-type mtDNA within each cell). Here we generated genetically corrected pluripotent stem cells (PSCs) from patients with mtDNA disease. Multiple induced pluripotent stem (iPS) cell lines were derived from patients with common heteroplasmic mutations including 3243A>G, causing mitochondrial encephalomyopathy and stroke-like episodes (MELAS), and 8993T>G and 13513G>A, implicated in Leigh syndrome. Isogenic MELAS and Leigh syndrome iPS cell lines were generated containing exclusively wild-type or mutant mtDNA through spontaneous segregation of heteroplasmic mtDNA in proliferating fibroblasts. Furthermore, somatic cell nuclear transfer (SCNT) enabled replacement of mutant mtDNA from homoplasmic 8993T>G fibroblasts to generate corrected Leigh-NT1 PSCs. Although Leigh-NT1 PSCs contained donor oocyte wild-type mtDNA (human haplotype D4a) that differed from Leigh syndrome patient haplotype (F1a) at a total of 47 nucleotide sites, Leigh-NT1 cells displayed transcriptomic profiles similar to those in embryo-derived PSCs carrying wild-type mtDNA, indicative of normal nuclear-to-mitochondrial interactions. Moreover, genetically rescued patient PSCs displayed normal metabolic function compared to impaired oxygen consumption and ATP production observed in mutant cells. We conclude that both reprogramming approaches offer complementary strategies for derivation of PSCs containing exclusively wild-type mtDNA, through spontaneous segregation of heteroplasmic mtDNA in individual iPS cell lines or mitochondrial replacement by SCNT in homoplasmic mtDNA-based disease.", "title": "Metabolic rescue in pluripotent cells from patients with mtDNA disease" }, { "docid": "14192687", "text": "The long-term goal of nuclear transfer or alternative reprogramming approaches is to create patient-specific donor cells for transplantation therapy, avoiding immunorejection, a major complication in current transplantation medicine. It was recently shown that the four transcription factors Oct4, Sox2, Klf4, and c-Myc induce pluripotency in mouse fibroblasts. However, the therapeutic potential of induced pluripotent stem (iPS) cells for neural cell replacement strategies remained unexplored. Here, we show that iPS cells can be efficiently differentiated into neural precursor cells, giving rise to neuronal and glial cell types in culture. Upon transplantation into the fetal mouse brain, the cells migrate into various brain regions and differentiate into glia and neurons, including glutamatergic, GABAergic, and catecholaminergic subtypes. Electrophysiological recordings and morphological analysis demonstrated that the grafted neurons had mature neuronal activity and were functionally integrated in the host brain. Furthermore, iPS cells were induced to differentiate into dopamine neurons of midbrain character and were able to improve behavior in a rat model of Parkinson's disease upon transplantation into the adult brain. We minimized the risk of tumor formation from the grafted cells by separating contaminating pluripotent cells and committed neural cells using fluorescence-activated cell sorting. Our results demonstrate the therapeutic potential of directly reprogrammed fibroblasts for neuronal cell replacement in the animal model.", "title": "Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease." }, { "docid": "3360421", "text": "We describe the derivation of pluripotent embryonic stem (ES) cells from human blastocysts. Two diploid ES cell lines have been cultivated in vitro for extended periods while maintaining expression of markers characteristic of pluripotent primate cells. Human ES cells express the transcription factor Oct-4, essential for development of pluripotential cells in the mouse. When grafted into SCID mice, both lines give rise to teratomas containing derivatives of all three embryonic germ layers. Both cell lines differentiate in vitro into extraembryonic and somatic cell lineages. Neural progenitor cells may be isolated from differentiating ES cell cultures and induced to form mature neurons. Embryonic stem cells provide a model to study early human embryology, an investigational tool for discovery of novel growth factors and medicines, and a potential source of cells for use in transplantation therapy.", "title": "Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro" }, { "docid": "10546779", "text": "Somatic cell nuclear transfer (SCNT) technology has recently been used to generate animals with a common genetic composition. In this study, we report the derivation of a pluripotent embryonic stem (ES) cell line (SCNT-hES-1) from a cloned human blastocyst. The SCNT-hES-1 cells displayed typical ES cell morphology and cell surface markers and were capable of differentiating into embryoid bodies in vitro and of forming teratomas in vivo containing cell derivatives from all three embryonic germ layers in severe combined immunodeficient mice. After continuous proliferation for more than 70 passages, SCNT-hES-1 cells maintained normal karyotypes and were genetically identical to the somatic nuclear donor cells. Although we cannot completely exclude the possibility that the cells had a parthenogenetic origin, imprinting analyses support a SCNT origin of the derived human ES cells.", "title": "Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst." }, { "docid": "3883485", "text": "Replacement of mitochondria through nuclear transfer between oocytes of two different women has emerged recently as a strategy for preventing inheritance of mtDNA diseases. Although experiments in human oocytes have shown effective replacement, the consequences of small amounts of mtDNA carryover have not been studied sufficiently. Using human mitochondrial replacement stem cell lines, we show that, even though the low levels of heteroplasmy introduced into human oocytes by mitochondrial carryover during nuclear transfer often vanish, they can sometimes instead result in mtDNA genotypic drift and reversion to the original genotype. Comparison of cells with identical oocyte-derived nuclear DNA but different mtDNA shows that either mtDNA genotype is compatible with the nucleus and that drift is independent of mitochondrial function. Thus, although functional replacement of the mitochondrial genome is possible, even low levels of heteroplasmy can affect the stability of the mtDNA genotype and compromise the efficacy of mitochondrial replacement.", "title": "Genetic Drift Can Compromise Mitochondrial Replacement by Nuclear Transfer in Human Oocytes." }, { "docid": "16375102", "text": "The simple yet powerful technique of induced pluripotency may eventually supply a wide range of differentiated cells for cell therapy and drug development. However, making the appropriate cells via induced pluripotent stem cells (iPSCs) requires reprogramming of somatic cells and subsequent redifferentiation. Given how arduous and lengthy this process can be, we sought to determine whether it might be possible to convert somatic cells into lineage-specific stem/progenitor cells of another germ layer in one step, bypassing the intermediate pluripotent stage. Here we show that transient induction of the four reprogramming factors (Oct4, Sox2, Klf4, and c-Myc) can efficiently transdifferentiate fibroblasts into functional neural stem/progenitor cells (NPCs) with appropriate signaling inputs. Compared with induced neurons (or iN cells, which are directly converted from fibroblasts), transdifferentiated NPCs have the distinct advantage of being expandable in vitro and retaining the ability to give rise to multiple neuronal subtypes and glial cells. Our results provide a unique paradigm for iPSC-factor-based reprogramming by demonstrating that it can be readily modified to serve as a general platform for transdifferentiation.", "title": "Direct reprogramming of mouse fibroblasts to neural progenitors." }, { "docid": "27279525", "text": "The present study was undertaken to detect, characterize, and study differentiation potential of stem cells in adult rabbit, sheep, monkey, and menopausal human ovarian surface epithelium (OSE). Two distinct populations of putative stem cells (PSCs) of variable size were detected in scraped OSE, one being smaller and other similar in size to the surrounding red blood cells in the scraped OSE. The smaller 1-3 μm very small embryonic-like PSCs were pluripotent in nature with nuclear Oct-4 and cell surface SSEA-4, whereas the bigger 4-7 μm cells with cytoplasmic localization of Oct-4 and minimal expression of SSEA-4 were possibly the tissue committed progenitor stem cells. Pluripotent gene transcripts of Oct-4, Oct-4A, Nanog, Sox-2, TERT, and Stat-3 in human and sheep OSE were detected by reverse transcriptase-polymerase chain reaction. The PSCs underwent spontaneous differentiation into oocyte-like structures, parthenote-like structures, embryoid body-like structures, cells with neuronal-like phenotype, and embryonic stem cell-like colonies, whereas the epithelial cells transformed into mesenchymal phenotype by epithelial-mesenchymal transition in 3 weeks of OSE culture. Germ cell markers like c-Kit, DAZL, GDF-9, VASA, and ZP4 were immuno-localized in oocyte-like structures. In conclusion, as opposed to the existing view of OSE being a bipotent source of oocytes and granulosa cells, mammalian ovaries harbor distinct very small embryonic-like PSCs and tissue committed progenitor stem cells population that have the potential to develop into oocyte-like structures in vitro, whereas mesenchymal fibroblasts appear to form supporting granulosa-like somatic cells. Research at the single-cell level, including complete gene expression profiling, is required to further confirm whether postnatal oogenesis is a conserved phenomenon in adult mammals.", "title": "Detection, characterization, and spontaneous differentiation in vitro of very small embryonic-like putative stem cells in adult mammalian ovary." }, { "docid": "13513790", "text": "Haploid cells are amenable for genetic analysis. Recent success in the derivation of mouse haploid embryonic stem cells (haESCs) via parthenogenesis has enabled genetic screening in mammalian cells. However, successful generation of live animals from these haESCs, which is needed to extend the genetic analysis to the organism level, has not been achieved. Here, we report the derivation of haESCs from androgenetic blastocysts. These cells, designated as AG-haESCs, partially maintain paternal imprints, express classical ESC pluripotency markers, and contribute to various tissues, including the germline, upon injection into diploid blastocysts. Strikingly, live mice can be obtained upon injection of AG-haESCs into MII oocytes, and these mice bear haESC-carried genetic traits and develop into fertile adults. Furthermore, gene targeting via homologous recombination is feasible in the AG-haESCs. Our results demonstrate that AG-haESCs can be used as a genetically tractable fertilization agent for the production of live animals via injection into oocytes.", "title": "Generation of Genetically Modified Mice by Oocyte Injection of Androgenetic Haploid Embryonic Stem Cells" }, { "docid": "86129154", "text": "Somatic cell nuclear transfer allows trans-acting factors present in the mammalian oocyte to reprogram somatic cell nuclei to an undifferentiated state. We show that four factors (OCT4, SOX2, NANOG, and LIN28) are sufficient to reprogram human somatic cells to pluripotent stem cells that exhibit the essential characteristics of embryonic stem (ES) cells. These induced pluripotent human stem cells have normal karyotypes, express telomerase activity, express cell surface markers and genes that characterize human ES cells, and maintain the developmental potential to differentiate into advanced derivatives of all three primary germ layers. Such induced pluripotent human cell lines should be useful in the production of new disease models and in drug development, as well as for applications in transplantation medicine, once technical limitations (for example, mutation through viral integration) are eliminated.", "title": "Induced pluripotent stem cell lines derived from human somatic cells." }, { "docid": "4405194", "text": "Somatic cell nuclear transfer, cell fusion, or expression of lineage-specific factors have been shown to induce cell-fate changes in diverse somatic cell types. We recently observed that forced expression of a combination of three transcription factors, Brn2 (also known as Pou3f2), Ascl1 and Myt1l, can efficiently convert mouse fibroblasts into functional induced neuronal (iN) cells. Here we show that the same three factors can generate functional neurons from human pluripotent stem cells as early as 6 days after transgene activation. When combined with the basic helix-loop-helix transcription factor NeuroD1, these factors could also convert fetal and postnatal human fibroblasts into iN cells showing typical neuronal morphologies and expressing multiple neuronal markers, even after downregulation of the exogenous transcription factors. Importantly, the vast majority of human iN cells were able to generate action potentials and many matured to receive synaptic contacts when co-cultured with primary mouse cortical neurons. Our data demonstrate that non-neural human somatic cells, as well as pluripotent stem cells, can be converted directly into neurons by lineage-determining transcription factors. These methods may facilitate robust generation of patient-specific human neurons for in vitro disease modelling or future applications in regenerative medicine.", "title": "Induction of human neuronal cells by defined transcription factors" }, { "docid": "4417177", "text": "As is the case for embryo-derived stem cells, application of reprogrammed human induced pluripotent stem cells is limited by our understanding of lineage specification. Here we demonstrate the ability to generate progenitors and mature cells of the haematopoietic fate directly from human dermal fibroblasts without establishing pluripotency. Ectopic expression of OCT4 (also called POU5F1)-activated haematopoietic transcription factors, together with specific cytokine treatment, allowed generation of cells expressing the pan-leukocyte marker CD45. These unique fibroblast-derived cells gave rise to granulocytic, monocytic, megakaryocytic and erythroid lineages, and demonstrated in vivo engraftment capacity. We note that adult haematopoietic programs are activated, consistent with bypassing the pluripotent state to generate blood fate: this is distinct from haematopoiesis involving pluripotent stem cells, where embryonic programs are activated. These findings demonstrate restoration of multipotency from human fibroblasts, and suggest an alternative approach to cellular reprogramming for autologous cell-replacement therapies that avoids complications associated with the use of human pluripotent stem cells.", "title": "Direct conversion of human fibroblasts to multilineage blood progenitors" }, { "docid": "4325137", "text": "Murine embryonic stem (ES) cells are pluripotent cell lines established directly from the early embryo1,2 which can contribute differentiated progeny to all adult tissues, including the germ-cell lineage3, after re-incorporation into the normal embryo. They provide both a cellular vector for the generation of transgenic animals4 and a useful system for the identification of polypeptide factors controlling differentiation processes in early development5. In particular, medium conditioned by Buffalo rat liver cells contains a polypeptide factor, ES cell differentiation inhibitory activity (DIA), which specifically suppresses the spontaneous differentiation of ES cells in vitro, thereby permitting their growth as homogeneous stem cell populations in the absence of heterologous feeder cells6. ES cell pluripotentiality, including the ability to give rise to functional gametes, is preserved after prolonged culture in Buffalo rat liver media as a source of DIA7. Here, we report that purified DIA is related in structure and function to the recently identified haemopoetic regulatory factors human interleukin for DA cells8,9 and leukaemia inhibitory factor10. DIA and human interleukin DA/leukaemia inhibitory factor have thus been identified as related multifunctional regulatory factors with distinct biological activities in both early embryonic and haemopoetic stem cell systems.", "title": "Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides" }, { "docid": "26374799", "text": "Human embryonic stem cells (hESCs) self-renew indefinitely and give rise to derivatives of all three primary germ layers, yet little is known about the signaling cascades that govern their pluripotent character. Because it plays a prominent role in the early cell fate decisions of embryonic development, we have examined the role of TGFbeta superfamily signaling in hESCs. We found that, in undifferentiated cells, the TGFbeta/activin/nodal branch is activated (through the signal transducer SMAD2/3) while the BMP/GDF branch (SMAD1/5) is only active in isolated mitotic cells. Upon early differentiation, SMAD2/3 signaling is decreased while SMAD1/5 signaling is activated. We next tested the functional role of TGFbeta/activin/nodal signaling in hESCs and found that it is required for the maintenance of markers of the undifferentiated state. We extend these findings to show that SMAD2/3 activation is required downstream of WNT signaling, which we have previously shown to be sufficient to maintain the undifferentiated state of hESCs. Strikingly, we show that in ex vivo mouse blastocyst cultures, SMAD2/3 signaling is also required to maintain the inner cell mass (from which stem cells are derived). These data reveal a crucial role for TGFbeta signaling in the earliest stages of cell fate determination and demonstrate an interconnection between TGFbeta and WNT signaling in these contexts.", "title": "TGFbeta/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells." }, { "docid": "22490293", "text": "Although it has now been 10 years since the first cloned mammals were generated from somatic cells using nuclear transfer (NT), most cloned embryos usually undergo developmental arrest prior to or soon after implantation, and the success rate for producing live offspring by cloning remains below 5%. The low success rate is believed to be associated with epigenetic errors, including abnormal DNA hypermethylation, but the mechanism of \"reprogramming\" is unclear. We have been able to develop a stable NT method in the mouse in which donor nuclei are directly injected into the oocyte using a piezo-actuated micromanipulator. Especially in the mouse, only a few laboratories can make clones from adult somatic cells, and cloned mice are never successfully produced from most mouse strains. However, this technique promises to be an important tool for future research in basic biology. For example, NT can be used to generate embryonic stem (NT-ES) cell lines from a patient's own somatic cells. We have shown that NT-ES cells are equivalent to ES cells derived from fertilized embryos and that they can be generated relatively easily from a variety of mouse genotypes and cell types of both sexes, even though it may be more difficult to generate clones directly. In general, NT-ES cell techniques are expected to be applied to regenerative medicine; however, this technique can also be applied to the preservation of genetic resources of mouse strain instead of embryos, oocytes and spermatozoa. This review describes how to improve cloning efficiency and NT-ES cell establishment and further applications.", "title": "Production of cloned mice and ES cells from adult somatic cells by nuclear transfer: how to improve cloning efficiency?" }, { "docid": "21387297", "text": "Cardiovascular disease is a leading cause of death worldwide. The limited capability of heart tissue to regenerate has prompted methodological developments for creating de novo cardiomyocytes, both in vitro and in vivo. Beyond uses in cell replacement therapy, patient-specific cardiomyocytes may find applications in drug testing, drug discovery, and disease modeling. Recently, approaches for generating cardiomyocytes have expanded to encompass three major sources of starting cells: human pluripotent stem cells (hPSCs), adult heart-derived cardiac progenitor cells (CPCs), and reprogrammed fibroblasts. We discuss state-of-the-art methods for generating de novo cardiomyocytes from hPSCs and reprogrammed fibroblasts, highlighting potential applications and future challenges.", "title": "Production of de novo cardiomyocytes: human pluripotent stem cell differentiation and direct reprogramming." }, { "docid": "4380451", "text": "Pluripotency pertains to the cells of early embryos that can generate all of the tissues in the organism. Embryonic stem cells are embryo-derived cell lines that retain pluripotency and represent invaluable tools for research into the mechanisms of tissue formation. Recently, murine fibroblasts have been reprogrammed directly to pluripotency by ectopic expression of four transcription factors (Oct4, Sox2, Klf4 and Myc) to yield induced pluripotent stem (iPS) cells. Using these same factors, we have derived iPS cells from fetal, neonatal and adult human primary cells, including dermal fibroblasts isolated from a skin biopsy of a healthy research subject. Human iPS cells resemble embryonic stem cells in morphology and gene expression and in the capacity to form teratomas in immune-deficient mice. These data demonstrate that defined factors can reprogramme human cells to pluripotency, and establish a method whereby patient-specific cells might be established in culture.", "title": "Reprogramming of human somatic cells to pluripotency with defined factors" }, { "docid": "25985964", "text": "Very small embryonic-like stem cells (VSELs) are possibly lost during cord blood banking and bone marrow (BM) processing for autologus stem cell therapy mainly because of their small size. The present study was conducted on human umbilical cord blood (UCB, n=6) and discarded red blood cells (RBC) fraction obtained after separation of mononuclear cells from human BM (n=6), to test this hypothesis. The results show that VSELs, which are pluripotent stem cells with maximum regenerative potential, settle along with the RBCs during Ficoll-Hypaque density separation. These cells are very small in size (3-5 μm), have high nucleo-cytoplasmic ratio, and express nuclear Oct-4, cell surface protein SSEA-4, and other pluripotent markers such as Nanog, Sox-2, Rex-1, and Tert as indicated by immunolocalization and quantitative polymerase chain reaction (Q-PCR) studies. Interestingly, a distinct population of slightly larger, round hematopoietic stem cells (HSCs) with cytoplasmic Oct-4 were detected in the \"buffy\" coat, which usually gets banked or used during autologus stem cell therapy. Immunohistochemical studies on the umbilical cord tissue (UCT) sections (n=3) showed the presence of nuclear Oct-4-positive VSELs and many fibroblast-like mesenchymal stem cells (MSCs) with cytoplasmic Oct-4. These VSELs with nuclear Oct-4, detected in UCB, UCT, and discarded RBC fraction obtained after BM processing, may persist throughout life, maintain tissue homeostasis, and undergo asymmetric cell division to self-renew as well as produce larger progenitor stem cells, viz. HSCs or MSCs, which follow differentiation trajectories depending on the somatic niche. Hence, it can be concluded that the true stem cells in adult body tissues are the VSELs, whereas the HSCs and MSCs are actually progenitor stem cells that arise by asymmetric cell division of VSELs. The results of the present study may help explain low efficacy reported during adult autologous stem cell trials, wherein unknowingly progenitor stem cells are injected rather than the pluripotent stem cells with maximum regenerative potential.", "title": "Very small embryonic-like stem cells with maximum regenerative potential get discarded during cord blood banking and bone marrow processing for autologous stem cell therapy." }, { "docid": "4462419", "text": "Mouse embryonic stem (ES) cells are isolated from the inner cell mass of blastocysts, and can be preserved in vitro in a naive inner-cell-mass-like configuration by providing exogenous stimulation with leukaemia inhibitory factor (LIF) and small molecule inhibition of ERK1/ERK2 and GSK3β signalling (termed 2i/LIF conditions). Hallmarks of naive pluripotency include driving Oct4 (also known as Pou5f1) transcription by its distal enhancer, retaining a pre-inactivation X chromosome state, and global reduction in DNA methylation and in H3K27me3 repressive chromatin mark deposition on developmental regulatory gene promoters. Upon withdrawal of 2i/LIF, naive mouse ES cells can drift towards a primed pluripotent state resembling that of the post-implantation epiblast. Although human ES cells share several molecular features with naive mouse ES cells, they also share a variety of epigenetic properties with primed murine epiblast stem cells (EpiSCs). These include predominant use of the proximal enhancer element to maintain OCT4 expression, pronounced tendency for X chromosome inactivation in most female human ES cells, increase in DNA methylation and prominent deposition of H3K27me3 and bivalent domain acquisition on lineage regulatory genes. The feasibility of establishing human ground state naive pluripotency in vitro with equivalent molecular and functional features to those characterized in mouse ES cells remains to be defined. Here we establish defined conditions that facilitate the derivation of genetically unmodified human naive pluripotent stem cells from already established primed human ES cells, from somatic cells through induced pluripotent stem (iPS) cell reprogramming or directly from blastocysts. The novel naive pluripotent cells validated herein retain molecular characteristics and functional properties that are highly similar to mouse naive ES cells, and distinct from conventional primed human pluripotent cells. This includes competence in the generation of cross-species chimaeric mouse embryos that underwent organogenesis following microinjection of human naive iPS cells into mouse morulas. Collectively, our findings establish new avenues for regenerative medicine, patient-specific iPS cell disease modelling and the study of early human development in vitro and in vivo.", "title": "Derivation of novel human ground state naive pluripotent stem cells" }, { "docid": "36651210", "text": "Embryonic stem cells have the ability to remain undifferentiated and proliferate indefinitely in vitro while maintaining the potential to differentiate into derivatives of all three embryonic germ layers. These cells have, therefore, potential for in vitro differentiation studies, gene function, and so on. The aim of this study was to produce a human embryonic stem cell line. An inner cell mass of a human blastocyst was separated and cultured on mouse embryonic fibroblasts in embryonic stem cell medium with related additives. The established line was evaluated by morphology; passaging; freezing and thawing; alkaline phosphatase; Oct-4 expression; anti-surface markers including Tra-1-60 and Tra-1-81; and karyotype and spontaneous differentiation. Differentiated cardiomyocytes and neurons were evaluated by transmission electron microscopy and immunocytochemistry. Here, we report the derivation of a new embryonic stem cell line (Royan H1) from a human blastocyst that remains undifferentiated in morphology during continuous passaging for more than 30 passages, maintains a normal XX karyotype, is viable after freezing and thawing, and expresses alkaline phosphatase, Oct-4, Tra-1-60, and Tra-1-81. These cells remain undifferentiated when grown on mouse embryonic fibroblast feeder layers in the presence or absence of recombinant human leukemia inhibitory factor. Royan H1 cells can differentiate in vitro in the absence of feeder cells and can produce embryoid bodies that can further differentiate into beating cardiomyocytes as well as neurons. These results define Royan H1 cells as a new human embryonic stem cell line.", "title": "Establishment and in vitro differentiation of a new embryonic stem cell line from human blastocyst." }, { "docid": "4399268", "text": "Spinal muscular atrophy is one of the most common inherited forms of neurological disease leading to infant mortality. Patients have selective loss of lower motor neurons resulting in muscle weakness, paralysis and often death. Although patient fibroblasts have been used extensively to study spinal muscular atrophy, motor neurons have a unique anatomy and physiology which may underlie their vulnerability to the disease process. Here we report the generation of induced pluripotent stem cells from skin fibroblast samples taken from a child with spinal muscular atrophy. These cells expanded robustly in culture, maintained the disease genotype and generated motor neurons that showed selective deficits compared to those derived from the child’s unaffected mother. This is the first study to show that human induced pluripotent stem cells can be used to model the specific pathology seen in a genetically inherited disease. As such, it represents a promising resource to study disease mechanisms, screen new drug compounds and develop new therapies.", "title": "Induced pluripotent stem cells from a spinal muscular atrophy patient" }, { "docid": "1630949", "text": "The four transcription factors Oct4, Sox2, Klf4, and c-Myc can induce pluripotency in mouse and human fibroblasts. We previously described direct reprogramming of adult mouse neural stem cells (NSCs) by Oct4 and either Klf4 or c-Myc. NSCs endogenously express Sox2, c-Myc, and Klf4 as well as several intermediate reprogramming markers. Here we report that exogenous expression of the germline-specific transcription factor Oct4 is sufficient to generate pluripotent stem cells from adult mouse NSCs. These one-factor induced pluripotent stem cells (1F iPS) are similar to embryonic stem cells in vitro and in vivo. Not only can these cells can be efficiently differentiated into NSCs, cardiomyocytes, and germ cells in vitro, but they are also capable of teratoma formation and germline transmission in vivo. Our results demonstrate that Oct4 is required and sufficient to directly reprogram NSCs to pluripotency.", "title": "Oct4-Induced Pluripotency in Adult Neural Stem Cells" }, { "docid": "2608447", "text": "Defined transcription factors can induce epigenetic reprogramming of adult mammalian cells into induced pluripotent stem cells. Although DNA factors are integrated during some reprogramming methods, it is unknown whether the genome remains unchanged at the single nucleotide level. Here we show that 22 human induced pluripotent stem (hiPS) cell lines reprogrammed using five different methods each contained an average of five protein-coding point mutations in the regions sampled (an estimated six protein-coding point mutations per exome). The majority of these mutations were non-synonymous, nonsense or splice variants, and were enriched in genes mutated or having causative effects in cancers. At least half of these reprogramming-associated mutations pre-existed in fibroblast progenitors at low frequencies, whereas the rest occurred during or after reprogramming. Thus, hiPS cells acquire genetic modifications in addition to epigenetic modifications. Extensive genetic screening should become a standard procedure to ensure hiPS cell safety before clinical use.", "title": "Somatic coding mutations in human induced pluripotent stem cells" }, { "docid": "7640058", "text": "The cloning of animals from adult cells has demonstrated that the developmental state of adult cells can be reprogrammed into that of embryonic cells by uncharacterized factors within the oocyte. More recently, transcription factors have been identified that can induce pluripotency in somatic cells without the use of oocytes, generating induced pluripotent stem (iPS) cells. iPS cells provide a unique platform to dissect the molecular mechanisms that underlie epigenetic reprogramming. Moreover, iPS cells can teach us about principles of normal development and disease, and might ultimately facilitate the treatment of patients by custom-tailored cell therapy.", "title": "Epigenetic reprogramming and induced pluripotency." }, { "docid": "25413327", "text": "Embryonic stem (ES) cell lines derived from human blastocysts have the developmental potential to form derivatives of all three embryonic germ layers even after prolonged culture. Here we describe the clonal derivation of two human ES cell lines, H9.1 and H9.2. At the time of the clonal derivation of the H9.1 and H9.2 ES cell lines, the parental ES cell line, H9, had already been continuously cultured for 6 months. After an additional 8 months of culture, H9.1 and H9.2 ES cell lines continued to: (1) actively proliferate, (2) express high levels of telomerase, and (3) retain normal karyotypes. Telomere lengths, while somewhat variable, were maintained between 8 and 12 kb in high-passage H9.1 and H9.2 cells. High-passage H9.1 and H9.2 cells both formed teratomas in SCID-beige mice that included differentiated derivatives of all three embryonic germ layers. These results demonstrate the pluripotency of single human ES cells, the maintenance of pluripotency during an extended period of culture, and the long-term self-renewing properties of cultured human ES cells. The remarkable developmental potential, proliferative capacity, and karyotypic stability of human ES cells distinguish them from adult cells.", "title": "Clonally derived human embryonic stem cell lines maintain pluripotency and proliferative potential for prolonged periods of culture." }, { "docid": "4427392", "text": "The functional heart is comprised of distinct mesoderm-derived lineages including cardiomyocytes, endothelial cells and vascular smooth muscle cells. Studies in the mouse embryo and the mouse embryonic stem cell differentiation model have provided evidence indicating that these three lineages develop from a common Flk-1+ (kinase insert domain protein receptor, also known as Kdr) cardiovascular progenitor that represents one of the earliest stages in mesoderm specification to the cardiovascular lineages. To determine whether a comparable progenitor is present during human cardiogenesis, we analysed the development of the cardiovascular lineages in human embryonic stem cell differentiation cultures. Here we show that after induction with combinations of activin A, bone morphogenetic protein 4 (BMP4), basic fibroblast growth factor (bFGF, also known as FGF2), vascular endothelial growth factor (VEGF, also known as VEGFA) and dickkopf homolog 1 (DKK1) in serum-free media, human embryonic-stem-cell-derived embryoid bodies generate a KDRlow/C-KIT(CD117)neg population that displays cardiac, endothelial and vascular smooth muscle potential in vitro and, after transplantation, in vivo. When plated in monolayer cultures, these KDRlow/C-KITneg cells differentiate to generate populations consisting of greater than 50% contracting cardiomyocytes. Populations derived from the KDRlow/C-KITneg fraction give rise to colonies that contain all three lineages when plated in methylcellulose cultures. Results from limiting dilution studies and cell-mixing experiments support the interpretation that these colonies are clones, indicating that they develop from a cardiovascular colony-forming cell. Together, these findings identify a human cardiovascular progenitor that defines one of the earliest stages of human cardiac development.", "title": "Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population" }, { "docid": "21271817", "text": "Ectopic expression of the four transcription factors Oct4, Sox2, c-Myc, and Klf4 is sufficient to confer a pluripotent state upon the fibroblast genome, generating induced pluripotent stem (iPS) cells. It remains unknown if nuclear reprogramming induced by these four factors globally resets epigenetic differences between differentiated and pluripotent cells. Here, using novel selection approaches, we have generated iPS cells from fibroblasts to characterize their epigenetic state. Female iPS cells showed reactivation of a somatically silenced X chromosome and underwent random X inactivation upon differentiation. Genome-wide analysis of two key histone modifications indicated that iPS cells are highly similar to ES cells. Consistent with these observations, iPS cells gave rise to viable high-degree chimeras with contribution to the germline. These data show that transcription factor-induced reprogramming leads to the global reversion of the somatic epigenome into an ES-like state. Our results provide a paradigm for studying the epigenetic modifications that accompany nuclear reprogramming and suggest that abnormal epigenetic reprogramming does not pose a problem for the potential therapeutic applications of iPS cells.", "title": "Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution." }, { "docid": "5145974", "text": "STUDY QUESTION In women undergoing IVF, are urinary bisphenol A (BPA) concentrations associated with ovarian response and early reproductive outcomes, including oocyte maturation and fertilization, Day 3 embryo quality and blastocyst formation? SUMMARY ANSWER Higher urinary BPA concentrations were found to be associated with decreased ovarian response, number of fertilized oocytes and decreased blastocyst formation. WHAT IS KNOWN ALREADY Experimental animal and in vitro studies have reported associations between BPA exposure and adverse reproductive outcomes. We previously reported an association between urinary BPA and decreased ovarian response [peak serum estradiol (E(2)) and oocyte count at the time of retrieval] in women undergoing IVF; however, there are limited human data on reproductive health outcomes, such as fertilization and embryo development. STUDY DESIGN, SIZE AND DURATION Prospective preconception cohort study. One hundred and seventy-four women aged 18-45 years and undergoing 237 IVF cycles were recruited at the Massachusetts General Hospital Fertility Center, Boston, MA, USA, between November 2004 and August 2010. These women were followed until they either had a live birth or discontinued treatment. Cryothaw and donor egg cycles were not included in the analysis. PARTICIPANTS/MATERIALS, SETTING AND METHODS Urinary BPA concentrations were measured by online solid-phase extraction-high-performance liquid chromatography-isotope dilution-tandem mass spectrometry. Mixed effect models, poisson regression and multivariate logistic regression models were used wherever appropriate to evaluate the association between cycle-specific urinary BPA concentrations and measures of ovarian response, oocyte maturation (metaphase II), fertilization, embryo quality and cleavage rate. We accounted for correlation among multiple IVF cycles in the same woman using generalized estimating equations. MAIN RESULTS AND THE ROLE OF CHANCE The geometric mean (SD) for urinary BPA concentrations was 1.50 (2.22) µg/l. After adjustment for age and other potential confounders (Day 3 serum FSH, smoking, BMI), there was a significant linear dose-response association between increased urinary BPA concentrations and decreased number of oocytes (overall and mature), decreased number of normally fertilized oocytes and decreased E(2) levels (mean decreases of 40, 253 and 471 pg/ml for urinary BPA quartiles 2, 3 and 4, when compared with the lowest quartile, respectively; P-value for trend = 0.001). The mean number of oocytes and normally fertilized oocytes decreased by 24 and 27%, respectively, for the highest versus the lowest quartile of urinary BPA (trend test P < 0.001 and 0.002, respectively). Women with urinary BPA above the lowest quartile had decreased blastocyst formation (trend test P-value = 0.08). LIMITATIONS AND REASONS FOR CAUTION Potential limitations include exposure misclassification due to the very short half-life of BPA and its high variability over time; uncertainty about the generalizability of the results to the general population of women conceiving naturally and limited sample. WIDER IMPLICATIONS OF THE FINDINGS The results from this extended study, using IVF as a model to study early reproductive health outcomes in humans, indicate a negative dose-response association between urinary BPA concentrations and serum peak E(2) and oocyte yield, confirming our previous findings. In addition, we found significantly decreased metaphase II oocyte count and number of normally fertilizing oocytes and a suggestive association between BPA urinary concentrations and decreased blastocyst formation, thus indicating that BPA may alter reproductive function in susceptible women undergoing IVF. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by grants ES009718 and ES000002 from the National Institute of Environmental Health Sciences and grant OH008578 from the National Institute for Occupational Safety and Health. None of the authors has actual or potential competing financial interests. DISCLAIMER The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.", "title": "Urinary bisphenol A concentrations and early reproductive health outcomes among women undergoing IVF." }, { "docid": "19204979", "text": "Cells derived from blood vessels of human skeletal muscle can regenerate skeletal muscle, similarly to embryonic mesoangioblasts. However, adult cells do not express endothelial markers, but instead express markers of pericytes, such as NG2 proteoglycan and alkaline phosphatase (ALP), and can be prospectively isolated from freshly dissociated ALP+ cells. Unlike canonical myogenic precursors (satellite cells), pericyte-derived cells express myogenic markers only in differentiated myotubes, which they form spontaneously with high efficiency. When transplanted into severe combined immune deficient–X-linked, mouse muscular dystrophy (scid–mdx) mice, pericyte-derived cells colonize host muscle and generate numerous fibres expressing human dystrophin. Similar cells isolated from Duchenne patients, and engineered to express human mini-dystrophin, also give rise to many dystrophin-positive fibres in vivo. These data show that myogenic precursors, distinct from satellite cells, are associated with microvascular walls in the human skeletal muscle, may represent a correlate of embryonic 'mesoangioblasts' present after birth and may be a promising candidate for future cell-therapy protocols in patients.", "title": "Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells" } ]
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Reduction of purity of cytoplasmic membranes isolated from overexpressors is indicated by stronger spots for OmpF in 2D BN-PAGE gels.
[ { "docid": "6836086", "text": "Gram-negative bacteria have an outer membrane (OM) that functions as a barrier to protect the cell from toxic compounds such as antibiotics and detergents. The OM is a highly asymmetric bilayer composed of phospholipids, glycolipids, and proteins. Assembly of this essential organelle occurs outside the cytoplasm in an environment that lacks obvious energy sources such as ATP, and the mechanisms involved are poorly understood. We describe the identification of a multiprotein complex required for the assembly of proteins in the OM of Escherichia coli. We also demonstrate genetic interactions between genes encoding components of this protein assembly complex and imp, which encodes a protein involved in the assembly of lipopolysaccharides (LPS) in the OM. These genetic interactions suggest a role for YfgL, one of the lipoprotein components of the protein assembly complex, in a homeostatic control mechanism that coordinates the overall OM assembly process.", "title": "Identification of a Multicomponent Complex Required for Outer Membrane Biogenesis in Escherichia coli" } ]
[ { "docid": "24541180", "text": "Current methods of nuclear isolation from liver disrupt the plasmalemmae via homogenization and separation of the nuclei by high centrifugal force (HCF) through gradients of sucrose or other substances for up to 80 min. The use of HCF for such a long time increases the potential for nuclear damage and degradation by endogenous proteases. We compared four combinations of alterations to classical nuclear isolation methods as follows. Mouse liver was gently crushed through a fine mesh with and without in vivo perfusion with collagenase. The cell suspension was centrifuged at 600 g to remove gross debris and then at moderate centrifugal force (MCF, 16,000 g) or high centrifugal force (HCF, 70,000 g) through sucrose gradients for 30 min. The purity of the isolated nuclei was assessed biologically and morphologically, including analyses of representative marker proteins for nuclei and cytoplasm. The results indicate that MCF and no collagenase provided the highest nuclear integrity and purity, whereas MCF with collagenase is a viable option if priority is given to yield. The method is especially suited for small samples and so should facilitate studies with human liver biopsies and livers from mice, the most widely used species for gene targeting.", "title": "Isolation of intact nuclei of high purity from mouse liver." }, { "docid": "24706198", "text": "The Tat system transports folded proteins across bacterial and thylakoid membranes. In Gram-negative organisms, a TatABC substrate-binding complex and separate TatA complex are believed to coalesce to form an active translocon, with all three subunits essential for translocation. Most Gram-positive organisms lack a tatB gene, indicating major differences in organization and possible differences in mode of action. Here, we have studied Tat complexes encoded by the tatAdCd genes of Bacillus subtilis. Expression of tatAdCd in an Escherichia coli tat null mutant results in efficient export of a large, cofactor-containing E. coli Tat substrate, TorA. We show that the tatAd gene complements E. coli mutants lacking either tatAE or tatB, indicating a bifunctional role for this subunit in B. subtilis. Second, we have identified and characterized two distinct Tat complexes that are novel in key respects: a TatAdCd complex of approximately 230 kDa that is significantly smaller than the analogous E. coli TatABC complex (approximately 370 kDa on BN gels) and a separate TatAd complex. The latter is a discrete entity of approximately 270 kDa as judged by gel filtration chromatography, very different from the highly heterogeneous E. coli TatA complex that ranges in size from approximately 50 kDa to over 600 kDa. TatA heterogeneity has been linked to the varying size of Tat substrates being translocated, but the singular nature of the B. subtilis TatAd complex suggests that discrete TatAC and TatA complexes may form a single form of translocon.", "title": "A minimal Tat system from a gram-positive organism: a bifunctional TatA subunit participates in discrete TatAC and TatA complexes." }, { "docid": "20457190", "text": "We have reported the existence of biochemical and conformational differences in the alphabeta T cell receptor (TCR) complex between CD4(+) and CD8(+) CD3gamma-deficient (gamma(-)) mature T cells. In the present study, we have furthered our understanding and extended the observations to primary T lymphocytes from normal (gamma(+)) individuals. Surface TCR.CD3 components from CD4(+) gamma(-) T cells, other than CD3gamma, were detectable and similar in size to CD4(+) gamma(+) controls. Their native TCR.CD3 complex was also similar to CD4(+) gamma(+) controls, except for an alphabeta(deltaepsilon)(2)zeta(2) instead of an alphabetagammaepsilondeltaepsilonzeta(2) stoichiometry. In contrast, the surface TCRalpha, TCRbeta, and CD3delta chains of CD8(+) gamma(-) T cells did not possess their usual sizes. Using confocal immunofluorescence, TCRalpha was hardly detectable in CD8(+) gamma(-) T cells. Blue native gels (BN-PAGE) demonstrated the existence of a heterogeneous population of TCR.CD3 in these cells. Using primary peripheral blood T lymphocytes from normal (gamma(+)) donors, we performed a broad epitopic scan. In contrast to all other TCR.CD3-specific monoclonal antibodies, RW2-8C8 stained CD8(+) better than it did CD4(+) T cells, and the difference was dependent on glycosylation of the TCR.CD3 complex but independent of T cell activation or differentiation. RW2-8C8 staining of CD8(+) T cells was shown to be more dependent on lipid raft integrity than that of CD4(+) T cells. Finally, immunoprecipitation studies on purified primary CD4(+) and CD8(+) T cells revealed the existence of TCR glycosylation differences between the two. Collectively, these results are consistent with the existence of conformational or topological lineage-specific differences in the TCR.CD3 from CD4(+) and CD8(+) wild type T cells. The differences may be relevant for cis interactions during antigen recognition and signal transduction.", "title": "Biochemical differences in the alphabeta T cell receptor.CD3 surface complex between CD8+ and CD4+ human mature T lymphocytes." }, { "docid": "8087082", "text": "The microtubule (MT) cytoskeleton is required for many aspects of cell function, including the transport of intracellular materials, the maintenance of cell polarity, and the regulation of mitosis. These functions are coordinated by MT-associated proteins (MAPs), which work in concert with each other, binding MTs and altering their properties. We have used a MT cosedimentation assay, combined with 1D and 2D PAGE and mass spectrometry, to identify over 250 MAPs from early Drosophila embryos. We have taken two complementary approaches to analyse the cellular function of novel MAPs isolated using this approach. First, we have carried out an RNA interference (RNAi) screen, identifying 21 previously uncharacterised genes involved in MT organisation. Second, we have undertaken a bioinformatics analysis based on binary protein interaction data to produce putative interaction networks of MAPs. By combining both approaches, we have identified and validated MAP complexes with potentially important roles in cell cycle regulation and mitosis. This study therefore demonstrates that biologically relevant data can be harvested using such a multidisciplinary approach, and identifies new MAPs, many of which appear to be important in cell division.", "title": "A Microtubule Interactome: Complexes with Roles in Cell Cycle and Mitosis" }, { "docid": "26117607", "text": "Down syndrome cell adhesion molecule (Dscam) seems likely to play a key role in the \"alternative adaptive immunity\" that has been reported in invertebrates. Dscam consists of a cytoplasmic tail that is involved in signal transduction and a hypervariable extracellular region that might use a pathogen recognition mechanism similar to that used by the vertebrate antibodies. In our previous paper, we isolated a unique tail-less form of Dscam from Litopenaeus vannamei. In this study, we report the first membrane-bound form of shrimp Dscam: PmDscam was isolated from Penaeus monodon, and it occurred in both membrane-bound and tail-less forms. Phylogenetic analysis showed that while the crustacean Dscams from shrimp and water flea did not share a single subclade, they were distinct from the invertebrate Dscam-like molecules and from the insecta Dscams. In the extracellular region, the variable regions of PmDscam were located in N-terminal Ig2, N-terminal Ig3 and the entire Ig7 domain. The PmDscam extracellular variants and transmembrane domain variants were produced by mutually exclusive alternative splicing events. The cytoplasmic tail variants were produced by exon inclusion/exclusion. Based on the genomic organization of Daphnia Dscam's cytoplasmic tail, we propose a model of how the shrimp Dscam genomic locus might use Type III polyadenylation to generate both the tail-less and membrane-bound forms.", "title": "Penaeus monodon Dscam (PmDscam) has a highly diverse cytoplasmic tail and is the first membrane-bound shrimp Dscam to be reported." }, { "docid": "5914739", "text": "The CD3ε and ζ cytoplasmic domains of the T cell receptor bind to the inner leaflet of the plasma membrane (PM), and a previous nuclear magnetic resonance structure showed that both tyrosines of the CD3ε immunoreceptor tyrosine-based activation motif partition into the bilayer. Electrostatic interactions between acidic phospholipids and clusters of basic CD3ε residues were previously shown to be essential for CD3ε and ζ membrane binding. Phosphatidylserine (PS) is the most abundant negatively charged lipid on the inner leaflet of the PM and makes a major contribution to membrane binding by the CD3ε cytoplasmic domain. Here, we show that TCR triggering by peptide--MHC complexes induces dissociation of the CD3ε cytoplasmic domain from the plasma membrane. Release of the CD3ε cytoplasmic domain from the membrane is accompanied by a substantial focal reduction in negative charge and available PS in TCR microclusters. These changes in the lipid composition of TCR microclusters even occur when TCR signaling is blocked with a Src kinase inhibitor. Local changes in the lipid composition of TCR microclusters thus render the CD3ε cytoplasmic domain accessible during early stages of T cell activation.", "title": "Local changes in lipid environment of TCR microclusters regulate membrane binding by the CD3ε cytoplasmic domain" }, { "docid": "87986426", "text": "Sugarcane bacilliform virus(SCBV) was detected by PCR from sugarcane showing chlorosis and mottle symptom from Kaiyuan,Yunnan Province. Part sequence of replicase gene of the isolate SCBV-Kaiyuan was determined. Sequence analysis indicated that the 589 bp of SCBV-Kaiyuan shared identities of 73.2%-74.0% and 83.1%-84.1% at nucleotide and amino acid levels with SCBV-Australia respectively,66.7%-68.4% and 65.6%-67.7% with SCBV-Morocco. The quality and yield of the sugarcane infected with SCBV-Kaiyuan was also investigated. The juice extraction,sucrose content,gravity purity and average stalk weight were decreased 1.55%,1.24%,2.22% and 0.26 kg in plants infected with SCBV-Kaiyuan,but reducing sugar was increased by 0.21% in infected plants.", "title": "Detection of Sugarcane bacilliform virus isolate and its influence on yield and quality of cane in Yunnan" }, { "docid": "623486", "text": "Centrifugal elutriation was used further to isolate human peripheral blood monocytes (HPBM) from mononuclear-enriched cells harvested as a secondary component following platelet concentration collection samples. HPBM were recovered in either one or two populations consisting of either total HPBM or small (SM) and large monocytes (LM). The elutriation was carried out at 3,500 +/- 5 rpm for the separation of lymphocytes and HPBM in Ca++- and Mg++-free PBS without EDTA. An average of 5.05 +/- 1.50 X 10(8) HPBM were recovered in the total HPBM with a purity of 95% +/- 3%. The SM and LM were obtained by splitting the total HPBM into two equal populations with an HPBM purity of 92% +/- 3% and 93% +/- 3, respectively, by nonspecific esterase staining. The elutriation media were shown to have no effect on viability by trypan blue exclusion. All three HPBM populations were shown to be histochemically (lack of reactivity to leu-1 and leu-7) and functionally (depletion of NK cell activity) purified from the lymphocyte population. The HPBM populations were enriched in HLA-Dr, OKM-1, OKM-5, MY-8, and leu M-3 monoclonal antibody marker staining. There were no differences in percent positive cells between SM and LM populations for any of the monocyte-specific monoclonal antibodies. All three monocyte populations mediated antibody-dependent cell-mediated cytotoxicity to human red blood cells, with LM mediating more lysis (27.0% +/- 5%) than SM (7% +/- 3%).(ABSTRACT TRUNCATED AT 250 WORDS)", "title": "Centrifugal elutriation as a method for isolation of large numbers of functionally intact human peripheral blood monocytes." }, { "docid": "34905328", "text": "The TCR:CD3 complex transduces signals that are critical for optimal T cell development and adaptive immunity. In resting T cells, the CD3ε cytoplasmic tail associates with the plasma membrane via a proximal basic-rich stretch (BRS). In this study, we show that mice lacking a functional CD3ε-BRS exhibited substantial reductions in thymic cellularity and limited CD4- CD8- double-negative (DN) 3 to DN4 thymocyte transition, because of enhanced DN4 TCR signaling resulting in increased cell death and TCR downregulation in all subsequent populations. Furthermore, positive, but not negative, T cell selection was affected in mice lacking a functional CD3ε-BRS, which led to limited peripheral T cell function and substantially reduced responsiveness to influenza infection. Collectively, these results indicate that membrane association of the CD3ε signaling domain is required for optimal thymocyte development and peripheral T cell function.", "title": "Membrane association of the CD3ε signaling domain is required for optimal T cell development and function." }, { "docid": "23664875", "text": "Termination of replication forks at the natural termini of the rDNA of Saccharomyces cerevisiae is controlled in a sequence-specific and polar mode by the interaction of the Fob1p replication terminator protein with the tandem Ter sites located in the nontranscribed spacers. Here we show, by both 2D gel analyses and chromatin immunoprecipitations (ChIP), that there exists a second level of global control mediated by the intra-S-phase checkpoint protein complex of Tof1p and Csm3p that protect stalled forks at Ter sites against the activity of the Rrm3p helicase (\"sweepase\"). The sweepase tends to release arrested forks presumably by the transient displacement of the Ter-bound Fob1p. Consistent with this mechanism, very few replication forks were arrested at the natural replication termini in the absence of the two checkpoint proteins. In the absence of the Rrm3p helicase, there was a slight enhancement of fork arrest at the Ter sites. Simultaneous deletions of the TOF1 (or CSM3), and the RRM3 genes restored fork arrest by removing both the fork-releasing and fork-protection activities. Other genes such as MRC1, WSS1, and PSY2 that are also involved in the MRC1 checkpoint pathway were not involved in this global control. This observation suggests that Tof1p-Csm3p function differently from MRC1 and the other above-mentioned genes. This mechanism is not restricted to the natural Ter sites but was also observed at fork arrest caused by the meeting of a replication fork with transcription approaching from the opposite direction.", "title": "The Tof1p-Csm3p protein complex counteracts the Rrm3p helicase to control replication termination of Saccharomyces cerevisiae." }, { "docid": "8903143", "text": "The T-cell receptor (TCR) consists of a TCRαβ heterodimer, a TCRζ homodimer, and CD3γε and CD3δε heterodimers. The precise mechanism of T-cell triggering following TCR ligand engagement remains elusive. Previous studies reported that the cytoplasmic tail of CD3ε binds to the plasma membrane through a basic residue-rich stretch (BRS) and proposed that dissociation from the membrane is required for phosphorylation thereof. In this report we show that BRS motifs within the cytoplasmic tail of TCRζ mediate association with the plasma membrane and that TCR engagement results in TCRζ dissociation from the membrane. This dissociation requires phosphorylation of the TCRζ immunoreceptor tyrosine-based activation motifs by lymphocyte cell-specificprotein tyrosine kinase (Lck) but not ζ-chain-associated protein kinase 70 binding. Mutations of the TCRζ BRS motifs that disrupt this membrane association attenuate proximal and distal responses induced by TCR engagement. These mutations appear to alter the localization of TCRζ with respect to Lck as well as the mobility of the TCR complex. This study reveals that tyrosine phosphorylation of the TCRζ cytoplasmic domain regulates its association with the plasma membrane and highlights the functional importance of TCRζ BRS motifs.", "title": "Basic residues in the T-cell receptor ζ cytoplasmic domain mediate membrane association and modulate signaling." }, { "docid": "22023404", "text": "CONTEXT Vitamin D deficiency is associated with many adverse health outcomes, yet little is known about the genetic epidemiology of vitamin D or its metabolites. OBJECTIVE Our objective was to examine the relationship among three vitamin D-related genes and levels of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] in Hispanics (HAs) and African Americans (AAs). DESIGN AND SETTING The cross-sectional Insulin Resistance Atherosclerosis Family Study recruited and examined subjects in: Los Angeles, California (AAs; 513 individuals from 42 families); San Luis Valley (SLV), Colorado (HAs; 513 individuals from 30 families); and San Antonio (SA), Texas (HAs; 504 individuals from 58 families). MAIN OUTCOME MEASURES Plasma levels of 25(OH)D and 1,25(OH)2D were measured. RESULTS Levels of 25(OH)D were highest in SLV-HAs [18.3 +/- 7.7 ng/ml (45.7 +/- 19.2 nmol/liter)], lower in SA-HAs [14.6 +/- 6.4 ng/ml (36.4 +/- 16.0 nmol/liter)], and lowest in AAs [11.0 +/- 5.4 ng/ml (27.5 +/- 13.5 nmol/liter)]. Levels of 1,25(OH)2D were similar in AAs [43.5 +/- 13.9 pg/ml (113.1 +/- 36.1 pmol/liter)] and SLV-HAs [43.2 +/- 13.3 pg/ml (112.3 +/- 34.6 pmol/liter)], but higher in SA-HAs [48.6 +/- 17.0 pg/ml (126.4 +/- 44.2 pmol/liter)]. After adjusting for gender and age within the site, two single nucleotide polymorphisms (SNPs) in the vitamin D binding protein gene (DBP), rs4588 and rs7041, were associated with 25(OH)D, and one SNP in the DBP, rs4588, was associated with 1,25(OH)2D at all three study centers. CONCLUSIONS SNPs in the DBP are associated with levels of 25(OH)D and 1,25(OH)2D in HA and AA participants in the Insulin Resistance Atherosclerosis Family Study.", "title": "Genetic and environmental determinants of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels in Hispanic and African Americans." }, { "docid": "21164071", "text": "Integrins are membrane receptors which mediate cell-cell or cell-matrix adhesion. Integrin alpha IIb beta 3 (glycoprotein IIb-IIIa) acts as a fibrinogen receptor of platelets and mediates platelet aggregation. Platelet activation is required for alpha IIb beta 3 to shift from noncompetent to competent for binding soluble fibrinogen. The steps involved in this transition are poorly understood. We have studied a variant of Glanzmann thrombasthenia, a congenital bleeding disorder characterized by absence of platelet aggregation and fibrinogen binding. The patient's platelets did not bind fibrinogen after platelet activation by ADP or thrombin, though his platelets contained alpha IIb beta 3. However, isolated alpha IIb beta 3 was able to bind to an Arg-Gly-Asp-Ser affinity column, and binding of soluble fibrinogen to the patient's platelets could be triggered by modulators of alpha IIb beta 3 conformation such as the Arg-Gly-Asp-Ser peptide and alpha-chymotrypsin. These data suggested that a functional Arg-Gly-Asp binding site was present within alpha IIb beta 3 and that the patient's defect was not secondary to a blockade of alpha IIb beta 3 in a noncompetent conformational state. This was evocative of a defect in the coupling between platelet activation and alpha IIb beta 3 up-regulation. We therefore sequenced the cytoplasmic domain of beta 3, following polymerase chain reaction (PCR) on platelet RNA, and found a T-->C mutation at nucleotide 2259, corresponding to a Ser-752-->Pro substitution. This mutation is likely to be responsible for the uncoupling of alpha IIb beta 3 from cellular activation because (i) it is not a polymorphism, (ii) it is the only mutation in the entire alpha IIb beta 3 sequence, and (iii) genetic analysis of the family showed that absence of the Pro-752 beta 3 allele was associated with the normal phenotype. Our data thus identify the C-terminal portion of the cytoplasmic domain of beta 3 as an intrinsic element in the coupling between alpha IIb beta 3 and platelet activation.", "title": "Ser-752-->Pro mutation in the cytoplasmic domain of integrin beta 3 subunit and defective activation of platelet integrin alpha IIb beta 3 (glycoprotein IIb-IIIa) in a variant of Glanzmann thrombasthenia." }, { "docid": "27768226", "text": "PLoS Biology publishes today a research article by Gunther Eysenbach that is not about biology. It is about citations. It provides robust evidence that open-access articles (OA articles) are more immediately recognized and cited than non-OA articles. As such, it adds objective support to the belief we have always held that open-access publication speeds up scientific dialog between researchers and, consequently, should be extended to the whole scientific literature as quickly as possible. It is therefore fitting that we publish such a paper. We have long argued that papers freely available in a journal will be more often read and cited than those behind a subscription barrier. However, solid evidence to support or refute such a claim has been surprisingly hard to find. Since most open-access journals are new, comparisons of the effects of open access with established subscription-based journals are easily confounded by age and reputation. In the current study, Eysenbach compared citations compiled by Thomson Scientific (formerly Thomson ISI) to individual articles published between June 2004 and December 2004 in the same journal—namely, Proceedings of the National Academy of Sciences (PNAS), which announced its open-access option for authors on June 8 of that year, with an associated publication charge of US$1,000. Non-OA articles in PNAS are subject to a six-month “toll-access” delay before the article becomes publicly available. The results of this natural experiment are clear: in the 4 to 16 months following publication, OA articles gained a significant citation advantage over non-OA articles during the same period. They are twice as likely to be cited 4 to 10 months after publication and almost three times as likely between 10 and 16 months. Given that PNAS delays open access for only six months, the disparity between OA and non-OA articles in journals where the delay is longer or where articles remain “toll-access” is likely to be even greater. Eysenbach also looked at the impact of self-archiving non-OA articles. One route to open access, it is argued, is for authors to archive their published articles on their own Web sites or in institutional repositories, although this does not include an explicit business model to cover the cost of peer-review and publishing. The analysis revealed that self-archived articles are also cited less often than OA articles from the same journal. Yes, you're right; we do have a strong and vested interest in publishing results that so obviously endorse our existence. Moreover, the author of the article is also an editor of an open-access journal. But sometimes a potential conflict of interest can actually help to ensure rigor. In this case, we have an acute interest in ensuring that the article meets the same, if not higher, standards as any other research article we publish. Not only must the conclusions provide a significant advance for the field, but the study must be technically sound, with appropriate evidence to support those conclusions. As with all our research articles, we consulted throughout the evaluation process with an academic editor with appropriate expertise—in this case, Carol Tenopir, professor of information sciences at the University of Tennessee (Knoxville, Tennessee, United States). The article was reviewed by two experts in bibliometric analyses and information science, and an experienced research biologist with expertise in statistics. They all enthusiastically supported publication, although one understandably questioned the suitability of PLoS Biology as the publication venue. We have no intention of making PLoS Biology a regular home for bibliometric studies (even when about open access). What makes this study worth publishing in PLoS Biology is not only the relative strength of evidence supporting the claim but also the extent to which many (especially other publishers) have anticipated such an analysis. As far as we are aware, no other study has compared OA and non-OA articles from the same journal and controlled for so many potentially confounding factors. Eysenbach's multivariate analysis took into account the number of days since publication, number of authors, article type, country of the corresponding author, funding type, subject area, submission track ( PNAS has three different ways that authors can submit a paper), and the previous citation record of the first and last authors. He even administered a supplementary questionnaire to assess whether authors choosing the OA option in PNAS chose to do so for only their most important research (they didn't). As Ian Rowlands from the Centre for Publishing at University College London—and one of the reviewers who agreed to be identified in this article—said at the start of his review: “Many (most) of the papers and presentations I have read/seen on this topic have completely failed to address the kinds of confounding issues that are so convincingly tackled here. For that reason alone, this paper deserves to be published and alerted to the widest possible audience. ” In addition to providing evidence for the immediate advantage of open access, Eysenbach's analysis also highlights several potential challenges to its long-term future. Although a limited dataset, the citation history of the first and last authors differed between those who chose the open-access option and those who did not. In the group that chose open access, last authors tended to have a “stronger” previous citation record, whereas this situation was reversed among the group that declined the open-access option—here, it was the first authors who tended to be stronger. This may reflect varying attitudes of authors at different stages of their career, a stronger influence from the leader of a particular group, or an age- or career-related difference in the ability to pay the publication charge (e.g., [ 1]). Indeed, access to appropriate funds may also be a reason why a lower proportion of authors from European countries tended to choose the open-access option. In many of these countries, funds for page charges—and, by extension, open-access publication fees—are often not included within research grants. PNAS was one of the first journals to offer an open-access option to its authors. However, such hybrid journals are increasing: Blackwell, Springer, and Oxford University Press now provide this option as well. This means that similar experiments can be replicated. Moreover, although the evidence from the current analysis argues most strongly for a time advantage in citation for OA articles, a study over longer periods will reveal whether this translates into a sustained increase in the number of citations. In the meantime, open-access advocates should be emboldened by tangible evidence for what has seemed obvious all along.", "title": "Open Access Increases Citation Rate" }, { "docid": "11721676", "text": "Primary afferent fibers are originated from pseudounipolar sensory cells in dorsal root ganglia (DRG) and transmit external stimuli received in the skin to the spinal cord. Here we undertook a proteomic approach to uncover the polarity of primary afferent fibers. Lumbar spinal nerve segments, peripheral and central to DRG, were dissected from 5-wk-old Wistar rats and the lysates were subjected to large-sized 2-DE at pH 5-6. Among approximately 800 protein spots detected in the central and peripheral fractions, one of the unique spots in the peripheral fraction with MW of 60 kDa and pI of 5.6 was identified as an isoform of collapsin response mediator protein-2 (CRMP-2) by MALDI-TOF MS and Western blots with anti-CRMP-2 antibodies that recognize 1-17 and 486-528 residues. Since this novel spot was detected only in the peripheral fraction, but not in the central fraction, DRG, and other regions of the brain, it was named periCRMP-2. The C-terminal fragment of CRMP-2 was not detected in periCRMP-2 by MS analyses. Expression of periCRMP-2 decreased following sciatic nerve injury. These results suggest that periCRMP-2 is a C-terminal truncated isoform polarized in the peripheral side of spinal nerves and may be involved in nerve degeneration and regeneration.", "title": "Proteomic identification of a novel isoform of collapsin response mediator protein-2 in spinal nerves peripheral to dorsal root ganglia." }, { "docid": "25994317", "text": "CACCC boxes are among the critical sequences present in regulatory elements of genes expressed in erythroid cells, as well as in selected other cell types. While an erythroid cell-specific CACCC-box-binding protein, EKLF, has been shown to be required in vivo for proper expression of the adult beta-globin gene, it is dispensable for the regulation of several other globin and nonglobin erythroid cell-expressed genes. In the work described here, we searched for additional CACCC-box transcription factors that might be active in murine erythroid cells. We identified a major gel shift activity (termed BKLF), present in yolk sac and fetal liver erythroid cells, that could be distinguished from EKLF by specific antisera. Through relaxed-stringency hybridization, we obtained the cDNA encoding BKLF, a highly basic, novel zinc finger protein that is related to EKLF and other Krüppel-like members in its DNA-binding domain but unrelated elsewhere. BKLF, which is widely but not ubiquitously expressed in cell lines, is highly expressed in the midbrain region of embryonic mice and appears to correspond to the gel shift activity TEF-2, a transcriptional activator implicated in regulation of the simian virus 40 enhancer and other CACCC-box-containing regulatory elements. Because BKLF binds with high affinity and preferentially over Sp1 to many CACCC sequences of erythroid cell expressed genes, it is likely to participate in the control of many genes whose expression appears independent of the action of EKLF.", "title": "Isolation and characterization of the cDNA encoding BKLF/TEF-2, a major CACCC-box-binding protein in erythroid cells and selected other cells." }, { "docid": "25439264", "text": "Abstract Hyperhomocysteinemia has been suggested as a possible risk factor in women suffering from habitual abortions, placental abruption or infarcts, preeclampsia, and/or intrauterine growth retardation. However, little is known about the pathogenic mechanisms underlying the action of homocysteine. The present study investigated the in vitro ability of homocysteine to affect trophoblast gonadotropin secretion and to induce cell death. In primary human trophoblast cells, homocysteine treatment (20 μmol/L) resulted in cellular flattening and enlargement, extension of pseudopodia, and cellular vacuolization. Cellular detachment, apoptosis, and necrosis were favored. With in situ nick end labeling, we investigated DNA degradation, and we used M30 CytoDEATH to selectively stain the cytoplasm of apoptotic cells. Cytochrome c release from mitochondria to the cytosol and DNA cleavage in agarose gel have been investigated. Homocysteine, but not cysteine, induced trophoblast apoptosis and significantly reduced human chorionic gonadotropin secretion. These findings suggest that trophoblast cell death might represent a pathogenic mechanism by which homocysteine may cause pregnancy complications related to placental diseases.", "title": "Homocysteine Induces Trophoblast Cell Death with Apoptotic Features1" }, { "docid": "25045244", "text": "Our previous studies in volunteers immunized with Salmonella enterica serovar Typhi (S. Typhi) have suggested an important role for CD8+ T cells in host defense. In this study we describe a novel subset of nonclassical human HLA-E-restricted S. Typhi-specific CD8+ T cells derived from PBMC of Ty21a typhoid vaccinees. CD3+CD8+CD4-CD56- T cells effectively killed S. Typhi-infected targets regardless of whether they share classical HLA class I molecules with them, by a FAS-independent, granule-dependent mechanism, as evidenced by induction of granzyme B release and the blocking effects of concanamycin and strontium ions. The expression of HLA-E Ags, but not CD1-a, -b, or -c, on the membrane of S. Typhi-infected targets rendered them susceptible to lysis. Moreover, anti-HLA-E Abs partially blocked these responses. We also demonstrated that presentation of S. Typhi Ags via HLA-E could stimulate IFN-gamma production. Increases in the net frequency of IFN-gamma spot-forming cells were observed in the presence of targets coated with peptides that contain S. Typhi GroEL HLA-E binding motifs. These results demonstrate that HLA-E binds nonamer peptides derived from bacterial proteins and trigger CD8+-mediated lysis and IFN-gamma production when exposed to infected targets, raising the possibility that this novel effector mechanism might contribute to host defense against intracellular bacterial infections.", "title": "Identification of a human HLA-E-restricted CD8+ T cell subset in volunteers immunized with Salmonella enterica serovar Typhi strain Ty21a typhoid vaccine." }, { "docid": "24863571", "text": "The mammalian mitochondrial genome contains 37 genes, 13 of which encode polypeptide subunits in the enzyme complexes of the oxidative phosphorylation system. The other genes encode the rRNAs and tRNAs necessary for their translation. The mitochondrial translation machinery is located in the mitochondrial matrix, and is exclusively dedicated to the synthesis of these 13 enzyme subunits. Mitochondrial disease in humans is often associated with defects in mitochondrial translation. This can manifest as a global decrease in the rate of mitochondrial protein synthesis, a decrease in the synthesis of specific polypeptides, the synthesis of abnormal polypeptides, or in altered stability of specific translation products. All of these changes in the normal pattern of mitochondrial translation can be assessed by a straightforward technique that takes advantage of the insensitivity of the mitochondrial translation machinery to antibiotics that completely inhibit cytoplasmic translation. Thus, specific radioactive labeling of the mitochondrial translation products can be achieved in cultured cells, and the results can be visualized on gradient gels. The analysis of mitochondrial translation in cells cultured from patient biopsies is useful in the study of disease-causing mutations in both the mitochondrial and the nuclear genomes.", "title": "Radioactive labeling of mitochondrial translation products in cultured cells." }, { "docid": "39668245", "text": "Conventional in vivo assays to determine the relative pathogenicity of yeast isolates rely upon the use of a range of mammalian species. The purpose of the work presented here was to investigate the possibility of using an insect (Galleria mellonella) as a model system for in vivo pathogenicity testing. The haemolymph of G. mellonella larvae was inoculated with PBS containing different concentrations of stationary phase yeasts of the genus Candida by injection at the last pro-leg. Larvae were incubated at 30 degrees C and monitored over 72 hours. Results indicate that G. mellonella can be killed by the pathogenic yeast Candida albicans and by a range of other Candida species but not to a significant extent by the yeast Saccharomyces cerevisiae. The kill kinetics for larvae inoculated with clinical and laboratory isolates of C. albicans indicate the former class of isolates to be more pathogenic. Differences in the relative pathogenicity of a range of Candida species may be distinguished using G. mellonella as a model. This work indicates that G. mellonella may be employed to give results consistent with data previously obtained using mammals in conventional in vivo pathogenicity testing. Larvae of G. mellonella are inexpensive to culture, easy to manipulate and their use may reduce the need to employ mammals for routine in vivo pathogenicity testing with a concomitant reduction in mammalian suffering.", "title": "Development of an insect model for the in vivo pathogenicity testing of yeasts." }, { "docid": "41256402", "text": "Neither the restoration of the centrosome during fertilization nor its reduction during gametogenesis is fully understood, but both are pivotal events in development. During each somatic cell cycle, the chromosomes, cytoplasm, and centrosomes duplicate in interphase, and all three split in two during each cell division. While it has long been recognized that both the sperm and the egg contribute equal haploid genomes during fertilization and that the vast majority of the cytoplasm is contributed by the egg, the relative contributions of the centrosome by each gamete are still in question. This article explores centrosome inheritance patterns and considers nine integral and secondarily derived activities of the centrosome. Boveri once hypothesized that \"The ripe egg possesses all of the elements necessary for development save an active division-center. The sperm, on the other hand, possesses such a center but lacks the protoplasmic substratum in which to operate. In this respect the egg and sperm are complementary structures; their union in syngamy thus restores to each the missing element necessary to further development. \" This article reviews the evidence gathered from 11 experimental strategies used to test this theory. While the majority of these approaches supports the hypothesis that the sperm introduces the centrosome at fertilization, the pattern did not reveal itself as universal, since parthenogenesis occurs in nature and can be induced artificially, since centrosome and centriole form de novo in extracts from unfertilized eggs and since the centrosome is derived from maternal sources during fertilization in some systems--notably, in mice. Models of the centrosome are proposed, along with speculative mechanisms which might lead to the cloaking of the reproducing element of the maternal centrosome during oogenesis and the retention of this structure by the paternal centrosome during spermatogenesis. Proteins essential for microtubule nucleation, like gamma-tubulin, are retained in the cytoplasm during oogenesis, but are largely lost during spermatogenesis. It is further postulated that the restoration of the zygotic centrosome at fertilization requires the attraction of maternal centrosomal components (in particular, gamma-tubulin and the 25S \"gamma-some\" particle) to the paternal reproducing element; this, along with post-translational modifications (including phosphorylation, disulfide reduction, and calcium ion binding), creates a functional zygote centrosome by blending both maternal and paternal constituents.(ABSTRACT TRUNCATED AT 400 WORDS)", "title": "The centrosome and its mode of inheritance: the reduction of the centrosome during gametogenesis and its restoration during fertilization." }, { "docid": "36991551", "text": "Abstract Some cocoas and chocolates are rich in ()epicatechin and its related oligomers, the procyanidins. Fractions of these compounds, isolated from the seeds of Theobroma cacao, caused dosedependent inhibition of isolated rabbit 15-lipoxygenase-1 with the larger oligomers being more active; the decamer fraction revealed an IC 50 of 0.8 M. Among the monomeric flavanols, epigallocatechin gallate (IC 50 = 4 M) and epicatechin gallate (5 M) were more potent than ()epicatechin (IC50 = 60 M). ()Epicatechin and procyanidin nonamer also inhibited the formation of 15-hydroxyeicosatetraenoic acid from arachidonic acid in rabbit smooth muscle cells transfected with human 15-lipoxygenase-1. In contrast, inhibition of the lipoxygenase pathway in J774A.1 cells transfected with porcine leukocytetype 12- lipoxygenase (another representative of the 12/15- lipoxygenase family) was only observed upon sonication of the cells, suggesting a membrane barrier for flavanols in these cells. Moreover, epicatechin (IC50 approx. 15 M) and the procyanidin decamer inhibited recombinant human platelet 12-lipoxygenase. These observations suggest general lipoxygenase inhibitory potency of flavanols and procyanidins that may contribute to their putative beneficial effects on the cardiovascular system in man. Thus, they may provide a plausible explanation for recent literature reports indicating that procyanidins decrease the leukotriene/prostacyclin ratio in humans and human aortic endothelial cells.", "title": "Polyphenols of Cocoa: Inhibition of Mammalian 15-Lipoxygenase" }, { "docid": "22561064", "text": "The twin-arginine translocation (Tat) system transports folded proteins across bacterial plasma membranes and the chloroplast thylakoid membrane. Here, we investigate the composition and structural organization of three different purified Tat complexes from Escherichia coli, Salmonella typhimurium and Agrobacterium tumefaciens. First, we demonstrate the functional activity of these Tat systems in vivo, since expression of the tatABC operons from S.typhimurium or A.tumefaciens in an E.coli tat null mutant strain resulted in efficient Tat-dependent export of an E.coli cofactor-containing substrate, TMAO reductase. The three isolated, affinity-tagged Tat complexes comprised TatA, TatB and TatC in each case, demonstrating a strong interaction between these three subunits. Single-particle electron microscopy studies of all three complexes revealed approximately oval-shaped, asymmetric particles with maximal dimensions up to 13 nm. A common feature is a number of stain-excluding densities surrounding more or less central pools of stain, suggesting protein-lined pores or cavities. The characteristics of size variation among the particles suggest a modular form of assembly and/or the recruitment of varying numbers of TatBC/TatA units. Despite low levels of sequence homology, the combined data indicate structural and functional conservation in the Tat systems of these three bacterial species.", "title": "Consensus structural features of purified bacterial TatABC complexes." }, { "docid": "43390777", "text": "Macroautophagy, the process by which cytosolic components and organelles are engulfed and degraded by a double-membrane structure, could be viewed as a specialized, multistep membrane transport process. As such, it intersects with the exocytic and endocytic membrane trafficking pathways. A number of Rab GTPases which regulate secretory and endocytic membrane traffic have been shown to play either critical or accessory roles in autophagy. The biogenesis of the pre-autophagosomal isolation membrane (or phagophore) is dependent on the functionality of Rab1. A non-canonical, Atg5/Atg7-independent mode of autophagosome generation from the trans-Golgi or endosome requires Rab9. Other Rabs, such as Rab5, Rab24, Rab33, and Rab7 have all been shown to be required, or involved at various stages of autophagosomal genesis and maturation. Another small GTPase, RalB, was very recently demonstrated to induce isolation membrane formation and maturation via its engagement of the exocyst complex, a known Rab effector. We summarize here what is now known about the involvement of Rabs in autophagy, and discuss plausible mechanisms with future perspectives.", "title": "Involvement of members of the Rab family and related small GTPases in autophagosome formation and maturation" }, { "docid": "4452659", "text": "Macroautophagy (hereafter referred to as autophagy) is a catabolic membrane trafficking process that degrades a variety of cellular constituents and is associated with human diseases. Although extensive studies have focused on autophagic turnover of cytoplasmic materials, little is known about the role of autophagy in degrading nuclear components. Here we report that the autophagy machinery mediates degradation of nuclear lamina components in mammals. The autophagy protein LC3/Atg8, which is involved in autophagy membrane trafficking and substrate delivery, is present in the nucleus and directly interacts with the nuclear lamina protein lamin B1, and binds to lamin-associated domains on chromatin. This LC3-lamin B1 interaction does not downregulate lamin B1 during starvation, but mediates its degradation upon oncogenic insults, such as by activated RAS. Lamin B1 degradation is achieved by nucleus-to-cytoplasm transport that delivers lamin B1 to the lysosome. Inhibiting autophagy or the LC3-lamin B1 interaction prevents activated RAS-induced lamin B1 loss and attenuates oncogene-induced senescence in primary human cells. Our study suggests that this new function of autophagy acts as a guarding mechanism protecting cells from tumorigenesis.", "title": "Autophagy mediates degradation of nuclear lamina" }, { "docid": "37964706", "text": "Ca2+ entry through store-operated Ca2+ channels drives the production of the pro-inflammatory molecule leukotriene C4 (LTC4) from mast cells through a pathway involving Ca2+-dependent protein kinase C, mitogen-activated protein kinases ERK1/2, phospholipase A2, and 5-lipoxygenase. Here we examine whether local Ca2+ influx through store-operated Ca2+ release-activated Ca2+ (CRAC) channels in the plasma membrane stimulates this signaling pathway. Manipulating the amplitude and spatial extent of Ca2+ entry by altering chemical and electrical gradients for Ca2+ influx or changing the Ca2+ buffering of the cytoplasm all impacted on protein kinase C and ERK activation, generation of arachidonic acid and LTC4 secretion, with little change in the bulk cytoplasmic Ca2+ rise. Similar bulk cytoplasmic Ca2+ concentrations were achieved when CRAC channels were activated in 0.25 mm external Ca2+ versus 2 mm Ca2+ and 100 nm La3+, an inhibitor of CRAC channels. However, despite similar bulk cytoplasmic Ca2+, protein kinase C activation and LTC4 secretion were larger in 2 mm Ca2+ and La3+ than in 0.25 mm Ca2+, consistent with the central involvement of a subplasmalemmal Ca2+ rise. The nonreceptor tyrosine kinase Syk coupled CRAC channel opening to protein kinase C and ERK activation. Recombinant TRPC3 channels also activated protein kinase C, suggesting that subplasmalemmal Ca2+ rather than a microdomain exclusive to CRAC channels is the trigger. Hence a subplasmalemmal Ca2+ increase in mast cells is highly versatile in that it triggers cytoplasmic responses through generation of intracellular messengers as well as long distance changes through increased secretion of paracrine signals.", "title": "Local Ca2+ influx through Ca2+ release-activated Ca2+ (CRAC) channels stimulates production of an intracellular messenger and an intercellular pro-inflammatory signal." }, { "docid": "350542", "text": "BACKGROUND Pleurocidin, a 25-mer antimicrobial peptide (AMP), is known to exert bactericidal activity. However, the synergistic activity and mechanism(s) of pleurocidin in combination with conventional antibiotics, and the antibiofilm effect of the peptide are poorly understood. METHODS The interaction between pleurocidin and antibiotics was evaluated using checkerboard assay. To study the mechanism(s) involved in their synergism, we detected hydroxyl radical formation using 3'-(p-hydroxyphenyl) fluorescein, measured the NAD(+)/NADH ratio by NAD(+) cycling assay, observed change in bacterial viability with the hydroxyl radical scavenger thiourea, and investigated cytoplasmic membrane damage using propidium iodide. Also, the antibiofilm effect of pleurocidin was examined with the tissue culture plate method. RESULTS All combinations of pleurocidin and antibiotics showed synergistic interaction against bacterial strains (fractional inhibitory concentration index (FICI)≤0.5) except for Enterococcus faecium treated with a combination of the peptide and ampicillin (FICI=0.75). We identified that pleurocidin alone and in combinations with antibiotics induced formation of hydroxyl radicals. The oxidative stress was caused by a transient NADH depletion and the addition of thiourea prevented bacterial death, especially in the case of the combined treatment of pleurocidin and ampicillin showing synergisms. The combination of pleurocidin and erythromycin increased permeability of bacterial cytoplasmic membrane. Additionally, pleurocidin exhibited a potent inhibitory effect on preformed biofilm of bacterial organisms. In conclusion, pleurocidin synergized with antibiotics through hydroxyl radical formation and membrane-active mechanism, and exerted antibiofilm activity. GENERAL SIGNIFICANCE The synergistic effect between pleurocidin and antibiotics suggests the AMP is a potential therapeutic agent and adjuvant for antimicrobial chemotherapy.", "title": "Antimicrobial peptide pleurocidin synergizes with antibiotics through hydroxyl radical formation and membrane damage, and exerts antibiofilm activity." }, { "docid": "4381486", "text": "Stem cells are proposed to segregate chromosomes asymmetrically during self-renewing divisions so that older (‘immortal’) DNA strands are retained in daughter stem cells whereas newly synthesized strands segregate to differentiating cells. Stem cells are also proposed to retain DNA labels, such as 5-bromo-2-deoxyuridine (BrdU), either because they segregate chromosomes asymmetrically or because they divide slowly. However, the purity of stem cells among BrdU-label-retaining cells has not been documented in any tissue, and the ‘immortal strand hypothesis’ has not been tested in a system with definitive stem cell markers. Here we tested these hypotheses in haematopoietic stem cells (HSCs), which can be highly purified using well characterized markers. We administered BrdU to newborn mice, mice treated with cyclophosphamide and granulocyte colony-stimulating factor, and normal adult mice for 4 to 10 days, followed by 70 days without BrdU. In each case, less than 6% of HSCs retained BrdU and less than 0.5% of all BrdU-retaining haematopoietic cells were HSCs, revealing that BrdU has poor specificity and poor sensitivity as an HSC marker. Sequential administration of 5-chloro-2-deoxyuridine and 5-iodo-2-deoxyuridine indicated that all HSCs segregate their chromosomes randomly. Division of individual HSCs in culture revealed no asymmetric segregation of the label. Thus, HSCs cannot be identified on the basis of BrdU-label retention and do not retain older DNA strands during division, indicating that these are not general properties of stem cells.", "title": "Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU" }, { "docid": "16939583", "text": "Variation in cerebral cortex size and complexity is thought to contribute to differences in cognitive ability between humans and other animals. Here we compare cortical progenitor cell output in humans and three nonhuman primates using directed differentiation of pluripotent stem cells (PSCs) in adherent two-dimensional (2D) and organoid three-dimensional (3D) culture systems. Clonal lineage analysis showed that primate cortical progenitors proliferate for a protracted period of time, during which they generate early-born neurons, in contrast to rodents, where this expansion phase largely ceases before neurogenesis begins. The extent of this additional cortical progenitor expansion differs among primates, leading to differences in the number of neurons generated by each progenitor cell. We found that this mechanism for controlling cortical size is regulated cell autonomously in culture, suggesting that primate cerebral cortex size is regulated at least in part at the level of individual cortical progenitor cell clonal output.", "title": "2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size." }, { "docid": "30041340", "text": "BACKGROUND Histone deimination regulates gene function and contributes to antimicrobial response, allowing the formation of neutrophil extracellular traps (NETs). Deiminated proteins are target of anti-citrullinated peptides antibodies (ACPA) in rheumatoid arthritis (RA). OBJECTIVE The objective of this paper is to test the hypothesis that RA sera react with deiminated histones contained in NETs. METHODS Neutrophils from peripheral blood were stimulated with A23187 and acid treated; NETosis was induced by phorbol myristate acetate, and NET proteins were isolated. Sera were tested by immunoblot on acid extracted proteins from neutrophils and from NETs, and by ELISA on deiminated histone H4 or H4-derived peptides. Bands reactive with RA sera were excised from gels, digested with trypsin and subjected to matrix-assisted laser desorption/ionisation time of flight (MALDI-TOF) analysis, before and after derivatisation to detect citrullinated peptides. RESULTS RA sera reacted with a deiminated antigen of 11 KDa from activated neutrophils, recognised also by anti-H4 and antideiminated H4 antibodies. A similar reactivity was observed with NET proteins. The antigen from neutrophils or NETs was identified as citrullinated H4 by MALDI-TOF analysis. By ELISA, RA sera bound in vitro citrullinated H4. Citrullinated H4 14-34 and 31-50 peptides detected antibodies in 67% and 63% of RA sera and in less than 5% of controls; antibody titre was correlated with anti-CCP2. CONCLUSIONS Citrullinated H4 from activated neutrophils and NETs is a target of antibodies in RA, and synthetic citrullinated H4-derived peptides are a new substrate for ACPA detection. As NETosis can generate antigens for ACPA, these data suggest a novel connection between innate and adaptive immunity in RA.", "title": "Antibodies from patients with rheumatoid arthritis target citrullinated histone 4 contained in neutrophils extracellular traps." } ]
788
Microcin J25 inhibits nucleoside triphosphate (NTP) binding.
[ { "docid": "4740447", "text": "The antibacterial peptide microcin J25 (MccJ25) inhibits transcription by bacterial RNA polymerase (RNAP). Biochemical results indicate that inhibition of transcription occurs at the level of NTP uptake or NTP binding by RNAP. Genetic results indicate that inhibition of transcription requires an extensive determinant, comprising more than 50 amino acid residues, within the RNAP secondary channel (also known as the \"NTP-uptake channel\" or \"pore\"). Biophysical results indicate that inhibition of transcription involves binding of MccJ25 within the RNAP secondary channel. Molecular modeling indicates that binding of MccJ25 within the RNAP secondary channel obstructs the RNAP secondary channel. We conclude that MccJ25 inhibits transcription by binding within and obstructing the RNAP secondary channel--acting essentially as a \"cork in a bottle. \" Obstruction of the RNAP secondary channel represents an attractive target for drug discovery.", "title": "Antibacterial peptide microcin J25 inhibits transcription by binding within and obstructing the RNA polymerase secondary channel." } ]
[ { "docid": "4393153", "text": "RNA polymerase (Pol) II catalyses DNA-dependent RNA synthesis during gene transcription. There is, however, evidence that Pol II also possesses RNA-dependent RNA polymerase (RdRP) activity. Pol II can use a homopolymeric RNA template, can extend RNA by several nucleotides in the absence of DNA, and has been implicated in the replication of the RNA genomes of hepatitis delta virus (HDV) and plant viroids. Here we show the intrinsic RdRP activity of Pol II with only pure polymerase, an RNA template–product scaffold and nucleoside triphosphates (NTPs). Crystallography reveals the template–product duplex in the site occupied by the DNA–RNA hybrid during transcription. RdRP activity resides at the active site used during transcription, but it is slower and less processive than DNA-dependent activity. RdRP activity is also obtained with part of the HDV antigenome. The complex of transcription factor IIS (TFIIS) with Pol II can cleave one HDV strand, create a reactive stem-loop in the hybrid site, and extend the new RNA 3′ end. Short RNA stem-loops with a 5′ extension suffice for activity, but their growth to a critical length apparently impairs processivity. The RdRP activity of Pol II provides a missing link in molecular evolution, because it suggests that Pol II evolved from an ancient replicase that duplicated RNA genomes.", "title": "Molecular basis of RNA-dependent RNA polymerase II activity" }, { "docid": "25014337", "text": "We previously identified a rare mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), I132M, which confers high-level resistance to the nonnucleoside RT inhibitors (NNRTIs) nevirapine and delavirdine. In this study, we have further characterized the role of this mutation in viral replication capacity and in resistance to other RT inhibitors. Surprisingly, our data show that I132M confers marked hypersusceptibility to the nucleoside analogs lamivudine (3TC) and tenofovir at both the virus and enzyme levels. Subunit-selective mutagenesis studies revealed that the mutation in the p51 subunit of RT was responsible for the increased sensitivity to the drugs, and transient kinetic analyses showed that this hypersusceptibility was due to I132M decreasing the enzyme's affinity for the natural dCTP substrate but increasing its affinity for 3TC-triphosphate. Furthermore, the replication capacity of HIV-1 containing I132M is severely impaired. This decrease in viral replication capacity could be partially or completely compensated for by the A62V or L214I mutation, respectively. Taken together, these results help to explain the infrequent selection of I132M in patients for whom NNRTI regimens are failing and furthermore demonstrate that a single mutation outside of the polymerase active site and inside of the p51 subunit of RT can significantly influence nucleotide selectivity.", "title": "The human immunodeficiency virus type 1 nonnucleoside reverse transcriptase inhibitor resistance mutation I132M confers hypersensitivity to nucleoside analogs." }, { "docid": "393001", "text": "A human placental soluble \"high Km\" 5'-nucleotidase has been separated from \"low Km\" 5'-nucleotidase and nonspecific phosphatase by AMP-Sepharose affinity chromatography. The enzyme was purified 8000-fold to a specific activity of 25.6 mumol/min/mg. The subunit molecular mass is 53 kDa, and the native molecular mass is 210 kDa, suggesting a tetrameric structure. Soluble high Km 5'-nucleotidase is most active with IMP and GMP and their deoxy derivatives. IMP is hydrolyzed 15 times faster than AMP. The enzyme has a virtually absolute requirement for magnesium ions and is regulated by them. Purine nucleoside 5'-triphosphates strongly activate the enzyme with the potency order dATP greater than ATP greater than GTP. 2,3-Diphosphoglycerate activates the enzyme as potently as ATP. Three millimolar ATP decreased the Km for IMP from 0.33 to 0.09 mM and increased the Vmax 12-fold. ATP activation was modified by the IMP concentration. At 20 microM IMP the ATP-dependent activation curve was sigmoidal, while at 2 mM IMP it was hyperbolic. The A0.5 values for ATP were 2.26 and 0.70 mM, and the relative maximal velocities were 32.9 and 126.0 nmol/min, respectively. Inorganic phosphate shifts the hyperbolic substrate velocity relationship for IMP to a sigmoidal one. With physiological concentrations of cofactors (3 mM ATP, 1-4 mM Pi, 150 mM KCl) at pH 7.4, the enzyme is 25-35 times more active toward 100 microM IMP than 100 microM AMP. These data show that: (a) soluble human placental high Km 5'-nucleotidase coexists in human placenta with the low Km enzyme; (b) under physiological conditions the enzyme favors the hydrolysis of IMP and is critically regulated by IMP, ATP, and Pi levels; and (c) kinetic properties of ATP and IMP are each modified by the other compound suggesting complex interaction of the associated binding sites.", "title": "High Km soluble 5'-nucleotidase from human placenta. Properties and allosteric regulation by IMP and ATP." }, { "docid": "25543207", "text": "Platelet inhibitors are the mainstay treatment for patients with vascular diseases. The current 'gold standard' antiplatelet agent clopidogrel has several pharmacological and clinical limitations that have prompted the search for more effective platelet antagonists. The candidates include various blockers of the purinergic P2Y12 receptor such as prasugrel, an oral irreversible thienopyridine; two adenosine triphosphate analogues that bind reversibly to the P2Y12 receptor: ticagrelor (oral) and cangrelor (intravenous); elinogrel, a direct-acting reversible P2Y12 receptor inhibitor (the only antiplatelet compound that can be administered both intravenously and orally); BX 667, an orally active and reversible small-molecule P2Y12 receptor antagonist; SCH 530348, SCH 205831, SCH 602539 and E5555, highly selective and orally active antagonists on the protease-activated receptor 1. A number of drugs also hit new targets: terutroban, an oral, selective and specific inhibitor of the thromboxane receptor; ARC1779, a second-generation, nuclease resistant aptamer which inhibits von Willebrand factor-dependent platelet aggregation; ALX-0081, a bivalent humanized nanobody targeting the GPIb binding site of von Willebrand factor and AJW200, an IgG4 monoclonal antibody of von Willebrand factor. The pharmacology and clinical profiles of new platelet antagonists indicate that they provide more consistent, more rapid and more potent platelet inhibition than agents currently used. Whether these potential advantages will translate into clinical advantages will require additional comparisons in properly powered, randomized, controlled trials.", "title": "Pharmacokinetic, pharmacodynamic and clinical profile of novel antiplatelet drugs targeting vascular diseases." }, { "docid": "21186109", "text": "Low case detection rates of new smear-positive pulmonary tuberculosis (PTB) patients globally are a cause for concern. The aim of this study was to determine for patients registered for TB in Malawi the number and percentage who lived in a neighbouring country and the registration, recording and reporting practices for these 'foreign' patients. All 44 non-private hospitals, which register and treat all TB patients in the public health sector in Malawi, were visited. Ten (23%) hospitals in 2001 and 14 (32%) in 2002 maintained a separate register for cross-border TB cases. Patients recorded in these registers were not formally reported to the Malawi National TB Programme (NTP), the neighbouring country's NTP, nor to WHO. They therefore constitute missing cases. In Malawi, the number of cross-border new smear-positive PTB cases was 77 in 2001 and 91 in 2002, constituting about 3% of missing smear-positive cases in those hospitals that maintain cross-border registers and about 1% of missing cases nationally.", "title": "The missing cases of tuberculosis in Malawi: the contribution from cross-border registrations." }, { "docid": "6426919", "text": "Recently, mutations in the connection subdomain (CN) and RNase H domain of HIV-1 reverse transcriptase (RT) were observed to exhibit dual resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs). To elucidate the mechanism by which CN and RH mutations confer resistance to NNRTIs, we hypothesized that these mutations reduce RNase H cleavage and provide more time for the NNRTI to dissociate from the RT, resulting in the resumption of DNA synthesis and enhanced NNRTI resistance. We observed that the effect of the reduction in RNase H cleavage on NNRTI resistance is dependent upon the affinity of each NNRTI to the RT and further influenced by the presence of NNRTI-binding pocket (BP) mutants. D549N, Q475A, and Y501A mutants, which reduce RNase H cleavage, enhance resistance to nevirapine (NVP) and delavirdine (DLV), but not to efavirenz (EFV) and etravirine (ETR), consistent with their increase in affinity for RT. Combining the D549N mutant with NNRTI BP mutants further increases NNRTI resistance from 3- to 30-fold, supporting the role of NNRTI-RT affinity in our NNRTI resistance model. We also demonstrated that CNs from treatment-experienced patients, previously reported to enhance NRTI resistance, also reduce RNase H cleavage and enhance NNRTI resistance in the context of the patient RT pol domain or a wild-type pol domain. Together, these results confirm key predictions of our NNRTI resistance model and provide support for a unifying mechanism by which CN and RH mutations can exhibit dual NRTI and NNRTI resistance.", "title": "A novel molecular mechanism of dual resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors." }, { "docid": "15419873", "text": "Retinoic acid inducible-gene I (RIG-I) is a cytosolic multidomain protein that detects viral RNA and elicits an antiviral immune response. Two N-terminal caspase activation and recruitment domains (CARDs) transmit the signal, and the regulatory domain prevents signaling in the absence of viral RNA. 5'-triphosphate and double-stranded RNA (dsRNA) are two molecular patterns that enable RIG-I to discriminate pathogenic from self-RNA. However, the function of the DExH box helicase domain that is also required for activity is less clear. Using single-molecule protein-induced fluorescence enhancement, we discovered a robust adenosine 5'-triphosphate-powered dsRNA translocation activity of RIG-I. The CARDs dramatically suppress translocation in the absence of 5'-triphosphate, and the activation by 5'-triphosphate triggers RIG-I to translocate preferentially on dsRNA in cis. This functional integration of two RNA molecular patterns may provide a means to specifically sense and counteract replicating viruses.", "title": "Cytosolic viral sensor RIG-I is a 5'-triphosphate-dependent translocase on double-stranded RNA." }, { "docid": "4402497", "text": "Innate immune defences are essential for the control of virus infection and are triggered through host recognition of viral macromolecular motifs known as pathogen-associated molecular patterns (PAMPs). Hepatitis C virus (HCV) is an RNA virus that replicates in the liver, and infects 200 million people worldwide. Infection is regulated by hepatic immune defences triggered by the cellular RIG-I helicase. RIG-I binds PAMP RNA and signals interferon regulatory factor 3 activation to induce the expression of interferon-α/β and antiviral/interferon-stimulated genes (ISGs) that limit infection. Here we identify the polyuridine motif of the HCV genome 3′ non-translated region and its replication intermediate as the PAMP substrate of RIG-I, and show that this and similar homopolyuridine or homopolyriboadenine motifs present in the genomes of RNA viruses are the chief feature of RIG-I recognition and immune triggering in human and murine cells. 5′ terminal triphosphate on the PAMP RNA was necessary but not sufficient for RIG-I binding, which was primarily dependent on homopolymeric ribonucleotide composition, linear structure and length. The HCV PAMP RNA stimulated RIG-I-dependent signalling to induce a hepatic innate immune response in vivo, and triggered interferon and ISG expression to suppress HCV infection in vitro. These results provide a conceptual advance by defining specific homopolymeric RNA motifs within the genome of HCV and other RNA viruses as the PAMP substrate of RIG-I, and demonstrate immunogenic features of the PAMP–RIG-I interaction that could be used as an immune adjuvant for vaccine and immunotherapy approaches.", "title": "Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA" }, { "docid": "2991954", "text": "Production of Ran-guanosine triphosphate (GTP) around chromosomes induces local nucleation and plus end stabilization of microtubules (MTs). The nuclear protein TPX2 is required for RanGTP-dependent MT nucleation. To find the MT stabilizer, we affinity purify nuclear localization signal (NLS)-containing proteins from Xenopus laevis egg extracts. This NLS protein fraction contains the MT stabilization activity. After further purification, we used mass spectrometry to identify proteins in active fractions, including cyclin-dependent kinase 11 (Cdk11). Cdk11 localizes on spindle poles and MTs in Xenopus culture cells and egg extracts. Recombinant Cdk11 demonstrates RanGTP-dependent MT stabilization activity, whereas a kinase-dead mutant does not. Inactivation of Cdk11 in egg extracts blocks RanGTP-dependent MT stabilization and dramatically decreases the spindle assembly rate. Simultaneous depletion of TPX2 completely inhibits centrosome-dependent spindle assembly. Our results indicate that Cdk11 is responsible for RanGTP-dependent MT stabilization around chromosomes and that this local stabilization is essential for normal rates of spindle assembly and spindle function.", "title": "Cdk11 is a RanGTP-dependent microtubule stabilization factor that regulates spindle assembly rate" }, { "docid": "2319305", "text": "Drug resistance-associated mutations in HIV-1 reverse transcriptase (RT) can affect the balance between polymerase and ribonuclease H (RNase H) activities of the enzyme. We have recently demonstrated that the N348I mutation in the connection domain causes selective dissociation from RNase H-competent complexes, whereas the functional integrity of the polymerase-competent complex remains largely unaffected. N348I has been associated with resistance to the non-nucleoside RT inhibitor (NNRTI), nevirapine; however, a possible mechanism that links changes in RNase H activity to changes in NNRTI susceptibility remains to be established. To address this problem, we consider recent findings suggesting that NNRTIs may affect the orientation of RT on its nucleic acid substrate and increase RNase H activity. Here we demonstrate that RNase H-mediated primer removal is indeed more efficient in the presence of NNRTIs; however, the N348I mutant enzyme is able to counteract this effect. Efavirenz, a tight binding inhibitor, restricts the influence of the mutation. These findings provide strong evidence to suggest that N348I can thwart the inhibitory effects of nevirapine during initiation of (+)-strand DNA synthesis, which provides a novel mechanism for resistance. The data are in agreement with clinical data, which demonstrate a stronger effect of N348I on susceptibility to nevirapine as compared with efavirenz.", "title": "N348I in HIV-1 reverse transcriptase can counteract the nevirapine-mediated bias toward RNase H cleavage during plus-strand initiation." }, { "docid": "6421792", "text": "Acute lymphoblastic leukemia (ALL) is an aggressive hematological tumor resulting from the malignant transformation of lymphoid progenitors. Despite intensive chemotherapy, 20% of pediatric patients and over 50% of adult patients with ALL do not achieve a complete remission or relapse after intensified chemotherapy, making disease relapse and resistance to therapy the most substantial challenge in the treatment of this disease. Using whole-exome sequencing, we identify mutations in the cytosolic 5'-nucleotidase II gene (NT5C2), which encodes a 5'-nucleotidase enzyme that is responsible for the inactivation of nucleoside-analog chemotherapy drugs, in 20/103 (19%) relapse T cell ALLs and 1/35 (3%) relapse B-precursor ALLs. NT5C2 mutant proteins show increased nucleotidase activity in vitro and conferred resistance to chemotherapy with 6-mercaptopurine and 6-thioguanine when expressed in ALL lymphoblasts. These results support a prominent role for activating mutations in NT5C2 and increased nucleoside-analog metabolism in disease progression and chemotherapy resistance in ALL.", "title": "Activating mutations in the NT5C2 nucleotidase gene drive chemotherapy resistance in relapsed ALL" }, { "docid": "1569031", "text": "The chemical identity and integrity of the genome is challenged by the incorporation of ribonucleoside triphosphates (rNTPs) in place of deoxyribonucleoside triphosphates (dNTPs) during replication. Misincorporation is limited by the selectivity of DNA replicases. We show that accumulation of ribonucleoside monophosphates (rNMPs) in the genome causes replication stress and has toxic consequences, particularly in the absence of RNase H1 and RNase H2, which remove rNMPs. We demonstrate that postreplication repair (PRR) pathways-MMS2-dependent template switch and Pol ζ-dependent bypass-are crucial for tolerating the presence of rNMPs in the chromosomes; indeed, we show that Pol ζ efficiently replicates over 1-4 rNMPs. Moreover, cells lacking RNase H accumulate mono- and polyubiquitylated PCNA and have a constitutively activated PRR. Our findings describe a crucial function for RNase H1, RNase H2, template switch, and translesion DNA synthesis in overcoming rNTPs misincorporated during DNA replication, and may be relevant for the pathogenesis of Aicardi-Goutières syndrome.", "title": "RNase H and Postreplication Repair Protect Cells from Ribonucleotides Incorporated in DNA" }, { "docid": "20996244", "text": "Productive infection by human immunodeficiency virus type 1 (HIV-1) requires the activation of target cells. Infection of quiescent peripheral CD4 lymphocytes by HIV-1 results in incomplete, labile, reverse transcripts. We have previously identified G1b as the cell cycle stage required for the optimal completion of the reverse transcription process in T lymphocytes. However, the mechanism(s) involved in the blockage of reverse transcription remains undefined. In this study we investigated whether nucleotide levels influence viral reverse transcription in G0 cells. For this purpose the role of the enzyme ribonucleotide reductase was bypassed, by adding exogenous deoxyribonucleosides to highly purified T cells in the G0 or the G1a phase of the cell cycle. Our data showed a significant increase in the efficiency of the reverse transcription process following the addition of the deoxyribonucleosides. To define the stability and functionality of these full reverse transcripts, we used an HIV-1 reporter virus that expresses the murine heat-stable antigen on the surfaces of infected cells. Following activation of infected quiescent cells treated with exogenous nucleosides, no increased rescue of productive infection was seen. Thus, in addition to failure to complete reverse transcription, there was an additional nonreversible blockage of productive infection in quiescent T cells. These experiments have important relevance in the gene therapy arena, in terms of improving the ability of lentivirus vectors to enter metabolically inactive cells, such as hematopoietic stem cells.", "title": "Nonproductive human immunodeficiency virus type 1 infection in nucleoside-treated G0 lymphocytes." }, { "docid": "34498325", "text": "Transfer RNAs specific for Gln, Lys, and Glu from all organisms (except Mycoplasma) and organelles have a 2-thiouridine derivative (xm(5)s(2)U) as wobble nucleoside. These tRNAs read the A- and G-ending codons in the split codon boxes His/Gln, Asn/Lys, and Asp/Glu. In eukaryotic cytoplasmic tRNAs the conserved constituent (xm(5)-) in position 5 of uridine is 5-methoxycarbonylmethyl (mcm(5)). A protein (Tuc1p) from yeast resembling the bacterial protein TtcA, which is required for the synthesis of 2-thiocytidine in position 32 of the tRNA, was shown instead to be required for the synthesis of 2-thiouridine in the wobble position (position 34). Apparently, an ancient member of the TtcA family has evolved to thiolate U34 in tRNAs of organisms from the domains Eukarya and Archaea. Deletion of the TUC1 gene together with a deletion of the ELP3 gene, which results in the lack of the mcm(5) side chain, removes all modifications from the wobble uridine derivatives of the cytoplasmic tRNAs specific for Gln, Lys, and Glu, and is lethal to the cell. Since excess of the unmodified form of these three tRNAs rescued the double mutant elp3 tuc1, the primary function of mcm(5)s(2)U34 seems to be to improve the efficiency to read the cognate codons rather than to prevent mis-sense errors. Surprisingly, overexpression of the mcm(5)s(2)U-lacking tRNA(Lys) alone was sufficient to restore viability of the double mutant.", "title": "A conserved modified wobble nucleoside (mcm5s2U) in lysyl-tRNA is required for viability in yeast." }, { "docid": "984825", "text": "Post-transcriptional modification of RNA nucleosides occurs in all living organisms. Pseudouridine, the most abundant modified nucleoside in non-coding RNAs, enhances the function of transfer RNA and ribosomal RNA by stabilizing the RNA structure. Messenger RNAs were not known to contain pseudouridine, but artificial pseudouridylation dramatically affects mRNA function--it changes the genetic code by facilitating non-canonical base pairing in the ribosome decoding centre. However, without evidence of naturally occurring mRNA pseudouridylation, its physiological relevance was unclear. Here we present a comprehensive analysis of pseudouridylation in Saccharomyces cerevisiae and human RNAs using Pseudo-seq, a genome-wide, single-nucleotide-resolution method for pseudouridine identification. Pseudo-seq accurately identifies known modification sites as well as many novel sites in non-coding RNAs, and reveals hundreds of pseudouridylated sites in mRNAs. Genetic analysis allowed us to assign most of the new modification sites to one of seven conserved pseudouridine synthases, Pus1-4, 6, 7 and 9. Notably, the majority of pseudouridines in mRNA are regulated in response to environmental signals, such as nutrient deprivation in yeast and serum starvation in human cells. These results suggest a mechanism for the rapid and regulated rewiring of the genetic code through inducible mRNA modifications. Our findings reveal unanticipated roles for pseudouridylation and provide a resource for identifying the targets of pseudouridine synthases implicated in human disease.", "title": "Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells" }, { "docid": "25251625", "text": "The use of caspase inhibitors has revealed the existence of alternative backup cell death programs for apoptosis. The broad-spectrum caspase inhibitor zVAD-fmk modulates the three major types of cell death. Addition of zVAD-fmk blocks apoptotic cell death, sensitizes cells to necrotic cell death, and induces autophagic cell death. Several studies have shown a crucial role for the kinase RIP1 and the adenosine nucleotide translocator (ANT)-cyclophilin D (CypD) complex in necrotic cell death. The underlying mechanism of zVAD-fmk-mediated sensitization to necrotic cell death involves the inhibition of caspase-8-mediated proteolysis of RIP1 and disturbance of the ANT-CypD interaction. RIP1 is also involved in autophagic cell death. Caspase inhibitors and knockdown studies have revealed negative roles for catalase and caspase-8 in autophagic cell death. The positive role of RIP1 and the negative role of caspase-8 in both necrotic and autophagic cell death suggest that the pathways of these two types of cell death are interconnected. Necrotic cell death represents a rapid cellular response involving mitochondrial reactive oxygen species (ROS) production, decreased adenosine triphosphate concentration, and other cellular insults, whereas autophagic cell death first starts as a survival attempt by cleaning up ROS-damaged mitochondria. However, when this process occurs in excess, autophagy itself becomes cytotoxic and eventually leads to autophagic cell death. A better understanding of the molecular mechanisms of these alternative cell death pathways may provide therapeutic tools to combat cell death associated with neurodegenerative diseases, ischemia-reperfusion pathologies, and infectious diseases, and may also facilitate the development of alternative cytotoxic strategies in cancer treatment.", "title": "Caspase inhibitors promote alternative cell death pathways." }, { "docid": "778436", "text": "The yeast transcriptional activator GAL4 binds specific sites on DNA to activate transcription of adjacent genes1–5. The distinct activating regions of GAL4 are rich in acidic residues and it has been suggested that these regions interact with another protein component of the transcriptional machinery (such as the TATA-binding protein or RNA polymerase II) while the DNA-binding region serves to position the activating region near the gene6,7,8. Here we show that various GAL4 derivatives, when expressed at high levels in yeast, inhibit transcription of certain genes lacking GAL4 binding sites, that more efficient activators inhibit more strongly and that inhibition does not depend on the DNA-binding domain. We suggest that this inhibition, which we call squelching, reflects titration of a transcription factor by the activating region of GAL4.", "title": "Negative effect of the transcriptional activator GAL4" }, { "docid": "14806256", "text": "CONTEXT Use of antiretroviral drugs, including protease inhibitors, for treatment of human immunodeficiency virus (HIV) infection has been anecdotally associated with hepatotoxicity, particularly in persons coinfected with hepatitis C or B virus. OBJECTIVES To ascertain if incidence of severe hepatotoxicity during antiretroviral therapy is similar for all antiretroviral drug combinations, and to define the role of chronic viral hepatitis in its development. DESIGN Prospective cohort study. SETTING University-based urban HIV clinic. PATIENTS A total of 298 patients who were prescribed new antiretroviral therapies between January 1996 and January 1998, 211 (71%) of whom received protease inhibitors as part of combination therapy (median follow-up, 182 days) and 87 (29%) of whom received dual nucleoside analog regimens (median follow-up, 167 days). Chronic hepatitis C and B virus infection was present in 154 (52%) and 8 (2.7%) patients, respectively. MAIN OUTCOME MEASURE Severe hepatotoxicity, defined as a grade 3 or 4 change in levels of serum alanine aminotransferase and aspartate aminotransferase, evaluated before and during therapy. RESULTS Severe hepatotoxicity was observed in 31 (10.4%) of 298 patients (95% confidence interval [CI], 7.2%-14.4%). Ritonavir use was associated with a higher incidence of toxicity (30%; 95% CI, 17.9% -44.6%). However, no significant difference was detected in hepatotoxicity incidence in other treatment groups, ie, nucleoside analogs (5.7%; 95% CI, 1.2%-12.9%), nelfinavir (5.9%; 95% CI, 1.2%-16.2%), saquinavir (5.9%; 95% CI, 0.15%-28.7%), and indinavir(6.8%; 95% CI, 3.0%-13.1 %). Although chronicviral hepatitis was associated with an increased risk of severe hepatotoxicity among patients prescribed nonritonavir regimens (relative risk, 3.7; 95% CI, 1.0-11.8), most patients with chronic hepatitis C or B virus infection (88%) did not experience significant toxic effects. Rate of severe toxicity with use of any protease inhibitor in patients with hepatitis C infection was 12.2% (13/107; 95% CI, 6.6%-19.9%). In multivariate logistic regression, only ritonavir (adjusted odds ratio [AOR], 8.6; 95% CI, 3.0-24.6) and a CD4 cell count increase of more than 0.05 x 10(9)/L (AOR, 3.6; 95% CI, 1.0-12.9) were associated with severe hepatotoxicity. No irreversible outcomes were seen in patients with severe hepatotoxicity. CONCLUSIONS Our data indicate that use of ritonavir may increase risk of severe hepatotoxicity. Although hepatotoxicity may be more common in persons with chronic viral hepatitis, these data do not support withholding protease inhibitor therapy from persons coinfected with hepatitis B or C virus.", "title": "Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection." }, { "docid": "8065561", "text": "Fluorometric titration of E. coli single-stranded DNA binding protein with various RNAs showed that the protein specifically and cooperatively binds to its own mRNA. The binding inhibited in vitro expression of ssb and bla but not nusA. This inhibition takes place at a physiological concentration of SSB. The function of the protein in gene regulation is discussed.", "title": "Specific and cooperative binding of E. coli single-stranded DNA binding protein to mRNA." }, { "docid": "40500438", "text": "Silibinin is a flavonoid with antihepatotoxic properties and pleiotropic anticancer capabilities. This study investigated silibinin inhibition of cell invasion by down-regulating matrix metalloproteinase-2 (MMP-2) expression, via attenuation of activator protein-1 (AP-1) in IL-6-stimulated LoVo colon cancer cells. Western blot data showed that the expression of MMP-2 protein was reduced 1.6- or 1.7-fold over the control by treatment with silibinin or JNK inhibitor in the models. Similar results were revealed in zymography and confocal microscopy. Pretreatment with silibinin also abolished the binding activity of AP-1 and MMP-2 promoter activity via AP-1 binding, as observed by EMSA and luciferase assay. Finally, a [(3)H]-thymidine incorporation proliferation assay and cell migration assay demonstrated that silibinin inhibited IL-6-stimulated LoVo cell proliferation and invasion. Taken together, these data indicated that silibinin inhibits LoVo cell invasion with the reduction of MMP-2 presentation by attenuating AP-1 binding activity, suggesting a novel antimetastatic application for silibinin in colon cancer chemoprevention.", "title": "Silibinin inhibits the invasion of IL-6-stimulated colon cancer cells via selective JNK/AP-1/MMP-2 modulation in vitro." }, { "docid": "4425507", "text": "Since it was discovered that the anti-hypertensive agent ifenprodil has neuroprotective activity through its effects on NMDA (N-methyl-D-aspartate) receptors, a determined effort has been made to understand the mechanism of action and to develop improved therapeutic compounds on the basis of this knowledge. Neurotransmission mediated by NMDA receptors is essential for basic brain development and function. These receptors form heteromeric ion channels and become activated after concurrent binding of glycine and glutamate to the GluN1 and GluN2 subunits, respectively. A functional hallmark of NMDA receptors is that their ion-channel activity is allosterically regulated by binding of small compounds to the amino-terminal domain (ATD) in a subtype-specific manner. Ifenprodil and related phenylethanolamine compounds, which specifically inhibit GluN1 and GluN2B NMDA receptors, have been intensely studied for their potential use in the treatment of various neurological disorders and diseases, including depression, Alzheimer's disease and Parkinson's disease. Despite considerable enthusiasm, mechanisms underlying the recognition of phenylethanolamines and ATD-mediated allosteric inhibition remain limited owing to a lack of structural information. Here we report that the GluN1 and GluN2B ATDs form a heterodimer and that phenylethanolamine binds at the interface between GluN1 and GluN2B, rather than within the GluN2B cleft. The crystal structure of the heterodimer formed between the GluN1b ATD from Xenopus laevis and the GluN2B ATD from Rattus norvegicus shows a highly distinct pattern of subunit arrangement that is different from the arrangements observed in homodimeric non-NMDA receptors and reveals the molecular determinants for phenylethanolamine binding. Restriction of domain movement in the bi-lobed structure of the GluN2B ATD, by engineering of an inter-subunit disulphide bond, markedly decreases sensitivity to ifenprodil, indicating that conformational freedom in the GluN2B ATD is essential for ifenprodil-mediated allosteric inhibition of NMDA receptors. These findings pave the way for improving the design of subtype-specific compounds with therapeutic value for neurological disorders and diseases.", "title": "Subunit Arrangement and Phenylethanolamine Binding in GluN1/GluN2B NMDA Receptors" }, { "docid": "23440856", "text": "The type VI secretion system (T6SS) is the most prevalent bacterial secretion system and an important virulence mechanism utilized by Gram-negative bacteria, either to target eukaryotic cells or to combat other microbes. The components show much variability, but some appear essential for the function, and two homologues, denoted VipA and VipB in Vibrio cholerae, have been identified in all T6SSs described so far. Secretion is dependent on binding of an α-helical region of VipA to VipB, and in the absence of this binding, both components are degraded within minutes and secretion is ceased. The aim of the study was to investigate if this interaction could be blocked, and we hypothesized that such inhibition would lead to abrogation of T6S. A library of 9,600 small-molecule compounds was screened for their ability to block the binding of VipA-VipB in a bacterial two-hybrid system (B2H). After excluding compounds that showed cytotoxicity toward eukaryotic cells, that inhibited growth of Vibrio, or that inhibited an unrelated B2H interaction, 34 compounds were further investigated for effects on the T6SS-dependent secretion of hemolysin-coregulated protein (Hcp) or of phospholipase A1 activity. Two compounds, KS100 and KS200, showed intermediate or strong effects in both assays. Analogues were obtained, and compounds with potent inhibitory effects in the assays and desirable physicochemical properties as predicted by in silico analysis were identified. Since the compounds specifically target a virulence mechanism without affecting bacterial replication, they have the potential to mitigate the virulence with minimal risk for development of resistance.", "title": "Screening for inhibition of Vibrio cholerae VipA-VipB interaction identifies small-molecule compounds active against type VI secretion." }, { "docid": "9881829", "text": "The conserved histone variant H2AZ has an important role in the regulation of gene expression and the establishment of a buffer to the spread of silent heterochromatin. How histone variants such as H2AZ are incorporated into nucleosomes has been obscure. We have found that Swr1, a Swi2/Snf2-related adenosine triphosphatase, is the catalytic core of a multisubunit, histone-variant exchanger that efficiently replaces conventional histone H2A with histone H2AZ in nucleosome arrays. Swr1 is required for the deposition of histone H2AZ at specific chromosome locations in vivo, and Swr1 and H2AZ commonly regulate a subset of yeast genes. These findings define a previously unknown role for the adenosine triphosphate-dependent chromatin remodeling machinery.", "title": "ATP-driven exchange of histone H2AZ variant catalyzed by SWR1 chromatin remodeling complex." }, { "docid": "15548965", "text": "Ionotropic glutamate receptor (iGluR) subunits contain a large N-terminal domain (NTD) that precedes the agonist-binding domain (ABD) and participates in subunit oligomerization. In NMDA receptors (NMDARs), the NTDs of NR2A and NR2B subunits also form binding sites for the endogenous inhibitor Zn(2+) ion. Although these allosteric sites have been characterized in detail, the molecular mechanisms by which the NTDs communicate with the rest of the receptor to promote its inhibition remain unknown. Here, we identify the ABD dimer interface as a major structural determinant that permits coupling between the NTDs and the channel gate. The strength of this interface also controls proton inhibition, another form of allosteric modulation of NMDARs. Conformational rearrangements at the ABD dimer interface thus appear to be a key mechanism conserved in all iGluR subfamilies, but have evolved to fulfill different functions: fast desensitization at AMPA and kainate receptors, allosteric inhibition at NMDARs.", "title": "Structural Rearrangements of NR1/NR2A NMDA Receptors during Allosteric Inhibition" }, { "docid": "4320424", "text": "The KRAS oncogene product is considered a major target in anticancer drug discovery. However, direct interference with KRAS signalling has not yet led to clinically useful drugs. Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ, which sustains the spatial organization of KRAS by facilitating its diffusion in the cytoplasm. Here we report that interfering with binding of mammalian PDEδ to KRAS by means of small molecules provides a novel opportunity to suppress oncogenic RAS signalling by altering its localization to endomembranes. Biochemical screening and subsequent structure-based hit optimization yielded inhibitors of the KRAS–PDEδ interaction that selectively bind to the prenyl-binding pocket of PDEδ with nanomolar affinity, inhibit oncogenic RAS signalling and suppress in vitro and in vivo proliferation of human pancreatic ductal adenocarcinoma cells that are dependent on oncogenic KRAS. Our findings may inspire novel drug discovery efforts aimed at the development of drugs targeting oncogenic RAS.", "title": "Small molecule inhibition of the KRAS–PDEδ interaction impairs oncogenic KRAS signalling" }, { "docid": "14380875", "text": "Glucocorticoids repress NFkappaB-mediated activation of proinflammatory genes such as interleukin-8 (IL-8) and ICAM-1. Our experiments suggest that the glucocorticoid receptor (GR) confers this effect by associating through protein-protein interactions with NFkappaB bound at each of these genes. That is, we show that the GR zinc binding region (ZBR), which includes the DNA binding and dimerization functions of the receptor, binds directly to the dimerization domain of the RelA subunit of NFkappaB in vitro and that the ZBR is sufficient to associate with RelA bound at NFkappaB response elements in vivo. Moreover, we demonstrate in vivo and in vitro that GR does not disrupt DNA binding by NFkappaB. In transient transfections, we found that the GR ligand binding domain is essential for repression of NFkappaB but not for association with it and that GR can repress an NFkappaB derivative bearing a heterologous activation domain. We used chromatin immunoprecipitation assays in untransfected A549 cells to infer the mechanism by which the tethered GR represses NFkappaB-activated transcription. As expected, we found that the inflammatory signal TNFalpha stimulated preinitiation complex (PIC) assembly at the IL-8 and ICAM-1 promoters and that the largest subunit of RNA polymerase II (pol II) in those complexes became phosphorylated at serines 2 and 5 in its carboxy-terminal domain (CTD) heptapeptide repeats (YSPTSPS); these modifications are required for transcription initiation. Remarkably, GR did not inhibit PIC assembly under repressing conditions, but rather interfered with phosphorylation of serine 2 of the pol II CTD.", "title": "The Glucocorticoid Receptor Inhibits" }, { "docid": "20428155", "text": "Various active anticancer agents are derived from plants and terrestrial microorganisms. The isolation of C-nucleosides from the Caribbean sponge, Cryptotheca crypta, four decades ago, provided the basis for the synthesis of cytarabine, the first marine-derived anticancer agent to be developed for clinical use. Cytarabine is currently used in the routine treatment of patients with leukaemia and lymphoma. Gemcitabine, one of its fluorinated derivatives, has also been approved for use in patients with pancreatic, breast, bladder, and non-small-cell lung cancer. Over the past decade, several new experimental anticancer agents derived from marine sources have entered preclinical and clinical trials. This field has expanded significantly as a result of improvements in the technology of deep-sea collection, extraction, and large-scale production through aquaculture and synthesis. In this paper, examples of marine-derived experimental agents that are currently undergoing preclinical and early clinical evaluation are briefly discussed. A summary of the available information on the results of phase I and II trials of agents such as aplidine, ecteinascidin-734 (ET-734), dolastatin 10 and bryostatin 1 is also presented.", "title": "Marine organisms as a source of new anticancer agents." }, { "docid": "641786", "text": "Relapsed childhood acute lymphoblastic leukemia (ALL) carries a poor prognosis, despite intensive retreatment, owing to intrinsic drug resistance. The biological pathways that mediate resistance are unknown. Here, we report the transcriptome profiles of matched diagnosis and relapse bone marrow specimens from ten individuals with pediatric B-lymphoblastic leukemia using RNA sequencing. Transcriptome sequencing identified 20 newly acquired, novel nonsynonymous mutations not present at initial diagnosis, with 2 individuals harboring relapse-specific mutations in the same gene, NT5C2, encoding a 5'-nucleotidase. Full-exon sequencing of NT5C2 was completed in 61 further relapse specimens, identifying additional mutations in 5 cases. Enzymatic analysis of mutant proteins showed that base substitutions conferred increased enzymatic activity and resistance to treatment with nucleoside analog therapies. Clinically, all individuals who harbored NT5C2 mutations relapsed early, within 36 months of initial diagnosis (P = 0.03). These results suggest that mutations in NT5C2 are associated with the outgrowth of drug-resistant clones in ALL.", "title": "Relapse specific mutations in NT5C2 in childhood acute lymphoblastic leukemia" }, { "docid": "20620012", "text": "Through phosphorylation, protein kinases can alter the activity, localization, protein association, and stability of their targets. Despite the importance to our understanding of all aspects of cell biology, progress toward identifying bona fide substrates of specific protein kinases has been slow. Traditionally used techniques to identify true kinase substrates, such as genetics, yeast two-hybrid screens, and biochemical purification, are often laborious and unreliable. However, several new approaches have recently been developed and used successfully to identify genuine in vivo substrates of certain protein kinases. These methods include screening for phosphorylation of proteins from phage expression libraries, peptide library screens to determine optimal motifs favored by specific kinases, the use of phospho-motif antibodies, and an approach that uses structurally altered kinases and allele-specific adenosine triphosphate analogs and kinase inhibitors. We describe these approaches and discuss their utility and inherent caveats.", "title": "Hitting the target: emerging technologies in the search for kinase substrates." }, { "docid": "36464673", "text": "We show that, in vitro, Ca2+-dependent protein kinase C (PKC) phosphorylates recombinant murine p53 protein on several residues contained within a conserved basic region of 25 amino acids, located in the C-terminal part of the protein. Accordingly, synthetic p53-(357-381)-peptide is phosphorylated by PKC at multiple Ser and Thr residues, including Ser360, Thr365, Ser370 and Thr377. We also establish that p53-(357-381)-peptide at micromolar concentrations has the ability to stimulate sequence-specific DNA binding by p53. That stimulation is lost upon phosphorylation by PKC. To further characterise the mechanisms that regulate PKC-dependent phosphorylation of p53-(357-381)-peptide, the phosphorylation of recombinant p53 and p53-(357-381)-peptide by PKC were compared. The results suggest that phosphorylation of full-length p53 on the C-terminal PKC sites is highly dependent on the accessibility of the phosphorylation sites and that a domain on p53 distinct from p53-(357-381)-peptide is involved in binding PKC. Accordingly, we have identified a conserved 27-amino-acid peptide, p53-(320-346)-peptide, within the C-terminal region of p53 and adjacent to residues 357-381 that interacts with PKC in vitro. The interaction between p53-(320-346)-peptide and PKC inhibits PKC autophosphorylation and the phosphorylation of substrates, including p53-(357-381)-peptide, neurogranin and histone H1. Conventional Ca2+-dependent PKC alpha, beta and gamma and the catalytic fragment of PKC (PKM) were nearly equally susceptible to inhibition by p53-(320-346)-peptide. The Ca2+-independent PKC delta was much less sensitive to inhibition. The significance of these findings for understanding the in vivo phosphorylation of p53 by PKC are discussed.", "title": "The in vitro phosphorylation of p53 by calcium-dependent protein kinase C--characterization of a protein-kinase-C-binding site on p53." } ]
1453
West Hollywood, California is a city.
[ { "docid": "West_Hollywood,_California", "text": "West Hollywood , occasionally referred to locally as WeHo ( -LSB- ˈwiːhoʊ -RSB- ) , is a city in Los Angeles County , California , United States . Incorporated in 1984 , it is home to the Sunset Strip . As of the 2010 census , its population was 34,399 . It is considered one of the most prominent gay villages in the United States .", "title": "" } ]
[ { "docid": "West_Hollywood_(disambiguation)", "text": "West Hollywood may refer to : West Hollywood , California ; a city in Los Angeles County , California West Hollywood , Hollywood , Florida ; a neighborhood within the city limits of Hollywood , Florida", "title": "" }, { "docid": "John_Heilman", "text": "John Heilman is an American municipal politician and frequent mayor of West Hollywood , California . A native of Cleveland , Ohio , Heilman moved to Southern California to attend the University of Southern California Law School . Heilman was active in the incorporation of the City of West Hollywood . He was elected to the City 's first City Council in November 1984 and has served continuously since then . John Heilman was chosen as the City 's second Mayor in 1985 , and also served as Mayor in 1990 , 1995 , 1999 , 2001 and 2006 . He began his most recent turn as Mayor in April 2010 . Since his earliest days on the City Council , one of Heilman 's main concerns has been domestic partner rights . Heilman was instrumental in the establishment of West Hollywood 's domestic partnership registration program that permitted city employee partners to register and obtain domestic partner benefits for same-sex couples and seniors , regardless of gender , who are at least 62.5 years old and living together . Heilman is a past board member of the American Civil Liberties Union of Southern California . Openly gay , Heilman is also the past president of the Gay , Lesbian and Bisexual Local Officials Group and past co-chair of the International Network of Lesbian and Gay Officials . His 2007 re-election campaign has won the support of the Gay & Lesbian Victory Fund . He holds an active membership of the Stonewall Democratic Club . Heilman is also a member of the Coalition for Economic Survival . As a result of Heilman 's leadership on the issue of AIDS , he received the U.S. Conference of Mayor 's Award in 1990 . John Heilman is an avid runner and was responsible for bringing Frontrunners Annual 5k/10k Pride Run to West Hollywood as part of the city 's annual Christopher Street West/CSW Pride event held in June of each year . John Heilman currently teaches law at both Southwestern Law School and the University of Southern California Law School .", "title": "" }, { "docid": "Hollywood_Park", "text": "Hollywood Park may be several places : Hollywood Park , Barrow , retail and leisure complex in Cumbria , England Hollywood Park , Chicago , one of the neighborhoods in North Park , Chicago Hollywood Park , Texas , a town in Bexar County surrounded by the City of San Antonio Hollywood Park , Inc. , owner of several racetracks including Hollywood Park Racetrack Hollywood Park Racetrack ( New Jersey ) in West End , Monmouth County , New Jersey Hollywood Park Racetrack , former thoroughbred racetrack in Inglewood , California Hollywood Park Casino , casino in Inglewood , California Hollywood Memorial Park Cemetery in Los Angeles , California Lake Hollywood Park , surrounding the Hollywood Reservoir , Hollywood Hills , Los Angeles", "title": "" }, { "docid": "Sal_Guarriello", "text": "Salvatore Joseph `` Sal '' Guarriello ( March 2 , 1919 -- April 16 , 2009 ) was a member of the City Council of the City of West Hollywood , California . He was elected to the City Council in 1990 , and reelected four times . He served four one-year terms as mayor . He was an advocate for West Hollywood residents , protected tenants of low-income housing , promoted West Hollywood 's businesses , and upheld public safety .", "title": "" }, { "docid": "West_Hollywood_Memorial_Walk", "text": "West Hollywood Memorial Walk ( Memorial Walk ) is a memorial and landmark in West Hollywood , California , along the sidewalks of Santa Monica Boulevard between Fairfax Avenue and Doheny Drive , at the eastern border of the City of Beverly Hills . Bronze plaques engraved with the names of those who died from acquired immune deficiency syndrome ( AIDS ) are embedded in the sidewalk as a tribute . Funds from the purchase of plaques support the programs of California non-profit Aid For AIDS to assist impoverished people in Los Angeles County living with HIV/AIDS .", "title": "" }, { "docid": "West_Hollywood_West", "text": "West Hollywood West is a residential neighborhood in West Hollywood , California . It encompasses the area bound by Doheny Drive and Beverly Hills on the west , Melrose Avenue on the north , La Cienega Boulevard on the east and Beverly Boulevard on the south . The east-west streets of the area are Rangely , Dorrington , Ashcroft and Rosewood Avenues , and Bonner Drive . The north-south streets are Doheny Drive , Almont Drive , Robertson Boulevard , Sherbourne Drive , San Vicente Boulevard and Norwich , Huntley , Westbourne , Westmount and West Knoll Drives . The neighborhood is walkable , with cafes and restaurants , malls and movie theatres , parks , libraries , galleries , design shops and the Pacific Design Center in close proximity . The West Hollywood West neighborhood is represented by West Hollywood West Residents Association ( `` WHWRA '' ) , one of the city 's largest and most organized residents associations . The purpose of the West Hollywood West Residents Association ( WHWRA ) is to protect the integrity and quality of life within West Hollywood West . WHWRA 's current president is Lauren Meister , who has served as President of the organization for over six years .", "title": "" }, { "docid": "Hollywood_Hills_West,_Los_Angeles", "text": "Hollywood Hills West is an urban neighborhood within Central Los Angeles , California . There are three city parks and one elementary school .", "title": "" }, { "docid": "Fairfax_High_School_(Los_Angeles,_California)", "text": "Fairfax High School ( officially Fairfax Senior High School ) is a Los Angeles Unified School District high school located in Los Angeles , California , near the border of West Hollywood in the Fairfax District . The school is located on a 24.2 acre campus at the intersection of Fairfax Avenue and trendy Melrose Avenue . Several sections of Los Angeles , including the Fairfax District , Park La Brea , portions of Hancock Park , and Larchmont , and the city of West Hollywood are served by Fairfax . Some areas ( including parts of West Hollywood ) are jointly zoned to Fairfax High School and Hollywood High School . In fall 2007 , some neighborhoods zoned to Hamilton High School were rezoned to Fairfax High School . Bancroft Middle School , Emerson Middle School , Le Conte Middle School , and John Burroughs Middle School feed into Fairfax . In 2009 some territory from the Los Angeles High School attendance boundary was transferred to Fairfax High School .", "title": "" }, { "docid": "Richard_Bloom", "text": "Richard Hershel Bloom ( born June 22 , 1953 ) is an American politician currently serving in the California State Assembly . He is a Democrat representing the 50th Assembly District , which encompasses West Los Angeles , Beverly Hills , Agoura Hills , Malibu , Topanga , Pacific Palisades , Bel Air , Brentwood , Santa Monica , Beverly Hills , West Hollywood , Hancock Park , and Hollywood . Bloom is a member of the California Legislative Jewish Caucus . Prior to being elected to the Assembly in 2012 , he was Mayor of Santa Monica and served on the Santa Monica City Council for 13 years .", "title": "" }, { "docid": "Palladium_Theatre", "text": "Palladium Theatre or Palladium Theater may refer to : Palladium ( New York City ) Palladium Theatre ( St. Petersburg , Florida ) Worcester Palladium London Palladium , a 2,286 seat West End theatre located off Oxford Street in the City of Westminster The Hollywood Palladium , a theater located at 6215 Sunset Boulevard in Hollywood , California", "title": "" }, { "docid": "Chamberlain_West_Hollywood_Hotel", "text": "The Chamberlain West Hollywood is a hotel located in the centre of West Hollywood , California . The hotel has 114 suites , each with a private balcony and a gas-log fireplace . The suites average over 500 sqft and include amenities such as 42 in HD televisions , iHome docking stations and designer bath products . The Chamberlain Bistro , the hotel restaurant , is run by Chef Emilio Noselotl and serves American and California cuisine . Other amenities of the Chamberlain West Hollywood include a rooftop pool and boardroom .", "title": "" }, { "docid": "Little_Armenia,_Los_Angeles", "text": "Little Armenia is a community that is part of the Hollywood district of Los Angeles , California . It falls within the area referred to as East Hollywood . The area is served by the Metro Red Line at the Hollywood/Western station . Little Armenia is defined by the Los Angeles City Council as `` the area bounded on the north by Hollywood Boulevard between the 101 Freeway and Vermont Avenue , on the east by Vermont Avenue from Hollywood Boulevard to Santa Monica Boulevard , on the south by Santa Monica Boulevard between Vermont Avenue and U.S. Route 101 and on the west by Route 101 from Santa Monica Boulevard to Hollywood Boulevard '' ( adopted on 6 October 2000 ) . It also overlaps substantially with Thai Town .", "title": "" }, { "docid": "West_Hollywood_Gateway_Project", "text": "The West Hollywood Gateway is a regional shopping center in West Hollywood , California , United States .", "title": "" }, { "docid": "The_Real_World:_Hollywood", "text": "The Real World : Hollywood is the twentieth season of MTV 's reality television series The Real World , which focuses on a group of diverse strangers living together for several months in a different city each season , as cameras follow their lives and interpersonal relationships . It is the fifth season of The Real World to be filmed in the Pacific States region of the United States , specifically in California , after The Real World : San Diego . The season features a total of nine cast members over the course of the season , as one cast member is evicted and replaced , and another is replaced after he voluntarily leaves the show . It is the only season to be set in the district of Hollywood and the second season to take place in a city that has hosted a previous season , as the show 's second season was set in Los Angeles in 1993 . This season also makes California the most commonly used state to be used as a setting for the series . Production started from August to December 2007 . The season premiered on April 16 , 2008 and consisted of 13 episodes . Comedian Andy Dick appears in Episode 3 , when the cast begins their work at the Hollywood comedy club iO WEST .", "title": "" }, { "docid": "Robertson_Boulevard", "text": "Robertson Boulevard is a street in Los Angeles , in the U.S. state of California , that also passes through the incorporated cities of West Hollywood , Beverly Hills , and Culver City .", "title": "" }, { "docid": "The_Day_of_the_Locust", "text": "The Day of the Locust is a 1939 novel by American author Nathanael West set in Hollywood , California . The novel follows a young artist from the Yale School of Fine Arts named Tod Hackett , who has been hired by a Hollywood studio to do scenic design and painting . While he works he plans an important painting to be called `` The Burning of Los Angeles , '' a portrayal of the chaotic and fiery holocaust which will destroy the city . While the cast of characters Tod befriends are a conglomerate of Hollywood stereotypes , his greater discovery is a part of society whose `` eyes filled with hatred , '' and `` had come to California to die . '' This undercurrent of society captures the despair of Americans who worked and saved their entire lives only to realize , too late , that the American dream was more elusive than they imagine . Their anger boils into rage , and the craze over the latest Hollywood premiere erupts violently into mob rule and absolute chaos . In the introduction to The Day of the Locust , Richard Gehman writes , the novel was `` more ambitious '' than Miss Lonelyhearts , and `` showed marked progress in West 's thinking and in his approach toward maturity as a writer . '' Gehman calls the novel `` episodic in structure , but panoramic in form . ''", "title": "" }, { "docid": "Saint_Victor_Catholic_Church_(West_Hollywood,_California)", "text": "Saint Victor Catholic Church , located at 8634 Holloway Drive , is a Roman Catholic church in West Hollywood , California .", "title": "" }, { "docid": "Wallichs_Music_City", "text": "Wallichs Music City was a famous record store in Hollywood , California , USA , founded by Glenn E. Wallichs , that also had satellite stores as far away as West Covina .", "title": "" }, { "docid": "Pink_Taco", "text": "Pink Taco is a restaurant chain in Los Angeles , California , with locations in West Hollywood on the Sunset Strip and in Century City , located on the premises of the Westfield Century City mall . It serves Mexican food .", "title": "" }, { "docid": "John_Duran", "text": "John J. Duran is an American municipal politician and a member of the city council of West Hollywood , California .", "title": "" }, { "docid": "June_L._Mazer_Lesbian_Archives", "text": "The June L. Mazer Lesbian Archives is a grass roots archive founded in 1981 in Oakland , California as the `` West Coast Lesbian Collections '' . It is one of the largest archives in the world dedicated to collecting protecting and preserving lesbian and feminist women 's history . 1985 the Archives moved to Southern California with the help of the Connexxus Women 's Center and into the home of June Mazer and her partner Bunny Mac Culloch in Altadena , California . They took care of the Archives until June 's death from cancer in 1987 . Bunny changed the name and continued to run the Archives with the help of volunteers . In 1989 the Archive was moved from Altadena into the Wherle Building in West Hollywood . The Archives has been run strictly by volunteers for twenty-eight of its thirty-two years and has continued on supported by private donors and the City of West Hollywood . The Archives has created an outreach and collection-building partnership with the UCLA Libraries . In 2011 , Mazer co-hosted the 3rd GLBT ALMS ( Archives , Libraries , Museums & Special Collections ) Conference . In 2015 , Wolfe Video donated its complete library of lesbian movies to the Archives .", "title": "" }, { "docid": "Harlem_on_the_Prairie", "text": "Harlem on the Prairie ( 1937 ) is a race movie , billed as the first `` all-colored '' western musical . The movie reminded audiences that there were black cowboys and corrected a popular Hollywood image of an all-white Old West . It was produced by Associated Features , which was organized in 1937 . The picture premiered at the Paramount Theatre in Hollywood and was first shown in New York City at the Rialto Theatre on Broadway . The company had offices at 937 N. Sycamore Ave. , Hollywood , California , and the officers of the company were Jed Buell , president ; Bert Sternbach , vice president ; and Sabin W. Carr , secretary-treasurer . Harlem on the Prairie was filmed on location at Murray 's Dude Ranch , Apple Valley , California . The ranch was founded by N.B. Murray , a black businessman from Los Angeles . President and chief producer Jed Buell , spent less than $ 50,000 on this picture .", "title": "" }, { "docid": "Fairfax_Avenue", "text": "Fairfax Avenue is a street in the north central area of the city of Los Angeles , California . It runs from La Cienega Boulevard with Culver City at its southern end to Hollywood Boulevard in Hollywood on its northern end . From La Cienega Boulevard ( between Culver City and Mid-City ) to Sunset Boulevard ( between West Hollywood and Hollywood ) , it separates the Westside from the central part of the city along with Venice Boulevard , La Cienega Boulevard , Hauser Boulevard , San Vicente Boulevard , South Cochran Avenue , Wilshire Boulevard , 6th Street , Cochran Avenue , 4th Street , La Brea Avenue , Fountain Avenue and Sunset Boulevard , Fairfax Avenue forms the western boundary of Hancock Park as well as Park La Brea , an 160-acre ( 0.6-km ² ) , 4,222-unit apartment complex with over 10,000 residents . Since World War II , the Fairfax District has been a heavily Jewish neighborhood in Mid-City West . Fairfax High School , on the corner of Fairfax and Melrose Avenue , was known as the alma mater of many entertainment industry personalities . Canter 's Deli has been a late night hangout in Los Angeles since the 1940s . CBS 's Television City is located on the corner of Fairfax and Beverly Boulevard , where thousands camp out to wait for a chance to watch The Price is Right . The former site of Gilmore Stadium , where the minor league baseball team , the Hollywood Stars , used to play prior to the Dodgers moving from Brooklyn . World-famous recording studio , Cherokee Studios , home to over 250 gold and platinum recorders , is just above Melrose Avenue . The Grove is off 3rd Street and Fairfax . Due to the volume of high density attractions , Fairfax is one of the most congested streets in Los Angeles . Little Ethiopia is further south by Olympic Blvd and north by Pico Boulevard in the Pico-Robertson neighborhood in West Los Angeles . South of Olympic , Fairfax narrows to two lanes , Pico Boulevard between and through the Crestview and Pico-Robertson neighborhoods in West Los Angeles and Venice Boulevard between and through the Crestview and Pico-Robertson neighborhoods in West Los Angeles and Lafayette Square in Mid-City . At the northeast corner of Wilshire Boulevard and Fairfax is the former May Company department store building , which was converted to the Los Angeles County Museum of Art and will be the future home of the Academy Museum of Motion Pictures . The Petersen Automotive Museum is located on the south corner . Metro Local line 35 , 37 , 38 and 175 , 217 and Metro Rapid line 780 are bus lines that serve Fairfax Avenue .", "title": "" }, { "docid": "Laurel_Canyon_Boulevard", "text": "Laurel Canyon Boulevard is a major street in the city of Los Angeles , California . It starts off at Polk Street in Sylmar in the northern San Fernando Valley near the junction of the San Diego ( Interstate 405 ) and the Golden State ( I-5 ) ) freeways . Laurel Canyon Boulevard bypasses the city of San Fernando to the west , running parallel to I-5 in the vicinity of Pacoima and Arleta . The portion through Sun Valley passes through rock quarries and a great deal of open space . From the intersection with Webb Avenue , Laurel Canyon Boulevard heads due south , cutting through North Hollywood , closely following the Hollywood Freeway ( SR 170 ) . Laurel Canyon Boulevard passes through the Valley Village neighborhood , one mile ( 1.6 km ) west of the Hollywood Split ( the intersection of the Hollywood ( U.S. 101/SR 170 ) and Ventura ( U.S. 101/SR 134 ) freeways . This would have been the start of the proposed Laurel Canyon Freeway , which would have provided a direct freeway connection from the southeastern San Fernando Valley to the Los Angeles International Airport . The proposed route was along the current routing of Laurel Canyon Blvd , but the emergence of the Laurel Canyon neighborhood as a movie star enclave doomed the project , as did local opposition . Laurel Canyon itself found counterculture fame in the 1960s as home to many of L.A. 's top rock musicians , such as Frank Zappa . The bohemian spirit endures . Every year , residents gather for a group photograph at the country market . Laurel Canyon Boulevard was also immortalized by the Doors in their 1968 song `` Love Street . '' Laurel Canyon Boulevard crosses an Orange Line station at its intersection with Chandler Boulevard in Valley Village . Laurel Canyon Boulevard is served by Metro Local lines 218 ( south of Ventura Boulevard ) and 230 ( north of Ventura Boulevard ) . South of Ventura Boulevard in Studio City , Laurel Canyon Boulevard ascends the Santa Monica Mountains , where it maintains a width of four lanes until the intersection of Mulholland Drive . The road climbs up Lookout Mountain before descending into West Hollywood , passing through Hollywood Boulevard . Laurel Canyon Blvd 's southern terminus is at Sunset Boulevard , where it becomes Crescent Heights Boulevard . Laurel Canyon Blvd and Coldwater Canyon Avenue to the west between the southern San Fernando Valley and West Hollywood are also popular alternate routes to the Hollywood Freeway ( US 101 ) during rush hour .", "title": "" }, { "docid": "Andaz_West_Hollywood", "text": "The Andaz West Hollywood is a 239-room Hyatt hotel located at 8401 Sunset Boulevard , West Hollywood , California ( at Kings Road ) . The hotel opened in 1963 as the Gene Autry Hotel . Sold in 1967 , it was renamed the Continental Hyatt House . In 1976 it became the Hyatt on Sunset until February 1997 when the hotel was renamed the Hyatt West Hollywood . In January 2009 the hotel was renovated and renamed the Andaz West Hollywood . In the late 1960s and 1970s the hotel 's proximity to popular clubs such as the Whisky a Go Go made it the preferred Los Angeles accommodation for touring rock groups , notably English bands Led Zeppelin , The Who and the Rolling Stones .", "title": "" }, { "docid": "Colonial_House_(West_Hollywood,_California)", "text": "Colonial House is a historic seven-story building in West Hollywood , California , U.S. . It was built in 1930 , and it was designed by architect Leland A. Bryant . It has been listed on the National Register of Historic Places since April 15 , 1982 .", "title": "" }, { "docid": "Highland_Avenue_(Los_Angeles)", "text": "Highland Avenue is a major north/south road that runs from Cahuenga Boulevard and the US 101 Freeway in Hollywood , Los Angeles from the north end to Olympic Boulevard in Mid-City Los Angeles on the south end . ( However , it is not a major thoroughfare in its southernmost portion ; it is a small residential street from Olympic Boulevard to Adams Boulevard . For through access , Highland swerves west into Edgewood Place which accesses La Brea Avenue ) Highland runs parallel to La Brea Avenue on the east and Vine Street on the west . The neighborhood east of Highland on Wilshire Boulevard and Melrose Avenue is officially known as Hancock Park . At the northern end of Highland is the Hollywood Bowl , a major amphitheater and Los Angeles landmark . To the south is the famous intersection of Hollywood and Highland , location of the Hollywood & Highland Center and its Kodak Theater ( venue of the Academy Awards since 2002 ) , and the Hollywood/Highland Metro station for the Red Line subway to Downtown and the Valley . Half a block further south is the Hollywood Museum , located in the historic Max Factor Building , which houses a collection of items from the history of motion pictures and television . Hollywood High School , the alma mater for many celebrities , is located on the corner of Sunset Boulevard and Highland . Further south , near Beverly Boulevard , Highland is adjacent to the Wilshire Country Club in Hancock Park . Highland Avenue 's median parkway with historic palm trees , between Melrose Avenue and Wilshire Boulevard , was designated a Los Angeles Historic-Cultural Monument in 1972 . The Queen palms ( Syagrus romanzoffiana ) and Mexican fan palms ( Washingtonia robusta ) were planted in 1928 . For most of its length Highland is four lanes wide , but narrows to two lanes south of Wilshire Boulevard . Metro Local line 237 runs along Highland Avenue from Santa Monica Boulevard north , and on to the Valley . The segment from the US 101 Freeway south to Santa Monica Boulevard used to be designated as part of California State Route 170 . California 's legislature has since relinquished state control of that segment , and thus that portion is now maintained by the City of Los Angeles .", "title": "" }, { "docid": "Plummer_Park", "text": "Plummer Park is a park in West Hollywood , California , on the eastern side of the city . The east side of West Hollywood is dominated by Russian immigrants , and the park is a popular gathering place for Russians . In 2005 , a controversial monument to Soviet Army dead in World War II was built in the park . While supported by many local residents , it was criticized as being inappropriate given that some might interpret it as honoring the USSR under Joseph Stalin . In 1874 , Col. Eugenio Plummer acquired official title to 160 acres from Señora Francisca Perez , who had occupied this land under preemption law in 1869 . Plummer Park and Plummer House were acquired by Los Angeles County from Senor Plummer in 1937 for $ 15,000 . The Los Angeles Audubon Society ( LAAS ) has been headquartered in Plummer House since then and ( in 1983 ) moved into another building in Plummer Park ( Great Hall Long Hall ) which was originally constructed by the Works Progress Administration ( WPA ) in 1937 . In May 2011 the Audubon Society was given notice to leave by the city of West Hollywood who are planning to demolish the building in 2012 and create underground parking as part of a controversial plan to create a modern park . A group of residents called Protect Plummer Park was organized in early 2011 to preserve the historic Plummer Park . Plummer Park and Plummer House ( which was built in 1870 and moved to the Leonis Adobe grounds in Calabasas in 1983 ) have been designated a State Historic Landmark by the State of California in 1956 . The park is between Santa Monica Boulevard and Fountain Ave , bordered by N. Vista St. and N Fuller Ave. 6 blocks west of La Brea Avenue . There is a farmers ' market every Monday morning in the north parking lot . In 2001 a new community center was completed on the site designed by Koning Eizenberg Architecture , Inc. ( see photograph ) .", "title": "" }, { "docid": "Broadway_Hollywood_Building", "text": "The Broadway Hollywood Building ( sometimes Broadway Building or Broadway Department Store Building ) is a building in Los Angeles ' Hollywood district . The building is situated in the Hollywood Walk of Fame monument area on the southwest corner of the intersection referred to as Hollywood and Vine , marking the intersection of Hollywood Boulevard and Vine Street . It was originally built as the B. H. Dyas Building in 1927 . The Broadway Hollywood Building is referred to by both its main address of 6300 Hollywood Boulevard and its side address of 1645 Vine Street . The Broadway Hollywood Building is a contributing property to the National Register of Historic Places U.S. Historic District-listed Hollywood Boulevard Commercial and Entertainment District . It has been listed as both a historic district contributing property and individually registered historic property by the city of Los Angeles and the state of California . The building has a neon sign above it that is considered notable and historic . The Broadway Hollywood Building was built as a department store , but has been refurbished as both commercial office space and as its current form of residential condominiums . For several decades it hosted The Broadway . The building had an annex built to the west in 1939 and is also associated with the address 6316 Hollywood Boulevard . As a residential building , the building 's units have had numerous famous owners .", "title": "" }, { "docid": "Paul_Koretz", "text": "Paul Koretz ( born April 3 , 1955 ) is an American politician . He is a member of the Los Angeles City Council , representing the Fifth Council District . He was previously a member of the California State Assembly and the West Hollywood City Council . He is a member of the Democratic Party .", "title": "" } ]
5513
Can you explain why these items are considered negatives on my credit report?
[ { "docid": "442230", "text": "Creditworthiness is proven over time. The longer your track record of making payments on time, the more probable you will stick to credit agreements in future (or so the reasoning goes). Conversely, someone who has only just started applying for credit could be someone whose finances were previously stable but have now started to get into difficulty. Obviously this is not necessarily the case but it is one possible inference. This inference is strengthened when same person applies for further credit in a short space of time. Ultimately, what is considered positive is a stable credit record over a reasonable period of time, because it indicates you stick to payment schedules and don't suddenly need credit due to money problems. Credit card accounts are considered a good indicator of credit status because they imply what kind of borrower you are. Whereas many credit arrangements present a straightforward case of arrears / no arrears (e.g. think of a mobile phone account – either you pay your bill or you don't), with credit cards there is an element of flexibility in how much you borrow, and how much of that you repay. If you run up four figure monthly balances but clear them in full each month without fail, that is a good sign. If your average balance is increasing and you are paying on time but just the minimum amount, that is a potential flag. In other words, credit cards are of particular interest because they paint a more nuanced picture. Provided you use one responsibly, getting and using a credit card may improve your status with credit reference agencies.", "title": "" }, { "docid": "117429", "text": "I'm going to give the succinct, plain language version of the answers: 1. Your oldest active credit agreement is not very old You don't have much experience or history for me to base my analysis on -- how do I know I can trust you to pay back the money? 2. You have no active credit card accounts Other people haven't trusted you with credit or you haven't trusted yourself with credit and there's no active good behavior of paying credit cards on time -- you want me to be the first one to go out on a limb and loan you money? How do I know I can trust you to pay back the money?", "title": "" }, { "docid": "44063", "text": "Consider that however high your credit score gets, there is a 'worst piece of it'. The automated software will always report your 'weakest' two points, even if they are already at the top 0.0001% of everyone; that's just how it is coded.", "title": "" }, { "docid": "193641", "text": "\"1. Your oldest active credit agreement is not very old This is fairly straight forward. If you've not been exposed to borrowing for a reasonable length of time, people won't want to lend you money. They have no reason to have any confidence in your ability to repay them. As other said, it's pretty much a case of proving yourself by being good with credit over a period of time. 2. You have no active credit card accounts Credit reference agencies have to consider a variety of factors for a variety of purposes. Notably, they will be used for credit cards, unsecured loans, mortgages, and secured loans such as vehicle finance applications. These all have varying types of customer, and some will be inherently more risky than others. For instance, someone with a mortgage on a home is far more likely to make payments because they would be homeless without, however someone with a finance agreement on a car is relatively less likely to make those payments because all they stand to lose is their car. Consider that the most fruitful information the lender will get is a score and some breakdown of how it's generated, it's a very general understanding of your history. For that reason, having a wide variety of credit is very important. A good variety of credit to have would be one secured loan (e.g car finance) to get started, as well as at least one revolving unsecured credit account (e.g a credit card), and later on in your \"\"credit life\"\" an unsecured fixed term loan (e.g a loan for something which has nothing secured against it). I say the above reluctantly, because that's how I increased my credit score from 450 to 999 - first step was the car finance where in 3 months or so I changed from 450 to around 600, with a credit card I was approaching 900, and once I had an unsecured loan for 8 months I hit 999 - now I have all of the above plus a competitive mortgage and remain at 999. Whether each is mandatory to maintain 999 is debatable but based on personal experience, it seems reasonable.\"", "title": "" } ]
[ { "docid": "92659", "text": "From MyFICO: A foreclosure remains on your credit report for 7 years, but its impact to your FICO® score will lessen over time. While a foreclosure is considered a very negative event by your FICO score, it's a common misconception that it will ruin your score for a very long time. In fact, if you keep all of your other credit obligations in good standing, your FICO score can begin to rebound in as little as 2 years. The important thing to keep in mind is that a foreclosure is a single negative item, and if you keep this item isolated, it will be much less damaging to your FICO score than if you had a foreclosure in addition to defaulting on other credit obligations. (personal note - I tip my hat to you, sir. Regardless of party, we owe our Vets a debt of gratitude. If I had my way, a VA loan would ignore the past short sale. I wish you well. And thank you for serving)", "title": "" }, { "docid": "189662", "text": "\"First of all, whatever you do, DON'T PAY! Credit reporting agencies operate on aged records, and paying it now will most certainly not improve your score. For example, let's say that you had an unpaid debt that was reported as a \"\"charge-off\"\" to the credit bureaus. After, say, six months, the negative effect on your score is reduced. It is reduced even further after a year or two, and after two years, the negative effect on your score is negligible. Now, say you were to pay the debt after the two years. This would \"\"refresh\"\" the record, and show as a \"\"paid charge-off\"\". Sure, now it shows as paid, but it also shows the date of the record as being today, which increases the effect on your credit drastically. In other words, you would have just shot yourself in the foot, big-time. As others have noted, the best option is to dispute the item. If, for some reason, it isn't removed, you are allowed to submit an annotation to the item, explaining your side of the story. Anyone pulling your credit record would see this note, which can help you in some instances. In any case, these scam artists don't deserve your money. Finally, you should check who is the local ombusdman, and report this agent to them. She could lose her license for such a practice.\"", "title": "" }, { "docid": "428694", "text": "Why do you want to improve your credit score? Did you want to buy something? If not, I don't see the point in improving it. If you want to buy something, you can work towards long-term solutions like others have mentioned. In the short term, you can dispute the accuracy of all the negative line items in your report. This will give you a short boost in your credit report while the line items are being investigated as they will be taken off your credit report in the mean time. If you're looking to get a car or mortgage a home, you could time your dispute with purchasing the high dollar assets. This is a trick that does work, but you have to make your move while your credit score is the best it can be.", "title": "" }, { "docid": "362313", "text": "Collections companies buy debt for a fraction of the face value of the debt (as little as 5-7 cents on the dollar), and you can often settle debt for a fraction of the face amount (perhaps 10-25 cents on the dollar). But there are several considerations. Do you owe the debt (is it a legitimate debt), can you afford to pay the debt, what is the age of the debt (remember, there is a statute of limitations on debt, varies by state), and what are the consequences of non-payment or settlement of the debt. Rather than confirm that you owe the debt, tell the debt collector that you need proof that the debt is yours (you should do this by certified letter). Be careful not to confirm the debt, or agree to pay it, or make any payments (yet). You said that your doctor ordered the product for you. You said the company sent you a product (you have the product). Once you have confirmed that the debt is yours, you should determine the age of the debt (when was the last time you paid on the debt). Each state has statute of limitations on debt, depending upon the age of the debt (this is why it is important not to send the collector money until you have verified the debt). You did not state when the debt was incurred (assume under SoL). Ask yourself whether you can afford to pay the debt. The amount of the debt, and your ability to pay, and whether you want to avoid the time and expense of dealing with the collector (they are trained to be annoying) are all factors to consider. You should also consider the negative consequences (credit score effects), and whether the cost of a derogatory entry is worth fighting the debt. You did not explain your financial situation; paying the $55 may be trivial, or it may be a hardship. Before you settle any debt, you should send a letter (keep a copy and proof you sent it, certified), and demand that the debt collector provide proof that you owe the debt. Often this proof does not exist, or is insufficient to gain a judgement (you would need legal help here). And should a debt collector agree to settle the debt for a lower amount, you need to get that agreement in writing. Be aware that when you settle a debt, the collector can (and will) send you a 1099 for the portion of the debt which has been forgiven, and can report to the credit bureaus that you settled a debt for less than the full amount (negative mark against credit). Derogatory credit items will haunt you for years. Decide whether saving $20, $30 or even $55 is worth the trouble. Probably not. Learn from this. When a company sends you something you did not order, contact them, and send it back or demand they pay shipping, and send them a letter demanding $5/day storage and $20 handling fee to ship it back to them. Disclaimer: Heed the insane ravings of a deranged heretic at your peril... hire a lawyer.", "title": "" }, { "docid": "352046", "text": "\"The blurb from the law site is accurate. I'm not going to say any other info from them is or isn't accurate though as I have not read their site at all. If you check the public resources from Fair Issac directly you will get similar wording to that of the law firm: Presence of adverse public records (bankruptcy, judgements, suits, liens, wage attachments, etc.), collection items, and/or delinquency (past due items) Once the items are on your report they will weigh the score down (though less over time). Also, paying the accounts off, other than a successful Pay For Delete (PFD), can have a negative impact on your score. By paying the account off you'll trigger a status change that will allow the account record to stick around for up to 7 more years (10 for medical debts). Which is why it is a better idea to let accounts fall off than it is to pay them once they are over a certain age. Be aware that paying off a collection account on which you previously missed a payment, will not remove it from your credit report. Your FICO score will still consider this information, because it reflects your past credit pattern. Source: Fair Issac: Understanding your FICO Score [PDF] Paying an account off and getting it marked \"\"Paid in Full\"\" or \"\"Settled\"\" or anything else really won't help you at all. The adverse account record drags on your score just for being there.\"", "title": "" }, { "docid": "588719", "text": "From Experian's FAQ How long does an item remain on my credit report? A credit reporting agency stores information from credit grantors and public records, including bankruptcies, judgments and liens. Potentially negative information, such as missed payments and most public record items, remain on a personal credit report for seven years. The exceptions are Chapters 7, 11 and 12 bankruptcies, which remain for 10 years, and unpaid tax liens, which remain for 15 years. A paid tax lien will remain for seven years. Positive information may remain on a report indefinitely. Paid closed accounts generally display for 10 years. Requests for your credit history remain on your personal credit report for two years. (This is a 'comment' to SpecKK's reply, but too long to make it as an actual comment)", "title": "" }, { "docid": "245447", "text": "\"For simplicity, let's start by just considering cash back. In general, cash back from credit cards for personal use is not taxable, but for business use it is taxable (sort of, I'll explain later). The reason is most personal purchases are made with after tax dollars; you typically aren't deducting the cost of what you purchased from your personal income, so if you purchase something that costs $100 and you receive $2 back from the CC company, effectively you have paid $98 for that item but that wouldn't affect your tax bill. However, since businesses typically deduct most expenses, that same $100 deduction would have only been a $98 deduction for business tax purposes, so in this case the $2 should be accounted for. Note, you should not consider that $2 as income though; that would artificially inflate your revenue. It should be treated as a negative expense, similar to how you would handle returning an item you purchased and receiving a CC refund. Now for your specific questions: Part 1: As a small business owner, I wish to attend an annual seminar to improve my business. I have enough credit card reward points to cover the airfare, hotel, and rental car. Will those expenses still be deductible at the value displayed on the receipt? Effectively no, these expenses are not deductible. If you deduct them they will be completely counter-acted by the \"\"refund\"\" you receive for the payments. Part 2: Does it matter if those points are accrued on my personal credit card, rather than a business credit card? This is where it gets hairy. Suppose your company policy is that employees make purchases with their own personal credit cards and submit receipts for reimbursement. In this case the employer can simply reimburse and would not know or care if the employee is racking up rewards/points/cashback. The trick is, as the employee, you must always purchase business related items normally so you have receipts to show, and if you receive cashback on the side there seems to be a \"\"don't ask, don't tell\"\" rule that the IRS is OK with. It works the same way with heavy business travelers and airline miles- the free vacations those users get as perks are not treated as taxable income. However, I would not go out of my way to abuse this \"\"loophole\"\". Typically, things like travel (airfare, hotel, car rental, meals) are expected. But I wouldn't go purchase 100 company laptops on your personal card and ask the company to reimburse you. The company should purchase those 100 laptops on a company card and effectively reduce the sale price by the cashback received. (Or more realistically, negotiate a better discount with your account rep and just cut them a check.) Part 3: Would there be any difference between credit card points and brand-loyalty points? If the rental car were paid for with points earned directly on the rental car company's loyalty system (not a CC), would that yield a different result? There is no difference. Perhaps the simplest way to think about this is you can only deduct an expense that you actually incur. In other words, the expense should show up on a bank or CC statement. This is why when you volunteer and work 10 hours for a charity, you can't call that a \"\"donation\"\" of any amount of money because there is no actual payment made that would show up on a bank statement. Instead you could have billed the charity for your 10 hours of work, and then turned around and donated that same amount back to them, but it ends up being a wash.\"", "title": "" }, { "docid": "404814", "text": "\"Just a word of warning: Most of the companies that promise to repair your credit are scams or close to them. You could just as easily do yourself what they are going to charge you for. Essentially they write a letter to the credit agencies disputing most or all of the bad stuff on your credit report. When you do that, the credit agency sends an inquiry to the company that reported the negative information requiring them to justify it. If that company doesn't respond within x days, they remove the item from your credit report. These companies depend on the fact that some companies aren't going to hit that deadline or even respond. Perhaps they are just too busy to hassle with providing backup documentation for a $20 late payment. They are banking on getting a few of these cheap \"\"outs\"\" to your benefit and charging you for what amounts to sending out a bunch of form letters. If you don't mind writing a bunch of letters, then you can save a lot of money and get the exact same results. These companies want to pretend they have some insider knowledge or fancy lawyers that know special credit-magic, but they generally don't. The only option I'd consider legitimate and not a waste of your time is a referral from the non-profit National Federation for Credit Counseling. They aren't going to \"\"fix your credit\"\", but will give you advice on budgeting and repairing your credit on your own.\"", "title": "" }, { "docid": "40888", "text": "If you are not banking with a credit union, open an account. Speak with a person there an explain you are wanting to build your credit history. They will likely have a product designed for the purpose. Also, to agree with duffbeer703, why is your score so low at this point? Make sure your three credit reports do not have anything incorrect on them and challenge wrong items. If everything is fine on the report, you just to have more credit and use it for a longer period of time. I presume you are building credit for a large purchase such as a house. Please be very careful with borrowing money and do your best to avoid carrying balances.", "title": "" }, { "docid": "57229", "text": "Your clients should not send you 1099-MISC if they paid with a credit card. You can refer them to this text in the instructions for the form 1099-MISC: Payments made with a credit card or payment card and certain other types of payments, including third party network transactions, must be reported on Form 1099-K by the payment settlement entity under section 6050W and are not subject to reporting on Form 1099-MISC. See the separate Instructions for Form 1099-K. By sending out the 1099-MISC, your clients are essentially saying that they paid you directly (check or cash) in addition to the payment they made with a credit card (which will be reported on 1099-K). In case of an audit, you'll have trouble convincing the IRS that it didn't happen. I suggest asking the clients not to do this to you, since it may cost you significant amounts to fight the IRS later on. In any case, you report on your tax return what you really got, not what the 1099 says. If you have two 1099's covering the same income - there's no legal obligation to report the income twice. You do not have to pay twice the tax just because you have stupid clients. But you may have troubles explaining it to the IRS, especially if you're dealing with cash in your business. If you want to avoid matching issues, consider reporting all the 1099s, and then subtracting the duplicates and attaching a statement (the software will do it automatically when you add the description in the miscellaneous item) about what it is.", "title": "" }, { "docid": "522734", "text": "You need to find out if the credit card has been reporting these failed automated payments as late or missed payments to your credit report. To do this, go to annualcreditreport.com (the official site to get your free credit reports) and request your report from all three bureaus. If you see late or missing payments reported for the months where you made a payment but then they did an automatic payment anyway, you should call up the credit card company, explain the situation, and ask them to retract those negative reports. If they refuse, you should dispute the reports directly with the credit bureaus. If they have been reporting late payments even though you have been making the payments, that will impact your credit much more than the fact that they closed your account. Unfortunately, they can turn off your credit account for any reason they like, and there isn't much you can do about that. Find yourself another job as soon as you can, get back on your feet, pay off your debt, and think very carefully before you open another credit card in the future. Don't start a new credit card unless you can ensure that you will pay it off in full every month.", "title": "" }, { "docid": "206267", "text": "\"First, a note of my personal experience: up until a year ago, my credit lines were composed exclusively of credit cards with perfect payment histories, and my credit score is fine. If you mean that credit cards have no impact on a person's credit score until they miss a payment, that is certainly not correct. FICO's website identifies \"\"payment history\"\" as 35% of your FICO score: The first thing any lender wants to know is whether you’ve paid past credit accounts on time. This is one of the most important factors in a FICO® Score. ... Credit payment history on many types of accounts Account types considered for payment history include: ... Details on late or missed payments (\"\"delinquencies\"\") and public record and collection items FICO® Scores consider: How many accounts show no late payment A good track record on most of your credit accounts will increase your FICO® Scores. Clearly, from the last item alone, we see that credit lines (a category which includes credit cards) with no late payments is a factor in computing your FICO score, and certainly other credit bureaus behave similarly. Possibly the banker was trying to explain some other point, like \"\"If you're careful not to spend more on your card than you have in the bank, you can functionally treat your credit card as a debit line,\"\" but did so in a confusing way.\"", "title": "" }, { "docid": "313896", "text": "Several factors are considered in loans as significant as a home mortgage. I believe the most major factors are 1) Credit report, 2) Income, and 3) Employment status If you borrow jointly, all joint factors are included, not just the favorable ones. Some wrinkles this can cause may include: Credit Report - The second person on the loan may have poor credit or no credit. This can/will hurt your rate or even prevent them from being listed on the loan at all, which will also mean you can't include their income. In addition, there are future consequences: that any late payments, default, foreclosure, etc. will be listed on all borrower's reports. If you both have solid work history, great credit, and want to jointly own the home, then there shouldn't be any negatives. If this is not the case, compare both cases (fully, not just rates, as some agents could sneakily say you can get the same rate either way but then not tell you closing costs in one scenario are higher), and pick the one that is best overall. This is just information from my recollection so make sure to verify and ask plenty of questions, don't go forward on assumptions.", "title": "" }, { "docid": "44632", "text": "In a nutshell, not really. That's the risk you take when you co-sign for someone. The lender only made the loan because of the strength of your brother's credit, not your mother's, so his reputation (in the form of his credit rating) is going to take the hit because of his mother's behaviors. The one thing he can do is this: The credit bureaus allow you to add a comment or explanation to your credit file which may be helpful, provided potential creditors read it, which is never a guarantee. It's worth trying though, so suggest to him to look into it. Here's a link for him/you/anyone to look at that can help explain how this works and what effects it can have: Adding a comment to your credit file for negative items I hope this helps. Good luck!", "title": "" }, { "docid": "90632", "text": "What can I do to make sure it won't happen? Who is the right person to report this to? (apparently, the police can't make sure that it won't be used for identity theft) You want to contact any one of the credit bureaus and put a fraud alert on your account. Once you contact one, they automatically contact the other bureaus for you. As part of this, they should send you a credit report. Review it carefully and note any items that are not yours. You'll then need to dispute any items that are a result of this identity theft. You may be required to file a police report regarding the stolen identity, but if you filed one for your stolen wallet, that may be sufficient. If the person who stole your wallet wants to steal your identity, it may be months before it shows up on your credit report. Make it a practice to regularly check your credit reports. How do I check at any given time whether my identity was stolen? Unfortunately, there is no easy way to check if your identity was stolen. The most common way is to check your credit report, but that only checks things that are reported to the credit reporting bureaus. If they use your information to start an account with a utility company at a rental house that typically won't go on your credit report until they are substantially delinquent. If they use your information to check into a hospital, that information typically won't show up on your credit report until the hospital sends the bill to collections. I've had a case where the identity theft happened at Chase, but was never reported on my credit. So my credit report was clear, but Chase disallowed me from banking with them because the identity thief had delinquent accounts with Chase that for whatever reason were not reported to the bureaus. How likely is it that it will be used in any form of identity theft? My gut feeling is that someone who snatches a wallet and immediately runs up the credit cards isn't looking to steal identities, but rather for a quick score. I don't know if there are statistics that back up my hunch.", "title": "" }, { "docid": "574065", "text": "\"The fact that you pay the bill reliably is going to count more for your credit rating than anything else, even if you are paying it off in full every month. Lenders seem to like to see at least one instance where you charged a large balance, held it a couple months, then paid it off in full... but I wouldn't go out of my way to do that. Remember that the credit card company is making money on transaction fees as well as interest. If you're pushing money through their system, they're happy. They'd be happier if you were paying them interest too -- reportedly, they actually refer to those of us who pay in full every month as \"\"deadbeats\"\" -- but they aren't going to kick you out or ding your credit rating for it. The quote you give says that a small balance \"\"may be slightly better\"\". I submit that \"\"may be slightly\"\" is too small a difference to be worth worrying about, unless you have reason to believe that your credit rating actively needs to be repaired. (And as noted in the comments, it's actually stated even less strongly than that!) Personal recommendation: You can get a free credit report each year from each of the \"\"big three\"\" credit rating agencies. Those reports usually include a brief explanation of what they think the most negative item on your record is. The phrasing of those explanations is often somewhat misleading, but I'd still suggest that you get these reports and see what they think would improve your rating. I'm willing to bet it won't be \"\"doesn't carry a high enough debt balance.\"\"\"", "title": "" }, { "docid": "85252", "text": "\"In this answer, I won't elaborate on the possibilities of fraud (or pure human error), because something can always go wrong. I will, however, explain why I think you should always keep receipts. When the (monthly or so) time comes to pay your credit card bill, your credit card company sends you a list of transactions. That list has two primary purposes, both of which I would consider equally important: While for the former item, a receipt is not necessary (though it certainly does not hurt showing the receipt along with the bill to provide further proof that the payment was indeed connected to that bill), the latter point does require you to store the receipts so you can check, item-by-item, whether each of the sums is correct (and matched with a receipt at all). So, unless you can actually memorize all the credit card transactions you did throughout the past one or two months, the receipts are the most convenient way of keeping that information until the bill arrives. Yes, your credit card company probably has some safeguards in place to reveal fraud, which might kick in in time (the criteria are mostly heuristical, it seems, with credit cards or legitimate transactions here getting blocked every now and then simply because some travelling of the actual owner was misinterpreted as theft). However, it is your money, it is your responsibility to discover any issues with the bill, just as you would check the monthly transaction list from your bank account line by line. Ultimately, that is why you sign the vendor copy of the receipt when buying something offline; if you discover an issue in your list of transactions, you have to notify your credit card company that you dispute one of the charges, and then the charging vendor has to show that they have your signature for the respective transaction. So, to summarize: Do keep your receipts, use them to check the list of transactions before paying your credit card bill. EDIT: The receipt often cannot be replaced with the bill from the vendor. The bill is useful for seeing how the sum charged by the respective vendor was created, but in turn, such bills often do not contain any payment information, or (when payment was concluded before the bill was printed, as sometimes happens in pre-paid scenarios such as hotel booking) nondescript remarks such as \"\"- PAYMENT RECEIVED -\"\", without any further indication of which one of your credit cards, debit cards, bank accounts, stored value cards, or cash was used.\"", "title": "" }, { "docid": "358651", "text": "\"Different states have different laws, check your local laws concerning credit. Some states even guarantee you to get one free credit report per year. If you recently apply for an apartment, a mortgage or denied a credit card or loan, you can usually get a free copy from whomever you authorized to pull your credit report. Sign up credit monitoring service, there are quite a few of these. Most credit card companies offer such service, Amex, Chase, Citibank, etc. It' costs around $10-$20 per month. If you sign up a service and pull your own credit report, it's considered a \"\"soft\"\" pull which won't affect your score negatively.\"", "title": "" }, { "docid": "347269", "text": "\"The term for money owed to you by a company would be a credit balance. Consider, when an item is credited to your account, it's in your favor. Whereas, money you owe to a company may be referred to simply as a balance, or balance owing, or less frequently a debit balance. A related term balance due would be the payment you owe in the current period, i.e. not representative of the entire amount owed. I don't think the terms \"\"positive balance\"\" or \"\"negative balance\"\" are considered idiomatic in business. Rather, accounting terms like debit and credit have taken hold instead – and are often a source of confusion. But I suggest that if you have a negative balance on a credit card, it's a credit balance in your favor. Unless they mix it up.\"", "title": "" }, { "docid": "91788", "text": "\"(I'm a bit surprised that nobody talked about the impact of multiple inquiries on a loan, since OP is concerned with credit building. Probably an answer as opposed to a comment is justified.) Yes. In fact when you shop for auto loan you are expected to have your credit score/report be pulled by different banks, credit unions, and/or the financing arm of the car manufacturer or the dealership, so that you can hopefully get the best rate possible. This is especially true if the dealer is requesting quotes on rates on your behalf, as they would probably use a batch process to send out applications to multiple financial institutions all at once. Yes, and a bit unusual - CALVERT TOYO (your dealer) pulled your report twice on the same day. Presumably they are not getting any new information on the second pull. Maybe a fat finger? Regardless, you should not worry about this too much (to be explained below). I would say \"\"don't bother\"\". The idea behind hard inquiries lowering credit score is that lenders see the number of hard inquiries as your desire for credit. Too high a number is often viewed as either \"\"desperate for credit\"\" or \"\"unable to qualify for credit\"\". But as explained above, it is very common for a person to request quotes for multiple financial institutions and thus to have multiple hard inquiries in a short period of time when shopping for loans. To account for that, the credit bureau's model would usually combine hard inquiries for a same type of loan (auto, mortgage, etc.) within 30 days. Hence a person sending quote request to 3 banks won't be rated higher for credit than if he were to request quotes from 5 banks. Therefore in your case your credit profile is not going to be different if you had been pulled just once. my credit score goes down for 15 points I'm assuming you are talking about the credit score provided by Credit Karma. The score CK provided is FAKO. The score lenders care about is FICO. They are well correlated but still different. Google these two terms and you should be able to figure out the difference quickly. You can also refer to my answer to a different question here: Equifax credit score discrepancy in 1 month, why?\"", "title": "" }, { "docid": "230297", "text": "\"tl;dr: Your best course of action is probably to do a soft pull (check your own credit) and provide that to the lender for an unofficial pre-approval to get the ball rolling. The long of it: The loan officer is mostly correct, and I have recent personal evidence that corroborates that. A few months ago I looked into refinancing a mortgage on a rental property, and I allowed 3 different lenders to do a hard inquiry within 1 week of each other. I saw all 3 inquires appear on reports from each of the 3 credit bureaus (EQ/TU/EX), but it was only counted as a single inquiry in my score factors. But as you have suggested, this breaks down when you know that you won't be purchasing right away, because then you will have multiple hard inquiries at least a few months apart which could possibly have a (minor) negative impact on your score. However minor it is, you might as well try to avoid it if you can. I have played around with the simulator on myfico.com, and have found inquiries to have the following effect on your credit score using the FICO Score 8 model: With one inquiry, your scores will adjust as such: Two inquiries: Three inquiries: Here's a helpful quote from the simulator notes: \"\"Credit inquiries remain on your credit report for 2 years, but FICO Scores only consider credit inquiries from the past 12 months.\"\" Of course, take that with a grain of salt, as myfico provides the following disclaimer: The Simulator is provided for informational purposes only and should not be expected to provide accurate predictions in all situations. Consequently, we make no promise or guarantee with regard to the Simulator. Having said all that, in your situation, if you know with certainty that you will not be purchasing right away, then I would recommend doing a soft pull to get your scores now (check your credit yourself), and see if the lender will use those numbers to estimate your pre-approval. One possible downside of this is the lender may not be able to give you an official pre-approval letter based on your soft pull. I wouldn't worry too much about that though since if you are suddenly ready to purchase you could just tell them to go ahead with the hard pull so they can furnish an official pre-approval letter. Interesting Side Note: Last month I applied for a new mortgage and my score was about 40 points lower than it was 3 months ago. At first I thought this was due to my recent refinancing of property and the credit inquiries that came along with it, but then I noticed that one of my business credit cards had recently accrued a high balance. It just so happens that this particular business CC reports to my personal credit report (most likely in error but I never bothered to do anything about it). I immediately paid that CC off in full, and checked my credit 20 days later after it had reported, and my score shot back up by over 30 points. I called my lender and instructed them to re-pull my credit (hard inquiry), which they did, and this pushed me back up into the best mortgage rate category. Yes, I purposely requested another hard pull, but it shouldn't affect my score since it was within 45 days, and that maneuver will save me thousands in the long run.\"", "title": "" }, { "docid": "190225", "text": "If you have no credit history but you have a job, buying an inexpensive used car should still be doable with only a marginally higher interest rate on the car. This can be offset with a cosigner, but it probably isn't that big of a deal if you purchase a car that you can pay off in under a year. The cost of insurance for a car is affected by your credit score in many locations, so regardless you should also consider selling your other car rather than maintaining and insuring it while it's not your primary mode of transportation. The main thing to consider is that the terms of the credit will not be advantageous, so you should pay the full balance on any credit cards each month to not incur high interest expenses. A credit card through a credit union is advantageous because you can often negotiate a lower rate after you've established the credit with them for a while (instead of closing the card and opening a new credit card account with a lower rate--this impacts your credit score negatively because the average age of open accounts is a significant part of the score. This advice is about the same except that it will take longer for negative marks like missed payments to be removed from your report, so expect 7 years to fully recover from the bad credit. Again, minimizing how long you have money borrowed for will be the biggest benefit. A note about cosigners: we discourage people from cosigning on other people's loans. It can turn out badly and hurt a relationship. If someone takes that risk and cosigns for you, make every payment on time and show them you appreciate what they have done for you.", "title": "" }, { "docid": "184175", "text": "\"Credit reports have line items that, if all is well, say \"\"paid as agreed.\"\" A car loan almost certainly gets reported. In your case it probably says the happy \"\"paid as agreed.\"\" It will continue to say that if you pay it off in full. You can get the happy \"\"paid as agreed\"\" from a credit card too. You can get it by paying the balance by the due date every month, or paying the mininum, or anything in between, on time. But you'll blow less money in interest if you pay each bill in full each month. You don't have to carry a balance. In the US you can get a free credit report once a year from each of the three credit bureaus. Here's the way to do that with minimal upsell/cross-sell hassles. https://www.annualcreditreport.com/ In your situation you'd probably be smart to ask for a credit report every four months (from each bureau in turn) so you can see how things are going. They don't give you your FICO score for free, but you don't really care about that until you're going for a big loan, like for a condo. It might be good to take a look at one of those free credit reports real soon, as you prepare to close out your car loan. If you need other loans, consider working with a credit union. They sometimes offer better interest rates, and they often are diligent about making credit bureau reports for their good customers; they help you build credit. You mentioned wanting to cut back on insurance coverage. It's a worthy goal, but it's generally called \"\"self-insuring\"\" in the business. If you cancel your collision coverage and then wreck your car, you absorb the cost of replacing it. So think about your personal ability to handle that kind of risk.\"", "title": "" }, { "docid": "419475", "text": "First thing, ask your real estate agent who should have been involved in writing the contract, and can explain your options regarding the contingency. That being said... The inspection report is the decision point. For every issue/problem mentioned you have decide: Ignore; have the seller fix; have the seller give you money to fix; have the seller drop the price; or walk away. Minor things you can have the seller fix. They need to be done, but they can be done by the seller. Expensive things that are difficult to estimate the price in advance should also be done by the seller. The difficultly estimating the cost to repair will make it risky for you to negotiate a price break. Getting a credit of $1,000 when it ends up costing you $20,000 is something you want to avoid. For items that you want to do the fix yourself you want money at closing to do them, or ask for a price break. Items in this category include replacing an appliance. You can take the money and get exactly the one you want, or let the seller of the house buy one that has the least options and won't match the color. Buyers also take this option when they were going to renovate soon anyway. Walking away. This happens when there is a large expensive issue that is hard to fix. Or a very large list of mid-size problems. Issues in this category can include foundation cracks, major electrical problems, extensive leaks, mold. It can also include beautifully constructed additions that aren't up to code and were done without permits and inspections. Which category is your Radon in? You need to ask your agent, and read the inspection report. The agent can explain your options, and how likely the seller will be to agree. They can also tell you how likely you are to not lose the deposit if you do walk away.", "title": "" }, { "docid": "188903", "text": "\"I am interested in seeing what happens to your report after you test this, but I don't think it's possible in practice, would not affect your credit score, and also wouldn't be worth it for you to carry a negative balance like that. Having a -1% credit utilization essentially means that you are lending the credit card company money, which isn't really something that the credit card companies \"\"do\"\". They would likely not accept an agreement where you are providing the credit to them. Having credit is a more formal agreement than just 'I paid you too much this month'. Even if your payment does post before the transaction and it says you have a negative balance and gets reported to the credit bureau like that, this would probably get flagged for human review, and a negative credit utilization doesn't really reflect what is happening. Credit utilization is 'how much do you owe / amount of credit available to you', and it's not really correct to say that you owe negative dollars. Carrying a negative balance like that is money that could be invested elsewhere. My guess is that the credit card company is not paying you the APR of your card on the amount they owe you (if they are please provide the name of your card!). They probably don't pay you anything for that negative balance and it's money that's better used elsewhere. Even if it does benefit your credit score you're losing out on any interest (each month!) you could have earned with that money to get maybe 1-2% better rate on your next home or car loan (when will that be?). TLDR: I think credit utilization approaches a limit at 0% because it's based on the amount you owe and you don't really owe negative dollars. I am very interested in seeing the results of this experiment, please update us when you find out!\"", "title": "" }, { "docid": "51873", "text": "I used to work for Ally Auto (formerly known as GMAC) and I'd advise not to pay off the account unless you need to free up some debt in your credit report since until the account is paid off it will show that you owe your financial institution the original loan amount. The reason why I am saying not to pay-off the account is because good/bad payments are sent to the credit bureau 30 days after the due date of the payment, and if you want to increase your credit score then its best to pay it on a monthly basis, the negative side to this is you will pay more interest by doing this. If ever you decide to leave $1.00 in loan, I am pretty much sure that the financial institution will absorb the remaining balance and consider the account paid off. What exactly is your goal here? Do you plan to increase your credit score? Do you need to free up some debt?", "title": "" }, { "docid": "299211", "text": "\"-Alain Wertheimer I'm a hobbyist... Most (probably all) of those older items were sold both prior to my establishing the LLC This is a hobby of yours, this is not your business. You purchased all of these goods for your pleasure, not for their future profit. The later items that you bought after your LLC was establish served both purposes (perks of doing what you love). How should I go about reporting this income for the items I don't have records for how much I purchased them for? There's nothing you can do. As noted above, these items (if you were to testify in court against the IRS). \"\"Losses from the sale of personal-use property, such as your home or car, aren't tax deductible.\"\" Source Do I need to indicate 100% of the income because I can't prove that I sold it at a loss? Yes, if you do not have previous records you must claim a 100% capital gain. Source Addition: As JoeTaxpayer has mentioned in the comments, the second source I posted is for stocks and bonds. So at year begin of 2016, I started selling what I didn't need on eBay and on various forums [January - September]. Because you are not in the business of doing this, you do not need to explain the cost; but you do need to report the income as Gross Income on your 1040. Yes, if you bought a TV three years ago for a $100 and sold it for $50, the IRS would recognize you earning $50. As these are all personal items, they can not be deducted; regardless of gain or loss. Source Later in the year 2016 (October), I started an LLC (October - December) If these are items that you did not record early in the process of your LLC, then it is reported as a 100% gain as you can not prove any business expenses or costs to acquire associated with it. Source Refer to above answer. Refer to above answer. Conclusion Again, this is a income tax question that is split between business and personal use items. This is not a question of other's assessment of the value of the asset. It is solely based on the instruments of the IRS and their assessment of gains and losses from businesses. As OP does not have the necessary documents to prove otherwise, a cost basis of $0 must be assumed; thus you have a 100% gain on sale.\"", "title": "" }, { "docid": "170248", "text": "\"If you were making that large of a payment (via a cashiers check or other withdrawal means from a cash account) to a credit card, would the payment generate a Cash Transaction Report? Probably, yes. If it does require the bank to make a CTR, then is there any harm in that or anything to be concerned about (like that transaction appearing suspicious, personal reporting implications, etc.)? Are there any other reasons why one might want to make sure payments to a credit card are broken up made* in amounts smaller than $10K? You should be concerned if you cannot explain the source of the money (legally...). If you withdrew cash from your own account and paid your credit card with it, in case of questions asked you can show the account statement with the matching withdrawal, and you're done. The point in this report is to point at people who move around large amounts of cash. Usually, people pay credit cards with checks or ACH transactions, but if you want cash - it's your right, as long as the cash was obtained legally. But if you're paying your credit cards off with the cash you got as a bribe or by selling cocaine on the streets, then you should be worried. By the way, breaking into smaller payments may not save you from being reported to the money laundering detection agencies. The report is per transaction, not per payment, so if the credit card statement is $11K and you pay $5K and $6K - the transaction is still $11K. Also, the bank can file a report even if it is not required (it was clarified in the other answer to the same question you're referring to), if the clerk thinks the transaction is suspicious. This leaves the decision on filing a report solely on the banks \"\"common sense\"\" and internal policies which you don't know. So even paying $10 in cash may trigger a report if the bank suspects wrongdoing.\"", "title": "" }, { "docid": "125204", "text": "I can't address the psychology of trust involved in your question, but here are some common sense guidelines for dealing with your issue. Make sure you know who you are talking to. Call the company you need to speak to via a publicly available phone number. An email or something you got in a letter might be from a different source. If you use a website, you should be sure you are on the correct website. Keep careful records. Make good notes of each phone call and keep all emails and letters forever. Note the time, name and/or ID of the person you spoke to and numbers called in addition to keeping notes on what actions should be done. Keep your faxing transmission receipts and shipping tracking numbers too. If you are nervous, ask them why they want the info. The fraud department should be able to explain it to you. For example, they probably want your social because that is how your credit report is identified. If they are going to fix a credit report, they will need a social. It is doubtful they would have a good explanation why they need your mother's maiden name. Ask for secure transmission, or confirm they have it. Postal mail isn't so secure, but I'll go out on a limb and say most fax machines today are not really fax machines, but software that deals in PDFs. At some point you will have to realize you will have to transmit something. No method is perfect, but you can limit your exposure. Help them do their jobs. If you are (understandably) nervous, consider their motivations: corporate profit. BUT that could very well mean not running afoul of the law and (with any luck) treating customers the best way they know to earn business. If you stymy the fraud department, how can they help you? If the ID theft was serious enough, document your issue for future law enforcement so you getting pulled over for speeding doesn't result in you going to jail for whatever crime the other person did. Perhaps the fraud department you are dealing with can assist there. Finally, while you work with fraud departments to clear up your name and account, work on the other end to limit future damage. Freeze your credit. See if you bank or credit card have monitoring. Use CreditKarma.com or a similar if you cannot find a free service. (Please don't ever pay for credit monitoring.)", "title": "" }, { "docid": "306197", "text": "I have been charting the CPI reported inflation rate vs . the yeald on the 10-year T-note. Usually, the two like to keep pace with each other. Sometimes the T-note is a bit higher than the inflation rate, sometimes the inflation rate is a bit higher than the T-note yeald. One does not appear to follow the other, but (until recently) the two do not diverge from each other by much. But all that changed recently and I am without an explanation as to why. Inflation dropped to zero (or a bit negative) yet the yeald on the 10-year T-note seemed to seek 2%. Edit: If you give this response a downvote then please be kind enough to explain why in a comment. Edit-2: CPI and 10-year T-note are what I have tracked, and continue to track. If you do not like my answer then provide a better one, yourself.", "title": "" } ]
PLAIN-2695
Testing Your Diet with Pee & Purple Cabbage
[ { "docid": "MED-3215", "text": "The average American diet, which is high in protein and low in fruits and vegetables, generates a large amount of acid, mainly as sulfates and phosphates. The kidneys respond to this dietary acid challenge with net acid excretion, as well as ammonium and titratable acid excretion. Concurrently, the skeleton supplies buffer by active resorption of bone. Indeed, calciuria is directly related to net acid excretion. Different food proteins differ greatly in their potential acid load, and therefore in their acidogenic effect. A diet high in acid-ash proteins causes excessive calcium loss because of its acidogenic content. The addition of exogenous buffers, as chemical salts or as fruits and vegetables, to a high protein diet results in a less acid urine, a reduction in net acid excretion, reduced ammonium and titratable acid excretion, and decreased calciuria. Bone resorption may be halted, and bone accretion may actually occur. Alkali buffers, whether chemical salts or dietary fruits and vegetables high in potassium, reverse acid-induced obligatory urinary calcium loss. We conclude that excessive dietary protein from foods with high potential renal acid load adversely affects bone, unless buffered by the consumption of alkali-rich foods or supplements.", "title": "Excess dietary protein can adversely affect bone." }, { "docid": "MED-3237", "text": "The modern Western-type diet is deficient in fruits and vegetables and contains excessive animal products, generating the accumulation of non-metabolizable anions and a lifespan state of overlooked metabolic acidosis, whose magnitude increases progressively with aging due to the physiological decline in kidney function. In response to this state of diet-derived metabolic acidosis, the kidney implements compensating mechanisms aimed to restore the acid-base balance, such as the removal of the non-metabolizable anions, the conservation of citrate, and the enhancement of kidney ammoniagenesis and urinary excretion of ammonium ions. These adaptive processes lower the urine pH and induce an extensive change in urine composition, including hypocitraturia, hypercalciuria, and nitrogen and phosphate wasting. Low urine pH predisposes to uric acid stone formation. Hypocitraturia and hypercalciuria are risk factors for calcium stone disease. Even a very mild degree of metabolic acidosis induces skeletal muscle resistance to the insulin action and dietary acid load may be an important variable in predicting the metabolic abnormalities and the cardiovascular risk of the general population, the overweight and obese persons, and other patient populations including diabetes and chronic kidney failure. High dietary acid load is more likely to result in diabetes and systemic hypertension and may increase the cardiovascular risk. Results of recent observational studies confirm an association between insulin resistance and metabolic acidosis markers, including low serum bicarbonate, high serum anion gap, hypocitraturia, and low urine pH. Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.", "title": "Diet-induced metabolic acidosis." }, { "docid": "MED-3229", "text": "High-protein (HP) diets exert a hypercalciuric effect at constant levels of calcium intake, even though the effect may depend on the nature of the dietary protein. Lower urinary pH is also consistently observed for subjects consuming HP diets. The combination of these two effects was suspected to be associated with a dietary environment favorable for demineralization of the skeleton. However, increased calcium excretion due to HP diet does not seem to be linked to impaired calcium balance. In contrast, some data indicate that HP intakes induce an increase of intestinal calcium absorption. Moreover, no clinical data support the hypothesis of a detrimental effect of HP diet on bone health, except in a context of inadequate calcium supply. In addition, HP intake promotes bone growth and retards bone loss and low-protein diet is associated with higher risk of hip fractures. The increase of acid and calcium excretion due to HP diet is also accused of constituting a favorable environment for kidney stones and renal diseases. However, in healthy subjects, no damaging effect of HP diets on kidney has been found in either observational or interventional studies and it seems that HP diets might be deleterious only in patients with preexisting metabolic renal dysfunction. Thus, HP diet does not seem to lead to calcium bone loss, and the role of protein seems to be complex and probably dependent on other dietary factors and the presence of other nutrients in the diet.", "title": "Protein intake, calcium balance and health consequences." }, { "docid": "MED-4499", "text": "Fourier transform infrared (FT-IR) spectroscopy and Raman spectroscopy were used to study the cell injury and inactivation of Campylobacter jejuni from exposure to antioxidants from garlic. C. jejuni was treated with various concentrations of garlic concentrate and garlic-derived organosulfur compounds in growth media and saline at 4, 22, and 35°C. The antimicrobial activities of the diallyl sulfides increased with the number of sulfur atoms (diallyl sulfide < diallyl disulfide < diallyl trisulfide). FT-IR spectroscopy confirmed that organosulfur compounds are responsible for the substantial antimicrobial activity of garlic, much greater than those of garlic phenolic compounds, as indicated by changes in the spectral features of proteins, lipids, and polysaccharides in the bacterial cell membranes. Confocal Raman microscopy (532-nm-gold-particle substrate) and Raman mapping of a single bacterium confirmed the intracellular uptake of sulfur and phenolic components. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were employed to verify cell damage. Principal-component analysis (PCA), discriminant function analysis (DFA), and soft independent modeling of class analogs (SIMCA) were performed, and results were cross validated to differentiate bacteria based upon the degree of cell injury. Partial least-squares regression (PLSR) was employed to quantify and predict actual numbers of healthy and injured bacterial cells remaining following treatment. PLSR-based loading plots were investigated to further verify the changes in the cell membrane of C. jejuni treated with organosulfur compounds. We demonstrated that bacterial injury and inactivation could be accurately investigated by complementary infrared and Raman spectroscopies using a chemical-based, “whole-organism fingerprint” with the aid of chemometrics and electron microscopy.", "title": "Investigating Antibacterial Effects of Garlic (Allium sativum) Concentrate and Garlic-Derived Organosulfur Compounds on Campylobacter jejuni by Using Fourier Transform Infrared Spectroscopy, Raman Spectroscopy, and Electron Microscopy" }, { "docid": "MED-4497", "text": "Purple discoloration of the large bowel at autopsy was related to beetroot ingestion and post-mortem changes.", "title": "The case of the purple colon." }, { "docid": "MED-4502", "text": "Kidney stones are increasingly common in wealthy industrialized countries. The most frequent form (80%) is idiopathic calcium stone disease. Eating habits and lifestyle have a direct effect on the lithogenic urinary risk factors and the pathogenesis of this condition. A diet characterized by a high intake of fluids, fruits, and vegetables; a low consumption of salt and protein; and a balanced intake of calcium, fats, and carbohydrates constitutes an efficacious approach to the prevention and treatment of this illness. A correct body weight, regular exercise, and a reduction in stressful life events are also useful preventive actions. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Lifestyle recommendations to reduce the risk of kidney stones." }, { "docid": "MED-3226", "text": "Context and Objective: Dietary intake of animal proteins is associated with an increase in urinary calcium and nephrolithiasis risk. We tested the hypothesis that the acid load imposed by dietary proteins causes this hypercalciuria. Design and Setting: In a short-term crossover metabolic study, an alkali salt was provided with a high-protein diet (HPD) to neutralize the acid load imparted by dietary proteins. Participants and Interventions: Eleven healthy volunteers were evaluated at the end of each of four phases while consuming metabolic diets with fixed calcium and sodium content. Phases 1 and 3 consisted of a control diet (CD). Phases 2 and 4 consisted of a eucaloric HPD (60 g/d animal proteins added to CD). Along with HPD in phases 2 and 4, subjects ingested 30 mEq twice daily of either potassium citrate (KCitrate, alkaline salt) or potassium chloride (KCl, control neutral salt). Results: KCitrate completely neutralized the acid load imparted by HPD (based on changes in urine pH and net acid excretion) and increased urinary citrate. Urinary calcium increased during both HPD phases compared with CD but was not significantly different between the HPD + KCl and HPD + KCitrate phases (182 ± 85 vs. 170 ± 85 mg/d; P = 0.28). Increased urinary saturation with respect to calcium oxalate and uric acid with HPD was abrogated by KCitrate. Conclusions: This study suggests that, at least in the short-term, mechanism(s) other than acid load account for hypercalciuria induced by HPD. The beneficial effect of KCitrate on nephrolithiasis risk with HPD is through correction of declines in urine pH and citrate.", "title": "Hypercalciuria Associated with High Dietary Protein Intake Is Not Due to Acid Load" }, { "docid": "MED-3220", "text": "Background Maintaining muscle mass while aging is important to prevent falls and fractures. Metabolic acidosis promotes muscle wasting, and the net acid load from diets that are rich in net acid–producing protein and cereal grains relative to their content of net alkali–producing fruit and vegetables may therefore contribute to a reduction in lean tissue mass in older adults. Objective We aimed to determine whether there was an association of 24-h urinary potassium and an index of fruit and vegetable content of the diet with the percentage lean body mass (%LBM) or change in %LBM in older subjects. Design Subjects were 384 men and women ≥65 y old who participated in a 3-y trial comparing calcium and vitamin D with placebo. Potassium was measured in 24-h urine collections at baseline. The %LBM, defined as total body nonfat, nonbone tissue weight ÷ weight × 100, was measured by using dual-energy X-ray absorptiometry at baseline and at 3 y. Physical activity, height, and weight were assessed at baseline and at 3 y. Results At baseline, the mean urinary potassium excretion was 67.0 ± 21.1 mmol/d. Urinary potassium (mmol/d) was significantly positively associated with %LBM at baseline (β = 0.033, P = 0.006; adjusted for sex, weight, and nitrogen excretion) but not with 3-y change in %LBM. Over the 3-y study, %LBM increased by 2.6 ± 3.6%. Conclusion Higher intake of foods rich in potassium, such as fruit and vegetables, may favor the preservation of muscle mass in older men and women.", "title": "Alkaline diets favor lean tissue mass in older adults" }, { "docid": "MED-4501", "text": "Beeturia, the passage of pink or red urine after the ingestion of beetroot, is said to occur in 10-14% of the population, and is more common in iron deficiency and malabsorption. A specific HPLC assay for betacyanins, the red beetroot pigments, in biological fluids was developed to study the prevalence of this apparent polymorphism in humans, and to investigate its basis in rats. Two major peaks were observed in chromatograms of extracts of unpickled beetroot. They had identical UV absorption spectra (lambda max = 535 nm) by diode array analysis, and mass spectrometry indicated that one (betacyanin 1) was betanin or its epimer and the other (betacyanin 2) a disaccharide of betacyanin 1. In a population of 100 normal subjects the 0-8 h urinary recoveries after an oral dose of 60 mg beetroot extract were 0.06-0.54% for betacyanin 1 and 0.01-0.6% for betacyanin 2. The distributions of these data were skewed but not clearly bimodal by visual inspection or by kernel density analysis. Four subjects produced visibly red urine and had betacyanin recoveries at the upper end of the population range. Studies using in situ isolated perfused rat jejunum and liver preparations indicated a negligible absorption of the pigments after 1 h and no detectable metabolism or biliary secretion. Intact anaesthetized rats given i.v. bolus doses of beetroot extract cleared both betacyanins from plasma at the rate of 3.3 +/- 0.9 (SD) ml min-1 (n = 5). The total urinary recovery of both pigments amounted to 80% of the dose, and their renal clearances approached their plasma clearances. These data suggest that beeturia does not arise from deficiencies in hepatic metabolism or renal excretion of betacyanins. After oral administration of beetroot extract to rats the betacyanin content of the stomach decreased rapidly with time but neither the intestines nor the bile duct were stained visibly red. These findings together with those showing instability of the betacyanins in acid conditions suggest that variability in the biological fate of beetroot pigments may be determined largely by gastric pH and emptying rate.", "title": "Beeturia and the biological fate of beetroot pigments." }, { "docid": "MED-3231", "text": "This review looks at the role of an alkaline diet in health. Pubmed was searched looking for articles on pH, potential renal acid loads, bone health, muscle, growth hormone, back pain, vitamin D and chemotherapy. Many books written in the lay literature on the alkaline diet were also reviewed and evaluated in light of the published medical literature. There may be some value in considering an alkaline diet in reducing morbidity and mortality from chronic diseases and further studies are warranted in this area of medicine.", "title": "The Alkaline Diet: Is There Evidence That an Alkaline pH Diet Benefits Health?" }, { "docid": "MED-3230", "text": "OBJECTIVE: Diet affects urine pH and acid-base balance. Both excess acid/alkaline ash (EAA) and estimated net acid excretion (NAE) calculations have been used to estimate the effects of diet on urine pH. This study's goal was to determine if free-living vegans, lacto-ovo vegetarians, and omnivores have increasingly acidic urine, and to assess the ability of EAA and estimated NAE calculations to predict urine pH. DESIGN: This study used a cross-sectional design. SETTING AND PARTICIPANTS: This study assessed urine samples of 10 vegan, 16 lacto-ovo vegetarian, and 16 healthy omnivorous women in the Boston metropolitan area. Six 3-day food records from each dietary group were analyzed for EAA content and estimated NAE, and correlations with measured urine pH were calculated. RESULTS: The mean (+/- SD) urine pH was 6.15 +/- 0.40 for vegans, 5.90 +/- 0.36 for lacto-ovo vegetarians, and 5.74 +/- 0.21 for omnivores (analysis of variance, P = .013). Calculated EAA values were not significantly different among the three groups, whereas mean estimated NAE values were significantly different: 17.3 +/- 14.5 mEq/day for vegans, 31.3 +/- 8.5 mEq/day for lacto-ovo vegetarians, and 42.6 +/- 13.2 mEq/day for omnivores (analysis of variance, P = .01). The average deattenuated correlation between urine pH and EAA was 0.333; this value was -0.768 for estimated NAE and urine pH, with a regression equation of pH = 6.33 - 0.014 NAE (P = .02, r = -0.54). CONCLUSIONS: Habitual diet and estimated NAE calculations indicate the probable ranking of urine pH by dietary groups, and may be used to determine the likely acid-base status of an individual; EAA calculations were not predictive of urine pH.", "title": "Estimated net acid excretion inversely correlates with urine pH in vegans, lacto-ovo vegetarians, and omnivores." }, { "docid": "MED-3216", "text": "Increasing dietary protein results in an increase in urinary calcium. Despite over 80 y of research, the source of the additional urinary calcium remains unclear. Because most calcium balance studies found little effect of dietary protein on intestinal calcium absorption, it was assumed that the skeleton was the source of the calcium. The hypothesis was that the high endogenous acid load generated by a protein-rich diet would increase bone resorption and skeletal fracture. However, there are no definitive nutrition intervention studies that show a detrimental effect of a high protein diet on the skeleton and the hypothesis remains unproven. Recent studies from our laboratory demonstrate that dietary protein affects intestinal calcium absorption. We conducted a series of short-term nutrition intervention trials in healthy adults where dietary protein was adjusted to either low, medium or high. The highest protein diet resulted in hypercalciuria with no change in serum parathyroid hormone. Surprisingly, within 4 d, the low protein diet induced secondary hyperparathyroidism that persisted for 2 wk. The secondary hyperparathyroidism induced by the low protein diet was attributed to a reduction in intestinal calcium absorption (as assessed by dual stable calcium isotopes). The long-term consequences of these low protein-induced changes in calcium metabolism are not known, but they could be detrimental to skeletal health. Several recent epidemiological studies demonstrate reduced bone density and increased rates of bone loss in individuals habitually consuming low protein diets. Therefore, studies are needed to determine whether low protein intakes directly affect rates of bone resorption, bone formation or both.", "title": "Low protein intake: the impact on calcium and bone homeostasis in humans." }, { "docid": "MED-3236", "text": "A first objective of the present study was to estimate the acid-base balance of the food intake in vegetarians and non-vegetarians. A second objective was to evaluate if additional input of specific food items on the existing potential renal acid load (PRAL) list was necessary for the comparison of the two dietary patterns. Thirty vegetarians between the age of 18 and 30 years were matched for sex, age and BMI with 30 non-vegetarians. Based on the 3-days food diaries the acid-base status of the food intake was estimated using the PRAL method. Mean PRAL values as estimated with the standard table yielded an alkaline load of -5.4 +/- 14.4 mEq/d in the vegetarians compared to an acid load of 10.3 +/- 14.4 mEq/d in the nonvegetarians (p<0.001). Mean PRAL values as estimated with the extended table yielded an alkaline load of -10.9 +/-19.7 mEq/d in the vegetarians compared to an acid load of 13.8 +/- 17.1 mEq/d for the non-vegetarians (p<0.001). The findings of this study indicate that vegetarian food intake produces more alkaline outcomes compared to non-vegetarian diets. The use of the standard PRAL table was sufficient for discrimination between the two diets.", "title": "Nutrient based estimation of acid-base balance in vegetarians and non-vegetarians." }, { "docid": "MED-3227", "text": "Although high-protein diets induce hypercalciuria in humans, the source of the additional urinary calcium remains unclear. One hypothesis is that the high endogenous acid load of a high-protein diet is partially buffered by bone, leading to increased skeletal resorption and hypercalciuria. We used dual stable calcium isotopes to quantify the effect of a high-protein diet on calcium kinetics in women. The study consisted of 2 wk of a lead-in, well-balanced diet followed by 10 d of an experimental diet containing either moderate (1.0 g/kg) or high (2.1 g/kg) protein. Thirteen healthy women received both levels of protein in random order. Intestinal calcium absorption increased during the high-protein diet in comparison with the moderate (26.2 +/- 1.9% vs. 18.5 +/- 1.6%, P < 0.0001, mean +/- sem) as did urinary calcium (5.23 +/- 0.37 vs. 3.57 +/- 0.35 mmol/d, P < 0.0001, mean +/- sem). The high-protein diet caused a significant reduction in the fraction of urinary calcium of bone origin and a nonsignificant trend toward a reduction in the rate of bone turnover. There were no protein-induced effects on net bone balance. These data directly demonstrate that, at least in the short term, high-protein diets are not detrimental to bone.", "title": "The impact of dietary protein on calcium absorption and kinetic measures of bone turnover in women." }, { "docid": "MED-4454", "text": "The aim of this study was to determine the bioavailability and kinetics of the supposed anticarcinogen sulforaphane, the hydrolysis product of glucoraphanin, from raw and cooked broccoli. Eight men consumed 200 g of crushed broccoli, raw or cooked, with a warm meal in a randomized, free-living, open cross-over trial. Higher amounts of sulforaphane were found in the blood and urine when broccoli was eaten raw (bioavailability of 37%) versus cooked (3.4%, p ) 0.002). Absorption of sulforaphane was delayed when cooked broccoli was consumed (peak plasma time ) 6 h) versus raw broccoli (1.6 h, p ) 0.001). Excretion half-lives were comparable, 2.6 and 2.4 h on average, for raw and cooked broccoli, respectively (p ) 0.5). This study gives complete kinetic data and shows that consumption of raw broccoli results in faster absorption, higher bioavailability, and higher peak plasma amounts of sulforaphane, compared to cooked broccoli.", "title": "Bioavailability and kinetics of sulforaphane in humans after consumption of cooked versus raw broccoli." }, { "docid": "MED-4498", "text": "We present a case of a critically ill infant with severe multidrug-resistant Pseudomonas aeruginosa pneumonia and bacteremia who was treated with garlic and antibiotics after in vitro demonstration of a change in the resistance pattern via the disc diffusion method on garlic-treated Mueller Hinton agar. To our knowledge, this is the first report of therapeutic garlic use in a critically ill infant in the literature.", "title": "Trial of garlic as an adjunct therapy for multidrug resistant Pseudomonas aeruginosa pneumonia in a critically ill infant." }, { "docid": "MED-4722", "text": "BACKGROUND: There has been a resurgence of interest in the controversial relation between dietary protein and bone health. OBJECTIVE: This article reports on the first systematic review and meta-analysis of the relation between protein and bone health in healthy human adults. DESIGN: The MEDLINE (January 1966 to September 2007) and EMBASE (1974 to July 2008) databases were electronically searched for all relevant studies of healthy adults; studies of calcium excretion or calcium balance were excluded. RESULTS: In cross-sectional surveys, all pooled r values for the relation between protein intake and bone mineral density (BMD) or bone mineral content at the main clinically relevant sites were significant and positive; protein intake explained 1-2% of BMD. A meta-analysis of randomized placebo-controlled trials indicated a significant positive influence of all protein supplementation on lumbar spine BMD but showed no association with relative risk of hip fractures. No significant effects were identified for soy protein or milk basic protein on lumbar spine BMD. CONCLUSIONS: A small positive effect of protein supplementation on lumbar spine BMD in randomized placebo-controlled trials supports the positive association between protein intake and bone health found in cross-sectional surveys. However, these results were not supported by cohort study findings for hip fracture risk. Any effects found were small and had 95% CIs that were close to zero. Therefore, there is a small benefit of protein on bone health, but the benefit may not necessarily translate into reduced fracture risk in the long term.", "title": "Dietary protein and bone health: a systematic review and meta-analysis." }, { "docid": "MED-4977", "text": "Background/Aim Harmane [1-methyl-9H-pyrido(3,4-b)indole] is a tremor-producing neurotoxin. Blood harmane concentrations are elevated in essential tremor (ET) patients for unclear reasons. Potential mechanisms include increased dietary harmane intake (especially through well-cooked meat) or genetic-metabolic factors. We tested the hypothesis that meat consumption and level of meat doneness are higher in ET cases than in controls. Methods Detailed data were collected using the Lawrence Livermore National Laboratory Meat Questionnaire. Results Total current meat consumption was greater in men with than without ET (135.3 ± 71.1 vs. 110.6 ± 80.4 g/day, p = 0.03) but not in women with versus without ET (80.6 ± 50.0 vs. 79.3 ± 51.0 g/day, p = 0.76). In an adjusted logistic regression analysis in males, higher total current meat consumption was associated with ET (OR = 1.006, p = 0.04, i.e., with 10 additional g/day of meat, odds of ET increased by 6%). Male cases had higher odds of being in the highest than lowest quartile of total current meat consumption (adjusted OR = 21.36, p = 0.001). Meat doneness level was similar in cases and controls. Conclusion This study provides evidence of a dietary difference between male ET cases and male controls. The etiological ramifications of these results warrant additional investigation. Copyright © 2008 S. Karger AG, Basel", "title": "Dietary Epidemiology of Essential Tremor: Meat Consumption and Meat Cooking Practices" }, { "docid": "MED-3228", "text": "A precise understanding of the role of dietary protein in bone health has been evasive despite decades of research. It is known that a dietary acid load is harmful to bone, and sulfur-containing amino acids are metabolized to provide such an acid load. It is also known that protein elevates urine calcium loss. However, recent clinical studies and a meta-analysis have indicated either no effect or a modest benefit associated with higher protein intakes. These contradictory considerations may be explained by the existence of a two-faced relationship between protein and bone, with simultaneous positive and negative pathways. In opposition to the negative effects of dietary acid load, protein may exert positive effects related to improving calcium absorption, increasing insulin-like growth factor 1, or improving lean body mass, which, in turn, improves bone strength. Putative mechanisms behind these pathways are reviewed here, and some limitations in the historical literature as well as suggested measures to counter these in the future are identified. When positive and negative pathways are considered in tandem, protein may offer modest benefits to bone in the presence of adequate dietary calcium and acid-neutralizing fruits and vegetables. © 2011 International Life Sciences Institute.", "title": "Dietary protein and bone health: harmonizing conflicting theories." }, { "docid": "MED-3221", "text": "Background The finding reported in a previous paper - alkalization of urine facilitates uric acid excretion - is contradictory to what one might expect to occur: because food materials for the alkalization of urine contain fewer purine bodies than those for acidification, less uric acid in alkaline urine should have been excreted than in acid urine. To make clear what component of uric acid excretion mechanisms is responsible for this unexpected finding, we simultaneously collected data for the concentration of both creatinine and uric acid in serum as well as in urine, in order to calculate both uric acid and creatinine clearances. Methods Within the framework of the Japanese government’s health promotion program, we made recipes which consisted of protein-rich and less vegetable-fruit food materials for H + -load (acidic diet) and others composed of less protein and more vegetable-fruit rich food materials (alkaline diet). This is a crossover study within some limitations. Healthy female students, who had no medical problems at the regular physical examination provided by the university, were enrolled in this consecutive 5-day study for each test. From whole-day collected urine, total volume, pH, organic acid, creatinine, uric acid, titratable acid and all cations (Na+,K+,Ca2+,Mg2+,NH4+) and anions (Cl−,SO42−,PO4−) necessary for the estimation of acid–base balance were measured. In the early morning before breakfast of the 1st, 3rd and 5th experimental day, we sampled 5 mL of blood to estimate the creatinine and uric acid concentration in serum. Results and discussion Urine pH reached a steady state 3 days after switching from ordinary daily diets to specified regimens. The amount of acid generated ([SO42−] + organic acid − gut alkali)was linearly related with the excretion of acid (titratable acid + [NH4+] − [HCO3−]), indicating that H + in urine is generated by the metabolic degradation of food materials. Uric acid and excreted urine pH retained a linear relationship, as reported previously. Among the five factors which are associated with calculating clearances for both uric acid and creatinine, we identified a conspicuous difference between acidic and alkaline diets in the uric acid concentration in serum as well as in urine; uric acid in the serum was higher in the acidic group than in the alkaline group, while uric acid in the urine in the acidic group was lower than that in the alkaline group. These changes of uric acid in acidic urine and in serum were reflected in the reduction of its clearance. From these observations, it is considered that uric acid may be reabsorbed more actively in acidic urine than in alkaline urine. Conclusion We conclude that alkalization of urine by eating nutritionally well-designed alkaline -prone food is effective for removing uric acid from the body.", "title": "Effect of urine pH changed by dietary intervention on uric acid clearance mechanism of pH-dependent excretion of urinary uric acid" }, { "docid": "MED-4829", "text": "BACKGROUND: Statin therapy can cause myopathy, however it is unclear whether this exacerbates age-related muscle function declines. AIM: To describe differences between statin users and non-users in muscle mass, muscle function and falls risk in a group of community-dwelling older adults. DESIGN: A prospective, population-based cohort study with a mean follow-up of 2.6 years. METHODS: Total 774 older adults [48% female; mean (standard deviation) age = 62 (7) years] were examined at baseline and follow-up. Differences in percentage appendicular lean mass (%ALM), leg strength, leg muscle quality (LMQ; specific force) and falls risk were compared for statin users and non-users. RESULTS: There were 147 (19%) statin users at baseline and 179 (23%) at follow-up. Longitudinal analyses revealed statin use at baseline predicted increased falls risk scores over 2.6 years (0.14, 95% CI 0.01 to 0.27) and a trend towards increased %ALM (0.45%, 95% CI -0.01 to 0.92). Statin users at both time points demonstrated decreased leg strength (-5.02 kg, 95% CI -9.65 to -0.40) and LMQ (-0.30 kg/kg, 95% CI -0.59 to -0.01), and trended towards increased falls risk (0.13, 95% CI -0.01 to 0.26) compared to controls. Finally, statin users at both baseline and follow-up demonstrated decreased leg strength (-16.17 kg, 95% CI -30.19 to -2.15) and LMQ (-1.13 kg/kg, 95% CI -2.02 to -0.24) compared to those who had ceased statin use at follow-up. CONCLUSION: Statin use may exacerbate muscle performance declines and falls risk associated with aging without a concomitant decrease in muscle mass, and this effect may be reversible with cessation.", "title": "Statin therapy, muscle function and falls risk in community-dwelling older adults." }, { "docid": "MED-3217", "text": "To investigate whether systemic acid-base equilibrium changes with aging in normal adult humans, we reviewed published articles reporting the acid-base composition of arterial, arterialized venous, or capillary blood in age-identified healthy subjects. We extracted or calculated blood hydrogen ion concentration ([H+]), plasma bicarbonate concentration ([HCO3(-)]), blood PCO2, and age, and computed a total of 61 age-group means, distributed among eight 10-year intervals from age 20 to 100 years. Using linear regression analysis, we found that with increasing age, there is a significant increase in the steady-state blood [H+] (p < .001), and reduction in steady-state plasma [HCO3(-)] (p < .001), indicative of a progressively worsening low-level metabolic acidosis. Blood PCO2 decreased with age (p < .05), in keeping with the expected respiratory adaptation to metabolic acidosis. Such age-related increasing metabolic acidosis may reflect in part the normal decline of renal function with increasing age. The role of age-related metabolic acidosis in the pathogenesis of the degenerative diseases of aging warrants consideration.", "title": "Age and systemic acid-base equilibrium: analysis of published data." }, { "docid": "MED-4828", "text": "Background Many patients taking statins often complain of muscle pain and weakness. The extent to which muscle pain reflects muscle injury is unknown. Methods We obtained biopsy samples from the vastus lateralis muscle of 83 patients. Of the 44 patients with clinically diagnosed statin-associated myopathy, 29 were currently taking a statin, and 15 had discontinued statin therapy before the biopsy (minimal duration of discontinuation 3 weeks). We also included 19 patients who were taking statins and had no myopathy, and 20 patients who had never taken statins and had no myopathy. We classified the muscles as injured if 2% or more of the muscle fibres in a biopsy sample showed damage. Using reverse transcriptase polymerase chain reaction, we evaluated the expression levels of candidate genes potentially related to myocyte injury. Results Muscle injury was observed in 25 (of 44) patients with myopathy and in 1 patient without myopathy. Only 1 patient with structural injury had a circulating level of creatine phosphokinase that was elevated more than 1950 U/L (10× the upper limit of normal). Expression of ryanodine receptor 3 was significantly upregulated in patients with biopsy evidence of structural damage (1.7, standard error of the mean 0.3). Interpretation Persistent myopathy in patients taking statins reflects structural muscle damage. A lack of elevated levels of circulating creatine phosphokinase does not rule out structural muscle injury. Upregulation of the expression of ryanodine receptor 3 is suggestive of an intracellular calcium leak.", "title": "Association between statin-associated myopathy and skeletal muscle damage" }, { "docid": "MED-3233", "text": "Our objective in this study was to determine the effects of a high-protein and high-potential renal acid load (PRAL) diet on calcium (Ca) absorption and retention and markers of bone metabolism. In a randomized crossover design, 16 postmenopausal women consumed 2 diets: 1 with low protein and low PRAL (LPLP; total protein: 61 g/d; PRAL: -48 mEq/d) and 1 with high protein and high PRAL (HPHP; total protein: 118 g/d; PRAL: 33 mEq/d) for 7 wk each separated by a 1-wk break. Ca absorption was measured by whole body scintillation counting of radio-labeled (47)Ca. Compared with the LPLP diet, the HPHP diet increased participants' serum IGF-I concentrations (P < 0.0001), decreased serum intact PTH concentrations (P < 0.001), and increased fractional (47)Ca absorption (mean ± pooled SD: 22.3 vs. 26.5 ± 5.4%; P < 0.05) and urinary Ca excretion (156 vs. 203 ± 63 mg/d; P = 0.005). The net difference between the amount of Ca absorbed and excreted in urine did not differ between 2 diet periods (55 vs. 28 ± 51 mg/d). The dietary treatments did not affect other markers of bone metabolism. In summary, a diet high in protein and PRAL increases the fractional absorption of dietary Ca, which partially compensates for increased urinary Ca, in postmenopausal women. The increased IGF-I and decreased PTH concentrations in serum, with no change in biomarkers of bone resorption or formation, indicate a high-protein diet has no adverse effects on bone health.", "title": "A diet high in meat protein and potential renal acid load increases fractional calcium absorption and urinary calcium excretion without affecting m..." }, { "docid": "MED-4830", "text": "Muscle pain and weakness are frequent complaints in patients receiving 3-hydroxymethylglutaryl coenzymeA (HMG CoA) reductase inhibitors (statins). Many patients with myalgia have creatine kinase levels that are either normal or only marginally elevated, and no obvious structural defects have been reported in patients with myalgia only. To investigate further the mechanism that mediates statin-induced skeletal muscle damage, skeletal muscle biopsies from statin-treated and non-statin-treated patients were examined using both electron microscopy and biochemical approaches. The present paper reports clear evidence of skeletal muscle damage in statin-treated patients, despite their being asymptomatic. Though the degree of overall damage is slight, it has a characteristic pattern that includes breakdown of the T-tubular system and subsarcolemmal rupture. These characteristic structural abnormalities observed in the statin-treated patients were reproduced by extraction of cholesterol from skeletal muscle fibres in vitro. These findings support the hypothesis that statin-induced cholesterol lowering per se contributes to myocyte damage and suggest further that it is the specific lipid/protein organization of the skeletal muscle cell itself that renders it particularly vulnerable. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.", "title": "Statin therapy induces ultrastructural damage in skeletal muscle in patients without myalgia." } ]
[ { "docid": "MED-2098", "text": "Bile acid binding capacity has been related to the cholesterol-lowering potential of foods and food fractions. Lowered recirculation of bile acids results in utilization of cholesterol to synthesize bile acid and reduced fat absorption. Secondary bile acids have been associated with increased risk of cancer. Bile acid binding potential has been related to lowering the risk of heart disease and that of cancer. Previously, we have reported bile acid binding by several uncooked vegetables. However, most vegetables are consumed after cooking. How cooking would influence in vitro bile acid binding of various vegetables was investigated using a mixture of bile acids secreted in human bile under physiological conditions. Eight replicate incubations were conducted for each treatment simulating gastric and intestinal digestion, which included a substrate only, a bile acid mixture only, and 6 with substrate and bile acid mixture. Cholestyramine (a cholesterol-lowering, bile acid binding drug) was the positive control treatment and cellulose was the negative control. Relative to cholestyramine, in vitro bile acid binding on dry matter basis was for the collard greens, kale, and mustard greens, 13%; broccoli, 10%; Brussels sprouts and spinach, 8%; green bell pepper, 7%; and cabbage, 5%. These results point to the significantly different (P < or = .05) health-promoting potential of collard greens = kale = mustard greens > broccoli > Brussels sprouts = spinach = green bell pepper > cabbage as indicated by their bile acid binding on dry matter basis. Steam cooking significantly improved the in vitro bile acid binding of collard greens, kale, mustard greens, broccoli, green bell pepper, and cabbage compared with previously observed bile acid binding values for these vegetables raw (uncooked). Inclusion of steam-cooked collard greens, kale, mustard greens, broccoli, green bell pepper, and cabbage in our daily diet as health-promoting vegetables should be emphasized. These green/leafy vegetables, when consumed regularly after steam cooking, would lower the risk of cardiovascular disease and cancer, advance human nutrition research, and improve public health.", "title": "Steam cooking significantly improves in vitro bile acid binding of collard greens, kale, mustard greens, broccoli, green bell pepper, and cabbage." }, { "docid": "MED-842", "text": "The accumulation of thallium (Tl) in brassicaceous crops is widely known, but both the uptake extents of Tl by the individual cultivars of green cabbage and the distribution of Tl in the tissues of green cabbage are not well understood. Five commonly available cultivars of green cabbage grown in the Tl-spiked pot-culture trials were studied for the uptake extent and subcellular distribution of Tl. The results showed that all the trial cultivars mainly concentrated Tl in the leaves (101∼192 mg/kg, DW) rather than in the roots or stems, with no significant differences among cultivars (p = 0.455). Tl accumulation in the leaves revealed obvious subcellular fractionation: cell cytosol and vacuole >> cell wall > cell organelles. The majority (∼ 88%) of leaf-Tl was found to be in the fraction of cytosol and vacuole, which also served as the major storage site for other major elements such as Ca and Mg. This specific subcellular fractionation of Tl appeared to enable green cabbage to avoid Tl damage to its vital organelles and to help green cabbage tolerate and detoxify Tl. This study demonstrated that all the five green cabbage cultivars show a good application potential in the phytoremediation of Tl-contaminated soils.", "title": "High Accumulation and Subcellular Distribution of Thallium in Green Cabbage (Brassica Oleracea L. Var. Capitata L.)." }, { "docid": "MED-887", "text": "Colored-flesh potatoes are an excellent source of health-benefiting dietary polyphenols, but are stored for up to 3-6 months before consumption. This study investigated the effect of simulated commercial storage conditions on antioxidant activity (DPPH, ABTS), phenolic content (FCR) and composition (UPLC-MS), and anticancer properties (early, HCT-116 and advanced stage, HT-29 human colon cancer cell lines) of potato bioactive compounds. Extracts from seven potato clones of differing flesh colors (white, yellow, and purple) before and after 90 days of storage were used in this study. The antioxidant activity of all clones increased with storage; however, an increase in total phenolic content was observed only in purple-fleshed clones. Advanced purple-fleshed selection CO97227-2P/PW had greater levels of total phenolics, monomeric anthocyanins, antioxidant activity and a diverse anthocyanin composition as compared with Purple Majesty. Purple-fleshed potatoes were more potent in suppressing proliferation and elevating apoptosis of colon cancer cells compared with white- and yellow-fleshed potatoes. The extracts from both fresh and stored potatoes (10-30 μg/mL) suppressed cancer cell proliferation and elevated apoptosis compared with the solvent control, but these anticancer effects were more pronounced with the fresh potatoes. Storage duration had a strong positive correlation with antioxidant activity and percentage of viable cancer cells and a negative correlation with apoptosis induction. These results suggest that although the antioxidant activity and phenolic content of potatoes were increased with storage, the antiproliferative and pro-apoptotic activities were suppressed. Thus, in the assessment of the effects of farm to fork operations on the health-benefiting properties of plant foods, it is critical to use quantitative analytical techniques in conjunction with in vitro and/or in vivo biological assays.", "title": "Storage elevates phenolic content and antioxidant activity but suppresses antiproliferative and pro-apoptotic properties of colored-flesh potatoes ..." }, { "docid": "MED-2292", "text": "In industrialized nations, diverticular disease affects up to 70% of individuals by 60 years of age, with symptoms that can range from mild gastrointestinal disturbance to incapacitating pain. Diverticular disease appears to be related to increasing affluence and changed diet: Current theory holds that diverticular disease's origin is low-fiber diet. This explains why its incidence is highest and accelerating in the more prosperous countries where intake of fiber has decreased and intake of milled grains and refined sugars has increased over time. Not all patients develop symptoms, but if they do, the most frequent complaints associated with diverticulosis are cramping in the left-lower quadrant, bloating, constipation, and soiling. If diverticula perforate the gut's wall into the pericolic tissue, small and large abscesses, accompanied by bleeding, can form. Fistulization, when it occurs, most often penetrates to the bladder. Treatment addresses symptoms and may require hospitalization. During symptomatic periods, patients do best on low-fiber, bland diets. Once the acute episode or highly symptomatic period resolves or chronic disease is managed, patients should gradually increase dietary fiber to 20 to 30 grams daily or take dietary fiber in the form of bulk stimulants like psyllium.", "title": "Diverticular disease: eat your fiber!" }, { "docid": "MED-4256", "text": "This systematic review collated seventy-eight studies exploring waist-to-height ratio (WHtR) and waist circumference (WC) or BMI as predictors of diabetes and CVD, published in English between 1950 and 2008. Twenty-two prospective analyses showed that WHtR and WC were significant predictors of these cardiometabolic outcomes more often than BMI, with similar OR, sometimes being significant predictors after adjustment for BMI. Observations from cross-sectional analyses, forty-four in adults, thirteen in children, supported these predictions. Receiver operator characteristic (ROC) analysis revealed mean area under ROC (AUROC) values of 0·704, 0·693 and 0·671 for WHtR, WC and BMI, respectively. Mean boundary values for WHtR, covering all cardiometabolic outcomes, from studies in fourteen different countries and including Caucasian, Asian and Central American subjects, were 0·50 for men and 0·50 for women. WHtR and WC are therefore similar predictors of diabetes and CVD, both being stronger than, and independent of, BMI. To make firmer statistical comparison, a meta-analysis is required. The AUROC analyses indicate that WHtR may be a more useful global clinical screening tool than WC, with a weighted mean boundary value of 0·5, supporting the simple public health message 'keep your waist circumference to less than half your height'.", "title": "A systematic review of waist-to-height ratio as a screening tool for the prediction of cardiovascular disease and diabetes: 0·5 could be a suitable..." }, { "docid": "MED-4350", "text": "Potatoes have the highest daily per capita consumption of all vegetables in the U.S. diet. Pigmented potatoes contain high concentrations of antioxidants, including phenolic acids, anthocyanins, and carotenoids. In a single-dose study six to eight microwaved potatoes with skins or a comparable amount of refined starch as cooked biscuits was given to eight normal fasting subjects; repeated samples of blood were taken over an 8 h period. Plasma antioxidant capacity was measured by ferric reducing antioxidant power (FRAP). A 24 h urine was taken before and after each regimen. Urine antioxidant capacity due to polyphenol was measured by Folin reagent after correction for nonphenolic interferences with a solid phase (Polyclar) procedure. Potato caused an increase in plasma and urine antioxidant capacity, whereas refined potato starch caused a decrease in both; that is, it acted as a pro-oxidant. In a crossover study 18 hypertensive subjects with an average BMI of 29 were given either six to eight small microwaved purple potatoes twice daily or no potatoes for 4 weeks and then given the other regimen for another 4 weeks. There was no significant effect of potato on fasting plasma glucose, lipids, or HbA1c. There was no significant body weight increase. Diastolic blood pressure significantly decreased 4.3%, a 4 mm reduction. Systolic blood pressure decreased 3.5%, a 5 mm reduction. This blood pressure drop occurred despite the fact that 14 of 18 subjects were taking antihypertensive drugs. This is the first study to investigate the effect of potatoes on blood pressure. Thus, purple potatoes are an effective hypotensive agent and lower the risk of heart disease and stroke in hypertensive subjects without weight gain.", "title": "High-antioxidant potatoes: acute in vivo antioxidant source and hypotensive agent in humans after supplementation to hypertensive subjects." }, { "docid": "MED-2083", "text": "Coronary artery disease is responsible for much mortality and morbidity around the world. Platelets are involved in atherosclerotic disease development and the reduction of platelet activity by medications reduces the incidence and severity of disease. Red wine and grapes contain polyphenolic compounds, including flavonoids, which can reduce platelet aggregation and have been associated with lower rates of cardiovascular disease. Citrus fruits contain different classes of polyphenolics that may not share the same properties. This study evaluated whether commercial grape, orange and grapefruit juices, taken daily, reduce ex vivo platelet activity. In a randomized cross-over design, ten healthy human subjects (ages 26-58 y, five of each gender) drank 5-7.5 mL/(kg. d) of purple grape juice, orange juice or grapefruit juice for 7-10 d each. Platelet aggregation (whole blood impedance aggregometry, Chronolog Model #590) at baseline was compared to results after consumption of each juice. Drinking purple grape juice for one week reduced the whole blood platelet aggregation response to 1 mg/L of collagen by 77% (from 17.9 +/- 2.3 to 4.0 +/- 6.8 ohms, P = 0.0002). Orange juice and grapefruit juice had no effect on platelet aggregation. The purple grape juice had approximately three times the total polyphenolic concentration of the citrus juices and was a potent platelet inhibitor in healthy subjects while the citrus juices showed no effect. The platelet inhibitory effect of the flavonoids in grape juice may decrease the risk of coronary thrombosis and myocardial infarction.", "title": "Grape juice, but not orange juice or grapefruit juice, inhibits human platelet aggregation." }, { "docid": "MED-2577", "text": "A case-control study probing the role of diet on the incidence of colorectal cancer was undertaken in Athens, Greece, in a population characterized by ethnic homogeneity but substantial heterogeneity with respect to dietary habits. The case series consisted of 100 consecutive patients with histologically confirmed colorectal cancer admitted to two large hospitals of Athens during a 16-month period; the control series consisted of orthopaedic patients, admitted to the same hospitals during the same time period, individually matched to the index cases by age and sex. Dietary histories concerning the frequency of consumption (per month or per week) of about 80 food items were obtained by the same interviewer. Cases reported significantly less frequent consumption of vegetables (particularly beets, spinach, lettuce and cabbage) and, independently, significantly more frequent consumption of meat (notably lamb and beef). Between the two extremes (high-vegetable, low-meat diet versus high-meat, low-vegetable diet) a risk ratio of about 8 appears to exist, sufficient (in size and direction) to explain a substantial part of the international variation in the incidence of colorectal cancer. Significant associations were not found with beer or other alcoholic beverages, and significant interactions were not noted with respect to age, sex and anatomic localization (colon vs. rectum).", "title": "Diet and colorectal cancer: a case-control study in Greece." }, { "docid": "MED-940", "text": "Saffron (Crocus sativus Linn.) have been perceived by the public as a strong aphrodisiac herbal product. However, studies addressing the potential beneficial effects of saffron on erectile function (EF) in men with ED are lacking. Our aim was to evaluate the efficacy and safety of saffron administration on EF in men with ED. After a 4-week baseline assessment, 346 men with ED (mean age 46.6+/-8.4 years) were randomized to receive on-demand sildenafil for 12 weeks followed by 30 mg saffron twice daily for another 12 weeks or vice versa, separated by a 2-week washout period. To determine the type of ED, penile color duplex Doppler ultrasonography before and after intracavernosal injection with 20 microg prostaglandin E(1), pudendal nerve conduction tests and impaired sensory-evoked potential studies were performed. Subjects were assessed with an International Index of Erectile Function (IIEF) questionnaire, Sexual Encounter Profile (SEP) diary questions, patient and partner versions of the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire and the Global Efficacy Question (GEQ) 'Has the medication you have been taking improved your erections?' No significant improvements were observed with regard to the IIEF sexual function domains, SEP questions and EDITS scores with saffron administration. The mean changes from baseline values in IIEF-EF domain were +87.6% and +9.8% in sildenafil and placebo groups, respectively (P=0.08). We did not observe any improvement in 15 individual IIEF questions in patients while taking saffron. Treatment satisfaction as assessed by partner versions of EDITS was found to be very low in saffron patients (72.4 vs 25.4, P=0.001). Mean per patient 'yes' responses to GEQ was 91.2 and 4.2% for sildenafil and saffron, respectively (P=0.0001). These findings do not support a beneficial effect of saffron administration in men with ED.", "title": "An open label, randomized, fixed-dose, crossover study comparing efficacy and safety of sildenafil citrate and saffron (Crocus sativus Linn.) for t..." }, { "docid": "MED-3552", "text": "The study evaluated the protective effects of purple rice (Oryza sativa L.) bran extract (PRE) and its constituents, cyanidin and peonidin, against angiogenesis induced by vascular endothelial growth factor (VEGF). The effects of VEGF and PRE were examined by in vitro tube formation assays and following 14-day co-culture of human umbilical vein endothelial cells (HUVECs) and fibroblasts. The antiangiogenic mechanism of PRE was evaluated by VEGF-induced proliferation and migration of HUVECs and/or human retinal microvascular endothelial cells (HRMECs) and phosphorylation of extracellular signal-regulated kinase (ERK) and p38. The PRE significantly suppressed VEGF-induced tube formation, proliferation and migration in HUVECs and HRMECs as well as phosphorylation of ERK and p38. Cyanidin and peonidin also suppressed the proliferation and migration induced by VEGF. These findings indicate that PRE and anthocyanidins suppress VEGF-induced angiogenesis by inhibiting proliferation and migration and suggest that the inhibition of phosphorylated-ERK and -p38 may be involved in the underlying mechanism. Copyright © 2011 John Wiley & Sons, Ltd.", "title": "Purple rice (Oryza sativa L.) extract and its constituents inhibit VEGF-induced angiogenesis." }, { "docid": "MED-888", "text": "The purpose of the current study was to determine the anti-obesity and anti-inflammatory effects of an extract of purple sweet potatoes (PSPs) on 3T3-L1 adipocytes. For this purpose, differentiated 3T3-L1 adipocytes were treated with a PSP extract at concentrations of 1,000, 2,000, and 3,000 μg/mL for 24 hours. Then, we measured the changes in the sizes of the adipocytes, the secretion of leptin, and the mRNA/protein expression of lipogenic, inflammatory, and lipolytic factors after the treatment with the PSP extract. The PSP extract diminished leptin secretion, indicating that growth of fat droplets was suppressed. The extract also suppressed the expression of mRNAs of lipogenic and inflammatory factors and promoted lipolytic action. The antioxidative activity of the PSP extract was also measured using three different in vitro methods: 1,1-diphenyl-2-picrylhydrazyl free radical scavenging activity, ferric reducing ability potential assay, and chelating activity of transition metal ions. Taken together, our study shows that PSP extract has antilipogenic, anti-inflammatory, and lipolytic effects on adipocytes and has radical scavenging and reducing activity.", "title": "Anti-obesity and antioxidative effects of purple sweet potato extract in 3T3-L1 adipocytes in vitro." }, { "docid": "MED-4585", "text": "The total phenolic content of 13 commercially available fruit juices and juice drinks, selected to represent the most popular juice flavors in the United Kingdom, were analyzed using the Folin-Ciocalteu assay. Individual phenolic compounds were identified and quantified using HPLC-PDA-MS2. The catechin content and degree of polymerization of proanthocyanidins were also analyzed. Purple grape juice contained the largest number of individual phenolic compounds and also the highest concentration of total phenolics. The main components were flavan-3-ols, anthocyanins, and hydroxycinnamates, which accounted for 93% of the total phenolic content. In contrast, white grape juice, which contained principally hydroxycinnamates, had the lowest total phenolic content. Antioxidant activity was measured using the ORAC and FRAP assays, and the data obtained were in broad agreement with total phenol content. In view of the recent findings of the Kame project indicating that long-term fruit juice consumption can provide protection against Alzheimer's disease (Dai et al. Am. J. Med. 2006, 379, 464-475), it is suggested that the protective effects may be enhanced by consumption of a combination of juices rich in phenolics and containing a diverse variety of individual phenolic compounds, namely, juices derived from purple grapes, grapefruit, cranberries, and apples.", "title": "Evaluation of phenolic compounds in commercial fruit juices and fruit drinks." }, { "docid": "MED-1293", "text": "In the domain of nutrition, exploring the diet-health linkages is major area of research. The outcomes of such interventions led to widespread acceptance of functional and nutraceutical foods; however, augmenting immunity is a major concern of dietary regimens. Indeed, the immune system is incredible arrangement of specific organs and cells that enabled humans to carry out defense against undesired responses. Its proper functionality is essential to maintain the body homeostasis. Array of plants and their components hold immunomodulating properties. Their possible inclusion in diets could explore new therapeutic avenues to enhanced immunity against diseases. The review intended to highlight the importance of garlic (Allium sativum), green tea (Camellia sinensis), ginger (Zingiber officinale), purple coneflower (Echinacea), black cumin (Nigella sativa), licorice (Glycyrrhiza glabra), Astragalus and St. John's wort (Hypericum perforatum) as natural immune boosters. These plants are bestowed with functional ingredients that may provide protection against various menaces. Modes of their actions include boosting and functioning of immune system, activation and suppression of immune specialized cells, interfering in several pathways that eventually led to improvement in immune responses and defense system. In addition, some of these plants carry free radical scavenging and anti-inflammatory activities that are helpful against cancer insurgence. Nevertheless, interaction between drugs and herbs/botanicals should be well investigated before recommended for their safe use, and such information must be disseminated to the allied stakeholders.", "title": "Immunity: plants as effective mediators." }, { "docid": "MED-2194", "text": "Scope Anthocyanins, the natural pigments in plant foods, have been associated with cancer prevention. However, the content of anthocyanins in staple foods is typically low and the mechanisms by which they exert anti-cancer activity is not yet fully defined. Methods and results We selected an anthocyanin-enriched purple-fleshed sweet potato clone, P40, and investigated its potential anti-cancer effect in both in vitro cell culture and in vivo animal model. In addition to a high level of total phenolics and antioxidant capacity, P40 possesses a high content of anthocyanins at 7.5 mg/g dry matter. Treatment of human colonic SW480 cancer cells with P40 anthocyanin extracts at 0–40 μM of peonidin-3-glucoside equivalent resulted in a dose-dependent decrease in cell number due to cytostatic arrest of cell cycle at G1 phase but not cytotoxicity. Furthermore, dietary P40 at 10–30% significantly suppressed azoxymethane-induced formation of aberrant crypt foci in the colons of CF-1 mice in conjunction with, at least in part, a lesser proliferative PCNA and a greater apoptotic caspase-3 expression in the colon mucosal epithelial cells. Conclusion These observations, coupled with both in vitro and in vivo studies reported here, suggest anthocyanin-enriched sweet potato P40 may protect against colorectal cancer by inducing cell cycle arrest, anti-proliferative and apoptotic mechanisms.", "title": "Role of Anthocyanin-enriched Purple-fleshed Sweet Potato P40 in Colorectal Cancer Prevention" }, { "docid": "MED-2417", "text": "BACKGROUND: Inconsistent associations have been reported between diet and breast cancer. OBJECTIVE: We prospectively examined the association between dietary patterns and postmenopausal breast cancer risk in a US-wide cohort study. DESIGN: Data were analyzed from 40 559 women who completed a self-administered 61-item Block food-frequency questionnaire in the Breast Cancer Detection Demonstration Project, 1987-1998; 1868 of those women developed breast cancer. Dietary patterns were defined by using principal components factor analysis. Cox proportional hazard regression was used to assess breast cancer risk. RESULTS: Three major dietary patterns emerged: vegetable-fish/poultry-fruit, beef/pork-starch, and traditional southern. The vegetable-fish/poultry-fruit pattern was associated with higher education than were the other patterns, but was similar in nutrient intake to the traditional southern pattern. After adjustment for confounders, there was no significant association between the vegetable-fish/poultry-fruit and beef/pork-starch patterns and breast cancer. The traditional southern pattern, however, was associated with a nonsignificantly reduced breast cancer risk among all cases (in situ and invasive) that was significant for invasive breast cancer (relative hazard = 0.78; 95% CI = 0.65, 0.95; P for trend = 0.003). This diet was also associated with a reduced risk in women without a family history of breast cancer (P = 0.05), who were underweight or normal weight [body mass index (in kg/m(2)) < 25; P = 0.02], or who had tumors positive for estrogen receptor (P = 0.01) or progesterone receptor (P = 0.003). Foods in the traditional southern pattern associated with reduced breast cancer risk were legumes, low mayonnaise-salad dressing intake, and possibly cabbage. CONCLUSIONS: The traditional southern diet or its components are associated with a reduced risk of invasive breast cancer in postmenopausal women.", "title": "Empirically derived dietary patterns and risk of postmenopausal breast cancer in a large prospective cohort study." }, { "docid": "MED-3381", "text": "Background: The proposition that synthetic food colors can induce adverse behavioral effects in children was first enunciated in 1975 by Feingold [Why Your Child Is Hyperactive. New York:Random House (1975)], who asserted that elevated sensitivity to food additives underlies the signs of hyperactivity observed in some children. Although the evidence suggested that some unknown proportion of children did respond to synthetic food colors, the U.S. Food and Drug Administration (FDA) interpreted the evidence as inconclusive. A study published in 2007 [McCann et al. Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled trial. Lancet 370:1560–1567 (2007)] drew renewed attention to the hypothesis because of the study’s size and scope. It led the FDA to review the evidence, hold a public hearing, and seek the advice of its Food Advisory Committee. In preparation for the hearing, the FDA reviewed the available evidence and concluded that it did not warrant further agency action. Objectives: In this commentary I examine the basis of the FDA’s position, the elements of the review that led to its decision and that of the Food Advisory Committee, and the reasons that this is an environmental health issue. Discussion: The FDA review confined itself, in essence, to the clinical diagnosis of hyperactivity, as did the charge to the committee, rather than asking the broader environmental question of behavioral effects in the general population; it failed to recognize the significance of vulnerable subpopulations; and it misinterpreted the meaning of effect size as a criterion of risk. The FDA’s response would have benefited from adopting the viewpoints and perspectives common to environmental health research. At the same time, the food color debate offers a lesson to environmental health researchers; namely, too narrow a focus on a single outcome or criterion can be misleading.", "title": "Synthetic Food Colors and Neurobehavioral Hazards: The View from Environmental Health Research" }, { "docid": "MED-4429", "text": "Epidemiological studies show that poultry meat and eggs are important sources for consumers' exposure to pathogens such as Salmonella and Campylobacter. There is a focus in many countries to reduce the level of human illness from food-borne pathogens. Reduction of the prevalence of contaminated poultry meat or eggs is one major area of focus. The other is risk communication to the consumer, where information aimed at changing the food preparation behaviour has been utilised as a risk management tool. The efficacy of messages such as 'cook poultry meat and eggs thoroughly' or 'wash your hands' will depend both on the ability to change consumer behaviour as well as where the risk can best be mitigated. In order to prioritise what message should be given to the consumer, the relative contribution of different exposure pathways finally leading to ingestion of the pathogens and resulting in illness needs to be known. It is important to know whether cross-contamination events or undercooking are the greatest risk lurking in consumers' kitchens. A review of studies looking at the location of pathogens in food products has been performed and data regarding internal and external (surface) contamination of poultry meat with Salmonella spp. and Campylobacter jejuni and C. coli is presented. In the case of eggs, data on internal contamination with Salmonella and for contamination of egg shells with Salmonella and Campylobacter are discussed. The results from published risk assessments for these pathogen-food commodity combinations have been evaluated and conclusions regarding the relative risk of internal and external contamination of poultry meat and eggs were drawn. In conclusion, cross-contamination events from activities such as use of the same cutting board for chicken meat and salad without intermediate cleaning or spreading of pathogens via the kitchen environment seem to be of greater importance than the risk associated with undercooking of poultry meat or eggs. Risk management options are discussed against the background of risk communication strategies used in different countries.", "title": "Cross-contamination versus undercooking of poultry meat or eggs - which risks need to be managed first?" }, { "docid": "MED-4455", "text": "The importance of dietary sulforaphane in helping maintain good health continues to gain support within the health-care community and awareness among U.S. consumers. In addition to the traditional avenue for obtaining sulforaphane, namely, the consumption of appropriate cruciferous vegetables, other consumer products containing added glucoraphanin, the natural precursor to sulforaphane, are now appearing in the United States. Crucifer seeds are a likely source for obtaining glucoraphanin, owing to a higher concentration of glucoraphanin and the relative ease of processing seeds as compared to vegetative parts. Seeds of several commonly consumed crucifers were analyzed not only for glucoraphanin but also for components that might have negative health implications, such as certain indole-containing glucosinolates and erucic acid-containing lipids. Glucoraphanin, 4-hydroxyglucobrassicin, other glucosinolates, and lipid erucic acid were quantified in seeds of 33 commercially available cultivars of broccoli, 4 cultivars each of kohlrabi, radish, cauliflower, Brussels sprouts, kale, and cabbage, and 2 cultivars of raab.", "title": "Glucoraphanin and 4-hydroxyglucobrassicin contents in seeds of 59 cultivars of broccoli, raab, kohlrabi, radish, cauliflower, brussels sprouts, kal..." }, { "docid": "MED-2066", "text": "Glucosinolates (GLSs) are found in Brassica vegetables. Examples of these sources include cabbage, Brussels sprouts, broccoli, cauliflower and various root vegetables (e.g. radish and turnip). A number of epidemiological studies have identified an inverse association between consumption of these vegetables and the risk of colon and rectal cancer. Animal studies have shown changes in enzyme activities and DNA damage resulting from consumption of Brassica vegetables or isothiocyanates, the breakdown products (BDP) of GLSs in the body. Mechanistic studies have begun to identify the ways in which the compounds may exert their protective action but the relevance of these studies to protective effects in the human alimentary tract is as yet unproven. In vitro studies with a number of specific isothiocyanates have suggested mechanisms that might be the basis of their chemoprotective effects. The concentration and composition of the GLSs in different plants, but also within a plant (e.g. in the seeds, roots or leaves), can vary greatly and also changes during plant development. Furthermore, the effects of various factors in the supply chain of Brassica vegetables including breeding, cultivation, storage and processing on intake and bioavailability of GLSs are extensively discussed in this paper.", "title": "Glucosinolates in Brassica vegetables: the influence of the food supply chain on intake, bioavailability and human health." }, { "docid": "MED-2075", "text": "Isothiocyanates are found in cruciferous vegetables such as broccoli, Brussels sprouts, cauliflower, and cabbage. Epidemiologic studies suggest that cruciferous vegetable intake may lower overall cancer risk, including colon and prostate cancer. Sulforaphane (SFN) is an isothiocyanate found in cruciferous vegetables and is especially high in broccoli and broccoli sprouts. SFN has proved to be an effective chemoprotective agent in cell culture, carcinogen-induced and genetic animal cancer models, as well as in xenograft models of cancer. Early research focused on the “blocking activity” of SFN via Phase 2 enzyme induction, as well as inhibition of enzymes involved in carcinogen activation, but there has been growing interest in other mechanisms of chemoprotection by SFN. Recent studies suggest that SFN offers protection against tumor development during the “post-initiation” phase and mechanisms for suppression effects of SFN, including cell cycle arrest and apoptosis induction are of particular interest. In humans, a key factor in determining the efficacy of SFN as a chemoprevention agent is gaining an understanding of the metabolism, distribution and bioavailability of SFN and the factors that alter these parameters. This review discusses the established anti-cancer properties of SFN, with an emphasis on the possible chemoprevention mechanisms. The current status of SFN in human clinical trials also is included, with consideration of the chemistry, metabolism, absorption and factors influencing SFN bioavailability.", "title": "Multi-targeted prevention of cancer by sulforaphane" }, { "docid": "MED-4587", "text": "A polyphenol-rich (P-R) juice drink was developed as a potential approach to increase intake of dietary polyphenols. Analysis of the beverage by HPLC with PDA, fluorescence, and MS detection facilitated the identification/partial identification of 40 flavonoids and related phenolic compounds. The main constituents were (-)-epigallocatechin and other green tea flavan-3-ols, phloretin-2'-O-glucoside, gallic acid, hesperetin-7-O-rutinoside, 5-O-caffeoylquinic acid, and procyanidins, with trace levels of several flavonols and purple grape juice anthocyanins also being present. Healthy human subjects (n = 10) consumed 350 mL of the P-R juice drink, after which plasma and urine samples were collected over a 0-24 h period. HPLC-MS analysis identified 13 metabolites in plasma and a further 20 in urine. Qualitatively, the profiles of the glucuronide, sulfated, and methylated metabolites were very similar to those detected in earlier investigations when the main components in the juice drink were consumed separately in feeding studies with coffee, green tea, orange juice, and apple cider.", "title": "Identification of metabolites in human plasma and urine after consumption of a polyphenol-rich juice drink." }, { "docid": "MED-2065", "text": "Sulforaphane [1-isothiocyanate-(4R)-(methylsulfinyl)butane] is a natural dietary isothiocyanate produced by the enzymatic action of the myrosinase on glucopharanin, a 4-methylsulfinylbutyl glucosinolate contained in cruciferous vegetables of the genus Brassica such as broccoli, brussel sprouts, and cabbage. Studies on this compound is increasing because its anticarcinogenic and cytoprotective properties in several in vivo experimental paradigms associated with oxidative stress such as focal cerebral ischemia, brain inflammation, intracerebral hemorrhage, ischemia and reperfusion induced acute renal failure, cisplatin induced-nephrotoxicity, streptozotocin-induced diabetes, carbon tetrachloride-induced hepatotoxicity and cardiac ischemia and reperfusion. This protective effect also has been observed in in vitro studies in different cell lines such as human neuroblastoma SH-SY5Y, renal epithelial proximal tubule LLC-PK1 cells and aortic smooth muscle A10 cells. Sulforaphane is considered an indirect antioxidant; this compound is able to induce many cytoprotective proteins, including antioxidant enzymes, through the Nrf2-antioxidant response element pathway. Heme oxygenase-1, NAD(P)H: quinone oxidoreductase, glutathione-S-transferase, gamma-glutamyl cysteine ligase, and glutathione reductase are among the cytoprotective proteins induced by sulforaphane. In conclusion, sulforaphane is a promising antioxidant agent that is effective to attenuate oxidative stress and tissue/cell damage in different in vivo and in vitro experimental paradigms. Copyright © 2010 Elsevier GmbH. All rights reserved.", "title": "Protective effect of sulforaphane against oxidative stress: recent advances." }, { "docid": "MED-2816", "text": "Plants contain numerous polyphenols, which have been shown to reduce inflammation and hereby to increase resistance to disease. Examples of such polyphenols are isothiocyanates in cabbage and broccoli, epigallocatechin in green tee, capsaicin in chili peppers, chalones, rutin and naringenin in apples, resveratrol in red wine and fresh peanuts and curcumin/curcuminoids in turmeric. Most diseases are maintained by a sustained discreet but obvious increased systemic inflammation. Many studies suggest that the effect of treatment can be improved by a combination of restriction in intake of proinflammatory molecules such as advanced glycation end products (AGE), advanced lipoperoxidation end products (ALE), and rich supply of antiinflammatory molecules such as plant polyphenols. To the polyphenols with a bulk of experimental documentation belong the curcuminoid family and especially its main ingredient, curcumin. This review summarizes the present knowledge about these turmericderived ingredients, which have proven to be strong antioxidants and inhibitors of cyclooxigenase-2 (COX-2), lipoxygenase (LOX) and nuclear factor kappa B (NF-kappaB) but also AGE. A plethora of clinical effects are reported in various experimental diseases, but clinical studies in humans are few. It is suggested that supply of polyphenols and particularly curcuminoids might be value as complement to pharmaceutical treatment, but also prebiotic treatment, in conditions proven to be rather therapy-resistant such as Crohn's, long-stayed patients in intensive care units, but also in conditions such as cancer, liver cirrhosis, chronic renal disease, chronic obstructive lung disease, diabetes and Alzheimer's disease.", "title": "Plant-derived health: the effects of turmeric and curcuminoids." }, { "docid": "MED-860", "text": "Microgreens (seedlings of edible vegetables and herbs) have gained popularity as a new culinary trend over the past few years. Although small in size, microgreens can provide surprisingly intense flavors, vivid colors, and crisp textures and can be served as an edible garnish or a new salad ingredient. However, no scientific data are currently available on the nutritional content of microgreens. The present study was conducted to determine the concentrations of ascorbic acid, carotenoids, phylloquinone, and tocopherols in 25 commercially available microgreens. Results showed that different microgreens provided extremely varying amounts of vitamins and carotenoids. Total ascorbic acid contents ranged from 20.4 to 147.0 mg per 100 g fresh weight (FW), while β-carotene, lutein/zeaxanthin, and violaxanthin concentrations ranged from 0.6 to 12.1, 1.3 to 10.1, and 0.9 to 7.7 mg/100 g FW, respectively. Phylloquinone level varied from 0.6 to 4.1 μg/g FW; meanwhile, α-tocopherol and γ-tocopherol ranged from 4.9 to 87.4 and 3.0 to 39.4 mg/100 g FW, respectively. Among the 25 microgreens assayed, red cabbage, cilantro, garnet amaranth, and green daikon radish had the highest concentrations of ascorbic acids, carotenoids, phylloquinone, and tocopherols, respectively. In comparison with nutritional concentrations in mature leaves (USDA National Nutrient Database), the microgreen cotyledon leaves possessed higher nutritional densities. The phytonutrient data may provide a scientific basis for evaluating nutritional values of microgreens and contribute to food composition database. These data also may be used as a reference for health agencies' recommendations and consumers' choices of fresh vegetables.", "title": "Assessment of vitamin and carotenoid concentrations of emerging food products: edible microgreens." }, { "docid": "MED-5131", "text": "The usual dietary sources of vitamin B(12) are animal foods, meat, milk, egg, fish, and shellfish. As the intrinsic factor-mediated intestinal absorption system is estimated to be saturated at about 1.5-2.0 microg per meal under physiologic conditions, vitamin B(12) bioavailability significantly decreases with increasing intake of vitamin B(12) per meal. The bioavailability of vitamin B(12) in healthy humans from fish meat, sheep meat, and chicken meat averaged 42%, 56%-89%, and 61%-66%, respectively. Vitamin B(12) in eggs seems to be poorly absorbed (< 9%) relative to other animal food products. In the Dietary Reference Intakes in the United States and Japan, it is assumed that 50% of dietary vitamin B(12) is absorbed by healthy adults with normal gastro-intestinal function. Some plant foods, dried green and purple lavers (nori) contain substantial amounts of vitamin B(12), although other edible algae contained none or only traces of vitamin B(12). Most of the edible blue-green algae (cyanobacteria) used for human supplements predominantly contain pseudovitamin B(12), which is inactive in humans. The edible cyanobacteria are not suitable for use as vitamin B(12) sources, especially in vegans. Fortified breakfast cereals are a particularly valuable source of vitamin B(12) for vegans and elderly people. Production of some vitamin B(12)-enriched vegetables is also being devised.", "title": "Vitamin B12 sources and bioavailability." }, { "docid": "MED-3942", "text": "Background The purpose of this study was to evaluate the effect of açai fruit pulp on risk factors for metabolic disorders in overweight subjects. The açaí palm (Euterpe oleracea Mart.), which is native to South America, produces a small, black-purple fruit which is edible. The fruit has recently become popular as a functional food due to its antioxidant potential. Although several studies have been conducted in vitro and with animals, little is known about the potential health benefits in humans aside from an increase in plasma anti-oxidant capacity. Metabolic syndrome is a condition which is defined by a cluster of risk factors for cardiovascular disease and/or type-2 diabetes. Preliminary studies indicate that a reduction in reactive oxygen species can assist in the normalization of the metabolic pathways involved in this syndrome. Methods This was an open label pilot study conducted with 10 overweight adults (BMI ≥ 25 kg/m2 and ≤ 30 kg/m2) who took 100 g açai pulp twice daily for 1 month. The study endpoints included levels of fasting plasma glucose, insulin, cholesterol, triglycerides, exhaled (breath) nitric oxide metabolites (eNO) and plasma levels of high sensitivity C-reactive protein (hs-CRP). The response of blood glucose, blood pressure and eNO to a standardized meal was determined at baseline and following the 30 day treatment. Results Compared to baseline, there were reductions in fasting glucose and insulin levels following the 30 day treatment (both p < 0.02). There was also a reduction in total cholesterol (p = 0.03), as well as borderline significant reductions in LDL-cholesterol and the ratio of total cholesterol to HDL-cholesterol (both p = 0.051). Compared to baseline, treatment with açai ameliorated the post-prandial increase in plasma glucose following the standardized meal, measured as the area under the curve (p = 0.047). There was no effect on blood pressure, hs-CRP or eNO. Conclusion In this uncontrolled pilot study, consumption of açai fruit pulp reduced levels of selected markers of metabolic disease risk in overweight adults, indicating that further studies are warranted.", "title": "Effects of Açai (Euterpe oleracea Mart.) berry preparation on metabolic parameters in a healthy overweight population: A pilot study" }, { "docid": "MED-1131", "text": "To clarify the role of the faecal flora in the diet-induced decrease of rheumatoid arthritis (RA) activity, 43 RA patients were randomized into two groups: the test group to receive living food, a form of uncooked vegan diet rich in lactobacilli, and the control group to continue their ordinary omnivorous diets. Based on clinical assessments before, during and after the intervention period, a disease improvement index was constructed for each patient. According to the index, patients were assigned either to a group with a high improvement index (HI) or to a group with a low improvement index (LO). Stool samples collected from each patient before the intervention and at 1 month were analysed by direct stool sample gas-liquid chromatography of bacterial cellular fatty acids. This method has proved to be a simple and sensitive way to detect changes and differences in the faecal microbial flora between individual stool samples or groups of them. A significant, diet-induced change in the faecal flora (P = 0.001) was observed in the test group, but not in the control group. Further, in the test group, a significant (P = 0.001) difference was detected between the HI and LO categories at 1 month, but not in the pre-test samples. We conclude that a vegan diet changes the faecal microbial flora in RA patients, and changes in the faecal flora are associated with improvement in RA activity.", "title": "Faecal microbial flora and disease activity in rheumatoid arthritis during a vegan diet." }, { "docid": "MED-885", "text": "Oxalate bioavailability from sugar beet fibre (40 g), spinach (25 g) and a solution of sodium oxalate (182 mg) was tested in nine women using a triplicated 3 x 3 Latin square arrangement. Each test substance provided 120 mg oxalic acid. Throughout the study the volunteers consumed a control diet and the test substances were administered at breakfast on specified days. After an initial 2-day control period, oxalate was administered in three test periods that consisted of one test day followed by one control day. Urine collected during 24-hr periods was analysed daily for oxalate. Oxalate excretion did not differ among the five control days and was not increased significantly following the ingestion of sugar beet fibre by the volunteers. Oxalate excretion was greater (P less than 0.0001) for the mean of the spinach and sodium oxalate solution diets than for the mean of the sugar beet fibre and control diets. Oxalate bioavailability from sugar beet fibre was 0.7% compared with bioavailabilities of 4.5 and 6.2% for spinach and oxalate solutions, respectively. The low bioavailability of oxalate from sugar beet fibre may be attributable to its high ratio of minerals (calcium and magnesium) to oxalate, its complex fibre matrix or the loss of the soluble oxalate during processing of sugar beets.", "title": "Bioavailability of oxalic acid from spinach, sugar beet fibre and a solution of sodium oxalate consumed by female volunteers." }, { "docid": "MED-1696", "text": "Summary To assess sources of variability in platelet function tests in normal subjects, 64 healthy young adults were tested on 2–6 occasions at 2 week intervals using 4 methods: platelet aggregation (AGG) in platelet-rich plasma (PRP) in the Bio/Data PAP-4 Aggregometer (BD) and Chrono-Log Lumi-Aggregometer (CL); and AGG in whole blood (WB) in the CL and Multiplate Platelet Function Analyzer (MP), with ATP release (REL) in CL-PRP and CL-WB. Food and medication exposures were recorded prospectively for 2 weeks prior to each blood draw. At least one AGG abnormality was seen in 21% of 81 drug-free specimens with CL-PRP, 15% with CL-WB, 13% with BD-PRP, and 6% with MP-WB, increasing with inclusion of REL to 28% for CL-PRP and 30% for CL-WB. Epinephrine AGG and REL were significantly reduced in males (P<0.0001). Ristocetin AGG and collagen and thrombin REL were significantly reduced in Blacks (P<0.0001). One-third of specimens drawn following flavonoid-rich food exposures had aberrant results, compared to 8.5% of specimens without such exposures (P=0.0035). PRP tests had less intra-individual variation than WB tests. Gender, race, diet, and test system affected results of platelet function testing in healthy subjects, suggesting caution when interpreting the results of platelet function testing in patients.", "title": "Gender, Race, and Diet Affect Platelet Function Tests in Normal Subjects Contributing to a High Rate of Abnormal Results" }, { "docid": "MED-1630", "text": "Despite its widespread use, the artificial sweetener aspartame remains one of the most controversial food additives, due to mixed evidence on its neurobehavioral effects. Healthy adults who consumed a study-prepared high-aspartame diet (25 mg/kg body weight/day) for 8 days and a low-aspartame diet (10 mg/kg body weight/day) for 8 days, with a 2-week washout between the diets, were examined for within-subject differences in cognition, depression, mood, and headache. Measures included weight of foods consumed containing aspartame, mood and depression scales, and cognitive tests for working memory and spatial orientation. When consuming high-aspartame diets, participants had more irritable mood, exhibited more depression, and performed worse on spatial orientation tests. Aspartame consumption did not influence working memory. Given that the higher intake level tested here was well below the maximum acceptable daily intake level of 40-50 mg/kg body weight/day, careful consideration is warranted when consuming food products that may affect neurobehavioral health. © 2014 Wiley Periodicals, Inc.", "title": "Neurobehavioral effects of aspartame consumption." } ]
PLAIN-2634
Food Antioxidants, Stroke, and Heart Disease
[ { "docid": "MED-2704", "text": "Lipid peroxidation is, in most instances, a free radical chain reaction that can be described in terms of initiation, propagation, branching and termination processes. With regard to lipid peroxidation, one of the most important questions concerns the source of the primary catalysts that initiate peroxidation in situ in muscle foods. When cells are injured, such as in muscle foods after slaughtering, lipid peroxidation is favored, and traces of O(2) and H(2)O(2), indicating lipid peroxides, are formed. The stability of a muscle food product will depend on the 'tone' of these peroxides and especially from the involvement of metal ions in the process. The cytosol contains not only prooxidants but also antioxidants and the tone of both affects the overall oxidation. Lipid peroxidation is one of the primary mechanisms of quality deterioration in foods and especially in meat products. The changes in quality can be manifested by deterioration in flavor, color, texture, nutritive value and the production of toxic compounds. Copyright © 1993. Published by Elsevier Ltd.", "title": "Oxidative processes in meat and meat products: Quality implications." }, { "docid": "MED-3000", "text": "An increased risk for colorectal cancer has been consistently reported for long-time consumption of cooked and processed red meat. This has frequently been attributed to chemical carcinogens arising during the cooking process of meat. Long-time fish or poultry consumption apparently does not increase the risk, although similar or higher concentrations of chemical carcinogens were recorded in their preparation for consumption. The geographic epidemiology of colorectal cancer seems to correspond to regions with a high rate of beef consumption. Countries with a virtual absence of beef in the diet (India) or where preferably lamb or goat meat is consumed (several Arabic countries) reveal low rates of colorectal cancer. In China, pork consumption has a long tradition, with an intermediate colorectal cancer rate. In Japan and Korea, large scale beef and pork imports started after World War II or after the Korean War. A steep rise in colorectal cancer incidence was noted after 1970 in Japan and 1990 in Korea. The consumption of undercooked beef (e.g., shabu-shabu, Korean yukhoe and Japanese yukke) became very popular in both countries. The available data are compatible with the interpretation that a specific beef factor, suspected to be one or more thermoresistant potentially oncogenic bovine viruses (e.g., polyoma-, papilloma- or possibly single-stranded DNA viruses) may contaminate beef preparations and lead to latent infections in the colorectal tract. Preceding, concomitant or subsequent exposure to chemical carcinogens arising during cooking procedures should result in increased risk for colorectal cancer synergistic with these infections. Copyright © 2011 UICC.", "title": "Red meat consumption and cancer: reasons to suspect involvement of bovine infectious factors in colorectal cancer." }, { "docid": "MED-3253", "text": "OBJECTIVES: Atherosclerosis begins in childhood and progresses during adolescence and young adulthood. The Pathobiological Determinants of Atherosclerosis in Youth Study previously reported risk scores to estimate the probability of advanced atherosclerotic lesions in young individuals aged 15 to 34 years using the coronary heart disease risk factors (gender, age, serum lipoprotein concentrations, smoking, hypertension, obesity, and hyperglycemia). In this study we investigated the relation of these risk scores to the early atherosclerotic lesions. METHODS: We measured atherosclerotic lesions in the left anterior descending coronary artery, right coronary artery, and abdominal aorta and the coronary heart disease risk factors in persons 15 to 34 years of age who died as a result of external causes and were autopsied in forensic laboratories. RESULTS: Risk scores computed from the modifiable risk factors were associated with prevalence of microscopically demonstrable lesions of atherosclerosis (American Heart Association grade 1) in the left anterior descending coronary artery and with the extent of the earliest detectable gross lesion (fatty streaks) in the right coronary artery and abdominal aorta. Risk scores computed from the modifiable risk factors also were associated with prevalence of lesions of higher degrees of microscopic severity (intermediate as well as advanced) in the left anterior descending coronary artery and with extent of lesions of higher degrees of severity (intermediate and raised lesions) in the right coronary artery and abdominal aorta. CONCLUSIONS: Risk scores calculated from traditional coronary heart disease risk factors to identify individual young persons with high probability of having advanced atherosclerotic lesions also are associated with earlier atherosclerotic lesions, including the earliest anatomically demonstrable atherosclerotic lesion. These results support lifestyle modification in youth to prevent development of the initial lesions and the subsequent progression to advanced lesions and, thereafter, to prevent or delay coronary heart disease.", "title": "Pathobiological determinants of atherosclerosis in youth risk scores are associated with early and advanced atherosclerosis." }, { "docid": "MED-4413", "text": "Estimation of total antioxidant intake is the first step to investigate the protective effects of antioxidants on oxidative stress-mediated disease. The present study was designed to develop an algorithm to estimate total antioxidant capacity (TAC) of the US diet. TAC of individual antioxidants and 50 popular antioxidant-rich food items in the US diet were determined by 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) assay and the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Theoretical TAC of foods was calculated as the sum of individual antioxidant capacities of compounds. The top 10 TAC food items in the US diet according to standard serving size were blueberry > plum > green tea > strawberry > green tea (decaffeinated) > red wine > grape juice > black tea > cherry > grape. Major contributors to TAC were the total phenolic content (r = 0.952, P < 0.001) and flavonoid content (r = 0.827, P < 0.001) of 50 foods. Theoretical TAC was positively correlated to experimental TAC of 50 foods determined by the ABTS assay (r = 0.833, P < 0.001) and the DPPH assay (r = 0.696, P < 0.001), and to TAC from the USDA database for the oxygen radical absorbance capacity (r = 0.484, P = 0.001, n = 44). The TAC database of the US diet has been established and validated. In future studies, TAC of the US diet can be linked to biomarkers of chronic disease.", "title": "Development and validation of an algorithm to establish a total antioxidant capacity database of the US diet." }, { "docid": "MED-4523", "text": "Both lipophilic and hydrophilic antioxidant capacities were determined using the oxygen radical absorbance capacity (ORAC(FL)) assay with fluorescein as the fluorescent probe and 2,2'-azobis(2-amidinopropane) dihydrochloride as a peroxyl radical generator on over 100 different kinds of foods, including fruits, vegetables, nuts, dried fruits, spices, cereals, infant, and other foods. Most of the foods were collected from four different regions and during two different seasons in U.S. markets. Total phenolics of each sample were also measured using the Folin-Ciocalteu reagent. Hydrophilic ORAC(FL) values (H-ORAC(FL)) ranged from 0.87 to 2641 micromol of Trolox equivalents (TE)/g among all of the foods, whereas lipophilic ORAC(FL) values (L-ORAC(FL)) ranged from 0.07 to 1611 micromol of TE/g. Generally, L-ORAC(FL) values were <10% of the H-ORAC(FL) values except for a very few samples. Total antioxidant capacity was calculated by combining L-ORAC(FL) and H-ORAC(FL). Differences of ORAC(FL) values in fruits and vegetables from different seasons and regions were relatively large for some foods but could not be analyzed in detail because of the sampling scheme. Two different processing methods, cooking and peeling, were used on selected foods to evaluate the impact of processing on ORAC(FL). The data demonstrated that processing can have significant effects on ORAC(FL). Considering all of the foods analyzed, the relationship between TP and H-ORAC(FL) showed a very weak correlation. Total hydrophilic and lipophilic antioxidant capacity intakes were calculated to be 5558 and 166 micromol of TE/day, respectively, on the basis of data from the USDA Continuing Survey of Food Intakes by Individuals (1994-1996).", "title": "Lipophilic and hydrophilic antioxidant capacities of common foods in the United States." }, { "docid": "MED-4524", "text": "This review summarizes the multifaceted aspects of antioxidants and the basic kinetic models of inhibited autoxidation and analyzes the chemical principles of antioxidant capacity assays. Depending upon the reactions involved, these assays can roughly be classified into two types: assays based on hydrogen atom transfer (HAT) reactions and assays based on electron transfer (ET). The majority of HAT-based assays apply a competitive reaction scheme, in which antioxidant and substrate compete for thermally generated peroxyl radicals through the decomposition of azo compounds. These assays include inhibition of induced low-density lipoprotein autoxidation, oxygen radical absorbance capacity (ORAC), total radical trapping antioxidant parameter (TRAP), and crocin bleaching assays. ET-based assays measure the capacity of an antioxidant in the reduction of an oxidant, which changes color when reduced. The degree of color change is correlated with the sample's antioxidant concentrations. ET-based assays include the total phenols assay by Folin-Ciocalteu reagent (FCR), Trolox equivalence antioxidant capacity (TEAC), ferric ion reducing antioxidant power (FRAP), \"total antioxidant potential\" assay using a Cu(II) complex as an oxidant, and DPPH. In addition, other assays intended to measure a sample's scavenging capacity of biologically relevant oxidants such as singlet oxygen, superoxide anion, peroxynitrite, and hydroxyl radical are also summarized. On the basis of this analysis, it is suggested that the total phenols assay by FCR be used to quantify an antioxidant's reducing capacity and the ORAC assay to quantify peroxyl radical scavenging capacity. To comprehensively study different aspects of antioxidants, validated and specific assays are needed in addition to these two commonly accepted assays.", "title": "The chemistry behind antioxidant capacity assays." }, { "docid": "MED-4864", "text": "To elucidate the health benefit of herbal teas on the cytotoxicity induced by H(2)O(2) in V79-4 cells, herbal extracts and its flavonoids were tested using lactate dehydrogenase release and determining intracellular reactive oxygen species generation and antioxidant activity with superoxide radical scavenging assay. Significant decrease in cell viability was observed on V79-4 cells treated with H(2)O(2) (1 mM), while herbal extracts and its flavonoids including catechin and epigallocatechin gallate prevented the LDH release from H(2)O(2) cytotoxicity. Total catechin contents of green tea (65.6 mg/g of dry matter) were significantly higher than other herbal teas (35.8 to 1.2 mg/g of DM). The relative concentration of the 4 major tea catechins ranked EGCG > EGC > EC > C. Green tea exhibited the lowest IC(50) values (2 g fresh herb/100 mL) of superoxide radical scavenging activity among the tested herbal tea, which indicates powerful antioxidant activity in O(2)(*-) radicals scavenging, followed by black tea, dandelion, hawthorn, rose hip, chamomile.", "title": "Comparative flavonoids contents of selected herbs and associations of their radical scavenging activity with antiproliferative actions in V79-4 cells." }, { "docid": "MED-2693", "text": "Antioxidants, primarily from fruits and vegetables, have been hypothesized to protect against non-Hodgkin lymphoma (NHL). The Oxygen Radical Absorbance Capacity (ORAC) assay, which measures total antioxidant capacity of individual foods and accounts for synergism, can be estimated using a food-frequency questionnaire (FFQ). We tested the hypothesis that higher intake of antioxidant nutrients from foods, supplements, and FFQ-based ORAC values are associated with a lower risk of NHL in a clinic-based study of 603 incident cases and 1007 frequency-matched controls. Diet was assessed with a 128-item FFQ. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals adjusted for age, sex, residence and total energy. Dietary intake of α-tocopherol (OR=0.50; p-trend=0.0002), β-carotene (OR=0.58; p-trend=0.0005), lutein/zeaxanthin (OR=0.62; p-trend=0.005), zinc (OR=0.54; p-trend=0.003) and chromium (OR=0.68; p-trend=0.032) were inversely associated with NHL risk. Inclusion of supplement use had little impact on these associations. Total vegetables (OR=0.52; p-trend<0.0001), particularly green leafy (OR=0.52; p-trend<0.0001) and cruciferous (OR=0.68; p-trend=0.045) vegetables, were inversely associated with NHL risk. NHL risk was inversely associated with both hydrophilic ORAC (OR=0.61, p-trend=0.003) and lipophilic ORAC (OR=0.48, p-trend=0.0002), although after simultaneous adjustment for other antioxidants or total vegetables only the association for lipophilic ORAC remained significant. There was no striking heterogeneity in results across the common NHL subtypes. Higher antioxidant intake as estimated by the FFQ-ORAC, particularly the lipophilic component, was associated with a lower NHL risk after accounting for other antioxidant nutrients and vegetable intake, supporting this as potentially useful summary measure of total antioxidant intake.", "title": "Food-Frequency Questionnaire Based Estimates of Total Antioxidant Capacity and Risk of Non-Hodgkin Lymphoma" }, { "docid": "MED-2694", "text": "Lipid peroxidation (LPO) product accumulation in human tissues is a major cause of tissular and cellular dysfunction that plays a major role in ageing and most age-related and oxidative stress-related diseases. The current evidence for the implication of LPO in pathological processes is discussed in this review. New data and literature review are provided evaluating the role of LPO in the pathophysiology of ageing and classically oxidative stress-linked diseases, such as neurodegenerative diseases, diabetes and atherosclerosis (the main cause of cardiovascular complications). Striking evidences implicating LPO in foetal vascular dysfunction occurring in pre-eclampsia, in renal and liver diseases, as well as their role as cause and consequence to cancer development are addressed.", "title": "Pathological aspects of lipid peroxidation." }, { "docid": "MED-3255", "text": "BACKGROUND: Early childhood introduction of nutritional habits aimed at atherosclerosis prevention reduces children's serum total cholesterol concentration, but its effect on vascular endothelial function is unknown. METHODS AND RESULTS: Between 1990 and 1992, we randomized healthy 7-month-old infants (n=1062) to intervention (low-saturated-fat diet) and control (unrestricted diet) groups. At the age of 11 years, endothelium-dependent (flow-mediated) and endothelium-independent (nitrate-mediated) vasodilatory responses of the brachial artery were measured with high-resolution ultrasound in 179 intervention and 190 control children. The effect of intervention on endothelial function was significant in boys (P=0.0034) but not in girls (P=0.69). The maximum endothelium-dependent dilation response (mean+/-SD) was 9.62+/-3.53% and 8.36+/-3.85% in intervention boys and control boys and 8.84+/-4.00% and 8.44+/-3.60% in intervention girls and control girls, respectively. Intervention had no effect on nitrate-mediated dilation. The difference in endothelial function in boys remained significant after adjustment for current serum total or LDL cholesterol but became nonsignificant after adjustment for mean cholesterol measured under 3 years of age (adjusted means: 9.46% [CI 8.68% to 10.24%] versus 8.54% [CI 7.75% to 9.32%], P=0.11). CONCLUSIONS: A low-saturated-fat diet introduced in infancy and maintained during the first decade of life is associated with enhanced endothelial function in boys. The effect is explained in part by the diet-induced reduction in serum cholesterol concentration.", "title": "Endothelial function in healthy 11-year-old children after dietary intervention with onset in infancy: the Special Turku Coronary Risk Factor Inter..." }, { "docid": "MED-3729", "text": "Oxidative stress is a key component in linking environmental toxicity to the multistage carcinogenic process. Reactive oxygen species (ROS) are generated in response to both endogenous and exogenous stimuli. To counterbalance ROS-mediated injury, an endogenous antioxidants defense system exists; however, when oxidation exceeds the control mechanisms, oxidative stress arises. Chronic and cumulative oxidative stress induces deleterious modifications to a variety of macromolecular components, such as DNA, lipids, and proteins. A primary mechanism of many chemotherapy drugs against cancer cells is the formation of ROS, or free radicals. Radiotherapy is based on the fact that ionizing radiation destroys tumor cells. Radiotherapy induces direct lesions in the DNA or biological molecules, which eventually affect DNA. Free radicals produced by oncology therapy are often a source of serious side effects as well. The objective of this review is to provide information about the effects of antioxidants during oncology treatments and to discuss the possible events and efficacy. Much debate has arisen about whether antioxidant supplementation alters the efficacy of cancer chemotherapy. There is still limited evidence in both quality and sample size, suggesting that certain antioxidant supplements may reduce adverse reactions and toxicities. Significant reductions in toxicity may alleviate dose-limiting toxicities so that more patients are able to complete prescribed chemotherapy regimens and thus, in turn, improve the potential for success in terms of tumor response and survival. Copyright © 2013 Elsevier Inc. All rights reserved.", "title": "Role of antioxidants in cancer therapy." }, { "docid": "MED-4106", "text": "OBJECTIVES: The objective of this study was to assess the relation between the level of habitual potassium intake and the incidence of cardiovascular disease (CVD). BACKGROUND: Prospective cohort studies have evaluated the relationship between habitual potassium intake and incidence of vascular disease, but their results have not been not entirely consistent. METHODS: We performed a systematic search for prospective studies published, without language restrictions (1966 to December 2009). Criteria for inclusion were prospective adult population study, assessment of baseline potassium intake, assessment of vascular events as outcome, and follow-up of at least 4 years. For each study, relative risks (RRs) and 95% confidence intervals (CIs) were extracted and pooled using a random-effect model, weighted for the inverse of the variance. Heterogeneity, publication bias, subgroup, and meta-regression analyses were performed. RESULTS: Eleven studies were identified, providing 15 cohort samples that included 247,510 male and female participants (follow-up 5 to 19 years), 7,066 strokes, 3,058 coronary heart disease (CHD) events, and 2,497 total CVD events. Potassium intake was assessed by 24-h dietary recall (n = 2), food frequency questionnaire (n = 6), or 24-h urinary excretion (n = 3). In the pooled analysis, a 1.64-g (42 mmol) per day higher potassium intake was associated with a 21% lower risk of stroke (RR: 0.79; 95% CI: 0.68 to 0.90; p = 0.0007), with a trend toward lower risk of CHD and total CVD that attained statistical significance after the exclusion of a single cohort, based on sensitivity analysis (RR: 0.93; 95% CI: 0.87 to 0.99; p = 0.03 and RR: 0.74; 95% CI: 0.60 to 0.91; p = 0.0037). CONCLUSIONS: Higher dietary potassium intake is associated with lower rates of stroke and might also reduce the risk of CHD and total CVD. These results support recommendations for higher consumption of potassium-rich foods to prevent vascular diseases. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.", "title": "Potassium intake, stroke, and cardiovascular disease a meta-analysis of prospective studies." }, { "docid": "MED-2705", "text": "Atherosclerosis may result partly from processes that occur following food consumption and that involve oxidized lipids in chylomicrons. We investigated reactions that could occur in the acidic pH of the stomach and accelerate the generation of lipid hydroperoxides and co-oxidation of dietary constituents. The ability of dietary polyphenols to invert catalysis from pro-oxidation to antioxidation was examined. The acidic pH of gastric fluid amplified lipid peroxidation catalyzed by metmyoglobin or iron ions. Metmyoglobin catalyzed peroxidation of edible oil, resulting in 8-fold increase of hydroperoxide concentration. The incubation of heated muscle tissue in simulated gastric fluid for 2 h enhanced hydroperoxides accumulation by 6-fold to 1200 microM. In the presence of catechin or red wine polyphenols, metmyoglobin catalyzed the breakdown of hydroperoxides to zero, totally preventing lipid peroxidation and beta-carotene cooxidation. We suggest that human gastric fluid may be an excellent medium for enhancing the oxidation of lipids and other dietary constituents. The results indicate the potentially harmful effects of oxidized fats intake in the presence of endogenous catalysts found in foods, and the major benefit of including in the meal plant dietary antioxidants.", "title": "The stomach as a bioreactor: dietary lipid peroxidation in the gastric fluid and the effects of plant-derived antioxidants." }, { "docid": "MED-3001", "text": "Over the last three decades, the concept of Western disease has become well established. Medicine has approached this group of diseases by searching for new cures but has achieved relatively little success. We argue that medicine should now accept the failure of this strategy and place a major emphasis on prevention. The key objective is to change the climate of opinion so that prevention is taken seriously by the general population. The chief activity should be a wide ranging public education campaign so as to persuade people to live a healthier lifestyle. Medicine will require restructuring in order to carry out this work. Medical education needs to be reformed so that medical students receive the necessary training. This must be done as part of an integrated approach in which government, industry and medical research all play a major role. Governments should use taxation and subsidies in areas such as food and tobacco so as to shift consumption patterns towards healthier products. Governments must also tighten laws on tobacco sales and advertising, support health education, and improve food labelling. Industry must be made far more responsive to the health needs of the population. This should be done both by public education, so as to alter demand, and by government action. Medical research should change its emphasis from studying the detailed mechanisms of disease (\"complex research\") to studying the role of lifestyle factors (\"simple research\").", "title": "Towards a new system of health: the challenge of Western disease." }, { "docid": "MED-2698", "text": "BACKGROUND AND PURPOSE: Consumption of antioxidant-rich foods may reduce the risk of stroke by inhibition of oxidative stress and inflammation. Total antioxidant capacity (TAC) takes into account all antioxidants and the synergistic effects between them. We examined the association between dietary TAC and stroke incidence in cardiovascular disease (CVD)-free women and in women with CVD history at baseline. METHODS: The study included women (31,035 CVD-free and 5680 with CVD history at baseline), aged 49 to 83 years, from the Swedish Mammography Cohort. Diet was assessed with a food frequency questionnaire. Dietary TAC was calculated using oxygen radical absorbance capacity values. Stroke cases were ascertained by linkage with the Swedish Hospital Discharge Registry. RESULTS: During follow-up (September 1997 to December 2009), we identified 1322 stroke cases (988 cerebral infarctions, 226 hemorrhagic strokes, and 108 unspecified strokes) among CVD-free women and 1007 stroke cases (796 cerebral infarctions, 100 hemorrhagic strokes, and 111 unspecified strokes) among women with a CVD history. The multivariable hazard ratio of total stroke comparing the highest with the lowest quintile of dietary TAC was 0.83 (95% CI, 0.70-0.99; P for trend=0.04) in CVD-free women. Among women with a CVD history, the hazard ratios for the highest versus lowest quartile of TAC were 0.90 (95% CI, 0.75-1.07; P for trend=0.30) for total stroke and 0.55 (95% CI, 0.32-0.95; P for trend=0.03) for hemorrhagic stroke. CONCLUSIONS: These findings suggest that dietary TAC is inversely associated with total stroke among CVD-free women and hemorrhagic stroke among women with CVD history.", "title": "Total antioxidant capacity of diet and risk of stroke: a population-based prospective cohort of women." }, { "docid": "MED-2997", "text": "If disease patterns emerge which show that certain diseases can be related, this is a valuable pointer to a common cause. This article traces the principle of interpreting disease relationships, illustrated by several common conditions of western civilization, for which the common cause is postulated as being removal of fiber from the diet.", "title": "The Etiological Significance of Related Diseases" }, { "docid": "MED-2697", "text": "OBJECTIVES: The purpose of this study was to test the hypothesis that intake of used cooking fat is associated with impaired endothelial function. BACKGROUND: Diets containing high levels of lipid oxidation products may accelerate atherogenesis, but the effect on endothelial function is unknown. METHODS: Flow-mediated endothelium-dependent dilation and glyceryl trinitrate-induced endothelium-independent dilation of the brachial artery were investigated in 10 men. Subjects had arterial studies before and 4 h after three test meals: 1) a meal (fat 64.4 g) rich in cooking fat that had been used for deep frying in a fast food restaurant; 2) the same meal (fat 64.4 g) rich in unused cooking fat, and 3) a corresponding low fat meal (fat 18.4 g) without added fat. RESULTS: Endothelium-dependent dilation decreased between fasting and postprandial studies after the used fat meal (5.9 +/- 2.3% vs. 0.8 +/- 2.2%, p = 0.0003), but there was no significant change after the unused fat meal (5.3 +/- 2.1% vs. 6.0 +/- 2.5%) or low fat meal (5.3 +/- 2.3% vs. 5.4 +/- 3.3%). There was no significant difference in endothelium-independent dilation after any of the meals. Plasma free fatty acid concentration did not change significantly during any of the meals. The level of postprandial hypertriglyceridemia was not associated with change in endothelial function. CONCLUSIONS: Ingestion of a meal rich in fat previously used for deep frying in a commercial fast food restaurant resulted in impaired arterial endothelial function. These findings suggest that intake of degradation products of heated fat contribute to endothelial dysfunction.", "title": "Impaired endothelial function following a meal rich in used cooking fat." }, { "docid": "MED-4099", "text": "OBJECTIVE: A meta-analysis was performed on epidemiologic studies to assess the relation between β-glucan consumption from oats and from barley on blood cholesterol level, triglyceride/triacylglycerol (TGL/TAG) level, and blood glucose level (BGL) in humans. In addition, the effect of β-glucan on total cholesterol (TC) and BGL was translated into an empirical dose-response model. METHODS: Thirty research articles that evaluated the effect of different exposure levels of β-glucan on blood cholesterol and BGL were analyzed, yielding 126 clinical studies. RESULTS: There was a significant inverse relation in TC (-0.60 mmol/L, 95% confidence interval [CI] -0.85 to -0.34), low-density lipoprotein (-0.66 mmol/L, 95% CI -0.96 to -0.36), and TGL/TAG (-0.04 mmol/L, 95% CI -0.15 to 0.07) after consumption of β-glucan. In contrast, an increase in high-density lipoprotein cholesterol was noted (0.03 mmol/L, 95% CI -0.06 to 0.13) with the random-effect model. The analysis showed a significant change in BGL (-2.58 mmol/L, 95% CI -3.22 to -1.84) with high heterogeneity between (I(2) = 97%) and across (τ(2) = 5.88) the studies. The fixed-effect model showed a significant change in TC, low-density lipoprotein, and BGL, whereas it showed no significant changes in high-density lipoprotein and TGL/TAG. The dose-response model showed that a 3-g/d dose of oat or barley β-glucan was sufficient to decrease TC. CONCLUSION: Consumption of 3 g/d of oat or barley β-glucan is sufficient to decrease blood cholesterol, whereas the effect on BGL is still inconclusive, with high heterogeneity, and requires further clinical research studies with longer intervention periods. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Meta-analysis of the effect of β-glucan intake on blood cholesterol and glucose levels." }, { "docid": "MED-2699", "text": "Significance: The free radical theory of aging has provided a theoretical framework for an enormous amount of work leading to significant advances in our understanding of aging. Up to the turn of the century, the theory received abundant support from observations coming from fields as far apart as comparative physiology or molecular biology. Recent Advances: Work from many laboratories supports the theory, for instance showing that overexpression of antioxidant enzymes results in increases in life-span. But other labs have shown that in some cases, there is an increased oxidative stress and increased longevity. The discovery that free radicals can not only cause molecular damage to cells, but also serve as signals; led to the proposal that they act as modulators of physiological processes. For instance, reactive oxygen species (ROS) stimulate physiological adaptations to physical exercise. Critical Issues: A critical blow to the free radical theory of aging came from epidemiological studies showing that antioxidant supplementation did not lower the incidence of many age-associated diseases but, in some cases, increased the risk of death. Moreover, recent molecular evidence has shown that increasing generation of ROS, in some cases, increases longevity. Future Directions: Gerontologists interested in free radical biology are at a crossroads and clearly new insights are required to clarify the role of ROS in the process of aging. The hurdles are, no doubt, very high, but the intellectual and practical promise of these studies is of such magnitude that we feel that all efforts will be generously rewarding. Antioxid. Redox Signal. 19, 779–787.", "title": "The Free Radical Theory of Aging Revisited: The Cell Signaling Disruption Theory of Aging" }, { "docid": "MED-2999", "text": "Many of the commonest diseases in the economically more developed communities are characteristic of modern Western culture. Evidence is presented suggesting that they represent a failure of adaptation to the dramatic changes in diet that have been associated with the emergence of modern Western culture. Dietary changes aimed at the alleviation and prevention of these diseases are discussed and recommended.", "title": "Western diseases and their emergence related to diet." }, { "docid": "MED-4545", "text": "Reducing oxidative damage is thought to be an effective aging intervention. Açai, a fruit indigenous to the Amazon, is rich in phytochemicals that possesses high anti-oxidant activities, and has anti-inflammatory, anti-cancer and anti-cardiovascular disease properties. However, little is known about its potential anti-aging properties especially at the organismal level. Here we evaluated the effect of açai pulp on modulating lifespan in Drosophila melanogaster. We found that açai supplementation at 2% in the food increased the lifespan of female flies fed a high fat diet compared to the non-supplemented control. We measured transcript changes induced by açai for age-related genes. Although transcript levels of most genes tested were not altered, açai increased the transcript level of l(2)efl, a small heat-shock-related protein, and two detoxification genes, gstD1 and mtnA, while decreasing the transcript level of phosphoenolpyruvate carboxykinase (Pepck), a key gene involved in gluconeogenesis. Furthermore, açai increased the lifespan of oxidative stressed females caused by sod1 RNAi. This suggests that açai improves survival of flies fed a high fat diet through activation of stress response pathways and suppression of Pepck expression. Açai has the potential to antagonize the detrimental effect of fat in the diet and alleviate oxidative stress in aging.", "title": "Açai Palm Fruit (Euterpe oleracea Mart.) Pulp Improves Survival of Flies on a High Fat Diet" }, { "docid": "MED-5326", "text": "The effect of meat consumption on cancer risk is a controversial issue. However, recent meta-analyses show that high consumers of cured meats and red meat are at increased risk of colorectal cancer. This increase is significant but modest (20-30%). Current WCRF-AICR recommendations are to eat no more than 500 g per week of red meat, and to avoid processed meat. Moreover, our studies show that beef meat and cured pork meat promote colon carcinogenesis in rats. The major promoter in meat is heme iron, via N-nitrosation or fat peroxidation. Dietary additives can suppress the toxic effects of heme iron. For instance, promotion of colon carcinogenesis in rats by cooked, nitrite-treated and oxidized high-heme cured meat was suppressed by dietary calcium and by α-tocopherol, and a study in volunteers supported these protective effects in humans. These additives, and others still under study, could provide an acceptable way to prevent colorectal cancer. Copyright © 2011 Elsevier B.V. All rights reserved.", "title": "Red meat and colon cancer: should we become vegetarians, or can we make meat safer?" }, { "docid": "MED-2696", "text": "A high intake of dietary antioxidant compounds has been hypothesized to be an appropriate strategy to reduce gastric cancer (GC) development. We investigated the effect of dietary total antioxidant capacity (TAC) in relation to GC in the European Prospective Investigation into Cancer (EPIC) study including 23 centers in 10 European countries. A total of 521,457 subjects (153,447 men) aged mostly 35-70 years old, were recruited largely between 1992 and 1998. Ferric reducing antioxidant potential (FRAP) and total radical-trapping antioxidant parameter (TRAP), measuring reducing and chain-breaking antioxidant capacity were used to measure dietary TAC from plant foods. Dietary antioxidant intake is associated with a reduction in the risk of GC for both FRAP (adjusted HR 0.66; 95%CI (0.46-0.95) and TRAP (adjusted HR 0.61; 95%CI (0.43-0.87) (highest vs. lowest quintile). The association was observed for both cardia and noncardia cancers. A clear effect was observed in smokers with a significant reduction in GC risk for the fifth quintile of intake for both assays (highest vs. lowest quintile: adjusted HR 0.41; 95%CI (0.22-0.76) p for trend <0.001 for FRAP; adjusted HR 0.52; 95%CI (0.28-0.97) p for trend <0.001 for TRAP) but not in nonsmokers. In former smokers, the association with FRAP intake was statistically significant (highest vs. lowest quintile: adjusted HR 0.4; 95%CI (0.21-0.75) p < 0.05); no association was observed for TRAP. Dietary antioxidant capacity intake from different sources of plant foods is associated with a reduction in the risk of GC. Copyright © 2011 UICC.", "title": "Dietary total antioxidant capacity and gastric cancer risk in the European prospective investigation into cancer and nutrition study." }, { "docid": "MED-2695", "text": "BACKGROUND: There are no previous studies investigating the effect of all dietary antioxidants in relation to myocardial infarction. The total antioxidant capacity of diet takes into account all antioxidants and synergistic effects between them. The aim of this study was to examine how total antioxidant capacity of diet and antioxidant-containing foods were associated with incident myocardial infarction among middle-aged and elderly women. METHODS: In the population-based prospective Swedish Mammography Cohort of 49-83-year-old women, 32,561 were cardiovascular disease-free at baseline. Women completed a food-frequency questionnaire, and dietary total antioxidant capacity was calculated using oxygen radical absorbance capacity values. Information on myocardial infarction was identified from the Swedish Hospital Discharge and the Cause of Death registries. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazard models. RESULTS: During the follow-up (September 1997-December 2007), we identified 1114 incident cases of myocardial infarction (321,434 person-years). In multivariable-adjusted analysis, the HR for women comparing the highest quintile of dietary total antioxidant capacity to the lowest was 0.80 (95% CI, 0.67-0.97; P for trend=0.02). Servings of fruit and vegetables and whole grains were nonsignificantly inversely associated with myocardial infarction. CONCLUSIONS: These data suggest that dietary total antioxidant capacity, based on fruits, vegetables, coffee, and whole grains, is of importance in the prevention of myocardial infarction. Copyright © 2012 Elsevier Inc. All rights reserved.", "title": "Total antioxidant capacity from diet and risk of myocardial infarction: a prospective cohort of women." }, { "docid": "MED-2700", "text": "Blood components, especially hemoglobin, are powerful promoters of lipid oxidation and may decrease the shelf life of meat products. Therefore, this study examined different slaughter techniques to determine their effects on pH (24 h), color (L*a*b* values at 24 h), lipid oxidation, residual hemoglobin concentration (24 h), and sensory evaluation (d 1 and 4 postmortem; PM) in broiler breast fillets. The treatments included 1) CO(2) slaughter and not bled, 2) no stunning and bled, 3) electrical stunning (ES) and bled, 4) CO(2) stunning and bled, and 5) ES and decapitation. The birds were conventionally processed, and analyses were performed at 24 h PM except residual hemoglobin for which the samples were frozen (-80 degrees C) until analyses ( < 2 mo). There were no significant differences in pH or b* values at 24 h PM among any of the treatments. L* values were significantly higher, indicating lighter fillets in the ES and decapitated birds compared with the darker fillets from the CO(2) stunned and bled birds. The CO(2) slaughter and not bled birds had significantly higher a* values, indicating more red color, when compared with the ES and bled and decapitated birds. There were no significant differences in the residual hemoglobin contents in the broiler breast muscle when comparing all of the treatments except CO(2) slaughter and not bled, which was significantly (around 15%) greater. Overall TBA-reactive substances (TBARS; raw, cooked at 24 h, and cooked at 72 h PM) indicated that ES and bled birds had the lowest TBARS when compared with the remaining treatments. Consumer panels detected increased aroma (chicken meaty and warmed-over aromas) and flavor (chicken meaty and warmed-over flavors) in not bled samples at 24 h PM. By 72 h PM, however, there were no significant differences in aroma or flavor. Therefore, different slaughter and bleeding method may affect color and sensory properties of the broiler breast fillets, and the ES and decapitation method had the most favorable results for sensory quality.", "title": "The effect of blood removal on oxidation and shelf life of broiler breast meat." }, { "docid": "MED-2703", "text": "Extensive experimental data have revealed a central role for oxidative stress in atherogenesis and suggested a potential role for 'antioxidant' treatment in cardiovascular disease (CVD) [1-11]. Experimental data, however, have not translated into clinical benefit: most antioxidant vitamin trials have failed to reduce cardiovascular morbidity and mortality [12]. Moreover, recent clinical trials have suggested that mono-therapy with certain antioxidant vitamins like vitamin E may, in fact, be detrimental [13]. As a result of the disappointing outcome of 'antioxidant' vitamin trials, some authors have questioned both the utility of 'antioxidant' treatment in CVD and the supposedly central role of oxidative stress in atherogenesis [14-19]. Other investigators, however, sustain that the beneficial effects of lipid lowering and anti-hypertensive treatment are at least, in part, due to their 'antioxidant' properties, in addition to their specific pharmacological properties [20, 21]. Oxidant stress plays a pivotal role in atherogenesis, however, the clinical promise of antioxidant vitamins has failed to translate into clinical benefit. Increasing evidence suggests that more rigorous clinical trial designs are necessary to effectively divulge antioxidant utility and that a multifaceted antioxidant approach to atherosclerosis may yield the most clinical reward. This article reviews currently available evidence on the role of oxidant stress in atherosclerosis, analyzes the results of large anti-oxidant trials, and suggests ways to investigate the true role of antioxidant treatment in the clinical setting.", "title": "Atherosclerosis and oxidant stress: the end of the road for antioxidant vitamin treatment?" }, { "docid": "MED-2702", "text": "BACKGROUND: Oxidative stress can cause cancer. Our aim was to establish whether antioxidant supplements reduce the incidence of gastrointestinal cancer and mortality. METHODS: With the Cochrane Collaboration methodology, we reviewed all randomised trials comparing antioxidant supplements with placebo for prevention of gastrointestinal cancers. We searched electronic databases and reference lists (February, 2003). Outcome measures were incidence of gastrointestinal cancers, overall mortality, and adverse effects. Outcomes were analysed with fixed-effect and random-effects model meta-analyses and were reported as relative risk with 95% CIs. FINDINGS: We identified 14 randomised trials (n=170,525). Trial quality was generally high. Heterogeneity of results was low to moderate. Neither the fixed-effect (relative risk 0.96, 95% CI 0.88-1.04) nor random-effects meta-analyses (0.90, 0.77-1.05) showed significant effects of supplementation with beta-carotene, vitamins A, C, E, and selenium (alone or in combination) versus placebo on oesophageal, gastric, colorectal, pancreatic, and liver cancer incidences. In seven high-quality trials (n=131727), the fixed-effect model showed that antioxidant significantly increased mortality (1.06, 1.02-1.10), unlike the random-effects meta-analysis (1.06, 0.98-1.15). Low-quality trials showed no significant effect of antioxidant supplementation on mortality. The difference between the mortality estimates in high-quality and low-quality trials was significant (Z=2.10, p=0.04 by test of interaction). beta-carotene and vitamin A (1.29, 1.14-1.45) and beta-carotene and vitamin E (1.10, 1.01-1.20) significantly increased mortality, whereas beta-carotene alone only tended to increase mortality (1.05, 0.99-1.11). In four trials (three with unclear or inadequate methodology), selenium showed significant beneficial effect on the incidence of gastrointestinal cancer. INTERPRETATION: We could not find evidence that antioxidant supplements can prevent gastrointestinal cancers; on the contrary, they seem to increase overall mortality. The potential preventive effect of selenium should be studied in adequate randomised trials.", "title": "Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis." }, { "docid": "MED-3254", "text": "We assessed the relation of risk factors for cardiovascular disease to early atherosclerotic lesions in the aorta and coronary arteries in 35 persons (mean age at death, 18 years). Aortic involvement with fatty streaks was greater in blacks than in whites (37 vs. 17 percent, P less than 0.01). However, aortic fatty streaks were strongly related to antemortem levels of both total and low-density lipoprotein cholesterol (r = 0.67, P less than 0.0001 for each association), independently of race, sex, and age, and were inversely correlated with the ratio of high-density lipoprotein cholesterol to low-density plus very-low-density lipoprotein cholesterol (r = -0.35, P = 0.06). Coronary-artery fatty streaks were correlated with very-low-density lipoprotein cholesterol (r = 0.41, P = 0.04). Mean systolic blood-pressure levels also tended to be higher in the four subjects with coronary-artery fibrous plaques than in those without them: 112 mm Hg as compared with 104 (P = 0.09). These results document the importance of risk-factor levels to early anatomical changes in the aorta and coronary arteries. The progression of fatty streaks to fibrous plaques is uncertain, but these data suggest that a rational approach to the prevention of cardiovascular disease should begin early in life.", "title": "Relation of serum lipoprotein levels and systolic blood pressure to early atherosclerosis. The Bogalusa Heart Study." } ]
[ { "docid": "MED-5039", "text": "Epidemiological data demonstrate that regular dietary intake of plant-derived foods and beverages reduces the risk of coronary heart disease and stroke. Among many ingredients, cocoa might be an important mediator. Indeed, recent research demonstrates a beneficial effect of cocoa on blood pressure, insulin resistance, and vascular and platelet function. Although still debated, a range of potential mechanisms through which cocoa might exert its benefits on cardiovascular health have been proposed, including activation of nitric oxide and antioxidant and antiinflammatory effects. This review summarizes the available data on the cardiovascular effects of cocoa, outlines potential mechanisms involved in the response to cocoa, and highlights the potential clinical implications associated with its consumption.", "title": "Cocoa and cardiovascular health." }, { "docid": "MED-5290", "text": "OBJECTIVE: To determine whether the reduction in blood pressure achieved in trials of dietary salt reduction is quantitatively consistent with estimates derived from blood pressure and sodium intake in different populations, and, if so, to estimate the impact of reducing dietary salt on mortality from stroke and ischaemic heart disease. DESIGN: Analysis of the results of 68 crossover trials and 10 randomised controlled trials of dietary salt reduction. MAIN OUTCOME MEASURE: Comparison of observed reductions in systolic blood pressure for each trial with predicted values calculated from between population analysis. RESULTS: In the 45 trials in which salt reduction lasted four weeks or less the observed reductions in blood pressure were less than those predicted, with the difference between observed and predicted reductions being greatest in the trials of shortest duration. In the 33 trials lasting five weeks or longer the predicted reductions in individual trials closely matched a wide range of observed reductions. This applied for all age groups and for people with both high and normal levels of blood pressure. In people aged 50-59 years a reduction in daily sodium intake of 50 mmol (about 3 g of salt), attainable by moderate dietary salt reduction would, after a few weeks, lower systolic blood pressure by an average of 5 mm Hg, and by 7 mm Hg in those with high blood pressure (170 mm Hg); diastolic blood pressure would be lowered by about half as much. It is estimated that such a reduction in salt intake by a whole Western population would reduce the incidence of stroke by 22% and of ischaemic heart disease by 16% [corrected]. CONCLUSIONS: The results from the trials support the estimates from the observational data in the accompanying two papers. The effect of universal moderate dietary salt reduction on mortality from stroke and ischaemic heart disease would be substantial--larger, indeed, than could be achieved by fully implementing recommended policy for treating high blood pressure with drugs. However, reduction also in the amount of salt added to processed foods would lower blood pressure by at least twice as much and prevent some 75,000 [corrected] deaths a year in Britain as well as much disability.", "title": "By how much does dietary salt reduction lower blood pressure? III--Analysis of data from trials of salt reduction." }, { "docid": "MED-4350", "text": "Potatoes have the highest daily per capita consumption of all vegetables in the U.S. diet. Pigmented potatoes contain high concentrations of antioxidants, including phenolic acids, anthocyanins, and carotenoids. In a single-dose study six to eight microwaved potatoes with skins or a comparable amount of refined starch as cooked biscuits was given to eight normal fasting subjects; repeated samples of blood were taken over an 8 h period. Plasma antioxidant capacity was measured by ferric reducing antioxidant power (FRAP). A 24 h urine was taken before and after each regimen. Urine antioxidant capacity due to polyphenol was measured by Folin reagent after correction for nonphenolic interferences with a solid phase (Polyclar) procedure. Potato caused an increase in plasma and urine antioxidant capacity, whereas refined potato starch caused a decrease in both; that is, it acted as a pro-oxidant. In a crossover study 18 hypertensive subjects with an average BMI of 29 were given either six to eight small microwaved purple potatoes twice daily or no potatoes for 4 weeks and then given the other regimen for another 4 weeks. There was no significant effect of potato on fasting plasma glucose, lipids, or HbA1c. There was no significant body weight increase. Diastolic blood pressure significantly decreased 4.3%, a 4 mm reduction. Systolic blood pressure decreased 3.5%, a 5 mm reduction. This blood pressure drop occurred despite the fact that 14 of 18 subjects were taking antihypertensive drugs. This is the first study to investigate the effect of potatoes on blood pressure. Thus, purple potatoes are an effective hypotensive agent and lower the risk of heart disease and stroke in hypertensive subjects without weight gain.", "title": "High-antioxidant potatoes: acute in vivo antioxidant source and hypotensive agent in humans after supplementation to hypertensive subjects." }, { "docid": "MED-2301", "text": "Objective To determine the comparative effectiveness of exercise versus drug interventions on mortality outcomes. Design Metaepidemiological study. Eligibility criteria Meta-analyses of randomised controlled trials with mortality outcomes comparing the effectiveness of exercise and drug interventions with each other or with control (placebo or usual care). Data sources Medline and Cochrane Database of Systematic Reviews, May 2013. Main outcome measure Mortality. Data synthesis We combined study level death outcomes from exercise and drug trials using random effects network meta-analysis. Results We included 16 (four exercise and 12 drug) meta-analyses. Incorporating an additional three recent exercise trials, our review collectively included 305 randomised controlled trials with 339 274 participants. Across all four conditions with evidence on the effectiveness of exercise on mortality outcomes (secondary prevention of coronary heart disease, rehabilitation of stroke, treatment of heart failure, prevention of diabetes), 14 716 participants were randomised to physical activity interventions in 57 trials. No statistically detectable differences were evident between exercise and drug interventions in the secondary prevention of coronary heart disease and prediabetes. Physical activity interventions were more effective than drug treatment among patients with stroke (odds ratios, exercise v anticoagulants 0.09, 95% credible intervals 0.01 to 0.70 and exercise v antiplatelets 0.10, 0.01 to 0.62). Diuretics were more effective than exercise in heart failure (exercise v diuretics 4.11, 1.17 to 24.76). Inconsistency between direct and indirect comparisons was not significant. Conclusions Although limited in quantity, existing randomised trial evidence on exercise interventions suggests that exercise and many drug interventions are often potentially similar in terms of their mortality benefits in the secondary prevention of coronary heart disease, rehabilitation after stroke, treatment of heart failure, and prevention of diabetes.", "title": "Comparative effectiveness of exercise and drug interventions on mortality outcomes: metaepidemiological study" }, { "docid": "MED-5041", "text": "Substantial data suggest that flavonoid-rich food could help prevent cardiovascular disease and cancer. Cocoa is the richest source of flavonoids, but current processing reduces the content substantially. The Kuna living in the San Blas drink a flavanol-rich cocoa as their main beverage, contributing more than 900 mg/day and thus probably have the most flavonoid-rich diet of any population. We used diagnosis on death certificates to compare cause-specific death rates from year 2000 to 2004 in mainland and the San Blas islands where only Kuna live. Our hypothesis was that if the high flavanoid intake and consequent nitric oxide system activation were important the result would be a reduction in the frequency of ischemic heart disease, stroke, diabetes mellitus, and cancer – all nitric oxide sensitive processes. There were 77,375 deaths in mainland Panama and 558 deaths in the San Blas. In mainland Panama, as anticipated, cardiovascular disease was the leading cause of death (83.4 ± 0.70 age adjusted deaths/100,000) and cancer was second (68.4 ± 1.6). In contrast, the rate of CVD and cancer among island-dwelling Kuna was much lower (9.2 ± 3.1) and (4.4 ± 4.4) respectively. Similarly deaths due to diabetes mellitus were much more common in the mainland (24.1 ± 0.74) than in the San Blas (6.6 ± 1.94). This comparatively lower risk among Kuna in the San Blas from the most common causes of morbidity and mortality in much of the world, possibly reflects a very high flavanol intake and sustained nitric oxide synthesis activation. However, there are many risk factors and an observational study cannot provide definitive evidence.", "title": "Does Flavanol Intake Influence Mortality from Nitric Oxide-Dependent Processes? Ischemic Heart Disease, Stroke, Diabetes Mellitus, and Cancer in Panama" }, { "docid": "MED-1318", "text": "BACKGROUND: Rice consumption has been associated with risk of type 2 diabetes, but its relation with cardiovascular disease (CVD) is limited. OBJECTIVE: We examined the association between rice consumption and risk of CVD incidence and mortality in a Japanese population. DESIGN: This was a prospective study in 91,223 Japanese men and women aged 40-69 y in whom rice consumption was determined and updated from 3 self-administered food-frequency questionnaires, each 5 y apart. Follow-up for incidence was from 1990 to 2009 in cohort I and 1993 to 2007 in cohort II and for mortality was from 1990 to 2009 in cohort I and 1993 to 2009 in cohort II. HRs and 95% CIs of CVD incidence and mortality were calculated according to quintiles of cumulative average rice consumption. RESULTS: In 15-18 y of follow-up, we ascertained 4395 incident cases of stroke, 1088 incident cases of ischemic heart disease (IHD), and 2705 deaths from CVD. Rice consumption was not associated with risk of incident stroke or IHD; the multivariable HR (95% CI) in the highest compared with lowest rice consumption quintiles was 1.01 (0.90, 1.14) for total stroke and 1.08 (0.84, 1.38) for IHD. Similarly, there was no association between rice consumption and risk of mortality from CVD; the HR (95% CI) for mortality from total CVD was 0.97 (0.84, 1.13). There were no interactions with sex or effect modifications by body mass index for any endpoint. CONCLUSION: Rice consumption is not associated with risk of CVD morbidity or mortality. © 2014 American Society for Nutrition.", "title": "Rice consumption is not associated with risk of cardiovascular disease morbidity or mortality in Japanese men and women: a large population-based, ..." }, { "docid": "MED-1192", "text": "Objectives To determine the quantitative efficacy of different classes of blood pressure lowering drugs in preventing coronary heart disease (CHD) and stroke, and who should receive treatment. Design Meta-analysis. Data source Medline (1966-2007). Study selection Randomised trials of blood pressure lowering drugs recording CHD events and strokes. 108 trials studied differences in blood pressure between study drug and placebo (or control group not receiving the study drug) (“blood pressure difference trials”), and 46 trials compared drugs (“drug comparison trials”). Seven trials with three randomised groups fell into both categories. The results were interpreted in the context of those expected from the largest published meta-analysis of cohort studies, totalling 958 000 people. Participants 464 000 people defined into three mutually exclusive categories: participants with no history of vascular disease, a history of CHD, or a history of stroke. Results In the blood pressure difference trials β blockers had a special effect over and above that due to blood pressure reduction in preventing recurrent CHD events in people with a history of CHD: risk reduction 29% (95% confidence interval 22% to 34%) compared with 15% (11% to 19%) in trials of other drugs. The extra effect was limited to a few years after myocardial infarction, with a risk reduction of 31% compared with 13% in people with CHD with no recent infarct (P=0.04). In the other blood pressure difference trials (excluding CHD events in trials of β blockers in people with CHD), there was a 22% reduction in CHD events (17% to 27%) and a 41% (33% to 48%) reduction in stroke for a blood pressure reduction of 10 mm Hg systolic or 5 mm Hg diastolic, similar to the reductions of 25% (CHD) and 36% (stroke) expected for the same difference in blood pressure from the cohort study meta-analysis, indicating that the benefit is explained by blood pressure reduction itself. The five main classes of blood pressure lowering drugs (thiazides, β blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers) were similarly effective (within a few percentage points) in preventing CHD events and strokes, with the exception that calcium channel blockers had a greater preventive effect on stroke (relative risk 0.92, 95% confidence interval 0.85 to 0.98). The percentage reductions in CHD events and stroke were similar in people with and without cardiovascular disease and regardless of blood pressure before treatment (down to 110 mm Hg systolic and 70 mm Hg diastolic). Combining our results with those from two other studies (the meta-analyses of blood pressure cohort studies and of trials determining the blood pressure lowering effects of drugs according to dose) showed that in people aged 60-69 with a diastolic blood pressure before treatment of 90 mm Hg, three drugs at half standard dose in combination reduced the risk of CHD by an estimated 46% and of stroke by 62%; one drug at standard dose had about half this effect. The present meta-analysis also showed that drugs other than calcium channel blockers (with the exception of non-cardioselective β blockers) reduced the incidence of heart failure by 24% (19% to 28%) and calcium channel blockers by 19% (6% to 31%). Conclusions With the exception of the extra protective effect of β blockers given shortly after a myocardial infarction and the minor additional effect of calcium channel blockers in preventing stroke, all the classes of blood pressure lowering drugs have a similar effect in reducing CHD events and stroke for a given reduction in blood pressure so excluding material pleiotropic effects. The proportional reduction in cardiovascular disease events was the same or similar regardless of pretreatment blood pressure and the presence or absence of existing cardiovascular disease. Guidelines on the use of blood pressure lowering drugs can be simplified so that drugs are offered to people with all levels of blood pressure. Our results indicate the importance of lowering blood pressure in everyone over a certain age, rather than measuring it in everyone and treating it in some.", "title": "Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies" }, { "docid": "MED-4093", "text": "OBJECTIVE: The association between hyperuricemia and cardiovascular events has been documented in high-risk groups, but is still undetermined in general populations, especially Chinese. This study assessed the temporal association between serum uric acid level, hyperuricemia, and cardiovascular mortality. METHODS: A prospective cohort study of 41,879 men and 48,514 women ages > or = 35 years was conducted using data from the MJ Health Screening Centers in Taiwan. Mortality from all causes, total cardiovascular disease (CVD), ischemic stroke, congestive heart failure, hypertensive disease, and coronary heart disease were compared according to increasing serum uric acid levels. RESULTS: A total of 1,151 (21.2%) events of 5,427 total deaths were ascribed to CVD (mean followup 8.2 years). Hazard ratios (HRs) for hyperuricemia (serum uric acid level >7 mg/dl) were estimated with Cox regression model after adjusting for age, sex, body mass index, cholesterol, triglycerides, diabetes, hypertension, heavy cigarette smoking, and frequent alcohol consumption. In all patients, HRs were 1.16 (P < 0.001) for all-cause mortality, 1.39 (P < 0.001) for total CVD, and 1.35 (P = 0.02) for ischemic stroke. In subgroup analysis, the HRs for cardiovascular risk remained significant in patients with hypertension (1.44, P < 0.001) and in patients with diabetes (1.64, P < 0.001). In addition, in a low metabolic risk subgroup, the HRs for all-cause mortality and total cardiovascular morbidity were 1.24 (P = 0.02) and 1.48 (P = 0.16), respectively. CONCLUSION: Hyperuricemia was an independent risk factor of mortality from all causes, total CVD, and ischemic stroke in the Taiwanese general population, in high-risk groups, and potentially in low-risk groups.", "title": "Serum uric acid level as an independent risk factor for all-cause, cardiovascular, and ischemic stroke mortality: a Chinese cohort study." }, { "docid": "MED-1677", "text": "Background The combination of healthy lifestyle factors is associated with lower risk of coronary heart disease, diabetes and total cardiovascular disease. Little is known about the impact of multiple lifestyle factors on risk of stroke. Methods and results We conducted a prospective cohort study among 43,685 men from Health Professionals Follow-up Study and 71,243 women from the Nurses' Health Study. Diet and other lifestyle factors were updated from self-reported questionnaires. We defined a low-risk lifestyle as not smoking, a body mass index <25 kg/m 2, ≥30 minutes/day of moderate activity, consuming alcohol modestly (men:5–30g; women:5–15g alcohol/day), and scoring within the top 40% of a healthy diet score. We documented 1559 strokes (853 ischemic, 278 hemorrhagic) among women and 994 strokes (600 ischemic, 161 hemorrhagic) among men during follow-up. Women with all five low-risk factors had a relative risk of 0.21 (95%CI:0.12, 0.36) for total and 0.19 (95%CI:0.09, 0.40) for ischemic stroke, compared to women who had none of these factors. Among men, the relative risks were 0.31 (95%CI:0.19, 0.53) for total and 0.20 (95%CI: 0.10, 0.42) for ischemic stroke for the same comparison. Among the women, 47% (95%CI:18%, 69%) of total and 54% (95%CI:15%, 78%) of ischemic stroke cases were attributable to lack of adherence to a low-risk lifestyle; among the men, 35% (95%CI:7%, 58%) of total and 52% (95%CI:19%, 75%) of ischemic stroke may have been prevented. Conclusions A low-risk lifestyle that is associated with a reduced risk of multiple chronic diseases may also be beneficial in the prevention of stroke, especially ischemic stroke.", "title": "Primary prevention of stroke by healthy lifestyle" }, { "docid": "MED-1548", "text": "This document details the procedures and recommendations of the Goals and Metrics Committee of the Strategic Planning Task Force of the American Heart Association, which developed the 2020 Impact Goals for the organization. The committee was charged with defining a new concept, cardiovascular health, and determining the metrics needed to monitor it over time. Ideal cardiovascular health, a concept well supported in the literature, is defined by the presence of both ideal health behaviors (nonsmoking, body mass index <25 kg/m(2), physical activity at goal levels, and pursuit of a diet consistent with current guideline recommendations) and ideal health factors (untreated total cholesterol <200 mg/dL, untreated blood pressure <120/<80 mm Hg, and fasting blood glucose <100 mg/dL). Appropriate levels for children are also provided. With the use of levels that span the entire range of the same metrics, cardiovascular health status for the whole population is defined as poor, intermediate, or ideal. These metrics will be monitored to determine the changing prevalence of cardiovascular health status and define achievement of the Impact Goal. In addition, the committee recommends goals for further reductions in cardiovascular disease and stroke mortality. Thus, the committee recommends the following Impact Goals: \"By 2020, to improve the cardiovascular health of all Americans by 20% while reducing deaths from cardiovascular diseases and stroke by 20%.\" These goals will require new strategic directions for the American Heart Association in its research, clinical, public health, and advocacy programs for cardiovascular health promotion and disease prevention in the next decade and beyond.", "title": "Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association's strategic Impact Go..." }, { "docid": "MED-1556", "text": "Background: A reduction in dietary saturated fat has generally been thought to improve cardiovascular health. Objective: The objective of this meta-analysis was to summarize the evidence related to the association of dietary saturated fat with risk of coronary heart disease (CHD), stroke, and cardiovascular disease (CVD; CHD inclusive of stroke) in prospective epidemiologic studies. Design: Twenty-one studies identified by searching MEDLINE and EMBASE databases and secondary referencing qualified for inclusion in this study. A random-effects model was used to derive composite relative risk estimates for CHD, stroke, and CVD. Results: During 5–23 y of follow-up of 347,747 subjects, 11,006 developed CHD or stroke. Intake of saturated fat was not associated with an increased risk of CHD, stroke, or CVD. The pooled relative risk estimates that compared extreme quantiles of saturated fat intake were 1.07 (95% CI: 0.96, 1.19; P = 0.22) for CHD, 0.81 (95% CI: 0.62, 1.05; P = 0.11) for stroke, and 1.00 (95% CI: 0.89, 1.11; P = 0.95) for CVD. Consideration of age, sex, and study quality did not change the results. Conclusions: A meta-analysis of prospective epidemiologic studies showed that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD. More data are needed to elucidate whether CVD risks are likely to be influenced by the specific nutrients used to replace saturated fat.", "title": "Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease" }, { "docid": "MED-5030", "text": "Study Objectives: To examine sex-specific associations between sleep duration and mortality from cardiovascular disease and other causes. Design: Cohort study. Setting: Community-based study. Participants: A total of 98,634 subjects (41,489 men and 57,145 women) aged 40 to 79 years from 1988 to 1990 and were followed until 2003. Interventions: N/A. Measurements and Results: During a median follow-up of 14.3 years, there were 1964 deaths (men and women: 1038 and 926) from stroke, 881 (508 and 373) from coronary heart disease, 4287 (2297 and 1990) from cardiovascular disease, 5465 (3432 and 2033) from cancer, and 14,540 (8548 and 5992) from all causes. Compared with a sleep duration of 7 hours, sleep duration of 4 hours or less was associated with increased mortality from coronary heart disease for women and noncardiovascular disease/noncancer and all causes in both sexes. The respective multivariable hazard ratios were 2.32 (1.19–4.50) for coronary heart disease in women, 1.49 (1.02–2.18) and 1.47 (1.01–2.15) for noncardiovascular disease/noncancer, and 1.29 (1.02–1.64) and 1.28 (1.03–1.60) for all causes in men and women, respectively. Long sleep duration of 10 hours or longer was associated with 1.5- to 2-fold increased mortality from total and ischemic stroke, total cardiovascular disease, noncardiovascular disease/noncancer, and all causes for men and women, compared with 7 hours of sleep in both sexes. There was no association between sleep duration and cancer mortality in either sex. Conclusions: Both short and long sleep duration were associated with increased mortality from cardiovascular disease, noncardiovascular disease/noncancer, and all causes for both sexes, yielding a U-shaped relationship with total mortality with a nadir at 7 hours of sleep. Citation: Ikehara S; Iso H; Date C; Kikuchi S; Watanabe Y; Wada Y; Inaba Y; Tamakoshi A. Association of sleep duration with mortality from cardiovascular disease and other causes for Japanese men and women: the JACC study. SLEEP 2009;32(3):259–301.", "title": "Association of Sleep Duration with Mortality from Cardiovascular Disease and Other Causes for Japanese Men and Women: the JACC Study" }, { "docid": "MED-1410", "text": "In 15 cohorts of the Seven Countries Study, comprising 11,579 men aged 40-59 years and \"healthy\" at entry, 2,288 died in 15 years. Death rates differed among cohorts. Differences in mean age, blood pressure, serum cholesterol, and smoking habits \"explained\" 46% of variance in death rate from all causes, 80% from coronary heart disease, 35% from cancer, and 45% from stroke. Death rate differences were unrelated to cohort differences in mean relative body weight, fatness, and physical activity. The cohorts differed in average diets. Death rates were related positively to average percentage of dietary energy from saturated fatty acids, negatively to dietary energy percentage from monounsaturated fatty acids, and were unrelated to dietary energy percentage from polyunsaturated fatty acids, proteins, carbohydrates, and alcohol. All death rates were negatively related to the ratio of monounsaturated to saturated fatty acids. Inclusion of that ratio with age, blood pressure, serum cholesterol, and smoking habits as independent variables accounted for 85% of variance in rates of deaths from all causes, 96% coronary heart disease, 55% cancer, and 66% stroke. Oleic acid accounted for almost all differences in monounsaturates among cohorts. All-cause and coronary heart disease death rates were low in cohorts with olive oil as the main fat. Causal relationships are not claimed but consideration of characteristics of populations as well as of individuals within populations is urged in evaluating risks.", "title": "The diet and 15-year death rate in the seven countries study." }, { "docid": "MED-2402", "text": "Despite a proposed protective effect of fish intake on the risk of cardiovascular disease, epidemiologic evidence on fish intake and mortality is inconsistent. We investigated associations of fish intake, assessed through a validated food frequency questionnaire, with risks of total and cause-specific mortality in 2 prospective cohort studies of 134,296 Chinese men and women (1997–2009). Vital status and date and cause of death were ascertained through annual linkage to the Shanghai Vital Statistics Registry database and biennial home visits. Cox regression was used to calculate hazard ratios and corresponding 95% confidence intervals. After excluding the first year of observation, the analysis included 3,666 deaths among women and 2,170 deaths among men. Fish intake was inversely associated with risks of total, ischemic stroke, and diabetes mortality; the corresponding hazard ratios for the highest quintiles of intake compared with the lowest were 0.84 (95% confidence interval (CI): 0.76, 0.92), 0.63 (95% CI: 0.41, 0.94), and 0.61 (95% CI: 0.39, 0.95), respectively. No associations with cancer or ischemic heart disease mortality were observed. Further analyses suggested that the inverse associations with total, ischemic stroke, and diabetes mortality were primarily related to consumption of saltwater fish and intake of long-chain n-3 fatty acids. Overall, our findings support the postulated health benefits of fish consumption.", "title": "Fish Intake and Risks of Total and Cause-specific Mortality in 2 Population-based Cohort Studies of 134,296 Men and Women" }, { "docid": "MED-3435", "text": "INTRODUCTION: Previous cross-sectional studies have suggested that erectile dysfunction (ED) represents an independent risk factor for future cardiovascular events. However, very few studies have attempted to examine the association between ED and subsequent stroke. AIM: The aim of this study is to estimate the risk of stroke during a 5-year follow-up period after the first ambulatory care visit for the treatment of ED using nationwide, population-based data and a retrospective case-control cohort design in Taiwan. METHODS: This study used data sourced from the \"Longitudinal Health Insurance Database.\" The study cohort comprised 1,501 patients who received a principal diagnosis of ED between 1997 and 2001 and 7,505 randomly selected subjects as the comparison cohort. Each patient (N = 9,006) was then individually tracked for 5 years from their index ambulatory care visit to identify those who had diagnosed episodes of stroke. MAIN OUTCOME MEASURE: Stratified Cox proportional hazard regressions were performed as a means of comparing the 5-year stroke-free survival rate for the two cohorts. RESULTS: Of the sampled patients, 918 (10.2%) developed stroke within the 5-year follow-up period, that is, 188 individuals (12.5% of the patients with ED) from the study cohort and 730 individuals (9.7% of patients in the comparison cohort) from the comparison cohort. The log-rank test indicated that patients with ED had significantly lower 5-year stroke-free survival rates than those in the comparison cohort (P < 0.001). After adjusting for the patient's monthly income, geographical location, hypertension, diabetes, coronary heart disease, peripheral vascular disease, atrial fibrillation, and hyperlipidemia, patients with ED were more likely to have a stroke during the 5-year follow-up period than patients in the comparison cohort (hazard ratio = 1.29, 95% confidence interval = 1.08 - 1.54, P < 0.01). CONCLUSIONS: These results suggest that ED is a surrogate marker for future stroke in men. © 2010 International Society for Sexual Medicine.", "title": "Increased risk of stroke among men with erectile dysfunction: a nationwide population-based study." }, { "docid": "MED-1232", "text": "BACKGROUND & AIMS: This research was aimed at clarifying whether high dietary fiber intake has an impact on incidence and risk of stroke at a population level. METHODS: In 1647 unselected subjects, dietary fiber intake (DFI) was detected in a 12-year population-based study, using other dietary variables, anagraphics, biometrics, blood pressure, heart rate, blood lipids, glucose, insulin, uricaemia, fibrinogenaemia, erytrosedimentation rate, diabetes, insulin resistance, smoking, pulmonary disease and left ventricular hypertrophy as covariables. RESULTS: In adjusted Cox models, high DFI reduced the risk of stroke. In analysis based on quintiles of fiber intake adjusted for confounders, HR for incidence of stroke was lower when the daily intake of soluble fiber was >25 g or that of insoluble fiber was >47 g. In multivariate analyses, using these values as cut-off of DFI, the risk of stroke was lower in those intaking more that the cut-off of soluble (HR 0.31, 0.17-0.55) or insoluble (HR 0.35, 0.19-0.63) fiber. Incidence of stroke was also lower (-50%, p < 0.003 and -46%, p < 0.01, respectively). CONCLUSIONS: Higher dietary DFI is inversely and independently associated to incidence and risk of stroke in general population. Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.", "title": "High dietary fiber intake prevents stroke at a population level." }, { "docid": "MED-4603", "text": "Background The US diet is high in salt, with the majority coming from processed foods. Reducing dietary salt is an important potential public health target. Methods We used the Coronary Heart Disease (CHD) Policy Model to quantify the benefits of potentially achievable population-wide reductions in dietary salt of up to 3 gm/day (1200 mg/day of sodium). We estimated cardiovascular disease rates and costs in age, sex, and race subgroups, compared salt reduction with other interventions to reduce cardiovascular risk, and determined the cost-effectiveness of salt reduction compared with drug treatment of hypertension. Results Reducing salt by 3 gm/day is projected to result in 60,000–120,000 fewer new CHD cases, 32,000–66,000 fewer new strokes, 54,000–99,000 fewer myocardial infarctions, and 44,000–92,000 fewer deaths from any cause annually. All segments of the population would benefit, with blacks benefiting proportionately more, women benefiting particularly from stroke reduction, older adults from reductions in CHD events, and younger adults from lower mortality rates. The cardiovascular benefits from lower salt are on par with benefits from reducing tobacco, obesity, or cholesterol. A regulatory intervention designed to achieve 3 gm/day salt reduction would save 194,000–392,000 quality-adjusted life-years and $10–24 billion in healthcare costs annually. Such an intervention would be cost-saving even if only a modest 1 gm/day reduction were achieved gradually over the decade from 2010–2019 and would be more cost-effective than treating all hypertensive individuals with medications. Conclusions Modest reduction in dietary salt could substantially reduce cardiovascular events and medical costs and should be a public health target.", "title": "Reductions in Cardiovascular Disease Projected from Modest Reductions in Dietary Salt" }, { "docid": "MED-5301", "text": "Background The US diet is high in salt, with the majority coming from processed foods. Reducing dietary salt is an important potential public health target. Methods We used the Coronary Heart Disease (CHD) Policy Model to quantify the benefits of potentially achievable population-wide reductions in dietary salt of up to 3 gm/day (1200 mg/day of sodium). We estimated cardiovascular disease rates and costs in age, sex, and race subgroups, compared salt reduction with other interventions to reduce cardiovascular risk, and determined the cost-effectiveness of salt reduction compared with drug treatment of hypertension. Results Reducing salt by 3 gm/day is projected to result in 60,000–120,000 fewer new CHD cases, 32,000–66,000 fewer new strokes, 54,000–99,000 fewer myocardial infarctions, and 44,000–92,000 fewer deaths from any cause annually. All segments of the population would benefit, with blacks benefiting proportionately more, women benefiting particularly from stroke reduction, older adults from reductions in CHD events, and younger adults from lower mortality rates. The cardiovascular benefits from lower salt are on par with benefits from reducing tobacco, obesity, or cholesterol. A regulatory intervention designed to achieve 3 gm/day salt reduction would save 194,000–392,000 quality-adjusted life-years and $10–24 billion in healthcare costs annually. Such an intervention would be cost-saving even if only a modest 1 gm/day reduction were achieved gradually over the decade from 2010–2019 and would be more cost-effective than treating all hypertensive individuals with medications. Conclusions Modest reduction in dietary salt could substantially reduce cardiovascular events and medical costs and should be a public health target.", "title": "Reductions in Cardiovascular Disease Projected from Modest Reductions in Dietary Salt" }, { "docid": "MED-2082", "text": "BACKGROUND: Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex. METHODS: We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions. FINDINGS: In 2010, there were 52·8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24·9% of deaths worldwide in 2010, down from 15·9 million (34·1%) of 46·5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2·5 to 1·4 million), lower respiratory infections (from 3·4 to 2·8 million), neonatal disorders (from 3·1 to 2·2 million), measles (from 0·63 to 0·13 million), and tetanus (from 0·27 to 0·06 million). Deaths from HIV/AIDS increased from 0·30 million in 1990 to 1·5 million in 2010, reaching a peak of 1·7 million in 2006. Malaria mortality also rose by an estimated 19·9% since 1990 to 1·17 million deaths in 2010. Tuberculosis killed 1·2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34·5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1·5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12·9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1·3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5·1 million deaths) was marginally higher in 2010 (9·6%) compared with two decades earlier (8·8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1·3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted. INTERPRETATION: Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis. FUNDING: Bill & Melinda Gates Foundation. Copyright © 2012 Elsevier Ltd. All rights reserved.", "title": "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease S..." }, { "docid": "MED-3433", "text": "OBJECTIVES: Our goal was to evaluate the association between erectile dysfunction (ED) and risk of cardiovascular disease (CVD) and all-cause mortality by conducting a meta-analysis of prospective cohort studies. BACKGROUND: Observational studies suggest an association between ED and the incidence of CVD. However, whether ED is an independent risk factor of CVD remains controversial. METHODS: The PubMed database was searched through January 2011 to identify studies that met pre-stated inclusion criteria. Reference lists of retrieved articles were also reviewed. Two authors independently extracted information on the designs of the studies, the characteristics of the study participants, exposure and outcome assessments, and control for potential confounding factors. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. RESULTS: Twelve prospective cohort studies involving 36,744 participants were included in the meta-analysis. The overall combined relative risks for men with ED compared with the reference group were 1.48 (95% confidence interval [CI]: 1.25 to 1.74) for CVD, 1.46 (95% CI: 1.31 to 1.63) for coronary heart disease, 1.35 (95% CI: 1.19 to 1.54) for stroke, and 1.19 (95% CI: 1.05 to 1.34) for all-cause mortality. Sensitivity analysis restricted to studies with control for conventional cardiovascular risk factors yielded similar results. No evidence of publication bias was observed. CONCLUSIONS: This meta-analysis of prospective cohort studies suggests that ED significantly increases the risk of CVD, coronary heart disease, stroke, and all-cause mortality, and the increase is probably independent of conventional cardiovascular risk factors. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.", "title": "Erectile dysfunction and risk of cardiovascular disease: meta-analysis of prospective cohort studies." }, { "docid": "MED-5299", "text": "Background Knowledge of the number of deaths caused by risk factors is needed for health policy and priority setting. Our aim was to estimate the mortality effects of the following 12 modifiable dietary, lifestyle, and metabolic risk factors in the United States (US) using consistent and comparable methods: high blood glucose, low-density lipoprotein (LDL) cholesterol, and blood pressure; overweight–obesity; high dietary trans fatty acids and salt; low dietary polyunsaturated fatty acids, omega-3 fatty acids (seafood), and fruits and vegetables; physical inactivity; alcohol use; and tobacco smoking. Methods and Findings We used data on risk factor exposures in the US population from nationally representative health surveys and disease-specific mortality statistics from the National Center for Health Statistics. We obtained the etiological effects of risk factors on disease-specific mortality, by age, from systematic reviews and meta-analyses of epidemiological studies that had adjusted (i) for major potential confounders, and (ii) where possible for regression dilution bias. We estimated the number of disease-specific deaths attributable to all non-optimal levels of each risk factor exposure, by age and sex. In 2005, tobacco smoking and high blood pressure were responsible for an estimated 467,000 (95% confidence interval [CI] 436,000–500,000) and 395,000 (372,000–414,000) deaths, accounting for about one in five or six deaths in US adults. Overweight–obesity (216,000; 188,000–237,000) and physical inactivity (191,000; 164,000–222,000) were each responsible for nearly 1 in 10 deaths. High dietary salt (102,000; 97,000–107,000), low dietary omega-3 fatty acids (84,000; 72,000–96,000), and high dietary trans fatty acids (82,000; 63,000–97,000) were the dietary risks with the largest mortality effects. Although 26,000 (23,000–40,000) deaths from ischemic heart disease, ischemic stroke, and diabetes were averted by current alcohol use, they were outweighed by 90,000 (88,000–94,000) deaths from other cardiovascular diseases, cancers, liver cirrhosis, pancreatitis, alcohol use disorders, road traffic and other injuries, and violence. Conclusions Smoking and high blood pressure, which both have effective interventions, are responsible for the largest number of deaths in the US. Other dietary, lifestyle, and metabolic risk factors for chronic diseases also cause a substantial number of deaths in the US. Please see later in the article for Editors' Summary Editors' Summary A number of modifiable factors are responsible for many premature or preventable deaths. For example, being overweight or obese shortens life expectancy, while half of all long-term tobacco smokers in Western populations will die prematurely from a disease directly related to smoking. Modifiable risk factors fall into three main groups. First, there are lifestyle risk factors. These include tobacco smoking, physical inactivity, and excessive alcohol use (small amounts of alcohol may actually prevent diabetes and some types of heart disease and stroke). Second, there are dietary risk factors such as a high salt intake and a low intake of fruits and vegetables. Finally, there are “metabolic risk factors,” which shorten life expectancy by increasing a person's chances of developing cardiovascular disease (in particular, heart problems and strokes) and diabetes. Metabolic risk factors include having high blood pressure or blood cholesterol and being overweight or obese. Why Was This Study Done? It should be possible to reduce preventable deaths by changing modifiable risk factors through introducing public health policies, programs and regulations that reduce exposures to these risk factors. However, it is important to know how many deaths are caused by each risk factor before developing policies and programs that aim to improve a nation's health. Although previous studies have provided some information on the numbers of premature deaths caused by modifiable risk factors, there are two problems with these studies. First, they have not used consistent and comparable methods to estimate the number of deaths attributable to different risk factors. Second, they have rarely considered the effects of dietary and metabolic risk factors. In this new study, the researchers estimate the number of deaths due to 12 different modifiable dietary, lifestyle, and metabolic risk factors for the United States population. They use a method called “comparative risk assessment.” This approach estimates the number of deaths that would be prevented if current distributions of risk factor exposures were changed to hypothetical optimal distributions. What Did the Researchers Do and Find? The researchers extracted data on exposures to these 12 selected risk factors from US national health surveys, and they obtained information on deaths from difference diseases for 2005 from the US National Center for Health Statistics. They used previously published studies to estimate how much each risk factor increases the risk of death from each disease. The researchers then used a mathematical formula to estimate the numbers of deaths caused by each risk factor. Of the 2.5 million US deaths in 2005, they estimate that nearly half a million were associated with tobacco smoking and about 400,000 were associated with high blood pressure. These two risk factors therefore each accounted for about 1 in 5 deaths in US adults. Overweight–obesity and physical inactivity were each responsible for nearly 1 in 10 deaths. Among the dietary factors examined, high dietary salt intake had the largest effect, being responsible for 4% of deaths in adults. Finally, while alcohol use prevented 26,000 deaths from ischemic heart disease, ischemic stroke, and diabetes, the researchers estimate that it caused 90,000 deaths from other types of cardiovascular diseases, other medical conditions, and road traffic accidents and violence. What Do These Findings Mean? These findings indicate that smoking and high blood pressure are responsible for the largest number of preventable deaths in the US, but that several other modifiable risk factors also cause many deaths. Although the accuracy of some of the estimates obtained in this study will be affected by the quality of the data used, these findings suggest that targeting a handful of risk factors could greatly reduce premature mortality in the US. The findings might also apply to other countries, although the risk factors responsible for most preventable deaths may vary between countries. Importantly, effective individual-level and population-wide interventions are already available to reduce people's exposure to the two risk factors responsible for most preventable deaths in the US. The researchers also suggest that combinations of regulation, pricing, and education have the potential to reduce the exposure of US residents to other risk factors that are likely to shorten their lives. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000058.", "title": "The Preventable Causes of Death in the United States: Comparative Risk Assessment of Dietary, Lifestyle, and Metabolic Risk Factors" }, { "docid": "MED-5151", "text": "Cocoa and chocolate have recently been found to be rich plant-derived sources of antioxidant flavonoids with beneficial cardiovascular properties. These favorable physiological effects include: antioxidant activity, vasodilation and blood pressure reduction, inhibition of platelet activity, and decreased inflammation. Increasing evidence from experimental and clinical studies using cocoa-derived products and chocolate suggest an important role for these high-flavanol-containing foods in heart and vascular protection.", "title": "The emerging role of flavonoid-rich cocoa and chocolate in cardiovascular health and disease." }, { "docid": "MED-1387", "text": "BACKGROUND: Epidemiologic studies have shown inverse associations between nut consumption and diabetes, cardiovascular disease (CVD), and all-cause mortality, but results have not been consistent. OBJECTIVE: We assessed the relation between nut intake and incidence of type 2 diabetes, CVD, and all-cause mortality. DESIGN: We searched PubMed and EMBASE for all prospective cohort studies published up to March 2013 with RRs and 95% CIs for outcomes of interest. A random-effects model was used to pool risk estimates across studies. RESULTS: In 31 reports from 18 prospective studies, there were 12,655 type 2 diabetes, 8862 CVD, 6623 ischemic heart disease (IHD), 6487 stroke, and 48,818 mortality cases. The RR for each incremental serving per day of nut intake was 0.80 (95% CI: 0.69, 0.94) for type 2 diabetes without adjustment for body mass index; with adjustment, the association was attenuated [RR: 1.03; 95% CI: 0.91, 1.16; NS]. In the multivariable-adjusted model, pooled RRs (95% CIs) for each serving per day of nut consumption were 0.72 (0.64, 0.81) for IHD, 0.71 (0.59, 0.85) for CVD, and 0.83 (0.76, 0.91) for all-cause mortality. Pooled RRs (95% CIs) for the comparison of extreme quantiles of nut intake were 1.00 (0.84, 1.19; NS) for type 2 diabetes, 0.66 (0.55, 0.78) for IHD, 0.70 (0.60, 0.81) for CVD, 0.91 (0.81, 1.02; NS) for stroke, and 0.85 (0.79, 0.91) for all-cause mortality. CONCLUSIONS: Our meta-analysis indicates that nut intake is inversely associated with IHD, overall CVD, and all-cause mortality but not significantly associated with diabetes and stroke. The inverse association between the consumption of nuts and diabetes was attenuated after adjustment for body mass index. These findings support recommendations to include nuts as part of a healthy dietary pattern for the prevention of chronic diseases. © 2014 American Society for Nutrition.", "title": "Nut consumption and risk of type 2 diabetes, cardiovascular disease, and all-cause mortality: a systematic review and meta-analysis." }, { "docid": "MED-5250", "text": "Several prospective studies considered the relation between coffee consumption and mortality. Most studies, however, were underpowered to detect an association, since they included relatively few deaths. To obtain quantitative overall estimates, we combined all published data from prospective studies on the relation of coffee with mortality for all causes, all cancers, cardiovascular disease (CVD), coronary/ischemic heart disease (CHD/IHD) and stroke. A bibliography search, updated to January 2013, was carried out in PubMed and Embase to identify prospective observational studies providing quantitative estimates on mortality from all causes, cancer, CVD, CHD/IHD or stroke in relation to coffee consumption. A systematic review and meta-analysis was conducted to estimate overall relative risks (RR) and 95 % confidence intervals (CI) using random-effects models. The pooled RRs of all cause mortality for the study-specific highest versus low (≤1 cup/day) coffee drinking categories were 0.88 (95 % CI 0.84-0.93) based on all the 23 studies, and 0.87 (95 % CI 0.82-0.93) for the 19 smoking adjusting studies. The combined RRs for CVD mortality were 0.89 (95 % CI 0.77-1.02, 17 smoking adjusting studies) for the highest versus low drinking and 0.98 (95 % CI 0.95-1.00, 16 studies) for the increment of 1 cup/day. Compared with low drinking, the RRs for the highest consumption of coffee were 0.95 (95 % CI 0.78-1.15, 12 smoking adjusting studies) for CHD/IHD, 0.95 (95 % CI 0.70-1.29, 6 studies) for stroke, and 1.03 (95 % CI 0.97-1.10, 10 studies) for all cancers. This meta-analysis provides quantitative evidence that coffee intake is inversely related to all cause and, probably, CVD mortality.", "title": "A meta-analysis of prospective studies of coffee consumption and mortality for all causes, cancers and cardiovascular diseases." }, { "docid": "MED-5042", "text": "The Kuna Indians who reside in an archipelago on the Caribbean Coast of Panama have very low blood pressure levels, live longer than other Panamanians, and have a reduced frequency of myocardial infarction, stroke, diabetes mellitus, and cancer -- at least on their death certificates. One outstanding feature of their diet includes a very high intake of flavanol-rich cocoa. Flavonoids in cocoa activate nitric oxide synthesis in healthy humans. The possibility that the high flavanol intake protects the Kuna against high blood pressure, ischemic heart disease, stroke, diabetes mellitus, and cancer is sufficiently intriguing and sufficiently important that large, randomized controlled clinical trials should be pursued.", "title": "Flavanols, the Kuna, Cocoa Consumption, and Nitric Oxide" }, { "docid": "MED-5258", "text": "Background Coffee is one of the most widely consumed beverages, but the association between coffee consumption and the risk of death remains unclear. Methods We examined the association of coffee drinking with subsequent total and cause-specific mortality among 229,119 men and 173,141 women in the National Institutes of Health–AARP Diet and Health Study who were 50 to 71 years of age at baseline. Participants with cancer, heart disease, and stroke were excluded. Coffee consumption was assessed once at baseline. Results During 5,148,760 person-years of follow-up between 1995 and 2008, a total of 33,731 men and 18,784 women died. In age-adjusted models, the risk of death was increased among coffee drinkers. However, coffee drinkers were also more likely to smoke, and, after adjustment for tobacco-smoking status and other potential confounders, there was a significant inverse association between coffee consumption and mortality. Adjusted hazard ratios for death among men who drank coffee as compared with those who did not were as follows: 0.99 (95% confidence interval [CI], 0.95 to 1.04) for drinking less than 1 cup per day, 0.94 (95% CI, 0.90 to 0.99) for 1 cup, 0.90 (95% CI, 0.86 to 0.93) for 2 or 3 cups, 0.88 (95% CI, 0.84 to 0.93) for 4 or 5 cups, and 0.90 (95% CI, 0.85 to 0.96) for 6 or more cups of coffee per day (P<0.001 for trend); the respective hazard ratios among women were 1.01 (95% CI, 0.96 to 1.07), 0.95 (95% CI, 0.90 to 1.01), 0.87 (95% CI, 0.83 to 0.92), 0.84 (95% CI, 0.79 to 0.90), and 0.85 (95% CI, 0.78 to 0.93) (P<0.001 for trend). Inverse associations were observed for deaths due to heart disease, respiratory disease, stroke, injuries and accidents, diabetes, and infections, but not for deaths due to cancer. Results were similar in subgroups, including persons who had never smoked and persons who reported very good to excellent health at baseline. Conclusions In this large prospective study, coffee consumption was inversely associated with total and cause-specific mortality. Whether this was a causal or associational finding cannot be determined from our data. (Funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics.)", "title": "Association of Coffee Drinking with Total and Cause-Specific Mortality" }, { "docid": "MED-2077", "text": "Cardiovascular diseases are one of the leading causes of morbidity and mortality in industrialized countries, and although many processes play a role in the development of vascular disease, thrombosis is the primary event that precipitates stroke and acute coronary syndromes. The blood platelets are of significant importance in medicine. These cells are involved in many physiological processes, particularly haemostasis through their ability to aggregate and form clots in response to activation. In addition, these dynamic cells display activities that extend beyond thrombosis, including an important role in initiating and sustaining vascular inflammation. The expansion of knowledge from basic and clinical research has highlighted the critical position of platelets in several inflammatory diseases such as arthritis and atherosclerosis. Platelets are emerging as important mediators of inflammation and provide important signals to mediate phenotype of other blood and vascular cells. The important role of platelets in arterial thrombosis and the onset of acute myocardial infarction after atherosclerotic plaque rupture make inhibition of platelet aggregation a critical step in preventing thrombotic events associated with stroke, heart attack, and peripheral arterial thrombosis. However, the use of platelet inhibitors for thrombosis prevention must seek a delicate balance between inhibiting platelet activation and an associated increased bleeding risk. The aim of this review is to up-date the knowledge on platelets physiology and dysfunction in pathologies, such as diabetes mellitus, hypercholesterolemia, and hypertension, emphasizing the link between platelets and the inflammation-related atherosclerosis. The review evaluates the opportunities offered by the novel platelet inhibitors to efficiently alleviate the thrombotic events. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Platelet dysfunction in vascular pathologies and how can it be treated." }, { "docid": "MED-2376", "text": "Endothelial dysfunction is considered an important prognostic factor in atherosclerosis. To determine the long-term association of brachial artery flow-mediated dilation (FMD) and adverse cardiovascular (CV) events in healthy subjects, we prospectively assessed brachial FMD in 618 consecutive healthy subjects with no apparent heart disease, 387 men (63%), and mean age 54 ± 11 years. After overnight fasting and discontinuation of all medications for ≥12 hours, FMD was assessed using high-resolution linear array ultrasound. Subjects were divided into 2 groups: FMD ≤11.3% (n = 309) and >11.3% (n = 309), where 11.3% is the median FMD, and were comparable regarding CV risk factors, lipoproteins, fasting glucose, C-reactive protein, concomitant medications, and Framingham 10-year risk score. In a mean clinical follow-up of 4.6 ± 1.8 years, the composite CV events (all-cause mortality, nonfatal myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting, and percutaneous coronary interventions) were significantly more common in subjects with FMD ≤11.3% rather than >11.3% (15.2% vs 1.2%, p = 0.0001, respectively). Univariate analysis demonstrated that the median FMD significantly predicted CV events (odds ratio 2.78, 95% CI 1.35 to 5.71, p <0.001). Multivariate analysis, controlling for traditional CV risk factors, demonstrated that median FMD was the best independent predictor of long-term CV adverse events (odds ratio 2.93, 95% CI 1.28 to 6.68, p <0.001). In conclusion, brachial artery median FMD independently predicts long-term adverse CV events in healthy subjects with no apparent heart disease in addition to those derived from traditional risk factor assessment. Copyright © 2014 Elsevier Inc. All rights reserved.", "title": "Usefulness of brachial artery flow-mediated dilation to predict long-term cardiovascular events in subjects without heart disease." }, { "docid": "MED-5281", "text": "Alterations of endothelial cells and the vasculature play a central role in the pathogenesis of a broad spectrum of the most dreadful of human diseases, as endothelial cells have the key function of participating in the maintenance of patent and functional capillaries. The endothelium is directly involved in peripheral vascular disease, stroke, heart disease, diabetes, insulin resistance, chronic kidney failure, tumor growth, metastasis, venous thrombosis, and severe viral infectious diseases. Dysfunction of the vascular endothelium is thus a hallmark of human diseases. In this review the main endothelial abnormalities found in various human diseases such as cancer, diabetes mellitus, atherosclerosis, and viral infections are addressed.", "title": "The Vascular Endothelium and Human Diseases" }, { "docid": "MED-2667", "text": "Ample research indicates that age-related neuronal-behavioral decrements are the result of oxidative stress that may be ameliorated by antioxidants. Our previous study had shown that rats given dietary supplements of fruit and vegetable extracts with high antioxidant activity for 8 months beginning at 6 months of age retarded age-related declines in neuronal and cognitive function. The present study showed that such supplements (strawberry, spinach, or blueberry at 14.8, 9.1, or 18.6 gm of dried aqueous extract per kilogram of diet, respectively) fed for 8 weeks to 19-month-old Fischer 344 rats were also effective in reversing age-related deficits in several neuronal and behavioral parameters including: oxotremorine enhancement of K(+)-evoked release of dopamine from striatal slices, carbachol-stimulated GTPase activity, striatal Ca(45) buffering in striatal synaptosomes, motor behavioral performance on the rod walking and accelerod tasks, and Morris water maze performance. These findings suggest that, in addition to their known beneficial effects on cancer and heart disease, phytochemicals present in antioxidant-rich foods may be beneficial in reversing the course of neuronal and behavioral aging.", "title": "Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry ..." } ]
PLAIN-2277
Tuna Council
[ { "docid": "MED-4943", "text": "Fish and seal oil dietary supplements, marketed to be rich in omega-3 fatty acids, are frequently consumed by Canadians. Samples of these supplements (n = 30) were collected in Vancouver, Canada, between 2005 and 2007. All oil supplements were analyzed for polychlorinated biphenyls (PCBs) and organochlorine insecticides (OCs) and each sample was found to contain detectable residues. The highest SigmaPCB and SigmaDDT (1,1,1-trichloro-di-(4-chlorophenyl)ethane) concentrations (10400 ng/g and 3310 ng/g, respectively) were found in a shark oil sample while lowest levels were found in supplements prepared using mixed fish oils (anchovy, mackerel, and sardine) (0.711 ng SigmaPCB/g and 0.189 ng SigmaDDT/g). Mean SigmaPCB concentrations in oil supplements were 34.5, 24.2, 25.1, 95.3, 12.0, 5260, 321, and 519 ng/g in unidentified fish, mixed fish containing no salmon, mixed fish with salmon, salmon, vegetable with mixed fish, shark, menhaden (n = 1), and seal (n = 1), respectively. Maximum concentrations of the other OCs were generally observed in the seal oil. The hexachlorinated PCB congeners were the dominant contributors to SigmaPCB levels, while SigmaDDT was the greatest contributor to organochlorine levels. Intake estimates were made using maximum dosages on manufacturers' labels and results varied widely due to the large difference in residue concentrations obtained. Average SigmaPCB and SigmaDDT intakes were calculated to be 736 +/- 2840 ng/d and 304 +/- 948 ng/d, respectively.", "title": "Persistent organic pollutants in fish oil supplements on the Canadian market: polychlorinated biphenyls and organochlorine insecticides." } ]
[ { "docid": "MED-4375", "text": "There is widespread concern over the presence of Hg in fish consumed by humans. While studies have been focused on determining the Hg concentration in sport fish and some commercial fish, little attention has been directed to canned tuna; it is widely held that concentrations are low. In the present study, the amount of Hg present in canned tuna purchased in Las Vegas, Nevada, USA, was examined, and the brand, temporal variation, type, and packaging medium impacts on Hg concentrations in tuna were explored. A significant (p < 0.001) brand difference was noted: Brand 3 contained higher Hg concentrations ($\\bar x$ standard deviation (SD) (0.777 +/- 0.320 ppm) than Brands 1 (0.541 +/- 0.114 ppm) and 2 (0.550 +/- 0.199 ppm). Chunk white tuna (0.619 +/- 0.212 ppm) and solid white tuna (0.576 +/- 0.178 ppm) were both significantly (p < 0.001) higher in mean Hg than chunk light tuna (0.137 +/- 0.063 ppm). No significant temporal variation was noted, and packaging had no significant effect on Hg concentration. In total, 55% of all tuna examined was above the U.S. Environmental Protection Agency's (U.S. EPA) safety level for human consumption (0.5 ppm), and 5% of the tuna exceeded the action level established by the U.S. Food and Drug Administration (U.S. FDA) (1.0 ppm). These results indicate that stricter regulation of the canned tuna industry is necessary to ensure the safety of sensitive populations such as pregnant women, infants, and children. According to the U.S. EPA reference dose of 0.1 microg/kg body weight per day and a mean Hg value of 0.619 ppm, a 25-kg child may consume a meal (75 g) of canned chunk white tuna only once every 18.6 d. Continued monitoring of the industry and efforts to reduce Hg concentrations in canned tuna are recommended. Environ. Copyright 2009 SETAC.", "title": "An evaluation of mercury concentrations in three brands of canned tuna." }, { "docid": "MED-3629", "text": "The Fukushima Dai-ichi release of radionuclides into ocean waters caused significant local and global concern regarding the spread of radioactive material. We report unequivocal evidence that Pacific bluefin tuna, Thunnus orientalis, transported Fukushima-derived radionuclides across the entire North Pacific Ocean. We measured γ-emitting radionuclides in California-caught tunas and found 134Cs (4.0 ± 1.4 Bq kg−1) and elevated 137Cs (6.3 ± 1.5 Bq kg−1) in 15 Pacific bluefin tuna sampled in August 2011. We found no 134Cs and background concentrations (∼1 Bq kg−1) of 137Cs in pre-Fukushima bluefin and post-Fukushima yellowfin tunas, ruling out elevated radiocesium uptake before 2011 or in California waters post-Fukushima. These findings indicate that Pacific bluefin tuna can rapidly transport radionuclides from a point source in Japan to distant ecoregions and demonstrate the importance of migratory animals as transport vectors of radionuclides. Other large, highly migratory marine animals make extensive use of waters around Japan, and these animals may also be transport vectors of Fukushima-derived radionuclides to distant regions of the North and South Pacific Oceans. These results reveal tools to trace migration origin (using the presence of 134Cs) and potentially migration timing (using 134Cs:137Cs ratios) in highly migratory marine species in the Pacific Ocean.", "title": "Pacific bluefin tuna transport Fukushima-derived radionuclides from Japan to California" }, { "docid": "MED-4946", "text": "In order to assess early neurotoxic effects associated with relatively low levels of mercury absorbed through fish eating, two groups of 22 adult male subjects, habitual consumers of tuna fish, and 22 controls were examined using a cross-sectional field study. The assessment included neurobehavioral tests of vigilance and psychomotor function, hand tremor measurements and serum prolactin assessment. Mercury in urine (U-Hg) and serum prolactin (sPRL) were measured in all exposed subjects and controls, whereas measurements of the organic component of mercury in blood (O-Hg) were available for only 10 exposed and six controls. U-Hg was significant higher among exposed subjects (median 6.5 microg/g of creatinine, range 1.8-21.5) than controls (median 1.5 microg/g of creatinine, range 0.5-5.3). The median values of O-Hg were 41.5 microg/l among the tuna fish eaters and 2.6 microg/l in the control group. Both U-Hg and O-Hg were significantly correlated with the quantity of fish consumed per week. Significant differences in sPRL were found between exposed (12.6 ng/ml) and controls (9.1 ng/ml). Individual sPRL were significantly correlated with both U-Hg and O-Hg levels. The neurobehavioral performance of subjects who consumed tuna fish regularly was significantly worse on color word reaction time, digit symbol reaction time and finger tapping speed (FT). After considering the education level and other covariates, the multiple stepwise regression analysis indicated that O-Hg concentration was most significantly associated with individual performance on these tests, accounting for about 65% of the variance in test scores.", "title": "Sub-clinical neurobehavioral abnormalities associated with low level of mercury exposure through fish consumption." }, { "docid": "MED-1165", "text": "The cooking-induced changes in the levels of polybrominated diphenyl ethers (PBDEs), hexachlorobenzene (HCB), and 16 polycyclic aromatic hydrocarbons (PAHs) in various foodstuffs were investigated. Foods included fish (sardine, hake and tuna), meat (veal steak, loin of pork, breast and thigh of chicken, and steak and rib of lamb), string bean, potato, rice, and olive oil. For each food item, raw and cooked (fried, grilled, roasted, boiled) samples were analyzed. There were some variations in the concentrations of PBDEs before and after cooking. However, they depended not only on the cooking process, but mainly on the specific food item. The highest HCB concentrations were found in sardine, being lower in cooked samples. All cooking processes enhanced HCB levels in hake, while very scarce differences could be noted in tuna (raw and cooked). In general terms, the highest PAH concentrations were found after frying by being the values especially notable in fish, excepting hake, where the highest total PAH levels corresponded to roasted samples. The results of this study show that, in general, cooking processes are only of a limited value as a means of reducing PBDE, HCB and PAH concentrations in food.", "title": "Concentrations of polybrominated diphenyl ethers, hexachlorobenzene and polycyclic aromatic hydrocarbons in various foodstuffs before and after coo..." }, { "docid": "MED-3592", "text": "Levels of contaminants in fish are of particular interest because of the potential risk to humans who consume them. While attention has focused on self-caught fish, most of the fish eaten by the American public comes from commercial sources. We sampled 11 types of fish and shellfish obtained from supermarkets and specialty fish markets in New Jersey and analyzed them for arsenic, cadmium, chromium, lead, manganese, mercury, and selenium. We test the null hypothesis that metal levels do not vary among fish types, and we consider whether the levels of any metals could harm the fish themselves or their predators or pose a health risk for human consumers. There were significant interspecific differences for all metals, and no fish types had the highest levels of more than two metals. There were few significant correlations (Kendall tau) among metals for the three most numerous fish (yellowfin tuna, bluefish, and flounder), the correlations were generally low (below 0.40), and many correlations were negative. Only manganese and lead positively were correlated for tuna, bluefish, and flounder. The levels of most metals were below those known to cause adverse effects in the fish themselves. However, the levels of arsenic, lead, mercury, and selenium in some fish were in the range known to cause some sublethal effects in sensitive predatory birds and mammals and in some fish exceeded health-based standards. The greatest risk from different metals resided in different fish; the species of fish with the highest levels of a given metal sometimes exceeded the human health guidance or standards for that metal. Thus, the risk information given to the public (mainly about mercury) does not present a complete picture. The potential of harm from other metals suggests that people not only should eat smaller quantities of fish known to accumulate mercury but also should eat a diversity of fish to avoid consuming unhealthy quantities of other heavy metals. However, consumers should bear in mind that standards have a margin of safety.", "title": "Heavy metals in commercial fish in New Jersey." }, { "docid": "MED-4811", "text": "Many deep-sea fishes store large amounts of wax esters in their body for buoyancy control. Some of them are frequently caught as by-catch of tuna and other fishes. The most noteworthy ones include escolar and oilfish. The accumulation of the indigestible wax esters in the rectum through consumption of these fish engenders discharges or leakage per rectum as orange or brownish green oil, but without noticeable loss of water. This physiological response is called keriorrhea, which is variously described as \"oily diarrhea,\" \"oily orange diarrhea,\" or \"orange oily leakage\" by the mass media and bloggers on the internet. Outbreaks of keriorrhea have been repeatedly reported across continents. Additional symptoms including nausea, vomiting, abdominal cramps, and diarrhea were complained by the victims. They are probably due to anxiety or panic when suffering from keriorrhea. Escolar and oilfish are banned from import and sale in Italy, Japan, and South Korea. Rapid detection of the two fishes is imperative to ensure proper labeling and safeguarding of the public before and after any keriorrhea outbreak.", "title": "Fish-induced keriorrhea." }, { "docid": "MED-3618", "text": "BACKGROUND AND OVERVIEW: The National Council on Radiation Protection & Measurements updated its recommendations on radiation protection in dentistry in 2003, the Centers for Disease Control and Prevention published its Guidelines for Infection Control in Dental Health-Care Settings in 2003, and the U.S. Food and Drug Administration updated its selection criteria for dental radiographs in 2004. This report summarizes the recommendations presented in these documents and addresses additional topics such as patient selection criteria, film selection for conventional radiographs, collimation, beam filtration, patient protective equipment, film holders, operator protection, film exposure and processing, infection control, quality assurance, image viewing, direct digital radiography and continuing education of dental health care workers who expose radiographs. CONCLUSIONS: This report discusses implementation of proper radiographic practices. In addition to these guidelines, dentists should be aware of, and comply with, applicable federal and state regulations. CLINICAL IMPLICATIONS: Dentists should weigh the benefits of dental radiographs against the consequences of increasing a patient's exposure to radiation and implement appropriate radiation control procedures.", "title": "The use of dental radiographs: update and recommendations." }, { "docid": "MED-1193", "text": "Summary Background Statins reduce LDL cholesterol and prevent vascular events, but their net effects in people at low risk of vascular events remain uncertain. Methods This meta-analysis included individual participant data from 22 trials of statin versus control (n=134 537; mean LDL cholesterol difference 1·08 mmol/L; median follow-up 4·8 years) and five trials of more versus less statin (n=39 612; difference 0·51 mmol/L; 5·1 years). Major vascular events were major coronary events (ie, non-fatal myocardial infarction or coronary death), strokes, or coronary revascularisations. Participants were separated into five categories of baseline 5-year major vascular event risk on control therapy (no statin or low-intensity statin) (<5%, ≥5% to <10%, ≥10% to <20%, ≥20% to <30%, ≥30%); in each, the rate ratio (RR) per 1·0 mmol/L LDL cholesterol reduction was estimated. Findings Reduction of LDL cholesterol with a statin reduced the risk of major vascular events (RR 0·79, 95% CI 0·77–0·81, per 1·0 mmol/L reduction), largely irrespective of age, sex, baseline LDL cholesterol or previous vascular disease, and of vascular and all-cause mortality. The proportional reduction in major vascular events was at least as big in the two lowest risk categories as in the higher risk categories (RR per 1·0 mmol/L reduction from lowest to highest risk: 0·62 [99% CI 0·47–0·81], 0·69 [99% CI 0·60–0·79], 0·79 [99% CI 0·74–0·85], 0·81 [99% CI 0·77–0·86], and 0·79 [99% CI 0·74–0·84]; trend p=0·04), which reflected significant reductions in these two lowest risk categories in major coronary events (RR 0·57, 99% CI 0·36–0·89, p=0·0012, and 0·61, 99% CI 0·50–0·74, p<0·0001) and in coronary revascularisations (RR 0·52, 99% CI 0·35–0·75, and 0·63, 99% CI 0·51–0·79; both p<0·0001). For stroke, the reduction in risk in participants with 5-year risk of major vascular events lower than 10% (RR per 1·0 mmol/L LDL cholesterol reduction 0·76, 99% CI 0·61–0·95, p=0·0012) was also similar to that seen in higher risk categories (trend p=0·3). In participants without a history of vascular disease, statins reduced the risks of vascular (RR per 1·0 mmol/L LDL cholesterol reduction 0·85, 95% CI 0·77–0·95) and all-cause mortality (RR 0·91, 95% CI 0·85–0·97), and the proportional reductions were similar by baseline risk. There was no evidence that reduction of LDL cholesterol with a statin increased cancer incidence (RR per 1·0 mmol/L LDL cholesterol reduction 1·00, 95% CI 0·96–1·04), cancer mortality (RR 0·99, 95% CI 0·93–1·06), or other non-vascular mortality. Interpretation In individuals with 5-year risk of major vascular events lower than 10%, each 1 mmol/L reduction in LDL cholesterol produced an absolute reduction in major vascular events of about 11 per 1000 over 5 years. This benefit greatly exceeds any known hazards of statin therapy. Under present guidelines, such individuals would not typically be regarded as suitable for LDL-lowering statin therapy. The present report suggests, therefore, that these guidelines might need to be reconsidered. Funding British Heart Foundation; UK Medical Research Council; Cancer Research UK; European Community Biomed Programme; Australian National Health and Medical Research Council; National Heart Foundation, Australia.", "title": "The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials" }, { "docid": "MED-891", "text": "A method based on solid phase extraction followed by derivatization and gas chromatography-mass spectrometry analysis was validated for the determination of bisphenol A (BPA) in canned food products. This method was used to analyze 78 canned food products for BPA. Concentrations of BPA in canned food products differed considerably among food types, but all were below the specific migration limit of 0.6 mg/kg set by the European Commission Directive for BPA in food or food simulants. Canned tuna products had the highest BPA concentrations in general, with mean and maximum values of 137 and 534 ng/g, respectively. BPA concentrations in the condensed soup products were considerably higher than those in the ready-to-serve soup products, with mean and maximum values of 105 and 189 ng/g, respectively, for the condensed soups and 15 and 34 ng/g, respectively, for the ready-to-serve soups. BPA concentrations in canned vegetable products were relatively low; about 60% of the products had BPA concentrations of less than 10 ng/g. Canned tomato paste products had lower BPA concentrations than did canned pure tomato products. The mean and maximum BPA concentrations were 1.1 and 2.1 ng/g, respectively, for tomato paste products and 9.3 and 23 ng/g, respectively, for the pure tomato products.", "title": "Bisphenol a in canned food products from canadian markets." }, { "docid": "MED-1344", "text": "Is it ever right to prescribe placebos to patients in clinical practice? The General Medical Council is ambivalent about the issue; the American Medical Association asserts that placebos can be administered only if the patient is (somehow) 'informed'. The potential problem with placebos is that they may involve deception: indeed, if this is the case, an ethical tension arises over the patient's autonomy and the physician's requirement to be open and honest, and the notion that medical care should be the primary concern. This paper examines the case of depression as an entry point for understanding the complexities of the prescription of placebos. Recent important meta-analyses of antidepressants claim that they are not significantly more effective in a clinical setting than placebos. Given that antidepressants have numerous adverse side effects and are hugely expensive, this provocative research has serious potential ethical and practical implications for patients and medical providers. Should placebos be prescribed in place of antidepressants? The case of depression highlights another important issue which medical ethical codes have hitherto overlooked: well-being is not synonymous with being realistic about oneself, one's circumstances and the future. While severely depressed individuals are unduly pessimistic about themselves and the world around them, treatment of depressed individuals can be deemed successful when patients have successfully attained those positive illusions that are indicative of psychological health. This is exactly what successful psychological treatments of depression seem to achieve. It is therefore possible that there may be a limited unavoidable role for deception in medicine.", "title": "Deception as treatment: the case of depression." }, { "docid": "MED-5026", "text": "Background: Higher intakes of fruit, vegetables, and dark fish may prevent sudden cardiac death and arrhythmias, but the exact mechanisms are not fully understood. Objective: We examined whether high consumption of fruit, vegetables, and dark fish would be associated with beneficial changes in heart rate variability (HRV). Design: HRV variables were measured among 586 older men with 928 total observations from November 2000 to June 2007 in the Normative Aging Study, a community-based longitudinal study of aging. Dietary intake was evaluated with a self-administered semiquantitative food-frequency questionnaire and categorized into quartiles. Results: After controlling for potential confounders, intake of green leafy vegetables was positively associated with normalized high-frequency power and inversely associated with normalized low-frequency power (P for trend < 0.05). These significant associations were retained after further adjustment for healthy lifestyle factors, such as physical activity and use of multivitamins. No significant association was seen between HRV measures and intakes of other fruit and vegetables, vitamin C, carotenoids, tuna and dark-meat fish, or n–3 (omega-3) fatty acids. An effect modification of intake of noncitrus fruit by obesity and of total vegetables and cruciferous vegetables by cigarette smoking was seen, which warrants further investigation. Conclusion: These findings suggest that higher intake of green leafy vegetables may reduce the risk of cardiovascular disease through favorable changes in cardiac autonomic function.", "title": "Fruit, vegetable, and fish consumption and heart rate variability: the Veterans Administration Normative Aging Study" }, { "docid": "MED-5102", "text": "Due to the favourable health effects of LC n-3 PUFAs, marine products have been recognised as a food group of special importance in the human diet. However, seafood is susceptible to contamination by lipophilic organic pollutants. The objective of this study was to evaluate intake levels of PCDDs, PCDFs and dioxin-like PCBs, by a probabilistic Monte Carlo procedure, in relation to the recommendation on LC n-3 PUFAs given by Belgian Federal Health Council. Regarding the recommendation, two scenarios were developed differing in LC n-3 PUFAs intake: a 0.3 E% and a 0.46 E% scenario. Total exposure to dioxins and dioxin-like substances in the 0.3 E% LC n-3 PUFAs scenario ranges from 2.31 pg TEQ/kg bw/day at the 5th percentile, over 4.37 pg TEQ/kgbw/day at the 50th percentile to 8.41 pg TEQ/kgbw/day at the 95th percentile. In the 0.46 E% LC n-3 PUFAs scenario, 5, 50 and 95th percentile are exposed to 2.74, 5.52 and 9.98 pg TEQ/kgbw/day, respectively. Therefore, if the recommended LC n-3 PUFAs intake would be based on fish consumption as the only extra source, the majority of the study population would exceed the proposed health based guidance values for dioxins and dioxin-like substances.", "title": "Simulated impact of a fish based shift in the population n--3 fatty acids intake on exposure to dioxins and dioxin-like compounds." }, { "docid": "MED-4406", "text": "Objective To investigate longitudinal associations between community-level gasoline price and physical activity (PA). Method In the Coronary Artery Risk Development in Young Adults study, 5,115 black and white participants aged 18–30 at baseline 1985–86 were recruited from four U.S. cities (Birmingham, Chicago, Minneapolis and Oakland) and followed over time. We used data from 3 follow-up exams: 1992–93, 1995–96, and 2000–01, when the participants were located across 48 states. From questionnaire data, a total PA score was summarized in exercise units (EU) based on intensity and frequency of 13 PA categories. Using Geographic Information Systems, participants’ residential locations were linked to county-level inflation-adjusted gasoline price data collected by the Council for Community & Economic Research. We used a random-effect longitudinal regression model to examine associations between time-varying gasoline price and time-varying PA, controlling for age, race, gender, baseline study center, and time-varying education, marital status, household income, county cost of living, county bus fare, census block-group poverty, and urbanicity. Results Holding all control variables constant, a 25-cent increase in inflation-adjusted gasoline price was significantly associated with an increase of 9.9 EU in total PA (95%CI: 0.8–19.1). Conclusion Rising prices of gasoline may be associated with an unintended increase in leisure PA.", "title": "Longitudinal trends in gasoline price and physical activity: The CARDIA study" }, { "docid": "MED-1553", "text": "Although consumers say they are concerned about nutrition and are aware that eating a healthful diet is important for good health, this knowledge does not always translate into healthful diet behaviors or motivate behavior change. In an effort to better understand consumer attitudes about nutrition and to explore alternatives for communicating dietary advice in language that is meaningful and motivates behavior change, the International Food Information Council (IFIC) conducted qualitative research with consumers (using focus groups) and registered dietitians (using telephone interviews) in 1998 and 1999. Results of the research are presented using dietary fat as a case study. Findings from the IFIC research were reported to the Dietary Guidelines Advisory Committee to assist the Committee in developing meaningful and action-oriented dietary advice related to dietary fat for inclusion in the 2000 Dietary Guidelines for Americans that would be motivating and easy for consumers to implement. The recommendation to moderate fat intake in the new dietary guideline, \"Choose a diet that is low in saturated fat and cholesterol and moderate in total fat\" is consistent with communication recommendations in the IFIC research. Further, the moderate fat message is empowering because it suggests an achievable dietary regimen and reduces guilt and worry about foods. It allows flexibility to enjoy desired foods and promotes using common sense when it comes to diet. Several issues emerged from the IFIC research that apply to general nutrition communications with consumers, whether it be through national nutrition recommendations or in one-on-one counseling situations: to be effective, messages to consumers about nutrition, and specifically dietary fat, must address sources of discomfort about dietary choices; they must engender a sense of empowerment; and they should motivate both by providing clear information that propels toward taking action and appeals to the need to make personal choices.", "title": "Developing actionable dietary guidance messages: dietary fat as a case study." }, { "docid": "MED-5145", "text": "OBJECTIVE: To compare fracture rates in four diet groups (meat eaters, fish eaters, vegetarians and vegans) in the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Oxford). DESIGN: Prospective cohort study of self-reported fracture risk at follow-up. SETTING: The United Kingdom. SUBJECTS: A total of 7947 men and 26,749 women aged 20-89 years, including 19,249 meat eaters, 4901 fish eaters, 9420 vegetarians and 1126 vegans, recruited by postal methods and through general practice surgeries. METHODS: Cox regression. RESULTS: Over an average of 5.2 years of follow-up, 343 men and 1555 women reported one or more fractures. Compared with meat eaters, fracture incidence rate ratios in men and women combined adjusted for sex, age and non-dietary factors were 1.01 (95% CI 0.88-1.17) for fish eaters, 1.00 (0.89-1.13) for vegetarians and 1.30 (1.02-1.66) for vegans. After further adjustment for dietary energy and calcium intake the incidence rate ratio among vegans compared with meat eaters was 1.15 (0.89-1.49). Among subjects consuming at least 525 mg/day calcium the corresponding incidence rate ratios were 1.05 (0.90-1.21) for fish eaters, 1.02 (0.90-1.15) for vegetarians and 1.00 (0.69-1.44) for vegans. CONCLUSIONS: In this population, fracture risk was similar for meat eaters, fish eaters and vegetarians. The higher fracture risk in the vegans appeared to be a consequence of their considerably lower mean calcium intake. An adequate calcium intake is essential for bone health, irrespective of dietary preferences. SPONSORSHIP: The EPIC-Oxford study is supported by The Medical Research Council and Cancer Research UK.", "title": "Comparative fracture risk in vegetarians and nonvegetarians in EPIC-Oxford." }, { "docid": "MED-3034", "text": "In the 1970s several states in the Great Lakes region became concerned about mercury contamination in lakes and rivers and were the first to issue local fish consumption advisories. In 2001, the Food and Drug Administration (FDA) advised pregnant women, nursing mothers, young children, and women who may become pregnant not to consume shark, swordfish, king mackerel, and tilefish and recommended that these women not exceed 12 ounces of other fish per week. In 2004, FDA reissued this advice jointly with the U.S. Environmental Protection Agency (EPA) and modified it slightly to provide information about consumption of canned tuna and more details about consumption of recreationally caught fish. Though several studies have examined consumers' awareness of the joint FDA and EPA advisory as well as different state advisories, few used representative data. We examined the changes in awareness and knowledge of mercury as a problem in fish using the pooled nationally representative 2001 and 2006 Food Safety Surveys (FSS) with sample sizes of 4482 in 2001 and 2275 in 2006. Our results indicated an increase in consumers' awareness of mercury as a problem in fish (69% in 2001 to 80% in 2006, p<.001). In our regression models, we found that in both years, parents having children less than 5 years of age were more aware of mercury in fish and knowledgeable about the information contained in the national advisories about mercury in fish (p<.01) than other adults. In both 2001 and 2006, women of childbearing age (aged 18-45) were less aware and knowledgeable about this information than other women. However, women of all age groups had larger gains in awareness and knowledge than their male counterparts during this time. Participants' race, education, income, region, fish preparation experiences, having a foodborne illness in the past year, and risk perceptions about the safety of food were significant predictors of their awareness and knowledge. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Awareness and knowledge of methylmercury in fish in the United States." }, { "docid": "MED-2596", "text": "BACKGROUND Increased nut consumption has been associated with a reduced risk of major chronic diseases, including cardiovascular disease and type 2 diabetes mellitus. However, the association between nut consumption and mortality remains unclear. METHODS We examined the association between nut consumption and subsequent total and cause-specific mortality among 76,464 women in the Nurses’ Health Study (1980–2010) and 42,498 men in the Health Professionals Follow-up Study (1986–2010). Participants with a history of cancer, heart disease, or stroke were excluded. Nut consumption was assessed at baseline and updated every 2 to 4 years. RESULTS During 3,038,853 person-years of follow-up, 16,200 women and 11,229 men died. Nut consumption was inversely associated with total mortality among both women and men, after adjustment for other known or suspected risk factors. The pooled multivariate hazard ratios for death among participants who ate nuts, as compared with those who did not, were 0.93 (95% confidence interval [CI], 0.90 to 0.96) for the consumption of nuts less than once per week, 0.89 (95% CI, 0.86 to 0.93) for once per week, 0.87 (95% CI, 0.83 to 0.90) for two to four times per week, 0.85 (95% CI, 0.79 to 0.91) for five or six times per week, and 0.80 (95% CI, 0.73 to 0.86) for seven or more times per week (P<0.001 for trend). Significant inverse associations were also observed between nut consumption and deaths due to cancer, heart disease, and respiratory disease. CONCLUSIONS In two large, independent cohorts of nurses and other health professionals, the frequency of nut consumption was inversely associated with total and cause-specific mortality, independently of other predictors of death. (Funded by the National Institutes of Health and the International Tree Nut Council Nutrition Research and Education Foundation.)", "title": "Association of Nut Consumption with Total and Cause-Specific Mortality" }, { "docid": "MED-3627", "text": "BACKGROUND: The use of computed tomographic (CT) scans in the United States (US) has increased more than 3-fold since 1993 to approximately 70 million scans annually. Despite the great medical benefits, there is concern about the potential radiation-related cancer risk. We conducted detailed estimates of the future cancer risks from current CT scan use in the US according to age, sex, and scan type. METHODS: Risk models based on the National Research Council's \"Biological Effects of Ionizing Radiation\" report and organ-specific radiation doses derived from a national survey were used to estimate age-specific cancer risks for each scan type. These models were combined with age- and sex-specific scan frequencies for the US in 2007 obtained from survey and insurance claims data. We estimated the mean number of radiation-related incident cancers with 95% uncertainty limits (UL) using Monte Carlo simulations. RESULTS: Overall, we estimated that approximately 29 000 (95% UL, 15 000-45 000) future cancers could be related to CT scans performed in the US in 2007. The largest contributions were from scans of the abdomen and pelvis (n = 14 000) (95% UL, 6900-25 000), chest (n = 4100) (95% UL, 1900-8100), and head (n = 4000) (95% UL, 1100-8700), as well as from chest CT angiography (n = 2700) (95% UL, 1300-5000). One-third of the projected cancers were due to scans performed at the ages of 35 to 54 years compared with 15% due to scans performed at ages younger than 18 years, and 66% were in females. CONCLUSIONS: These detailed estimates highlight several areas of CT scan use that make large contributions to the total cancer risk, including several scan types and age groups with a high frequency of use or scans involving relatively high doses, in which risk-reduction efforts may be warranted.", "title": "Projected cancer risks from computed tomographic scans performed in the United States in 2007." }, { "docid": "MED-2211", "text": "BACKGROUND: China is increasingly facing the challenge of control of the growing burden of non-communicable diseases. We assessed the epidemiology of Alzheimer's disease and other forms of dementia in China between 1990, and 2010, to improve estimates of the burden of disease, analyse time trends, and inform health policy decisions relevant to China's rapidly ageing population. METHODS: In our systematic review we searched for reports of Alzheimer's disease or dementia in China, published in Chinese and English between 1990 and 2010. We searched China National Knowledge Infrastructure, Wanfang, and PubMed databases. Two investigators independently assessed case definitions of Alzheimer's disease and dementia: we excluded studies that did not use internationally accepted case definitions. We also excluded reviews and viewpoints, studies with no numerical estimates, and studies not done in mainland China. We used Poisson regression and UN demographic data to estimate the prevalence (in nine age groups), incidence, and standardised mortality ratio of dementia and its subtypes in China in 1990, 2000, and 2010. FINDINGS: Our search returned 12,642 reports, of which 89 met the inclusion criteria (75 assessed prevalence, 13 incidence, and nine mortality). In total, the included studies had 340,247 participants, in which 6357 cases of Alzheimer's disease were recorded. 254,367 people were assessed for other forms of dementia, of whom 3543 had vascular dementia, frontotemporal dementia, or Lewy body dementia. In 1990 the prevalence of all forms of dementia was 1·8% (95% CI 0·0-44·4) at 65-69 years, and 42·1% (0·0-88·9) at age 95-99 years. In 2010 prevalence was 2·6% (0·0-28·2) at age 65-69 years and 60·5% (39·7-81·3) at age 95-99 years. The number of people with dementia in China was 3·68 million (95% CI 2·22-5·14) in 1990, 5·62 million (4·42-6·82) in 2000, and 9·19 million (5·92-12·48) in 2010. In the same period, the number of people with Alzheimer's disease was 1·93 million (1·15-2·71) in 1990, 3·71 million (2·84-4·58) people in 2000, and 5·69 million (3·85-7·53) in 2010. The incidence of dementia was 9·87 cases per 1000 person-years, that of Alzheimer's disease was 6·25 cases per 1000 person-years, that of vascular dementia was 2·42 cases per 1000 person-years, and that of other rare forms of dementia was 0·46 cases per 1000 person-years. We retrieved mortality data for 1032 people with dementia and 20,157 healthy controls, who were followed up for 3-7 years. The median standardised mortality ratio was 1·94:1 (IQR 1·74-2·45). INTERPRETATION: Our analysis suggests that previous estimates of dementia burden, based on smaller datasets, might have underestimated the burden of dementia in China. The burden of dementia seems to be increasing faster than is generally assumed by the international health community. Rapid and effective government responses are needed to tackle dementia in low-income and middle-income countries. FUNDING: Nossal Institute of Global Health (University of Melbourne, Australia), the National 12th Five-Year Major Projects of China, National Health and Medical Research Council Australia-China Exchange Fellowship, Importation and Development of High-Calibre Talents Project of Beijing Municipal Institutions, and the Bill & Melinda Gates Foundation. Copyright © 2013 Elsevier Ltd. All rights reserved.", "title": "Epidemiology of Alzheimer's disease and other forms of dementia in China, 1990-2010: a systematic review and analysis." }, { "docid": "MED-1127", "text": "Rheumatoid arthritis is a crippling and disabling joint disease affecting over 20 million people. It occurs predominantly in women and smokers, and affects the HLA-DR1/4 individuals who carry the \"shared epitope\" of amino acids EQRRAA. The cause of this disease was investigated by the methods of the philosopher of science Karl Popper who suggested that scientific research should be based on bold conjectures and critical refutations. The \"Popper sequences\" generate new facts which then change or alter the original problem. The new facts must then be explained by any new theory. Using the \"molecular mimicry\" model, it was found that Proteus bacteria possess an amino acid sequence ESRRAL in haemolysin which resembles the, shared epitope, and another sequence in urease which resembles type XI collagen. Antibodies to Proteus bacteria have been found in 14 different countries. It would appear that rheumatoid arthritis is caused by an upper urinary tract infection by Proteus bacteria. Anti-Proteus therapy should be assessed in the management of this disease separately or in conjunction with existing modalities of therapy.", "title": "Rheumatoid arthritis is caused by Proteus: the molecular mimicry theory and Karl Popper." }, { "docid": "MED-3866", "text": "Background Obesity leads to an increase in inflammation and insulin resistance. This study determined antioxidant activity of flaxseed and its role in inflammation and insulin resistance in obese glucose intolerant people. Methods Using a randomized crossover design, nine obese glucose intolerant people consumed 40 g ground flaxseed or 40 g wheat bran daily for 12 weeks with a 4-week washout period. Plasma inflammation biomarkers (CRP, TNF-α, and IL-6), glucose, insulin, and thiobaribituric acid reactive substance (TBARS) were measured before and after of each supplementation. Results Flaxseed supplementation decreased TBARS (p = 0.0215) and HOMA-IR (p = 0.0382). Flaxseed or wheat bran supplementation did not change plasma inflammatory biomarkers. A positive relationship was found between TBARS and HOMA-IR (r = 0.62, p = 0.0003). Conclusions The results of the study weakly support that decreased insulin resistance might have been secondary to antioxidant activity of flaxseed. However, the mechanism(s) of decreased insulin resistance by flaxseed should be further determined using flaxseed lignan.", "title": "Flaxseed supplementation improved insulin resistance in obese glucose intolerant people: a randomized crossover design" }, { "docid": "MED-1496", "text": "Oxidative stress (OS) and damages due to excessive reactive oxygen species (ROS) are common causes of injuries to cells and organisms. The prevalence of neurodegenerative diseases (ND) increases with aging and much of the research involving ROS and OS has emerged from works in this field. This text reviews some recent published articles about the role of OS in ND. Since there are many reviews in this field, the focus was centered in articles published recently. The Scientific Journals Directory supported by the Brazilian Ministry of Education Office for the Coordination of Higher Educational Personnel Improvement (CAPES) was used to search, download, and review articles. The search engine looked for the terms 'oxidative stress AND neurodegenerative diseases AND nutrition' in 10 different scientific collections. Biochemical markers for ND lack sensitivity or specificity for diagnosis or for tracking response to therapy today. OS has an intimate connection with ND, albeit low levels of ROS seem to protect the brain. Deleterious changes in mitochondria, OS, calcium, glucocorticoids, inflammation, trace metals, insulin, cell cycle, protein aggregation, and hundreds to thousands of genes occur in ND. The interaction of genes with their environment, may explain ND. Although OS has received much attention over the years, which increased the number of scientific works on antioxidant interventions, no one knows how to stop or delay ND at present. Interventions in vitro, in vivo, and in humans will continue to contribute for a better understanding of these pathologies.", "title": "Brain rust: recent discoveries on the role of oxidative stress in neurodegenerative diseases." }, { "docid": "MED-1105", "text": "Multiple myeloma is a malignant plasma cell proliferative disorder that produces a monoclonal immunoglobulin protein. The skin involvement and the development of bullous disease are rarely seen features in multiple myeloma. We present a 55-year-old man with a longstanding, large, tense bullous eruption and hypertrophic scars over his body accompanied recently with weight loss and fatique. He had no response to the previous treatments, which included oral glucocorticoids and dapsone. Histologic examination of the lesions revealed subepidermal bullae, while no immunoflourescence staining was observed. In a further detailed labarotory examination, multiple myeloma was detected. After the treatment of multiple myeloma with chemotherapy, the lesions regressed. Patients with longstanding, recurrent, unusual bullous eruption should be investigated for the development of multiple myeloma.", "title": "A CASE OF MULTIPLE MYELOMA PRESENTING AS A BULLOUS DERMATOSIS" }, { "docid": "MED-1786", "text": "Fertility status may predict later mortality, but no studies have examined the effect of semen quality on subsequent mortality. Men referred to the Copenhagen Sperm Analysis Laboratory by general practitioners and urologists from 1963 to 2001 were, through a unique personal identification number, linked to the Danish central registers that hold information on all cases of cancer, causes of death, and number of children in the Danish population. The men were followed until December 31, 2001, death, or censoring, whichever occurred first, and the total mortality and cause-specific mortality of the cohort were compared with those of all age-standardized Danish men or according to semen characteristics. Among 43,277 men without azospermia referred for infertility problems, mortality decreased as the sperm concentration increased up to a threshold of 40 million/mL. As the percentages of motile and morphologically normal spermatozoa and semen volume increased, mortality decreased in a dose-response manner (P(trend) < 0.05). The decrease in mortality among men with good semen quality was due to a decrease in a wide range of diseases and was found among men both with and without children; therefore, the decrease in mortality could not be attributed solely to lifestyle and/or social factors. Semen quality may therefore be a fundamental biomarker of overall male health.", "title": "Good semen quality and life expectancy: a cohort study of 43,277 men." }, { "docid": "MED-1820", "text": "Background This study aims to comprehensively summarize the currently available evidences on the efficacy and safety of gemcitabine plus erlotinib for treating advanced pancreatic cancer. Methodology/Principal Findings PubMed, EMBASE, The Cochrane Library and abstracts of recent major conferences were systematically searched to identify relevant publications. Studies that were conducted in advanced pancreatic cancer patients treated with gemcitabine plus erlotinib (with or without comparison with gemcitabine alone) and reporting objective response rate, disease control rate, progression-free survival, time-to-progression, overall survival, 1-year survival rate and/or adverse events were included. Data on objective response rate, disease control rate, 1-year survival rate and adverse events rate, respectively, were combined mainly by using Meta-Analyst software with a random-effects model. Data on progression-free survival, time-to-progression and overall survival were summarized descriptively. Sixteen studies containing 1,308 advanced pancreatic cancer patients treated with gemcitabine plus erlotinib were included. The reported median progression-free survival (or time-to-progression), median overall survival, 1-year survival rates, objective response rates and disease control rates were 2–9.6 months, 5–12.5 months, 20%–51%, 0%–28.6% and 25.0%–83.3%, respectively. The weighted 1-year survival rate, objective response rate and disease control rate based on studies reporting robust results were 27.9%, 9.1% and 57.0%, respectively. According to the studies with relevant data, the incidences of total and severe adverse events were 96.3% and 62.9%, respectively. The most frequently reported adverse events were leucopenia, rash, diarrhea, vomitting, neutropenia, thrombocytopenia, anaemia, stomatitis, drug-induced liver injury, fatigue and fever. Compared with gemcitabine alone, the progression-free survival and overall survival with gemcitabine plus erlotinib were significantly longer, but there were also more deaths and interstitial lung disease-like syndrome related to this treatment. Conclusions/Significance Gemcitabine plus erlotinib represent a new option for the treatment of advanced pancreatic cancer, with mild but clinically meaningful additive efficacy compared with gemcitabine alone. Its safety profile is generally acceptable, although careful management is needed for some specific adverse events.", "title": "Gemcitabine Plus Erlotinib for Advanced Pancreatic Cancer: A Systematic Review with Meta-Analysis" }, { "docid": "MED-3209", "text": "The effects of grapefruit juice on the bioavailability of 17 alpha-ethinylestradiol (EE2) after a single oral administration of 50 micrograms EE2 have been investigated. The pharmacokinetics of EE2 were studied in an open, randomized, cross-over study in which 13 healthy volunteers were administered the drug with herbal tea or grapefruit juice (naringin, 887 mg/ml). In contrast to herbal tea, grapefruit juice increased the peak plasma concentration (Cmax) significantly to 137% (mean; range 64% to 214%, p = 0.0088) and increased the area under plasma concentration-time curve from 0 to 8 hours (AUC0-8) to 128% (mean; range 81% to 180%, p = 0.0186). This study shows that grapefruit juice increases the bioavailable amount of EE2. A possible explanation may be that grapefruit juice inhibits the metabolic degradation of EE2. Whether the increased bioavailability of EE2 following grapefruit juice administration is of clinical importance should be investigated in long-term studies.", "title": "Can grapefruit juice influence ethinylestradiol bioavailability?" }, { "docid": "MED-2754", "text": "BACKGROUND: Although previous randomized, double-blind, placebo-controlled trials reported the efficacy of omega-3 fatty acid supplements in the secondary prevention of cardiovascular disease (CVD), the evidence remains inconclusive. Using a meta-analysis, we investigated the efficacy of eicosapentaenoic acid and docosahexaenoic acid in the secondary prevention of CVD. METHODS: We searched PubMed, EMBASE, and the Cochrane Library in April 2011. Two of us independently reviewed and selected eligible randomized controlled trials. RESULTS: Of 1007 articles retrieved, 14 randomized, double-blind, placebo-controlled trials (involving 20 485 patients with a history of CVD) were included in the final analyses. Supplementation with omega-3 fatty acids did not reduce the risk of overall cardiovascular events (relative risk, 0.99; 95% CI, 0.89-1.09), all-cause mortality, sudden cardiac death, myocardial infarction, congestive heart failure, or transient ischemic attack and stroke. There was a small reduction in cardiovascular death (relative risk, 0.91; 95% CI, 0.84-0.99), which disappeared when we excluded a study with major methodological problems. Furthermore, no significant preventive effect was observed in subgroup analyses by the following: country location, inland or coastal geographic area, history of CVD, concomitant medication use, type of placebo material in the trial, methodological quality of the trial, duration of treatment, dosage of eicosapentaenoic acid or docosahexaenoic acid, or use of fish oil supplementation only as treatment. CONCLUSION: Our meta-analysis showed insufficient evidence of a secondary preventive effect of omega-3 fatty acid supplements against overall cardiovascular events among patients with a history of cardiovascular disease.", "title": "Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: ..." }, { "docid": "MED-5259", "text": "Objective To evaluate the association between coffee consumption and mortality from all causes and cardiovascular disease (CVD). Patients and Methods Data from the Aerobics Center Longitudinal Study (ACLS) representing a total of 43,727 participants contributing to 699,632 person-years of follow-up time, were included. Baseline data were collected by an in-person interview based on standardized questionnaires and a medical examination, including fasting blood chemistry analysis, anthropometry, blood pressure, electrocardiography, and a maximal graded exercise test, between February 3, 1971 and December 30, 2002. Cox regression analysis was used to quantify the association between coffee consumption and all-cause and cause-specific mortality. Results During the 17-year median follow-up period, 2512 deaths occurred (32% due to CVD). In multivariate analyses, coffee intake was positively associated with all-cause mortality in men. Men who drank >28 cups coffee per week had higher all-cause mortality (hazard ratio (HR): 1.21; 95% confidence interval (CI): 1.04–1.40). However, after stratification based on age, both younger (<55 years) men and women showed a statistically significant association between high coffee consumption (>28 cups/week) and all-cause mortality, after adjusting for potential confounders and fitness level (HR: 1.56; 95% CI: 1.30–1.87 for men and HR: 2.13; 95% CI: 1.26–3.59 for women, respectively). Conclusion In this large cohort, a positive association between coffee consumption and all-cause mortality was observed among men and both men and women <55 years of age. Based on our findings, it seems appropriate to suggest that younger people avoid heavy coffee consumption (ie, averaging >4 cups/day). However, this finding should be assessed in future studies from other populations.", "title": "Association of coffee consumption with all-cause and cardiovascular disease mortality" }, { "docid": "MED-3317", "text": "Twenty-four patients, all of whom were exposed to aerosolized porcine brain tissue through work-place environment (abattoir), developed a syndrome of immune-mediated polyradiculoneuropathy; three also had central nervous system manifestations (transverse myelitis, meningoencephalitis, and aseptic meningitis). Patients had characteristic electrophysiological findings of very distal and proximal conduction slowing (prolonged distal and F-wave latencies, regions where the blood-nerve barrier is the most permeable) and all patients' serum contained a novel IgG immunofluorescence pattern. Nerve pathology, when available, showed mild changes of segmental demyelination, axonal degeneration, and inflammatory changes. Patients had meaningful improvement of symptoms and electrophysiologic findings with immune therapy and with removal of exposure to aerosolized brain tissue. We postulate that this outbreak is an auto-immune polyradiculoneuropathy triggered by occupational exposure to multiple aerosolized porcine neural tissue antigens that result in neural damage where the blood-nerve barrier is the least robust. © 2011 Peripheral Nerve Society.", "title": "Auto-immune polyradiculoneuropathy and a novel IgG biomarker in workers exposed to aerosolized porcine brain." }, { "docid": "MED-2209", "text": "This study investigated the effect of different traditional cooking methods on glycemic index (GI) and glycemic response of ten Sweet potato (Ipomoea batatas) cultivars commonly eaten in Jamaica. Matured tubers were cooked by roasting, baking, frying, or boiling then immediately consumed by the ten nondiabetic test subjects (5 males and 5 females; mean age of 27 ± 2 years). The GI varied between 41 ± 5–93 ± 5 for the tubers studied. Samples prepared by boiling had the lowest GI (41 ± 5–50 ± 3), while those processed by baking (82 ± 3–94 ± 3) and roasting (79 ± 4–93 ± 2) had the highest GI values. The study indicates that the glycemic index of Jamaican sweet potatoes varies significantly with the method of preparation and to a lesser extent on intravarietal differences. Consumption of boiled sweet potatoes could minimize postprandial blood glucose spikes and therefore, may prove to be more efficacious in the management of type 2 diabetes mellitus.", "title": "Relationship between Processing Method and the Glycemic Indices of Ten Sweet Potato (Ipomoea batatas) Cultivars Commonly Consumed in Jamaica" } ]
145140
Eagles is a band.
[ { "docid": "Eagles_(band)", "text": "The Eagles are an American rock band formed in Los Angeles in 1971 by Glenn Frey , Don Henley , Bernie Leadon , and Randy Meisner . With five number-one singles , six Grammy Awards , five American Music Awards , and six number one albums , the Eagles were one of the most successful musical acts of the 1970s . At the end of the 20th century , two of their albums , Their Greatest Hits ( 1971 -- 1975 ) and Hotel California , were ranked among the 20 best-selling albums in the United States according to the Recording Industry Association of America . Hotel California is ranked 37th in Rolling Stones list of `` The 500 Greatest Albums of All Time '' and the band was ranked number 75 on the magazine 's 2004 list of the 100 Greatest Artists of All Time . The Eagles are one of the world 's best-selling bands of all time , having sold more than 150 million records -- 100 million in the U.S. alone -- including 42 million copies of Their Greatest Hits ( 1971 -- 1975 ) and 32 million copies of Hotel California . Their Greatest Hits ( 1971 -- 1975 ) was the best selling album of the 20th century in the U.S. . They are the fifth-highest-selling music act and the highest-selling American band in U.S. history . The band released their debut album , Eagles , in 1972 , which spawned three top 40 singles : `` Take It Easy , '' `` Witchy Woman , '' and `` Peaceful Easy Feeling . '' Their next album , Desperado ( 1973 ) , was less successful than the first , only reaching number 41 on the charts ; neither of its singles reached the top 40 . However , the album does contain what would go on to be two of the band 's most popular tracks : `` Desperado '' and `` Tequila Sunrise . '' The band released On the Border in 1974 , adding guitarist Don Felder as the fifth member midway through the recording of the album . The album generated two top 40 singles : `` Already Gone '' and their first number one , `` Best of My Love . '' Their 1975 album One of These Nights included three top 10 singles : `` One of These Nights , '' `` Lyin ' Eyes , '' and `` Take It to the Limit , '' the first hitting the top of the charts . Guitarist and vocalist , Joe Walsh , also joined the band in 1975 . The Eagles continued that success and hit their commercial peak in late 1976 with the release of Hotel California , which would go on to sell more than 16 million copies in the U.S. alone and more than 32 million copies worldwide . The album yielded two number-one singles , `` New Kid in Town '' and `` Hotel California . '' They released their last studio album for nearly 28 years in 1979 with The Long Run , which spawned three top 10 singles : `` Heartache Tonight , '' `` The Long Run , '' and `` I Ca n't Tell You Why , '' the lead single being another chart-topping hit . The Eagles disbanded in July 1980 but reunited in 1994 for the album Hell Freezes Over , a mix of live and new studio tracks . They toured consistently and were inducted into the Rock and Roll Hall of Fame in 1998 . In 2007 , the Eagles released Long Road Out of Eden , their first full studio album in 28 years and their sixth number one album . The next year they launched the Long Road Out of Eden Tour in support of the album . In 2013 , they began the extended History of the Eagles Tour in conjunction with the band 's documentary release , History of the Eagles . Following the death of Frey in January 2016 , Henley stated in several interviews that he did n't think the band would perform again . However , in March 2017 it was announced that the Eagles would be headlining two concerts in July 2017 .", "title": "" } ]
[ { "docid": "Fly_Like_an_Eagle", "text": "Fly Like an Eagle may refer to : Fly Like an Eagle ( album ) , 1976 , by Steve Miller Band `` Fly Like an Eagle '' ( song ) , by Steve Miller Band `` Fly Like an Eagle '' , a song from The Marshall Tucker Band 's 1977 album , Carolina Dreams `` Fly Like an Eagle '' , a song from Ten 's 1997 album The Robe `` Fly Like an Eagle '' , a song from Respect ( Shaquille O'Neal album ) , 1998 `` Fly Like an Eagle '' , a 1994 episode of Takin ' Over the Asylum `` Fly Like an Eagle '' , a 2015 episode of Lost in Transmission", "title": "" }, { "docid": "The_Eagle_Band", "text": "The Eagle Band was an American jazz band during the Ragtime and Early Jazz periods , ( 1895-1929 ) stationed in New Orleans , Louisiana . The instrumentation of the band was clarinet , drums , trombone , trumpet , guitar , and string bass , with one person on an instrument . The band was originally known as The Buddy Bolden Band , under the direction of Buddy Bolden from 1895-1906 . On September 3 , 1906 , while playing in the Labor Day parade with his band , Buddy Bolden suffered a memorable breakdown , which included staggering out of marching formation and screaming . He was removed from the parade ranks and would permanently resign from the band . After the resignation of Bolden , Frankie Dusen would be the one to lead the band , and change the name from The Buddy Bolden Band , to the Eagle Band , named after the Eagle Saloon on the corner of Perdido and Rampart Streets . The band maintained the popularity it had as The Buddy Bolden Band and primarily performed the same repertoire as before . Similar to the Hard Bop combo , Art Blakey and The Jazz Messengers , which would emerge in decades to come , The Eagle Band would serve as a stepping-stone for many prominent Hot Jazz players during the Early Jazz period . The Eagle Band was known as a very authentic , poignant band known for its ability to play slow gut-wrenching blues . Members of the Band", "title": "" }, { "docid": "Screaming_eagle", "text": "Screaming eagle may refer to : Screaming eagle ( wave ) , a tropical wave that resembles the head of an eagle Screaming Eagle Winery and Vineyards , a California boutique winery with limited production Screamin ' Eagle , a wooden roller coaster at Six Flags St. Louis `` Screamin ' Eagle '' , an instrumental by The Desert Sessions on the 1998 album Volume 2 : Status : Ships Commander Butchered The Boston College `` Screaming Eagles '' Marching Band , an alternative name for the Boston College Marching Band", "title": "" }, { "docid": "Southern_banded_snake_eagle", "text": "The southern banded snake eagle , also known as the East African snake eagle or fasciated snake eagle ( Circaetus fasciolatus ) is a species of snake eagle in the family Accipitridae which is found in eastern Sub-Saharan Africa .", "title": "" }, { "docid": "Spreadeagle", "text": "The term spreadeagle ( also spread eagle , spread-eagle ) can mean : Spreadeagle ( heraldry ) , a figure derived from a heraldic depiction of an eagle Spread Eagle ( horse ) , an 18th-century Thoroughbred racehorse and winner of the 1795 Epsom Derby Spreadeagle ( position ) , a position in which a person is figuratively in the same position as an eagle with its wings spread and legs well apart Spread eagle ( figure skating ) Blood eagle or `` spread-eagle '' , an alleged Viking method of execution Spread Eagle , Wisconsin Spread-eagleism , the 19th century precursor to the term `` Jingoism '' Spread Eagle ( band ) , an American hard rock band Spread Eagle ( album ) , a Peter Pan Speedrock album The Spread Eagle is the corporate logo of Barclays Bank , a UK bank , and the name of their staff magazine Spread Eagle , Wandsworth , a pub in London One of the most difficult split leaves in candlepin bowling , the 2-3-4-6-7-10 split", "title": "" }, { "docid": "New_Black_Eagle_Jazz_Band", "text": "The New Black Eagle Jazz Band is a New Orleans Style Jazz band founded in 1971 and based in New England . Four of the members had previously been in the Black Eagle Jazz Band led by Tommy Sancton . The band has seven core members . Music performed by the band has been used as soundtrack music in the Ken Burns documentaries Jazz and Baseball . The band has also been a guest on A Prairie Home Companion and NPR . They have released over 40 recordings .", "title": "" }, { "docid": "Blue_Mountain_Eagle", "text": "Blue Mountain Eagle may refer to : Blue Mountain Eagle ( band ) , an American rock band of the late 1960s-early 1970s Blue Mountain Eagle ( newspaper ) , a newspaper published in John Day , Oregon , United States", "title": "" }, { "docid": "Spread_Eagle_(band)", "text": "Spread Eagle is an American hard rock band from New York City . After only a few months of formation they were signed by MCA/Universal Records . They released two albums Spread Eagle ( 1990 ) and Open To The Public ( 1993 ) , then disbanded in 1995 . In 2006 the band reunited . In January 2011 the band officially announced their new line-up and according to bassist and founding member Rob De Luca there are plans for touring in North America and Europe .", "title": "" }, { "docid": "Eagles_(box_set)", "text": "Eagles is a compilation box set by the American rock band the Eagles . The box set includes material from the band 's time under the Elektra and Asylum labels between 1972 and 1980 .", "title": "" }, { "docid": "Allen_Eagle_Escadrille", "text": "The Allen Eagle Escadrille is the Allen High School high school marching band from Allen , Texas . The Escadrille , which consists of the Band , the Color Guard , and the Tallenettes ( drill team ) , claims to be the biggest marching band in the country , with over 800 members as of the 2015 marching season . The Allen Eagle Escadrille has marched overseas in 1994 , performed a halftime show at the Dallas Cowboys vs. St. Louis Rams game in 2013 at AT&T Stadium , and participated in large parades including the Macy 's Thanksgiving Day and the Tournament of Roses Parade . The Allen Eagle Escadrille began including grades 9th through 12th march during the 1999 marching season . During the 2011 and the 2012 marching seasons only 10th through 12th grades took the field for the UIL show , but in the 2013 season , the band reverted to having all four grade levels march .", "title": "" }, { "docid": "Boston_College_Marching_Band", "text": "The Boston College Marching Band ( BCMB ) , also known as the Boston College `` Screaming Eagles '' Marching Band , is the marching band for the Boston College Eagles . Founded in 1919 , The Band is the largest and most visible student organization at Boston College , and represents the school at home football games , most bowl games , international events , and parades .", "title": "" }, { "docid": "Take_It_Easy", "text": "`` Take It Easy '' is a song written by Jackson Browne and Glenn Frey , and recorded by the Eagles with Frey singing lead vocals . It was the band 's first single , released on May 1 , 1972 . It peaked at No. 12 on the July 22 , 1972 Billboard Hot 100 chart . It also was the opening track on the band 's debut album Eagles and it has become one of their signature songs , included on all of their live and compilation albums . It is listed as one of The Rock and Roll Hall of Fame 's 500 Songs that Shaped Rock and Roll . Jackson Browne later recorded the song as the lead track on his second album , For Everyman ( 1973 ) , and released it as a single as well , although it did not chart . Travis Tritt also covered the song for the 1993 Eagles ' tribute album Common Thread : The Songs of the Eagles ; the video for Tritt 's version is notable for the appearance of all five members of the Eagles together the first time in 13 years after their break-up , and it led to the reunion of the band a few months later .", "title": "" }, { "docid": "Eagles_Live", "text": "Eagles Live is the first live album by the American rock band Eagles , a two-LP set released on November 7 , 1980 . The Eagles effectively disbanded on July 31 , 1980 , after a concert in Long Beach , California that served as a fund-raiser for then-Senator Alan Cranston 's campaign , and where bandmates Glenn Frey and Don Felder nearly came to blows backstage . However , the band owed Elektra/Asylum Records one more album and fulfilled that obligation with a release of performances from the Hotel California and The Long Run tours . The Eagles rejected a $ 2 million offer from the label to record two new songs for the album . Eagles Live was mixed by Frey and Don Henley on opposite coasts in Los Angeles and Miami , respectively , and as producer Bill Szymczyk put it , the record 's harmony and instrument fixes were made `` courtesy of Federal Express . '' The 1983 Rolling Stone Record Guide said it is `` perhaps the most heavily overdubbed -LSB- live album -RSB- in history . '' `` Seven Bridges Road , '' a Steve Young cover , was released as a single and became a top-40 hit . The song was a showcase for the band 's close harmony singing , as the first and last verses feature vocals from all five members .", "title": "" }, { "docid": "Eagle's_Landing_High_School", "text": "Eagle 's Landing High School is a high school located in McDonough , Georgia , United States . It is operated by the Henry County School System . Eagle 's Landing was founded in 1990 . Today , the school has 1,200 students enrolled in grades 9-12 and is accredited by the Southern Association of Colleges and Schools . The school is home to an active NJROTC program , a nationally acclaimed band , and varsity sports teams that compete in the AAAA , region 4 of the Georgia High School Association . 2013 achievements : Eagle 's Landing High School received the award for Region 4-AAAA One Act Champions . Eagle 's Landing Marching Band won the Silver Grand Champion Award . Eagle 's Landing High School was ranked among `` Best High Schools '' by U.S. News and World Report . Eagle 's Landing High School was named `` One of the Most Challenging Schools '' . Barbara Rosolino was named one of ten finalists for State Teacher of the Year . Boys ' basketball were AAAA 2013 State Champions .", "title": "" }, { "docid": "Eagles_of_Death_Metal", "text": "Eagles of Death Metal is an American rock band from Palm Desert , California , formed in 1998 . Founded by Jesse Hughes ( vocals , guitar ) and Josh Homme ( drums ) , the band also includes a wide range of other musicians that perform both on the band 's studio albums and at live shows . Hughes and Homme are the only permanent members of the band , with Homme rarely performing at live shows due to commitments to his other bands . The band 's current touring line-up includes Hughes alongside Dave Catching ( guitar ) , Eden Galindo ( guitar ) , Jennie Vee ( bass ) and Jorma Vik ( drums ) . Despite their name , Eagles of Death Metal are not a death metal band , and the name is intended to be humorous . In a 2003 interview , Homme described the sound of the band as a combination of `` bluegrass slide guitar mixed with stripper drum beats and Canned Heat vocals . '' Hughes is known for his enthusiastic interaction with audiences at live performances . While the band were on stage at the Bataclan in Paris , France , on November 13 , 2015 , the audience was attacked by terrorists wielding automatic rifles , grenades and suicide vests . The death toll inside the venue was 89 , including the group 's merchandise manager , but the band members escaped safely out of the venue via a door backstage .", "title": "" }, { "docid": "Fish_eagle", "text": "Fish eagle is an animal common name . It may refer to any of several species of bird , including : Steller 's sea eagle , haliaeetus pelagicus , found along the coasts of north-eastern Asia African fish eagle , Haliaeetus vocifer , at large bodies of water throughout Africa except far southwest Madagascar fish eagle , Haliaeetus vociferoides , native to Madagascar Sanford 's fish eagle , Haliaeetus sanfordi , of the Solomon Islands Three that are often confused , of South Asia : Grey-headed fish eagle , Ichthyophaga ichthyaetus Lesser fish eagle , Ichthyophaga humilis , in Indian subcontinent , mostly in Himalayan foothills Pallas 's fish eagle or band-tailed fish eagle , Haliaeetus leucoryphus", "title": "" }, { "docid": "One_of_These_Nights", "text": "One of These Nights is the fourth studio album by the Eagles , released in 1975 . The record would become the Eagles ' first number one album on Billboard '' 's album chart in July that year , and yielded three Top 10 singles , `` One of These Nights '' , `` Lyin ' Eyes '' and `` Take It to the Limit '' . Its title song is the group 's second number one single on the Billboard Hot 100 . The album sold four million copies and was nominated for Grammy Album of the Year . A single from the album , `` Lyin ' Eyes '' , was also nominated for Record of the Year , and won the Eagles ' first Grammy for Best Pop Performance by a Duo or Group with Vocals.One of These Nights is the last Eagles album to feature guitarist Bernie Leadon , who was later replaced by Joe Walsh . Leadon left the band after the One Of These Nights '' tour . The seventh track , `` Visions '' , is the only Eagles song on which lead guitarist Don Felder sang the lead vocals , despite his desire to write and sing more songs . The album was the band 's commercial breakthrough , transforming them into international superstars and establishing them as America 's number one band . They went on a worldwide tour to promote the album .", "title": "" }, { "docid": "History_of_the_Eagles_–_Live_in_Concert", "text": "The History of the Eagles -- Live in Concert was the final concert tour by the American rock band the Eagles . It was launched in conjunction with the release of the 2013 documentary History of the Eagles . The tour visited North America and Europe between 2013 and 2014 as well as Oceania in early 2015 . It began in Louisville , Kentucky at the KFC Yum ! Center and concluded on July 29 , 2015 in Bossier City , Louisiana . The tour included Bernie Leadon , who was in the original line-up of the band , and would have also included Randy Meisner , but he was too ill to perform at the time . Don Felder was , however , excluded because of ongoing lawsuits against the group , despite settling them in 2007 . It was the last tour to involve Glenn Frey before his death in 2016 .", "title": "" }, { "docid": "Eagle_Rock", "text": "Eagle Rock can refer to one of the following : Places in the United States Eagle Rock , North Carolina , an unincorporated community in Wake County , North Carolina , west of Zebulon Eagle Rock , Virginia , a town in northern Botetourt County Eagle Rock ( Idaho ) , an early name for Idaho Falls , Idaho Eagle Rock , Los Angeles , a neighborhood Eagle Rock , Missouri Eagle Rock ( Santa Monica Mountains ) , a pinnacle in the Santa Monica Mountains , California Eagle Rock Reservation , New Jersey , on First Mountain in the Watchung Range Eagle Rock ( Pennsylvania ) , a ski and golf resort in Hazleton , Pennsylvania Eagle Rock ( West Virginia ) , a pinnacle in Smoke Hole Canyon , West Virginia Eagle Rock ( Pistol River , Oregon ) , listed on the NRHP in Oregon Eagle Rock ( Maryland ) , a pinnacle and abandoned sandstone quarry in Garrett County , Maryland Eagle Rock in Hill County , Montana Eagle Rock in Mineral County , Montana Places in Australia Eagle Rock Marine Sanctuary Music `` Eagle Rock '' ( song ) , a # 1 hit single in 1971 for Australian band Daddy Cool Eagle Rock , a track on The One to Sing the Blues by Motörhead Eagle Rock Entertainment , a record label Eagle Rock Records , a record label Aviation Alexander Eaglerock , a 1920s and 1930s American biplane", "title": "" }, { "docid": "Big_Eagle", "text": "Big Eagle ( Dakota : Waŋbdí Tháŋka , c. 1827 -- 1906 ) was the leader of a band of Mdewakanton Dakota Sioux in Minnesota . In 1862 he and his band joined Taoyateduta and took part in a Sioux uprising . He eventually surrendered .", "title": "" }, { "docid": "Pallas's_fish_eagle", "text": "Pallas 's fish eagle ( Haliaeetus leucoryphus ) , also known as Pallas 's sea eagle or band-tailed fish eagle , is a large , brownish sea-eagle . It breeds in Central Asia , between the Caspian Sea and the Yellow Sea , from Kazakhstan and Mongolia to the Himalayas , Bangladesh and northern India . It is partially migratory , with central Asian birds wintering among the southern Asian birds in northern India , and also further west to the Persian Gulf .", "title": "" }, { "docid": "Eagle_Seagull", "text": "Eagle Seagull ( sometimes stylized as Eagle * Seagull ) was an American indie rock band from Lincoln , Nebraska , United States that singer/songwriter Eli Mardock formed in 2004 .", "title": "" }, { "docid": "With_the_Wild_Crowd!_Live_in_Athens,_GA", "text": "With the Wild Crowd ! Live in Athens , GA is the first official live album and DVD release by American new wave band The B-52s . The concert was recorded on February 18 , 2011 at The Classic Center in the band 's hometown of Athens , Georgia , commemorating the 34th anniversary of their first performance as a group on February 14 , 1977 . The audio recording was released on October 10 , 2011 on CD and iTunes by Eagle Records , while a DVD and Blu-ray release followed on March 20 , 2012 by Eagle Records ' parent company , Eagle Rock Entertainment .", "title": "" }, { "docid": "Ichthyophaga", "text": "Ichthyophaga is a genus of two species of eagles , closely related to the sea eagles in the genus Haliaeetus . In fact , some taxonomic authorities place this genus within Haliaeetus . Both are native to southeastern Asia , from the Indian subcontinent southeast to Sulawesi . They are smaller than the Haliaeetus eagles , though overlapping in size with the smaller species of that genus . They share similar plumage , with grey heads grading into dull grey-brown wings and bodies , and white belly and legs . They differ in tail colour , with the lesser fish eagle having a brown tail , and the grey-headed fish eagle having a white tail with a black terminal band , and also in size , with the lesser fish eagle only about half of the weight of the grey-headed fish eagle .", "title": "" }, { "docid": "The_Eagle_Has_Landed_–_Part_II", "text": "The Eagle Has Landed -- Part II is a double live album by the band Saxon . It is the fourth live album by the band and the first recording to feature Doug Scarratt instead of Graham Oliver , who had left just after the release of Dogs of War .", "title": "" }, { "docid": "Desperado_(Eagles_album)", "text": "Desperado is the second studio album by the American band the Eagles . It was recorded at Island Studios in London , England and released in 1973 . The songs on Desperado are based on the themes of the Old West . The band members are featured on the album 's cover dressed like an outlaw gang ; Desperado remains the only Eagles album where the band members appear on the front cover . Although the title track is one of the Eagles ' signature songs , it was never released as a single . The song `` Desperado '' was ranked number 494 on Rolling Stone 2004 list of `` The 500 Greatest Songs of All Time '' . The album did yield two singles , though : `` Tequila Sunrise '' and `` Outlaw Man '' . Those two singles reached number 64 and number 59 respectively . The album reached number 41 on the Billboard album chart and was certified gold by the RIAA on September 23 , 1974 , and double platinum on March 20 , 2001 . Desperado was the last Asylum Records album to be distributed in North America by Atlantic Records ( catalog no . SD 5068 ) , prior to Asylum 's mid-1973 merger with Elektra Records by Asylum 's , Elektra 's and Atlantic 's parent company , Warner Communications .", "title": "" }, { "docid": "Common_Thread:_The_Songs_of_the_Eagles", "text": "Common Thread : The Songs of the Eagles is a tribute album to American rock band the Eagles . It was released in 1993 ( see 1993 in country music ) on Giant Records to raise funds for the Walden Woods Project . The album features covers of various Eagles songs , as performed by country music acts . It was certified 3 × Platinum in the United States by the RIAA on June 27 , 1994 . The video for the cover of `` Take It Easy '' by Travis Tritt featured the former members of the Eagles , the first time that the group had appeared together in 13 years . Two months after recording the video , Glenn Frey and Don Henley decided on the formal reunion of the Eagles .", "title": "" }, { "docid": "Chris_Mostert", "text": "Christiaan `` Chris '' Mostert is a Dutch saxophonist who has played with the Eagles during their `` Farewell 1 Tour '' in 2005 . He is part of the horns the Mighty Horns . Besides his work with the Eagles , Mostert has also played on solo tours of Don Henley , Joe Walsh and Glenn Frey , and been he also been a member of the bands , Goose Creek Symphony , Pollution , Sylvester and the Hot Band . He also performed on three solo albums by Glenn Frey , Soul Searchin ' , Strange Weather and After Hours . He also worked on the last studio album by the Eagles `` Long Road Out of Eden '' .", "title": "" }, { "docid": "Scopophobia_(DVD)", "text": "__ NOTOC __ `` Scopophobia '' is a DVD release by Therapy ? on Eagle Vision , a subsidiary of Eagle Rock Entertainment on 27 October 2003 . The bulk of the DVD is a full length 19 track concert recorded live at the Mandela Hall , Belfast on 6 June 2003 . Bonus features include 11 promo video clips , a quick Q&A session with the four band members , and a 30 minute hidden feature following the band on their European tour in May/June 2003 in support of their High Anxiety album . In 2004 , Eagle Vision released a 2-disk limited edition version of the DVD featuring an audio cd of the concert .", "title": "" }, { "docid": "The_Rave_/_Eagles_Club", "text": "The Rave/Eagles Club ( formerly known as the Milwaukee Eagles Club and Central Park Athletic Club and Entertainment Center ) is a concert venue and landmark in Milwaukee , Wisconsin . The Rave hosts touring bands from around the globe .", "title": "" } ]
1852
Can I cash a cashier's check at any bank?
[ { "docid": "297013", "text": "Cashiers check is as good as cash. I use them all the time as banks don't carry over 2-3k anymore. I can bring the cashiers check anywhere and thus cash it for u without an account. It's basically a piece of paper that says these funds are set aside from the issuers account just for and only for the check. That's why it's accepted anywhere. It's a gurantee from one bank to another that the funds are there waiting to be transferred. The whole point of the check is so the funds are available immediately. The bank will call the issuing bank verify the Check is real and than cash it immediately. You don't pay a fee to buy the cashiers check just to wait for it to clear like a normal free check. Its immediate and just as good as cash. I use them weekly/monthly for amounts from 5k up to over 100k.", "title": "" }, { "docid": "93451", "text": "Normally if the amount of a cashiers check is over $5,000, a bank (like Wells Fargo) may put a 10 business day hold on it to make sure the transaction is sound.", "title": "" }, { "docid": "78623", "text": "\"At least in the US, a Cashier's Check is just like a regular personal check - only it's guaranteed by the bank itself, so the person accepting it can be pretty certain the check won't be returned for insufficient funds...if the check is genuine! Most banks therefore have a policy for cashier's checks that is very similar to their policies on regular checks and money orders: if you are a member with an account in good standing, they'll make all or part of the money available to you according to their fund availability policy, which is usually anywhere from \"\"immediately\"\" to 7-10 days. With amounts over $5,000, banks will tend to put a hold on the funds to ensure it clears and they get their money. If you are not a member then many banks will refuse to cash the check at all, unless the cashier's check is drawn on on that brand of bank. So if the cashier's check is issued by, say, Chase Bank, Chase banks will usually be willing to cash out the entire check to you immediately (with properly provided ID). Because the bank is guaranteed by them they are able to check their system and ensure the check is real and can clear the check instantly. This policy isn't just up to individual banks entirely, as it is defined by United States federal banking policies and federal regulations on availability of funds. If you really must cash the check without a holding period and won't/can't have a bank account of your own to perform this, then you will generally need to go into a branch of the bank that is guaranteeing the check to be able to cash it out fully right away. Note that since the check might be issued by a bank with no branch near you, you should have a back-up plan. Generally banks will allow you to setup a special/limited savings-only account to deposit your check, even if you don't have a checking account, so if no other option works you might try that as well. The funds availability policies are the same, but at least you'll be able to cash it generally in 10 days time (and then close the account and withdraw your money).\"", "title": "" }, { "docid": "65797", "text": "The classic Nigerian scam involves sending fraudulent cashier's checks to unwitting recipients who then deposit them in their account. The bank reverses these deposits once they discover the check is not valid. At least in the US and in the parts of the EU I'm familiar with (the Netherlands), the method of the Nigerian scam is consistent and banks will reverse the deposit after some holding period. Given this, it's unlikely that most banks will convert an arbitrary cashier's check to cash without any means to recover the amount should the check be fraudulent.", "title": "" } ]
[ { "docid": "453641", "text": "\"My revised, bottom-line advice: offer to send a 2nd payment (preferably in the form of money order or cashier's check) for the difference you are agreeing to pay. I cannot imagine any reason why they would object to this - there is no fee to cash a check, there's less risk of error, and less work involved. Alternatively, offer to send a new check only once the other has been returned. Don't issue one more full-amount check while the other is still outstanding. There is a good reason not to accept partial payment by them, which is that accepting a partial payment of a debt comes with a varieties of strings attached depending on the nature of the debt (such as with evictions, court processes may need to be restarted, etc). They likely want to avoid such a situation - but this does not provide any support for why they can't just take a second payment and then cash it all at once as a single, full settlement of the debt. In a perfect world, you could skip all the non-sense by simply having your bank put a stop-payment on the old check before sending a new one. Unfortunately, this might not work with 100% accuracy - but in your case if the \"\"partial payment\"\" is a significant amount of money to you, I'd go ahead and spend the $20-40 to put in the order now as an extra safety on them not doing what they claim, if for some incredibly stupid reason you can't handle this with a 2nd payment instead of one single full one. It turns out banks have lots of surprising and stupid rules, like stop payments on a check expiring in 6 months (and they may even cash stale checks over a year old), no guarantee of a stop being successful, etc. The real rule is: they might cash the check unless you close the account. Sigh - this is one of many reasons I never, ever use checks. I am not aware of any law that requires a check to be physically returned if requested, or proof or destruction provided, or anything like that. It's a large part of the reason why we have the ability to stop payment on a check, and so void it through the bank without having any physical access to the check - but this process is spotty and imperfect, and cannot be relied upon. You can request them to do whatever you like, like void it and send it back, or destroy it, and they can just refuse - or say they'll do it and then just not do it, and you have no real useful recourse. The main goal should be to avoid losing money if someone \"\"accidentally\"\" (or intentionally) cashes both checks. So you can ask, or demand (refuse to pay until they return the check), etc - and they can respond more or less any way they want. As a final piece of future advice, consider no longer using checks for purposes like this. Switch to using something like a cashier's check or money order offered by your bank, which (by their very nature) takes the money out of your account immediately, severs all ongoing connection to your bank account, and is effectively like cash with the added benefit of a paper trail. Keep the stub and and receipt from the cashier's check/money order, in case it is lost or they claim they didn't get the money.\"", "title": "" }, { "docid": "38571", "text": "\"The answer probably varies with local law, and you haven't said where you're located. In most or all US states, it appears that after some statutory length of time, the bank would transfer the money to the state government, where it would be held indefinitely as \"\"unclaimed property\"\" in the name of the recipient (technically, the payee, the person to whom the check is made payable). This process is called escheatment. Most states publish a list of all unclaimed property, so at some later date the payee could find their name on this list, and realize they were entitled to the funds. There would then be a process by which the payee could claim the funds from the state. Usually the state keeps any interest earned on the money. As far as I know, there typically wouldn't be any way for you, the person who originated the payment, to collect the money after escheatment. (Before escheatment, if you have the uncashed check in your possession, you can usually return it to the bank and have it refunded to you.) I had trouble finding an authoritative source explaining this, but a number of informal sources (found by Googling \"\"cashier check escheatment\"\") seem to agree that this is generally how it works. Here is the web site for a law firm, saying that in California an uncashed cashier's check escheats to the state after 3 years. Until escheatment occurs, the recipient can cash the check at any time. I don't think that cashier's checks become \"\"stale\"\" like personal checks do, and there isn't any situation in which the funds would automatically revert to you.\"", "title": "" }, { "docid": "430696", "text": "From my reading of the wikipedia page (CRT), this only happens if you deposit or withdraw currency, not checks. The idea behind this is that checks, ACH, etc. leave paper trails that can be tracked. Cash doesn't, so it gets this extra level of scrutiny. If yu get a cashiers check or a money order to pay a bill, I don't think a CRT is created. If you withdraw $15,000 to buy a car in cash (1 stack of $100 bills), then a CRT would be generated. It still isn't a problem, as long as you can show a bill of sale showing where the money went (or came from, if you are the seller). The IRS has a FAQ about this. It says (taken from several spots at that page): Cash is money. It is currency and coins of the United States and any other country. A cashier’s check, bank draft, traveler’s check, or money order with a face amount of more than $10,000 is not treated as cash and a business does not have to file Form 8300 when it receives them. These items are not defined as cash because, if they were bought with currency, the bank or other financial institution that issued them must file a Currency Transaction Report. The exception to this is if you are buying something with a resale value of more than $10k with a check, money order, etc of less than $10k.", "title": "" }, { "docid": "547773", "text": "\"Generally cashiers checks do not expire, since they are \"\"like cash\"\" and fully funded at the time of issue. However, whether they can be cashed after a long period of time (and also what the definition of \"\"long\"\" is) depends on the bank. Eventually, if left uncashed it probably would be escheated to the state to wait for someone to claim it. Being that it's been less than a year I expect it could be cashed by the payee written on the check without any issues. If the payee is deceased then the check can be cashed by the estate, as it should be considered the property of the estate the same way it would be if it had already been cashed and was now sitting in a bank account in your mother's name. Under normal circumstances the \"\"estate\"\" in this case would go to your mother's spouse first, then to you (and your siblings if you have any), unless there is a will specifying otherwise. The only way your aunt would be able to deposit the check on her own is if she was listed as an \"\"OR\"\" on the check, or if she is the executor of OP's mother's estate. It sounds like the second line of the check is indeed referring to your aunt, however, from your description of the check it sounds like the second line is simply a designation of what the check is for rather than an additional payee. I bet a probate attorney in your state could easily tell by simply looking at the check.\"", "title": "" }, { "docid": "225030", "text": "\"It's a scam. The cashier's check will be forged. Craigslist has a warning about it here (item #3). What kind of payment do you think is not fakable? Or at least not likely to be used in scams? When on craigslist - deal only locally and in person. You can ask to see the person's ID if you're being paid by check When being paid by check, how can seeing his/her ID help? In case the check isn't cashable, I can find that person by keeping record of his/her ID? If you're paid by check, the payers details should be printed on the check. By checking the ID you can verify that the details match (name/address), so you can find the payer later. Of course the ID can be faked too, but there's so much you can do to protect yourself. You'll get better protection (including verified escrow service) by selling on eBay. Is being paid by cash the safest way currently, although cash can be faked too, but it is the least common thing that is faked currently? Do you recommend to first deposit the cash into a bank (so that let the bank verify if the cash is faked), before delivering the good? For Craigslist, use cash and meet locally. That rules out most scams as a seller. What payment methods do you think are relatively safe currently? Then getting checks must be the least favorite way of being paid. Do you think cash is better than money order or cashier order? You should only accept cash. If it is a large transaction, you can meet them at your bank, have them get cash, and you receive the cash from the bank. Back to the quoted scam, how will they later manipulate me? Are they interested in my stuffs on moving sale, or in my money? They will probably \"\"accidentally\"\" overpay you and ask for a refund of some portion of the overpayment. In that case you will be out the entire amount that you send back to them and possibly some fees from your bank for cashing a bad check.\"", "title": "" }, { "docid": "296769", "text": "I usually get a cashiers check to cover about 90% - 95% of the expected amount (whatever I think is just below my wet-dream-price), and bring the rest in cash. That doesn't require so much cash to be carried. Alternatively you can write a personal check for the exact reminder, or go to the bank for the reminder after the deal is made - with the majority already paid in a cashiers check nobody would disagree.", "title": "" }, { "docid": "346042", "text": "When you pay cash for a car, you don't always necessarily need to pay cash. You just aren't using credit or a loan is all. A few options you have are: Obviously no dealer expects anyone to just have the cash laying around for a car worth a few thousand dollars, nor would you bother going to your bank or credit union for the cash. You can simply get a cashier's check made out for the amount. Note that dealers may not accept personal checks as they may bounce. After negotiations at the dealer, you would explain you're paying cash, likely pay a deposit (depending on the price of the car, but $500 would probably be enough. Again, the deposit can be a check or bank deposit), and then come back later on with a cashier's check, or deposit into a bank account. You would be able to do this later that day or within a few days, but since you've purchased a new car you would probably want to return ASAP!", "title": "" }, { "docid": "66991", "text": "Deposit it into your Brazilian bank account. They'll charge you collection fee (shouldn't be high, its a cashier's check equivalent), and the currency exchange rate may not be the best ever, but that's the price to pay for the service. Another option would be to cash the check at check cashing places, but that would most likely require you being in the US (I don't know if any check-cashing store in Brazil would cash a US check).", "title": "" }, { "docid": "598834", "text": "\"There are two different issues at play here, and they are completely separate from each other: A bank or cashier's check is \"\"safer\"\" than a regular personal or business check because it avoids problem #1. Problem #2 exists with all kinds of paper checks. I assume the reason the warnings are about cashier's check moreso than personal checks, is simply because people already know to wait for personal checks to clear before handing over merchandise to the buyer. People are less likely to do that when receiving cashier's checks, but perhaps they still should if there is any doubt about the validity of the check. One could argue that a cashier's check actually provides a false sense of security due to this (to the receiver). On the flip side, if you are the payer, then a cashier's check could be thought of as more secure than a personal check because you don't have to reveal your bank account information to a stranger.\"", "title": "" }, { "docid": "450667", "text": "\"Money has to come from somewhere. It can't just appear. So if there is really an aunt at an agency, and she is sending checks, then she is writing checks from that company, and stealing from that company. If that is the case, then the person with whom you are in contact would be using you to launder money (hide its illegal origin) and when the aunt was caught, you would be also. If it is really being done between countries, then it might be more difficult for them to find you, but it is still illegal. However, it is also likely that your contact may be using a common scam, as described by another answerer, that of asking for money in return for a cashier's check. Although cashier's checks were designed to be \"\"safer\"\" than regular checks, in that they won't bounce, if it is a fake cashier's check, it was never worth anything in the first place. When the bank tries to claim the cash from the other bank, and finds it doesn't exist, or there is no record of that check, then the effect is similar to that of a personal check bouncing: the bank will want the money back. If you have already given a portion of that money to your contact, chances are, when your find this out, he will be long gone. I would not have anything further to do with this person. Good luck.\"", "title": "" }, { "docid": "406109", "text": "\"Anyone can walk into a bank, say \"\"Hi, I'm a messenger, I have an endorsed check and a filled out deposit slip for Joe Blow who has an account here, please deposit this check for him, as he is incapacitated. Straight deposit.\"\" They'll fiddle on their computer, to see if they can identify the deposit account definitively, and if they can, and the check looks legit, \"\"thanks for taking care of our customer sir.\"\" Of course, getting a balance or cashback is out of the question since you are not authenticated as the customer. I have done the same with balance transfer paperwork, in that case the bank knew the customer and the balance transfer was his usual. If the friend does not have an account there, then s/he should maybe open an account at an \"\"online bank\"\" that allows deposit by snapping photos on a phone, or phone up a branch, describe her/his situation and see if they have any options. Alternately, s/he could get a PayPal account. Or get one of those \"\"credit card swipe on your phone\"\" deals like Square or PayPal Here, which have fees very close to nil, normally cards are swiped but you can hand-enter the numbers. Those are fairly easy to get even if you have troubles with creditworthiness. S/he would need to return the check to the payer and ask the payer to pay her/him one of those ways. The payer may not be able to, e.g. if they are a large corporation. A last possibility is if the check is from a large corporation with whom s/he continues to do business with. For instance, the electric company cashiers out your account after you terminate service at your old location. But then you provision service at a new location and get a new bill, you can send their check right back to them and say \"\"Please apply this to my new account\"\". If s/he is unable to get any of those because of more serious problems like being in the country illegally, then, lawful behavior has its privileges, sorry. There are lots of unbanked people, and they pay through the nose for banking services at those ghastly check-cashing places, at least in America. I don't have a good answer for how to get a check cashed in that situation.\"", "title": "" }, { "docid": "213859", "text": "I'm not a finance professional by any means, but my understanding of cashier's checks is that they're more in favour of the person receiving. They're essentially guaranteeing that you have the money in your account to provide payment to the recipient. The advice I've always received is to treat cashier's checks and money orders as straight up cash, because that's essentially what they are. Hopefully someone else can come in with a better background, but I figured I'd pitch in.", "title": "" }, { "docid": "170248", "text": "\"If you were making that large of a payment (via a cashiers check or other withdrawal means from a cash account) to a credit card, would the payment generate a Cash Transaction Report? Probably, yes. If it does require the bank to make a CTR, then is there any harm in that or anything to be concerned about (like that transaction appearing suspicious, personal reporting implications, etc.)? Are there any other reasons why one might want to make sure payments to a credit card are broken up made* in amounts smaller than $10K? You should be concerned if you cannot explain the source of the money (legally...). If you withdrew cash from your own account and paid your credit card with it, in case of questions asked you can show the account statement with the matching withdrawal, and you're done. The point in this report is to point at people who move around large amounts of cash. Usually, people pay credit cards with checks or ACH transactions, but if you want cash - it's your right, as long as the cash was obtained legally. But if you're paying your credit cards off with the cash you got as a bribe or by selling cocaine on the streets, then you should be worried. By the way, breaking into smaller payments may not save you from being reported to the money laundering detection agencies. The report is per transaction, not per payment, so if the credit card statement is $11K and you pay $5K and $6K - the transaction is still $11K. Also, the bank can file a report even if it is not required (it was clarified in the other answer to the same question you're referring to), if the clerk thinks the transaction is suspicious. This leaves the decision on filing a report solely on the banks \"\"common sense\"\" and internal policies which you don't know. So even paying $10 in cash may trigger a report if the bank suspects wrongdoing.\"", "title": "" }, { "docid": "153121", "text": "\"Can you get a cashier's check from your bank, made out in the charity's name, and mail it to the charity? From what I recall of the last few times I've gotten a cashier's check from the bank, it didn't have anything on it that identified me. A determined person could probably trace it back to you, but you're not really looking for strong anonymity. Another possibility would be a postal money order, but I'm not sure whether you can leave the \"\"From\"\" section blank. The money order would have a fee, but the cashier's check should be free. (It is at both my local bank and my CU.)\"", "title": "" }, { "docid": "219033", "text": "It is possible to not use checks in the US. I personally use a credit card for almost everything and often have no cash in my wallet at all. I never carry checks with me. If we wanted to, we could pay all of our monthly bills without checks as well, and many people do this. 30 years ago, grocery stores didn't generally accept credit cards, so it was cash or check, though most other kinds of stores and restaurants did. Now, the only stores that I have encountered in years that do not accept credit cards are a local chicken restaurant, and the warehouse-shopping store Costco. (Costco accepts its own credit card, but not Mastercard or Visa.) Still, we do pay the majority of our monthly bills via check, and it would not be shocking to see someone paying for groceries with a check. I can't name the last time I saw someone write a check at a store exactly, but I've never seen any cashier or other patrons wonder what a check-writer was trying to do. Large transactions, like buying a car or house, would still use checks -- probably cashier's or certified checks and not personal checks, though.", "title": "" }, { "docid": "414777", "text": "A cashier's check costs money to get and is not connected to an account. You have cash. You should be able to get a bank to sell you one, even without an account. Find a bank where you would like to open an account and explain the situation. I can't guarantee that that will work, but I would expect it to do so. If not, the bank can probably suggest an alternative. You might also ask the landlord if you can do it with postal money orders. I am positive that you can buy those with cash. You might have to buy a bunch to reach your desired amount. Or perhaps a Western Union money order might be better. You also might be able to open an account with your passport and Social Security Number (SSN).", "title": "" }, { "docid": "281246", "text": "In addition to the money-laundering, lifestyle, income tax, etc issues discussed already in other answers, one other matter that might concern the bank is whether that cash you are bringing in to deposit is genuine currency or (some or all of) the bills are counterfeit and you are using this mechanism to get them into circulation. Even if you withdraw a very large amount in cash from your bank, step out the door and come back just a few minutes later saying that you have changed your mind and want to put that money back into your account, there is still the question as to whether the cash you have brought back is exactly the same as you took out or a substitution was made in the interim. I once needed a bank draft for $1000 and went to my bank to get it, taking with me a check made out to Cash for $1003 (the bank's fee was $3). The bank would not give me a bank draft in exchange for the check, or if I cashed the check right then and there and paid for the bank draft using the cash that the teller had just handed me. I had to tear up the check, write another one payable to the bank, and then I got my bank draft. As JoeTaxpayer says, it is a matter of paper trail. Additional matter added in edit: According to Wikipedia, because of the Bank Secrecy Act of 1970, Many banks will no longer sell negotiable instruments when they are purchased with cash, requiring the purchase to be withdrawn from an account at that institution. which was exactly my experience. Furthermore, even the banks that will still sell you a cashier's check or money order for cash must keep a Monetary Instrument Log (MIL) that records all such cash transactions for amounts between $3000 and $10,000, keep the records for at least five years, and produce it upon request of a bank examiner or auditor (and presumably upon subpoena by a district attorney or divorce lawyer). Cash transactions of $10,000 or over are, of course, reported to the IRS on Currency Transaction Reports. In short, a paper trail exists for some time even for cash transactions quite a bit smaller than $10,000.", "title": "" }, { "docid": "107887", "text": "\"the easiest thing would be to go to walmart and stock up on 1000$ money orders paying a 70 cents fee for each. your landlord would almost certainly accept money orders, but double check first just in case. i say stock up because you can't get a money order for more than 1000$ and they usually won't let you buy more than 3 per day. alternatively, you can probably open a bank account using your ssn and your passport. look for any bank offering \"\"free\"\" checking, and they should be able to give you a few \"\"starter\"\" checks on the spot when you open the account. in any case, they can certainly get you a cashier's check for free or a small fee. side note: if you want to shop around for a checking account, look for a bank or credit union offering a \"\"kasasa\"\" account.\"", "title": "" }, { "docid": "138934", "text": "When I moved banks. I had my old bank cut a cashier's check. It isn't a check you write. They write it and give it to you. I then took the cashier's check to my new bank to deposit it.", "title": "" }, { "docid": "274834", "text": "If you can get to a physical branch, get a cashier's check (or call them and have them send you one by mail). When they draft the cashier's check they remove the money from your account immediately and the check is drawn against the bank itself. You could hold onto that check for a little while even after your account closes and you make other arrangements for banking. If you cannot get a cashier's check, then you should try to expeditiously open a new account and do an ACH from old to new. This might take more days to set up than you have left though.", "title": "" }, { "docid": "214518", "text": "\"It is likely a scam. In fact the whole mystery shopping \"\"job\"\" may be a scam. There is a Snopes page about cashier's check scams, as well as a US government page which specifically mentions mystery shopping as a scam angle. As for how the scam works, from the occ.gov site I just linked: However, cashier’s checks lately have become an attractive vehicle for fraud when used for payments to consumers. Although, the amount of a cashier’s check quickly becomes \"\"available\"\" for withdrawal by the consumer after the consumer deposits the check, these funds do not belong to the consumer if the check proves to be fraudulent. It may take weeks to discover that a cashier’s check is fraudulent. In the meantime, the consumer may have irrevocably wired the funds to a scam artist or otherwise used the funds—only to find out later, when the fraud is detected—that the consumer owes the bank the full amount of the cashier’s check that had been deposited. It is somewhat unusual in that, from what you say, there has been no attempt thus far to get money back. However, your sister-in-law may have received that info separately, or received it as part of her mystery shopping job but didn't mention it to you with regard to this check. Typically the scam involves telling the recipient to transfer money to a third party (e.g., by buying goods as a mystery shopper, or via wire transfer to \"\"reimburse\"\" someone associated with a sham operation). By the time the cashier's check is revealed as fraudulent, the victim has already transferred away his/her own real money. It's probably worth taking the check to your or her bank and asking them about it. They may have more info. Also, banks usually want to know about scams like this because, in the long run, they accumulate data on them and share that with law enforcement and can eventually catch some of the scammers. Edit: Just to help anyone who may be reading this later. The letter you added confirms it is absolutely a scam. My boss was once contacted via a scam operation very similar to this. The huge red flag (in addition to others already mentioned) is that you are being \"\"given\"\" a check for over $2000, of which only $25 is purportedly for actual mystery shopping and $285 is payment for you, the mystery shopper. The whole rest of the $2000+ amount is for you to wire to \"\"another Mystery/Secret Shopper in order for them to complete their assignment\"\". They are giving you $2000 to give to someone else who is supposedly another one of their own employees/contractors. Ask yourself what sane business would conduct their operations in this way. If you work at a law office, or a hamburger stand, or a school, or anything you like, does your boss ever say \"\"Here is your paycheck for $5000. I know you only earned $1000, but I'm just going to give you the whole $5000, and you're supposed to use $4000 of it to pay your coworker Joe his wages.\"\" No. There is no reason to do that except that the \"\"other mystery shopper\"\" is actually the scammer.\"", "title": "" }, { "docid": "152827", "text": "\"Generally when you open a new account, you'd be given a checkbook (usually \"\"starter\"\" checks with no personal information, but some banks will later mail you a proper checkbook with your personal details) and a debit card (again, some banks will give you a \"\"starter\"\" one on the spot with a personalized following up in the mail, others will mail you). With the debit card you can use your bank's ATM to withdraw cash from your account, or use it for purchases (will debit, as the name says, directly from your account). You can also use it in other ATMs, but that will usually be with significant fees ($2-$5 per withdrawal to both the ATM owner and your bank). Checks - you can write a check to someone or use the check to go to the cashier in the bank and withdraw money (although usually they have special withdrawal slips for that in the branches, so you don't really need to waste your own checks). As to how to deposit money in your home country - you'll have to check with the bank you have an account at back at home. Usually, you can \"\"wire\"\" transfer money from your BoA account to the account back home, but that is usually comes at a fee of about $30-$50 per transfer (in the US, additional fees may be charged at the receiving end + currency conversion costs). You can also write yourself a check and deposit that check at the home country bank, but that depends on the specific bank whether it is possible, how much it would cost, and how long it would take for them to credit the money to your account after they take your check - may take weeks with personal checks.\"", "title": "" }, { "docid": "561653", "text": "\"This is fairly simple, actually. You should insist on payment for the rent payment you never received and stop accepting cash payments. If you want to be nice, and believe the story, allow the tenant additional time or payment in installments for the missing $750, but this is a textbook example of why it's a bad idea to transact with cash. Insist on cash equivalents that are traceable and verifiable - check, money order or cashier's check, made out to you or your company name. Also, for what it's worth, you are not out $750, unless you choose to be. Your tenant is. \"\"I put cash in your mailbox\"\" is not proof of payment, and doesn't fly as payment anywhere. If it did, I'd never pay any of my bills.\"", "title": "" }, { "docid": "233001", "text": "\"The only way to prevent it is to not use PayPal. The terms of usage are draconian, and by using the service you agree to them. I'm sure that when the case gets to a court of law, they will find where it is authorized. Paypal is not a bank, and the money there is basically \"\"entrusted\"\" with the company and is not insured by anyone. They don't need or have to be subject to the regulations on the banking industry, and they're no different than your neighbour carrying money for you to the grocery store when you're sick. Other options are wire transfer, services like Western Union or Moneygram, checks (better certified/cashier's checks), money orders or even cash. You can also charge via credit card, but you can get similar problems there (although it is still safer than PayPal because with credit card - the card owner must initiate the charge back, it doesn't appear on its own because they feel like it).\"", "title": "" }, { "docid": "279480", "text": "\"This answer is based on my understanding of the US banking system. We have check cashing businesses here too, which are just like what you describe, except for the spelling :-) Let's consider what \"\"cash it for free at the bank\"\" really means, and why it might not be an option for everyone. One key issue is \"\"which bank?\"\" As an example, suppose that I have an account at ABC Bank. I take out my checkbook for that account and write you a check for $500. (Terminology: In this case, I am the drawer or maker of the check, ABC Bank is the drawee bank, and you, user54609, are the payee. Disclaimer: \"\"You\"\" here is meant as a generic pronoun and I do not mean to insinuate that anything here actually applies to you personally.) There are two common things you might do with the check: If you have an account at some bank, say XYZ Bank, you might take the check to XYZ Bank and deposit it in your account. (You might be able to do this through an ATM, mobile app, or by mail, instead of in person.) XYZ Bank does not have a way to verify with certainty that the check is valid (e.g. they don't know what my signature looks like, nor whether I actually have $500 in my account at ABC), so they send it to ABC Bank, which verifies the check and transfers $500 to XYZ. (This is usually done through a central clearinghouse, such as the Federal Reserve in the US, and in some cases an image of the check may be sent electronically, instead of the physical check.) This process takes some time, so XYZ may not make the $500 available to you right away - there may be a hold period before you can withdraw that $500 from your account. You could take the check to ABC Bank, in person. They will verify on the spot that the check is valid and that you are in fact user54609. If everything looks good, they will hand you $500 in cash (perhaps subtracting a fee of a few dollars). Now we can see some possible problems with each of these approaches. For 1: Maybe you don't have a bank account at all. There are many possible reasons: You don't have enough money to meet the minimum balance that a bank account would require. You used to have an account, but you overdrew or otherwise misused an account, so the bank closed it. They then entered you in a registry such as ChexSystems which ensures that other banks know about this, and so no other bank will open a new account for you. You immigrated to the country illegally and cannot get the documents (driver's license, social security number, etc) that a bank normally requires to open an account. You simply don't like the idea of keeping your money in a bank. Maybe you do have an account at XYZ Bank, but it's in another town. You need the cash today, so you can't use mail or a mobile app, and third-party ATMs usually don't accept deposits. Maybe you need to spend the money today, and XYZ Bank would place a hold. For 2: ABC Bank may not have a branch you can conveniently visit. Maybe the nearest one is a long way away, in another city or across the country. Or maybe ABC is an online bank with no physical branches at all. Maybe it's in the same city, but you don't have transportation to get you there. Or maybe it's simply less convenient than the check-cashing business on the corner. Maybe it is after usual banking hours, or a weekend, and ABC Bank is closed, but you need cash now. In any of these situations, \"\"cash it at the bank\"\" might not be a viable option, and so you might reasonably turn to a check cashing business instead. As you say, you will pay a much higher fee there, but maybe it is worth it to you, or you just don't have any choice. Another possibility, of course, is that you are poorly educated about the banking system, and you don't really understand that 1 and 2 are options, or how to go about them. But there's this storefront on the corner that says \"\"Check Cashing\"\", so this seems like a low-stress, uncomplicated way to exchange this piece of paper for money. As such, there certainly are people who legitimately might want to cash a valid check at a check-cashing business. Check cashing business do of course take some risk of fraud, since they can't necessarily verify the check. There are sometimes steps they can take to minimize this risk. Sometimes they can call ABC Bank and check that I have sufficient money in my account. Maybe they'll only accept certain kinds of checks, such as payroll checks from well-known companies for which you can produce a matching pay stub. And they can demand identification from you (perhaps allowing more flexible options than a bank), which helps ensure that you are the payee, and would make you easier to track down if you did commit fraud. But they will probably lose some money this way, so they will have to make their fees high enough to cover those losses.\"", "title": "" }, { "docid": "157474", "text": "If they bring cash, meet at your bank to verify. If they want to use cashiers check, meet them at their bank. Large amounts use wires directly to your acct and verify (not only received, but deposited) before handing over the title/keys.", "title": "" }, { "docid": "491600", "text": "I was a involved in this same scam from my Craigslist item. The buyer texted me & said his assistant put the wrong check in my envelope & please let him know when I got it,cash the cashiers check, keep my part for money of my item & send him back the difference. Well, the check came to me for $1,350.00 for a $100 item. I immediately suspected something here. It was for way to big to be a mistake. I called the credit union in California to ask about this cashier's check & sure enough, they said it was a fake check. This scammer's phone he texted from was from a San Antonio,TX area code, the check was mailed from Madison, WI, & the check was on a California CU. They sure cover their tracks pretty good. So C/L'ers.....BEWARE! don't take checks for more than the amount & be asked to send back the difference. You will be HAD!", "title": "" }, { "docid": "339545", "text": "What I'm reading is that they subtracted the $85 you owe them and they're cutting you a cashier's check for the rest. Ethically speaking, you owed them the money, they subtracted it and made you a check for the rest. Once you cash that check, nobody owes anyone anything in this equation. Sounds like they're in the clear. Legally speaking, I have no idea, since I'm not a lawyer, but even if it was not legal, good luck getting the $85 back without spending far more in retaining a lawyer and fighting it in court. Even fighting it in small claims court will take more of your time than $85 is worth. If it's your time that is the problem, 12 days is not horrible in banking terms. Yes, we're spoiled now by ACH transfers and same day deposit availability, but since you're retired, I'm sure if you think back you'll remember when it used to take two business weeks to clear a check... TLDR; cancel future deposits to that bank, find a new bank, then forget this fiasco and get your revenge by enjoying your life.", "title": "" }, { "docid": "466317", "text": "buy a cashiers check with the cash (a CRT will be nec if over 10 K) and deposit the cashiers check", "title": "" }, { "docid": "108739", "text": "You can pay with a cashiers check or personal check. You can even pay cash, or combine payment methods. However, in the USA if you give the dealership $10,000 or more in actual cash, they will be required to fill out a form 8300 with the IRS.", "title": "" } ]
296
Cyclin A2 destruction is necessary to switch from unstable to stable kt-mt attachments in mitosis.
[ { "docid": "4398832", "text": "The most conspicuous event in the cell cycle is the alignment of chromosomes in metaphase. Chromosome alignment fosters faithful segregation through the formation of bi-oriented attachments of kinetochores to spindle microtubules. Notably, numerous kinetochore-microtubule (k-MT) attachment errors are present in early mitosis (prometaphase), and the persistence of those errors is the leading cause of chromosome mis-segregation in aneuploid human tumour cells that continually mis-segregate whole chromosomes and display chromosomal instability. How robust error correction is achieved in prometaphase to ensure error-free mitosis remains unknown. Here we show that k-MT attachments in prometaphase cells are considerably less stable than in metaphase cells. The switch to more stable k-MT attachments in metaphase requires the proteasome-dependent destruction of cyclin A in prometaphase. Persistent cyclin A expression prevents k-MT stabilization even in cells with aligned chromosomes. By contrast, k-MTs are prematurely stabilized in cyclin-A-deficient cells. Consequently, cells lacking cyclin A display higher rates of chromosome mis-segregation. Thus, the stability of k-MT attachments increases decisively in a coordinated fashion among all chromosomes as cells transit from prometaphase to metaphase. Cyclin A creates a cellular environment that promotes microtubule detachment from kinetochores in prometaphase to ensure efficient error correction and faithful chromosome segregation.", "title": "Cyclin A Regulates Kinetochore-Microtubules to Promote Faithful Chromosome Segregation" } ]
[ { "docid": "45875990", "text": "Cyclin A2 activates the cyclin-dependent kinases Cdk1 and Cdk2 and is expressed at elevated levels from S phase until early mitosis. We found that mutant mice that cannot elevate cyclin A2 are chromosomally unstable and tumor-prone. Underlying the chromosomal instability is a failure to up-regulate the meiotic recombination 11 (Mre11) nuclease in S phase, which leads to impaired resolution of stalled replication forks, insufficient repair of double-stranded DNA breaks, and improper segregation of sister chromosomes. Unexpectedly, cyclin A2 controlled Mre11 abundance through a C-terminal RNA binding domain that selectively and directly binds Mre11 transcripts to mediate polysome loading and translation. These data reveal cyclin A2 as a mechanistically diverse regulator of DNA replication combining multifaceted kinase-dependent functions with a kinase-independent, RNA binding–dependent role that ensures adequate repair of common replication errors.", "title": "Cyclin A2 is an RNA binding protein that controls Mre11 mRNA translation" }, { "docid": "600808", "text": "Cyclin A is a stable protein in S and G2 phases, but is destabilized when cells enter mitosis and is almost completely degraded before the metaphase to anaphase transition. Microinjection of antibodies against subunits of the anaphase-promoting complex/cyclosome (APC/C) or against human Cdc20 (fizzy) arrested cells at metaphase and stabilized both cyclins A and B1. Cyclin A was efficiently polyubiquitylated by Cdc20 or Cdh1-activated APC/C in vitro, but in contrast to cyclin B1, the proteolysis of cyclin A was not delayed by the spindle assembly checkpoint. The degradation of cyclin B1 was accelerated by inhibition of the spindle assembly checkpoint. These data suggest that the APC/C is activated as cells enter mitosis and immediately targets cyclin A for degradation, whereas the spindle assembly checkpoint delays the degradation of cyclin B1 until the metaphase to anaphase transition. The “destruction box” (D-box) of cyclin A is 10–20 residues longer than that of cyclin B. Overexpression of wild-type cyclin A delayed the metaphase to anaphase transition, whereas expression of cyclin A mutants lacking a D-box arrested cells in anaphase.", "title": "Anaphase-Promoting Complex/Cyclosome–Dependent Proteolysis of Human Cyclin a Starts at the Beginning of Mitosis and Is Not Subject to the Spindle Assembly Checkpoint" }, { "docid": "6472746", "text": "Chromosome segregation during cell division depends on stable attachment of kinetochores to spindle microtubules. Mitotic spindle formation and kinetochore-microtubule (K-MT) capture typically occur within minutes of nuclear envelope breakdown. In contrast, during meiosis I in mouse oocytes, formation of the acentrosomal bipolar spindle takes 3-4 h, and stabilization of K-MT attachments is delayed an additional 3-4 h. The mechanism responsible for this delay, which likely prevents stabilization of erroneous attachments during spindle formation, is unknown. Here we show that during meiosis I, attachments are regulated by CDK1 activity, which gradually increases through prometaphase and metaphase I. Partial reduction of CDK1 activity delayed formation of stable attachments, whereas a premature increase in CDK1 activity led to precocious formation of stable attachments and eventually lagging chromosomes at anaphase I. These results indicate that the slow increase in CDK1 activity in meiosis I acts as a timing mechanism to allow stable K-MT attachments only after bipolar spindle formation, thus preventing attachment errors.", "title": "Increased CDK1 activity determines the timing of kinetochore-microtubule attachments in meiosis I" }, { "docid": "14205246", "text": "The spindle apparatus is a microtubule (MT)-based machinery that attaches to and segregates the chromosomes during mitosis and meiosis. Self-organization of the spindle around chromatin involves the assembly of MTs, their attachment to the chromosomes, and their organization into a bipolar array. One regulator of spindle self-organization is RanGTP. RanGTP is generated at chromatin and activates a set of soluble, Ran-regulated spindle factors such as TPX2, NuMA, and NuSAP . How the spindle factors direct and attach MTs to the chromosomes are key open questions. Nucleolar and Spindle-Associated Protein (NuSAP) was recently identified as an essential MT-stabilizing and bundling protein that is enriched at the central part of the spindle . Here, we show by biochemical reconstitution that NuSAP efficiently adsorbs to isolated chromatin and DNA and that it can directly produce and retain high concentrations of MTs in the immediate vicinity of chromatin or DNA. Moreover, our data reveal that NuSAP-chromatin interaction is subject to Ran regulation and can be suppressed by Importin alpha (Impalpha) and Imp7. We propose that the presence of MT binding agents such as NuSAP, which can be directly immobilized on chromatin, are critical for targeting MT production to vertebrate chromosomes during spindle self-organization.", "title": "A Role for NuSAP in Linking Microtubules to Mitotic Chromosomes" }, { "docid": "14471161", "text": "Circadian disruption accelerates cancer progression, whereas circadian reinforcement could halt it. Mice with P03 pancreatic adenocarcinoma (n = 77) were synchronized and fed ad libitum (AL) or with meal timing (MT) from Zeitgeber time (ZT) 2 to ZT6 with normal or fat diet. Tumor gene expression profiling was determined with DNA microarrays at endogenous circadian time (CT) 4 and CT16. Circadian mRNA expression patterns were determined for clock genes Rev-erbalpha, Per2, and Bmal1, cellular stress genes Hspa8 and Cirbp, and cyclin A2 gene Ccna2 in liver and tumor. The 24-hour patterns in telemetered rest-activity and body temperature and plasma corticosterone and insulin-like growth factor-I (IGF-I) were assessed. We showed that MT inhibited cancer growth by approximately 40% as compared with AL (P = 0.011) irrespective of calorie intake. Clock gene transcription remained arrhythmic in tumors irrespective of feeding schedule or diet. Yet, MT upregulated or downregulated the expression of 423 tumor genes, according to CT. Moreover, 36 genes involved in cellular stress, cell cycle, and metabolism were upregulated at one CT and downregulated 12 h apart. MT induced >10-fold circadian expression of Hspa8, Cirbp, and Ccna2 in tumors. Corticosterone or IGF-I patterns played no role in tumor growth inhibition. In contrast, MT consistently doubled the circadian amplitude of body temperature. Peak and trough respectively corresponded to peak expressions of Hspa8 and Cirbp in tumors. The reinforcement of the host circadian timing system with MT induced 24-hour rhythmic expression of critical genes in clock-deficient tumors, which translated into cancer growth inhibition. Targeting circadian clocks represents a novel potential challenge for cancer therapeutics.", "title": "Cancer inhibition through circadian reprogramming of tumor transcriptome with meal timing." }, { "docid": "17805221", "text": "Sport fishermen keep tension on their lines to prevent hooked fish from releasing. A molecular version of this angler's trick, operating at kinetochores, ensures accuracy during mitosis: the mitotic spindle attaches randomly to chromosomes and then correctly bioriented attachments are stabilized due to the tension exerted on them by opposing microtubules. Incorrect attachments, which lack tension, are unstable and release quickly, allowing another chance for biorientation. Stabilization of molecular interactions by tension also occurs in other physiological contexts, such as cell adhesion, motility, hemostasis, and tissue morphogenesis. Here, we review models for the stabilization of kinetochore attachments with an eye toward emerging models for other force-activated systems. Although attention in the mitosis field has focused mainly on one kinase-based mechanism, multiple mechanisms may act together to stabilize properly bioriented kinetochores and some principles governing other tension-sensitive systems may also apply to kinetochores.", "title": "Catch and release: how do kinetochores hook the right microtubules during mitosis?" }, { "docid": "8087082", "text": "The microtubule (MT) cytoskeleton is required for many aspects of cell function, including the transport of intracellular materials, the maintenance of cell polarity, and the regulation of mitosis. These functions are coordinated by MT-associated proteins (MAPs), which work in concert with each other, binding MTs and altering their properties. We have used a MT cosedimentation assay, combined with 1D and 2D PAGE and mass spectrometry, to identify over 250 MAPs from early Drosophila embryos. We have taken two complementary approaches to analyse the cellular function of novel MAPs isolated using this approach. First, we have carried out an RNA interference (RNAi) screen, identifying 21 previously uncharacterised genes involved in MT organisation. Second, we have undertaken a bioinformatics analysis based on binary protein interaction data to produce putative interaction networks of MAPs. By combining both approaches, we have identified and validated MAP complexes with potentially important roles in cell cycle regulation and mitosis. This study therefore demonstrates that biologically relevant data can be harvested using such a multidisciplinary approach, and identifies new MAPs, many of which appear to be important in cell division.", "title": "A Microtubule Interactome: Complexes with Roles in Cell Cycle and Mitosis" }, { "docid": "23356816", "text": "The mammalian A-type cyclin family consists of two members, cyclin A1 (encoded by Ccna1) and cyclin A2 (encoded by Ccna2). Cyclin A2 promotes both G1/S and G2/M transitions, and targeted deletion of Ccna2 in mouse is embryonic lethal. Cyclin A1 is expressed in mice exclusively in the germ cell lineage and is expressed in humans at highest levels in the testis and certain myeloid leukaemia cells. To investigate the role of cyclin A1 and possible redundancy among the cyclins in vivo, we generated mice bearing a null mutation of Ccna1. Ccna1-/- males were sterile due to a block of spermatogenesis before the first meiotic division, whereas females were normal. Meiosis arrest in Ccna1–/– males was associated with increased germ cell apoptosis, desynapsis abnormalities and reduction of Cdc2 kinase activation at the end of meiotic prophase. Cyclin A1 is therefore essential for spermatocyte passage into the first meiotic division in male mice, a function that cannot be complemented by the concurrently expressed B-type cyclins.", "title": "Cyclin A1 is required for meiosis in the male mouse" }, { "docid": "7622767", "text": "We have used microinjection and time-lapse video microscopy to study the role of cyclin A in mitosis. We have injected purified, active cyclin A/cyclin-dependent kinase 2 (CDK2) into synchronized cells at specific points in the cell cycle and assayed its effect on cell division. We find that cyclin A/CDK2 will drive G2 phase cells into mitosis within 30 min of microinjection, up to 4 h before control cells enter mitosis. Often this premature mitosis is abnormal; the chromosomes do not completely condense and daughter cells fuse. Remarkably, microinjecting cyclin A/CDK2 into S phase cells has no effect on progress through the following G2 phase or mitosis. In complementary experiments we have microinjected the amino terminus of p21Cip1/Waf1/Sdi1 (p21N) into cells to inhibit cyclin A/CDK2 activity. We find that p21N will prevent S phase or G2 phase cells from entering mitosis, and will cause early prophase cells to return to interphase. These results suggest that cyclin A/CDK2 is a rate-limiting component required for entry into mitosis, and for progress through mitosis until late prophase. They also suggest that cyclin A/CDK2 may be the target of the recently described prophase checkpoint.", "title": "Human Cyclin a Is Required for Mitosis until Mid Prophase" }, { "docid": "11674596", "text": "A putative spindle matrix has been hypothesized to mediate chromosome motion, but its existence and functionality remain controversial. In this report, we show that Megator (Mtor), the Drosophila melanogaster counterpart of the human nuclear pore complex protein translocated promoter region (Tpr), and the spindle assembly checkpoint (SAC) protein Mad2 form a conserved complex that localizes to a nuclear derived spindle matrix in living cells. Fluorescence recovery after photobleaching experiments supports that Mtor is retained around spindle microtubules, where it shows distinct dynamic properties. Mtor/Tpr promotes the recruitment of Mad2 and Mps1 but not Mad1 to unattached kinetochores (KTs), mediating normal mitotic duration and SAC response. At anaphase, Mtor plays a role in spindle elongation, thereby affecting normal chromosome movement. We propose that Mtor/Tpr functions as a spatial regulator of the SAC, which ensures the efficient recruitment of Mad2 to unattached KTs at the onset of mitosis and proper spindle maturation, whereas enrichment of Mad2 in a spindle matrix helps confine the action of a diffusible \"wait anaphase\" signal to the vicinity of the spindle.", "title": "Spatiotemporal control of mitosis by the conserved spindle matrix protein Megator" }, { "docid": "493346", "text": "How sister kinetochores attach to microtubules from opposite spindle poles during mitosis (bi-orientation) remains poorly understood. In yeast, the ortholog of the Aurora B-INCENP protein kinase complex (Ipl1-Sli15) may have a role in this crucial process, because it is necessary to prevent attachment of sister kinetochores to microtubules from the same spindle pole. We investigated IPL1 function in cells that cannot replicate their chromosomes but nevertheless duplicate their spindle pole bodies (SPBs). Kinetochores detach from old SPBs and reattach to old and new SPBs with equal frequency in IPL1+ cells, but remain attached to old SPBs in ipl1 mutants. This raises the possibility that Ipl1-Sli15 facilitates bi-orientation by promoting turnover of kinetochore-SPB connections until traction of sister kinetochores toward opposite spindle poles creates tension in the surrounding chromatin.", "title": "Evidence that the Ipl1-Sli15 (Aurora Kinase-INCENP) Complex Promotes Chromosome Bi-orientation by Altering Kinetochore-Spindle Pole Connections" }, { "docid": "38127792", "text": "In mitosis the cell assembles the bipolar spindle, a microtubule (MT)-based apparatus that segregates the duplicated chromosomes into two daughter cells. Most animal cells enter mitosis with duplicated centrosomes that provide an active source of dynamic MTs. However, it is now established that spindle assembly relies on the nucleation of acentrosomal MTs occurring around the chromosomes after nuclear envelope breakdown, and on pre-existing microtubules. Where chromosome-dependent MT nucleation occurs, when MT amplification takes place and how the two pathways function are still key questions that generate some controversies. We reconcile the data and present an integrated model accounting for acentrosomal microtubule assembly in the dividing cell.", "title": "Acentrosomal Microtubule Assembly in Mitosis: The Where, When, and How." }, { "docid": "57121667", "text": "The ART-adherence club model described here provides patient-friendly access to antiretroviral therapy (ART) for clinically stable patients. It reduces the burden that stable patients place on healthcare facilities, increasing clinical human resources for new patients, and those clinically unstable and at risk of failing treatment. In the model, 30 patients are allocated to an ART club. The group meets either at a facility or community venue for less than an hour every 2 months. Group meetings are facilitated by a lay club facilitator who provides a quick clinical assessment, referral where necessary, and dispenses pre-packed ART. From January 2011 to December 2012, after adoption for phased rollout by the Western Cape Government, more than 600 ART clubs were established in Cape Town, providing ART care to over 16 000 patients. This extensive, rapid rollout demonstrates active buy-in from patients and facility staff. South Africa should consider a similar model for national rollout.", "title": "ART adherence clubs: A long-term retention strategy for clinically stable patients receiving antiretroviral therapy" }, { "docid": "2991954", "text": "Production of Ran-guanosine triphosphate (GTP) around chromosomes induces local nucleation and plus end stabilization of microtubules (MTs). The nuclear protein TPX2 is required for RanGTP-dependent MT nucleation. To find the MT stabilizer, we affinity purify nuclear localization signal (NLS)-containing proteins from Xenopus laevis egg extracts. This NLS protein fraction contains the MT stabilization activity. After further purification, we used mass spectrometry to identify proteins in active fractions, including cyclin-dependent kinase 11 (Cdk11). Cdk11 localizes on spindle poles and MTs in Xenopus culture cells and egg extracts. Recombinant Cdk11 demonstrates RanGTP-dependent MT stabilization activity, whereas a kinase-dead mutant does not. Inactivation of Cdk11 in egg extracts blocks RanGTP-dependent MT stabilization and dramatically decreases the spindle assembly rate. Simultaneous depletion of TPX2 completely inhibits centrosome-dependent spindle assembly. Our results indicate that Cdk11 is responsible for RanGTP-dependent MT stabilization around chromosomes and that this local stabilization is essential for normal rates of spindle assembly and spindle function.", "title": "Cdk11 is a RanGTP-dependent microtubule stabilization factor that regulates spindle assembly rate" }, { "docid": "1684489", "text": "BACKGROUND Production of the GTP-bound form of the Ran GTPase (RanGTP) around chromosomes induces spindle assembly by activating nuclear localization signal (NLS)-containing proteins. Several NLS proteins have been identified as spindle assembly factors, but the complexity of the process led us to search for additional proteins with distinct roles in spindle assembly. RESULTS We identify a chromatin-remodeling ATPase, CHD4, as a RanGTP-dependent microtubule (MT)-associated protein (MAP). MT binding occurs via the region containing an NLS and chromatin-binding domains. In Xenopus egg extracts and cultured cells, CHD4 largely dissociates from mitotic chromosomes and partially localizes to the spindle. Immunodepletion of CHD4 from egg extracts significantly reduces the quantity of MTs produced around chromatin and prevents spindle assembly. CHD4 RNAi in both HeLa and Drosophila S2 cells induces defects in spindle assembly and chromosome alignment in early mitosis, leading to chromosome missegregation. Further analysis in egg extracts and in HeLa cells reveals that CHD4 is a RanGTP-dependent MT stabilizer. Moreover, the CHD4-containing NuRD complex promotes organization of MTs into bipolar spindles in egg extracts. Importantly, this function of CHD4 is independent of chromatin remodeling. CONCLUSIONS Our results uncover a new role for CHD4 as a MAP required for MT stabilization and involved in generating spindle bipolarity.", "title": "CHD4 Is a RanGTP-Dependent MAP that Stabilizes Microtubules and Regulates Bipolar Spindle Formation" }, { "docid": "14145440", "text": "BACKGROUND DNA replication and mitosis are triggered by activation of kinase complexes, each made up of a cyclin and a cyclin-dependent kinase (Cdk). It had seemed possible that the association of Cdks with different classes of cyclins specifies whether S phase (replication) or M phase (mitosis) will occur. The recent finding that individual B-type cyclins (encoded by the genes CLB1-CLB6) can have functions in both processes in the budding yeast Saccharomyces cerevisiae casts doubt on this notion. RESULTS S. cerevisiae strains lacking C1b1-C1b4 undergo DNA replication once but fail to enter mitosis. We have isolated mutations in two genes, SIM1 and SIM2 (SIM2 is identical to SEC72), which allow such cells to undergo an extra round of DNA replication without mitosis. The Clb5 kinase, which promotes S phase, remains active during the G2-phase arrest of cells of the parental strain, but its activity declines rapidly in sim mutants. Increased expression of the CLB5 gene prevents re-replication. Thus, a cyclin B-kinase that promotes DNA replication in G1-phase cells can prevent re-replication in G2-phase cells. Inactivation of C1b kinases by expression of the specific C1b-Cdk1 inhibitor p40SIC1 is sufficient to induce a prereplicative state at origins of replication in cells blocked in G2/M phase by nocodazole. Re-activation of C1b-Cdk1 kinases induces a second round of DNA replication. CONCLUSIONS We propose that S-phase-promoting cyclin B--Cdk complexes prevent re-replication during S, G2 and M phases by inhibiting the transition of replication origins to a pre-replicative state. This model can explain both why origins 'fire' only once per S phase and why S phase is dependent on completion of the preceding M phase.", "title": "S-phase-promoting cyclin-dependent kinases prevent re-replication by inhibiting the transition of replication origins to a pre-replicative state" }, { "docid": "29863668", "text": "The P446L mutant Drosophila importin-beta (P446L-imp-beta) has been reported to prohibit--in dominant negative fashion--nuclear envelope (NE) assembly. Along elucidating the mode of action of P446L-imp-beta we studied in vitro NE assembly on Sepharose beads. While Drosophila embryo extracts support NE assembly over Sepharose beads coated with Ran, NE assembly does not take place in extracts supplied with exogenous P446L-imp-beta. A NE also forms over importin-beta-coated beads. Surprisingly, when immobilized to Sepharose beads P446L-imp-beta as efficiently recruits NE vesicles as normal importin-beta. The discrepancy in behavior of cytoplasmic and bead-bound P446L-imp-beta appears to be related to icreased--as compared to normal importin-beta--microtubule (MT) binding ability of P446L-imp-beta. While wild-type importin-beta is able to bind MTs and the binding decreases upon RanGTP interaction, P446L-imp-beta cannot be removed from the MTs by RanGTP. P446L-imp-beta, like normal importin-beta, binds some types of the nucleoporins that have been known to be required for NE assembly at the end of mitosis. It appears that the inhibitory effect of P446L-imp-beta on NE assembly is caused by sequestering some of the nucleoporins required for NE assembly to the MTs.", "title": "P446L-importin-beta inhibits nuclear envelope assembly by sequestering nuclear envelope assembly factors to the microtubules." }, { "docid": "8698857", "text": "TNF expression of macrophages is under stringent translational control that depends on the p38 MAPK/MK2 pathway and the AU-rich element (ARE) in the TNF mRNA. Here, we elucidate the molecular mechanism of phosphorylation-regulated translation of TNF. We demonstrate that translation of the TNF-precursor at the ER requires expression of the ARE-binding and -stabilizing factor human antigen R (HuR) together with either activity of the p38 MAPK/MK2 pathway or the absence of the ARE-binding and -destabilizing factor tristetraprolin (TTP). We show that phosphorylation of TTP by MK2 decreases its affinity to the ARE, inhibits its ability to replace HuR, and permits HuR-mediated initiation of translation of TNF mRNA. Since translation of TTP's own mRNA is also regulated by this mechanism, an intrinsic feedback control of the inflammatory response is ensured. The phosphorylation-regulated TTP/HuR exchange at target mRNAs provides a reversible switch between unstable/non-translatable and stable/efficiently translated mRNAs.", "title": "The p38/MK2-Driven Exchange between Tristetraprolin and HuR Regulates AU–Rich Element–Dependent Translation" }, { "docid": "39929509", "text": "Mutations in WT1 are associated with developmental syndromes that affect the urogenital system and neoplasms, including Wilms tumour, acute myeloid leukemia, and breast and prostate cancers. The WT1 protein belongs to the early growth response family of zinc-finger transcription factors. Uniquely to WT1, an evolutionarily conserved alternative splice event inserts the tripeptide KTS, between zinc fingers 3 and 4. Whereas -KTS isoforms bind DNA and activate or repress transcription, +KTS isoforms bind DNA less efficiently and interact with splice factors and RNA in vitro and in vivo. Although candidate DNA targets have been found, physiological mRNA targets are yet to be defined. We examined the distribution of WT1 in ribonucleoprotein (RNP) complexes in nuclear extract prepared from M15 cells, a mouse mesonephric fetal kidney cell line. WT1 cofractionated with the splice factor PSF in large RNP particles >or=2 MDa. We also found that PSF co-immunoprecipitated with WT1, suggesting a functional interaction between these 2 multifunctional proteins. Using yeast three-hybrid library constructed from the co-immunoprecipitated RNA we found that WT1 (+KTS) binds close to or at the start codon of alpha-actinin 1 (ACTN1) mRNA. A band shift assay confirmed the ability of the WT1 zinc-finger domain (+KTS) to bind this sequence in vitro. ACTN1 is the first likely physiological mRNA target of WT1.", "title": "The Wilms tumour suppressor protein WT1 (+KTS isoform) binds alpha-actinin 1 mRNA via its zinc-finger domain." }, { "docid": "23918031", "text": "The platelet precursor, the megakaryocyte, matures to a polyploid cell as a result of DNA replication in the absence of mitosis (endomitosis). The factors controlling endomitosis are accessible to analysis in our megakaryocytic cell line, MegT, generated by targeted expression of temperature-sensitive simian virus 40 large T antigen to megakaryocytes of transgenic mice. We aimed to define whether endomitosis consists of a continuous phase of DNA synthesis (S) or of S phases interrupted by gaps. Analysis of the cell cycle in MegT cells revealed that, upon inactivation of large T antigen, the cells shifted from a mitotic cell cycle to an endomitotic cell cycle consisting of S/Gap phases. The level of the G1/S cyclin, cyclin A, as well as of the G1 phase cyclin, cyclin D3, were elevated at the onset of DNA synthesis, either in MegT cells undergoing a mitotic cell cycle or during endomitosis. In contrast, the level of the mitotic cyclin, cyclin B1, cycled in cells displaying a mitotic cell cycle while not detectable during endomitosis. Comparable levels of the mitotic kinase protein, Cdc2, were detected during the mitotic cell cycle or during endomitosis; however, cyclin B1-dependent Cdc2 kinase activity was largely abolished in the polyploid cells. Fibroblasts immortalized with the same heat-labile oncogene do not display reduced levels of cyclin B1 upon shifting to high temperature nor do they become polyploid, indicating that reduced levels of cyclin B1 is a property of megakaryocytes and not of the T-antigen mutant. We conclude that cellular programming during endoreduplication in megakaryocytes is associated with reduced levels of cyclin B1.", "title": "The cell cycle in polyploid megakaryocytes is associated with reduced activity of cyclin B1-dependent cdc2 kinase." }, { "docid": "16736883", "text": "Kinetochores couple chromosomes to the assembling and disassembling tips of microtubules, a dynamic behavior that is fundamental to mitosis in all eukaryotes but poorly understood. Genetic, biochemical, and structural studies implicate the Ndc80 complex as a direct point of contact between kinetochores and microtubules, but these approaches provide only a static view. Here, using techniques for manipulating and tracking individual molecules in vitro, we demonstrate that the Ndc80 complex is capable of forming the dynamic, load-bearing attachments to assembling and disassembling tips required for coupling in vivo. We also establish that Ndc80-based coupling likely occurs through a biased diffusion mechanism and that this activity is conserved from yeast to humans. Our findings demonstrate how an ensemble of Ndc80 complexes may provide the combination of plasticity and strength that allows kinetochores to maintain load-bearing tip attachments during both microtubule assembly and disassembly.", "title": "The Ndc80 Kinetochore Complex Forms Load-Bearing Attachments to Dynamic Microtubule Tips via Biased Diffusion" }, { "docid": "1292369", "text": "Infectious prions propagate from peripheral entry sites into the central nervous system (CNS), where they cause progressive neurodegeneration that ultimately leads to death. Yet the pathogenesis of prion disease can vary dramatically depending on the strain, or conformational variant of the aberrantly folded and aggregated protein, PrP(Sc). Although most prion strains invade the CNS, some prion strains cannot gain entry and do not cause clinical signs of disease. The conformational basis for this remarkable variation in the pathogenesis among strains is unclear. Using mouse-adapted prion strains, here we show that highly neuroinvasive prion strains primarily form diffuse aggregates in brain and are noncongophilic, conformationally unstable in denaturing conditions, and lead to rapidly lethal disease. These neuroinvasive strains efficiently generate PrP(Sc) over short incubation periods. In contrast, the weakly neuroinvasive prion strains form large fibrillary plaques and are stable, congophilic, and inefficiently generate PrP(Sc) over long incubation periods. Overall, these results indicate that the most neuroinvasive prion strains are also the least stable, and support the concept that the efficient replication and unstable nature of the most rapidly converting prions may be a feature linked to their efficient spread into the CNS.", "title": "Biochemical Properties of Highly Neuroinvasive Prion Strains" }, { "docid": "4412772", "text": "Unicellular organisms such as yeasts require a single cyclin-dependent kinase, Cdk1, to drive cell division. In contrast, mammalian cells are thought to require the sequential activation of at least four different cyclin-dependent kinases, Cdk2, Cdk3, Cdk4 and Cdk6, to drive cells through interphase, as well as Cdk1 to proceed through mitosis. This model has been challenged by recent genetic evidence that mice survive in the absence of individual interphase Cdks. Moreover, most mouse cell types proliferate in the absence of two or even three interphase Cdks. Similar results have been obtained on ablation of some of the activating subunits of Cdks, such as the D-type and E-type cyclins. Here we show that mouse embryos lacking all interphase Cdks (Cdk2, Cdk3, Cdk4 and Cdk6) undergo organogenesis and develop to midgestation. In these embryos, Cdk1 binds to all cyclins, resulting in the phosphorylation of the retinoblastoma protein pRb and the expression of genes that are regulated by E2F transcription factors. Mouse embryonic fibroblasts derived from these embryos proliferate in vitro, albeit with an extended cell cycle due to inefficient inactivation of Rb proteins. However, they become immortal on continuous passage. We also report that embryos fail to develop to the morula and blastocyst stages in the absence of Cdk1. These results indicate that Cdk1 is the only essential cell cycle Cdk. Moreover, they show that in the absence of interphase Cdks, Cdk1 can execute all the events that are required to drive cell division.", "title": "Cdk1 is sufficient to drive the mammalian cell cycle" }, { "docid": "10692412", "text": "BACKGROUND Kulldorff's spatial scan statistic and its software implementation - SaTScan - are widely used for detecting and evaluating geographic clusters. However, two issues make using the method and interpreting its results non-trivial: (1) the method lacks cartographic support for understanding the clusters in geographic context and (2) results from the method are sensitive to parameter choices related to cluster scaling (abbreviated as scaling parameters), but the system provides no direct support for making these choices. We employ both established and novel geovisual analytics methods to address these issues and to enhance the interpretation of SaTScan results. We demonstrate our geovisual analytics approach in a case study analysis of cervical cancer mortality in the U.S. RESULTS We address the first issue by providing an interactive visual interface to support the interpretation of SaTScan results. Our research to address the second issue prompted a broader discussion about the sensitivity of SaTScan results to parameter choices. Sensitivity has two components: (1) the method can identify clusters that, while being statistically significant, have heterogeneous contents comprised of both high-risk and low-risk locations and (2) the method can identify clusters that are unstable in location and size as the spatial scan scaling parameter is varied. To investigate cluster result stability, we conducted multiple SaTScan runs with systematically selected parameters. The results, when scanning a large spatial dataset (e.g., U.S. data aggregated by county), demonstrate that no single spatial scan scaling value is known to be optimal to identify clusters that exist at different scales; instead, multiple scans that vary the parameters are necessary. We introduce a novel method of measuring and visualizing reliability that facilitates identification of homogeneous clusters that are stable across analysis scales. Finally, we propose a logical approach to proceed through the analysis of SaTScan results. CONCLUSION The geovisual analytics approach described in this manuscript facilitates the interpretation of spatial cluster detection methods by providing cartographic representation of SaTScan results and by providing visualization methods and tools that support selection of SaTScan parameters. Our methods distinguish between heterogeneous and homogeneous clusters and assess the stability of clusters across analytic scales. METHOD We analyzed the cervical cancer mortality data for the United States aggregated by county between 2000 and 2004. We ran SaTScan on the dataset fifty times with different parameter choices. Our geovisual analytics approach couples SaTScan with our visual analytic platform, allowing users to interactively explore and compare SaTScan results produced by different parameter choices. The Standardized Mortality Ratio and reliability scores are visualized for all the counties to identify stable, homogeneous clusters. We evaluated our analysis result by comparing it to that produced by other independent techniques including the Empirical Bayes Smoothing and Kafadar spatial smoother methods. The geovisual analytics approach introduced here is developed and implemented in our Java-based Visual Inquiry Toolkit.", "title": "Geovisual analytics to enhance spatial scan statistic interpretation: an analysis of U.S. cervical cancer mortality" }, { "docid": "17421851", "text": "BACKGROUND Interleukin (IL)-18 is a potent proinflammatory cytokine with potential atherogenic properties. Its expression and role in atherosclerosis, however, are unknown. METHODS AND RESULTS In the present study, we examined stable and unstable human carotid atherosclerotic plaques retrieved by endarterectomy for the presence of IL-18 using reverse transcription-polymerase chain reaction (PCR), Western blot, and immunohistochemical techniques. IL-18 was highly expressed in the atherosclerotic plaques compared with control normal arteries and was localized mainly in plaque macrophages. IL-18 receptor was also upregulated in plaque macrophages and endothelial cells, suggesting potential biological effects. To examine the role of IL-18 in atherosclerosis, we determined the relation between IL-18 mRNA expression and signs of plaque instability using real-time quantitative PCR. Interestingly, significantly higher levels of IL-18 mRNA were found in symptomatic (unstable) plaques than asymptomatic (stable) plaques (P<0.01). CONCLUSIONS These results suggest, for the first time, a major role for IL-18 in atherosclerotic plaque destabilization leading to acute ischemic syndromes.", "title": "Expression of interleukin-18 in human atherosclerotic plaques and relation to plaque instability." }, { "docid": "6812319", "text": "Chromosomal instability (CIN) is a hallmark of tumour initiation and progression. Some genomic regions are particularly unstable under replication stress, notably common fragile sites (CFSs) whose rearrangements in tumour cells contribute to cancer development. Recent work has shown that the Fanconi anaemia (FANC) pathway plays a role in preventing defective chromosome segregation and CIN under conditions of replication stress. Strikingly, FANCD2 is recruited to regions hosting CFSs on metaphase chromosomes. To decipher the mechanisms protecting CFSs in G2/M, we searched for proteins that co-localize with FANCD2 on mitotic chromosomes, and identified XPF–ERCC1 and MUS81–EME1, two structure-specific endonucleases. We show that depletion of either ERCC1 or MUS81–EME1 affects accurate processing of replication intermediates or under-replicated DNA that persist at CFSs until mitosis. Depletion of these endonucleases also leads to an increase in the frequency of chromosome bridges during anaphase that, in turn, favours accumulation of DNA damage in the following G1 phase.", "title": "ERCC1 and MUS81–EME1 promote sister chromatid separation by processing late replication intermediates at common fragile sites during mitosis" }, { "docid": "7114092", "text": "Megakaryocyte (MK) is the naturally polyploid cell that gives rise to platelets. Polyploidization occurs by endomitosis, which was a process considered to be an incomplete mitosis aborted in anaphase. Here, we used time-lapse confocal video microscopy to visualize the endomitotic process of primary human megakaryocytes. Our results show that the switch from mitosis to endomitosis corresponds to a late failure of cytokinesis accompanied by a backward movement of the 2 daughter cells. No abnormality was observed in the central spindle of endomitotic MKs. A furrow formation was present, but the contractile ring was abnormal because accumulation of nonmuscle myosin IIA was lacking. In addition, a defect in cell elongation was observed in dipolar endomitotic MKs during telophase. RhoA and F-actin were partially concentrated at the site of furrowing. Inhibition of the Rho/Rock pathway caused the disappearance of F-actin at midzone and increased MK ploidy level. This inhibition was associated with a more pronounced defect in furrow formation as well as in spindle elongation. Our results suggest that the late failure of cytokinesis responsible for the endomitotic process is related to a partial defect in the Rho/Rock pathway activation.", "title": "From bloodjournal.hematologylibrary.org at PENN STATE UNIVERSITY on February 23, 2013. For personal use only." }, { "docid": "4899981", "text": "Telomeres resemble common fragile sites (CFSs) in that they are difficult-to-replicate and exhibit fragility in mitosis in response to DNA replication stress. At CFSs, this fragility is associated with a delay in the completion of DNA replication until early mitosis, whereupon cells are proposed to switch to a RAD52-dependent form of break-induced replication. Here, we show that this mitotic DNA synthesis (MiDAS) is also a feature of human telomeres. Telomeric MiDAS is not restricted to those telomeres displaying overt fragility, and is a feature of a wide range of cell lines irrespective of whether their telomeres are maintained by telomerase or by the alternative lengthening of telomeres (ALT) mechanism. MiDAS at telomeres requires RAD52, and is mechanistically similar to CFS-associated MiDAS, with the notable exception that telomeric MiDAS does not require the MUS81-EME1 endonuclease. We propose a model whereby replication stress initiates a RAD52-dependent form of break-induced replication that bypasses a requirement for MUS81-EME1 to complete DNA synthesis in mitosis.", "title": "Human cancer cells utilize mitotic DNA synthesis to resist replication stress at telomeres regardless of their telomere maintenance mechanism" }, { "docid": "25742205", "text": "RanBP type proteins have been reported to increase the catalytic efficiency of the RanGAP-mediated GTPase reaction on Ran. Since the structure of the Ran-RanBP1-RanGAP complex showed RanBP1 to be located away from the active site, we reinvestigated the reaction using fluorescence spectroscopy under pre-steady-state conditions. We can show that RanBP1 indeed does not influence the rate-limiting step of the reaction, which is the cleavage of GTP and/or the release of product P(i). It does, however, influence the dynamics of the Ran-RanGAP interaction, its most dramatic effect being the 20-fold stimulation of the already very fast association reaction such that it is under diffusion control (4.5 x 10(8) M(-1) s(-1)). Having established a valuable kinetic system for the interaction analysis, we also found, in contrast to previous findings, that the highly conserved acidic C-terminal end of RanGAP is not required for the switch-off reaction. Rather, genetic experiments in Saccharomyces cerevisiae demonstrate a profound effect of the acidic tail on microtubule organization during mitosis. We propose that the acidic tail of RanGAP is required for a process during mitosis.", "title": "Biochemical characterization of the Ran-RanBP1-RanGAP system: are RanBP proteins and the acidic tail of RanGAP required for the Ran-RanGAP GTPase reaction?" }, { "docid": "19332616", "text": "Coronary atherosclerosis is by far the most frequent cause of ischemic heart disease, and plaque disruption with superimposed thrombosis is the main cause of the acute coronary syndromes of unstable angina, myocardial infarction, and sudden death.1 2 3 4 5 Therefore, for event-free survival, the vital question is not why atherosclerosis develops but rather why, after years of indolent growth, it suddenly becomes complicated by life-threatening thrombosis. The composition and vulnerability of plaque rather than its volume or the consequent severity of stenosis produced have emerged as being the most important determinants for the development of the thrombus-mediated acute coronary syndromes; lipid-rich and soft plaques are more dangerous than collagen-rich and hard plaques because they are more unstable and rupture-prone and highly thrombogenic after disruption.6 This review will explore potential mechanisms responsible for the sudden conversion of a stable atherosclerotic plaque to an unstable and life-threatening atherothrombotic lesion—an event known as plaque fissuring, rupture, or disruption.7 8 Atherosclerosis is the result of a complex interaction between blood elements, disturbed flow, and vessel wall abnormality, involving several pathological processes: inflammation, with increased endothelial permeability, endothelial activation, and monocyte recruitment9 10 11 12 13 14 ; growth, with smooth muscle cell (SMC) proliferation, migration, and matrix synthesis15 16 ; degeneration, with lipid accumulation17 18 ; necrosis, possibly related to the cytotoxic effect of oxidized lipid19 ; calcification/ossification, which may represent an active rather than a dystrophic process20 21 ; and thrombosis, with platelet recruitment and fibrin formation.1 22 23 Thrombotic factors may play a role early during atherogenesis, but a flow-limiting thrombus does not develop until mature plaques are present, which is why thrombosis often is classified as a complication rather than a genuine component of atherosclerosis. ### Mature Plaques: Atherosis and Sclerosis As the name atherosclerosis implies, mature …", "title": "Coronary plaque disruption." } ]
PLAIN-1944
prostate health
[ { "docid": "MED-3738", "text": "The human health benefits from consumption of cranberry products have been associated with the fruits' unique flavonoid composition, including a complex profile of anthocyanins and proanthocyanidins. However, when processed by techniques such as pressing, canning, concentrating, or drying, a number of these natural components may be compromised or inactivated due to physical separation, thermal degradation, or oxidation. Fresh cranberries were compared to freeze-dried berries and individual fruit tissues (skin and peeled fruit). Products examined included cranberry juices (commercial and prepared from concentrate), cranberry sauces (commercial and homemade), and sweetened-dried cranberries (commercial). Freeze-drying resulted in no detectable losses of anthocyanins or proanthocyanidins from cranberry fruits. Anthocyanins were localized in the skin. Proanthocyanins were higher in the skin than in the flesh, with the exception of procyanidin A-2 dimer which was concentrated in the flesh. Anthocyanins were significantly higher in not-from-concentrate juice than in reconstituted juice from concentrate (8.3 mg and 4.2 mg/100 mL, respectively). Similarly, proanthocyanidins were markedly higher in not-from-concentrate juice compared to juice from concentrate (23.0 mg and 8.9 mg/100 mL, respectively). Homemade sauce contained far higher anthocyanins and proanthocyanidins (15.9 and 87.9 mg/100 g, respectively) than canned sauces processed with whole berries (9.6 and 54.4 mg/100 g, respectively) or jelled-type (1.1 and 16 mg/100 g, respectively). Sweetened-dried cranberries were quite low in anthocyanins (7.9 mg/100 g), but they still retained considerable proanthocyanidins (64.2 mg/100 g). Commercially processed products contained significantly lower levels of polyphenols as compared to fresh and home-processed preparations. Anthocyanins were more sensitive to degradation than proanthocyanidins. PRACTICAL APPLICATION: As cranberry juices and other products are increasingly consumed for their recognized health benefits (including prophylaxis against urinary tract infection), it is relevant to consider how various degrees of commercial and home processing can alter innate levels of the biologically active flavonoids (especially anthocyanins and proanthocyanidins) characteristic to the intact fruits. © 2012 Institute of Food Technologists®", "title": "Comparison of health-relevant flavonoids in commonly consumed cranberry products." }, { "docid": "MED-2644", "text": "Alkylphenols are widely used as plastic additives and surfactants. We report the identification of an alkylphenol, nonylphenol, as an estrogenic substance released from plastic centrifuge tubes. This compound was extracted with methanol, purified by flash chromatography and reverse-phase high performance liquid chromatography, and identified by gas chromatography-mass spectrometry. Nonylphenol induced both cell proliferation and progesterone receptor in human estrogen-sensitive MCF7 breast tumor cells. Nonylphenol also triggered mitotic activity in rat endometrium; this result confirms the reliability of the MCF7 cell proliferation bioassay. The estrogenic properties of alkylphenols, specifically nonylphenols, indicate that the use of plasticware containing these chemicals in experimental and diagnostic tests may lead to spurious results, and these compounds as well as alkylphenol polyethoxylates may also be potentially harmful to exposed humans and the environment at large.", "title": "p-Nonyl-phenol: an estrogenic xenobiotic released from \"modified\" polystyrene." }, { "docid": "MED-2774", "text": "Concern has been expressed about the fact that cows' milk contains estrogens and could stimulate the growth of hormone-sensitive tumors. In this study, organic cows' milk and two commercial substitutes were digested in vitro and tested for their effects on the growth of cultures of prostate and breast cancer cells. Cows' milk stimulated the growth of LNCaP prostate cancer cells in each of 14 separate experiments, producing an average increase in growth rate of over 30%. In contrast, almond milk suppressed the growth of these cells by over 30%. Neither cows' milk nor almond milk affected the growth of MCF-7 breast cancer cells or AsPC-1 pancreatic cancer cells significantly. Soy milk increased the growth rate of the breast cancer cells. These data indicate that prostate and breast cancer patients should be cautioned about the possible promotional effects of commercial dairy products and their substitutes.", "title": "Milk stimulates growth of prostate cancer cells in culture." }, { "docid": "MED-4239", "text": "BACKGROUND: Prostate cancer is the most common solid-tumor cancer in US males but is rare in Asian males. When Asian men adopt the US lifestyle, clinical prostate cancer increases greatly. Epidemiological data from men in the US indicate that regular activity may reduce the risk for prostate cancer. METHODS: Serum was obtained from three groups of similar-aged men, Control, Diet and Exercise, and Exercise alone were used to stimulate LNCaP cells in culture. Growth and apoptosis of tumor cells were measured. Serum samples were also used to measure insulin, IGF-1, IGFBP-1. RESULTS: The Diet and Exercise and the Exercise alone groups had lower serum insulin and IGF-1 but higher IGFBP-1 compared to Controls. LNCaP cell growth was reduced in both groups compared to Control and there was a major increase in apoptosis of tumor cells. CONCLUSIONS: A low-fat diet and/or intensive exercise results in change in serum hormones and growth factors in vivo that can reduce growth and induce apoptosis of LNCaP prostate tumor cells in vitro. Copyright 2003 Wiley-Liss, Inc.", "title": "A low-fat diet and/or strenuous exercise alters the IGF axis in vivo and reduces prostate tumor cell growth in vitro." }, { "docid": "MED-2652", "text": "The exposure to some chemicals can lead to hormone disrupting effects. Presently, much attention is focused on so-called xeno-estrogens, synthetic compounds that interact with hormone receptors causing a number of reactions that eventually lead to effects related to reproduction and development. The current study was initiated to investigate the presence of a number of such compounds in precipitation as a follow-up on a previous study in which pesticide concentrations in air and precipitation were determined. Rainwater samples were collected at about 50 locations in The Netherlands in a four week period. The samples were analysed for bisphenol-A, alkylphenols and alkylphenol ethoxylates, phthalates, flame retardants and synthetic musk compounds. The results clearly indicated the presence of these compounds in precipitation. The concentrations ranged from the low ng l(-1) range for flame retardants to several thousands of ng l(-1) for the phthalates. Bisphenol-A was found in 30% of the samples in concentrations up to 130 ng l(-1), while alkylphenols and alkylphenol ethoxylates were found in virtually all locations in concentrations up to 920 ng l(-1) for the individual compounds. Phthalates were by far the most abundant xeno-estrogens in the precipitation samples and were found in every sample. Di-isodecyl phthalate was found in a surprisingly high concentration of almost 100 000 ng l(-1). Polybrominated flame retardants were found in the low ng l(-1) range and generally in less than 20% of the samples. Noticeable was the finding of hexabromocyclododecane, a replacement for the polybrominted diphenyl ethers at one location in a concentration of almost 2000 ng l(-1). Finally, as expected, synthetic musk compounds were detected in almost all samples. This is especially true for the polycyclic musks HHCB and AHTN. Nitro musks were found, but only on a few locations. Kriging techniques were used to calculate precipitation concentrations in between actual sampling locations to produce contour plots for a number of compounds. These plots clearly show located emission sources for a number of compounds such as bisphenol-A, nonylphenol ethoxylate, phthalates and AHTN. On the contrary, the results for HHCB and some phthalates indicated diffuse emission patterns, probably as the result of the use of consumer products containing these compounds.", "title": "Xeno-estrogenic compounds in precipitation." }, { "docid": "MED-4234", "text": "It has long been appreciated that a healthy lifestyle plays a critical role in cardiovascular health. It is now apparent that the same is true in the development of benign prostatic hyperplasia (BPH). Prospective cohort data originating from recently published randomized trials on the medical treatment of BPH and prevention of prostate cancer have been invaluable. A growing body of evidence suggests that exercise and the intake of specific macronutrients and micronutrients through regular diet play a beneficial role. Most strikingly, the magnitude of these effects is similar to medical therapies using alpha-blockers and 5-alpha-reductase inhibitors. The use of supplements for prostate disease is a multibillion dollar business in the United States, and supplements are more commonly prescribed than medical therapy in many countries. In contrast to consumption of micronutrients through regular diet, supplemental intake of micronutrients and phytotherapies currently lack evidence to support their efficacy.", "title": "Dietary patterns, supplement use, and the risk of benign prostatic hyperplasia." }, { "docid": "MED-2655", "text": "Background Broad dietary patterns have been linked to asthma but the relative contribution of specific nutrients is unclear. Soy genistein has important anti-inflammatory and other biological effects that might be beneficial in asthma. A positive association was previously reported between soy genistein intake and lung function but not with asthma exacerbations. Aims To conduct a post-hoc analysis of patients with inadequately controlled asthma enrolled in a prospective multicentre clinical trial to replicate this association. Methods A total of 300 study participants were included in the analysis. Dietary soy genistein intake was measured using the Block Soy Foods Screener. The level of soy genistein intake (little or no intake, moderate intake, or high intake) was compared with baseline lung function (pre-bronchodilator forced expiratory volume in 1 second (FEV1)) and asthma control (proportion of participants with an episode of poor asthma control (EPAC) and annualised rates of EPACs over a 6-month follow-up period. Results Participants with little or no genistein intake had a lower baseline FEV1 than those with a moderate or high intake (2.26L vs. 2.53L and 2.47L, respectively; p=0.01). EPACs were more common among those with no genistein intake than in those with a moderate or high intake (54% vs. 35% vs. 40%, respectively; p<0.001). These findings remained significant after adjustment for patient demographics and body mass index. Conclusions In patients with asthma, consumption of a diet with moderate to high amounts of soy genistein is associated with better lung function and better asthma control.", "title": "Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial" }, { "docid": "MED-2794", "text": "Turmeric, a plant rhizome that is often dried, ground and used as a cooking spice, has also been used medicinally for several thousand years. Curcumin, the phytochemical that gives turmeric its golden color, is responsible for most of the therapeutic effects of turmeric. In recent years curcumin has been studied for its effects on chronic diseases such as diabetes, Alzheimer's, and cancer. Though many researchers are investigating turmeric/curcumin in cancer therapy, there is little epidemiologic information on the effects of turmeric consumption. With limited availability of pharmacologic interventions in many areas of the world, use of turmeric in the diet may help to alleviate some of the disease burden through prevention. Here we provide a brief overview of turmeric consumption in different parts of the world, cancer rates in those regions, possible biochemical mechanisms by which turmeric acts and practical recommendations based on the information available.", "title": "Dietary turmeric potentially reduces the risk of cancer." }, { "docid": "MED-2660", "text": "BACKGROUND: Rapid socioeconomic development in Japan since the beginning of the Seven Countries Study in 1958 has brought remarkable changes in lifestyle and dietary patterns. We investigated the relationship between time trends in nutrient intake and serum cholesterol levels in a Japanese cohort of the Seven Countries Study, in Tanushimaru, a typical farming town on Kyushu Island. METHODS: Subjects totaled 628 in 1958, 539 in 1977, 602 in 1982, 752 in 1989, and 402 in 1999, and all of the subjects were men aged 40-64 years. Eating patterns were evaluated by 24-hour dietary recall from 1958 through 1989, and by a food frequency questionnaire in 1999. We also measured serum cholesterol levels in each health examination. RESULTS: The total daily energy intake decreased from 2837 kcal in 1958 to 2202 kcal in 1999. The carbohydrate intake in percentage of total daily energy intake decreased markedly, from 84% in 1958 to 62% in 1999, in contrast to large increases during this period in protein intake (from 11% to 18%) and fat intake (from 5% to 20%). In proportion to the dramatic change in protein and fat intake, serum cholesterol levels showed large increases (from 152.5mg/dl to 194.2 mg/ dL). CONCLUSIONS: In spite of such big dietary changes toward a westernized diet, the incidence of coronary artery disease in a rural Japanese area remains low. However, careful surveillance is needed in the future because of the remarkably increasing intake of fats, especially saturated fatty acids.", "title": "Trends in nutritional intake and serum cholesterol levels over 40 years in Tanushimaru, Japanese men." }, { "docid": "MED-3878", "text": "Diet, nutritional status, and certain dietary supplements are postulated to influence the development and progression of prostate cancer. Angiogenesis and inflammation are central to tumor growth and progression, but the effect of diet on these processes remains uncertain. We explored changes in 50 plasma cytokines and angiogenic factors (CAFs) in 145 men with prostate cancer enrolled in a pre-operative, randomized controlled phase-II trial with four arms: control (usual diet); low-fat (LF) diet; flaxseed-supplemented (FS) diet; and flaxseed-supplemented, low-fat diet. The mean duration of dietary intervention was 30–31 days. Among the individual arms, the largest number of significant changes (baseline vs pre-operative follow-up) was observed in the LF arm, with 19 CAFs decreasing and one increasing (p<.05). Compared to the control arm, 6 CAFs—including pro-angiogenic factors (stromal-cell derived-1α and myeloid factors (granulocyte-colony-stimulating factor, macrophage colony-stimulating factor — all decreased in the LF arm compared to controls; 3 and 4 CAFs changed in the FS and FS+LF arms, respectively. Weight loss occurred in the LF arms and significantly correlated with VEGF decreases (P <0.001). The CAFs that changed in the LF arm are all known to be regulated by nuclear factor-kappa B (NF-κB), and a pathway analysis identified NF-κB as the most likely regulatory network associated with these changes in the LF arm, but not in the FS-containing arms. These results suggest that a low-fat diet without flaxseed may reduce levels of specific inflammatory cytokines and angiogenic factors and suggests that the NF-κB pathway may be a mediator of these changes.", "title": "Effect of Low-fat Diets on Plasma Levels of NFκB-regulated Inflammatory Cytokines and Angiogenic Factors in Men with Prostate Cancer" }, { "docid": "MED-3790", "text": "Background: Processed meat and fish have been shown to be associated with the risk of advanced prostate cancer, but few studies have examined diet after prostate cancer diagnosis and risk of its progression. Objective: We examined the association between postdiagnostic consumption of processed and unprocessed red meat, fish, poultry, and eggs and the risk of prostate cancer recurrence or progression. Design: We conducted a prospective study in 1294 men with prostate cancer, without recurrence or progression as of 2004–2005, who were participating in the Cancer of the Prostate Strategic Urologic Research Endeavor and who were followed for an average of 2 y. Results: We observed 127 events (prostate cancer death or metastases, elevated prostate-specific antigen concentration, or secondary treatment) during 2610 person-years. Intakes of processed and unprocessed red meat, fish, total poultry, and skinless poultry were not associated with prostate cancer recurrence or progression. Greater consumption of eggs and poultry with skin was associated with 2-fold increases in risk in a comparison of extreme quantiles: eggs [hazard ratio (HR): 2.02; 95% CI: 1.10, 3.72; P for trend = 0.05] and poultry with skin (HR: 2.26; 95% CI: 1.36, 3.76; P for trend = 0.003). An interaction was observed between prognostic risk at diagnosis and poultry. Men with high prognostic risk and a high poultry intake had a 4-fold increased risk of recurrence or progression compared with men with low/intermediate prognostic risk and a low poultry intake (P for interaction = 0.003). Conclusions: Our results suggest that the postdiagnostic consumption of processed or unprocessed red meat, fish, or skinless poultry is not associated with prostate cancer recurrence or progression, whereas consumption of eggs and poultry with skin may increase the risk.", "title": "Intakes of meat, fish, poultry, and eggs and risk of prostate cancer progression" }, { "docid": "MED-4652", "text": "Ductal carcinoma in situ (DCIS) refers to breast epithelial cells that have become \"cancerous\" but still reside in their normal place in the ducts and lobules. In this setting, cancerous means that there is an abnormal increase in the growth of the epithelial cells, which accumulate within and greatly expand the ducts and lobules. DCIS is a nonlethal type of cancer because it stays in its normal place. However, DCIS is very important because it is the immediate precursor of invasive breast cancers, which are potentially lethal. This article provides a general overview of DCIS, including historical perspective, methods of classification, current perspective, and future goals.", "title": "Ductal carcinoma in situ: terminology, classification, and natural history." }, { "docid": "MED-3781", "text": "In this study, a panel of normal human prostate cells (HPCs) and tumor cells derived from metastases were studied by (1)H NMR spectroscopy to determine whether the malignant transformation of HPCs results in the elevation of choline compounds. Although an elevated choline signal has been observed previously in clinical studies, the contribution of the different Cho compounds to this elevation, as well as their quantification, has not been established until now. Here we have shown that HPCs derived from metastases exhibit significantly higher phosphocholine as well as glycerophosphocholine levels compared with normal prostate epithelial and stromal cells. Thus the elevation of the choline peak observed clinically in prostate cancer is attributable to an alteration of phospholipid metabolism and not simply to increased cell density, doubling time, or other nonspecific effects. Androgen deprivation of the androgen receptor-positive cell lines resulted in a significant increase of choline compounds after chronic androgen deprivation of the LNCaP cell line and in a decrease of choline compounds after a more acute androgen deprivation of the LAPC-4 cell line. These data strongly support the use of proton magnetic resonance spectroscopic imaging to detect the presence of prostate cancer for diagnosis, to detect response subsequent to androgen ablation therapy, and to detect recurrence.", "title": "Detection of increased choline compounds with proton nuclear magnetic resonance spectroscopy subsequent to malignant transformation of human prosta..." }, { "docid": "MED-2657", "text": "BACKGROUND: Japanese cedar pollinosis, caused by the pollen of the Japanese cedar tree (Cryptomeria japonica), is the commonest seasonal allergic disease in Japan. A number of epidemiological surveys have been reported on Japanese cedar pollinosis, but it has never been assessed systematically or quantitatively. To confirm the increasing prevalence of Japanese cedar pollinosis and related factors, we conducted a meta-regression analysis on population-based surveys in Japan. METHODS: We searched for data from population-based surveys in which serological methods were used to test all participants. Weighted regression of logit-transformed prevalence and sensitization rates were used to evaluate the effects of the year of survey, age, and degree of urbanization. We also analyzed the relationship between prevalence and sensitization rate. RESULTS: Thirty-eight reports with 27 subgroups for prevalence and 134 subgroups for sensitization rate were selected from the literature published in the years between 1986 and 2000. The Japanese cedar pollen sensitization rate was found to be significantly correlated with the year of survey, age, and degree of urbanization (adjusted R(2) = 0.55). The coefficient for the correlation between the prevalence and the sensitization rate revealed a statistically significant correlation (Pearson's r = 0.70, p < 0.001). CONCLUSIONS: The prevalence of Japanese cedar pollinosis among adolescents was predicted to be 28.7% in metropolitan areas and 24.5% in the general population in urban areas in the year 2004, derived from the estimated sensitization rate and the relationship between sensitization rate and prevalence. The prevalence of Japanese cedar pollinosis increased 2.6-fold between 1980 and 2000, and the prevalence differed considerably according to age and degree of urbanization. Copyright (c) 2005 S. Karger AG, Basel", "title": "Increasing prevalence of Japanese cedar pollinosis: a meta-regression analysis." }, { "docid": "MED-3877", "text": "OBJECTIVES: Dietary factors may influence the prostate and have an impact on prostatic growth and disease. A small number of studies have suggested that flaxseed-supplemented, fat-restricted diets may thwart prostate cancer growth in both animals and humans. Unknown, however, is the potential effect of such a diet on benign prostatic epithelium. METHODS: We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet affects the proliferation rates in benign epithelium. We also explored the effects on circulating levels of prostate-specific antigen (PSA), total testosterone, and cholesterol. Fifteen men who were scheduled to undergo repeat prostate biopsy were instructed to follow a low-fat (less than 20% kcal), flaxseed-supplemented (30 g/day) diet and were provided with a supply of flaxseed to last throughout the 6-month intervention period. The PSA, total testosterone, and cholesterol levels were determined at baseline and at 6 months of follow-up. Reports from the original and repeat biopsies were compared, and proliferation (MIB-1) rates were quantified in the benign prostatic epithelium. RESULTS: Statistically significant decreases in PSA (8.47 +/- 3.82 to 5.72 +/- 3.16 ng/mL; P = 0.0002) and cholesterol (241.1 +/- 30.8 to 213.3 +/- 51.2 mg/dL; P = 0.012) were observed. No statistically significant change was seen in total testosterone (434.5 +/- 143.6 to 428.3 +/- 92.5 ng/dL). Although 6-month repeat biopsies were not performed in 2 cases because of PSA normalization, of the 13 men who underwent repeat biopsy, the proliferation rates in the benign epithelium decreased significantly from 0.022 +/- 0.027 at baseline to 0.007 +/- 0.014 at 6 months of follow-up (P = 0.0168). CONCLUSIONS: These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect the biology of the prostate and associated biomarkers. A randomized controlled trial is needed to determine whether flaxseed supplementation, a low-fat diet, or a combination of the two regimens may be of use in controlling overall prostatic growth.", "title": "Pilot study to explore effects of low-fat, flaxseed-supplemented diet on proliferation of benign prostatic epithelium and prostate-specific antigen." }, { "docid": "MED-2771", "text": "We have previously found a positive association between milk consumption and prostate cancer risk using meta-analysis to analyze published case-control studies. In the present study, further meta-analysis was conducted to estimate the summary relative risk (RR) between the consumption of milk and dairy products and prostate cancer from cohort studies published between 1966- 2006. We found 18 relevant articles and 13 independent studies were available for our analysis. The summary RR was 1.13 (95% confidence interval = 1.02-1.24) when comparing the highest with the lowest quantile of consumption. The summary RRs by study stratification showed a positive association. A dose-response relationship was identified when combining the studies that partitioned the consumption by quintiles. We also evaluated the effects of some limitations, such as dairy classification, prostate cancer stages and publication bias, in the present study. These findings, together with the previous study, suggest that the consumption of milk and dairy products increases the risk of prostate cancer. This is biologically plausible since milk contains considerable amounts of fat, hormones, and calcium that are associated with prostate cancer risk.", "title": "Milk consumption is a risk factor for prostate cancer in Western countries: evidence from cohort studies." }, { "docid": "MED-5337", "text": "PURPOSE: Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS AND METHODS: Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group. RESULTS: None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. CONCLUSIONS: Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.", "title": "Intensive lifestyle changes may affect the progression of prostate cancer." }, { "docid": "MED-3919", "text": "The steroid hormone output of the adrenal gland is crucial in the maintenance of hormonal homeostasis, with hormonal imbalances being associated with numerous clinical conditions which include, amongst others, hypertension, metabolic syndrome, cardiovascular disease, insulin resistance and type 2 diabetes. Aspalathus linearis (Rooibos), which has been reported to aid stress-related symptoms linked to metabolic diseases, contains a wide spectrum of bioactive phenolic compounds of which aspalathin is unique. In this study the inhibitory effects of Rooibos and the dihydrochalcones, aspalathin and nothofagin, were investigated on adrenal steroidogenesis. The activities of both cytochrome P450 17α-hydroxylase/17,20 lyase and cytochrome P450 21-hydroxylase were significantly inhibited in COS-1 cells. In order to study the effect of these compounds in H295R cells, a human adrenal carcinoma cell line, a novel UPLC-MS/MS method was developed for the detection and quantification of twenty-one steroid metabolites using a single chromatographic separation. Under both basal and forskolin-stimulated conditions, the total amount of steroids produced in H295R cells significantly decreased in the presence of Rooibos, aspalathin and nothofagin. Under stimulated conditions, Rooibos decreased the total steroid output 4-fold and resulted in a significant reduction of aldosterone and cortisol precursors. Dehydroepiandrosterone-sulfate levels were unchanged, while the levels of androstenedione (A4) and 11β-hydroxyandrostenedione (11βOH-A4) were inhibited 5.5 and 2.3-fold, respectively. Quantification of 11βOH-A4 showed this metabolite to be a major product of steroidogenesis in H295R cells and we confirm, for the first time, that this steroid metabolite is the product of the hydroxylation of A4 by human cytochrome P450 11β-hydroxylase. Taken together our results demonstrate that Rooibos, aspalathin and nothofagin influence steroid hormone biosynthesis and the flux through the mineralocorticoid, glucocorticoid and androgen pathways, thus possibly contributing to the alleviation of negative effects arising from elevated glucocorticoid levels. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "The influence of Aspalathus linearis (Rooibos) and dihydrochalcones on adrenal steroidogenesis: quantification of steroid intermediates and end pro..." }, { "docid": "MED-4759", "text": "The human serum Sex Hormone-Binding Globulin (SHBG) plays an important role in breast cancer pathophysiology and risk definition, since it regulates the bioavailable fraction of circulating estradiol. We here summarize data reported over the years concerning the involvement of SHBG and SHBG polymorphisms in the definition of breast cancer risk. We also report what is known about the direct action of SHBG in breast cancer cells, illustrating its interaction with these cells and the subsequent initiation of a specific intracellular pathway leading to cross-talk with the estradiol-activated pathway and, finally, to the inhibition of several effects of estradiol in breast cancer cells. In conclusion, as a result of its unique property of regulating the estrogen free fraction and cross-talking with the estradiol pathways, by inhibiting estradiol-induced breast cancer cell growth and proliferation, SHBG is associated with a reduced risk of developing the neoplasm after estrogen exposure. 2009 Elsevier Ireland Ltd. All rights reserved.", "title": "Sex Hormone-Binding Globulin (SHBG), estradiol and breast cancer." }, { "docid": "MED-2815", "text": "Curcumin, an active polyphenol of the golden spice turmeric, is a highly pleiotropic molecule with the potential to modulate the biological activity of a number of signaling molecules. Traditionally, this polyphenol has been used in Asian countries to treat such human ailments as acne, psoriasis, dermatitis, and rash. Recent studies have indicated that curcumin can target newly identified signaling pathways including those associated with microRNA, cancer stem cells, and autophagy. Extensive research from preclinical and clinical studies has delineated the molecular basis for the pharmaceutical uses of this polyphenol against cancer, pulmonary diseases, neurological diseases, liver diseases, metabolic diseases, autoimmune diseases, cardiovascular diseases, and numerous other chronic diseases. Multiple studies have indicated the safety and efficacy of curcumin in numerous animals including rodents, monkeys, horses, rabbits, and cats and have provided a solid basis for evaluating its safety and efficacy in humans. To date, more than 65 human clinical trials of curcumin, which included more than 1000 patients, have been completed, and as many as 35 clinical trials are underway. Curcumin is now used as a supplement in several countries including the United States, India, Japan, Korea, Thailand, China, Turkey, South Africa, Nepal, and Pakistan. In this review, we provide evidence for the pharmaceutical uses of curcumin for various diseases. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.", "title": "Curcumin, a component of turmeric: from farm to pharmacy." }, { "docid": "MED-3782", "text": "Red and processed meat may increase risk of advanced prostate cancer. Data on post-diagnostic diet and prostate cancer are sparse, but post-diagnostic intake of poultry with skin and eggs may increase risk of disease progression. Therefore, we prospectively examined total, unprocessed, and processed red meat, poultry, and eggs in relation to risk of lethal prostate cancer (e.g. men without cancer at baseline who developed distant organ metastases or died from prostate cancer during follow-up) among 27, 607 men followed from 1994–2008. We also performed a case-only survival analysis to examine post-diagnostic consumption of these foods and risk of lethal prostate cancer among the 3,127 men initially diagnosed with non-metastatic prostate cancer during follow-up. In the incidence analysis, we observed 199 events during 306,715 person-years. Men who consumed 2.5 or more eggs per week had an 81% increased risk of lethal prostate cancer compared to men who consumed less than 0.5 eggs per week (HR: 1.81; 95% confidence interval (CI): 1.13, 2.89; p-trend: 0.01). In the case-only survival analysis, we observed 123 events during 19,354 person-years. There were suggestive, but not statistically significant, positive associations between post-diagnostic poultry (HR ≥3.5 vs. <1.5 servings per week: 1.69; 95%CI: 0.96, 2.99; p-trend: 0.07) and post-diagnostic processed red meat (HR ≥3 vs. <0.5 servings per week: 1.45; 95%CI: 0.73, 2.87; p-trend: 0.08) and risk of progression of localized prostate cancer to lethal disease. In conclusion, consumption of eggs may increase risk of developing a lethal-form of prostate cancer among healthy men.", "title": "Egg, red meat, and poultry intake and risk of lethal prostate cancer in the prostate specific antigen-era: incidence and survival" }, { "docid": "MED-4977", "text": "Background/Aim Harmane [1-methyl-9H-pyrido(3,4-b)indole] is a tremor-producing neurotoxin. Blood harmane concentrations are elevated in essential tremor (ET) patients for unclear reasons. Potential mechanisms include increased dietary harmane intake (especially through well-cooked meat) or genetic-metabolic factors. We tested the hypothesis that meat consumption and level of meat doneness are higher in ET cases than in controls. Methods Detailed data were collected using the Lawrence Livermore National Laboratory Meat Questionnaire. Results Total current meat consumption was greater in men with than without ET (135.3 ± 71.1 vs. 110.6 ± 80.4 g/day, p = 0.03) but not in women with versus without ET (80.6 ± 50.0 vs. 79.3 ± 51.0 g/day, p = 0.76). In an adjusted logistic regression analysis in males, higher total current meat consumption was associated with ET (OR = 1.006, p = 0.04, i.e., with 10 additional g/day of meat, odds of ET increased by 6%). Male cases had higher odds of being in the highest than lowest quartile of total current meat consumption (adjusted OR = 21.36, p = 0.001). Meat doneness level was similar in cases and controls. Conclusion This study provides evidence of a dietary difference between male ET cases and male controls. The etiological ramifications of these results warrant additional investigation. Copyright © 2008 S. Karger AG, Basel", "title": "Dietary Epidemiology of Essential Tremor: Meat Consumption and Meat Cooking Practices" }, { "docid": "MED-4749", "text": "For the first time in the field of steroid residues in humans, demonstration of 19-norandrosterone (19-NA: 3alpha-hydroxy-5alpha-estran-17-one) and 19-noretiocholanolone (19-NE: 3alpha-hydroxy-5beta-estran-17-one) excretion in urine subsequent to boar consumption is reported. Three male volunteers agreed to consume 310 g of tissues from the edible parts (meat, liver, heart and kidney) of a boar. The three individuals delivered urine samples before and during 24 h after meal intake. After deconjugation of phase II metabolites, purification and specific derivatisation of target metabolites, the urinary extracts were analysed by mass spectrometry. Identification was carried out using measurements obtained by gas chromatography/high resolution mass spectrometry (GC/HRMS) (R = 7000) and liquid chromatography/tandem mass spectrometry (LC/MS/MS) (positive electrospray ionisation (ESI+)). Quantification was realised using a quadrupole mass filter. 19-NA and 19-NE concentrations in urine reached 3.1 to 7.5 microg/L nearby 10 hours after boar tissue consumption. Levels returned to endogenous values 24 hours after. These two steroids are usually exploited to confirm the exogenous administration of 19-nortestosterone (19-NT: 17beta-hydroxyestr-4-en-3-one), especially in the antidoping field. We have thus proved that eating tissues of non-castrated male pork (in which 17beta-nandrolone is present) might induce some false accusations of the abuse of nandrolone in antidoping. Copyright 2000 John Wiley & Sons, Ltd.", "title": "Consequence of boar edible tissue consumption on urinary profiles of nandrolone metabolites. I. Mass spectrometric detection and quantification of ..." }, { "docid": "MED-2583", "text": "Inositol hexaphosphate (IP(6)), a naturally polyphosphorylated carbohydrate, has been reported to have significant in vivo and in vitro anticancer activity against numerous tumours, such as colon, prostate, breast, liver and rhabdomyosarcomas. To confirm this activity in haematological malignancies and to characterize some of the mechanisms of IP(6) action, we analysed its effects on human leukaemic cell lines and fresh chronic myelogenous leukaemia (CML) progenitor cells using a combined cellular and molecular approach. IP(6) had a dose-dependent cytotoxic effect on all of the evaluated cell lines, with accumulation in the G2M phase in two out of five cell lines tested. At the molecular level, cDNA microarray analysis after IP(6) exposure showed an extensive downmodulation of genes involved in transcription and cell cycle regulation and a coherent upregulation of cell cycle inhibitors. Furthermore, IP(6) treatment of fresh leukaemic samples of bone marrow CD34+ CML progenitor cells significantly inhibited granulocyte-macrophage colony-forming unit (CFU-GM) formation (P = 0.0062) in comparison to normal bone marrow specimens, which were not affected. No differentiating effect on HL60 cells was observed. Taken together, our results confirm the antiproliferative activity of IP(6) and suggest that it may have a specific antitumour effect also in chronic myeloid leukaemias, via active gene modulation.", "title": "Effect of inositol hexaphosphate (IP(6)) on human normal and leukaemic haematopoietic cells." }, { "docid": "MED-4384", "text": "PURPOSE: To explore the association between the consumption of fruits and vegetables and the presence of glaucoma. DESIGN: Cross-sectional cohort study. METHODS: In a sample of 1,155 women located in multiple centers in the United States, glaucoma specialists diagnosed glaucoma in at least one eye by assessing optic nerve head photographs and 76-point suprathreshold screening visual fields. Consumption of fruits and vegetables was assessed using the Block Food Frequency Questionnaire. The relationship between selected fruit and vegetable consumption and glaucoma was investigated using adjusted logistic regression models. RESULTS: Among 1,155 women, 95 (8.2%) were diagnosed with glaucoma. In adjusted analysis, the odds of glaucoma risk were decreased by 69% (odds ratio [OR], 0.31; 95% confidence interval [CI], 0.11 to 0.91) in women who consumed at least one serving per month of green collards and kale compared with those who consumed fewer than one serving per month, by 64% (OR, 0.36; 95% CI, 0.17 to 0.77) in women who consumed more than two servings per week of carrots compared with those who consumed fewer than one serving per week, and by 47% (OR, 0.53; 95% CI, 0.29 to 0.97) in women who consumed at least one serving per week of canned or dried peaches compared with those who consumed fewer than one serving per month. CONCLUSIONS: A higher intake of certain fruits and vegetables may be associated with a decreased risk of glaucoma. More studies are needed to investigate this relationship.", "title": "Glaucoma risk and the consumption of fruits and vegetables among older women in the study of osteoporotic fractures." }, { "docid": "MED-5176", "text": "A flaxseed lignan extract containing 33% secoisolariciresinol diglucoside (SDG) was evaluated for its ability to alleviate lower urinary tract symptoms (LUTS) in 87 subjects with benign prostatic hyperplasia (BPH). A randomized, double-blind, placebo-controlled clinical trial with repeated measurements was conducted over a 4-month period using treatment dosages of 0 (placebo), 300, or 600 mg/day SDG. After 4 months of treatment, 78 of the 87 subjects completed the study. For the 0, 300, and 600 mg/day SDG groups, respectively, the International Prostate Symptom Score (IPSS) decreased -3.67 +/- 1.56, -7.33 +/- 1.18, and -6.88 +/- 1.43 (mean +/- SE, P = .100, < .001, and < .001 compared to baseline), the Quality of Life score (QOL score) improved by -0.71 +/- 0.23, -1.48 +/- 0.24, and -1.75 +/- 0.25 (mean +/- SE, P = .163 and .012 compared to placebo and P = .103, < .001, and < .001 compared to baseline), and the number of subjects whose LUTS grade changed from \"moderate/severe\" to \"mild\" increased by three, six, and 10 (P = .188, .032, and .012 compared to baseline). Maximum urinary flows insignificantly increased 0.43 +/- 1.57, 1.86 +/- 1.08, and 2.7 +/- 1.93 mL/second (mean +/- SE, no statistical significance reached), and postvoiding urine volume decreased insignificantly by -29.4 +/- 20.46, -19.2 +/- 16.91, and -55.62 +/- 36.45 mL (mean +/- SE, no statistical significance reached). Plasma concentrations of secoisolariciresinol (SECO), enterodiol (ED), and enterolactone (EL) were significantly raised after the supplementation. The observed decreases in IPSS and QOL score were correlated with the concentrations of plasma total lignans, SECO, ED, and EL. In conclusion, dietary flaxseed lignan extract appreciably improves LUTS in BPH subjects, and the therapeutic efficacy appeared comparable to that of commonly used intervention agents of alpha1A-adrenoceptor blockers and 5alpha-reductase inhibitors.", "title": "Effects of dietary flaxseed lignan extract on symptoms of benign prostatic hyperplasia." }, { "docid": "MED-4237", "text": "OBJECTIVE: To evaluate the prevalence of benign prostatic hyperplasia (BPH) and prostatic cancer (CaP) in the mainland of China. METHODS: The incidence of BPH and CaP in urological hospital was investigated in 1997 in 26 provinces and 4 metropolises scattered over the mainland of China. The change of hospital incidences of BPH and CaP in the Institute of Urology, Beijing Medical University from 1951 to 1997 was also reviewed. RESULTS: The incidence of BPH and CaP in 1997 in 187 hospitals scattered over the mainland of China was 16.1% (15,459/95,749) and 1.5% (1389/95,749), respectively. The incidence of BPH and CaP in the Institute of Urology, Beijing University from 1951 to 1960 was 7.6% and 0.6%, respectively, while it was 18.5% and 3.4% from 1991 to 1997. CONCLUSION: The hospital incidence of BPH and CaP is rising rapidly in China, but CaP is still not a common disease in China.", "title": "Epidemiological survey of benign prostatic hyperplasia and prostatic cancer in China." }, { "docid": "MED-4752", "text": "A potent link to dairy seems to exist for three hormone-responsive glands. Acne, breast cancer and prostate cancer have all been linked epidemiologically to dairy intake. Although mechanisms postulated here remain to be accurately defined, the likely link involves Insulin-like Growth Factor-1 as a general stimulant, synergized by the steroid hormones present in milk. The IGF-1 may be either absorbed from milk, or stimulated by its ingestion, or both. The 5alpha-reduced compound 5alpha-pregnanedione (5α-P) present in milk is a direct precursor of dihydrotestosterone and may act through that pathway in prostate cancer, but 5α-P has also recently been shown to be capable of inducing estrogen receptors in breast cancer cells, upregulating cancer cells' sensitivity to estrogen. The introduction of exogenous hormones and growth factors into tissues that have not evolved defensive feedback inhibition of their corresponding endogenous sources is postulated as a direct stimulatory threat to these organ systems, whether for hyperplasia or neoplasia.", "title": "Acne, dairy and cancer" }, { "docid": "MED-4484", "text": "This study assesses the association between salt added at the table, processed meat and the risk of various cancers. Mailed questionnaires were completed by 19 732 patients with histologically confirmed incident cancer of the stomach, colon, rectum, pancreas, lung, breast, ovary, prostate, testis, kidney, bladder, brain, non-Hodgkin's lymphoma or leukaemia, and 5039 population controls,between 1994 and 1997. Measurement included information on socioeconomic status, lifestyle habits and diet. A 69-item food frequency questionnaire provided data on eating habits 2 years before the study. Odds ratios and 95% confidence intervals were derived through unconditional logistic regression. Compared with never adding salt at the table, always or often adding salt at the table was associated with an increased risk of stomach, lung, testicular and bladder cancer. Processed meat was significantly related to the risk of the stomach, colon, rectum, pancreas, lung, prostate, testis, kidney and bladder cancer and leukaemia; the odds ratios for the highest quartile ranged from 1.3 to 1.7. The findings add to the evidence that high consumption of salt and processed meat may play a role in the aetiology of several cancers.", "title": "Salt, processed meat and the risk of cancer." }, { "docid": "MED-2653", "text": "Human milk is the most important form of nourishment for newborn children. Its consumption is strongly recommended by health authorities also for other important advantages. Unfortunately, in the last three decades a great number of investigations have shown the occurrence of several environmental contaminants in human milk, especially those with lipophilic properties. This study investigates the presence of nonylphenol, octylphenol (OP), nonylphenol monoethoxylate (NP1EO) and two octylphenol ethoxylates (OPEOs) (namely OP1EO and OP2EO), in human breast milk of Italian women. NP was the contaminant found at the highest levels with mean concentrations of 32 ng/mL, about two orders of magnitude higher than OP (0.08 ng/mL), OP1EO (0.07 ng/mL) and OP2EO (0.16 ng/mL). In the group of study a positive correlation among fish consumption and levels of NP in the milk was observed, in accordance with the evidence that seafood represents one of the most important sources of exposure to this group of contaminants in Italy. On the basis of the concentrations found in the breast milk samples, a maximum NP daily intake of 3.94 microg/kg/day can be calculated, which is close to the Tolerable Daily Intake (TDI) of 5 microg/kg body weight (bw) proposed by the Danish Institute of Safety and Toxicology. In the cases of OP no TDI is available, but its intake is at least six orders of magnitude lower than the NOAEL of 10 mg/kg/day derived from a two generation study on rats.", "title": "Nonylphenol and octylphenol in human breast milk." }, { "docid": "MED-3243", "text": "OBJECTIVES: Considerable evidence has shown that diet can affect both the incidence and the progression of prostate cancer. The objective of this study was to determine whether men in this situation could make a change to a diet emphasizing plant-based foods and fish and to examine the effect on quality of life (QOL) and prostate-specific antigen (PSA) velocity. METHODS: A total of 36 men and their partners were randomly assigned to attend a series of 11 dietary and cooking classes that also integrated mindfulness practice as a support in making the change or a wait-list control group. Assessments were made of dietary intake, QOL, and PSA at baseline, after intervention (11 weeks), and 3 months after intervention. RESULTS: The intervention group showed significant reductions in the consumption of saturated fat and increased consumption of vegetable proteins with accompanying reductions in animal proteins, including dairy products. They also showed increased QOL. Although no significant change was found in the rate of PSA increase between the two groups, the mean PSA doubling time for the intervention group was substantially longer at the 3-month follow-up visit than that of the controls. CONCLUSIONS: Men with a increasing PSA level after primary treatment were able to make a change to a prostate-healthy diet, accompanied by increases in QOL. No significant difference was found in the log PSA slope between the two groups; however, the PSA doubling time increased substantially in the intervention group compared with that in the controls. Future trials should examine the effect of the prostate-healthy diet with a larger sample of men for a longer period.", "title": "A dietary intervention for recurrent prostate cancer after definitive primary treatment: results of a randomized pilot trial." }, { "docid": "MED-2770", "text": "Although breast and ovarian cancers are rare in Japan compared with other developed countries, the death rates for both are increasing. In Japan, dramatic lifestyle changes occurred after World War II. Over the past 50 years (1947-1997), the age-standardized death rates of breast and ovarian cancers increased about 2- and 4-fold, respectively, and the respective intake of milk, meat, and eggs increased 20-, 10-, and 7-fold. The increase in the annual death rates from breast and ovarian cancers might be due to the lifestyle changes (increased consumption of animal-derived food) that occurred after 1945. Among the food, milk and dairy products should receive particular attention since they contain considerable amounts of estrogens.", "title": "The experience of Japan as a clue to the etiology of breast and ovarian cancers: relationship between death from both malignancies and dietary prac..." }, { "docid": "MED-4485", "text": "Background Meat could be involved in bladder carcinogenesis via multiple potentially carcinogenic meat-related compounds related to cooking and processing, including nitrate, nitrite, heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons. We comprehensively investigated the association between meat and meat components and bladder cancer. Methods During 7 years of follow-up, 854 transitional cell bladder cancer cases were identified among 300,933 men and women who completed a validated food frequency questionnaire in the large prospective NIH-AARP Diet and Health Study. We estimated intake of nitrate and nitrite from processed meat and HCAs and PAHs from cooked meat using quantitative databases of measured values. We calculated total dietary nitrate and nitrite based on literature values. Results The hazard ratios (HR) and 95% confidence intervals (CI) for red meat (HR for fifth compared to first quintile=1.22, 95% CI=0.96–1.54, p-trend=0.07) and the HCA 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) (HR=1.19, 95% CI=0.95–1.48, p-trend=0.06) conferred a borderline statistically significant increased risk of bladder cancer. We observed positive associations in the top quintile for total dietary nitrite (HR=1.28, 95% CI=1.02–1.61, p-trend= 0.06) and nitrate plus nitrite intake from processed meat (HR=1.29 95% CI=1.00–1.67, p-trend= 0.11). Conclusions These findings provide modest support for a role for total dietary nitrite and nitrate plus nitrite from processed meat in bladder cancer. Our results also suggest a positive association between red meat and PhIP and bladder carcinogenesis.", "title": "Meat and components of meat and the risk of bladder cancer in the NIH-AARP Diet and Health Study" }, { "docid": "MED-3733", "text": "This study assessed the metabolic response to sweetened dried cranberries (SDC), raw cranberries (RC), and white bread (WB) in humans with type 2 diabetes. Development of palatable cranberry preparations associated with lower glycemic responses may be useful for improving fruit consumption and glycemic control among those with diabetes. In this trial, type 2 diabetics (n= 13) received WB (57 g, 160 cal, 1 g fiber), RC (55 g, 21 cal, 1 g fiber), SDC (40 g, 138 cal, 2.1 g fiber), and SDC containing less sugar (SDC-LS, 40 g, 113 cal, 1.8 g fiber + 10 g polydextrose). Plasma glucose (mmol/L) peaked significantly at 60 min for WB, and at 30 min for RC, SDC, and SDC-LS at 9.6 ± 0.4, 7.0 ± 0.4, 9.6 ± 0.5, and 8.7 ± 0.5, respectively, WB remained significantly elevated from the other treatments at 120 min. Plasma insulin (pmol/mL) peaked at 60 min for WB and SDC and at 30 min for RC and SDC-LS at 157 ± 15, 142 ± 27, 61 ± 8, and 97 ± 11, respectively. Plasma insulin for SDC-LS was significantly lower at 60 min than either WB or SDC. Insulin area under the curve (AUC) values for RC and SDC-LS were both significantly lower than WB or SDC. Phenolic content of SDC and SDC-LS was determined following extraction with 80% acetone prior to high-performance liquid chromatography (HPLC) and electronspray ionization-mass spectrometry (ESI-MS) and found to be rich in 5-caffeoylquinic cid, quercetin-3-galactoside, and quercetin-3-galactoside, and the proanthocyanidin dimer epicatechin. In conclusion, SDC-LS was associated with a favorable glycemic and insulinemic response in type 2 diabetics. Practical Application: This study compares phenolic content and glycemic responses among different cranberry products. The study seeks to expand the palatable and portable healthy food choices for persons with type 2 diabetes. The novel use of polydextrose as a bulking agent making possible a reduction in caloric content and potential glycemic response is also characterized in this study.", "title": "Glycemic responses to sweetened dried and raw cranberries in humans with type 2 diabetes." }, { "docid": "MED-5035", "text": "In this study, we examined the association between meat and fish intake and the risk of various cancers. Mailed questionnaires were completed by 19,732 incident, histologically confirmed cases of cancer of the stomach, colon, rectum, pancreas, lung, breast, ovary, prostate, testis, kidney, bladder, brain, non-Hodgkin's lymphomas (NHL), and leukemia and 5,039 population controls between 1994 and 1997 in 8 Canadian provinces. Measurement included information on socioeconomic status, lifestyle habits, and diet. A 69-item food frequency questionnaire provided data on eating habits 2 yr before data collection. Odds ratios and 95% confidence intervals were derived through unconditional logistic regression. Total meat and processed meat were directly related to the risk of stomach, colon, rectum, pancreas, lung, breast (mainly postmenopausal), prostate, testis, kidney, bladder, and leukemia. Red meat was significantly associated with colon, lung (mainly in men), and bladder cancer. No relation was observed for cancer of the ovary, brain, and NHL. No consistent excess risk emerged for fish and poultry, which were inversely related to the risk of a number of cancer sites. These findings add further evidence that meat, specifically red and processed meat, plays an unfavorable role in the risk of several cancers. Fish and poultry appear to be favorable diet indicators.", "title": "Meat and fish consumption and cancer in Canada." }, { "docid": "MED-5184", "text": "We examined the association of dietary lignan intake with estrogen receptor negative (ER-) and ER positive (ER+) breast cancer risk in a breast cancer case-control study. Among premenopausal women only, there was a reduced risk of ER- breast cancer for those in the highest compared to the lowest quartile of lignan intake suggesting that the observed negative association of lignans with breast cancer may be limited to ER- tumors.", "title": "Dietary lignan intakes and risk of breast cancer by tumor estrogen receptor status." }, { "docid": "MED-3279", "text": "Various pesticides are being used to destabilize, perturb, or inhibit crucial biochemical and physiological targets related to metabolism, growth, development, nervous communication, or behavior in pestiferous organisms. Chitin is an eukaryotic extracellular aminosugar biopolymer, massively produced by most fungal systems and by invertebrates, notably arthropods. Being an integral supportive component in fungal cell wall, insect cuticle, and nematode egg shell, chitin has been considered as a selective target for pesticide action. Throughout the elaborate processes of chitin formation and deposition, only the polymerization events associated with the cell membrane compartment are so far available for chemical interference. Currently, the actinomycetes-derived nucleoside peptide fungicides such as the polyoxins and the insecticidal benzoylaryl ureas have reached commercial pesticide status. The polyoxins and other structurally-related antibiotics like nikkomycins are strong competitive inhibitors of the polymerizing enzyme chitin synthase. The exact biochemical lesion inflicted by the benzoylaryl ureas is still elusive, but a post-polymerization event, such as translocation of chitin chains across the cell membrane, is suggested. Hydrolytic degradation of the chitin polymer is essential for hyphal growth, branching, and septum formation in fungal systems as well as for the normal molting of arthropods. Recently, insect chitinase activity was strongly and specifically suppressed by allosamidin, an actimomycetes-derived metabolite. In part, the defense mechanism in plants against invasion of pathogens is associated with induced chitinases. Chitin, chitosan, and their oligomers are able to act as elicitors which induce enhanced levels of chitinases in various plants. Lectins which bind to N-acetyl-D-glucosamine strongly interfere with fungal and insect chitin synthases. Plant lectins with similar properties may be involved in plant-pathogen interaction inter alia by suppressing fungal invasion.", "title": "Chitin synthesis and degradation as targets for pesticide action." }, { "docid": "MED-4233", "text": "OBJECTIVES: Dietary fat and fiber affect hormonal levels and may influence cancer progression. Flaxseed is a rich source of lignan and omega-3 fatty acids and may thwart prostate cancer. The potential effects of flaxseed may be enhanced with concomitant fat restriction. We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet could affect the biomarkers of prostatic neoplasia. METHODS: Twenty-five patients with prostate cancer who were awaiting prostatectomy were instructed on a low-fat (20% of kilocalories or less), flaxseed-supplemented (30 g/day) diet. The baseline and follow-up levels of prostate-specific antigen, testosterone, free androgen index, and total serum cholesterol were determined. The tumors of diet-treated patients were compared with those of historic cases (matched by age, race, prostate-specific antigen level at diagnosis, and biopsy Gleason sum) with respect to apoptosis (terminal deoxynucleotidyl transferase [TdT]-mediated dUTP-biotin nick end-labeling [TUNEL]) and proliferation (MIB-1). RESULTS: The average duration on the diet was 34 days (range 21 to 77), during which time significant decreases were observed in total serum cholesterol (201 +/- 39 mg/dL to 174 +/- 42 mg/dL), total testosterone (422 +/- 122 ng/dL to 360 +/- 128 ng/dL), and free androgen index (36.3% +/- 18.9% to 29.3% +/- 16.8%) (all P <0.05). The baseline and follow-up levels of prostate-specific antigen were 8.1 +/- 5.2 ng/mL and 8.5 +/- 7.7 ng/mL, respectively, for the entire sample (P = 0.58); however, among men with Gleason sums of 6 or less (n = 19), the PSA values were 7.1 +/- 3.9 ng/mL and 6.4 +/- 4.1 ng/mL (P = 0.10). The mean proliferation index was 7.4 +/- 7.8 for the historic controls versus 5.0 +/- 4.9 for the diet-treated patients (P = 0.05). The distribution of the apoptotic indexes differed significantly (P = 0.01) between groups, with most historic controls exhibiting TUNEL categorical scores of 0; diet-treated patients largely exhibited scores of 1. Both the proliferation rate and apoptosis were significantly associated with the number of days on the diet (P = 0.049 and P = 0.017, respectively). CONCLUSIONS: These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect prostate cancer biology and associated biomarkers. Further study is needed to determine the benefit of this dietary regimen as either a complementary or preventive therapy.", "title": "Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal l..." }, { "docid": "MED-3748", "text": "Berries have been recognized as a functional food with potential to protect against a variety of health conditions, including some cancers. Cranberry (Vaccinium macrocarpon) production and consumption have grown in recent years, warranting further evaluation of potential health benefits. Extracts and isolated constituents from cranberry fruit inhibit growth and proliferation of tumor cells in vitro, and recent data from animal studies lend further support to cranberry's reputation as a cancer fighter. Several likely mechanisms of action for cranberry against prostate and other cancers have been identified, including induction of apoptosis and inhibition of events linked to cellular invasion and migration. This article attempts to put into perspective what is known about cranberry's potential chemopreventive properties, what is yet to be determined, and some factors to consider as research moves forward. Copyright © 2011 Society of Chemical Industry.", "title": "Cranberries: ripe for more cancer research?" }, { "docid": "MED-5120", "text": "Human gammadeltaT lymphocytes are a subset of T cells and are a first line of defense against microbes and tumors. These gammadeltaT cells can be primed by nitrogen-containing bisphosphonates, and certain short-chain alkylamines. These primed gammadeltaT cells have an enhanced capacity to proliferate and to secrete cytokines upon ex vivo exposure to a wide variety of microbes and tumor cells. The largest dietary source of alkylamines is L-theanine, an amino acid unique to tea beverages that is catabolized to ethylamine. Supplementation of subjects with capsules containing L-theanine and catechins has recently been shown to decrease the incidence of cold and flu symptoms, while enhancing gammadeltaT cell function.", "title": "L-theanine intervention enhances human gammadeltaT lymphocyte function." }, { "docid": "MED-4481", "text": "The aim of this study was to investigate whether dietary fat and meat intakes are associated with reflux esophagitis (RE), Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). In this all-Ireland case-control study, dietary intake data was collected using a food frequency questionnaire in 219 RE patients, 220 BE patients, 224 EAC patients, and 256 frequency-matched controls between 2002 and 2005. Unconditional multiple logistic regression analysis was used to examine the association between dietary variables and disease risk using quartiles of intake, to attain odds ratios (OR) and 95% confidence intervals (95%CI), while adjusting for potential confounders. Patients in the highest quartile of total fat intake had a higher risk of RE (OR=3.54; 95%CI=1.32–9.46) and EAC (OR=5.44; 95%CI=2.08–14.27). A higher risk of RE and EAC was also reported for patients in the highest quartile of saturated fat intake (OR=2.79; 95%CI=1.11–7.04; OR=2.41; 95%CI=1.14–5.08, respectively) and monounsaturated fat intake (OR=2.63; 95%CI=1.01–6.86; OR=5.35; 95%CI=2.14–13.34, respectively). Patients in the highest quartile of fresh red meat intake had a higher risk of EAC (OR=3.15; 95%CI=1.38–7.20). Patients in the highest category of processed meat intake had a higher risk of RE (OR=4.67; 95%CI=1.71–12.74). No consistent associations were seen for BE with either fat or meat intakes. Further studies, investigating the association between dietary fat and food sources of fat are needed to confirm these results.", "title": "Dietary fat and meat intakes and risk of reflux esophagitis, Barrett’s esophagus and esophageal adenocarcinoma" }, { "docid": "MED-2662", "text": "A human breast cancer cell line (MCF-7) was used to develop an in vitro screening assay for the detection of xenoestrogenic environmental pollutants. MCF-7 cells were cultured in DMEM containing 5% fetal bovine serum (FBS). An estrogenic response was defined as an increase in the frequency of proliferating MCF-7 cells, and was measured using a thymidine analog, bromodeoxyuridine, and flow cytometry. Di-2-ethylhexyl phthalate (DEHP) and 4-n-nonylphenol (4-n-NP) were used as model chemicals. The proliferation rate of S-phase cells after 24 h of exposure to various concentrations of 17beta-estradiol and to model compounds was compared with a positive and a negative control, containing 1 nM 17beta-estradiol and 0.1% ethanol, respectively. DEHP and 4-n-NP increased the frequency of proliferating MCF-7 cells in a dose-dependent manner. The lowest concentration that significantly increased the proliferation of MCF-7 cells was 10 microM for DEHP and 1 microM for 4-n-NP. The results showed that the assay is accurate and quick to perform. It may prove a valuable tool for screening potential estrogen-mimicking environmental pollutants.", "title": "Effects of xenoestrogenic environmental pollutants on the proliferation of a human breast cancer cell line (MCF-7)." }, { "docid": "MED-2585", "text": "Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plant and mammalian cells. It was recently recognized to possess multiple biological functions. A striking anticancer effect of IP6 was demonstrated in different experimental models. Inositol is also a natural constituent possessing moderate anticancer activity. The most consistent and best anticancer results were obtained from the combination of IP6 plus inositol. In addition to reducing cell proliferation, IP6 increases differentiation of malignant cells, often resulting in a reversion to normal phenotype. Exogenously administered IP6 is rapidly taken into the cells and dephosphorylated to lower-phosphate inositol phosphates, which further interfere with signal transduction pathways and cell cycle arrest. Enhanced immunity and antioxidant properties can also contribute to tumor cell destruction. However, the molecular mechanisms underlying this anticancer action are not fully understood. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP6 holds great promise in our strategies for the prevention and treatment of cancer. IP6 plus inositol enhances the anticancer effect of conventional chemotherapy, controls cancer metastases, and improves the quality of life, as shown in a pilot clinical trial. The data strongly argue for the use of IP6 plus inositol in our strategies for cancer prevention and treatment. However, the effectiveness and safety of IP6 plus inositol at therapeutic doses needs to be determined in phase I and phase II clinical trials in humans.", "title": "Cancer inhibition by inositol hexaphosphate (IP6) and inositol: from laboratory to clinic." }, { "docid": "MED-2572", "text": "In traditional cultures, balancing health with a balanced lifestyle was a core belief. The diseases of modern civilization were rare. Indigenous people have patterns of illness very different from Western civilization; yet, they rapidly develop diseases once exposed to Western foods and lifestyles. Food and medicine were interwoven. All cultures used special or functional foods to prevent disease. Food could be used at different times either as food or medicine. Foods, cultivation, and cooking methods maximized community health and well-being. With methods passed down through generations, cooking processes were utilized that enhanced mineral and nutrient bioavailability. This article focuses on what researchers observed about the food traditions of indigenous people, their disease patterns, the use of specific foods, and the environmental factors that affect people who still eat traditional foods.", "title": "Traditional non-Western diets." }, { "docid": "MED-2820", "text": "Scope The incidence of cancer is significantly lower in regions where turmeric is heavily consumed. Whether lower cancer incidence is due to turmeric was investigated by examining its effects on tumor cell proliferation, on pro-inflammatory transcription factors NF-κB and STAT3, and on associated gene products. Methods and results Cell proliferation and cell cytotoxicity were measured by the MTT method, NF-κB activity by EMSA, protein expression by Western blot analysis, ROS generation by FACS analysis, and osteoclastogenesis by TRAP assay. Turmeric inhibited NF-κB activation and down-regulated NF-κB-regulated gene products linked to survival (Bcl-2, cFLIP, XIAP, and cIAP1), proliferation (cyclin D1 and c-Myc), and metastasis (CXCR4) of cancer cells. The spice suppressed the activation of STAT3, and induced the death receptors (DR)4 and DR5. Turmeric enhanced the production of ROS, and suppressed the growth of tumor cell lines. Furthermore, turmeric sensitized the tumor cells to chemotherapeutic agents capecitabine and taxol. Turmeric was found to be more potent than pure curcumin for cell growth inhibition. Turmeric also inhibited NF-κB activation induced by RANKL that correlated with the suppression of osteoclastogenesis. Conclusion Our results indicate that turmeric can effectively block the proliferation of tumor cells through the suppression of NF-κB and STAT3 pathways.", "title": "Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis" }, { "docid": "MED-4483", "text": "BACKGROUND: Humans are exposed to preformed N-nitroso compounds (NOCs) and endogenous NOCs. Several NOCs are potential human carcinogens, including N-nitrosodimethylamine (NDMA), but evidence from population studies is inconsistent. OBJECTIVE: We examined the relation between dietary NOCs (NDMA), the endogenous NOC index, and dietary nitrite and cancer incidence in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk, United Kingdom, study. DESIGN: This was a prospective study of 23,363 men and women, aged 40-79 y, who were recruited in 1993-1997 and followed up to 2008. The baseline diet was assessed with food-frequency questionnaires. RESULTS: There were 3268 incident cancers after a mean follow-up of 11.4 y. Dietary NDMA intake was significantly associated with increased cancer risk in men and women [hazard ratio (HR): 1.14; 95% CI: 1.03, 1.27; P for trend = 0.03] and in men (HR: 1.24; 95% CI: 1.07, 1.44; P for trend = 0.005) when the highest quartile was compared with the lowest quartile in age- and sex-adjusted analyses but not in multivariate analyses (HR: 1.10; 95% CI: 0.97, 1.24; HR for men: 1.18; 95% CI: 1.00, 1.40; P for trend ≥ 0.05). When continuously analyzed, NDMA was associated with increased risk of gastrointestinal cancers (HR: 1.13; 95% CI: 1.00, 1.28), specifically of rectal cancer (HR: 1.46; 95% CI: 1.16, 1.84) per 1-SD increase after adjustment for age, sex, body mass index, cigarette smoking status, alcohol intake, energy intake, physical activity, education, and menopausal status (in women). The endogenous NOC index and dietary nitrite were not significantly associated with cancer risk. There was a significant interaction between plasma vitamin C concentrations and dietary NDMA intake on cancer incidence (P for interaction < 0.00001). CONCLUSIONS: Dietary NOC (NDMA) was associated with a higher gastrointestinal cancer incidence, specifically of rectal cancer. Plasma vitamin C may modify the relation between NDMA exposure and cancer risk.", "title": "N-Nitroso compounds and cancer incidence: the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk Study." }, { "docid": "MED-2650", "text": "Over the last 40 years there have been constant reports concerning environmental chemicals with hormone-like effects in wildlife. An endocrine disruptor is an exogenous substance that causes adverse health effects in an intact organism or its progeny, secondary to changes in endocrine function. Endocrine disruptors of widely diverse chemical structures that have oestrogenic properties are known as oestrogenic xenobiotics or xenoestrogens. Some of these substances, such as phytoestrogens and mycoestrogens, can come from diet or from the environment. Although the oestrogenic activity of these substances is weaker than that of oestradiol, new chemicals with endocrine disrupting potential continue to be discovered, inadvertent forms of exposure are constantly being identified, and there is increasing concern about cumulative effects. Studies in the 1960s and 1970s characterized the oestrogenicity of a number of industrial compounds and the pesticides o,p-DDT, kepone, methoxychlor, phenolic derivatives and polychlorinated biphenyls (PCBs). In the last 5 years, several environmental chemicals have been added to the list of xenoestrogens, including the pesticides toxaphene, dieldrin and endosulphan, and several different compounds used in the food industry, antioxidants such a t-butylhydroxyanisole; plasticizers such as benzylbutylphthalate and 4-OH-alkylphenols; and substances used in dental restorations, such as bisphenol-A. The relevance of these newly discovered endocrine disruptors to human health is now starting to emerge. The few studies that have investigated their effect in humans point in the same direction: if there is indeed an association between exposure to substances with hormone-disruptive activity and certain disorders of endocrine organs, the incidence of such disorders would be greater in areas where exposure to agents with this activity is high. A closer scrutiny is required to determine whether these newly discovered endocrine disrupting chemicals contribute, together with oestrogenic pesticides, to the exposure of humans to xenoestrogens.", "title": "Inadvertent exposure to xenoestrogens." }, { "docid": "MED-4482", "text": "Consumption of red meat, particularly well done meat, has been associated with increased prostate cancer risk. High temperature cooking methods such as grilling and barbequeing may produce heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) which are known carcinogens. We assessed the association with meat consumption and estimated HCA and PAH exposure in a population-based case-control study of prostate cancer. Newly diagnosed cases aged 40–79 years (531 advanced cases, 195 localized cases) and 527 controls were asked about dietary intake, including usual meat cooking methods and doneness levels. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate logistic regression. For advanced prostate cancer, but not localized disease, increased risks were associated with higher consumption of hamburgers (OR=1.79. CI=1.10–2.92), processed meat (OR=1.57, CI=1.04, 2.36), grilled red meat (OR=1.63, CI=0.99–2.68), and well done red meat (OR=1.52, CI=0.93–2.46), and intermediate intake of 2-amino-1-methyl1-6-phenylimidazo[4,5-b]pyridine (PhIP) (quartile 2 vs. 1: OR=1.41, CI=0.98–2.01; quartile 3 vs. 1: OR=1.42, CI=0.98–2.04), but not for higher intake. White meat consumption was not associated with prostate cancer. These findings provide further evidence that consumption of processed meat and red meat cooked at high temperature is associated with increased risk of advanced, but not localized prostate cancer.", "title": "Meat consumption, Cooking Practices, Meat Mutagens and Risk of Prostate Cancer" }, { "docid": "MED-2654", "text": "4-Nonylphenols (NPs) are common products of biodegradation of a widely used group of nonionic surfactants, the nonylphenol ethoxylates (NPEs). These compounds are known to be persistent, toxic, and estrogen active. There is a worldwide scientific and public discussion on the potential consequences of human long term dietary exposure to such endocrine disrupters. Despite numerous determinations of NPs in environmental samples no systematical reports exist relating to concentrations of NPs in food. We analyzed NPs in 60 different foodstuff commercially available in Germany. The results indicate that NPs are ubiquitous in food. The concentrations of NPs on a fresh weight basis varied between 0.1 and 19.4 microg/kg regardless of the fat content of the foodstuff. Based on data on German food consumption rates and these first analyses of NPs in food, the daily intake for an adult was calculated to be 7.5 microg/day NPs. For infants exclusively fed with breast milk or infant formulas daily intakes of 0.2 microg/day and 1.4 microg/day NPs, respectively, can be estimated.", "title": "Endocrine disrupting nonylphenols are ubiquitous in food." }, { "docid": "MED-2643", "text": "The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand.", "title": "Endocrine-Disrupting Chemicals: Associated Disorders and Mechanisms of Action" }, { "docid": "MED-4753", "text": "BACKGROUND: Modern genetically improved dairy cows continue to lactate throughout almost the entire pregnancy. Therefore, recent commercial cow's milk contains large amounts of estrogens and progesterone. With regard to the exposure of prepubertal children to exogenous estrogens, the authors are particularly concerned about commercial milk produced from pregnant cows. The purpose of the present study was therefore to examine concentrations of serum and urine sex hormones after the intake of cow milk. METHODS: Subjects were seven men, six prepubertal children, and five women. The men and children drank 600 mL/m(2) of cow milk. Urine samples were collected 1 h before the milk intake and four times every hour after intake. In men the serum samples were obtained before and 15, 30, 45, 60, 90 and 120 min after milk intake. Women drank 500 mL of cow's milk every night for 21 days beginning on the first day of the second menstruation. In three successive menstrual cycles, the day of ovulation was examined using an ovulation checker. RESULTS: After the intake of cow milk, serum estrone (E1) and progesterone concentrations significantly increased, and serum luteinizing hormone, follicle-stimulating hormone and testosterone significantly decreased in men. Urine concentrations of E1, estradiol, estriol and pregnanediol significantly increased in all adults and children. In four out of five women, ovulation occurred during the milk intake, and the timing of ovulation was similar among the three menstrual cycles. CONCLUSIONS: The present data on men and children indicate that estrogens in milk were absorbed, and gonadotropin secretion was suppressed, followed by a decrease in testosterone secretion. Sexual maturation of prepubertal children could be affected by the ordinary intake of cow milk.", "title": "Exposure to exogenous estrogen through intake of commercial milk produced from pregnant cows." }, { "docid": "MED-4886", "text": "OBJECTIVES: Previous research has demonstrated that patients with prostate cancer participating in the Prostate Cancer Lifestyle Trial had a reduction in prostate-specific antigen (PSA) levels, inhibition of LNCaP cell growth, and fewer prostate cancer-related clinical events at the end of 1 year compared with controls. The aim of this study was to examine the clinical events in this trial during a 2-year period. METHODS: The Prostate Cancer Lifestyle Trial was a 1-year randomized controlled clinical trial of 93 patients with early-stage prostate cancer (Gleason score <7, PSA 4-10 ng/mL) undergoing active surveillance. The patients in the experimental arm were encouraged to adopt a low-fat, plant-based diet, to exercise and practice stress management, and to attend group support sessions. The control patients received the usual care. RESULTS: By 2 years of follow-up, 13 of 49 (27%) control patients and 2 of 43 (5%) experimental patients had undergone conventional prostate cancer treatment (radical prostatectomy, radiotherapy, or androgen deprivation, P < .05). No differences were found between the groups in other clinical events (eg, cardiac), and no deaths occurred. Three of the treated control patients but none of the treated experimental patients had a PSA level of >or=10 ng/mL, and 1 treated control patient but no treated experimental patients had a PSA velocity of >2 ng/mL/y before treatment. No significant differences were found between the untreated experimental and untreated control patients in PSA change or velocity at the end of 2 years. CONCLUSIONS: Patients with early-stage prostate cancer choosing active surveillance might be able to avoid or delay conventional treatment for at least 2 years by making changes in their diet and lifestyle.", "title": "Clinical events in prostate cancer lifestyle trial: results from two years of follow-up." }, { "docid": "MED-3271", "text": "Most metastatic tumors, such as those originating in the prostate, lung, and gastrointestinal tract, respond poorly to conventional chemotherapy. Novel treatment strategies for advanced cancer are therefore desperately needed. Dietary restriction of the essential amino acid methionine offers promise as such a strategy, either alone or in combination with chemotherapy or other treatments. Numerous in vitro and animal studies demonstrate the effectiveness of dietary methionine restriction in inhibiting growth and eventually causing death of cancer cells. In contrast, normal host tissues are relatively resistant to methionine restriction. These preclinical observations led to a phase I clinical trial of dietary methionine restriction for adults with advanced cancer. Preliminary findings from this trial indicate that dietary methionine restriction is safe and feasible for the treatment of patients with advanced cancer. In addition, the trial has yielded some preliminary evidence of antitumor activity. One patient with hormone-independent prostate cancer experienced a 25% reduction in serum prostate-specific antigen (PSA) after 12 weeks on the diet, and a second patient with renal cell cancer experienced an objective radiographic response. The possibility that methionine restriction may act synergistically with other cancer treatments such as chemotherapy is being explored. Findings to date support further investigation of dietary methionine restriction as a novel treatment strategy for advanced cancer.", "title": "Can dietary methionine restriction increase the effectiveness of chemotherapy in treatment of advanced cancer?" }, { "docid": "MED-3275", "text": "In tissue cultures of normal adult and malignant mammalian cells, homocystine has been substituted for methionine in a medium rich in folic acid and cyanocobalamin. Normal adult cells thrive. Three highly malignant cell types from three different species, including man, die.", "title": "The Effect of Replacement of Methionine by Homocystine on Survival of Malignant and Normal Adult Mammalian Cells in Culture" }, { "docid": "MED-3920", "text": "Green tea is reported to have wide ranging beneficial health outcomes across epidemiological studies, which have been attributed to its flavonoid content. We investigated whether the flavonoid epigallocatechin gallate (EGCG) modulates brain activity and self-reported mood in a double-blind, placebo controlled crossover study. Participants completed baseline assessments of cognitive and cardiovascular functioning, mood and a resting state electroencephalogram (EEG) before and then 120 min following administration of 300 mg EGCG or matched placebo. EGCG administration was associated with a significant overall increase in alpha, beta and theta activity, also reflected in overall EEG activity, more dominant in midline frontal and central regions, specifically in the frontal gyrus and medial frontal gyrus. In comparison to placebo the EGCG treatment also increased self-rated calmness and reduced self rated stress. This pattern of results suggests that participants in the EGCG condition may have been in a more relaxed and attentive state after consuming EGCG. This is in keeping with the widespread consumption of green tea for its purported relaxing/refreshing properties. The modulation of brain function due to EGCG is deserving of further controlled human studies. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Acute neurocognitive effects of epigallocatechin gallate (EGCG)." }, { "docid": "MED-3280", "text": "Conventional chemotherapies have showed their limits, notably for patients with advanced cancer. New therapeutic strategies must be identified, and the metabolic abnormalities of cancer cells offer such opportunities. Many human cancer cell lines and primary tumors have absolute requirements for methionine, an essential amino acid. In contrast, normal cells are relatively resistant to exogenous methionine restriction. The biochemical mechanism for methionine dependency has been studied extensively, but the fundamental mechanism remains unclear. A number of investigators have attempted to exploit the methionine dependence of tumors for therapeutic effects in vivo. To reduce in vivo methionine in plasma and tumours, dietary and pharmacological treatments have been used. Methionine-free diet or methionine-deprived total parenteral nutrition causes regression of a variety of animal tumours. Alternatively, methionine depletion was achieved by the use of methioninase. This enzyme specifically degrades methionine and inhibits tumour growth in preclinical models. Because of potential toxicity and quality of life problems, prolonged methionine restriction with diet or with methioninase is not suitable for clinical use. Methionine restriction may find greater application in association with various chemotherapeutic agents. Several preclinical studies have demonstrated synergy between methionine restriction and various cytotoxic chemotherapy drugs. The experimental results accumulated during the last three decades suggest that methionine restriction can become an additional cancer therapeutic strategy, notably in association with chemotherapy.", "title": "Methionine dependency and cancer treatment." }, { "docid": "MED-2574", "text": "Inositol hexaphosphate (IP(6)) is a naturally occurring polyphosphorylated carbohydrate, abundantly present in many plant sources and in certain high-fiber diets, such as cereals and legumes. In addition to being found in plants, IP(6) is contained in almost all mammalian cells, although in much smaller amounts, where it is important in regulating vital cellular functions such as signal transduction, cell proliferation, and differentiation. For a long time IP(6) has been recognized as a natural antioxidant. Recently IP(6) has received much attention for its role in cancer prevention and control of experimental tumor growth, progression, and metastasis. In addition, IP(6) possesses other significant benefits for human health, such as the ability to enhance immune system, prevent pathological calcification and kidney stone formation, lower elevated serum cholesterol, and reduce pathological platelet activity. In this review we show the efficacy and discuss some of the molecular mechanisms that govern the action of this dietary agent. Exogenously administered IP(6) is rapidly taken up into cells and dephosphorylated to lower inositol phosphates, which further affect signal transduction pathways resulting in cell cycle arrest. A striking anticancer action of IP(6) was demonstrated in different experimental models. In addition to reducing cell proliferation, IP(6) also induces differentiation of malignant cells. Enhanced immunity and antioxidant properties also contribute to tumor cell destruction. Preliminary studies in humans show that IP(6) and inositol, the precursor molecule of IP(6), appear to enhance the anticancer effect of conventional chemotherapy, control cancer metastases, and improve quality of life. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP(6) + inositol holds great promise in our strategies for cancer prevention and therapy. There is clearly enough evidence to justify the initiation of full-scale clinical trials in humans.", "title": "Protection against cancer by dietary IP6 and inositol." }, { "docid": "MED-2816", "text": "Plants contain numerous polyphenols, which have been shown to reduce inflammation and hereby to increase resistance to disease. Examples of such polyphenols are isothiocyanates in cabbage and broccoli, epigallocatechin in green tee, capsaicin in chili peppers, chalones, rutin and naringenin in apples, resveratrol in red wine and fresh peanuts and curcumin/curcuminoids in turmeric. Most diseases are maintained by a sustained discreet but obvious increased systemic inflammation. Many studies suggest that the effect of treatment can be improved by a combination of restriction in intake of proinflammatory molecules such as advanced glycation end products (AGE), advanced lipoperoxidation end products (ALE), and rich supply of antiinflammatory molecules such as plant polyphenols. To the polyphenols with a bulk of experimental documentation belong the curcuminoid family and especially its main ingredient, curcumin. This review summarizes the present knowledge about these turmericderived ingredients, which have proven to be strong antioxidants and inhibitors of cyclooxigenase-2 (COX-2), lipoxygenase (LOX) and nuclear factor kappa B (NF-kappaB) but also AGE. A plethora of clinical effects are reported in various experimental diseases, but clinical studies in humans are few. It is suggested that supply of polyphenols and particularly curcuminoids might be value as complement to pharmaceutical treatment, but also prebiotic treatment, in conditions proven to be rather therapy-resistant such as Crohn's, long-stayed patients in intensive care units, but also in conditions such as cancer, liver cirrhosis, chronic renal disease, chronic obstructive lung disease, diabetes and Alzheimer's disease.", "title": "Plant-derived health: the effects of turmeric and curcuminoids." }, { "docid": "MED-2649", "text": "Background Dietary fat exerts numerous complex effects on proinflammatory and immunologic pathways. Several epidemiological studies have examined the relationships between intake of fatty acids and/or foods high in fat and allergic rhinitis, but have provided conflicting findings. The current cross-sectional study investigated such relationships in Japan. Methods Study subjects were 1745 pregnant women. The definition of rhinoconjunctivitis was based on criteria from the International Study of Asthma and Allergies in Childhood. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for age; gestation; region of residence; number of older siblings; number of children; smoking; secondhand smoke exposure at home and at work; family history of asthma, atopic eczema, and allergic rhinitis; household income; education; and body mass index. Results The prevalence of rhinoconjunctivitis in the past 12 months was 25.9%. Higher meat intake was significantly associated with an increased prevalence of rhinoconjunctivitis: the adjusted odds ratio between extreme quartiles was 1.71 (95% confidence interval: 1.25-2.35, P for trend = 0.002). No measurable association was found between fish intake and rhinoconjunctivitis. Intake of total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid, and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid intake were not evidently related to the prevalence of rhinoconjunctivitis. Conclusions The current results suggest that meat intake may be positively associated with the prevalence of rhinoconjunctivitis in young adult Japanese women.", "title": "Dietary meat and fat intake and prevalence of rhinoconjunctivitis in pregnant Japanese women: baseline data from the Kyushu Okinawa Maternal and Child Health Study" }, { "docid": "MED-2661", "text": "This paper presents the results of an investigation on the occurrence of alkylphenols (APs) and their ethoxylates (APEs) in 8 edible marine species from the Adriatic Sea and tries to estimate the corresponding intake for the Italian population. Two crustaceans, Nephrops norvegicus (Norway lobster) and Squilla mantis (spottail mantis shrimp), plus six fish species, Engraulis enchrascicolus (anchovy), Scomber scombrus (Atlantic mackerel), Merluccius merluccius (European hake), Mullus barbatus (red mullet), Solea vulgaris (common sole) and Lophius piscatorius (angler) were analyzed for their content of nonylphenol (NP), octylphenol (OP) and octylphenol polyethoxylates (OPEs). These compounds were found in all analysed samples. NP was detected at the highest concentrations: 118-399 and 9.5-1431 ng g(-1) fresh weight (fw) respectively in crustaceans and fish. OP was found at respective levels of 2.7-4.7 and 0.3-3.8 ng g(-1) fw in crustaceans and fish, whereas OPE was determined at respective concentrations of 1.2-16.8 and 0.2-21.1 ng g(-1) fw in the same species. These results, together with those from a previous study on 4 edible mollusc, allow to estimate respective daily intakes for NP, OP, and OPE of about 12, 0.1, and 0.1 microg day(-1) for an Italian adult living along the Adriatic Coast. In relation to NP and OP, these intakes are much lower than the doses associated with toxic effects in laboratory animals (9 mg kg(-1) bw for rats). Nevertheless, data of exposure from other sources to these chemicals and others with similar biological characteristics are needed.", "title": "Alkylphenols and alkylphenol ethoxylates contamination of crustaceans and fishes from the Adriatic Sea (Italy)." }, { "docid": "MED-2646", "text": "BACKGROUND: Certain foods may increase or decrease the risk of developing asthma, rhinoconjunctivitis and eczema. We explored the impact of the intake of types of food on these diseases in Phase Three of the International Study of Asthma and Allergies in Childhood. METHODS: Written questionnaires on the symptom prevalence of asthma, rhinoconjunctivitis and eczema and types and frequency of food intake over the past 12 months were completed by 13-14-year-old adolescents and by the parents/guardians of 6-7-year-old children. Prevalence ORs were estimated using logistic regression, adjusting for confounders, and using a random (mixed) effects model. RESULTS: For adolescents and children, a potential protective effect on severe asthma was associated with consumption of fruit ≥3 times per week (OR 0.89, 95% CI 0.82 to 0.97; OR 0.86, 95% CI 0.76 to 0.97, respectively). An increased risk of severe asthma in adolescents and children was associated with the consumption of fast food ≥3 times per week (OR 1.39, 95% CI 1.30 to 1.49; OR 1.27, 95% CI 1.13 to 1.42, respectively), as well as an increased risk of severe rhinoconjunctivitis and severe eczema. Similar patterns for both ages were observed for regional analyses, and were consistent with gender and affluence categories and with current symptoms of all three conditions. CONCLUSIONS: If the association between fast foods and the symptom prevalence of asthma, rhinoconjunctivitis and eczema is causal, then the findings have major public health significance owing to the rising consumption of fast foods globally.", "title": "Do fast foods cause asthma, rhinoconjunctivitis and eczema? Global findings from the International Study of Asthma and Allergies in Childhood (ISAA..." }, { "docid": "MED-4714", "text": "This study investigated the association between pickled vegetable consumption and the risk of breast cancer using a validated food frequency questionnaire. A total of 358 patients with breast cancer who were matched to 360 healthy controls by age (using a 5-yr age distribution) were recruited from the National Cancer Center in South Korea. After adjusting for nondietary risk factors, total vegetable intake was inversely associated with risk of breast cancer. However, unlike nonpickled vegetables, pickled vegetable intake and its proportion relative to total vegetables were positively associated with the risk of breast cancer, and this association was more profound and consistent when pickled vegetable intake was considered as a proportion relative to total vegetables (odds ratio [OR] = 6.24, 95% confidence interval [CI] = 3.55-10.97; P for trend <0.001 for highest vs. lowest quartiles of intake) than as the absolute consumed amount (OR = 2.47, 95% CI = 1.45-4.21; P for trend = 0.015 for highest vs. lowest quartiles of intake). These results suggest that not only the amount of total vegetable intake but also the amounts of different types of vegetable (i.e., pickled or nonpickled) and their proportions relative to total vegetables are significantly associated with the risk of breast cancer.", "title": "Vegetables, but not pickled vegetables, are negatively associated with the risk of breast cancer." }, { "docid": "MED-5121", "text": "Chamomile (Matricaria chamomilla), a popular herb valued for centuries as a traditional medicine, has been used to treat various human ailments; however, its anticancer activity is unknown. We evaluated the anticancer properties of aqueous and methanolic extracts of chamomile against various human cancer cell lines. Exposure of chamomile extracts caused minimal growth inhibitory responses in normal cells, whereas a significant decrease in cell viability was observed in various human cancer cell lines. Chamomile exposure resulted in differential apoptosis in cancer cells but not in normal cells at similar doses. HPLC analysis of chamomile extract confirmed apigenin 7-O-glucoside as the major constituent of chamomile; some minor glycoside components were also observed. Apigenin glucosides inhibited cancer cell growth but to a lesser extent than the parent aglycone, apigenin. Ex vivo experiments suggest that deconjugation of glycosides occurs in vivo to produce aglycone, especially in the small intestine. This study represents the first reported demonstration of the anticancer effects of chamomile. Further investigations of the mechanism of action of chamomile are warranted in evaluating the potential usefulness of this herbal remedy in the management of cancer patients.", "title": "Antiproliferative and apoptotic effects of chamomile extract in various human cancer cells." }, { "docid": "MED-3245", "text": "Cruciferous vegetables, tomato sauce, and legumes have been associated with reduced risk of incident advanced prostate cancer. In vitro and animal studies suggest these foods may inhibit progression of prostate cancer, but there are limited data in men. Therefore, we prospectively examined whether intake of total vegetables, and specifically cruciferous vegetables, tomato sauce, and legumes, after diagnosis reduce risk of prostate cancer progression among 1,560 men diagnosed with non-metastatic prostate cancer and participating in the Cancer of the Prostate Strategic Urologic Research Endeavor, a United States prostate cancer registry. As a secondary analysis, we also examined other vegetable sub-groups, total fruit, and subgroups of fruits. The participants were diagnosed primarily at community-based clinics and followed from 2004–2009. We assessed vegetable and fruit intake via a semi-quantitative food frequency questionnaire, and ascertained prostate cancer outcomes via urologist report and medical records. We observed 134 events of progression (53 biochemical recurrences, 71 secondary treatments likely due to recurrence, six bone metastases, four prostate cancer deaths) during 3,171 person-yrs. Men in the fourth quartile of post-diagnostic cruciferous vegetable intake had a statistically significant 59% decreased risk of prostate cancer progression compared to men in the lowest quartile (hazard ratio (HR): 0.41; 95% confidence interval (CI): 0.22, 0.76; p-trend: 0.003). No other vegetable or fruit group was statistically significantly associated with risk of prostate cancer progression. In conclusion, cruciferous vegetable intake after diagnosis may reduce risk of prostate cancer progression.", "title": "Vegetable and fruit intake after diagnosis and risk of prostate cancer progression" }, { "docid": "MED-4647", "text": "Although multivitamin/mineral supplements are commonly used in the United States, the efficacy of these supplements in preventing chronic disease or premature death is unclear. To assess the relation of multivitamin use with mortality and cancer, the authors prospectively examined these associations among 182,099 participants enrolled in the Multiethnic Cohort Study between 1993 and 1996 in Hawaii and California. During an average 11 years of follow-up, 28,851 deaths were identified. In Cox proportional hazards models controlling for tobacco use and other potential confounders, no associations were found between multivitamin use and mortality from all causes (for users vs. nonusers: hazard ratio = 1.07, 95% confidence interval: 0.96, 1.19 for men; hazard ratio = 0.96, 95% confidence interval: 0.85, 1.09 for women), cardiovascular diseases, or cancer. The findings did not vary across subgroups by ethnicity, age, body mass index, preexisting illness, single vitamin/mineral supplement use, hormone replacement therapy use, and smoking status. There also was no evidence indicating that multivitamin use was associated with risk of cancer, overall or at major sites, such as lung, colorectum, prostate, and breast. In conclusion, there was no clear decrease or increase in mortality from all causes, cardiovascular disease, or cancer and in morbidity from overall or major cancers among multivitamin supplement users.", "title": "Multivitamin Use and the Risk of Mortality and Cancer Incidence" }, { "docid": "MED-4755", "text": "OBJECTIVE: To critically evaluate the clinical evidence, and when not available, the animal data, most relevant to concerns that isoflavone exposure in the form of supplements or soy foods has feminizing effects on men. DESIGN: Medline literature review and cross-reference of published data. RESULT(S): In contrast to the results of some rodent studies, findings from a recently published metaanalysis and subsequently published studies show that neither isoflavone supplements nor isoflavone-rich soy affect total or free testosterone (T) levels. Similarly, there is essentially no evidence from the nine identified clinical studies that isoflavone exposure affects circulating estrogen levels in men. Clinical evidence also indicates that isoflavones have no effect on sperm or semen parameters, although only three intervention studies were identified and none were longer than 3 months in duration. Finally, findings from animal studies suggesting that isoflavones increase the risk of erectile dysfunction are not applicable to men, because of differences in isoflavone metabolism between rodents and humans and the excessively high amount of isoflavones to which the animals were exposed. CONCLUSION(S): The intervention data indicate that isoflavones do not exert feminizing effects on men at intake levels equal to and even considerably higher than are typical for Asian males. Copyright 2010. Published by Elsevier Inc.", "title": "Soybean isoflavone exposure does not have feminizing effects on men: a critical examination of the clinical evidence." }, { "docid": "MED-4385", "text": "The idea that normal constituents of the diet can influence visual function is not new. As early as 1782, Buzzi identified the yellow of the macula and Schulze (1866) specifically postulated that the yellow pigments led to improvements in human vision. These pigments were later found to be derived from dietary lutein and zeaxanthin that are known to be oxygenated carotenoids (xanthophylls). Walls and Judd (1933) postulated that these yellow intraocular pigments could improve visual performance by absorbing light scattered both within (for example, glare) and outside of the eye (increasing visual range by absorbing blue light scattered in the atmosphere), and by improving spatial vision through enhancing contrast and reducing chromatic blur. In this article, evidence for these ideas is reviewed with particular emphasis towards more recent data on glare effects.", "title": "The influence of dietary lutein and zeaxanthin on visual performance." }, { "docid": "MED-2559", "text": "Inositol hexaphosphate (IP6) has anti-cancer properties, but recently other extracellular functions have been observed for IP6, including enhancing superoxide production and phagocytosis by neutrophils in the presence of microbial stimuli. This study investigated other inflammatory functions of IP6 on adherent neutrophils. The effect of IP6 on the release of IL-8, tumour necrosis factor (TNF-alpha) and IL-6 by neutrophils attached to either plastic or laminin for up to 6 hours in response to stimulation with lipopolysaccharide or N-formyl-Met-Leu-Phe (fMLP) was investigated. An increase in IL-8 secretion by stimulated cells occurred in the presence of IP6. The incubation of cells attached to laminin with IP6 alone (100-250 BM) did not effect cell morphology, but in the presence of 10(-7) M fMLP altered cell shape. A direct effect of IP6 on cell function was to trigger a sustained assembly of F-actin. Thus, exposure of neutrophils to low levels of IP6 appears to modulate selective neutrophil functions.", "title": "Effect of IP6 on human neutrophil cytokine production and cell morphology." }, { "docid": "MED-3744", "text": "Consumption of fruits and vegetables has been associated with reduced risk of chronic diseases such as cardiovascular disease and cancer. Phytochemicals, especially phenolics, in fruits and vegetables are suggested to be the major bioactive compounds for the health benefits. However, the phenolic contents and their antioxidant activities in fruits and vegetables were underestimated in the literature, because bound phenolics were not included. This study was designed to investigate the profiles of total phenolics, including both soluble free and bound forms in common fruits, by applying solvent extraction, base digestion, and solid-phase extraction methods. Cranberry had the highest total phenolic content, followed by apple, red grape, strawberry, pineapple, banana, peach, lemon, orange, pear, and grapefruit. Total antioxidant activity was measured using the TOSC assay. Cranberry had the highest total antioxidant activity (177.0 +/- 4.3 micromol of vitamin C equiv/g of fruit), followed by apple, red grape, strawberry, peach, lemon, pear, banana, orange, grapefruit, and pineapple. Antiproliferation activities were also studied in vitro using HepG(2) human liver-cancer cells, and cranberry showed the highest inhibitory effect with an EC(50) of 14.5 +/- 0.5 mg/mL, followed by lemon, apple, strawberry, red grape, banana, grapefruit, and peach. A bioactivity index (BI) for dietary cancer prevention is proposed to provide a new alternative biomarker for future epidemiological studies in dietary cancer prevention and health promotion.", "title": "Antioxidant and antiproliferative activities of common fruits." }, { "docid": "MED-3923", "text": "OBJECTIVE: Inadvertent exposure to the ubiquitous weed, Urtica dioica, called \"stinging nettles\" produces an immediate stinging and burning sensation on the skin. This investigation evaluates the structural effect that stinging nettle spicules may have on the clinical manifestation of these symptoms. This hypothesis was investigated by exposing murine skin to stinging nettles and then evaluating the skin using electron microscopy. It was hypothesized that the mechanism of action of stinging nettles is both biochemical and mechanical, which may have clinical significance regarding treatment for acute exposure. METHODS: Fresh post-mortem dermis samples from the carcasses of genetically modified hairless mice were brushed under the stem and leaf of a stinging nettle plant, mimicking the clinical method of exposure a patient might experience. Another set of mouse skin samples was obtained but not exposed to the nettles. Both sets of skin samples were imaged with scanning electron microscopy. RESULTS: The skin samples that were not exposed to nettle leaves were uniform, with occasional striated hairs on the skin surface and no nettle spicules. The skin samples exposed to nettle leaves showed many smooth nettle spicules piercing the skin surface. A few spicules retained their bases, which appear empty of any liquid contents. CONCLUSIONS: The mechanism of action of stinging nettles dermatitis appears to be both biochemical and mechanical. Impalement of spicules into the skin likely accounts for the mechanical irritation in addition to the known adverse chemical effects of stinging nettles. Further investigation of treatment modalities is warranted. Copyright © 2011 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.", "title": "Mechanism of action of stinging nettles." }, { "docid": "MED-2568", "text": "Inositol hexaphosphate (InsP6 or IP6) is ubiquitous. At 10 microM to 1 mM concentrations, IP6 and its lower phosphorylated forms (IP(1-5)) as well as inositol (Ins) are contained in most mammalian cells, wherein they are important in regulating vital cellular functions such as signal transduction, cell proliferation and differentiation. A striking anti-cancer action of IP6 has been demonstrated both in vivo and in vitro, which is based on the hypotheses that exogenously administered IP6 may be internalized, dephosphorylated to IP(1-5), and inhibit cell growth. There is additional evidence that Ins alone may further enhance the anti-cancer effect of IP6. Besides decreasing cellular proliferation, IP6 also causes differentiation of malignant cells often resulting in a reversion to normal phenotype. These data strongly point towards the involvement of signal transduction pathways, cell cycle regulatory genes, differentiation genes, oncogenes and perhaps, tumor suppressor genes in bringing about the observed anti-neoplastic action of IP6.", "title": "IP6: a novel anti-cancer agent." }, { "docid": "MED-4756", "text": "BACKGROUND/OBJECTIVES: Little is known about nutritional factors that influence circulating concentrations of steroid hormones, which are consistently associated with risk of breast cancer for postmenopausal women. We aimed to investigate the association between consumption of animal products and the plasma concentrations of steroid hormones and sex hormone-binding globulin (SHBG). SUBJECTS/METHODS: Cross-sectional analysis was conducted on plasma from 766 naturally postmenopausal women. We measured plasma concentrations of steroid hormones and SHBG, and estimated dietary intakes using a 121-item food frequency questionnaire. Log-transformed values of hormone concentrations were regressed on quartiles of intake of meat and dairy products among food items, and fats, proteins and cholesterol among nutrient intake. RESULTS: Total red and fresh red meat consumption was negatively associated with SHBG levels (P for trend=0.04 and <0.01, respectively). Mean SHBG concentrations were approximately 8% and 13% lower for women in the highest quartile compared with the lowest quartile of total red and fresh red meat consumption, respectively. Positive associations were observed between dairy product consumption and total and free estradiol concentrations (P for trend=0.02 and 0.03, respectively). Mean concentrations of total and free estradiol were 15 and 14% higher for women in the highest quartile of dairy product consumption than for those in the lowest quartile, respectively. No associations were observed with consumption of processed meat, chicken, fish, eggs, cholesterol, fats or protein. CONCLUSIONS: Our study suggests that greater consumption of total red and fresh red meat and dairy products might influence circulating concentrations of SHBG and estradiol, respectively. Confirmation and further investigation is required.", "title": "Consumption of animal products, their nutrient components and postmenopausal circulating steroid hormone concentrations." }, { "docid": "MED-2658", "text": "The prevalence of allergic diseases has increased in recent decades. Allergic diseases, particularly asthma, are complex diseases with strong gene-environment interactions. Epidemiological studies have identified a variety of risk factors for the development of allergic diseases. Among them, endocrine-disrupting chemicals (EDCs) play an important role in triggering or exacerbating these diseases. 4-Nonylphenol (NP) and 4-octylphenol (OP)--two major alkylphenols--have been recognized as common toxic and xenobiotic endocrine disrupters. Due to their low solubility, high hydrophobicity, and low estrogenic activity, they tend to accumulate in the human body and may be associated with the adverse effects of allergic diseases. Recently, new evidence has supported the importance of alkylphenols in the in vitro allergic response. This review focuses on the effects of alkylphenols on several key cell types in the context of allergic inflammation. Copyright © 2012. Published by Elsevier B.V.", "title": "Alkylphenols--potential modulators of the allergic response." }, { "docid": "MED-2575", "text": "Introduction Matrix metalloproteinases (MMPs) have repeatedly been shown to play a very active role in extracellular matrix degradation associated with tumor invasion and metastasis. Tissue inhibitors of MMPs (TIMPs) are well-known for their ability to inhibit MMP activity thereby inhibiting malignant progression. Inositol hexaphosphate (IP6 phytic acid) has been recognized to have both preventive and therapeutic effects against various cancers including that of colon. In in vitro studies, IP6 has been demonstrated to inhibit cancer cell adhesion and migration. In the present study, the effect of IP6 on the expression of MMP and TIMP genes was evaluated in unstimulated and IL-1β-stimulated colon cancer cell line Caco-2. Materials and methods Real-time QRT-PCR was used to validate the transcription level of selected MMP and TIMP genes in Caco-2 cells after treatment with 1 ng/ml of IL-1β, 2.5 mM of IP6, and both for 6, 12, and 24 h. Results Stimulation of cells with IL-1β only resulted in an overexpression of MMP and their TIMP mRNAs. A significant decrease in MMP-13, MMP-3, MMP-2, and TIMP-1 basal expression was achieved by IP6. IP6 was also an efficient downregulator of MMP-1, MMP-9, and TIMP-2 genes transcription stimulated by IL-1β in 6 h lasting culture. After 12 h, IL-1β-induced MMP-2 mRNA expression was significantly reduced by IP6. Conclusion Proinflammatory cytokine IL-1β upregulates MMP and TIMP mRNAs expression in colon cancer epithelial cells Caco-2. IP6 (2.5 mM) influences constitutive expression of both MMP and TIMP genes and downregulates IL-1β stimulated transcription of some of these genes. IP6 exerts its anti-metastatic activity through modulation of MMP and TIMP genes expression to prevent cancer cell migration and invasion.", "title": "The effect of inositol hexaphosphate on the expression of selected metalloproteinases and their tissue inhibitors in IL-1β-stimulated colon cancer cells" }, { "docid": "MED-5178", "text": "Lignans, derived from flaxseed, are phyto-oestrogens being increasingly studied for their health benefits. An 8-week, randomised, double-blind, placebo-controlled study was conducted in fifty-five hypercholesterolaemic subjects, using treatments of 0 (placebo), 300 or 600 mg/d of dietary secoisolariciresinol diglucoside (SDG) from flaxseed extract to determine the effect on plasma lipids and fasting glucose levels. Significant treatment effects were achieved (P < 0.05 to < 0.001) for the decrease of total cholesterol (TC), LDL-cholesterol (LDL-C) and glucose concentrations, as well as their percentage decrease from baseline. At weeks 6 and 8 in the 600 mg SDG group, the decreases of TC and LDL-C concentrations were in the range from 22.0 to 24.38 % respectively (all P < 0.005 compared with placebo). For the 300 mg SDG group, only significant differences from baseline were observed for decreases of TC and LDL-C. A substantial effect on lowering concentrations of fasting plasma glucose was also noted in the 600 mg SDG group at weeks 6 and 8, especially in the subjects with baseline glucose concentrations > or = 5.83 mmol/l (lowered 25.56 and 24.96 %; P = 0.015 and P = 0.012 compared with placebo, respectively). Plasma concentrations of secoisolariciresinol (SECO), enterodiol (ED) and enterolactone were all significantly raised in the groups supplemented with flaxseed lignan. The observed cholesterol-lowering values were correlated with the concentrations of plasma SECO and ED (r 0.128-0.302; P < 0.05 to < 0.001). In conclusion, dietary flaxseed lignan extract decreased plasma cholesterol and glucose concentrations in a dose-dependent manner.", "title": "Dietary flaxseed lignan extract lowers plasma cholesterol and glucose concentrations in hypercholesterolaemic subjects." }, { "docid": "MED-4230", "text": "PURPOSE OF REVIEW: Although age, genetics, and sex steroid hormones play prominent roles in the cause of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS), recent epidemiological studies suggest that modifiable lifestyle factors also contribute substantially to the pathogenesis of these conditions. RECENT FINDINGS: Lifestyle and metabolic factors associated with significantly increased risks of benign prostatic hyperplasia and lower urinary tract symptoms include obesity, diabetes, and meat and fat consumption. Factors associated with decreased risks include physical activity, moderate alcohol intake, and vegetable consumption. Factors for which no clear risk patterns have emerged include lipids and smoking. Randomized clinical trials of lifestyle alterations - such as weight loss, exercise, and diet - for the prevention or treatment of benign prostatic hyperplasia and lower urinary tract symptoms have yet to be performed. SUMMARY: Lifestyle factors present a novel opportunity for the prevention and treatment of benign prostatic hyperplasia and lower urinary tract symptoms. Although clinical trials of lifestyle modifications have not yet been undertaken, promotion of healthy lifestyle alternatives within the context of standard benign prostatic hyperplasia and lower urinary tract symptoms treatment algorithms is potentially beneficial.", "title": "Lifestyle factors, benign prostatic hyperplasia, and lower urinary tract symptoms." }, { "docid": "MED-3244", "text": "Diet may represent a modifiable prostate cancer (CaP) risk factor, but a vegetable-based prostate-healthy diet is a major change for most men. We used a ratio of animal:vegetable proteins (A:V ratio) to evaluate whether a comprehensive dietary change was self-sustaining following completion of 11 weekly dietary and cooking classes that integrated mindfulness training (MT). Thirty-six men with recurring CaP were randomized to the intervention or wait-list control. Assessments were at baseline, three months and six months. Of the 17 men randomized to the intervention, 14 completed the requirements. Nineteen were randomized to control and 17 completed requirements. Compared to controls, a significant post-intervention (3 months) decrease in A:V ratio in the intervention group (p=.01) was self-maintained 3 months post-intervention (p=0.049). At each assessment, the A:V ratio was correlated with lycopene, fiber, saturated fat, and dietary cholesterol; four dietary components linked to clinically relevant outcomes in CaP. Change in A:V ratio was also significantly correlated with changes in fiber, saturated fat and dietary cholesterol intake. Participants reported regular MT practice and there was a significant correlation between MT practice and changes in both initiation and maintenance of the change in the A:V ratio. These pilot results provide encouraging evidence for the feasibility of a dietary program that includes MT in supporting dietary change for men with recurrent CaP and invite further study to explore the possible role of MT as a means of supporting both initiation of dietary changes and maintenance of those changes over time.", "title": "A Novel Measure of Dietary Change in a Prostate Cancer Dietary Program Incorporating Mindfulness Training" }, { "docid": "MED-2578", "text": "The incidence of colonic cancer differs widely between various human populations. It has been suggested that dietary fiber content is of utmost importance and is inversely related to the occurrence of colonic cancer. However, high-fiber diets are not always correlated with low frequency of colonic cancer, suggesting the involvement of additional dietary constituents. Inositol hexaphosphate (phytic acid) is an abundant plant seed component present in many, but not all, fiber-rich diets. The authors have found that phytic acid is a potent inhibitor of iron-mediated generation of the hazardous oxidant, hydroxyl radical. Herein, the authors propose that inhibition of intracolonic hydroxyl radical generation, via the chelation of reactive iron by phytic acid, may help explain the suppression of colonic carcinogenesis and other inflammatory bowel diseases by diets rich in phytic acid.", "title": "Dietary suppression of colonic cancer. Fiber or phytate?" }, { "docid": "MED-4646", "text": "Objective We examined the association between adolescent fiber intake and proliferative BBD, a marker of increased breast cancer risk, in the Nurses’ Health Study II. Methods Among 29,480 women who completed a high school diet questionnaire in 1998, 682 proliferative BBD cases were identified and confirmed by centralized pathology review between 1991 and 2001. Multivariate-adjusted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results Women in the highest quintile of adolescent fiber intake had a 25% lower risk of proliferative BBD (multivariate HR (95% CI): 0.75 (0.59, 0.96), p-trend = 0.01) than women in the lowest quintile. High school intake of nuts and apples was also related to significantly reduced BBD risk. Women consuming ≥2 servings of nuts/week had a 36% lower risk (multivariate HR (95% CI): 0.64 (0.48, 0.85), p-trend < 0.01) than women consuming <1 serving/month. Results were essentially the same when the analysis was restricted to prospective cases (n = 142) diagnosed after return of the high school diet questionnaire. Conclusions These findings support the hypothesis that dietary intake of fiber and nuts during adolescence influence subsequent risk of breast disease and may suggest a viable means for breast cancer prevention.", "title": "Intake of Fiber and Nuts during Adolescence and Incidence of Proliferative Benign Breast Disease" }, { "docid": "MED-3922", "text": "The aqueous extracts of Hibiscus sabdariffa have been commonly used in folk medicine. Nevertheless, the compounds or metabolites responsible for its healthy effects have not yet been identified. The major metabolites present in rat plasma after acute ingestion of a polyphenol-enriched Hibiscus sabdariffa extract were characterized and quantified in order to study their bioavailability. The antioxidant status of the plasma samples was also measured through several complementary antioxidant techniques. High-performance liquid chromatography coupled to time-of-flight mass spectrometry (HPLC-ESI-TOF-MS) was used for the bioavailability study. The antioxidant status was measured by ferric reducing ability of plasma method, thiobarbituric acid reactive substances assay, and superoxide dismutase activity assay. Seventeen polyphenols and metabolites have been detected and quantified. Eleven of these compounds were metabolites. Although phenolic acids were found in plasma without any modification in their structures, most flavonols were found as quercetin or kaempferol glucuronide conjugates. Flavonol glucuronide conjugates, which show longer half-life elimination values, are proposed to contribute to the observed lipid peroxidation inhibitory activity in the cellular membranes. By contrast, phenolic acids appear to exert their antioxidant activity through ferric ion reduction and superoxide scavenging at shorter times. We propose that flavonol-conjugated forms (quercetin and kaempferol) may be the compounds responsible for the observed antioxidant effects and contribute to the healthy effects of H. sabdariffa polyphenolic extract. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.", "title": "Bioavailability study of a polyphenol-enriched extract from Hibiscus sabdariffa in rats and associated antioxidant status." }, { "docid": "MED-2769", "text": "The authors investigated whether early-life residency in certain areas of Iceland marked by distinct differences in milk intake was associated with risk of prostate cancer in a population-based cohort of 8,894 men born between 1907 and 1935. Through linkage to cancer and mortality registers, the men were followed for prostate cancer diagnosis and mortality from study entry (in waves from 1967 to 1987) through 2009. In 2002–2006, a subgroup of 2,268 participants reported their milk intake in early, mid-, and current life. During a mean follow-up period of 24.3 years, 1,123 men were diagnosed with prostate cancer, including 371 with advanced disease (stage 3 or higher or prostate cancer death). Compared with early-life residency in the capital area, rural residency in the first 20 years of life was marginally associated with increased risk of advanced prostate cancer (hazard ratio = 1.29, 95% confidence interval (CI): 0.97, 1.73), particularly among men born before 1920 (hazard ratio = 1.64, 95% CI: 1.06, 2.56). Daily milk consumption in adolescence (vs. less than daily), but not in midlife or currently, was associated with a 3.2-fold risk of advanced prostate cancer (95% CI: 1.25, 8.28). These data suggest that frequent milk intake in adolescence increases risk of advanced prostate cancer.", "title": "Milk Intake in Early Life and Risk of Advanced Prostate Cancer" }, { "docid": "MED-3734", "text": "Cranberry products and especially cranberry juice (CJ) have been consumed for health reasons primarily due to their effect on urinary tract infections. We investigated the quantity of both free and total (after hydrolysis) phenolic antioxidants in cranberry products using the Folin assay. The order of amount of total polyphenols in cranberry foods on a fresh weight basis was as follows: dried > frozen > sauce > jellied sauce. On a serving size basis for all cranberry products, the order was as follows: frozen > 100% juice > dried > 27% juice > sauce > jellied sauce. High fructose corn syrup (HFCS) is a major source of sugar consumption in the U.S. and contains both glucose and fructose, potential mediators of oxidative stress. We investigated the effect of the consumption of HFCS and ascorbate with CJ antioxidants or without CJ (control) given to 10 normal individuals after an overnight fast. Plasma antioxidant capacity, glucose, triglycerides, and ascorbate were measured 6 times over 7 h after the consumption of a single 240 mL serving of the two different beverages. The control HFCS caused a slight decrease in plasma antioxidant capacity at all time points and thus an oxidative stress in spite of the presence of ascorbate. CJ produced an increase in plasma antioxidant capacity that was significantly greater than control HFCS at all time points. Postprandial triglycerides, due to fructose in the beverages, were mainly responsible for the oxidative stress and were significantly correlated with the oxidative stress as measured by the antioxidant capacity. Cranberries are an excellent source of high quality antioxidants and should be examined in human supplementation studies.", "title": "Cranberries and cranberry products: powerful in vitro, ex vivo, and in vivo sources of antioxidants." }, { "docid": "MED-4891", "text": "The current annual incidence of sudden cardiac death in the US is likely to be in the range of 180–250,000 per year. Coinciding with the decreased mortality from coronary artery disease, there is evidence pointing toward a significant decrease in rates of sudden cardiac death in the US during the second half of the twentieth century. However the alarming rise in prevalence of obesity and diabetes in the first decade of the new millennium both in the US and worldwide, would indicate that this favorable trend is unlikely to persist. We are likely to witness a resurgence of coronary artery disease and heart failure, as a result of which sudden cardiac death will have to be confronted as a shared and indiscriminate, worldwide public health problem. There is also increasing recognition of the fact that discovery of meaningful and relevant risk stratification and prevention methodologies will require careful prospective community-wide analyses, with access to large archives of DNA, serum and tissue that link with well-phenotyped databases. The purpose of this review is to summarize current knowledge of sudden cardiac death epidemiology. We will discuss the significance and strengths of community-wide evaluations of sudden cardiac death, summarize recent observations from such studies, and finally highlight specific potential predictors that warrant further evaluation as determinants of sudden cardiac death in the general population.", "title": "Epidemiology of Sudden Cardiac Death: Clinical and Research Implications" }, { "docid": "MED-3274", "text": "Objective To determine whether dogs can be trained to identify people with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. Design Experimental, “proof of principle” study in which six dogs were trained to discriminate between urine from patients with bladder cancer and urine from diseased and healthy controls and then evaluated in tests requiring the selection of one bladder cancer urine sample from six controls. Participants 36 male and female patients (age range 48-90 years) presenting with new or recurrent transitional cell carcinoma of the bladder (27 samples used for training; 9 used for formal testing); 108 male and female controls (diseased and healthy, age range 18-85 years—54 samples used in training; 54 used for testing). Main outcome measure Mean proportion of successes per dog achieved during evaluation, compared with an expected value of 1 in 7 (14%). Results Taken as a group, the dogs correctly selected urine from patients with bladder cancer on 22 out of 54 occasions. This gave a mean success rate of 41% (95% confidence intervals 23% to 58% under assumptions of normality, 26% to 52% using bootstrap methods), compared with 14% expected by chance alone. Multivariate analysis suggested that the dogs' capacity to recognise a characteristic bladder cancer odour was independent of other chemical aspects of the urine detectable by urinalysis. Conclusions Dogs can be trained to distinguish patients with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. This suggests that tumour related volatile compounds are present in urine, imparting a characteristic odour signature distinct from those associated with secondary effects of the tumour, such as bleeding, inflammation, and infection.", "title": "Olfactory detection of human bladder cancer by dogs: proof of principle study" }, { "docid": "MED-4757", "text": "The purpose of the present study was to investigate the sex hormonal and metabolic profiles in vegetarians and compare these with the profiles in omnivores. The design of the present study was cross-sectional. The study sample of pre- and post-menopausal women included forty-one omnivores and twenty-one vegetarians. Thereafter we determined: (1) plasma sex hormones, (2) fasting insulin, NEFA as well as apo-A and apo-B, (3) BMI, (4) a dietary profile (3 d dietary records), (5) physical activity and (6) total faecal excretion per 72 h and total urinary excretion per 72 h. Vegetarians showed higher levels of sex hormone-binding globulin (SHBG), apo-A, total faecal excretion per 72 h and total fibre intake as well as lower levels of apo-B, free oestradiol, free testosterone, dehydroepiandrosterone sulfate (DHEA-s) and BMI. Interestingly, after controlling for BMI, significant differences between groups still persisted except for apo-B. Moreover, stepwise regression analysis showed that total fibre intake explained 15.2 % of the variation in SHBG in our cohort, which accounted for the greatest source of unique variance. Results of the present study indicate that pre- and post-menopausal vegetarians present higher concentrations of SHBG, which could be explained, in part, by higher levels of fibre intake. This may explain, at least in part, the lower risk of developing type 2 diabetes.", "title": "Comparison of sex hormonal and metabolic profiles between omnivores and vegetarians in pre- and post-menopausal women." }, { "docid": "MED-3276", "text": "Methionine is an essential amino acid with many key roles in mammalian metabolism such as protein synthesis, methylation of DNA and polyamine synthesis. Restriction of methionine may be an important strategy in cancer growth control particularly in cancers that exhibit dependence on methionine for survival and proliferation. Methionine dependence in cancer may be due to one or a combination of deletions, polymorphisms or alterations in expression of genes in the methionine de novo and salvage pathways. Cancer cells with these defects are unable to regenerate methionine via these pathways. Defects in the metabolism of folate may also contribute to the methionine dependence phenotype in cancer. Selective killing of methionine dependent cancer cells in co-culture with normal cells has been demonstrated using culture media deficient in methionine. Several animal studies utilizing a methionine restricted diet have reported inhibition of cancer growth and extension of a healthy life-span. In humans, vegan diets, which can be low in methionine, may prove to be a useful nutritional strategy in cancer growth control. The development of methioninase which depletes circulating levels of methionine may be another useful strategy in limiting cancer growth. The application of nutritional methionine restriction and methioninase in combination with chemotherapeutic regimens is the current focus of clinical studies. Copyright © 2012 Elsevier Ltd. All rights reserved.", "title": "A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension." }, { "docid": "MED-3785", "text": "PURPOSE: Components of one-carbon metabolism are believed to influence cancer development with suggested mechanisms, including DNA methylation and DNA repair mechanisms. However, few prospective studies have investigated one-carbon metabolism in relation to prostate cancer risk, and the results have been conflicting. The aim of this study was to do a comprehensive investigation of the components of one-carbon metabolism in relation to prostate cancer risk. A panel of seven circulating B vitamins and related metabolites was selected, most of which have not been studied before. MATERIALS AND METHODS: We analyzed plasma concentrations of betaine, choline, cysteine, methionine, methylmalonic acid (MMA), vitamin B2, and vitamin B6 in 561 cases and 1,034 controls matched for age and recruitment date, nested within the population-based Northern Sweden Health and Disease Cohort. Relative risks of prostate cancer were estimated by conditional logistic regression. RESULTS: Positive associations with prostate cancer risk were observed for choline and vitamin B2, and an inverse association was observed for MMA. The relative risks for a doubling in concentrations were 1.46 [95% confidence interval (95% CI), 1.04-2.05; P(trend) = 0.03] for choline, 1.11 (95% CI, 1.00-1.23; P(trend) = 0.04) for vitamin B2, and 0.78 (95% CI, 0.63-0.97; P(trend) = 0.03) for MMA. Concentrations of betaine, cysteine, methionine, and vitamin B6 were not associated with prostate cancer risk. CONCLUSION: The results of this large prospective study suggest that elevated plasma concentrations of choline and vitamin B2 may be associated with an increased risk of prostate cancer. These novel findings support a role of one-carbon metabolism in prostate cancer etiology and warrant further investigation.", "title": "One-carbon metabolism and prostate cancer risk: prospective investigation of seven circulating B vitamins and metabolites." }, { "docid": "MED-2651", "text": "The aims of this study were to determine the concentrations of 4-nonylphenol (NP) and 4-octylphenol (OP) in 59 human milk samples and to examine related factors including mothers' demographics and dietary habits. Women who consumed over the median amount of cooking oil had significantly higher OP concentrations (0.98 ng/g) than those who consumed less (0.39 ng/g) (P < 0.05). OP concentration was significantly associated with the consumption of cooking oil (beta = 0.62, P < 0.01) and fish oil capsules (beta = 0.39, P < 0.01) after adjustment for age and body mass index (BMI). NP concentration was also significantly associated with the consumption of fish oil capsules (beta = 0.38, P < 0.01) and processed fish products (beta = 0.59, P < 0.01). The food pattern of cooking oil and processed meat products from factor analysis was strongly associated with OP concentration in human milk (P < 0.05). These determinations should aid in suggesting foods for consumption by nursing mothers in order to protect their infants from NP/OP exposure. 2010 Elsevier Ltd. All rights reserved.", "title": "Alkylphenols in human milk and their relations to dietary habits in central Taiwan." }, { "docid": "MED-4711", "text": "Licorice is a common Chinese medicinal herb with antitumor activity. Some components in licorice root have been shown to induce cell cycle arrest or apoptosis in cancer cells. This paper demonstrates for the first time that licorice Glycyrrhiza glabra and its component licochalcone-A (LA) can induce autophagy in addition to apoptosis in human LNCaP prostate cancer cells. Exposure of cells to licorice or LA resulted in several confirmed characteristics of autophagy, including the appearance of autophagic vacuoles revealed by monodansylcadaverine (MDC) staining, formation of acidic vesicular organelles (AVOs), and autophagosome membrane association of microtubule-associated protein 1 light chain 3 (LC3) characterized by cleavage of LC3 and its punctuate redistribution, as well as ultrastructural observation of autophagic vacuoles by transmission electron microscopy. Autophagy induction was accompanied by down-regulation of Bcl-2 and inhibition of the mammalian target of rapamycin (mTOR) pathway. In summary, licorice can induce caspase-dependent and autophagy-related cell death in LNCaP cells.", "title": "Licorice and licochalcone-A induce autophagy in LNCaP prostate cancer cells by suppression of Bcl-2 expression and the mTOR pathway." }, { "docid": "MED-3921", "text": "BACKGROUND: To evaluate health benefits attributed to Hibiscus sabdariffa L. a randomized, open-label, two-way crossover study was undertaken to compare the impact of an aqueous H. sabdariffa L. extract (HSE) on the systemic antioxidant potential (AOP; assayed by ferric reducing antioxidant power (FRAP)) with a reference treatment (water) in eight healthy volunteers. The biokinetic variables were the areas under the curve (AUC) of plasma FRAP, ascorbic acid and urate that are above the pre-dose concentration, and the amounts excreted into urine within 24 h (Ae(0-24) ) of antioxidants as assayed by FRAP, ascorbic acid, uric acid, malondialdehyde (biomarker for oxidative stress), and hippuric acid (metabolite and potential biomarker for total polyphenol intake). RESULTS: HSE caused significantly higher plasma AUC of FRAP, an increase in Ae(0-24) of FRAP, ascorbic acid and hippuric acid, whereas malondialdehyde excretion was reduced. Furthermore, the main hibiscus anthocyanins as well as one glucuronide conjugate could be quantified in the volunteers' urine (0.02% of the administered dose). CONCLUSION: The aqueous HSE investigated in this study enhanced the systemic AOP and reduced the oxidative stress in humans. Furthermore, the increased urinary hippuric acid excretion after HSE consumption indicates a high biotransformation of the ingested HSE polyphenols, most likely caused by the colonic microbiota. Copyright © 2012 Society of Chemical Industry.", "title": "Consumption of Hibiscus sabdariffa L. aqueous extract and its impact on systemic antioxidant potential in healthy subjects." }, { "docid": "MED-4747", "text": "In contrast to the use of hormonal doping agents in sports to enhance the performance of athletes, in the livestock industry hormonal growth promoters (\"anabolics\") are used to increase the production of muscle meat. This leads to international disputes about the safety of meat originating from animals treated with such anabolics.As a consequence of the total ban in the EU of all hormonal active growth promoters (\"hormones\") in livestock production, in contrast to their legal use [e.g. of five such hormones (17beta-estradiol, testosterone, progesterone, trenbolone and zeranol) as small solid ear implants and two hormones as feed additives for feedlot heifers (melengestrol acetate) and for swine (ractopamine) in the USA], the regulatory controls also differ sharply between the EU and the USA.In the EU the treatment of slaughter animals is the regulatory offence that has to be controlled in inspection programs. In the USA testing for compliance of a regulatory maximum residue level in the edible product (muscle, fat, liver or kidney) is the purpose of the inspection program (if any).The EU inspection programs focus on sample materials that are more suitable for testing for banned substances, especially if the animals are still on the farm, such as urine and feces or hair. In the case of slaughtered animals, the more favored sample materials are bile, blood, eyes and sometimes liver. Only in rare occasions is muscle meat sampled. This happens only in the case of import controls or in monitoring programs of meat sampled in butcher shops or supermarkets.As a result, data on hormone concentrations in muscle meat samples from the EU market are very rare and are obtained in most cases from small programs on an ad hoc basis. EU data for natural hormones in meat are even rarer because of the absence of \"legal natural levels\" for these hormones in compliance testing. With the exception of samples from the application sites - in the EU the site of injection of liquid hormone preparations or the site of application of \"pour on\" preparations - the hormone concentrations observed in meat samples of illegally treated animals are typically in the range of a few micrograms per kilogram (ppb) down to a few tenths of a microgram per kilogram. In the EU dozens of illegal hormones are used and the number of active compounds is still expanding. Besides estrogenic, androgenic and progestagenic compounds also thyreostatic, corticosteroidal and beta-adrenergic compounds are used alone or in \"smart\" combinations.An overview is given of the compounds identified on the EU black market. An estimate is also given of the probability of consumption in the EU of \"highly\" contaminated meat from the application sites in cattle. Finally some data are presented on the concentration of estradiol in bovine meat from animals treated and not treated with hormone implants. These data are compared with the recent findings for estradiol concentrations in hen's eggs. From this comparison, the preliminary conclusion is that hen's eggs are the major source of 17alpha- and 17beta-estradiol in the consumer's daily \"normal\" diet.", "title": "Hormonal growth promoting agents in food producing animals." }, { "docid": "MED-4890", "text": "Epidemiological studies suggest a positive association between nutrient intake, hyperinsulinemia and risk of Benign prostatic hyperplasis (BPH). This study tests the hypothesis that a low-fat, high-fiber diet and daily exercise would lower serum insulin and reduce the growth of serum-stimulated primary prostate epithelial cells in culture. Serum samples were obtained from eight overweight men before and after the Pritikin residential, 2-week diet and exercise intervention and from seven men who were long-term followers of the low-fat, high-fiber diet and regular exercise lifestyle. The serum was used to stimulate primary prostate epithelial cells in culture. Growth was measured after 48 and 96 h and apoptosis after 96 h. At 48 h there was no significant difference in growth within the Pre, 2-week or Long-Term groups. At 96 h growth was significantly reduced in the 2-week (13%) and in the Long-Term (14%) groups compared to the Pre data. At 96 h, apoptosis was not significantly different among the three groups. Fasting insulin was reduced by 30% in the 2-week group and by 52% in the Long-Term group compared to the Pre data. Testosterone was unchanged in the 2-week group. The results of this study indicate that a low-fat, high-fiber diet and daily exercise lowers insulin and reduces growth of prostate primary epithelial cells and suggests that lifestyle may be an important factor in the development or progression of BPH. Future prospective trials should address the effects of this lifestyle modification on BPH symptomatology and progression.", "title": "Effect of diet and exercise intervention on the growth of prostate epithelial cells." }, { "docid": "MED-2579", "text": "There are now extensive scientific data suggesting the potential role of dietary and non-dietary phytochemicals in the prevention and control of prostate cancer (PCA) growth and progression. PCA is a disease of elderly male populations with a relatively slower rate of growth and progression as compared to most other cancers and, therefore, is a candidate disease for preventive intervention. Overall, PCA growth and progression involve aberrant mitogenic and survival signaling and deregulated cell cycle progression, accompanied by gradual accumulation of genetic and epigenetic changes over a period of years. Several mechanisms, including overexpression of growth, survival and angiogenic factors and their receptors, together with a loss/decrease of tumor suppressor p53, retinoblastoma and cyclin-dependent kinase inhibitor, have been implicated in PCA growth and progression. Therefore, phytochemicals targeting these molecular events could have a promising role in PCA prevention and/or therapy. Inositol hexaphosphate (IP6) is a major constituent of most cereals, legumes, nuts, oil seeds and soybean. Taken orally as an over-the-counter dietary/nutrient supplement, and is recognised as offering several health benefits without any known toxicity. In vitro anticancer efficacy of IP6 has been observed in many human, mouse and rat prostate cancer cells. Completed studies also show that oral feeding of IP6 inhibits human PCA xenograft growth in nude mice without toxicity. In a recently completed pilot study, we observed similar preventive effects of IP6 on prostate tumorigenesis in the TRAMP model. Mechanistic studies indicate that IP6 targets mitogenic and survival signaling, as well as cell cycle progression, in PCA cells. IP6 is also shown to target molecular events associated with angiogenesis. Moreover, IP6 has pleiotropic molecular targets for its overall efficacy against PCA and, therefore, could be a suitable candidate agent for preventive intervention of this malignancy in humans.", "title": "Prostate cancer and inositol hexaphosphate: efficacy and mechanisms." }, { "docid": "MED-4383", "text": "OBJECTIVE: We investigated the relation between plasma carotenoids, retinol and tocopherol levels and ovarian cancer risk in Korean women. DESIGN: Hospital-based case-control study. SETTING: Six tertiary medical institutes in Korea. POPULATION: Forty-five epithelial ovarian cancers and 135 age-matched controls. METHODS: Preoperative plasma concentrations of beta-carotene, lycopene, zeaxanthin plus lutein, retinol, alpha-tocopherol, and gamma-tocopherol were measured by reverse-phase, gradient high-pressure liquid chromatography. MAIN OUTCOME MEASURES: Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated by tertiles to evaluate the effect of micronutrients on endometrial cancer risk after adjustment for body mass (BMI) index, menopause, parity, oral contraceptive use, smoking status, and alcohol consumption status. RESULTS: Women in the highest tertile for beta-carotene had 0.12-times the risk of ovarian cancer of in the lowest tertile (OR 0.12; 95%CI 0.04-0.36). Women with the highest tertiles of lycopene (OR 0.09; 95%CI 0.03-0.32), zeaxanthin/lutein (OR 0.21; 95%CI 0.09-0.52), retinol (OR 0.45; 95%CI 0.21-0.98), alpha-tocopherol (OR 0.23; 95%CI 0.10-0.53) and gamma-tocopherol (OR 0.28; 95%CI 0.11-0.70) had lower risk of ovarian cancer than women in the lowest tertiles. Results were consistent across strata of socio-epidemiologic factors. CONCLUSIONS: Micronutrients, specifically ss-carotene, lycopene, zeaxanthin, lutein, retinol, alpha-tocopherol, and gamma-tocopherol, may play a role in reducing the risk of ovarian cancer.", "title": "Plasma carotenoids, retinol and tocopherol levels and the risk of ovarian cancer." }, { "docid": "MED-2570", "text": "The functional properties, including antioxidant and chemopreventative capacities as well as the inhibitory effects on angiotensin-converting enzyme (ACE), α-glucosidase and pancreatic lipase, of three Australian-grown faba bean genotypes (Nura, Rossa and TF(Ic*As)*483/13) were investigated using an array of in vitro assays. Chromatograms of on-line post column derivatisation assay coupled with HPLC revealed the existence of active phenolics (hump) in the coloured genotypes, which was lacking in the white-coloured breeding line, TF(Ic*As)*483/13. Roasting reduced the phenolic content, and diminished antioxidant activity by 10-40 % as measured by the reagent-based assays (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and oxygen radical absorbance capacity) in all genotypes. Cell culture-based antioxidant activity assay (cellular antioxidant activity) showed an increase of activity in the coloured genotypes after roasting. Faba bean extracts demonstrated cellular protection ability against H₂O₂-induced DNA damage (assessed using RAW264.7 cells), and inhibited the proliferation of all human cancer cell lines (BL13, AGS, Hep G2 and HT-29) evaluated. However, the effect of faba bean extracts on the non-transformed human cells (CCD-18Co) was negligible. Flow cytometric analyses showed that faba bean extracts successfully induced apoptosis of HL-60 (acute promyelocytic leukaemia) cells. The faba bean extracts also exhibited ACE, α-glucosidase and pancreatic lipase inhibitory activities. Overall, extracts from Nura (buff-coloured) and Rossa (red-coloured) were comparable, while TF(Ic*As)*483/13 (white-coloured) contained the lowest phenolic content and exhibited the least antioxidant and enzyme inhibition activities. These results are important to promote the utilisation of faba beans in human diets for various health benefits.", "title": "In vitro investigations of the potential health benefits of Australian-grown faba beans (Vicia faba L.): chemopreventative capacity and inhibitory ..." }, { "docid": "MED-4235", "text": "We studied the obstruction-relieving capabilities of transurethral electrovaporization of the prostate (TVP) in 32 symptomatic patients with benign prostatic hyperplasia (BPH). Urodynamic studies with pressure-flow analysis were performed before and 6 months after treatment. All 32 patients showed significant improvement of both subjective and objective obstruction parameters. There were few postoperative irritative symptoms and one patient required recatheterization. In conclusion, TVP is a promising modification of performing transurethral resection of the prostate, and it is indeed capable of relieving bladder outflow obstruction.", "title": "Transurethral electrovaporization of the prostate in benign prostatic hyperplasia. Evaluation of results using different urodynamic parameters." }, { "docid": "MED-3875", "text": "BACKGROUND: Mammalian lignans, enterolactone (EL) and enterodiol (ED), have been shown to inhibit breast and colon carcinoma. To date, there have been no reports of the effect of lignans on prostatic carcinoma. We investigated the effects of ED and EL on three human prostate cancer cell lines (PC-3, DU-145 and LNCaP). MATERIALS AND METHODS: Cells were treated with either 0.1% (v/v) DMSO (vehicle) or 10-100 microM of EL, ED or genistein (positive control) for 72 hours. Cell viability was measured by the propidium iodide nuclei staining fluorometric assay with each assay performed in triplicate. RESULTS: At 10-100 microM, EL significantly inhibited the growth of all cell lines, whereas ED only inhibited PC-3 and LNCaP cells. While EL was a more potent growth inhibitor than ED, both were less potent than genistein. The dose for 50% growth inhibition of LNCaP cells (IC50) by EL was 57 microM, whereas IC50 was 100 microM for ED, (the observed IC50 for genistein was 25 microM). CONCLUSION: ED and EL suppress the growth of prostate cancer cells, and may do so via hormonally-dependent and independent mechanisms.", "title": "Effect of mammalian lignans on the growth of prostate cancer cell lines." }, { "docid": "MED-4247", "text": "In a prospective, randomised, controlled trial to determine whether comprehensive lifestyle changes affect coronary atherosclerosis after 1 year, 28 patients were assigned to an experimental group (low-fat vegetarian diet, stopping smoking, stress management training, and moderate exercise) and 20 to a usual-care control group. 195 coronary artery lesions were analysed by quantitative coronary angiography. The average percentage diameter stenosis regressed from 40.0 (SD 16.9)% to 37.8 (16.5)% in the experimental group yet progressed from 42.7 (15.5)% to 46.1 (18.5)% in the control group. When only lesions greater than 50% stenosed were analysed, the average percentage diameter stenosis regressed from 61.1 (8.8)% to 55.8 (11.0)% in the experimental group and progressed from 61.7 (9.5)% to 64.4 (16.3)% in the control group. Overall, 82% of experimental-group patients had an average change towards regression. Comprehensive lifestyle changes may be able to bring about regression of even severe coronary atherosclerosis after only 1 year, without use of lipid-lowering drugs.", "title": "Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial." }, { "docid": "MED-2775", "text": "The incidence and mortality rates of testicular and prostatic cancers in 42 countries were correlated with the dietary practices in these countries using the cancer rates (1988-92) provided by the International Agency for Research on Cancer (IARC) and the food supply data (1961-90) provided by the Food and Agriculture Organization (FAO). Among the food items we examined, cheese was most closely correlated with the incidence of testicular cancer at ages 20-39, followed by animal fats and milk. The correlation coefficient (r) was highest (r = 0.804) when calculated for cheese consumed during the period 1961-65 (maternal or prepubertal consumption). Stepwise-multiple-regression analysis revealed that milk + cheese (1961-65) made a significant contribution to the incidence of testicular cancer (standardized regression coefficient [R] = 0.654). Concerning prostatic cancer, milk (1961-90) was most closely correlated (r = 0.711) with its incidence, followed by meat and coffee. Stepwise-multiple-regression analysis identified milk + cheese as a factor contributing to the incidence of prostatic cancer (R = 0.525). The food that was most closely correlated with the mortality rate of prostatic cancer was milk (r = 0.766), followed by coffee, cheese and animal fats. Stepwise-multiple-regression analysis revealed that milk + cheese was a factor contributing to mortality from prostatic cancer (R = 0.580). The results of our study suggest a role of milk and dairy products in the development and growth of testicular and prostatic cancers. The close correlation between cheese and testicular cancer and between milk and prostatic cancer suggests that further mechanistic studies should be undertaken concerning the development of male genital organ cancers. Copyright 2001 Wiley-Liss, Inc.", "title": "Incidence and mortality of testicular and prostatic cancers in relation to world dietary practices." }, { "docid": "MED-3270", "text": "Aging affects all organisms and its basic mechanisms are expected to be conserved across species. Oxidation of proteins has been proposed to be one of the basic mechanisms linking oxygen radicals with the basic aging process. If oxidative damage to proteins is involved in aging, long-lived animals (which age slowly) should show lower levels of markers of this kind of damage than short-lived ones. However, this possibility has not been investigated yet. In this study, steady-state levels of markers of different kinds of protein damage--oxidation (glutamic and aminoadipic semialdehydes), mixed glyco- and lipoxidation (carboxymethyl- and carboxyethyllysine), lipoxidation (malondialdehydelysine) and amino acid composition--were measured in the heart of eight mammalian species ranging in maximum life span (MLSP) from 3.5 to 46 years. Oxidation markers were directly correlated with MLSP across species. Mixed glyco- and lipoxidation markers did not correlate with MLSP. However, the lipoxidation marker malondialdehydelysine was inversely correlated with MLSP (r2=0.85; P<0.001). The amino acid compositional analysis revealed that methionine is the only amino acid strongly correlated MLSP and that such correlation is negative (r2=0.93; P<0.001). This trait may contribute to lower steady-state levels of oxidized methionine residues in cellular proteins. These results reinforce the notion that high longevity in homeothermic vertebrates is achieved in part by constitutively decreasing the sensitivity of both tissue proteins and lipids to oxidative damage. This is obtained by modifying the constituent structural components of proteins and lipids, selecting those less sensitive to oxidative modifications.", "title": "Protein methionine content and MDA-lysine adducts are inversely related to maximum life span in the heart of mammals." }, { "docid": "MED-3277", "text": "Methionine dependence is a metabolic defect that occurs in many human tumor cell lines but not normal in unestablished cell strains. Methionine-dependent tumor cell lines are unable to proliferate and arrest in the late S/G2 phase of the cell cycle when methionine is replaced by its immediate precursor homocysteine in the culture medium (MET-HCY+ medium). However, it is not known whether methionine dependence occurs in fresh patient tumors as it does in cell lines. In order to determine whether methionine dependence occurs in fresh patient tumors as well as whether methionine dependence occurs in fresh patient tumors as well as in cell lines we took advantage of the technique of sponge-gel-supported histoculture to grow tumors directly from surgery. We then measured nuclear DNA content by image analysis to determine the cell cycle position in MET-HCY+ compared to MET+HCY- medium in 21 human patient tumors. Human tumor cell lines found to be methionine dependent by cell count were used as positive controls and were found to have marked reduction of cells in G1 compared to total cells in the cell cycle in MET-HCY+ medium with respect to the G1: total cell ratio in MET+HCY- medium. Therefore late cell cycle arrest was used as a marker of methionine dependence for histocultured patient tumors. We found that 5 human tumors of 21, including tumors of the colon, breast, ovary, prostate, and a melanoma, were methionine dependent based on cell cycle analysis. These data on fresh human tumors indicate that methionine dependence may frequently occur in the cancer patient population. Implications for potential therapy based on methionine dependence are discussed.", "title": "Expression of the biochemical defect of methionine dependence in fresh patient tumors in primary histoculture." }, { "docid": "MED-4487", "text": "Background The evidence that red and processed meat influences colorectal carcinogenesis was judged convincing in the 2007 World Cancer Research Fund/American Institute of Cancer Research report. Since then, ten prospective studies have published new results. Here we update the evidence from prospective studies and explore whether there is a non-linear association of red and processed meats with colorectal cancer risk. Methods and Findings Relevant prospective studies were identified in PubMed until March 2011. For each study, relative risks and 95% confidence intervals (CI) were extracted and pooled with a random-effects model, weighting for the inverse of the variance, in highest versus lowest intake comparison, and dose-response meta-analyses. Red and processed meats intake was associated with increased colorectal cancer risk. The summary relative risk (RR) of colorectal cancer for the highest versus the lowest intake was 1.22 (95% CI  = 1.11−1.34) and the RR for every 100 g/day increase was 1.14 (95% CI  = 1.04−1.24). Non-linear dose-response meta-analyses revealed that colorectal cancer risk increases approximately linearly with increasing intake of red and processed meats up to approximately 140 g/day, where the curve approaches its plateau. The associations were similar for colon and rectal cancer risk. When analyzed separately, colorectal cancer risk was related to intake of fresh red meat (RR for 100 g/day increase  = 1.17, 95% CI  = 1.05−1.31) and processed meat (RR for 50 g/day increase  = 1.18, 95% CI  = 1.10−1.28). Similar results were observed for colon cancer, but for rectal cancer, no significant associations were observed. Conclusions High intake of red and processed meat is associated with significant increased risk of colorectal, colon and rectal cancers. The overall evidence of prospective studies supports limiting red and processed meat consumption as one of the dietary recommendations for the prevention of colorectal cancer.", "title": "Red and Processed Meat and Colorectal Cancer Incidence: Meta-Analysis of Prospective Studies" }, { "docid": "MED-4750", "text": "Androgenic steroids always exist in different animal tissues at trace level, with significant numbers of interfering compounds, which makes their determination difficult. To solve some of the problems in quantification of the natural steroids in those tissues, a new GC-MS method was developed in this study. By using a surrogate analyte approach, which was developed in the authors' previous studies, and extensive sample preparation procedure, which successfully eliminates many of the interfering compounds and resulting in a cleaner extract, accuracy, precision, sensitivity and selectivity of the method for the determination of steroids in complex matrices such as meat, liver and testis were improved. By aid of this method, the levels of androgens in different tissues of Iranian native cross-breed bulls and male sheep were determined. According to the results obtained in the present study, although the androgenic profile (contents and ratios of precursors and metabolites to the main hormones) is similar between the same tissues of both animals, the total androgenic content of each tissue is higher in the bull than the same tissue in male sheep. In addition, in both animals higher amount of androgens were found in liver in comparison with meat and testis.", "title": "Assessment of endogenous androgen levels in meat, liver and testis of Iranian native cross-breed male sheep and bull by gas chromatography-mass spe..." }, { "docid": "MED-4748", "text": "BACKGROUND: Adrenarche is the increase in adrenal androgen (AA) production starting in childhood. Until now, it has been unknown whether or not nutritional factors modulate adrenarche. OBJECTIVE: The objective was to examine whether body composition and certain dietary intakes are associated with AA production in children after accounting for urinary indicators of major adrenarche-related steroidogenic enzymes. DESIGN: Androgen and glucocorticoid metabolites were profiled by gas chromatography-mass spectrometry in 24-h urine samples of 137 healthy prepubertal children aged 3-12 y, for whom birth characteristics, growth velocity data, and 3-d weighed-diet record information were available. Associations of the sum of C19 metabolites (reflecting daily AA secretion) with nutritional factors [fat mass (FM), fat-free mass (FFM), nutrient intakes, glycemic index, and glycemic load] and AA-relevant estimates of steroidogenic enzyme were examined in stepwise multiple regression models adjusted for age, sex, urine volume, and total energy intake. Enzyme activity estimates were calculated by using specific urinary steroid metabolite ratios. RESULTS: Of the nutrition-relevant predictors, FM (P < 0.0001) explained most of the variation of AA secretion (R(2) = 5%). Animal protein intake was also positively associated with AA secretion (P < 0.05), which explained 1% of its variation. FFM (P = 0.1) and total protein intake (P = 0.05) showed positive trends. The difference in daily AA secretion between the lowest and highest quartile of FM was comparable to that between the lowest and highest estimated activity of one of the major steroidogenic enzymes. CONCLUSIONS: Body fat mass may relevantly influence prepubertal adrenarchal androgen status. In addition, animal protein intake may also make a small contribution to AA secretion in children.", "title": "Body fat and animal protein intakes are associated with adrenal androgen secretion in children." }, { "docid": "MED-2648", "text": "The aim of this study was to compare results obtained by eight different short-term assays of estrogenlike actions of chemicals conducted in 10 different laboratories in five countries. Twenty chemicals were selected to represent direct-acting estrogens, compounds with estrogenic metabolites, estrogenic antagonists, and a known cytotoxic agent. Also included in the test panel were 17beta++-estradiol as a positive control and ethanol as solvent control. The test compounds were coded before distribution. Test methods included direct binding to the estrogen receptor (ER), proliferation of MCF-7 cells, transient reporter gene expression in MCF-7 cells, reporter gene expression in yeast strains stably transfected with the human ER and an estrogen-responsive reporter gene, and vitellogenin production in juvenile rainbow trout. 17beta-Estradiol, 17alpha-ethynyl estradiol, and diethylstilbestrol induced a strong estrogenic response in all test systems. Colchicine caused cytotoxicity only. Bisphenol A induced an estrogenic response in all assays. The results obtained for the remaining test compounds--tamoxifen, ICI 182.780, testosterone, bisphenol A dimethacrylate, 4-n-octylphenol, 4-n-nonylphenol, nonylphenol dodecylethoxylate, butylbenzylphthalate, dibutylphthalate, methoxychlor, o,p'-DDT, p,p'-DDE, endosulfan, chlomequat chloride, and ethanol--varied among the assays. The results demonstrate that careful standardization is necessary to obtain a reasonable degree of reproducibility. Also, similar methods vary in their sensitivity to estrogenic compounds. Thus, short-term tests are useful for screening purposes, but the methods must be further validated by additional interlaboratory and interassay comparisons to document the reliability of the methods.", "title": "Comparison of Short-Term Estrogenicity Tests for Identification of Hormone-Disrupting Chemicals" }, { "docid": "MED-4236", "text": "PURPOSE: We reviewed recent literature and treatment guidelines regarding the prevalence, pathophysiology, and management of BPO related to BPH; and management of lower urinary tract symptoms secondary to BPH. MATERIALS AND METHODS: Published literature and current treatment concepts were reviewed regarding the diagnosis and treatment options for BPO. RESULTS: BPH is a histological diagnosis that can contribute to medical problems, including enlargement of the prostate and BPO. These conditions should be treated only if the symptoms are troublesome, there is considerable risk of progression, and/or cancer is suspected. Very effective medical and surgical options are available to treat BPO and improve patient quality of life. CONCLUSIONS: BPO is highly treatable, but should be managed in close collaboration with the patient. Pharmacological agents and minimally invasive procedures, when appropriate, are generally preferred to more invasive surgery. Patients with mild or moderate symptoms usually can be treated by a primary care physician; more complicated cases should be referred to a urologist for evaluation and management.", "title": "Benign prostatic hyperplasia in primary care: what you need to know." }, { "docid": "MED-3242", "text": "Previous studies have suggested that dietary factors may be important in the development of bladder cancer. We examined macronutrient intake in relation to risk of urothelial cell carcinoma among 469,339 men and women in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by sex, age at recruitment and centre and further adjusted for smoking status and duration, body mass index and total energy intake. After an average of 11.3 years of follow-up, 1,416 new cases of urothelial cell carcinoma were identified. After allowing for measurement error, a 3% increase in the consumption of energy intake from animal protein was associated with a 15% higher risk (95% confidence interval [CI]: 3-30%; p(trend) = 0.01) and a 2% increase in energy from plant protein intake was associated with a 23% lower risk (95% CI: 36-7%, p(trend) = 0.006). Dietary intake of fat, carbohydrate, fibre or calcium was not associated with risk. These findings suggest that animal and/or plant protein may affect the risk of urothelial cell carcinoma, and examination of these associations in other studies is needed. Copyright © 2012 UICC.", "title": "Macronutrient intake and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition." }, { "docid": "MED-4887", "text": "Cardiovascular symptom relief is a major indicator for revascularization procedures. To examine the effects of intensive lifestyle modification on symptom relief, we investigated changes in angina pectoris, coronary risk factors, quality of life, and lifestyle behaviors in patients with stable coronary artery disease enrolled in the multisite cardiac lifestyle intervention program, an ongoing health insurance-covered lifestyle intervention conducted at 22 sites in the united states. Patients with coronary artery disease (nonsmokers; 757 men, 395 women; mean age 61 years) were asked to make changes in diet (10% calories from fat, plant based), engage in moderate exercise (3 hours/week), and practice stress management (1 hour/day). At baseline, 108 patients (43% women) reported mild angina and 174 patients (37% women) reported limiting angina. By 12 weeks, 74% of these patients were angina free, and an additional 9% moved from limiting to mild angina. This improvement in angina was significant for patients with mild and limiting angina at baseline regardless of gender (p <0.01). Significant improvements in cardiac risk factors, quality of life, and lifestyle behaviors were observed, and patients with angina who became angina free by 12 weeks showed the greatest improvements in exercise capacity, depression, and health-related quality of life (p <0.05). In conclusion, the observed improvements in angina in patients making intensive lifestyle changes could drastically reduce their need for revascularization procedures.", "title": "Angina pectoris and atherosclerotic risk factors in the multisite cardiac lifestyle intervention program." }, { "docid": "MED-4479", "text": "The objective of this study is to investigate the risk of esophageal carcinoma in a cohort with long-term occupational exposure to sodium nitrite. The method used was a retrospective cohort study. A small wood screw manufacturer was founded in 1977 and closed down in 2000. In their production process, the sodium nitrite solution was used to serve as anticorrosive and coolant fluid. One hundred sixty workers in turning and milling shops had direct exposure to sodium nitrite through skin, mouth, and airway because of lack of occupational protective knowledge (study group), whereas 255 workers from other workshops without direct contact with sodium nitrite served as control group. The incidence, diagnosis, and treatment of esophageal carcinoma as well as other malignant tumors in these two groups were followed until the end of 2007. The sodium nitrite exposure time in the study group ranged from 16 to 23 years, with an average of 22.1 years. During 30 years of follow-up, there were 11 esophageal carcinomas and 10 other malignant tumors (4 hepatic cell carcinomas, 3 lung cancers, 2 breast cancers, and 1 leukemia) documented in the study group, while no cancer developed in the control group. The risk for esophageal carcinoma was significantly increased in the study group compared with the control group (relative risk = 1.26, 95% confidence interval = 1.08-1.46, chi-square = 116.83, P < 0.001). Long-term exposure to sodium nitrite markedly increases the risk of esophageal carcinoma in human body. © 2010 Copyright the Authors. Journal compilation © 2010, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.", "title": "Long-term exposure to sodium nitrite and risk of esophageal carcinoma: a cohort study for 30 years." }, { "docid": "MED-4319", "text": "The article gives an overview of phytic acid in food and of its significance for human nutrition. It summarises phytate sources in foods and discusses problems of phytic acid/phytate contents of food tables. Data on phytic acid intake are evaluated and daily phytic acid intake depending on food habits is assessed. Degradation of phytate during gastro-intestinal passage is summarised, the mechanism of phytate interacting with minerals and trace elements in the gastro-intestinal chyme described and the pathway of inositol phosphate hydrolysis in the gut presented. The present knowledge of phytate absorption is summarised and discussed. Effects of phytate on mineral and trace element bioavailability are reported and phytate degradation during processing and storage is described. Beneficial activities of dietary phytate such as its effects on calcification and kidney stone formation and on lowering blood glucose and lipids are reported. The antioxidative property of phytic acid and its potentional anticancerogenic activities are briefly surveyed. Development of the analysis of phytic acid and other inositol phosphates is described, problems of inositol phosphate determination and detection discussed and the need for standardisation of phytic acid analysis in foods argued.", "title": "Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis." }, { "docid": "MED-3283", "text": "Available information indicates that long-lived mammals have low rates of reactive oxygen species (ROS) generation and oxidative damage at their mitochondria. On the other hand, many studies have consistently shown that dietary restriction (DR) in rodents also decreases mitochondrial ROS (mtROS) production and oxidative damage to mitochondrial DNA and proteins. It has been observed that protein restriction also decreases mtROS generation and oxidative stress in rat liver, whereas neither carbohydrate nor lipid restriction change these parameters. This is interesting because protein restriction also increases maximum longevity in rodents (although to a lower extent than DR) and is a much more practicable intervention for humans than DR, whereas neither carbohydrate nor lipid restriction seem to change rodent longevity. Moreover, it has been found that isocaloric methionine restriction also decreases mtROS generation and oxidative stress in rodent tissues, and this manipulation also increases maximum longevity in rats and mice. In addition, excessive dietary methionine also increases mtROS generation in rat liver. These studies suggest that the reduced intake of dietary methionine can be responsible for the decrease in mitochondrial ROS generation and the ensuing oxidative damage that occurs during DR, as well as for part of the increase in maximum longevity induced by this dietary manipulation. In addition, the mean intake of proteins (and thus methionine) of Western human populations is much higher than needed. Therefore, decreasing such levels to the recommended ones has a great potential to lower tissue oxidative stress and to increase healthy life span in humans while avoiding the possible undesirable effects of DR diets.", "title": "Lowered methionine ingestion as responsible for the decrease in rodent mitochondrial oxidative stress in protein and dietary restriction possible i..." }, { "docid": "MED-2581", "text": "A hospital-based case-control study of diet and colorectal cancer was conducted among Chinese in Singapore (who constitute 77% of the population). A total of 203 cases and 425 controls were included. A history of the usual dietary intake one year prior to interview was taken using a quantitative food frequency questionnaire. Daily intakes of nutrients and selected food items were computed and stratified by tertiles of the control range, to assess risk in low-, medium- and high-intake categories. Effects were adjusted in analysis for age, sex, Chinese dialect group and occupation. For cancers of colon and rectum combined, significant observations were a protective effect of high cruciferous vegetable intake (OR = 0.50, p less than 0.01) and a predisposing effect of a high meat/vegetable consumption ratio (OR = 1.77, p less than 0.05). Similar results were observed for colon cancer alone. For rectal cancer alone (only 71 cases), significant (p less than 0.05) protective effects were observed for high intakes of protein (OR = 0.61), fibre (OR = 0.46), beta-carotene (OR = 0.54), cruciferous vegetables (OR = 0.51) and total vegetables (OR = 0.51). When further assessed by multiple logistic regression, tests for trend and assessment of risk in the extreme highest and lowest quintiles of the control range, the factors consistently significant were cruciferous vegetable intake and the meat/vegetable ratio. A particularly high relative risk was also noted in association with low coffee consumption (OR = 1.59, with p less than 0.05 for trend). No consistent trends were noted for fat or fibre intakes. For non-dietary variables investigated, a history of cholecystectomy increased the risk of both cancers combined (OR = 3.43, p less than 0.05) and colon cancer alone (OR = 4.39, p less than 0.01). This study in an Asian population of countries of Southern and Eastern Asia newly undergoing industrialization and in which rapid economic change is reflected in changing cancer patterns, suggests that the protective effects of certain dietary constituents, notably the cruciferous vegetables, may be more important than the hitherto stressed carcinogenic potential of fat and protein.", "title": "Colorectal cancer and diet in an Asian population--a case-control study among Singapore Chinese." }, { "docid": "MED-5177", "text": "The objective of this study was to evaluate, in a phase 2 pilot study, tolerability and the effect of 6 weeks of flaxseed therapy on hot flash scores in women not wishing to receive estrogen therapy. Eligibility included 14 hot flashes per week for at least 1 month. In the baseline week, participants took no study medication and documented the characteristics of their hot flashes. Thereafter, crushed flaxseed was administered at 40 g daily. Participants provided weekly toxicity reports and health-related quality of life information. The primary end point was a change in hot flash score prospectively reported in a daily hot flash diary. Thirty women were enrolled between June 17 and November 8, 2005. The mean decrease in hot flash scores after flaxseed therapy was 57% (median decrease 62%). The mean reduction in daily hot flash frequency was 50% (median reduction 50%), from 7.3 hot flashes to 3.6. Fourteen of the 28 participants (50%) experienced mild or moderate abdominal distention. Eight participants (29%) experienced mild diarrhea, one experienced flatulence, and six (21%) withdrew because of toxicities. This study suggests that dietary therapy decreases hot flash activity in women not taking estrogen therapy. This reduction is greater than what would be expected with placebo.", "title": "Pilot evaluation of flaxseed for the management of hot flashes." }, { "docid": "MED-3273", "text": "Recent studies confirm that dietary methionine restriction increases both mean and maximal lifespan in rats and mice, achieving \"aging retardant\" effects very similar to those of caloric restriction, including a suppression of mitochondrial superoxide generation. Although voluntary caloric restriction is never likely to gain much popularity as a pro-longevity strategy for humans, it may be more feasible to achieve moderate methionine restriction, in light of the fact that vegan diets tend to be relatively low in this amino acid. Plant proteins - especially those derived from legumes or nuts - tend to be lower in methionine than animal proteins. Furthermore, the total protein content of vegan diets, as a function of calorie content, tends to be lower than that of omnivore diets, and plant protein has somewhat lower bioavailability than animal protein. Whole-food vegan diets that moderate bean and soy intake, while including ample amounts of fruit and wine or beer, can be quite low in methionine, while supplying abundant nutrition for health (assuming concurrent B12 supplementation). Furthermore, low-fat vegan diets, coupled with exercise training, can be expected to promote longevity by decreasing systemic levels of insulin and free IGF-I; the latter effect would be amplified by methionine restriction - though it is not clear whether IGF-I down-regulation is the sole basis for the impact of low-methionine diets on longevity in rodents.", "title": "The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy." }, { "docid": "MED-4645", "text": "Background Many studies have evaluated the association between vitamin and mineral supplement use and the risk of prostate cancer, with inconclusive results. Methods The authors examined the relation of use of multivitamins as well as several single vitamin and mineral supplements to the risk of prostate cancer risk among 1,706 prostate cancer cases and 2,404 matched controls using data from the hospital-based Case-Control Surveillance Study conducted in the United States. Odds ratios (OR) and 95% confidence intervals (CI) for risk of prostate cancer were estimated using conditional logistic regression model. Results For use of multivitamins that did not contain zinc the multivariable odds ratios of prostate cancer were 0.6 for 1–4 years, 0.8 for 5–9 years, and 1.2 for 10 years of more, respectively (p for trend =0.70). Men who used zinc for 10 years or more, either in a multivitamin or as a supplement, had an approximately 2-fold (OR=1.9, 95% CI: 1.0, 3.6) increased risk of prostate cancer. Vitamin E, beta-carotene, folate, and selenium use were not significantly associated with increased risk of prostate cancer. Conclusion The finding that long-term zinc intake from multivitamins or single supplements was associated with a doubling in risk of prostate cancer adds to the growing evidence for an unfavorable effect of zinc on prostate cancer carcinogenesis.", "title": "Vitamin and Mineral Use and Risk of Prostate Cancer: The Case-Control Surveillance Study" }, { "docid": "MED-2656", "text": "The aim of previous research into the causes of allergic diseases, including asthma was mostly to identify potential risk factors in the environment. No major risk factors have been identified, however. Over the past 10 years, focus has, therefore, more been directed towards protective factors that could enhance the development of tolerance to allergens which were previously encountered early in life, but are now lost in modern affluent societies. In particular, the role of childhood infections has been discussed, but so far these studies have not been conclusive. Recent epidemiological studies and experimental research suggest that the microbial environment and exposure to microbial products in infancy modifies immune responses and enhances the development of tolerance to ubiquitous allergens. The intestinal microflora may play a particular role in this respect, as it is the major external driving force in the maturation of the immune system after birth, and animal experiments have shown it to be a prerequisite for normal development of oral tolerance. Recent studies have shown differences in the composition of the microflora between healthy and allergic infants in countries with a high and low prevalence of allergies and between healthy and allergic infants within such countries. These differences are apparent within the first week of life and thus precede clinical symptoms. The use of live microorganisms that might be beneficial to health has a long tradition and the safety is well documented. Very recently, several prospective intervention studies, modifying the gut flora from birth have yielded encouraging results and may suggest a new mode of primary prevention of allergy in the future.", "title": "Effects of intestinal microflora and the environment on the development of asthma and allergy." }, { "docid": "MED-3924", "text": "PURPOSE: To determine the effects of therapy with Urtica dioica for symptomatic relief of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). MATERIAL AND METHODS: A 6-month, double-blind, placebo-controlled, randomized, partial crossover, comparative trial of Urtica dioica with placebo in 620 patients was conducted. Patients were evaluated using the International Prostate Symptom Score (IPSS), the maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), Serum Prostatic- Specific Antigen (PSA), testosterone levels, and prostate size. At the end of 6-month trial, unblinding revealed that patients who initially received the placebo were switched to Urtica dioica. Both groups continued the medication up to 18 months. RESULTS: 558 patients (90%) completed the study (287/305, 91% in the Urtica dioica group, and 271/315, 86% in the placebo group). By intention- to-treat analysis, at the end of 6-month trial, 232 (81%) of 287 patients in the Urtica dioica group reported improved LUTS compared with 43 (16%) of 271 patients in the placebo group (P < 0.001). Both IPSS and Qmax showed greater improvement with drug than with placebo. The IPSS went from 19.8 down to 11.8 with Urtica dioica and from 19.2 to 17.7 with placebo (P = 0.002). Peak flow rates improved by 3.4 mL/s for placebo recipients and by 8.2 mL/s for treated patients (P < 0.05). In Urtica dioica group, PVR decreased from an initial value of 73 to 36 mL (P < 0.05). No appreciable change was seen in the placebo group. Serum PSA and testosterone levels were unchanged in both groups. A modest decrease in prostate size as measured by transrectal ultrasonography (TRUS) was seen in Urtica dioica group (from 40.1 cc initially to 36.3 cc; P < 0.001). There was no change in the prostate volume at the end of study with placebo. At 18-month follow-up, only patients who continued therapy, had a favorable treatment variables value. No side effects were identified in either group. CONCLUSION: In the present study, Urtica dioica have beneficial effects in the treatment of symptomatic BPH. Further clinical trials should be conducted to confirm these results before concluding that Urtica dioica is effective.", "title": "Urtica dioica for treatment of benign prostatic hyperplasia: a prospective, randomized, double-blind, placebo-controlled, crossover study." }, { "docid": "MED-3282", "text": "BACKGROUND AND AIMS: The mechanisms of cancer cell growth and metastasis are still not entirely understood, especially from the viewpoint of chemical reactions in tumours. Glycolytic metabolism is markedly accelerated in cancer cells, causing the accumulation of glucose (a reducing sugar) and methionine (an amino acid), which can non-enzymatically react and form carcinogenic substances. There is speculation that this reaction produces gaseous sulfur-containing compounds in tumour tissue. The aims of this study were to clarify the products in tumour and to investigate their effect on tumour proliferation. METHODS: Products formed in the reaction between glucose and methionine or its metabolites were analysed in vitro using gas chromatography. Flatus samples from patients with colon cancer and exhaled air samples from patients with lung cancer were analysed using near-edge x-ray fine adsorption structure spectroscopy and compared with those from healthy individuals. The tumour proliferation rates of mice into which HT29 human colon cancer cells had been implanted were compared with those of mice in which the cancer cells were surrounded by sodium hyaluronate gel to prevent diffusion of gaseous material into the healthy cells. RESULTS: Gaseous sulfur-containing compounds such as methanethiol and hydrogen sulfide were produced when glucose was allowed to react with methionine or its metabolites homocysteine or cysteine. Near-edge x-ray fine adsorption structure spectroscopy showed that the concentrations of sulfur-containing compounds in the samples of flatus from patients with colon cancer and in the samples of exhaled air from patients with lung cancer were significantly higher than in those from healthy individuals. Animal experiments showed that preventing the diffusion of sulfur-containing compounds had a pronounced antitumour effect. CONCLUSIONS: Gaseous sulfur-containing compounds are the main products in tumours and preventing the diffusion of these compounds reduces the tumour proliferation rate, which suggests the possibility of a new approach to cancer treatment.", "title": "Generation of gaseous sulfur-containing compounds in tumour tissue and suppression of gas diffusion as an antitumour treatment." }, { "docid": "MED-5179", "text": "OBJECTIVE: Alpha-linolenic acid (ALA) is the natural precursor of the cardioprotective long-chain n-3 fatty acids. Available data indicate a possible beneficial effect of ALA on cardiovascular disease (CVD), but the response of various CVD risk factors to increased ALA intake is not well characterized. The purpose of the present study was to examine the effect of increased ALA intake on blood pressure in man. DESIGN, SETTING, SUBJECTS AND INTERVENTIONS: We used a prospective, two-group, parallel-arm design to examine the effect of a 12-week dietary supplementation with flaxseed oil, rich in ALA (8 g/day), on blood pressure in middle-aged dyslipidaemic men (n=59). The diet of the control group was supplemented with safflower oil, containing the equivalent n-6 fatty acid (11 g/day linoleic acid (LA); n=28). Arterial blood pressure was measured at the beginning and at the end of the dietary intervention period. RESULTS: Supplementation with ALA resulted in significantly lower systolic and diastolic blood pressure levels compared with LA (P=0.016 and P=0.011, respectively, from analysis of variance (ANOVA) for repeated measures). CONCLUSIONS: We observed a hypotensive effect of ALA, which may constitute another mechanism accounting in part for the apparent cardioprotective effect of this n-3 fatty acid.", "title": "Dietary supplementation with flaxseed oil lowers blood pressure in dyslipidaemic patients." }, { "docid": "MED-2580", "text": "Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial–based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18–0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial–based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence.", "title": "High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial" }, { "docid": "MED-3787", "text": "Background Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8). Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.", "title": "11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma" }, { "docid": "MED-3747", "text": "Prostate cancer is one of the most common cancers in the world, and its prevalence is expected to increase appreciably in the coming decades. As such, more research is necessary to understand the etiology, progression and possible preventative measures to delay or to stop the development of this disease. Recently, there has been interest in examining the effects of whole extracts from commonly harvested crops on the behaviour and progression of cancer. Here, we describe the effects of whole cranberry extract (WCE) on the behaviour of DU145 human prostate cancer cells in vitro. Following treatment of DU145 human prostate cancer cells with 10, 25 and 50 μg ml⁻¹ of WCE, respectively for 6 h, WCE significantly decreased the cellular viability of DU145 cells. WCE also decreased the proportion of cells in the G2-M phase of the cell cycle and increased the proportion of cells in the G1 phase of the cell cycle following treatment of cells with 25 and 50 μg ml⁻¹ treatment of WCE for 6 h. These alterations in cell cycle were associated with changes in cell cycle regulatory proteins and other cell cycle associated proteins. WCE decreased the expression of CDK4, cyclin A, cyclin B1, cyclin D1 and cyclin E, and increased the expression of p27. Changes in p16(INK4a) and pRBp107 protein expression levels also were evident, however, the changes noted in p16(INK4a) and pRBp107 protein expression levels were not statistically significant. These findings demonstrate that phytochemical extracts from the American cranberry (Vaccinium macrocarpon) can affect the behaviour of human prostate cancer cells in vitro and further support the potential health benefits associated with cranberries.", "title": "American cranberry (Vaccinium macrocarpon) extract affects human prostate cancer cell growth via cell cycle arrest by modulating expression of cell..." }, { "docid": "MED-3876", "text": "BACKGROUND: Chinese men have lower incidences of prostate cancer compared to men from Europe and North America. Asians consume large quantities of soya, a rich source of isoflavanoids phyto-oestrogens and have high plasma and urinary levels of these compounds. The mammalian lignans, enterolactone and enterodiol, are another group of weak plant oestrogens and are derived from seeds, cereals and grains. Vegetarians have high plasma and urinary concentrations of lignans. METHODS: The concentrations lignans and isoflavonic phyto-oestrogens were determined by gas chromatography-mass spectrometry (GC-MS) in plasma and prostatic fluid from Portuguese, Chinese and British men consuming their traditional diets. RESULTS: In prostatic fluid the mean concentrations of enterolactone were 31, 162 and 20.3 ng/ml for Hong Kong, Portugal and Britain respectively. Very high levels of enterolactone (> 600 ng/ml) were observed in the prostatic fluid of some of the men from Portugal. High concentrations of equol (3270 ng/ml) and daidzein (532 ng/ml) were found in a sample of prostatic fluid from Hong Kong. Higher mean levels of daidzein were observed in prostatic fluid from Hong Kong at 70 ng/ml, compared to 4.6 and 11.3 ng/ml in samples from Portugal and Britain respectively. Mean levels of daidzein were higher in the plasma samples from Hong Kong (31.3 ng/ml) compared to those from Portugal (1.3 ng/ml) and Britain (8.2 ng/ml). In general, the mean plasma concentrations of enterolactone from the three centres were similar, at 6.2, 3.9 and 3.9 ng/ml in samples from Hong Kong Portugal and Britain respectively. CONCLUSIONS: Higher concentrations of the isoflavanoid phyto-oestrogens, daidzein and equol, were found in the plasma and prostatic fluid of men from Hong Kong compared to those from Britain and Portugal. However, the levels of the lignan, enterolactone, were very much higher in prostatic fluid of Portuguese men. Isoflavanoids and lignans have many interesting properties and may, in part, be responsible for lower incidences of prostate cancer in men from Asia and also some Mediterranean countries. The isoflavanoids from soya, which are present in high concentrations in the prostatic fluid of Asian men, may be protective against prostate disease.", "title": "Lignans and isoflavonoids in plasma and prostatic fluid in men: samples from Portugal, Hong Kong, and the United Kingdom." }, { "docid": "MED-3113", "text": "Chronic diseases with a lifestyle-based aetiology currently make up a significant proportion of primary care consultations, but management often falls between the demands of public and clinical health. A modified clinical approach, based around the concept of \"lifestyle medicine\", helps fill the gap by adding behavioural, motivational and environmental skills to conventional medical practice. When used in a multidisciplinary setting, lifestyle medicine offers potential cost and effectiveness benefits, which are beginning to be realised.", "title": "The emergence of \"lifestyle medicine\" as a structured approach for management of chronic disease." }, { "docid": "MED-4231", "text": "OBJECTIVE: To analyze the relationship between onion and garlic intake and benign prostatic hyperplasia (BPH), using data from a multicenter case-control study conducted in Italy. METHODS: A multicenter case-control study of 1369 patients with BPH and 1451 controls, admitted to the same hospitals for a wide spectrum of acute, non-neoplastic conditions, was conducted in Italy between 1991 and 2002. Information was collected by trained interviewers using a validated and reproducible food frequency questionnaire. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were obtained after allowance for recognized confounding factors and energy intake. RESULTS: Compared with nonusers, the multivariate ORs for the highest category of onion and garlic intake were 0.41 (95% CI 0.24 to 0.72) and 0.72 (95% CI 0.57 to 0.91), respectively. The combined OR for frequent users versus nonusers of both onion and garlic was 0.65 (95% CI 0.49 to 0.86). The inverse relationships were consistent across age strata. CONCLUSIONS: This uniquely large data set from European populations showed an inverse association between allium vegetable consumption and BPH.", "title": "Onion and garlic intake and the odds of benign prostatic hyperplasia." }, { "docid": "MED-4480", "text": "Purpose To perform pattern analyses of dietary and lifestyle factors in relation to risk of esophageal and gastric cancers. Methods We evaluated risk factors for esophageal adenocarcinoma (EA), esophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma (GCA), and other gastric cancers (OGA) using data from a population-based case-control study conducted in Connecticut, New Jersey, and western Washington state. Dietary/lifestyle patterns were created using principal component analysis (PCA). Impact of the resultant scores on cancer risk was estimated through logistic regression. Results PCA identified six patterns: meat/nitrite, fruit/vegetable, smoking/alcohol, legume/meat alternate, GERD/BMI, and fish/vitamin C. Risk of each cancer under study increased with rising meat/nitrite score. Risk of EA increased with increasing GERD/BMI score, and risk of ESCC rose with increasing smoking/alcohol score and decreasing GERD/BMI score. Fruit/vegetable scores were inversely associated with EA, ESCC, and GCA. Conclusions PCA may provide a useful approach for summarizing extensive dietary/lifestyle data into fewer interpretable combinations that discriminate between cancer cases and controls. The analyses suggest that meat/nitrite intake is associated with elevated risk of each cancer under study, while fruit/vegetable intake reduces risk of EA, ESCC, and GCA. GERD/obesity were confirmed as risk factors for EA and smoking/alcohol as risk factors for ESCC.", "title": "Principal component analysis of dietary and lifestyle patterns in relation to risk of subtypes of esophageal and gastric cancer" }, { "docid": "MED-5034", "text": "The association between cured and broiled meat consumption by the mother during pregnancy and by the child was examined in relation to childhood cancer. Five meat groups (ham, bacon, or sausage; hot dogs; hamburgers; bologna, pastrami, corned beef, salami, or lunch meat; charcoal broiled foods) were assessed. Exposures among 234 cancer cases (including 56 acute lymphocytic leukemia [ALL], 45 brain tumor) and 206 controls selected by random-digit dialing in the Denver, Colorado (United States) standard metropolitan statistical area were compared, with adjustment for confounders. Maternal hot-dog consumption of one or more times per week was associated with childhood brain tumors (odds ratio [OR] = 2.3, 95 percent confidence interval [CI] = 1.0-5.4). Among children, eating hamburgers one or more times per week was associated with risk of ALL (OR = 2.0, CI = 0.9-4.6) and eating hot dogs one or more times per week was associated with brain tumors (OR = 2.1, CI = 0.7-6.1). Among children, the combination of no vitamins and eating meats was associated more strongly with both ALL and brain cancer than either no vitamins or meat consumption alone, producing ORs of two to seven. The results linking hot dogs and brain tumors (replicating an earlier study) and the apparent synergism between no vitamins and meat consumption suggest a possible adverse effect of dietary nitrites and nitrosamines.", "title": "Cured and broiled meat consumption in relation to childhood cancer: Denver, Colorado (United States)" }, { "docid": "MED-2659", "text": "U.S. and European regulators and researchers disagree over risks of a common class of surfactants.", "title": "European bans on surfactant trigger transatlantic debate." }, { "docid": "MED-4696", "text": "Several epidemiologic studies have shown that chronic inflammation predisposes individuals to various types of cancer. Many cancers arise from sites of infection, chronic irritation, and inflammation. Conversely, an oncogenic change induces an inflammatory microenvironment that promotes the development of tumors. Natural bioactive compounds in dietary plant products including fruits, vegetables, grains, legumes, tea, and wine are claimed to help prevent cancer, degenerative diseases, and chronic and acute inflammation. Modern methods in cell and molecular biology allow us to understand the interactions of different natural bioactive compounds with basic mechanisms of inflammatory response. The molecular pathways of this cancer-related inflammation are now unraveled. Natural bioactive compounds exert anti-inflammatory activity by modulating pro-inflammatory gene expressions have shown promising chemopreventive activity. This review summarizes current knowledge on natural bioactive compounds that act through the signaling pathways and modulate inflammatory gene expressions, thus providing evidence for these substances in cancer chemopreventive action.", "title": "Modulation of inflammatory genes by natural dietary bioactive compounds." }, { "docid": "MED-2577", "text": "A case-control study probing the role of diet on the incidence of colorectal cancer was undertaken in Athens, Greece, in a population characterized by ethnic homogeneity but substantial heterogeneity with respect to dietary habits. The case series consisted of 100 consecutive patients with histologically confirmed colorectal cancer admitted to two large hospitals of Athens during a 16-month period; the control series consisted of orthopaedic patients, admitted to the same hospitals during the same time period, individually matched to the index cases by age and sex. Dietary histories concerning the frequency of consumption (per month or per week) of about 80 food items were obtained by the same interviewer. Cases reported significantly less frequent consumption of vegetables (particularly beets, spinach, lettuce and cabbage) and, independently, significantly more frequent consumption of meat (notably lamb and beef). Between the two extremes (high-vegetable, low-meat diet versus high-meat, low-vegetable diet) a risk ratio of about 8 appears to exist, sufficient (in size and direction) to explain a substantial part of the international variation in the incidence of colorectal cancer. Significant associations were not found with beer or other alcoholic beverages, and significant interactions were not noted with respect to age, sex and anatomic localization (colon vs. rectum).", "title": "Diet and colorectal cancer: a case-control study in Greece." }, { "docid": "MED-2571", "text": "Background Prospective, randomized, pilot clinical study was conducted to evaluate the beneficial effects of inositol hexaphosphate (IP6) + Inositol in breast cancer patients treated with adjuvant therapy. Patients and methods Patients with invasive ductal breast cancer where polychemotherapy was indicated were monitored in the period from 2005-2007. Fourteen patients in the same stage of ductal invasive breast cancer were involved in the study, divided in two randomized groups. One group was subjected to take IP6 + Inositol while the other group was taking placebo. In both groups of patients the same laboratory parameters were monitored. When the treatment was finished, all patients have filled questionnaires QLQ C30 and QLQ-BR23 to determine the quality of life. Results Patients receiving chemotherapy, along with IP6 + Inositol did not have cytopenia, drop in leukocyte and platelet counts. Red blood cell counts and tumor markers were unaltered in both groups. However, patients who took IP6 + Inositol had significantly better quality of life (p = 0.05) and functional status (p = 0.0003) and were able to perform their daily activities. Conclusion IP6 + Inositol as an adjunctive therapy is valuable help in ameliorating the side effects and preserving quality of life among the patients treated with chemotherapy.", "title": "Efficacy of IP6 + inositol in the treatment of breast cancer patients receiving chemotherapy: prospective, randomized, pilot clinical study" }, { "docid": "MED-3281", "text": "INTRODUCTION: Amino acid auxotrophy or the metabolic defect which renders cancer incapable of surviving under amino acid depleted conditions is being exploited and explored as a therapeutic against cancer. Early clinical data on asparagine- and arginine-depleting drugs have demonstrated low toxicity and efficacy in melanoma, hepatocellular carcinoma and acute lymphoblastic leukemia. Methionine auxotrophy is a novel niche currently under exploration for targeting certain cancers. AREAS COVERED: In this review we explore the discovery of methionine auxotrophy followed by in vitro, in vivo and patient data on targeting cancer with methionine depletion. We end with a small discussion on bioengineering, pegylation and red blood cell encapsulation as mechanisms for decreasing immunogenicity of methionine-depleting drugs. We hope to provide a platform for future pharmacology, toxicology and cytotoxicity studies with methionine depletion therapy and drugs. EXPERT OPINION: Although methionine auxotrophy seems as a viable target, extensive research addressing normal versus cancer cell toxicity needs to be conducted. Further research also needs to be conducted into the molecular mechanism associated with methionine depletion therapy. Finally, novel methods need to be developed to decrease the immunogenicity of methionine-depleting drugs, a current issue with protein therapeutics.", "title": "Targeting methionine auxotrophy in cancer: discovery & exploration." }, { "docid": "MED-3742", "text": "Background: Dietary flavonoids have beneficial effects on blood pressure in intervention settings, but there is limited information on habitual intake and risk of hypertension in population-based studies. Objective: We examined the association between habitual flavonoid intake and incident hypertension in a prospective study in men and women. Design: A total of 87,242 women from the Nurses' Health Study (NHS) II, 46,672 women from the NHS I, and 23,043 men from the Health Professionals Follow-Up Study (HPFS) participated in the study. Total flavonoid and subclass intakes were calculated from semiquantitative food-frequency questionnaires collected every 4 y by using an updated and extended US Department of Agriculture database. Results: During 14 y of follow-up, 29,018 cases of hypertension in women and 5629 cases of hypertension in men were reported. In pooled multivariate-adjusted analyses, participants in the highest quintile of anthocyanin intake (predominantly from blueberries and strawberries) had an 8% reduction in risk of hypertension [relative risk (RR): 0.92; 95% CI: 0.86, 0.98; P < 0.03] compared with that for participants in the lowest quintile of anthocyanin intake; the risk reduction was 12% (RR: 0.88; 95% CI: 0.84, 0.93; P < 0.001) in participants ≤60 y of age and 0.96 (0.91, 1.02) in participants >60 y of age (P for age interaction = 0.02). Although intakes of other subclasses were not associated with hypertension, pooled analyses for individual compounds suggested a 5% (95% CI: 0.91, 0.99; P = 0.005) reduction in risk for the highest compared with the lowest quintiles of intake of the flavone apigenin. In participants ≤60 y of age, a 6% (95% CI: 0.88, 0.97; P = 0.002) reduction in risk was observed for the flavan-3-ol catechin when the highest and the lowest quintiles were compared. Conclusions: Anthocyanins and some flavone and flavan-3-ol compounds may contribute to the prevention of hypertension. These vasodilatory properties may result from specific structural similarities (including the B-ring hydroxylation and methyoxylation pattern).", "title": "Habitual intake of flavonoid subclasses and incident hypertension in adults" }, { "docid": "MED-2772", "text": "Prostate cancer has become the most common cancer among men in the United States. Although milk consumption is considered to be a risk factor in some epidemiological studies, the results are inconsistent. A meta-analysis method was conducted to estimate the combined odds ratio (OR) between milk consumption and prostate cancer from case-control studies published between 1984 and 2003 using commercial software (comprehensive meta-analysis). The combined OR was 1.68 (95% confidence interval = 1.34-2.12) in the 11 published case-control studies. The combined OR varied little by study stratification. Additionally, we evaluated the possible risk factors in milk for prostate cancer. In conclusion, we found a positive association between milk consumption and prostate cancer. The underlying mechanisms, including fat, calcium, hormones, and other factors, should be investigated further. Copyright 2004 Lawrence Erlbaum Associates, Inc.", "title": "Milk consumption is a risk factor for prostate cancer: meta-analysis of case-control studies." }, { "docid": "MED-3874", "text": "Background Prostate cancer affects one-out-of-six men during their lifetime. Dietary factors are postulated to influence the development and progression of prostate cancer. Low-fat diets and flaxseed supplementation may offer potentially protective strategies. Methods We undertook a multi-site, randomized controlled trial to test the effects of low-fat and/or flaxseed-supplemented diets on the biology of the prostate and other biomarkers. Prostate cancer patients (n=161) scheduled at least 21 days before prostatectomy were randomly assigned to one of the following arms: 1) control (usual diet); 2) flaxseed-supplemented diet (30 g/day); 2) low-fat diet (<20% total energy); or 4) flaxseed-supplemented, low-fat diet. Blood was drawn at baseline and prior to surgery and analyzed for prostate specific antigen (PSA), sex hormone binding globulin, testosterone, insulin-like growth factor-1 and binding protein-3, c-reactive protein, and total and low density lipoprotein cholesterol. Tumors were assessed for proliferation (Ki-67, the primary endpoint) and apoptosis. Results Men were on protocol an average of 30 days. Proliferation rates were significantly lower (P < 0.002) among men assigned to the flaxseed arms. Median Ki-67 positive cells/total nuclei ratios (x100) were 1.66 (flaxseed-supplemented diet) and 1.50 (flaxseed-supplemented, low-fat diet) vs. 3.23 (control) and 2.56 (low-fat diet). No differences were observed between arms with regard to side effects, apoptosis, and most serological endpoints; however, men on low-fat diets experienced significant decreases in serum cholesterol (P=0.048). Conclusions Findings suggest that flaxseed is safe, and associated with biologic alterations that may be protective for prostate cancer. Data also further support low-fat diets to manage serum cholesterol.", "title": "Flaxseed Supplementation (not Dietary Fat Restriction) Reduces Prostate Cancer Proliferation Rates in Men Presurgery" }, { "docid": "MED-4888", "text": "Epidemiological and prospective studies indicate that comprehensive lifestyle changes may modify the progression of prostate cancer. However, the molecular mechanisms by which improvements in diet and lifestyle might affect the prostate microenvironment are poorly understood. We conducted a pilot study to examine changes in prostate gene expression in a unique population of men with low-risk prostate cancer who declined immediate surgery, hormonal therapy, or radiation and participated in an intensive nutrition and lifestyle intervention while undergoing careful surveillance for tumor progression. Consistent with previous studies, significant improvements in weight, abdominal obesity, blood pressure, and lipid profile were observed (all P < 0.05), and surveillance of low-risk patients was safe. Gene expression profiles were obtained from 30 participants, pairing RNA samples from control prostate needle biopsy taken before intervention to RNA from the same patient's 3-month postintervention biopsy. Quantitative real-time PCR was used to validate array observations for selected transcripts. Two-class paired analysis of global gene expression using significance analysis of microarrays detected 48 up-regulated and 453 down-regulated transcripts after the intervention. Pathway analysis identified significant modulation of biological processes that have critical roles in tumorigenesis, including protein metabolism and modification, intracellular protein traffic, and protein phosphorylation (all P < 0.05). Intensive nutrition and lifestyle changes may modulate gene expression in the prostate. Understanding the prostate molecular response to comprehensive lifestyle changes may strengthen efforts to develop effective prevention and treatment. Larger clinical trials are warranted to confirm the results of this pilot study.", "title": "Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention" }, { "docid": "MED-5033", "text": "This year, more than 1 million Americans and more than 10 million people worldwide are expected to be diagnosed with cancer, a disease commonly believed to be preventable. Only 5–10% of all cancer cases can be attributed to genetic defects, whereas the remaining 90–95% have their roots in the environment and lifestyle. The lifestyle factors include cigarette smoking, diet (fried foods, red meat), alcohol, sun exposure, environmental pollutants, infections, stress, obesity, and physical inactivity. The evidence indicates that of all cancer-related deaths, almost 25–30% are due to tobacco, as many as 30–35% are linked to diet, about 15–20% are due to infections, and the remaining percentage are due to other factors like radiation, stress, physical activity, environmental pollutants etc. Therefore, cancer prevention requires smoking cessation, increased ingestion of fruits and vegetables, moderate use of alcohol, caloric restriction, exercise, avoidance of direct exposure to sunlight, minimal meat consumption, use of whole grains, use of vaccinations, and regular check-ups. In this review, we present evidence that inflammation is the link between the agents/factors that cause cancer and the agents that prevent it. In addition, we provide evidence that cancer is a preventable disease that requires major lifestyle changes.", "title": "Cancer is a Preventable Disease that Requires Major Lifestyle Changes" }, { "docid": "MED-4232", "text": "OBJECTIVES: To evaluate the role of a wide range of foods on the risk of benign prostatic hyperplasia (BPH), we conducted a case-control study in Italy between 1991 and 2002. Although BPH is an extremely common condition, particularly among older men, its risk factors, including dietary ones, remain largely undefined. METHODS: Included in the study were 1369 patients younger than 75 years old surgically treated for BPH and 1451 controls younger than 75 years of age who had been admitted to the same hospitals as cases for a wide spectrum of acute, non-neoplastic conditions. A validated and reproducible food frequency questionnaire, including 78 foods and beverages, plus a separate section on alcoholic beverages, was used to assess patients' dietary habits 2 years before diagnosis or hospital admission. Multivariate odds ratios (OR) were obtained after allowance for energy intake and other major potential confounding factors. RESULTS: A significant trend of increasing risk with more frequent consumption was found for cereals (OR 1.55 for the greatest versus lowest quintile), bread (OR 1.69), eggs (OR 1.43), and poultry (OR 1.39). Inverse associations were observed for soups (OR 0.74), pulses (OR 0.74), cooked vegetables (OR 0.66), and citrus fruit (OR 0.82). No association was observed for milk and yogurt products, coffee and tea, pasta and rice, fish, cheese, row vegetables, potatoes, fruit, or desserts. CONCLUSIONS: The results of this study suggest a role for dietary habits on the risk of BPH. In particular, a diet rich in cereals and some types of meat and poor in vegetables and pulses may have an unfavorable effect in this Italian population.", "title": "Food groups and risk of benign prostatic hyperplasia." }, { "docid": "MED-4751", "text": "The continued increase in incidence of some hormone-related cancers worldwide is of great concern. Although estrogen-like substances in the environment were blamed for this increase, the possible role of endogenous estrogens from food has not been widely discussed. We are particularly concerned about cows' milk, which contains a considerable quantity of estrogens. When we name cows' milk as one of the important routes of human exposure to estrogens, the general response of Western people is that \"man has been drinking cows' milk for around 2000 years without apparent harm.\" However, the milk that we are now consuming is quite different from that consumed 100 years ago. Unlike their pasture-fed counterparts of 100 years ago, modern dairy cows are usually pregnant and continue to lactate during the latter half of pregnancy, when the concentration of estrogens in blood, and hence in milk, increases. The correlation of incidence and mortality rates with environmental variables in worldwide countries provides useful clues to the etiology of cancer. In this study, we correlated incidence rates for breast, ovarian, and corpus uteri cancers (1993-97 from Cancer Incidence in Five Continents) with food intake (1961-97 from FAOSTAT) in 40 countries. Meat was most closely correlated with the breast cancer incidence (r=0.827), followed by milk (0.817) and cheese (0.751). Stepwise multiple-regression analysis (SMRA) identified meat as the factor contributing most greatly to the incidence of breast cancer ([R]=0.862). Milk was most closely correlated with the incidence of ovarian cancer (r=0.779), followed by animal fats (0.717) and cheese (0.697). SMRA revealed that milk plus cheese make the greatest contribution to the incidence of ovarian cancer ([R]=0.767). Milk was most closely correlated with corpus uteri cancer (r=0.814), followed by cheese (0.787). SMRA revealed that milk plus cheese make the most significant contribution to the incidence of corpus uteri cancer ([R]=0.861). In conclusion, increased consumption of animal-derived food may have adverse effects on the development of hormone-dependent cancers. Among dietary risk factors, we are most concerned with milk and dairy products, because the milk we drink today is produced from pregnant cows, in which estrogen and progesterone levels are markedly elevated.", "title": "The possible role of female sex hormones in milk from pregnant cows in the development of breast, ovarian and corpus uteri cancers." }, { "docid": "MED-2647", "text": "Continuing evidence of the feminising effects of xenoestrogens on a range of wildlife species increases the need to assess the human health risk of these estrogen mimics. We have estimated the exposure of New Zealand males, females and young men to a range of naturally occurring and synthetic xenoestrogens found in food. Only estrogenic compounds that act by interaction with the estrogen receptor have been included. Theoretical plasma estrogen activity levels were derived from estrogen exposure estimates and estrogenic potency data. Theoretical plasma levels were compared with published data for specific xenoestrogens. There was surprisingly close agreement. Xenoestrogenicity from dietary intake was almost equally attributed to naturally occurring and synthetic xenoestrogens. Relative contributions for a male, for example were isoflavones (genistein and daidzein) (36%) and bisphenol A (34%) with smaller contributions from alkyl phenols (18%) and the flavonoids (phloretin and kaempferol) (12%). It is suggested that dietary xenoestrogens might have a pharmacological effect on New Zealand males and postmenopausal women, but are unlikely to be significant for pre-menopausal women.", "title": "Dietary exposure to xenoestrogens in New Zealand." }, { "docid": "MED-3745", "text": "Cranberries (Vaccinium macrocarpon Ait.) are an excellent dietary source of phytochemicals that include flavonol glycosides, anthocyanins, proanthocyanidins (condensed tannins), and organic and phenolic acids. Using C-18 and Sephadex Lipophilic LH-20 column chromatography, HPLC, and tandem LC-ES/MS, the total cranberry extract (TCE) has been analyzed, quantified, and separated into fractions enriched in sugars, organic acids, total polyphenols, proanthocyanidins, and anthocyanins (39.4, 30.0, 10.6, 5.5, and 1.2% composition, respectively). Using a luminescent ATP cell viability assay, the antiproliferative effects of TCE (200 microg/mL) versus all fractions were evaluated against human oral (KB, CAL27), colon (HT-29, HCT116, SW480, SW620), and prostate (RWPE-1, RWPE-2, 22Rv1) cancer cell lines. The total polyphenol fraction was the most active fraction against all cell lines with 96.1 and 95% inhibition of KB and CAL27 oral cancer cells, respectively. For the colon cancer cells, the antiproliferative activity of this fraction was greater against HCT116 (92.1%) than against HT-29 (61.1%), SW480 (60%), and SW620 (63%). TCE and all fractions showed >/=50% antiproliferative activity against prostate cancer cells with total polyphenols being the most active fraction (RWPE-1, 95%; RWPE-2, 95%; 22Rv1, 99.6%). Cranberry sugars (78.8 microg/mL) did not inhibit the proliferation of any cancer cell lines. The enhanced antiproliferative activity of total polyphenols compared to TCE and its individual phytochemicals suggests synergistic or additive antiproliferative interactions of the anthocyanins, proanthocyanidins, and flavonol glycosides within the cranberry extract.", "title": "Total cranberry extract versus its phytochemical constituents: antiproliferative and synergistic effects against human tumor cell lines." }, { "docid": "MED-3918", "text": "The study material consisted of five herbs: chamomile (flowers), mint (leaves), St John's wort (flowers and leaves), sage (leaves) and nettle (leaves), sourced from three producers. The calcium, magnesium, iron, zinc and copper contents were determined for both dried herb samples and prepared infusions, and the extraction rates were calculated. Mineral components were determined using atomic absorption spectrometry. Analysis showed that the contents of individual elements in herbs and infusions depended on the type of raw material, as well as on its origin. Moreover, it was found that iron penetrated the herbal infusions to the lowest degree (4.4-12.4%), while copper did so to the highest (26.7-50.7%). It is felt that in average consumption the herbal infusions are not important as calcium, magnesium, iron, zinc and copper sources in human nutrition.", "title": "Herbal infusions as a source of calcium, magnesium, iron, zinc and copper in human nutrition." }, { "docid": "MED-5032", "text": "The relation between the intake of certain food items thought to be precursors or inhibitors of N-nitroso compounds (NOC) and risk of leukemia was investigated in a case-control study among children from birth to age 10 years in Los Angeles County, California (United States). Cases were ascertained through a population-based tumor registry from 1980 to 1987. Controls were drawn from friends and by random-digit dialing. Interviews were obtained from 232 cases and 232 controls. Food items of principal interest were: breakfast meats (bacon, sausage, ham); luncheon meats (salami, pastrami, lunch meat, corned beef, bologna); hot dogs; oranges and orange juice; and grapefruit and grapefruit juice. We also asked about intake of apples and apple juice, regular and charcoal broiled meats, milk, coffee, and coke or cola drinks. Usual consumption frequencies were determined for both parents and the child. When the risks were adjusted for each other and other risk factors, the only persistent significant associations were for children's intake of hot dogs (odds ratio [OR] = 9.5, 95 percent confidence interval [CI] = 1.6-57.6 for 12 or more hot dogs per month, trend P = 0.01), and fathers' intake of hot dogs (OR = 11.0, CI = 1.2-98.7 for highest intake category, trend P = 0.01). There was no evidence that fruit intake provided protection. While these results are compatible with the experimental animal literature and the hypothesis that human NOC intake is associated with leukemia risk, given potential biases in the data, further study of this hypothesis with more focused and comprehensive epidemiologic studies is warranted.", "title": "Processed meats and risk of childhood leukemia (California, USA)." }, { "docid": "MED-3272", "text": "Objective Early detection and early treatment are of vital importance to the successful treatment of various cancers. The development of a novel screening method that is as economical and non-invasive as the faecal occult blood test (FOBT) for early detection of colorectal cancer (CRC) is needed. A study was undertaken using canine scent detection to determine whether odour material can become an effective tool in CRC screening. Design Exhaled breath and watery stool samples were obtained from patients with CRC and from healthy controls prior to colonoscopy. Each test group consisted of one sample from a patient with CRC and four control samples from volunteers without cancer. These five samples were randomly and separately placed into five boxes. A Labrador retriever specially trained in scent detection of cancer and a handler cooperated in the tests. The dog first smelled a standard breath sample from a patient with CRC, then smelled each sample station and sat down in front of the station in which a cancer scent was detected. Results 33 and 37 groups of breath and watery stool samples, respectively, were tested. Among patients with CRC and controls, the sensitivity of canine scent detection of breath samples compared with conventional diagnosis by colonoscopy was 0.91 and the specificity was 0.99. The sensitivity of canine scent detection of stool samples was 0.97 and the specificity was 0.99. The accuracy of canine scent detection was high even for early cancer. Canine scent detection was not confounded by current smoking, benign colorectal disease or inflammatory disease. Conclusions This study shows that a specific cancer scent does indeed exist and that cancer-specific chemical compounds may be circulating throughout the body. These odour materials may become effective tools in CRC screening. In the future, studies designed to identify cancer-specific volatile organic compounds will be important for the development of new methods for early detection of CRC.", "title": "Colorectal cancer screening with odour material by canine scent detection" }, { "docid": "MED-2584", "text": "In a 6-year prospective study, the authors examined the relation between diet and incident colon cancer among 32,051 non-Hispanic white cohort members of the Adventist Health Study (California, 1976-1982) who, at baseline, had no documented or reported history of cancer. The risk of colon cancer was determined from proportional hazards regression with adjustment for age and other covariates. The authors found a positive association with total meat intake (risk ratio (RR) for > or =1 time/week vs. no meat intake = 1.85, 95% confidence interval (CI) 1.19-2.87; p for trend = 0.01) and, among subjects who favored specific types of meat, positive associations with red meat intake (RR for > or =1 time/week vs. no red meat intake = 1.90, 95% CI 1.16-3.11; p for trend = 0.02) and white meat intake (RR for > or =1 time/week vs. no white meat intake = 3.29, 95% CI 1.60-6.75; p for trend = 0.006). An inverse association with legume intake (RR for >2 times/week vs. <1 time/week = 0.53, 95% CI 0.33-0.86; p for trend = 0.03) was observed. Among men, a positive association with body mass index was observed (relative to the RR for tertile III (>25.6 kg/m2) vs. tertile I (<22.5 kg/m2) = 2.63, 95% CI 1.12-6.13; p for trend = 0.05). A complex relation was identified whereby subjects exhibiting a high red meat intake, a low legume intake, and a high body mass experienced a more than threefold elevation in risk relative to all other patterns based on these variables. This pattern of putative risk factors would likely contribute to increases in both insulin resistance (high body mass, high red meat intake) and glycemic load (low legume intake), a synergism that, if causal, implicates hyperinsulinemic exposure in colon carcinogenesis. The overall findings from this cohort identify both red meat intake and white meat intake as important dietary risk factors for colon cancer and raise the possibility that the risk due to red meat intake reflects a more complex etiology.", "title": "Dietary risk factors for colon cancer in a low-risk population." }, { "docid": "MED-2773", "text": "In Japan dramatic lifestyle changes occurred after World War 2. To examine the experience of Japan as a clue to the etiology, trends in the mortality rates of testicular and prostatic cancers from 1947 to 1998 were related to changes in dietary practices. The male population born before 1945 had a peak in death from testicular cancer in their thirties or forties, whereas those born after 1946 had a peak in their twenties. The death rate of prostatic cancer increased 25-fold almost linearly after the war. The intake of milk, meat, and eggs increased 20-, 9-, and 7-fold, respectively, after the war. In connection with the development and growth of testicular and prostatic cancers in Japan, particular attention should be paid to milk, because the increase in its consumption in this country is a recent occurrence and because milk contains considerable amounts of estrogens plus saturated fats.", "title": "The experience of Japan as a clue to the etiology of testicular and prostatic cancers." }, { "docid": "MED-4885", "text": "Background Prostate cancer affects one-out-of-six men during their lifetime. Dietary factors are postulated to influence the development and progression of prostate cancer. Low-fat diets and flaxseed supplementation may offer potentially protective strategies. Methods We undertook a multi-site, randomized controlled trial to test the effects of low-fat and/or flaxseed-supplemented diets on the biology of the prostate and other biomarkers. Prostate cancer patients (n=161) scheduled at least 21 days before prostatectomy were randomly assigned to one of the following arms: 1) control (usual diet); 2) flaxseed-supplemented diet (30 g/day); 2) low-fat diet (<20% total energy); or 4) flaxseed-supplemented, low-fat diet. Blood was drawn at baseline and prior to surgery and analyzed for prostate specific antigen (PSA), sex hormone binding globulin, testosterone, insulin-like growth factor-1 and binding protein-3, c-reactive protein, and total and low density lipoprotein cholesterol. Tumors were assessed for proliferation (Ki-67, the primary endpoint) and apoptosis. Results Men were on protocol an average of 30 days. Proliferation rates were significantly lower (P < 0.002) among men assigned to the flaxseed arms. Median Ki-67 positive cells/total nuclei ratios (x100) were 1.66 (flaxseed-supplemented diet) and 1.50 (flaxseed-supplemented, low-fat diet) vs. 3.23 (control) and 2.56 (low-fat diet). No differences were observed between arms with regard to side effects, apoptosis, and most serological endpoints; however, men on low-fat diets experienced significant decreases in serum cholesterol (P=0.048). Conclusions Findings suggest that flaxseed is safe, and associated with biologic alterations that may be protective for prostate cancer. Data also further support low-fat diets to manage serum cholesterol.", "title": "Flaxseed Supplementation (not Dietary Fat Restriction) Reduces Prostate Cancer Proliferation Rates in Men Presurgery" }, { "docid": "MED-2824", "text": "Cancer is primarily a disease of old age, and that life style plays a major role in the development of most cancers is now well recognized. While plant-based formulations have been used to treat cancer for centuries, current treatments usually involve poisonous mustard gas, chemotherapy, radiation, and targeted therapies. While traditional plant-derived medicines are safe, what are the active principles in them and how do they mediate their effects against cancer is perhaps best illustrated by curcumin, a derivative of turmeric used for centuries to treat a wide variety of inflammatory conditions. Curcumin is a diferuloylmethane derived from the Indian spice, turmeric (popularly called \"curry powder\") that has been shown to interfere with multiple cell signaling pathways, including cell cycle (cyclin D1 and cyclin E), apoptosis (activation of caspases and down-regulation of antiapoptotic gene products), proliferation (HER-2, EGFR, and AP-1), survival (PI3K/AKT pathway), invasion (MMP-9 and adhesion molecules), angiogenesis (VEGF), metastasis (CXCR-4) and inflammation (NF-kappaB, TNF, IL-6, IL-1, COX-2, and 5-LOX). The activity of curcumin reported against leukemia and lymphoma, gastrointestinal cancers, genitourinary cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers, and sarcoma reflects its ability to affect multiple targets. Thus an \"old-age\" disease such as cancer requires an \"age-old\" treatment.", "title": "Curcumin and cancer: an \"old-age\" disease with an \"age-old\" solution." }, { "docid": "MED-4758", "text": "AIM: To examine the relation between meat intake and diabetes occurrence in adults. METHODS: In a prospective cohort study we examined the relation between diet and incident diabetes recorded among 8,401 cohort members (ages 45-88 years) of the Adventist Mortality Study and Adventist Health Study (California, USA) who were non-diabetic at baseline. During the 17-year follow-up, we identified 543 incident diabetes cases. RESULTS: (1) Subjects who were weekly consumers of all meats were 29% (OR = 1.29; 95% CI 1.08, 1.55) more likely (relative to zero meat intake) to develop diabetes. (2) Subjects who consumed any processed meats (salted fish and frankfurters) were 38% (OR = 1.38; 95% CI 1.05-1.82) more likely to develop diabetes. (3) Long-term adherence (over a 17-year interval) to a diet that included at least weekly meat intake was associated with a 74% increase (OR = 1.74; 95% CI 1.36-2.22) in odds of diabetes relative to long-term adherence to a vegetarian diet (zero meat intake). Further analyses indicated that some of this risk may be attributable to obesity and/or weight gain--both of which were strong risk factors in this cohort. It is noteworthy that even after control for weight and weight change, weekly meat intake remained an important risk factor (OR = 1.38; 95% CI 1.06-1.68) for diabetes [corrected]. CONCLUSIONS: Our findings raise the possibility that meat intake, particularly processed meats, is a dietary risk factor for diabetes. 2008 S. Karger AG, Basel.", "title": "Meats, processed meats, obesity, weight gain and occurrence of diabetes among adults: findings from Adventist Health Studies." }, { "docid": "MED-3278", "text": "Lung cancer (LC) continues to represent a heavy burden for health care systems worldwide. Epidemiological studies predict that its role will increase in the near future. While patient prognosis is strongly associated with tumour stage and early detection of disease, no screening test exists so far. It has been suggested that electronic sensor devices, commonly referred to as ‘electronic noses’, may be applicable to identify cancer-specific volatile organic compounds in the breath of patients and therefore may represent promising screening technologies. However, three decades of research did not bring forward a clinically applicable device. Here, we propose a new research approach by involving specially trained sniffer dogs into research strategies by making use of their ability to identify LC in the breath sample of patients.", "title": "Sniffer dogs as part of a bimodal bionic research approach to develop a lung cancer screening" }, { "docid": "MED-2573", "text": "A significant anticancer activity of the naturally occurring carbohydrate inositol hexaphosphate (IP(6)) has been reported against numerous cancer models. Since tumors require angiogenesis for growth and metastasis, we hypothesize that IP(6) reduces tumor growth by inhibiting angiogenesis. Because angiogenesis depends on the interaction between endothelial and tumor cells, we investigated the effect of IP(6) on both. IP(6) inhibited the proliferation and induced the differentiation of endothelial cells in vitro; the growth of bovine aortic endothelial cells (BAECs) evaluated by MTT proliferation assay was inhibited in a dose-dependent manner (IC(50) = 0.74 mM). The combination of IP(6) and vasostatin, a calreticulin fragment with anti-angiogenic activity, was synergistically superior in growth inhibition than either compound. IP(6) inhibited human umbilical vein endothelial cell (HUVEC) tube formation (in vitro capillary differentiation) on a reconstituted extracellular matrix, Matrigel, and disrupted pre-formed tubes. IP(6) significantly reduced basic fibroblast growth factor (bFGF)-induced vessel formation (P < 0.01) in vivo in Matrigel plug assay. Exposure of HepG2, a human hepatoma cell line, to IP(6) for 8 h, resulted in a dose-dependent decrease in the mRNA levels of vascular endothelial growth factor (VEGF), as assessed by RT-PCR. IP(6) treatment of HepG2 cells for 24 h also significantly reduced the VEGF protein levels in conditioned medium, in a concentration-dependent manner (P = 0.012). Thus, IP(6) has an inhibitory effect on induced angiogenesis.", "title": "Anti-angiogenic activity of inositol hexaphosphate (IP6)." }, { "docid": "MED-3743", "text": "Anthocyanins were isolated from male bracts of 10 wild species of bananas (Musa spp. and Ensete spp.) distributed in Thailand. Six major anthocyanin pigments were identified by high performance liquid chromatography (HPLC), mass spectrometry (MS), and tandem mass spectrometry (MS/MS). They are delphinidin-3-rutinoside (m/z 611.2), cyanidin-3-rutinoside (m/z 595.8), petunidin-3-rutinoside (m/z 624.9), pelargonidin-3-rutinoside (m/z 579.4), peonidin-3-rutinoside (m/z 608.7), and malvidin-3-rutinoside (m/z 638.8). On the basis of the types of pigment present, the wild bananas can be divided into 5 groups. The first group comprises M. itinerans, Musa sp. one, Musa sp. two, and M. acuminata accessions, which contain almost or all anthocyanin pigments except for pelargonidin-3-rutinoside, including both nonmethylated and methylated anthocyanins. The second group, M. acuminata subsp. truncata, contains only malvidin-3-rutinoside while the third group, M. coccinea, contains cyanidin-3-rutinoside and pelargonidin-3-rutinoside. The forth group, M. acuminata yellow bract and E. glaucum do not appear to contain any anthocyanin pigment. The fifth group consists of M. balbisiana, M. velutina, M. laterita, and E. superbum which contain only nonmethylated anthocyanin, delphinidin-3-rutinoside, and cyanidin-3-rutinoside. Total anthocyanin content in the analyzed bracts ranged from 0-119.70 mg/100 g bract fresh weight. The differences in the type of anthocyanin and variation in the amounts present indicate that wild bananas show biochemical diversity, which may be useful for identifying specific groups of bananas or for clarifying the evolution of flavonoid metabolism in each banana group.", "title": "Anthocyanin composition of wild bananas in Thailand." }, { "docid": "MED-4486", "text": "Diet plays an important role in the etiology of certain cancers, but there is limited evidence with regard to the association between diet and risk of endometrial cancer. Few prospective studies have investigated meat intake as a potential determinant of endometrial cancer risk. The objective of this study was to examine the association between endometrial cancer risk and total meat, red meat, processed meat, fish, and poultry intake. We conducted a case-cohort analysis within the Canadian Study of Diet, Lifestyle, and Health, a prospective cohort of 73 909 adults (39 614 women). Participants were recruited from 1992 to 1999, predominantly from three Canadian universities. We conducted a linkage with the Ontario Cancer Registry for the years 1992-2007 for the female cohort members, who resided in Ontario at the time of enrollment (n=26 024), to yield data on cancer incidence. The analytic sample was comprised of 107 incident cases and 1830 subcohort members, the latter being an age-stratified sample of the full cohort. A nonsignificant increase in the risk of endometrial cancer was associated with increased consumption of red meat [hazard ratio (HR)=1.62, 95% confidence intervals (CI)=0.86-3.08, for high vs. low intake; P trend=0.13)], processed meat (HR=1.45, 95% CI=0.80-2.61, for high vs. low intake; P trend=0.058), and all meat combined (HR=1.50, 95% CI=0.78-2.89, for high vs. low intake; P trend=0.14). No clear patterns were noted for poultry or fish. The results of this study, although based on a limited number of cases, suggest that relatively high meat intake may be associated with increased risk of endometrial cancer.", "title": "Endometrial cancer and meat consumption: a case-cohort study." }, { "docid": "MED-2645", "text": "The development of the male reproductive ducts and external genitalia in vertebrates is dependent on elevated androgen concentrations during embryonic development and the period of postnatal growth. We have observed that a population of juvenile alligators living on Lake Apopka exhibit significantly smaller penis size (24% average decrease) and lower plasma concentrations of testosterone (70% lower concentrations) when compared to animals of similar size on Lake Woodruff. In addition to smaller phalli, no relationship exists between plasma testosterone concentrations and penile size in males from Lake Apopka, whereas a positive relationship exists for males from Lake Woodruff. The alligators on Lake Apopka are known to have elevated concentrations of the antiandrogenic DDT breakdown product p.p'-DDE stored in their fat. We suggest a number of hypotheses that could explain the modification in the phenotype of the juvenile male living in Lake Apopka. These modifications in phenotype include a smaller penis size, lower plasma androgen concentrations, and lack of responsiveness of the penis to the plasma androgens present.", "title": "Reduction in penis size and plasma testosterone concentrations in juvenile alligators living in a contaminated environment." }, { "docid": "MED-5122", "text": "BACKGROUND: Drinking mate has been associated with cancers of the esophagus, oropharynx, larynx, lung, kidney, and bladder. We conducted this study to determine whether drinking mate could lead to substantial exposure to polycyclic aromatic hydrocarbons (PAH), including known carcinogens, such as benzo[a]pyrene. METHODS: The concentrations of 21 individual PAHs were measured in dry leaves of eight commercial brands of yerba mate and in infusions made with hot (80 degrees C) or cold (5 degrees C) water. Measurements were done using gas chromatography/mass spectrometry, with deuterated PAHs as the surrogates. Infusions were made by adding water to the leaves, removing the resulting infusion after 5 min, and then adding more water to the remaining leaves. This process was repeated 12 times for each infusion temperature. RESULTS: The total concentrations of the 21 PAHs in different brands of yerba mate ranged from 536 to 2,906 ng/g dry leaves. Benzo[a]pyrene concentrations ranged from 8.03 to 53.3 ng/g dry leaves. For the mate infusions prepared using hot water and brand 1, 37% (1,092 of 2,906 ng) of the total measured PAHs and 50% (25.1 of 50 ng) of the benzo[a]pyrene content were released into the 12 infusions. Similar results were obtained for other hot and cold infusions. CONCLUSION: Very high concentrations of carcinogenic PAHs were found in yerba mate leaves and in hot and cold mate infusions. Our results support the hypothesis that the carcinogenicity of mate may be related to its PAH content.", "title": "High levels of carcinogenic polycyclic aromatic hydrocarbons in mate drinks." }, { "docid": "MED-2988", "text": "This review describes the present state of knowledge about phytic acid (phytate), which is often present in legume seeds. The antinutritional effects of phytic acid primarily relate to the strong chelating associated with its six reactive phosphate groups. Its ability to complex with proteins and particularly with minerals has been a subject of investigation from chemical and nutritional viewpoints. The hydrolysis of phytate into inositol and phosphates or phosphoric acid occurs as a result of phytase or nonenzymatic cleavage. Enzymes capable of hydrolysing phytates are widely distributed in micro-organisms, plants and animals. Phytases act in a stepwise manner to catalyse the hydrolysis of phytic acid. To reduce or eliminate the chelating ability of phytate, dephosphorylation of hexa- and penta-phosphate forms is essential since a high degree of phosphorylation is necessary to bind minerals. There are several methods of decreasing the inhibitory effect of phytic acid on mineral absorption (cooking, germination, fermentation, soaking, autolysis). Nevertheless, inositol hexaphosphate is receiving increased attention owing to its role in cancer prevention and/or therapy and its hypocholesterolaemic effect.", "title": "The role of phytic acid in legumes: antinutrient or beneficial function?" }, { "docid": "MED-3789", "text": "Background: Meat, milk, and eggs have been inconsistently associated with the risk of advanced prostate cancer. These foods are sources of choline—a nutrient that may affect prostate cancer progression through cell membrane function and one-carbon metabolism. No study has examined dietary choline and the risk of lethal prostate cancer. Objective: Our objective was to examine whether dietary choline, choline-containing compounds, and betaine (a choline metabolite) increase the risk of lethal prostate cancer. Design: We prospectively examined the intake of these nutrients and the risk of lethal prostate cancer among 47,896 men in the Health Professionals Follow-Up Study. In a case-only survival analysis, we examined the postdiagnostic intake of these nutrients and the risk of lethal prostate cancer among 4282 men with an initial diagnosis of nonmetastatic disease during follow-up. Diet was assessed with a validated questionnaire 6 times during 22 y of follow-up. Results: In the incidence analysis, we observed 695 lethal prostate cancers during 879,627 person-years. Men in the highest quintile of choline intake had a 70% increased risk of lethal prostate cancer (HR: 1.70; 95% CI: 1.18, 2.45; P-trend = 0.005). In the case-only survival analysis, we observed 271 lethal cases during 33,679 person-years. Postdiagnostic choline intake was not statistically significantly associated with the risk of lethal prostate cancer (HR for quintile 5 compared with quintile 1: 1.69; 95% CI: 0.93, 3.09; P-trend = 0.20). Conclusion: Of the 47,896 men in our study population, choline intake was associated with an increased risk of lethal prostate cancer.", "title": "Choline intake and risk of lethal prostate cancer: incidence and survival" }, { "docid": "MED-4551", "text": "Interest has increased in the possibility that maternal dietary intake during pregnancy might influence the development of allergic disorders in children. The present prospective study examined the association of maternal intake of selected foods high in fatty acids and specific types of fatty acids during pregnancy with the risk of suspected atopic eczema among Japanese infants aged 3-4 months. Subjects were 771 mother-child pairs. Information on maternal dietary intake during pregnancy was assessed with a validated self-administered diet history questionnaire. The term 'suspected atopic eczema' was used to define an outcome based on results of our questionnaire completed by mothers 3-4 months postpartum. The risk of suspected atopic eczema was 8.4% (n = 65). Higher maternal intake of meat during pregnancy was significantly associated with an increased risk of suspected atopic eczema in the offspring: the multivariate odds ratio (OR) for the highest vs. lowest quartile was 2.59 [95% confidence interval (CI): 1.15-6.17, p for trend = 0.01]. The positive association was strengthened when the definition of the outcome was confined to a definite physician's diagnosis of atopic eczema (n = 35): the multivariate OR between extreme quartiles was 3.53 (95% CI: 1.19-12.23, p for trend = 0.02). No material exposure-response relationships were observed between maternal intake of eggs, dairy products, fish, total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid consumption and the risk of suspected atopic eczema. Higher maternal meat intake may increase the risk of infantile atopic eczema, whereas we found no evidence that maternal intake of fish and n-3 polyunsaturated fatty acids are preventive against infantile atopic eczema. (c) 2009 John Wiley & Sons A/S", "title": "Maternal meat and fat consumption during pregnancy and suspected atopic eczema in Japanese infants aged 3-4 months: the Osaka Maternal and Child He..." } ]
[ { "docid": "MED-5355", "text": "OBJECTIVE: High intake of whole-grain products may protect against prostate cancer, but overall evidence is limited and inconclusive. The aim of the present study was to investigate the relationship between the intake of whole-grain products and risk of prostate cancer in a large prospective cohort. METHODS: A total of 26,691 men aged 50-64 years participated in the Diet, Cancer and Health cohort study and provided information about diet and potential prostate cancer risk factors. During a median follow-up of 12.4 years, we identified 1,081 prostate cancer cases. Associations between whole-grain product intake and prostate cancer incidence were analyzed using Cox's regression model. RESULTS: Overall, there was no association between total intake of whole-grain products and prostate cancer risk (adjusted incidence rate ratio per 50 g day(-1): 1.00 (95% confidence interval: 0.96, 1.05)) as well as between intake of the specific whole-grain products: whole-grain rye bread, whole-grain bread, and oatmeal, and risk of prostate cancer. No risk estimates did differ according to either stage or grade of disease. CONCLUSIONS: Results from this prospective study suggest that higher intakes of total or specific whole-grain products are not associated with risk of prostate cancer in a population of Danish middle-aged men.", "title": "Intake of whole-grain products and risk of prostate cancer among men in the Danish Diet, Cancer and Health cohort study." }, { "docid": "MED-865", "text": "Prostate cancer remains the second leading cause of cancer deaths among American men. Earlier diagnosis increases survival rate in patients. However, treatments for advanced disease are limited to hormone ablation techniques and palliative care. Thus, new methods of treatment and prevention are necessary for inhibiting disease progression to a hormone refractory state. One of the approaches to control prostate cancer is prevention through diet, which inhibits one or more neoplastic events and reduces the cancer risk. For centuries, Ayurveda has recommended the use of bitter melon (Momordica charantia) as a functional food to prevent and treat human health related issues. In this study, we have initially used human prostate cancer cells, PC3 and LNCaP, as an in vitro model to assess the efficacy of bitter melon extract (BME) as an anti-cancer agent. We observed that prostate cancer cells treated with BME accumulate during the S phase of the cell cycle, and modulate cyclin D1, cyclin E and p21 expression. Treatment of prostate cancer cells with BME enhanced Bax expression, and induced poly(ADP-ribose) polymerase cleavage. Oral gavage of BME, as a dietary compound, delayed the progression to high grade prostatic intraepithelial neoplasia (PIN) in TRAMP (transgenic adenocarcinoma of mouse prostate) mice (31%). Prostate tissue from BME-fed mice displayed ~51% reduction of PCNA expression. Together, our results suggest for the first time that oral administration of BME inhibits prostate cancer progression in TRAMP mice by interfering cell cycle progression and proliferation.", "title": "Bitter melon extract impairs prostate cancer cell cycle progression and delays prostatic intraepithelial neoplasia in TRAMP model" }, { "docid": "MED-2120", "text": "In a recent study, prostatectomy specimens from which Propionibacterium acnes was cultured were more likely to have inflammation than culture-negative specimens or specimens positive for other bacteria, leading the authors to hypothesize that P. acnes-mediated inflammation may contribute to prostate carcinogenesis. To indirectly explore associations between P. acnes and prostate cancer, we investigated severe acne, as measured by tetracycline use for four or more years, in relation to incident prostate cancer in the Health Professionals Follow-up Study. On the 1992 follow-up questionnaire, participants were asked whether they had ever used “tetracycline for at least two months at a time (e.g., for acne or other reason)” and their duration of use. Prostate cancer diagnoses were ascertained on each subsequent biennial questionnaire and confirmed by medical record review. Between 1992 and 2002, 2,147 cases of prostate cancer were reported among 34,629 eligible participants. Men who used tetracycline for four or more years had a significantly higher risk of prostate cancer (16 cases, 1,569 person-years) than men who did not use tetracycline (2,071 cases, 304,822 person-years, multivariable-adjusted RR=1.70, 95% CI:1.03–2.80). Although intriguing, this finding should be viewed cautiously because of the small number of exposed cases, indirect assessment of severe acne, and complex etiology of acne, which is not limited to P. acnes infection. Therefore, additional biologic and epidemiologic studies are necessary to determine and elucidate the possible role of P. acnes infection in prostate carcinogenesis.", "title": "ACNE AND RISK OF PROSTATE CANCER" }, { "docid": "MED-1532", "text": "Although substantial nutrition transition, characterized by an increased intake of energy, animal fat, and red meats, has occurred during the last several decades in East Asia, few studies have systematically evaluated temporal trends in cancer incidence or mortality among populations in this area. Therefore, we sought to investigate this question with tremendous public health implications. Data on mortality rates of cancers of the breast, colon, prostate, esophagus, and stomach for China (1988-2000), Hong Kong (1960-2006), Japan (1950-2006), Korea (1985-2006), and Singapore (1963-2006) were obtained from WHO. Joinpoint regression was used to investigate trends in mortality of these cancers. A remarkable increase in mortality rates of breast, colon, and prostate cancers and a precipitous decrease in those of esophageal and stomach cancers have been observed in selected countries (except breast cancer in Hong Kong) during the study periods. For example, the annual percentage increase in breast cancer mortality was 5.5% (95% confidence interval: 3.8, 7.3%) for the period 1985-1993 in Korea, and mortality rates for prostate cancer significantly increased by 3.2% (95% confidence interval: 3.0, 3.3%) per year from 1958 to 1993 in Japan. These changes in cancer mortality lagged ∼ 10 years behind the inception of the nutrition transition toward a westernized diet in selected countries or regions. There have been striking changes in mortality rates of breast, colon, prostate, esophageal, and stomach cancers in East Asia during the last several decades, which may be at least in part attributable to the concurrent nutrition transition.", "title": "Trends in mortality from cancers of the breast, colon, prostate, esophagus, and stomach in East Asia: role of nutrition transition." }, { "docid": "MED-2136", "text": "Prostate cancer (PCa) is dependent on androgen receptor signaling and aberrations of the PI3K-Akt-mTORC1 pathway mediating excessive and sustained growth signaling. The nutrient-sensitive kinase mTORC1 is upregulated in nearly 100% of advanced human PCas. Oncogenic mTORC1 signaling activates key subsets of mRNAs that cooperate in distinct steps of PCa initiation and progression. Epidemiological evidence points to increased dairy protein consumption as a major dietary risk factor for the development of PCa. mTORC1 is a master regulator of protein synthesis, lipid synthesis and autophagy pathways that couple nutrient sensing to cell growth and cancer. This review provides evidence that PCa initiation and progression are promoted by cow´s milk, but not human milk, stimulation of mTORC1 signaling. Mammalian milk is presented as an endocrine signaling system, which activates mTORC1, promotes cell growth and proliferation and suppresses autophagy. Naturally, milk-mediated mTORC1 signaling is restricted only to the postnatal growth phase of mammals. However, persistent consumption of cow´s milk proteins in humans provide highly insulinotropic branched-chain amino acids (BCAAs) provided by milk´s fast hydrolysable whey proteins, which elevate postprandial plasma insulin levels, and increase hepatic IGF-1 plasma concentrations by casein-derived amino acids. BCAAs, insulin and IGF-1 are pivotal activating signals of mTORC1. Increased cow´s milk protein-mediated mTORC1 signaling along with constant exposure to commercial cow´s milk estrogens derived from pregnant cows may explain the observed association between high dairy consumption and increased risk of PCa in Westernized societies. As well-balanced mTORC1-signaling plays an important role in appropriate prostate morphogenesis and differentiation, exaggerated mTORC1-signaling by high cow´s milk consumption predominantly during critical growth phases of prostate development and differentiation may exert long-term adverse effects on prostate health. Attenuation of mTORC1 signaling by contemporary Paleolithic diets and restriction of dairy protein intake, especially during mTORC1-dependent phases of prostate development and differentiation, may offer protection from the most common dairy-promoted cancer in men of Western societies.", "title": "The impact of cow's milk-mediated mTORC1-signaling in the initiation and progression of prostate cancer" }, { "docid": "MED-2760", "text": "Context Multivitamin preparations are the most common dietary supplement, taken by at least one-third of all US adults. Limited observational studies have not provided evidence regarding associations of multivitamin use with total and site-specific cancer incidence or mortality. Objective To determine whether long-term multivitamin supplementation decreases the risk of total and site-specific cancer events among men. Design The Physicians’ Health Study II is a randomized, double-blind, placebo-controlled trial of a common multivitamin that began in 1997 with treatment and follow-up through June 1, 2011. Setting and Participants A total of 14,641 male U.S. physicians initially aged ≥50 years (mean [± SD] age; 64.3 [± 9.2] years), including 1,312 men with a history of cancer at randomization, were enrolled. Intervention Daily multivitamin, as Centrum Silver. Main Outcome Measures A primary outcome was total cancer (excluding non-melanoma skin cancer), with prostate, colorectal, and other site-specific cancers among secondary endpoints included in this report. Results During a median (interquartile range) follow-up of 11.2 (10.7 to 13.3) years, there were 2,669 men with confirmed cancer, including 1,373 cases of prostate cancer and 210 cases of colorectal cancer. Compared with placebo, men taking a daily multivitamin had a statistically significant reduction in the incidence of total cancer (active and placebo multivitamin groups, 17.0 and 18.3 events, respectively, per 1,000 person-years; hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.86–0.998; P=0.044). There was no significant effect of a daily multivitamin on prostate cancer (HR, 0.98; 95% CI, 0.88–1.09; P=0.76), colorectal cancer (HR, 0.89; 95% CI, 0.68–1.17; P=0.39), or other site-specific cancers There was a lower risk of cancer mortality that did not reach statistical significance (HR, 0.88; 95% CI, 0.77–1.01; P=0.07). Daily multivitamin use was associated with a reduction in total cancer among 1,312 men with a baseline history of cancer (HR, 0.73; 95% CI, 0.56–0.96; P=0.022), but this did not differ significantly from that among 13,329 men initially free of cancer (HR, 0.94; 95% CI, 0.87–1.02; P=0.15) (P, interaction = 0.07). Conclusions In this large prevention trial of male physicians, daily multivitamin supplementation modestly but significantly reduced the risk of total cancer.", "title": "Multivitamins in the Prevention of Cancer in Men: The Physicians’ Health Study II Randomized Controlled Trial" }, { "docid": "MED-4827", "text": "Background Several prospective studies suggest that use of cholesterol-lowering statin drugs is inversely associated with advanced stage and possibly high-grade prostate cancer. One study reported that men with low cholesterol had a lower risk of high-grade prostate cancer. Given these findings, we investigated the association between low serum cholesterol and prostate cancer risk in the Prostate Cancer Prevention Trial (PCPT). Methods We conducted a cohort study of 5,586 men aged ≥ 55 years old who were randomized to the placebo arm of the PCPT between 1993 and 1996. Serum cholesterol was measured enzymatically at entry. By the end of follow-up, 1,251 prostate cancer cases were confirmed. We used logistic regression to calculate the multivariable odds ratio (OR) of total, and Gleason 2-6 (n=993), 7 (n=199), and 8-10 (n=59) prostate cancer comparing low (normal: < 200 mg/dL) to high (borderline and elevated cholesterol: ≥ 200 mg/dL) serum cholesterol. Results Men with low cholesterol had a lower risk of Gleason 8-10 prostate cancer (OR=0.41, 95% confidence interval (CI) 0.22-0.77) than men with high cholesterol. No association was present for prostate cancer overall (OR=0.97, 95% CI 0.85-1.11), Gleason 2-6 disease (OR=1.03, 95% CI 0.89-1.18), or Gleason 7 disease (OR=0.93, 95% CI 0.69-1.24). Conclusion These prospective results support that men with low cholesterol have a reduced risk of high-grade prostate cancer. These and other contemporary data suggest that cholesterol metabolism should be investigated further in the etiology of prostate cancer.", "title": "Men with Low Serum Cholesterol Have a Lower Risk of High-Grade Prostate Cancer in the Placebo Arm of the Prostate Cancer Prevention Trial" }, { "docid": "MED-5192", "text": "High dietary intakes of calcium and dairy products have been hypothesized to enhance prostate cancer risk, but available prospective data regarding these associations are inconsistent. We examined dietary intakes of calcium and dairy products in relation to risk of prostate cancer in the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study, a cohort of 29,133 male smokers aged 50-69 years at study entry. Dietary intake was assessed at baseline using a validated 276-item food use questionnaire. Cox proportional hazards regression was used to adjust for known or suspected risk factors for prostate cancer. During 17 years of follow-up, we ascertained 1,267 incident cases of prostate cancer. High versus low intake of dietary calcium was associated with a marked increase in prostate cancer risk. The multivariate relative risk (RR) of prostate cancer for > or =2,000 mg/day compared to <1,000 mg/day of calcium intake was 1.63 (95% confidence interval (CI), 1.27-2.10; p trend < 0.0001). Total dairy intake was also positively associated with risk of prostate cancer. The multivariate RR of prostate cancer comparing extreme quintiles of intake was 1.26 (95% CI, 1.04-1.51; p trend = 0.03). However, no association with total dairy intake remained after we adjusted for calcium (p trend = 0.17). Findings were similar by stage and grade of prostate cancer. The results from this large prospective study suggest that intake of calcium or some related component contained in dairy foods is associated with increased prostate cancer risk.", "title": "A prospective study of dietary calcium, dairy products and prostate cancer risk (Finland)." }, { "docid": "MED-5242", "text": "PURPOSE: Epidemiological studies in women have revealed an association between caffeine intake and urinary incontinence, although evidence among men is limited. Therefore, we evaluated the association between caffeine intake and urinary incontinence in United States men. MATERIALS AND METHODS: Data were used from male NHANES (National Health and Nutrition Examination Surveys) 2005-2006 and 2007-2008 participants. Urinary incontinence was defined using a standard questionnaire with Incontinence Severity Index scores 3 or greater categorized as moderate to severe. Structured dietary recall was used to determine caffeine consumption (mg per day), water intake (gm per day) and total dietary moisture (gm per day). Stepwise multivariable logistic regression models were used to assess the association between caffeine intake at or above the 75th and 90th percentiles and moderate to severe urinary incontinence, controlling for potential confounders, urinary incontinence risk factors and prostate conditions in men age 40 years or older. RESULTS: Of the 5,297 men 3,960 (75%) were 20 years old or older with complete data. Among these men the prevalence of any urinary incontinence was 12.9% and moderate to severe urinary incontinence was 4.4%. Mean caffeine intake was 169 mg per day. Caffeine intake at the upper 75th percentile (234 mg or more daily) and 90th percentile (392 mg or more per day) was significantly associated with having moderate to severe urinary incontinence (1.72, 95% 1.18-2.49 and 2.08, 95% 1.15-3.77, respectively). In addition, after adjusting for prostate conditions, the effect size for the association between caffeine intake and moderate to severe urinary incontinence remained. CONCLUSIONS: Caffeine consumption equivalent to approximately 2 cups of coffee daily (250 mg) is significantly associated with moderate to severe urinary incontinence in United States men. Our findings support the further study of caffeine modification in men with urinary incontinence. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.", "title": "Caffeine intake and its association with urinary incontinence in United States men: results from National Health and Nutrition Examination Surveys ..." }, { "docid": "MED-5052", "text": "OBJECTIVE: Habitual green tea consumption has long been associated with health benefits including chemoprevention and cardiovascular protection. This non-systematic literature review presents the clinical evidence to date. METHOD: A literature review of peer-reviewed articles on observational and interventional studies was conducted to include green tea, its extract or its purified polyphenol (-)-epigallocatechin-3-gallate (EGCG). Electronic databases searched included PubMed (1966-2009) and the Cochrane Library (Issue 4, 2008). RESULTS: Observational studies are inconclusive on the benefits of habitual consumption of green tea in the prevention of most cancers. However, there are trends towards prevention in breast and prostate cancers. Interventional studies have demonstrated reduction in relapses following surgical resection in colorectal adenomas and increased survival rates in epithelial ovarian cancer. Observational studies indicate that green tea may provide protection against hypertension and reduce the risk for stroke, and interventional studies are providing biochemical and physiological evidence. CONCLUSION: Although the overall clinical evidence is inconclusive, habitual green tea consumption may be providing some level of chemoprevention in prostate and breast cancer. Green tea may also attenuate the risk factors association with the development of atherosclerosis thus reducing the incidence of cardiovascular events and stoke.", "title": "Can green tea do that? A literature review of the clinical evidence." }, { "docid": "MED-951", "text": "BACKGROUND: Vitamin supplementation is used for many purposes with mainly alleged benefits. One of these is the use of various vitamins for the prevention of prostate cancer. METHODS: We conducted a systematic review and meta-analysis on this topic. Pubmed, Embase and the Cochrane Database were searched; as well, we hand searched the references in key articles. Randomized controlled trials (RCTs), cohort studies and case-control studies were included. The review assessed the effect of supplemental vitamins on the risk of prostate cancer and on disease severity and death in men with prostate cancer. RESULTS: Fourteen articles were included in the final assessment. Individually, a few of these studies showed a relationship between the ingestion of supplemental vitamins or minerals and the incidence or severity of prostate cancer, especially in smokers. However, neither the use of multivitamin supplementation nor the use of individual vitamin/mineral supplementation affected the overall occurrence of prostate cancer or the occurrence of advanced/metastatic prostate cancer or death from prostate cancer when the results of the studies were combined in a meta-analysis. We also conducted several sensitivity analyses by running meta-analysis using just the higher quality studies and just the RCTs. There were still no associations found. CONCLUSIONS: There is no convincing evidence that the use of supplemental multivitamins or any specific vitamin affects the occurrence or severity of prostate cancer. There was high heterogeneity among the studies so it is possible that unidentified subgroups may benefit or be harmed by the use of vitamins.", "title": "The effect of supplemental vitamins and minerals on the development of prostate cancer: a systematic review and meta-analysis." }, { "docid": "MED-5359", "text": "The authors investigated whether early-life residency in certain areas of Iceland marked by distinct differences in milk intake was associated with risk of prostate cancer in a population-based cohort of 8,894 men born between 1907 and 1935. Through linkage to cancer and mortality registers, the men were followed for prostate cancer diagnosis and mortality from study entry (in waves from 1967 to 1987) through 2009. In 2002–2006, a subgroup of 2,268 participants reported their milk intake in early, mid-, and current life. During a mean follow-up period of 24.3 years, 1,123 men were diagnosed with prostate cancer, including 371 with advanced disease (stage 3 or higher or prostate cancer death). Compared with early-life residency in the capital area, rural residency in the first 20 years of life was marginally associated with increased risk of advanced prostate cancer (hazard ratio = 1.29, 95% confidence interval (CI): 0.97, 1.73), particularly among men born before 1920 (hazard ratio = 1.64, 95% CI: 1.06, 2.56). Daily milk consumption in adolescence (vs. less than daily), but not in midlife or currently, was associated with a 3.2-fold risk of advanced prostate cancer (95% CI: 1.25, 8.28). These data suggest that frequent milk intake in adolescence increases risk of advanced prostate cancer.", "title": "Milk Intake in Early Life and Risk of Advanced Prostate Cancer" }, { "docid": "MED-4228", "text": "Insulin-like growth factors (IGF-I, IGF-II) and their binding proteins (IGFBP-1-6) play a key role in cell proliferation, differentiation and apoptosis, suggesting possible involvement in carcinogenesis. Several epidemiological studies show associations of IGFs with prostate cancer. We searched the published literature for all studies relating levels of IGFs or IGFBPs with prostate cancer. We performed random effects meta-analysis to calculate summary odds ratios. The number of studies (prostate cancer cases) included in each meta-analysis were 42 (7,481) IGF-I; 10 (923) IGF-II; 3 (485) IGFBP-1; 5 (577) IGFBP-2; 29 (6,541) IGFBP-3; and 11 (3,545) IGF-1:IGFBP-3 ratio. The pooled odds ratios (95% confidence intervals) per standard deviation increase in peptide, were: IGF-I, OR = 1.21 (1.07, 1.36); IGF-II, OR = 1.17 (0.93, 1.47); IGFBP-1, OR = 1.21 (0.62, 2.33); IGFBP-2, OR = 1.18 (0.90, 1.54); IGFBP-3, OR = 0.88 (0.79, 0.98); IGFI:IGFBP-3 ratio, OR = 1.10 (0.97, 1.24). For all exposures, there was substantial heterogeneity (all I2 > 75%), partly explained by study design: the magnitude of associations was smaller in prospective versus retrospective studies, and for IGFBP-3 the inverse association with prostate cancer risk was seen in retrospective but not prospective studies. There was weak evidence that associations of IGF-I and IGFBP-3 with prostate cancer were stronger for advanced disease. Our meta-analysis confirms that raised circulating lGF-I is positively associated with prostate cancer risk. Associations between IGFBP-3 and prostate cancer were inconsistent, and there was little evidence for a role of IGF-II, IGFBP-1 or IGFBP-2 in prostate cancer risk.", "title": "Circulating insulin-like growth factor (IGF) peptides and prostate cancer risk: a systematic review and meta-analysis" }, { "docid": "MED-4452", "text": "Background: Evidence for the role of diet and physical activity in cancer incidence is well documented, but owing to increased cancer survivorship, an understanding of these lifestyle factors after a cancer diagnosis is of crucial importance. The purpose of this review was to update the literature in a review undertaken for the National Cancer Survivorship Initiative and to include observational studies that were not included in the WCRF survivorship systematic review. Methods: Evidence was initially gathered from pre-defined searches of the Cochrane Library Database and PubMed from March 2006 to February 2010. After a comprehensive review regarding lifestyle and cancer, for the purpose of this article, any studies not related to diet and physical activity, prognostic outcomes, and breast, colorectal or prostate cancers were excluded. Another search of 2011 literature was conducted to update the evidence. Results: A total of 43 records were included in this review. Evidence from observational studies suggests that a low-fat, high-fibre diet might be protective against cancer recurrence and progression. However, there is a paucity of RCTs substantiating this. There is more support for physical activity, with a dose response for better outcomes. When synthesized with findings from the World Cancer Research Fund review of RCTs investigating the effect of diet and physical activity interventions on cancer survival, evidence suggests that the mechanism of benefit from diet and physical activity pertains to body weight, with excess body weight being a risk factor, which is modifiable through lifestyle. Implications: Cancer survivors would like to have a more active role in their health care and to know how to look after themselves after diagnosis, including what diet and lifestyle changes they should make. The challenge is in integrating lifestyle support into standardised models of aftercare.", "title": "The role of diet and physical activity in breast, colorectal, and prostate cancer survivorship: a review of the literature" }, { "docid": "MED-5350", "text": "The short-term effects of rye bran bread intake in prostate cancer were investigated. Ten men with conservatively treated prostate cancer were randomised to a daily supplement of 295 g of rye bran bread and eight men to 275 g of wheat bread (control) with similar fibre content for three weeks. Blood samples, ultrasound-guided core biopsies of the prostate, and urine samples were taken. In the rye group, there was a significant increase in plasma enterolactone, and the apoptotic index increased significantly from 2.1% (SD 1.3) to 5.9% (SD 1.8), P<0.005 as measured by a TUNEL index in four cases in the rye group and seven cases in the control group. Besides a significant decrease in weight in both groups, only small changes were observed in plasma concentrations of prostate specific antigen (PSA), circulating sex hormones, excreted oestrogens, insulin-like growth factor (IGF)-I, and in the endothelial fibrinolytical system. High intake of rye bran bread is suggested to increase apoptosis in prostate tumours.", "title": "Randomised controlled short-term intervention pilot study on rye bran bread in prostate cancer." }, { "docid": "MED-5356", "text": "Rye whole grain and bran intake has shown beneficial effects on prostate cancer progression in animal models, including lower tumor take rates, smaller tumor volumes, and reduced prostate specific antigen (PSA) concentrations. A human pilot study showed increased apoptosis after consumption of rye bran bread. In this study, we investigated the effect of high intake of rye whole grain and bran on prostate cancer progression as assessed by PSA concentration in men diagnosed with prostate cancer. Seventeen participants were provided with 485 g rye whole grain and bran products (RP) or refined wheat products with added cellulose (WP), corresponding to ~50% of daily energy intake, in a randomized controlled, crossover design. Blood samples were taken from fasting men before and after 2, 4, and 6 wk of treatment and 24-h urine samples were collected before the first intervention period and after treatment. Plasma total PSA concentrations were lower after treatment with RP compared with WP, with a mean treatment effect of -14% (P = 0.04). Additionally, fasting plasma insulin and 24-h urinary C-peptide excretion were lower after treatment with RP compared with WP (P < 0.01 and P = 0.01, respectively). Daily excretion of 5 lignans was higher after the RP treatment than after the WP treatment (P < 0.001). We conclude that whole grain and bran from rye resulted in significantly lower plasma PSA compared with a cellulose-supplemented refined wheat diet in patients with prostate cancer. The effect may be related to inhibition of prostate cancer progression caused by decreased exposure to insulin, as indicated by plasma insulin and urinary C-peptide excretion.", "title": "Rye whole grain and bran intake compared with refined wheat decreases urinary C-peptide, plasma insulin, and prostate specific antigen in men with ..." }, { "docid": "MED-861", "text": "OBJECTIVE: To investigate the association of whole-blood fatty acids and reported intakes of fats with risk of prostate cancer (PCa). DESIGN: Case-control study of 209 men 40-80 years old with newly diagnosed, histologically confirmed prostate cancer and 226 cancer-free men attending the same urology clinics. Whole-blood fatty acid composition (mol%) was measured by gas chromatography and diet assessed by food frequency questionnaire. RESULTS: High whole-blood oleic acid composition (tertile 3 vs. tertile 1: OR, 0.37; CI, 0.14-0.0.98) and moderate palmitic acid proportions (tertile 2: OR, 0.29; CI, 0.12-0.70) (tertile 3: OR, 0.53; CI, 0.19-1.54) were inversely related to risk of PCa, whereas men with high linolenic acid proportions were at increased likelihood of PCa (tertile 3 vs. tertile 1: OR, 2.06; 1.29-3.27). Blood myristic, stearic and palmitoleic acids were not associated with PCa. Higher intakes of dietary MUFA were inversely related to prostate cancer (tertile 3 vs. tertile 1: OR, 0.39; CI 0.16-0.92). The principal source of dietary MUFA was avocado intake. Dietary intakes of other fats were not associated with PCa. CONCLUSIONS: Whole-blood and dietary MUFA reduced the risk of prostate cancer. The association may be related to avocado intakes. High blood linolenic acid was directly related to prostate cancer. These associations warrant further investigation.", "title": "Associations of whole-blood fatty acids and dietary intakes with prostate cancer in Jamaica." }, { "docid": "MED-5089", "text": "BACKGROUND: Acrylamide, a probable human carcinogen, was recently detected in various heat-treated carbohydrate-rich foods. Epidemiologic studies on the relation with cancer have been few and largely negative. OBJECTIVE: We aimed to prospectively examine the association between dietary acrylamide intake and renal cell, bladder, and prostate cancers. DESIGN: The Netherlands Cohort Study on diet and cancer includes 120,852 men and women aged 55-69 y. At baseline (1986), a random subcohort of 5000 participants was selected for a case-cohort analysis approach using Cox proportional hazards analysis. Acrylamide intake was assessed with a food-frequency questionnaire at baseline and was based on chemical analysis of all relevant Dutch foods. RESULTS: After 13.3 y of follow-up, 339, 1210, and 2246 cases of renal cell, bladder, and prostate cancer, respectively, were available for analysis. Compared with the lowest quintile of acrylamide intake (mean intake: 9.5 microg/d), multivariable-adjusted hazard rates for renal cell, bladder, and prostate cancer in the highest quintile (mean intake: 40.8 microg/d) were 1.59 (95% CI: 1.09, 2.30; P for trend = 0.04), 0.91 (95% CI: 0.73, 1.15; P for trend = 0.60), and 1.06 (95% CI: 0.87, 1.30; P for trend = 0.69), respectively. There was an inverse nonsignificant trend for advanced prostate cancer in never smokers. CONCLUSIONS: We found some indications for a positive association between dietary acrylamide and renal cell cancer risk. There were no positive associations with bladder and prostate cancer risk.", "title": "Dietary acrylamide intake and the risk of renal cell, bladder, and prostate cancer." }, { "docid": "MED-4898", "text": "We examined consumption of animal foods, protein and calcium in relation to risk of prostate cancer among 142 251 men in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by recruitment centre and adjusted for height, weight, education, marital status and energy intake. After an average of 8.7 years of follow-up, there were 2727 incident cases of prostate cancer, of which 1131 were known to be localised and 541 advanced-stage disease. A high intake of dairy protein was associated with an increased risk, with a hazard ratio for the top versus the bottom fifth of intake of 1.22 (95% confidence interval (CI): 1.07–1.41, Ptrend=0.02). After calibration to allow for measurement error, we estimated that a 35-g day−1 increase in consumption of dairy protein was associated with an increase in the risk of prostate cancer of 32% (95% CI: 1–72%, Ptrend=0.04). Calcium from dairy products was also positively associated with risk, but not calcium from other foods. The results support the hypothesis that a high intake of protein or calcium from dairy products may increase the risk for prostate cancer.", "title": "Animal foods, protein, calcium and prostate cancer risk: the European Prospective Investigation into Cancer and Nutrition" }, { "docid": "MED-857", "text": "Individual-based studies that investigated the relation between dietary alpha-linolenic acid (ALA) intake and prostate cancer risk have shown inconsistent results. We carried out a meta-analysis of prospective studies to examine this association. We systematically searched studies published up to December 2008. Log relative risks (RRs) were weighted by the inverse of their variances to obtain a pooled estimate with its 95% confidence interval (CI). We identified five prospective studies that met our inclusion criteria and reported risk estimates by categories of ALA intake. Comparing the highest to the lowest ALA intake category, the pooled RR was 0.97 (95% CI:0.86-1.10) but the association was heterogeneous. Using the reported numbers of cases and non-cases in each category of ALA intake, we found that subjects who consumed more than 1.5 g/day of ALA compared with subjects who consumed less than 1.5 g/day had a significant decreased risk of prostate cancer: RR = 0.95 (95% CI:0.91-0.99). Divergences in results could partly be explained by differences in sample sizes and adjustment but they also highlight limits in dietary ALA assessment in such prospective studies. Our findings support a weak protective association between dietary ALA intake and prostate cancer risk but further research is needed to conclude on this question.", "title": "Prospective studies of dietary alpha-linolenic acid intake and prostate cancer risk: a meta-analysis." }, { "docid": "MED-4216", "text": "High levels of insulin-like growth factor 1 (IGF-1) are associated with increased risk of prostate cancer, whereas increased levels of some of its binding proteins (IGFBPs) seem to be protective. High intakes of dietary protein, especially animal and soy protein, appear to increase IGF-1. However, soy isoflavones have demonstrated anti-proliferative and apoptotic effects both in vitro and in vivo. We evaluated dietary intakes of total protein and soy isoflavones in relation to the IGF axis in prostate cancer patients making comprehensive lifestyle changes including a very low-fat vegan diet supplemented with soy protein (58 g/day). After one year, intervention group patients reported significantly higher intakes of dietary protein and soy isoflavones compared to usual-care controls (P < 0.001). IGF-1 increased significantly in both groups, whereas IGFBP-1 rose in the experimental group only (P < 0.01). Increases in vegetable protein over one year were associated with increases in IGFBP-1 among intervention group patients (P < 0.05). These results suggest that dietary protein and soy isoflavones, in the context of comprehensive lifestyle changes, may not significantly alter IGF-1. However, given the recent literature indicating that high intake of protein rich in essential amino acids (animal or soy protein) may increase IGF-1, it may be prudent for men with early stage prostate cancer not to exceed dietary protein recommendations.", "title": "Relationship of dietary protein and soy isoflavones to serum IGF-1 and IGF binding proteins in the Prostate Cancer Lifestyle Trial." }, { "docid": "MED-2418", "text": "Background Evidence suggests that high-heat cooking methods may increase the risk of prostate cancer (PCa). The addition of oil/fat, as in deep-frying, may be of particular concern, and has not specifically been investigated in relation to PCa. Potential mechanisms include the formation of potentially carcinogenic agents such as aldehydes, acrolein, heterocyclic amines, polycyclic aromatic hydrocarbons, and acrylamide. Methods We estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between tertiles of intake of deep-fried foods from a food frequency questionnaire (French fries, fried chicken, fried fish, doughnuts and snack chips) and PCa risk, adjusted for potential confounders, among 1,549 cases and 1,492 controls. We additionally examined associations with more aggressive PCa (defined as regional/distant stage, elevated Gleason score or prostate specific antigen level). Results Compared with <1/week, there was a positive association with PCa risk for intake ≥ 1/week of French fries (OR=1.37; 95% CI, 1.11–1.69), fried chicken (OR=1.30; 95% CI, 1.04–1.62), fried fish (OR=1.32; 95% CI, 1.05–1.66), and doughnuts (OR=1.35; 95% CI, 1.11–1.66). There was no association for snack chips (OR=1.08; 95% CI, 0.89–1.32). Most of the estimates were slightly stronger for more aggressive disease (OR=1.41; 95% CI, 1.04–1.92 for fried fish). Conclusion Regular consumption of select deep-fried foods is associated with increased PCa risk. Whether this risk is specific to deep-fried foods, or whether it represents risk associated with regular intake of foods exposed to high heat and/or other aspects of the Western lifestyle, such as fast food consumption, remains to be determined.", "title": "Consumption of deep-fried foods and risk of prostate cancera,b" }, { "docid": "MED-2255", "text": "Background Diet is a major source of cadmium intake among the non-smoking general population. Recent studies have determined that cadmium exposure may produce adverse health effects at lower exposure levels than previously predicted. We conducted a meta-analysis to combine and analyze the results of previous studies that have investigated the association of dietary cadmium intake and cancer risk. Methods We searched PubMed, EMBASE, and MEDLINE database for case-control and cohort studies that assessed the association of dietary cadmium intake and cancer risk. We performed a meta-analysis using eight eligible studies to summarize the data and summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a random effects model. Results Overall, dietary cadmium intake showed no statistically significant association with cancer risk (RR = 1.10; 95% CI: 0.99–1.22, for highest vs. lowest dietary cadmium group). However, there was strong evidence of heterogeneity, and subgroup analyses were conducted using the study design, geographical location, and cancer type. In subgroup analyses, the positive associations between dietary cadmium intake and cancer risk were observed among studies with Western populations (RR = 1.15; 95% CI: 1.08–1.23) and studies investigating some hormone-related cancers (prostate, breast, and endometrial cancers). Conclusion Our analysis found a positive association between dietary cadmium intake and cancer risk among studies conducted in Western countries, particularly with hormone-related cancers. Additional experimental and epidemiological studies are required to verify our findings.", "title": "Dietary Cadmium Intake and the Risk of Cancer: A Meta-Analysis" }, { "docid": "MED-5194", "text": "BACKGROUND: Dairy consumption affects biological pathways associated with carcinogenesis. Evidence for a link between cancer risk and dairy consumption in adulthood is increasing, but associations with childhood dairy consumption have not been studied adequately. OBJECTIVE: We investigated whether dairy consumption in childhood is associated with cancer incidence and mortality in adulthood. DESIGN: From 1937 through 1939, some 4,999 children living in England and Scotland participated in a study of family food consumption, assessed from 7-d household food inventories. The National Health Service central register was used to ascertain cancer registrations and deaths between 1948 and 2005 in the 4,383 traced cohort members. Per capita household intake estimates for dairy products and calcium were used as proxy for individual intake. RESULTS: During the follow-up period, 770 cancer registrations or cancer deaths occurred. High childhood total dairy intake was associated with a near-tripling in the odds of colorectal cancer [multivariate odds ratio: 2.90 (95% CI: 1.26, 6.65); 2-sided P for trend = 0.005] compared with low intake, independent of meat, fruit, and vegetable intakes and socioeconomic indicators. Milk intake showed a similar association with colorectal cancer risk. High milk intake was weakly inversely associated with prostate cancer risk (P for trend = 0.11). Childhood dairy intake was not associated with breast and stomach cancer risk; a positive association with lung cancer risk was confounded by smoking behavior during adulthood. CONCLUSIONS: A family diet rich in dairy products during childhood is associated with a greater risk of colorectal cancer in adulthood. Confirmation of possible underlying biological mechanisms is needed.", "title": "Childhood dairy intake and adult cancer risk: 65-y follow-up of the Boyd Orr cohort." }, { "docid": "MED-3854", "text": "Phytoestrogens are polyphenolic secondary plant metabolites that have structural and functional similarities to 17beta-oestradiol and have been associated with a protective effect against hormone-related cancers. Most foods in the UK only contain small amounts of phytoestrogens (median content 21 microg/100 g) and the highest content is found in soya and soya-containing foods. The highest phytoestrogen content in commonly consumed foods is found in breads (average content 450 microg/100 g), the main source of isoflavones in the UK diet. The phytoestrogen consumption in cases and controls was considerably lower than in Asian countries. No significant associations between phytoestrogen intake and breast cancer risk in a nested case-control study in EPIC Norfolk were found. Conversely, colorectal cancer risk was inversely associated with enterolignan intake in women but not in men. Prostate cancer risk was positively associated with enterolignan intake, however this association became non-significant when adjusting for dairy intake, suggesting that enterolignans can act as a surrogate marker for dairy or calcium intake. 2010 Elsevier Inc. All rights reserved.", "title": "Phytoestrogen consumption and association with breast, prostate and colorectal cancer in EPIC Norfolk." }, { "docid": "MED-4089", "text": "Studies have shown an inverse relationship between the consumption of apples and the risk of several cancers. The peels of apple, which have been shown to possess exceptionally high concentrations of antioxidants, are often discarded. In this study, we evaluated the antiproliferative effects of apple peel extract (APE) in variety of cancer cell types. Our data demonstrated that APE, obtained from organic Gala apples, imparted significant reduction in the viability of a variety of cancer cell lines. Further, our data showed a significant decrease in growth and clonogenic survival of human prostate carcinoma CWR22Rnu1 and DU145 cells and breast carcinoma Mcf-7 and Mcf-7:Her18 cells. Also, the antiproliferative effects of APE were found to be accompanied by a G0-G1 phase arrest of prostate and breast cancer cells. Furthermore, APE treatment resulted in a marked concentration-dependent decrease in the protein levels of proliferative cell nuclear antigen, a marker for proliferation. In addition, APE treatment resulted in a marked increase in maspin, a tumor suppressor protein that negatively regulates cell invasion, metastasis, and angiogenesis. Our data suggested that APE possesses strong antiproliferative effects against cancer cells, and apple peels should not be discarded from the diet. Detailed mechanistic studies, especially in appropriate in vivo animal models, are needed to further examine the antiproliferative and preventive effects of APE against cancer.", "title": "Antiproliferative effects of apple peel extract against cancer cells." }, { "docid": "MED-1362", "text": "The aim of this research study was to meta-analyze the effects of adherence to Mediterranean diet (MD) on overall cancer risk, and different cancer types. Literature search was performed using the electronic databases MEDLINE, SCOPUS and EMBASE until January 10, 2014. Inclusion criteria were cohort or case-control studies. Study specific risk ratios (RRs) were pooled using a random effect model by the Cochrane software package Review Manager 5.2. Twenty-one cohort studies including 1,368,736 subjects and 12 case-control studies with 62,725 subjects met the objectives and were enclosed for meta-analyses. The highest adherence to MD category resulted in a significantly risk reduction for overall cancer mortality/incidence (cohort; RR: 0.90, 95% CI 0.86-0.95, p < 0.0001; I(2) = 55%), colorectal (cohort/case-control; RR: 0.86, 95% CI 0.80-0.93, p < 0.0001; I(2) = 62%], prostate (cohort/case-control; RR: 0.96, 95% CI 0.92-0.99, p = 0.03; I(2) = 0%) and aerodigestive cancer (cohort/case-control; RR: 0.44, 95% CI 0.26-0.77, p = 0.003; I(2) = 83%). Nonsignificant changes could be observed for breast cancer, gastric cancer and pancreatic cancer. The Egger regression tests provided limited evidence of substantial publication bias. High adherence to a MD is associated with a significant reduction in the risk of overall cancer mortality (10%), colorectal cancer (14%), prostate cancer (4%) and aerodigestive cancer (56%). © 2014 UICC.", "title": "Adherence to Mediterranean diet and risk of cancer: a systematic review and meta-analysis of observational studies." }, { "docid": "MED-1779", "text": "The imbalance between reactive oxygen species (ROS) production and total antioxidant capacity (TAC) in seminal fluid indicates oxidative stress and is correlated with male infertility. A composite ROS-TAC score may be more strongly correlated with infertility than ROS or TAC alone. We measured ROS, TAC, and ROS-TAC scores in semen from 127 patients and 24 healthy controls. Of the patients, 56 had varicocele, eight had varicocele with prostatitis, 35 had vasectomy reversals, and 28 had idiopathic infertility. ROS levels were higher among infertile men, especially those with varicocele with prostatitis (mean +/- SE, 3.25 +/- 0.89) and vasectomy reversals (2.65 +/- 1.01). All infertile groups had significantly lower ROS-TAC scores than control. ROS-TAC score identified 80% of patients and was significantly better than ROS at identifying varicocele and idiopathic infertility. The 13 patients whose partners later achieved pregnancies had a mean ROS-TAC score of 47.7 +/- 13.2, similar to controls but significantly higher than the 39 patients who remained infertile (35.8 +/- 15.0; P < 0.01). ROS-TAC score is a novel measure of oxidative stress and is superior to ROS or TAC alone in discriminating between fertile and infertile men. Infertile men with male factor or idiopathic diagnoses had significantly lower ROS-TAC scores than controls, and men with male factor diagnoses that eventually were able to initiate a successful pregnancy had significantly higher ROS-TAC scores than those who failed.", "title": "The reactive oxygen species-total antioxidant capacity score is a new measure of oxidative stress to predict male infertility." }, { "docid": "MED-4220", "text": "OBJECTIVE: Accumulating evidence indicates that prostate cancer is associated with high levels of serum IGF-I. This study was conducted to determine whether a low-fat diet and exercise (DE) intervention may modulate the IGF axis and reduce prostate cancer cell growth in vitro. METHODS: Fasting serum was obtained from 14 men (age 60 +/- 3 years) participating in an 11-day DE program and from eight similarly aged men who had followed the DE program for 14.2 +/- 1.7 years (long-term). Insulin, IGF-I, IGFBP-1, and IGFBP-3 were measured by ELISA, and serum was used to stimulate LNCaP cell growth in vitro. RESULTS: Serum IGF-I levels decreased by 20% while IGFBP-1 increased by 53% after 11-day DE. In the long-term group, IGF-I was 55% lower, while IGFBP-1 was 150% higher relative to baseline. Serum insulin decreased by 25% after 11-day DE and was 68% lower in the long-term group, relative to baseline. No changes in serum IGFBP-3 were observed. Serum-stimulated LNCaP cell growth was reduced by 30% in post-11-day serum and by 44% in long-term serum relative to baseline. LNCaP cells incubated with post-DE serum showed increased apoptosis/ necrosis, compared to baseline. CONCLUSIONS: A low-fat diet and exercise intervention induces in-vivo changes in the circulating IGF axis and is associated with reduced growth and enhanced apoptosis/necrosis of LNCaP tumor cells in vitro.", "title": "Effect of diet and exercise on serum insulin, IGF-I, and IGFBP-1 levels and growth of LNCaP cells in vitro (United States)." }, { "docid": "MED-1720", "text": "BACKGROUND: Insulin-like growth factor (IGF)-I and its main binding protein, IGFBP-3, modulate cell growth and survival, and are thought to be important in tumour development. Circulating concentrations of IGF-I might be associated with an increased risk of cancer, whereas IGFBP-3 concentrations could be associated with a decreased cancer risk. METHODS: We did a systematic review and meta-regression analysis of case-control studies, including studies nested in cohorts, of the association between concentrations of IGF-I and IGFBP-3 and prostate, colorectal, premenopausal and postmenopausal breast, and lung cancer. Study-specific dose-response slopes were obtained by relating the natural log of odds ratios for different exposure levels to blood concentrations normalised to a percentile scale. FINDINGS: We identified 21 eligible studies (26 datasets), which included 3609 cases and 7137 controls. High concentrations of IGF-I were associated with an increased risk of prostate cancer (odds ratio comparing 75th with 25th percentile 1.49, 95% CI 1.14-1.95) and premenopausal breast cancer (1.65, 1.26-2.08) and high concentrations of IGFBP-3 were associated with increased risk of premenopausal breast cancer (1.51, 1.01-2.27). Associations were larger in assessments of plasma samples than in serum samples, and in standard case-control studies compared with nested studies. INTERPRETATION: Circulating concentrations of IGF-I and IGFBP-3 are associated with an increased risk of common cancers, but associations are modest and vary between sites. Although laboratory methods need to be standardised, these epidemiological observations could have major implications for assessment of risk and prevention of cancer.", "title": "Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis." } ]
4
1-1% of colorectal cancer patients are diagnosed with regional or distant metastases.
[ { "docid": "22942787", "text": "CONTEXT Medicare's reimbursement policy was changed in 1998 to provide coverage for screening colonoscopies for patients with increased colon cancer risk, and expanded further in 2001 to cover screening colonoscopies for all individuals. OBJECTIVE To determine whether the Medicare reimbursement policy changes were associated with an increase in either colonoscopy use or early stage colon cancer diagnosis. DESIGN, SETTING, AND PARTICIPANTS Patients in the Surveillance, Epidemiology, and End Results Medicare linked database who were 67 years of age and older and had a primary diagnosis of colon cancer during 1992-2002, as well as a group of Medicare beneficiaries who resided in Surveillance, Epidemiology, and End Results areas but who were not diagnosed with cancer. MAIN OUTCOME MEASURES Trends in colonoscopy and sigmoidoscopy use among Medicare beneficiaries without cancer were assessed using multivariate Poisson regression. Among the patients with cancer, stage was classified as early (stage I) vs all other (stages II-IV). Time was categorized as period 1 (no screening coverage, 1992-1997), period 2 (limited coverage, January 1998-June 2001), and period 3 (universal coverage, July 2001-December 2002). A multivariate logistic regression (outcome = early stage) was used to assess temporal trends in stage at diagnosis; an interaction term between tumor site and time was included. RESULTS Colonoscopy use increased from an average rate of 285/100,000 per quarter in period 1 to 889 and 1919/100,000 per quarter in periods 2 (P<.001) and 3 (P vs 2<.001), respectively. During the study period, 44,924 eligible patients were diagnosed with colorectal cancer. The proportion of patients diagnosed at an early stage increased from 22.5% in period 1 to 25.5% in period 2 and 26.3% in period 3 (P<.001 for each pairwise comparison). The changes in Medicare coverage were strongly associated with early stage at diagnosis for patients with proximal colon lesions (adjusted relative risk period 2 vs 1, 1.19; 95% confidence interval, 1.13-1.26; adjusted relative risk period 3 vs 2, 1.10; 95% confidence interval, 1.02-1.17) but weakly associated, if at all, for patients with distal colon lesions (adjusted relative risk period 2 vs 1, 1.07; 95% confidence interval, 1.01-1.13; adjusted relative risk period 3 vs 2, 0.97; 95% confidence interval, 0.90-1.05). CONCLUSIONS Expansion of Medicare reimbursement to cover colon cancer screening was associated with an increased use of colonoscopy for Medicare beneficiaries, and for those who were diagnosed with colon cancer, an increased probability of being diagnosed at an early stage. The selective effect of the coverage change on proximal colon lesions suggests that increased use of whole-colon screening modalities such as colonoscopy may have played a pivotal role.", "title": "Relation between Medicare screening reimbursement and stage at diagnosis for older patients with colon cancer." } ]
[ { "docid": "1387104", "text": "CONTEXT Venous thrombosis is a common complication in patients with cancer, leading to additional morbidity and compromising quality of life. OBJECTIVE To identify individuals with cancer with an increased thrombotic risk, evaluating different tumor sites, the presence of distant metastases, and carrier status of prothrombotic mutations. DESIGN, SETTING, AND PATIENTS A large population-based, case-control (Multiple Environmental and Genetic Assessment [MEGA] of risk factors for venous thrombosis) study of 3220 consecutive patients aged 18 to 70 years, with a first deep venous thrombosis of the leg or pulmonary embolism, between March 1, 1999, and May 31, 2002, at 6 anticoagulation clinics in the Netherlands, and separate 2131 control participants (partners of the patients) reported via a questionnaire on acquired risk factors for venous thrombosis. Three months after discontinuation of the anticoagulant therapy, all patients and controls were interviewed, a blood sample was taken, and DNA was isolated to ascertain the factor V Leiden and prothrombin 20210A mutations. MAIN OUTCOME MEASURE Risk of venous thrombosis. RESULTS The overall risk of venous thrombosis was increased 7-fold in patients with a malignancy (odds ratio [OR], 6.7; 95% confidence interval [CI], 5.2-8.6) vs persons without malignancy. Patients with hematological malignancies had the highest risk of venous thrombosis, adjusted for age and sex (adjusted OR, 28.0; 95% CI, 4.0-199.7), followed by lung cancer and gastrointestinal cancer. The risk of venous thrombosis was highest in the first few months after the diagnosis of malignancy (adjusted OR, 53.5; 95% CI, 8.6-334.3). Patients with cancer with distant metastases had a higher risk vs patients without distant metastases (adjusted OR, 19.8; 95% CI, 2.6-149.1). Carriers of the factor V Leiden mutation who also had cancer had a 12-fold increased risk vs individuals without cancer and factor V Leiden (adjusted OR, 12.1; 95% CI, 1.6-88.1). Similar results were indirectly calculated for the prothrombin 20210A mutation in patients with cancer. CONCLUSIONS Patients with cancer have a highly increased risk of venous thrombosis especially in the first few months after diagnosis and in the presence of distant metastases. Carriers of the factor V Leiden and prothrombin 20210A mutations appear to have an even higher risk.", "title": "Malignancies, prothrombotic mutations, and the risk of venous thrombosis." }, { "docid": "24980622", "text": "PURPOSE To investigate hypoxia measured by pimonidazole binding, glucose transporter 1 (GLUT1) and carbonic anhydrase IX (CA-IX) expression, proliferation, and vascularity in liver metastases of colorectal cancer and to compare GLUT1 and CA-IX expression in corresponding primary tumors. METHODS AND MATERIALS Twenty-five patients with liver metastases of colorectal cancer, planned for metastasectomy, were included. The hypoxia marker pimonidazole and proliferation marker iododeoxyuridine were administered before surgery. After immunofluorescent staining of the frozen metastases, pimonidazole binding, vascularity, and proliferation were analyzed quantitatively. Thirteen paraffin-embedded primary tumors were stained immunohistochemically for GLUT1 and CA-IX expression, which was analyzed semiquantitatively in primary tumors and corresponding liver metastases. RESULTS In liver metastases, pimonidazole binding showed a pattern consistent with diffusion-limited hypoxia. The mean pimonidazole-positive fraction was 0.146; the mean distance from vessels to pimonidazole-positive areas was 80 microm. When expressed, often co-localization was observed between pimonidazole binding and GLUT1 or CA-IX expression, but microregional areas of mismatch were also observed. No correlation between the level of pimonidazole binding and GLUT1 or CA-IX expression was observed. In some patients, a large fraction (up to 30%) of proliferating cells was present in pimonidazole-stained areas. Expression of CA-IX in primary tumors and metastases showed a significant correlation, which was absent for GLUT1 expression. CONCLUSIONS Compared with other tumor types, liver metastases of colorectal cancer contain large amounts of hypoxic cells. The lack of correlation with pimonidazole binding brings into question the value of GLUT1 and CA-IX as endogenous markers of hypoxia.", "title": "Hypoxia in relation to vasculature and proliferation in liver metastases in patients with colorectal cancer." }, { "docid": "10958594", "text": "The aim of this study was to determine trends in incidence, treatment and survival of colorectal cancer (CRC) patients with synchronous metastases (Stage IV) in the Netherlands. This nationwide population-based study included 160,278 patients diagnosed with CRC between 1996 and 2011. We evaluated changes in stage distribution, location of synchronous metastases and treatment in four consecutive periods, using Chi square tests for trend. Median survival in months was determined, using Kaplan–Meier analysis. The proportion of Stage IV CRC patients (n = 33,421) increased from 19 % (1996–1999) to 23 % (2008–2011, p < 0.001). This was predominantly due to a major increase in the incidence of lung metastases (1.7–5.0 % of all CRC patients). During the study period, the primary tumor was resected less often in Stage IV patients (65–46 %) and the use of systemic treatment has increased (29–60 %). Also an increase in metastasectomy was found in patients with one metastatic site, especially in patients with liver-only disease (5–18 %, p < 0.001). Median survival of all Stage IV CRC patients increased from 7 to 12 months. Especially in patients with metastases confined to the liver or lungs this improvement in survival was apparent (9–16 and 12–24 months respectively, both p < 0.001). In the last two decades, more lung metastases were detected and an increasing proportion of Stage IV CRC patients was treated with systemic therapy and/or metastasectomy. Survival of patients has significantly improved. However, the prognosis of Stage IV patients becomes increasingly diverse.", "title": "Nationwide trends in incidence, treatment and survival of colorectal cancer patients with synchronous metastases" }, { "docid": "5641851", "text": "OBJECTIVE Cancer outcomes vary between and within countries with patients from deprived backgrounds known to have inferior survival. The authors set out to explore the effect of deprivation in relation to the accessibility of hospitals offering diagnostic and therapeutic services on stage at presentation and receipt of treatment. DESIGN Analysis of a Cancer Registry Database. Data included stage and treatment details from the first 6 months. The socioeconomic status of the immediate area of residence and the travel time from home to hospital was derived from the postcode. SETTING Population-based study of patients resident in a large area in the north of England. PARTICIPANTS 39 619 patients with colorectal cancer diagnosed between 1994 and 2002. OUTCOMES MEASURED Stage of diagnosis and receipt of treatment in relation to deprivation and distance from hospital. RESULTS Patients in the most deprived quartile were significantly more likely to be diagnosed at stage 4 for rectal cancer (OR 1.516, p<0.05) but less so for colonic cancer. There was a trend for both sites for patients in the most deprived quartile to be less likely to receive chemotherapy for stage 4 disease. Patients with colonic cancer were very significantly less likely to receive any treatment if they came from any but the most affluent area (ORs 0.639, 0.603 and 0.544 in increasingly deprived quartiles), this may have been exacerbated if the hospital was distant from their residence (OR for forth quartile for both travel and deprivation 0.731, not significant). The effect was less for rectal cancer and no effect of distance was seen. CONCLUSIONS Residing in a deprived area is associated with tendencies to higher stage at diagnosis and especially in the case of colonic cancer to reduced receipt of treatment. These observations are consistent with other findings and indicate that access to diagnosis requires further investigation.", "title": "Social and geographical factors affecting access to treatment of colorectal cancer: a cancer registry study" }, { "docid": "52188256", "text": "This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.", "title": "Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries." }, { "docid": "18062308", "text": "STUDY OBJECTIVE We assessed whether transpleural methods for diagnosing peripheral lung cancer, such as needle aspiration or tumor excision, affect relapse and prognosis, because these techniques have potential to spread malignant cells from the tumor. DESIGN A retrospective study. SETTING National referral hospital. PATIENTS We reviewed 239 patients who underwent surgery between 1990 and 1998 and for whom non-small cell lung cancer (NSCLC) of < 3 cm in maximum diameter was completely resected. The duration of postoperative follow-up ranged from 12 to 105 months, with a median period of 45 months. INTERVENTIONS We defined the transbronchial method as using a bronchoscope, and the transpleural method as using needle aspiration cytology or tumor excision. Dichotomous variables included gender, histologic type of squamous cell carcinoma or other type of carcinoma, pathologic stage, and whether the diagnostic method was the transbronchial type only (first-line method) or the transpleural type (second-line method). RESULTS NSCLC was diagnosed in 45 patients by the transpleural technique and in 194 patients by the transbronchial technique. There were no significant statistical differences in age of patients, gender, histologic type, pathologic stage, and tumor size. There were 42 relapses, 7 in the transpleural technique group and 35 in the transbronchial technique group (p = 0.90). Of the 7 patients in the transpleural group, there were 4 distant metastasis and 3 local relapses; of the 35 patients in the transbronchial group, there were 20 distant metastasis and 15 local relapses (p = 0.99). Pleural carcinomatosis occurred in none of the 45 patients in the transpleural group and in 1 case (0.5%) in the 194 patients in the transbronchial group (p = 0.99). Patients in the transpleural group had a statistically better 5-year survival rate than patients in the transbronchial group (79.4% vs 60.3%, p = 0.04). This is also confirmed as an independent prognostic factor in a multivariate analysis. CONCLUSIONS Transpleural methods seem to be an advisable way to diagnose operable lung cancer that is difficult to diagnose using bronchoscopy, because these methods did not affect relapse and prognosis in the patients in our study.", "title": "Operable non-small cell lung cancer diagnosed by transpleural techniques : do they affect relapse and prognosis?" }, { "docid": "9831859", "text": "Pancreatic stellate cells (PSC) produce the stromal reaction in pancreatic cancer, but their role in cancer progression is not fully elucidated. We examined the influence of PSCs on pancreatic cancer growth using (a) an orthotopic model of pancreatic cancer and (b) cultured human PSCs (hPSC) and human pancreatic cancer cell lines MiaPaCa-2 and Panc-1. Athymic mice received an intrapancreatic injection of saline, hPSCs, MiaPaCa-2 cells, or hPSCs + MiaPaCa-2. After 7 weeks, tumor size, metastases, and tumor histology were assessed. In vitro studies assessed the effect of cancer cell secretions on PSC migration and the effect of hPSC secretions on cancer cell proliferation, apoptosis, and migration. Possible mediators of the effects of hPSC secretions on cancer cell proliferation were examined using neutralizing antibodies. Compared with mice receiving MiaPaCa-2 cells alone, mice injected with hPSCs + MiaPaCa-2 exhibited (a) increased tumor size and regional and distant metastasis, (b) fibrotic bands (desmoplasia) containing activated PSCs within tumors, and (c) increased tumor cell numbers. In vitro studies showed that, in the presence of pancreatic cancer cells, PSC migration was significantly increased. Furthermore, hPSC secretions induced the proliferation and migration, but inhibited the apoptosis, of MiaPaCa-2 and Panc-1 cells. The proliferative effect of hPSC secretions on pancreatic cancer cells was inhibited in the presence of neutralizing antibody to platelet-derived growth factor. Our studies indicate a significant interaction between pancreatic cancer cells and stromal cells (PSCs) and imply that pancreatic cancer cells recruit stromal cells to establish an environment that promotes cancer progression.", "title": "Pancreatic stellate cells: partners in crime with pancreatic cancer cells." }, { "docid": "39580129", "text": "OBJECTIVES Several miRNAs are aberrantly expressed in cancer. miR-24-3p is involved in cancer-related cellular processes, including cell cycle control, cell growth, proliferation, and apoptosis. In this study, we examined the potential diagnostic and prognostic significance of miR-24-3p expression in colorectal adenocarcinoma. DESIGN AND METHODS Total RNA was isolated from 182 colorectal adenocarcinoma specimens and 86 paired non-cancerous colorectal mucosae. After polyadenylation of 2μg total RNA and reverse transcription into first-strand cDNA using an oligo-dT-adapter primer, miR-24-3p expression was quantified using an in-house-developed reverse-transcription real-time quantitative PCR method, based on the SYBR Green chemistry. SNORD43 (RNU43) was used as a reference gene. RESULTS miR-24-3p levels do not significantly differ between colorectal adenocarcinoma and non-cancerous colorectal mucosae. Thus, miR-24-3p expression cannot be used for diagnostic purposes. However, high miR-24-3p expression predicts poor disease-free survival (DFS) and overall survival (OS) of colorectal adenocarcinoma patients. Multivariate Cox regression analysis confirmed that miR-24-3p overexpression is a significant predictor of relapse in colorectal adenocarcinoma and that its prognostic significance is independent of other established prognostic factors and treatment of patients. Of note, miR-24-3p overexpression retains its rather unfavorable prognostic value in the subgroup of patients with advanced yet locally restricted colorectal adenocarcinoma (T3) and in those without distant metastasis (M0). Moreover, miR-24-3p overexpression is a potentially unfavorable prognosticator for patients who were not treated with radiotherapy. CONCLUSIONS Strong expression of miR-24-3p predicts poor DFS and OS of colorectal adenocarcinoma patients, independently of clinicopathological parameters that are currently used for prognosis in this human malignancy.", "title": "Elevated expression of miR-24-3p is a potentially adverse prognostic factor in colorectal adenocarcinoma." }, { "docid": "13030852", "text": "Plasma alkaline phosphatase isoenzyme activities were determined in patients with breast cancer to diagnose and monitor bone and liver metastases. Bone alkaline phosphatase activity was increased in 21 of 50 patients (42%) with radiologically confirmed bone metastases, while total alkaline phosphatase activity was increased in only 10 of 50 (20%); liver alkaline phosphatase activity was raised in 12 of 25 patients (48%) with liver metastases. All patients with liver metastases had bone metastases. Bone alkaline phosphatase activity was significantly higher in patients with symptomatic bone disease. Isoenzyme determination provided additional information that would have changed patient management in five of 20 patients who were monitored serially. Measurement of alkaline phosphatase isoenzyme activity, though less sensitive than imaging procedures, can assist in screening for, and in early detection of, a high proportion of bone and liver metastases, and can provide useful objective evidence of their response to treatment.", "title": "Identification of bone and liver metastases from breast cancer by measurement of plasma alkaline phosphatase isoenzyme activity." }, { "docid": "3329824", "text": "BACKGROUND Central nervous system (CNS) disease as the site of first relapse after exposure to adjuvant trastuzumab has been reported. We carried out comprehensive meta-analysis to determine the risk of CNS metastases as the first site of recurrence in patients with HER2-positive breast cancer who received adjuvant trastuzumab. METHODS Eligible studies include randomized trials of adjuvant trastuzumab administered for 1 year to patients with HER2-positive breast cancer who reported CNS metastases as first site of disease recurrence. Statistical analyses were conducted to calculate the incidence, relative risk (RR), and 95% confidence intervals (CIs) using fixed-effects inverse variance and random-effects models. RESULTS A total of 9020 patients were included. The incidence of CNS metastases as first site of disease recurrence in HER2-positive patients receiving adjuvant trastuzumab was 2.56% (95% CI 2.07% to 3.01%) compared with 1.94% (95% CI 1.54% to 2.38%) in HER2-positive patients who did not receive adjuvant trastuzumab. The RR of the CNS as first site of relapse in trastuzumab-treated patients was 1.35 (95% CI 1.02-1.78, P = 0.038) compared with control arms without trastuzumab therapy. The ratio of CNS metastases to total number of recurrence events was 16.94% (95% CI 10.85% to 24.07%) and 8.33% (95% CI 6.49% to 10.86%) for the trastuzumab-treated and control groups, respectively. No statistically significant differences were found based on trastuzumab schedule or median follow-up time. No evidence of publication bias was observed. CONCLUSIONS Adjuvant trastuzumab is associated with a significant increased risk of CNS metastases as the site of first recurrence in HER2-positive breast cancer patients.", "title": "Incidence and risk of central nervous system metastases as site of first recurrence in patients with HER2-positive breast cancer treated with adjuvant trastuzumab." }, { "docid": "2058909", "text": "UNLABELLED The objective of this study was to examine differences in cancer survival between socioeconomic groups in England, with particular attention to survival in the short term of follow-up. PATIENTS AND METHODS Individuals diagnosed with colorectal cancer between 1996 and 2004 in England were identified from cancer registry records. Five-year cumulative relative survival and excess death rates were computed. RESULTS For colon cancer there was a very high excess death rate in the first month of follow-up, and the excess death rate was highest in the socioeconomically deprived groups. In subsequent periods, excess mortality rates were much lower and there was less socioeconomic variation. The pattern of variation in excess death rates was generally similar in rectal cancer but the socioeconomic difference in death rates persisted several years longer. If the excess death rates in the entire colorectal cancer patient population were the same as those observed in the most affluent socioeconomic quintile, the annual reduction would be 360 deaths in colon cancer and 336 deaths in rectal cancer patients. These deaths occurred almost entirely in the first month and the first year after diagnosis. CONCLUSION Recent developments in the national cancer control agenda have included an increasing emphasis on outcome measures, with short-term cancer survival an operational measure of variation and progress in cancer control. In providing clues to the nature of the survival differences between socioeconomic groups, the results presented here give strong support for this strategy.", "title": "Colorectal cancer survival in socioeconomic groups in England: variation is mainly in the short term after diagnosis." }, { "docid": "23639838", "text": "Brain metastases occur in up to 40% of patients with cancer. Their management has been revolutionized in the last decade by three developments: improved imaging and detection of metastases, better treatment of systemic disease with the result that metastases occur more often; and improved surgical techniques including image-guided surgery to treat metastatic lesions. Class 1 data suggest that surgery is a better treatment for metastases than whole brain radiation. Other data suggest that metastases even in eloquent cortex can be removed safely. The complication rate is low and the recurrence rate is less than 10%. In general, indications for surgery include a mass with an unknown primary; a symptomatic mass including one in eloquent areas; a mass with considerable edema requiring high dose steroids; a mass greater than 3 cm; or patient preference when radiosurgery may also be an option. The question of radiosurgery or whole brain radiation as adjunct to surgical removal requires further evaluation.", "title": "Surgical Resection for Patients with Solid Brain Metastases: Current Status" }, { "docid": "15476777", "text": "BACKGROUND Elderly and frail patients with cancer, although often treated with chemotherapy, are under-represented in clinical trials. We designed FOCUS2 to investigate reduced-dose chemotherapy options and to seek objective predictors of outcome in frail patients with advanced colorectal cancer. METHODS We undertook an open, 2 × 2 factorial trial in 61 UK centres for patients with previously untreated advanced colorectal cancer who were considered unfit for full-dose chemotherapy. After comprehensive health assessment (CHA), patients were randomly assigned by minimisation to: 48-h intravenous fluorouracil with levofolinate (group A); oxaliplatin and fluorouracil (group B); capecitabine (group C); or oxaliplatin and capecitabine (group D). Treatment allocation was not masked. Starting doses were 80% of standard doses, with discretionary escalation to full dose after 6 weeks. The two primary outcome measures were: addition of oxaliplatin ([A vs B] + [C vs D]), assessed with progression-free survival (PFS); and substitution of fluorouracil with capecitabine ([A vs C] + [B vs D]), assessed by change from baseline to 12 weeks in global quality of life (QoL). Analysis was by intention to treat. Baseline clinical and CHA data were modelled against outcomes with a novel composite measure, overall treatment utility (OTU). This study is registered, number ISRCTN21221452. FINDINGS 459 patients were randomly assigned (115 to each of groups A-C, 114 to group D). Factorial comparison of addition of oxaliplatin versus no addition suggested some improvement in PFS, but the finding was not significant (median 5·8 months [IQR 3·3-7·5] vs 4·5 months [2·8-6·4]; hazard ratio 0·84, 95% CI 0·69-1·01, p=0·07). Replacement of fluorouracil with capecitabine did not improve global QoL: 69 of 124 (56%) patients receiving fluorouracil reported improvement in global QoL compared with 69 of 123 (56%) receiving capecitabine. The risk of having any grade 3 or worse toxic effect was not significantly increased with oxaliplatin (83/219 [38%] vs 70/221 [32%]; p=0·17), but was higher with capecitabine than with fluorouracil (88/222 [40%] vs 65/218 [30%]; p=0·03). In multivariable analysis, fewer baseline symptoms (odds ratio 1·32, 95% CI 1·14-1·52), less widespread disease (1·51, 1·05-2·19), and use of oxaliplatin (0·57, 0·39-0·82) were predictive of better OTU. INTERPRETATION FOCUS2 shows that with an appropriate design, including reduced starting doses of chemotherapy, frail and elderly patients can participate in a randomised controlled trial. On balance, a combination including oxaliplatin was preferable to single-agent fluoropyrimidines, although the primary endpoint of PFS was not met. Capecitabine did not improve QoL compared with fluorouracil. Comprehensive baseline assessment holds promise as an objective predictor of treatment benefit. FUNDING Cancer Research UK and the Medical Research Council.", "title": "Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial" }, { "docid": "825728", "text": "The epithelial-mesenchymal transition (EMT) is required in the embryo for the formation of tissues for which cells originate far from their final destination. Carcinoma cells hijack this program for tumor dissemination. The relevance of the EMT in cancer is still debated because it is unclear how these migratory cells colonize distant tissues to form macrometastases. We show that the homeobox factor Prrx1 is an EMT inducer conferring migratory and invasive properties. The loss of Prrx1 is required for cancer cells to metastasize in vivo, which revert to the epithelial phenotype concomitant with the acquisition of stem cell properties. Thus, unlike the classical EMT transcription factors, Prrx1 uncouples EMT and stemness, and is a biomarker associated with patient survival and lack of metastasis.", "title": "Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1." }, { "docid": "17482507", "text": "OBJECTIVE To review the evidence for the use of bisphosphonates to reduce skeletal morbidity in cancer patients with bone metastases. DATA SOURCES Electronic databases, scanning reference lists, and consultation with experts and pharmaceutical companies. Foreign language papers were included. STUDY SELECTION Included trials were randomised controlled trials of patients with malignant disease and bone metastases who were treated with oral or intravenous bisphosphonate compared with another bisphosphonate, placebo, or standard care. All trials measured at least one outcome of skeletal morbidity. RESULTS 95 articles were identified; 30 studies fulfilled inclusion criteria. In studies that lasted > or = 6 months, compared with placebo bisphosphonates significantly reduced the odds ratio for fractures (vertebral 0.69, 95% confidence interval 0.57 to 0.84, P < 0.0001; non-vertebral 0.65, 0.54 to 0.79, P < 0.0001; combined 0.65, 0.55 to 0.78, P < 0.0001), radiotherapy (0.67, 0.57 to 0.79, P < 0.0001), and hypercalcaemia (0.54, 0.36 to 0.81, P = 0.003) but not for orthopaedic surgery (0.70, 0.46 to 1.05, P = 0.086) or spinal cord compression (0.71, 0.47 to 1.08, P = 0.113). The reduction in orthopaedic surgery was significant in studies that lasted over a year (0.59, 0.39 to 0.88, P = 0.009). Use of bisphosphonates significantly increased time to first skeletal related event but did not increase survival. Subanalyses showed that most evidence supports use of intravenous aminobisphosphonates. CONCLUSIONS In people with metastatic bone disease bisphosphonates significantly decrease skeletal morbidity, except for spinal cord compression and increased time to first skeletal related event. Treatment should start when bone metastases are diagnosed and continue until it is no longer clinically relevant.", "title": "Systematic review of role of bisphosphonates on skeletal morbidity in metastatic cancer." }, { "docid": "4429932", "text": "Metastasis is a multistep process responsible for most cancer deaths, and it can be influenced by both the immediate microenvironment (cell–cell or cell–matrix interactions) and the extended tumour microenvironment (for example vascularization). Hypoxia (low oxygen) is clinically associated with metastasis and poor patient outcome, although the underlying processes remain unclear. Microarray studies have shown the expression of lysyl oxidase (LOX) to be elevated in hypoxic human tumour cells. Paradoxically, LOX expression is associated with both tumour suppression and tumour progression, and its role in tumorigenesis seems dependent on cellular location, cell type and transformation status. Here we show that LOX expression is regulated by hypoxia-inducible factor (HIF) and is associated with hypoxia in human breast and head and neck tumours. Patients with high LOX-expressing tumours have poor distant metastasis-free and overall survivals. Inhibition of LOX eliminates metastasis in mice with orthotopically grown breast cancer tumours. Mechanistically, secreted LOX is responsible for the invasive properties of hypoxic human cancer cells through focal adhesion kinase activity and cell to matrix adhesion. Furthermore, LOX may be required to create a niche permissive for metastatic growth. Our findings indicate that LOX is essential for hypoxia-induced metastasis and is a good therapeutic target for preventing and treating metastases.", "title": "Lysyl oxidase is essential for hypoxia-induced metastasis" }, { "docid": "16390264", "text": "OBJECTIVES To determine the extent to which type of hospital admission (emergency compared with elective) and surgical procedure varied by socioeconomic circumstances, age, sex, and year of admission for colorectal, breast, and lung cancer. DESIGN Repeated cross sectional study with data from individual patients, 1 April 1999 to 31 March 2006. SETTING Hospital episode statistics (HES) dataset. PARTICIPANTS 564 821 patients aged 50 and over admitted with a diagnosis of colorectal, breast, or lung cancer. MAIN OUTCOME MEASURES Proportion of patients admitted as emergencies, and the proportion receiving the recommended surgical treatment. RESULTS Patients from deprived areas, older people, and women were more likely to be admitted as emergencies. For example, the adjusted odds ratio for patients with breast cancer in the least compared with most deprived fifth of deprivation was 0.63 (95% confidence interval 0.60 to 0.66) and the adjusted odds ratio for patients with lung cancer aged 80-89 compared with those aged 50-59 was 3.13 (2.93 to 3.34). There were some improvements in disparities between age groups but not for patients living in deprived areas over time. Patients from deprived areas were less likely to receive preferred procedures for rectal, breast, and lung cancer. These findings did not improve with time. For example, 67.4% (3529/5237) of patients in the most deprived fifth of deprivation had anterior resection for rectal cancer compared with 75.5% (4497/5959) of patients in the least deprived fifth (1.34, 1.22 to 1.47). Over half (54.0%, 11 256/20 849) of patients in the most deprived fifth of deprivation had breast conserving surgery compared with 63.7% (18 445/28 960) of patients in the least deprived fifth (1.21, 1.16 to 1.26). Men were less likely than women to undergo anterior resection and lung cancer resection and older people were less likely to receive breast conserving surgery and lung cancer resection. For example, the adjusted odds ratio for lung cancer patients aged 80-89 compared with those aged 50-59 was 0.52 (0.46 to 0.59). Conclusions Despite the implementation of the NHS Cancer Plan, social factors still strongly influence access to and the provision of care.", "title": "Social variations in access to hospital care for patients with colorectal, breast, and lung cancer between 1999 and 2006: retrospective analysis of hospital episode statistics" }, { "docid": "25915873", "text": "PURPOSE Therapies to target prostate cancer bone metastases have only limited effects. New treatments are focused on the interaction between cancer cells, bone marrow cells and the bone matrix. Osteoclasts play an important role in the development of bone tumors caused by prostate cancer. Since Src kinase has been shown to be necessary for osteoclast function, we hypothesized that dasatinib, a Src family kinase inhibitor, would reduce osteoclast activity and prostate cancer (PC-3) cell-induced osteoclast formation. RESULTS Dasatinib inhibited RANKL-induced osteoclast differentiation of bone marrow-derived monocytes with an EC(50) of 7.5 nM. PC-3 cells, a human prostate cancer cell line, were able to differentiate RAW 264.7 cells, a murine monocytic cell line, into osteoclasts, and dasatinib inhibited this differentiation. In addition, conditioned medium from PC-3 cell cultures was able to differentiate RAW 264.7 cells into osteoclasts and this too, was inhibited by dasatinib. Even the lowest concentration of dasatinib, 1.25 nmol, inhibited osteoclast differentiation by 29%. Moreover, dasatinib inhibited osteoclast activity by 58% as measured by collagen 1 release. EXPERIMENTAL DESIGN We performed in vitro experiments utilizing the Src family kinase inhibitor dasatinib to target osteoclast activation as a means of inhibiting prostate cancer bone metastases. CONCLUSION Dasatinib inhibits osteoclast differentiation of mouse primary bone marrow-derived monocytes and PC-3 cell-induced osteoclast differentiation. Dasatinib also inhibits osteoclast degradation activity. Inhibiting osteoclast differentiation and activity may be an effective targeted therapy in patients with prostate cancer bone metastases.", "title": "Dasatinib inhibits both osteoclast activation and prostate cancer PC-3-cell-induced osteoclast formation." }, { "docid": "5372432", "text": "BACKGROUND There is some previous evidence that diagnosis of cancer at death, recorded as registry death certificate only records, is associated with problems of access to care. METHODS Records from the Northern and Yorkshire Cancer Registry for patients registered with breast, colorectal, lung, ovarian or prostate cancer between 1994 and 2002 were supplemented with measures of travel time to general practitioner and hospital services, and social deprivation. Logistic regression was used to identify predictors of records where diagnosis was at death. RESULTS There was no association between the odds diagnosis at death and access to primary care. For all sites except breast, the highest odds of being a cancer diagnosed at death fell among those living in the highest quartile of hospital travel time, although it was only statistically significant for colorectal and ovary tumours. Those in the most deprived and furthest travel time to hospital quartile were 2.6 times more likely to be a diagnosis at death case compared with those in the most affluent and proximal areas. CONCLUSIONS There is some evidence that poorer geographical access to tertiary care, in particular when coupled with social disadvantages, may be associated with increased odds of diagnosis at death.", "title": "Geographical access to healthcare in Northern England and post-mortem diagnosis of cancer." }, { "docid": "520579", "text": "OBJECTIVE Experimental evidence suggests that 1,25-dihydroxyvitamin D and its precursor, 25-hydroxyvitamin D [25(OH)D], may aid in the prevention of colorectal cancer. We therefore examined risk in relation to plasma concentrations of these vitamin D metabolites. METHODS In a nested case-control study among women in the Nurses' Health Study, we identified 193 colorectal cancer cases, ages 46 to 78 years, diagnosed up to 11 years after blood collection. Two controls were matched per case on year of birth and month of blood draw. Odds ratios (OR) for risk of colorectal cancer were calculated using conditional logistic regression adjusted for body mass index, physical activity, smoking, family history, use of hormone replacement therapy, aspirin use, and dietary intakes. RESULTS We found a significant inverse linear association between plasma 25(OH)D and risk of colorectal cancer (P = 0.02). Among women in the highest quintile, the OR (95% confidence interval) was 0.53 (0.27-1.04). This inverse association remained strong when limited to women > or =60 years at blood collection (P = 0.006) but was not apparent among the younger women (P = 0.70). Benefit from higher 25(OH)D concentrations was observed for cancers at the distal colon and rectum (P = 0.02) but was not evident for those at the proximal colon (P = 0.81). In contrast to 25(OH)D, we did not observe an association between 1,25-dihydroxyvitamin D and colorectal cancer, although risk was elevated among the women in the highest quintile if they were also in the lower half of the 25(OH)D distribution (OR, 2.52; 95% confidence interval, 1.04-6.11). CONCLUSION From these results and supporting evidence from previous studies, we conclude that higher plasma levels of 25(OH)D are associated with a lower risk of colorectal cancer in older women, particularly for cancers at the distal colon and rectum.", "title": "Plasma vitamin D metabolites and risk of colorectal cancer in women." }, { "docid": "24974080", "text": "New blood vessel formation (angiogenesis) is a fundamental event in the process of tumor growth and metastatic dissemination. Hence, the molecular basis of tumor angiogenesis has been of keen interest in the field of cancer research. The vascular endothelial growth factor (VEGF) pathway is well established as one of the key regulators of this process. The VEGF/VEGF-receptor axis is composed of multiple ligands and receptors with overlapping and distinct ligand-receptor binding specificities, cell-type expression, and function. Activation of the VEGF-receptor pathway triggers a network of signaling processes that promote endothelial cell growth, migration, and survival from pre-existing vasculature. In addition, VEGF mediates vessel permeability, and has been associated with malignant effusions. More recently, an important role for VEGF has emerged in mobilization of endothelial progenitor cells from the bone marrow to distant sites of neovascularization. The well-established role of VEGF in promoting tumor angiogenesis and the pathogenesis of human cancers has led to the rational design and development of agents that selectively target this pathway. Studies with various anti-VEGF/VEGF-receptor therapies have shown that these agents can potently inhibit angiogenesis and tumor growth in preclinical models. Recently, an anti-VEGF antibody (bevacizumab), when used in combination with chemotherapy, was shown to significantly improve survival and response rates in patients with metastatic colorectal cancer and thus, validate VEGF pathway inhibitors as an important new treatment modality in cancer therapy.", "title": "Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis." }, { "docid": "3944632", "text": "CONTEXT In patients with brain metastases, it is unclear whether adding up-front whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) has beneficial effects on mortality or neurologic function compared with SRS alone. OBJECTIVE To determine if WBRT combined with SRS results in improvements in survival, brain tumor control, functional preservation rate, and frequency of neurologic death. DESIGN, SETTING, AND PATIENTS Randomized controlled trial of 132 patients with 1 to 4 brain metastases, each less than 3 cm in diameter, enrolled at 11 hospitals in Japan between October 1999 and December 2003. INTERVENTIONS Patients were randomly assigned to receive WBRT plus SRS (65 patients) or SRS alone (67 patients). MAIN OUTCOME MEASURES The primary end point was overall survival; secondary end points were brain tumor recurrence, salvage brain treatment, functional preservation, toxic effects of radiation, and cause of death. RESULTS The median survival time and the 1-year actuarial survival rate were 7.5 months and 38.5% (95% confidence interval, 26.7%-50.3%) in the WBRT + SRS group and 8.0 months and 28.4% (95% confidence interval, 17.6%-39.2%) for SRS alone (P = .42). The 12-month brain tumor recurrence rate was 46.8% in the WBRT + SRS group and 76.4% for SRS alone group (P<.001). Salvage brain treatment was less frequently required in the WBRT + SRS group (n = 10) than with SRS alone (n = 29) (P<.001). Death was attributed to neurologic causes in 22.8% of patients in the WBRT + SRS group and in 19.3% of those treated with SRS alone (P = .64). There were no significant differences in systemic and neurologic functional preservation and toxic effects of radiation. CONCLUSIONS Compared with SRS alone, the use of WBRT plus SRS did not improve survival for patients with 1 to 4 brain metastases, but intracranial relapse occurred considerably more frequently in those who did not receive WBRT. Consequently, salvage treatment is frequently required when up-front WBRT is not used. TRIAL REGISTRATION umin.ac.jp/ctr Identifier: C000000412.", "title": "Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial." }, { "docid": "17775228", "text": "Epigenetic alterations in human cancers include global DNA hypomethylation,gene hypomethylation and promoter hypermethylation, and loss of imprinting (LOI) of the insulin-like growth factor-II gene (IGF2). A mechanism for LOI described previously is hypermethylation of a differentially methylated region (DMR) upstream of the H19 gene, allowing activation of the normally silent maternal allele of IGF2. Here we show that this mechanism does not apply to colorectal cancers, which show hypomethylation of the H19 DMR as well as a DMR upstream of exon 3 of IGF2. This hypomethylation is found in both colorectal cancers and normal mucosa from the same patients, and in cell lines with somatic cell knockout of DNA methyltransferases DNMT1 and DNMT3B. These data suggest that hypomethylation is a mechanism for LOI, that the popular IGF2-H19 enhancer competition model for IGF2 imprinting does not apply to the human colon, and that an alternative model for LOI would involve a transcriptional repressor acting on the normally silent maternal allele of IGF2.", "title": "Loss of imprinting in colorectal cancer linked to hypomethylation of H19 and IGF2." }, { "docid": "9394119", "text": "IMPORTANCE Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists. OBJECTIVE To identify mutation-specific cancer risks for carriers of BRCA1/2. DESIGN, SETTING, AND PARTICIPANTS Observational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. The international sample comprised 19,581 carriers of BRCA1 mutations and 11,900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents. We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position. We also estimated RHR, the ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk. EXPOSURES Mutations of BRCA1 or BRCA2. MAIN OUTCOMES AND MEASURES Breast and ovarian cancer risks. RESULTS Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer. Among BRCA2 mutation carriers, 6180 women (52%) were diagnosed with breast cancer, 682 (6%) with ovarian cancer, 272 (2%) with breast and ovarian cancer, and 4766 (40%) without cancer. In BRCA1, we identified 3 breast cancer cluster regions (BCCRs) located at c.179 to c.505 (BCCR1; RHR = 1.46; 95% CI, 1.22-1.74; P = 2 × 10(-6)), c.4328 to c.4945 (BCCR2; RHR = 1.34; 95% CI, 1.01-1.78; P = .04), and c. 5261 to c.5563 (BCCR2', RHR = 1.38; 95% CI, 1.22-1.55; P = 6 × 10(-9)). We also identified an ovarian cancer cluster region (OCCR) from c.1380 to c.4062 (approximately exon 11) with RHR = 0.62 (95% CI, 0.56-0.70; P = 9 × 10(-17)). In BRCA2, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1; RHR = 1.71; 95% CI, 1.06-2.78; P = .03), c.772 to c.1806 (BCCR1'; RHR = 1.63; 95% CI, 1.10-2.40; P = .01), and c.7394 to c.8904 (BCCR2; RHR = 2.31; 95% CI, 1.69-3.16; P = .00002). We also identified 3 OCCRs: the first (OCCR1) spanned c.3249 to c.5681 that was adjacent to c.5946delT (6174delT; RHR = 0.51; 95% CI, 0.44-0.60; P = 6 × 10(-17)). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR = 0.57; 95% CI, 0.41-0.80; P = .001). Mutations conferring nonsense-mediated decay were associated with differential breast or ovarian cancer risks and an earlier age of breast cancer diagnosis for both BRCA1 and BRCA2 mutation carriers. CONCLUSIONS AND RELEVANCE Breast and ovarian cancer risks varied by type and location of BRCA1/2 mutations. With appropriate validation, these data may have implications for risk assessment and cancer prevention decision making for carriers of BRCA1 and BRCA2 mutations.", "title": "Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer." }, { "docid": "30226988", "text": "The EUROCARE project analysed cancer survival data from 45 population-based cancer registries in 17 European countries, revealing wide international differences in cancer survival. We calculated 5-year relative survival for 1836287 patients diagnosed with one of 13 cancers during the period 1978-1989. The data, from 20 cancer registries in 13 countries, were grouped into four regions: Finland, Sweden, Iceland (Northern Europe); Denmark, England and Scotland (UK and Denmark); France, The Netherlands, Germany, Italy and Switzerland (Western Europe); Estonia and Poland (Eastern Europe), and broken down into four periods (1978-1980, 1981-1983, 1984-1986, 1987-1989). For each cancer, mean European and regional survival was estimated as the weighted mean of 5-year relative survival in each country. Survival increased with time for all tumours, particularly for cancers of testis (12% increase, i.e. from 79.9 to 91.9%), breast, large bowel, skin melanoma (approximately 9-10%), and lymphomas (approximately 7%). For most solid tumours, survival was highest in Northern Europe and lowest in Eastern Europe, and also low in the UK and Denmark. Regional variation was less marked for the lymphomas. Survival improved more in Western than Northern Europe, and the differences between these regions fell for bowel cancer (from 8.0% for those diagnosed in 1978-1980 to 2% for those diagnosed in 1987-1989), breast cancer (from 7.4% to 3.9%), skin melanoma (from 13.4% to 11.0%) and Hodgkin's disease (from 7.2 to 0.6%). For potentially curable malignancies such as Hodgkin's disease, large bowel, breast and testicular cancers, there were substantial increases in survival, suggesting an earlier diagnosis and more effective treatment. The persisting regional differences suggest there are corresponding differences in the availability of diagnostic and therapeutic facilities, and in the effectiveness of healthcare systems.", "title": "Cancer survival increases in Europe, but international differences remain wide." }, { "docid": "32787042", "text": "AIM To determine the outcome of patients that underwent liver resection for metastases from uveal melanoma. METHODS Over a 9-year period, patients referred with uveal melanoma metastases were included. Following treatment of primary uveal melanoma, high-risk patients were offered to be enrolled into a 6-monthly non-contrast liver magnetic resonance imaging (MRI) surveillance. Following detection of liver metastases, patients were staged with a contrast-enhanced (Primovist(®)) liver MRI, computer tomography (CT) of the thorax and staging laparoscopy. RESULTS 155 patients were referred with uveal melanoma liver metastases, of which 17 (11.0%) patients had liver resection and one patient was treated with percutaneous radio-frequency ablation. The majority of patients undergoing liver resection were treated with multiple metastectomies (n = 8) and three patients had major liver resections. The overall median survival for patients treated with surgery/ablation was 27 (14-90) months, and this was significantly better compared to patients treated palliatively [median = 8(1-30) months, P < 0.001]. Following surgery, 11 patients had recurrent disease [median = 13(6-36) months]. Patients who had undergone a major liver resection had a significantly poorer disease-free survival (P = 0.037). CONCLUSIONS Patients who can undergo surgical resection for metastatic uveal melanoma have a more favorable survival compared to those who do not.", "title": "The Liverpool uveal melanoma liver metastases pathway: outcome following liver resection." }, { "docid": "24205118", "text": "OBJECTIVE To investigate the clinical significance of Bmi-1 expression as a prognostic marker for cervical cancer. Design. Retrospectively collected data from a population-based cohort. SETTING Jiangsu Province Hospital. Population. Eighty-eight women diagnosed with cervical carcinoma between 2000 and 2003. METHODS RT-PCR assay was performed to determine Bmi-1 mRNA expression in 18 cervical cancer and noncancerous tissue samples and immunohistochemistry to detect Bmi-1 protein expression in 88 cervical cancer samples. The correlation between Bmi-1 expression and clinicopathological factors was analyzed. Additionally, statistical analyses were applied to test for prognostic associations. RNA interference was used to downregulate Bmi-1 expression in a cervical cancer cell line (HeLa). In vitro cytotoxicity was measured by the methylthiazoletetrazolium and colony formation assays. Effects of Bmi-1 inhibition on in vivo growth of cancer cells was detected by the tumorigenicity assay. Cell cycle distribution and cell apoptosis were measured by flow cytometry. MAIN OUTCOME MEASURES The levels of Bmi-1 mRNA and protein expression in tissues were evaluated by RT-PCR and Western Blot assays. RESULTS The level of Bmi-1 mRNA expression in cervical cancer tissues was significantly higher than that in corresponding noncancerous tissues. High Bmi-1 expression was significantly correlated with poor tumor differentiation, advanced International Federation of Gynecology and Obstetrics stage and positive lymph node metastasis. Patients with high Bmi-1 expression showed shorter overall survival than those with low expression. Univariate and multivariate analyses showed that high Bmi-1 expression was an independent prognostic factor. CONCLUSIONS RNA interference-mediated Bmi-1 inhibition could inhibit in vitro and in vivo growth, enhance apoptosis and induce cell cycle arrest of cervical cancer cells. Bmi-1 might be an independent prognostic marker for cervical cancer patients.", "title": "Clinicopathological and prognostic significance of Bmi-1 expression in human cervical cancer." }, { "docid": "7165938", "text": "PURPOSE The circadian clock gene Bmal1 is involved in cancer cell proliferation and DNA damage sensitivity. The aim of this study was to explore the effect of Bmal1 on oxaliplatin sensitivity and to determine its clinical significance in colorectal cancer. EXPERIMENTAL DESIGN Three colorectal cancer cell lines, HCT116, THC8307 and HT29, were used. The Bmal1-mediated control of colorectal cancer cell proliferation was tested in vitro and in vivo. MTT and colony formation assays were performed to determine the sensitivity of colorectal cancer cells to oxaliplatin. Flow cytometry was used to examine changes in the cell-cycle distribution and apoptosis rate. Proteins expressed downstream of Bmal1 upon its overexpression were determined by Western blotting. Immunohistochemistry was used to analyze Bmal1 expression in 82 archived colorectal cancer tumors from patients treated with oxaliplatin-based regimens. RESULTS Bmal1 overexpression inhibited colorectal cancer cell proliferation and increased colorectal cancer sensitivity to oxaliplatin in three colorectal cancer cell lines and HCT116 cells model in vivo. Furthermore, the overall survival of patients with colorectal cancer with high Bmal1 levels in their primary tumors was significantly longer than that of patients with low Bmal1 levels (27 vs. 19 months; P = 0.043). The progression-free survival of patients with high Bmal1 expression was also significantly longer than that of patients with low Bmal1 expression (11 vs. 5 months; P = 0.015). Mechanistically, the effect of Bmal1 was associated with its ability to regulate G2-M arrest by activating the ATM pathway. CONCLUSION Bmal1 shows the potential as a novel prognostic biomarker and may represent a new therapeutic target in colorectal cancer.", "title": "Overexpression of the circadian clock gene Bmal1 increases sensitivity to oxaliplatin in colorectal cancer." }, { "docid": "9558539", "text": "Cancer stem cells drive tumor formation and metastasis, but how they acquire metastatic traits is not well understood. Here, we show that all colorectal cancer stem cells (CR-CSCs) express CD44v6, which is required for their migration and generation of metastatic tumors. CD44v6 expression is low in primary tumors but demarcated clonogenic CR-CSC populations. Cytokines hepatocyte growth factor (HGF), osteopontin (OPN), and stromal-derived factor 1α (SDF-1), secreted from tumor associated cells, increase CD44v6 expression in CR-CSCs by activating the Wnt/β-catenin pathway, which promotes migration and metastasis. CD44v6(-) progenitor cells do not give rise to metastatic lesions but, when treated with cytokines, acquire CD44v6 expression and metastatic capacity. Importantly, phosphatidylinositol 3-kinase (PI3K) inhibition selectively killed CD44v6 CR-CSCs and reduced metastatic growth. In patient cohorts, low levels of CD44v6 predict increased probability of survival. Thus, the metastatic process in colorectal cancer is initiated by CSCs through the expression of CD44v6, which is both a functional biomarker and therapeutic target.", "title": "CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis." }, { "docid": "8963413", "text": "PD-L1 is an immunoinhibitory molecule that suppresses the activation of T cells, leading to the progression of tumors. Overexpression of PD-L1 in cancers such as gastric cancer, hepatocellular carcinoma, renal cell carcinoma, esophageal cancer, pancreatic cancer, ovarian cancer, and bladder cancer is associated with poor clinical outcomes. In contrast, PD-L1 expression correlates with better clinical outcomes in breast cancer and merkel cell carcinoma. The prognostic value of PD-L1 expression in lung cancer, colorectal cancer, and melanoma is controversial. Blocking antibodies that target PD-1 and PD-L1 have achieved remarkable response rates in cancer patients who have PD-L1-overexpressing tumors. However, using PD-L1 as an exclusive predictive biomarker for cancer immunotherapy is questionable due to the low accuracy of PD-L1 immunohistochemistry staining. Factors that affect the accuracy of PD-L1 immunohistochemistry staining are as follows. First, antibodies used in different studies have different sensitivity. Second, in different studies, the cut-off value of PD-L1 staining positivity is different. Third, PD-L1 expression in tumors is not uniform, and sampling time and location may affect the results of PD-L1 staining. Therefore, better understanding of tumor microenvironment and use of other biomarkers such as gene marker and combined index are necessary to better identify patients who will benefit from PD-1/PD-L1 checkpoint blockade therapy.", "title": "PD-L1 expression in human cancers and its association with clinical outcomes" } ]
3398
Which countries allow eChecks?
[ { "docid": "259890", "text": "eChecks (and ACH) are a (desperate?) try of the US banking system to get into the 21st century. All EU countries (and some others) have direct deposits and transfers as the standard way of transferring money since about 20 years, and since about 5 years it is cost-free and one-day across all the EU. The rest of the world runs mostly country specific system, as there is not that large a demand for cross country shifting, and exchange rates are also an issue in any such transaction. Because they have different ways that work fine since decades, other countries will consider the eCheck idea as a step backwards and will probably ignore it, so your answer is 'none'. International companies work with banks in a different relationship than retail customers, so they can do things you and me cannot do - depending on size and volume. Some large companies get a banking license and then handle their own stuff; medium sized companies make favorable contracts with banks (they are golden goose customers - never an issue, no brick and mortar presence needed, banks love them), or they simply suck up the transfer cost (if you move millions, who cares about a 40 $ fee). Small businesses whine and live with what they get...", "title": "" } ]
[ { "docid": "280822", "text": "So apparently ACH and eCheck are interchangeable. The confusion arises from PayPal's ambiguous use of terminology. According to this thread ( https://www.paypal-community.com/t5/Sending-money-Archive/how-do-i-change-from-a-echeck-to-an-instant-payment/td-p/92459 ) the payment process PayPal takes is a bit complicated, but if you try to send money to another person via PayPal:", "title": "" }, { "docid": "512282", "text": "You can't just emigrate from a country like Pakistan to the USA, Canada or Australia; they will refuse you entry to their country. E.g. for the USA, even if you're are skilled enough that an American company will hire you (which is obviously the first step – so called 'economic refugees' are sent back immediately), you're a long way from obtaining a green card. Right now, Pakistan isn't even allowed to participate in the Green Card Lottery. What you also need to consider is that the cost of living in those countries is a lot higher. There are websites, like this one which allows you to compare them between cities all over the world. So while you would earn a lot more money, you also need to spend a lot more.", "title": "" }, { "docid": "230961", "text": "Linking the card is primarily to give you (and Paypal) a fall-back option for funding your spending if your bank account doesn't have sufficient funds to process the charge. If the bank account has sufficient funds, it will work fine in many cases without a credit card. If you have both linked (bank and a credit card), Paypal will transfer funds immediately, as Paypal knows it has an option for getting the funds if the bank has insufficient funds. However, if you have no credit card linked or remove your only card: If you remove your only card and have a confirmed bank account, you’ll no longer be able to make instant bank payments. Instead they’ll be sent as eChecks, which take 3 to 4 working days to process. This may not matter in many cases, but it may delay things some. There may also be services who require immediate payment (and won't support PayPal if it's not immediate). There may also be some functional limitations. The one I see is primarily that some services that are geo-location-specific, Spotify for one example, use the credit card to verify that you are in a particular location (in Spotify's case, for licensing purposes). They don't seem to accept Paypal unless it's linked to a credit or debit card (even if it's verified via a bank account). I'm not sure if this is common with other services, but it's something to consider.", "title": "" }, { "docid": "3181", "text": "&gt; Operating in a country that allows you to make profit, in my opinion, establishes a duty to pay one's fair share of taxes. Paying legislators to make laws enabling tax avoidance is, in my mind, unethical. Clearly we have a different idea of what is ethical and not. You have stumbled upon the heart of exactly why Burger King's actions (and those of other companies that do similar things) are perfectly justified, although perhaps not in the manner you intended. In the entire developed world, corporations are taxed at a certain rate on the income that they make as a result of business operations in that country. In the US, US headquartered corporations are taxed at a certain rate not only on the income that they make a result of business operations in that country, but also on the income that they make as the result of business operations in other countries. Operating in a country that allows you to make a profit established a duty to pay one's fair share of taxes. Operating in a country that allows you to make a profit does not establish any duty to pay one's fair share of taxes *to an entirely different country*. Or at least, no moral or ethical obligation to do so. The US may try to make a legal obligation to do so, but I certainly can't fault any company which tries to avoid that obligation, since the obligation is inherently unjust in the first place. If you don't want companies doing stuff like this, might I suggest that your country should stop imposing such ridiculous tax laws, and get in line with the rest of the developed world. Every other country in the world is content to tax their fair slice of the pie for stuff that happens in their borders; only the US expects a bite out of everyone else's pie too. Same should go for personal income earned by US citizens living abroad. They should have no obligation to pay US income taxes.", "title": "" }, { "docid": "94477", "text": "Usually, you can buy ETFs through brokerages. I looked at London to see if there's any familiar brokerage names, and it appears that the address below is to Fidelity Investments Worldwide and their site indicates that you can buy securities. Any brokerage, in theory, should allow you to invest in securities. You could always call and ask if they allow you to invest in ETFs. Some brokerages may also allow you to purchase securities in other countries; for instance, some of the firms in the U.S. allow investors to invest in the ETF HK:2801, which is not a U.S. ETF. Many countries have ETF securities available to local and foreign investors. This site appears to help point people to brokers in London. Also, see this answer on this site (a UK investor who's invested in the U.S. through Barclays).", "title": "" }, { "docid": "95390", "text": "\"Where are you from? The Netherlands has tax treaties with different countries that may offer you some additional options. The Netherlands calculates a maximum tax free contribution to your pension each year based on your income. If you contributed less than you were allowed to (pensioengat), you can invest the difference between your actual and allowed contributions in special retirement investments that usually offer tax advantages. A gap like this can be due to getting a bonus or a raise. After looking around, the investments available are either a special savings account (banksparen) or an annuity (lijfrente). Your allowed contributions to both will be tax deductible and the investment itself is excluded from wealth tax (box 3 taxes). I also see Aegon offering an \"\"investment annuity\"\" that lets you invest in any of 7 of their mutual funds until a certain date at which time you liquidate and use the proceeds to fund an annuity. With the Dutch retirement options, wou will not in general get the same freedom of choice or low costs associated with IRAs in the US. I'm not sure about ISAs in the UK. It's also important to check any tax agreements between countries to ensure your chosen investment vehicle gets the tax advantaged treatment in your home country as it does in the Netherlands. For US citizens, this is important even when living abroad. For others, it is important if you return to your home country and still have this investment. If you are a US citizen, you have an additional option. The US / Dutch tax treaty allows you to make these contributions to preexisting (i.e. you had these before moving to NL) retirement accounts in the US like an IRA. Note that in practice it may be difficult to contribute to an existing Roth IRA because you would need to have earned income after the foreign income tax deduction but less than the maximum income for a Roth contribution.\"", "title": "" }, { "docid": "325113", "text": "In the UK you have an allowance of £40,000 per annum for tax relief into a pension. This amount includes both your and your employer's contributions. If you earn more than £150,000 per annum this allowance starts to reduce and if you earn less than the allowance, your allowance is limited to what you earn. You can also carry over unused allowance from up to 3 years previously. If you stick within this allowance you won't pay tax on your pension contributions, if you go over the excess will be subject to tax. Salary exchange normally lets you avoid the National Insurance value of your contribution being taxed. If you paid your own money into your pension (without going through salary exchange), your contributions would have the 20% basic rate of tax credited to them and if you're a higher rate taxpayer you could reclaim the difference between the basic rate of tax and the higher rate of tax you pay but the National Insurance you've paid on your own money would not be reclaimable. You can't get the money back you've paid into your pension till you are are 58 (given that you are 27 now), the minimum age has risen from its historic 55 for your age group. That's the pension trade off, you forgo tax now in the expectation that, once retired, you will be paying tax at a lower rate (because your income will be lower and you are much less likely to be subject to higher rate taxation) in return for locking in your money till you're older. Your pension income will be subject to tax when you eventually take it. There are other options such as ISAs which have lower annual limits (£20,000 currently) and on which your contributions do not attract tax relief, but which are not taxed as income when you eventually spend them. ISAs and pensions are not mutually exclusive so if you have the money, you can do both. It's up to you to determine what mix of savings will be appropriate to generate income for your eventual retirement. If you are living in some other country when you retire your pension will be paid net of UK tax. You might then be able to claim (or pay) any difference between that and your local tax rate depending on what agreement exists between the UK government and the other country's government.", "title": "" }, { "docid": "558501", "text": "This is a good example of the hellish cycle of dictatorship and corruption. It happens time and time again: a dictator strangles the country and its institutions for years. He finally dies/gives up power and those in line behind him quickly start attacking the remnants of his family and regime. But are they doing it for the good of the country or for their own benefit, so that they can expunge the previous regime only to get their own iron grip on power? On the one hand, prosecuting a corrupt regime is necessary. On the other hand, it only brings up lasting positive results if it's because the free, independent institutions are actually acting in the public interest rather than to allow a new regime to establish total power. At the end of the day this shows one thing: people don't matter, what matters are processes, laws, and institutional independence. As long as the country's institutions are vulnerable, the people at the top will change but the way the country is run will not. Time will tell which one it is in Uzbekistan.", "title": "" }, { "docid": "575241", "text": "Part 1 Quite a few [or rather most] countries allow USD account. So there is no conversion. Just to illustrare; In India its allowed to have a USD account. The funds can be transfered as USD and withdrawn as USD, the interest is in USD. There no conversion at any point in time. Typically the rates for CD on USD account was Central Bank regulated rate of 5%, recently this was deregulated, and some banks offer around 7% interest. Why is the rate high on USD in India? - There is a trade deficit which means India gets less USD and has to pay More USD to buy stuff [Oil and other essential items]. - The balance is typically borrowed say from IMF or other countries etc. - Allowing Banks to offer high interest rate is one way to attract more USD into the country in short term. [because somepoint in time they may take back the USD out of India] So why isn't everyone jumping and making USD investiments in India? - The Non-Residents who eventually plan to come back have invested in USD in India. - There is a risk of regulation changes, ie if the Central Bank / Country comes up pressure for Forex Reserves, they may make it difficut to take back the USD. IE they may impose charges / taxes or force conversion on such accounts. - The KYC norms make it difficult for Indian Bank to attract US citizens [except Non Resident Indians] - Certain countries would have explicit regulations to prevent Other Nationals from investing in such products as they may lead to volatility [ie all of them suddenly pull out the funds] - There would be no insurance to foreign nationals. Part 2 The FDIC insurance is not the reason for lower rates. Most countires have similar insurance for Bank deposits for account holdes. The reason for lower interst rate is all the Goverments [China etc] park the excess funds in US Treasuries because; 1. It is safe 2. It is required for any international purchase 3. It is very liquid. Now if the US Fed started giving higher interest rates to tresaury bonds say 5%, it essentially paying more to other countries ... so its keeping the interest rates low even at 1% there are enough people [institutions / governemnts] who would keep the money with US Treasury. So the US Treasury has to make some revenue from the funds kept at it ... it lends at lower interest rates to Bank ... who in turn lend it to borrowers [both corporate and retail]. Now if they can borrow cheaply from Fed, why would they pay more to Individual Retail on CD?, they will pay less; because the lending rates are low as well. Part 3 Check out the regulations", "title": "" }, { "docid": "326167", "text": "\"In the US: In the UK: You can set up a CAF (Charities Aid foundation) Charity Account. This allows you to donate to charities anonymously, while still allowing the recipient to benefit from Gift Aid (where they can reclaim the income tax you'd paid on the donation). You can even use this account to donate to overseas charities if you're donating at least £250. Or you can use a different intermediary such as BT MyDonate or The Big Give or another intermediary. See the Wikipedia article \"\"Comparison of online charity donation services in the United Kingdom\"\". In Canada: If there's a United Way charity in your country, it may have a donor choice program which may be able to forward a designated donation to any other charity in your country. The United Way probably charges a fee for this service. I'm not sure whether or not the United Way would be willing to keep you anonymous, and I'm not sure whether or not the United Way would add you to its mailing list. More details may be available elsewhere online.\"", "title": "" }, { "docid": "440774", "text": "Yes, that is correct. Note, when there is a tax treaty between Canada and the other country -- [which is pretty much anywhere you have active business](http://www.fin.gc.ca/treaties-conventions/in_force--eng.asp) -- the tax credits are equal to the income received, making it tax free. Here is a better explanation: &gt; The greatest advantage of having a foreign affiliate in the international business setting is to repatriate foreign profits back to Canada tax free under certain conditions, for example, if a foreign affiliate carries on an active business in a designated treaty country (i.e. a country with which Canada has a tax treaty). The after-tax profit is included in a pool called “exempt surplus”. If the repatriation of profit in the form of dividend was paid out of the “exempt surplus” pool to a Canadian corporate shareholder, such dividend is included in its income and the same amount is allowed to be deducted in computing its taxable income. In other words, the dividend is not subject to Canadian tax if received by a Canadian corporate shareholder. [Source, p3](http://www.canadataxplan.com/test/canadataxplan/files/Book%20-%20English_summary_12-22-2008.pdf) Edit... here from the NRC site: &gt; Treaty Countries: **Active business income earned in a treaty country is classified as “exempt surplus.”** The exempt surplus of an FA also includes inter-affiliate dividends received out of the exempt surplus of other foreign affiliates, the exempt portion (25%) of all capital gains, and certain taxable capital gains. **Dividends paid out of the exempt surplus of an FA can be received free of additional taxes in Canada**, since the profits out of which they are paid are considered to have borne a rate of tax in the treaty country comparable to that of Canada. [Source](http://www.nrcan.gc.ca/mining-materials/taxation/8880) see the section on Subsidiary Income. This is the reason BK is moving to Canada. [Also here is a very interesting deck on corporate tax minimization in latin america by the Canadian mining industry.](http://miningtaxcanada.com/wp-content/uploads/2010/05/TOR01-5160395-v1-RMLF_Cartagena_Slides.pdf)", "title": "" }, { "docid": "503836", "text": "Virtual Credit Card: It there something like virtual credit card? Yes there is. We have banks in India HDFC and Kotak bank that allows you to generate a virtual credit card which could be used for payments on websites. These cards are one time use cards and will expire as soon as you use it once. The mail objective behind such virtual card service is to protect the actually card information to be shared on websites. Take a look: Its call Netsafe and remember HDFC is a very reputed bank in India Moving further about the company Entropay. Take a look at the website. Most of the information you need to know about the company starts from the website data: Lets take a look at the contact us page: Any company that deals in financial services business has to be registered under financial services authority of the country they are doing business in. This company is based in Malta and should definitely be registered with Malta Financial Services Authority (MFSA). The company claims that they are registered with FSA under license registration number 540990. Sounds great everything is perfect but just to make sure I thought of taking a look at the MFSA website on the activity of the company. Here's a link: http://www.mfsa.com.mt/ Under License Holder Tried searching for the company Ixaris Systems Ltd. and here is what I found: There was no record of the company on the MFSA database. I even tried not searching and looking into the complete database but no such company on the list. By the way look I found Western Union there: What I mean to say here is only one thing. Any company that deals in financial transactions need to be registered with the local financial services of the country they have their physical address in. If suppose western union is an american company with physical existence in 100 countries they not only have to be registered with Financial Services Authority in US but also in every other countries they have their physical address in. I know many of you will still argue that it has a valid verisign logo which means it's a company with physical address and its been verified. But please remember its very easy to fool those verisign guys coz almost every verification is done online. Also the verisign information of this company shows its a company registered in UK not Malta. Just to be very sure again I also checked the FSA website of UK. There is no such company under FSA regulations even in UK. I would want to give you the answer to your question very boldly but I had a bad experience today on this same website so I would rather allow you make the decision wether its a legit company or a SCAM.", "title": "" }, { "docid": "521684", "text": "\"I believe that an understanding of the taxation system can help to understand our place in it, and how that impacts each of our personal finances. I will try to remain unbiased here but this is a somewhat subjective question, so please bear with me if you disagree on any point. Some of these tax savings are well-advertised, and can be used by many people, such as tax credits for mass-transit passes which exists in some countries. But some of these tax savings are things you never heard of before, until it winds up on the news. Why do some people seem to get tax savings that you and I cannot get, and why do those people always seem to have so much more money than us? A simplistic answer can show this in three parts: (1) The source of one's income; (2) Transaction costs; and (3) \"\"tax loopholes\"\". Tax savings occur proportionately to one's income, and if the savings apply to investment income, they occur proportionately to one's wealth. If someone living paycheck to paycheck with a minimal amount in a bank account \"\"saves tax on investment income\"\", they might reduce their taxable interest from $50 to $0. That's because they simply don't have any other investment income to reduce. All of their income comes in the form of employment, which is typically very hard to save taxes on. Most governments have a very firm grasp on the taxation of employment income, because it is a huge proportion of income in the country (and therefore has the largest amount of tax associated), and because it is very straightforward (work for someone = employment income). A more cynical person than I might point out that investment income is earned by the very wealthy, who can afford to lobby for politicians to pass favourable investment income laws. Even very straightforward tax saving opportunities may cost money to enable. The simplest example would be: if a tax saving opportunity is so complicated that an average person can't understand it themselves, then an accountant, lawyer, or banker will need to be the one to explain it. And that can cost you money. If your tax isn't so much to begin with, then the transaction costs to achieve the tax savings could be higher than the tax savings themselves. For example, most countries have tax savings / deferrals if you start a corporation. These rules typically exist to promote investment in the local economy. But someone who earns $10k in a side-business might not be able to afford the $3k in incorporation costs just to save $2k in taxes. The more income and wealth you have, the more these transaction costs become worthwhile. I'm going to generally define \"\"tax loopholes\"\" for the purposes of this answer as something where a somewhat arbitrary situation allows for taxes that a layman would consider unfair or unexpected. This often occurs with good intentions but poor legislation - the government tries to provide a benefit to a deserving group or to promote an activity, but ends up allowing another group to take advantage. For example in Canada, there existed until a few years ago tax saving rules about passing on wealth to children at lower tax rates, only when a close family member is near-death [setting up a 'testamentary trust' between a grandparent and a grandchild could in some circumstances allow that trust to be created with additional 'tax brackets', meaning more income would be taxed at a less-than top tax rate before being distributed to the grandchildren]. The rules were put in place with the idea that \"\"oh gee, a family member has died, and the dang ol' family is grieving so hard they can't distribute the wealth to the next generation for a few months on account of all the crying. We should make it so that the estate is taxed like a person, and if they earn only a little income, they have a low tax rate, and they only get taxed at the full rate if they have a lot of income\"\". Seems reasonable enough, but if a family is ready to pass on wealth at the same time as someone is nudging the bucket with their foot, a morbid discussion with your lawyer and accountant could set your children up for life with forever reduced taxes on massive inheritances. In the case of the Panama / Paradise leaks, tax savings are due to all 3 of the above: Those who have massive wealth (and therefore earn the majority of their income from investments instead of employment) can afford the transaction costs associated with taking advantage of specific \"\"tax loopholes\"\". The simplest example of which is just that income earned in a foreign country might have a lower tax rate than income earned domestically. This is often a result of \"\"cracks\"\" in the foreign tax treaties between countries, which exist generally to promote business between countries and prevent double-taxing individuals who need activity in both countries for whatever reason. Take for example the \"\"Apple loophole\"\". Apple has operations around the world. Some activity occurs in low-tax jurisdictions. Apple reports a high percentage of the value of R&D as being associated with those jurisdictions. Those branches in low-tax jurisdictions charge the high-tax branches (such as the US) with fees for use of their valuable research. So much of Apple's income is reported in those foreign jurisdictions. It won't be taxed in the US until Apple \"\"repatriates\"\" the cash back to the US. Until then, the cash sits in the foreign jurisdiction, accruing less tax. This and similar rules can be used by individuals wealthy enough to hold corporations in foreign jurisdictions with low tax rates. How each particular rule / \"\"loophole\"\" works will depend on the nature of a specific case - tax law is complex, and the rules between countries are even more so. These foreign tax loopholes are closing every year. It is getting harder and harder to hide money offshore, and it is getting less and less likely that you will be able to find a country with juuuust the right loopholes for your own offshore wealth. These types of news leaks will only help to expedite those changes.\"", "title": "" }, { "docid": "198996", "text": "ok so greece and ireland- funding of the banks has added quite a bit of deficit over the past couple of years. this has been problematic, as countries become unwilling to ask for help to save the bank because of the poor public image that it carries - no politician wants to increase the deficit in favor of bank (expect americans ? LOL) additionally, it has a negative impact on economy (discussed below) this year, ECB has agreed to allow direct recapitalization of banks. This means that the Spanish Govt will not be responsible for bank funding when the bailout is established - thus reducing the impact on spain's economy. there will not be an increase in deficit when spanish banks are recapitalized in the past, with ireland and greece, it was difficult because - countries had to implement austerity measure and accept funding to recapitalize bank. weakened balance sheet of troubled countries drove up the cost of money, making it more difficult to recapitalize the banks, which worked in a cycle. direct recapitalization has been implemented to limit this effect", "title": "" }, { "docid": "286635", "text": "Supply and demand... It creates an equilibrium. Right now there is a food surplus so prices and production should go down. If there is a food shortage... Prices should be allowed to go up which will create money-making opportunities and food production will increase. The Communist types of US agriculture policies don't fix pricing, supply or demand issues. Being able to produce agriculture products below cost creates a surplus that winds up getting dumped on other countries. Government subsidy corn from the US has decimated the agriculture industries in countries that don't subsidize agriculture like Mexico. Our communist types of agriculture policies hurt WAY more farmers than they help.", "title": "" }, { "docid": "526384", "text": "What happens to consumer debt if a country defaults on its debt? Nothing, just as nothing happens to your debt when your neighbor defaults. If you have debts that have floating interest rates - those may (and probably will) hike. how will a debt default by a country affect government-backed loans such as mortgages and student loans? Those that are already closed will probably not be affected, as you've got the money already and signed the loan agreement. Those that are not closed - will probably be delayed or not funded at all. However, if any of the debts allows the debtor to request an early collection (which I think is rather rare on the consumer market) - someone else's default may lead to the debtor's request for the money earlier than expected.", "title": "" }, { "docid": "5219", "text": "Most US banks don't allow you the ability to draft a foreign currency check from USD. Though, I know Canadian banks are more workable. For instance, TD allows you to do this from CAD to many other currencies for a small fee. I believe even as a US Citizen you can quite easily open a TD Trust account and you'd be good to go. Also, at one time Zions bank was one of the few which lets US customers do this add-hoc. And there is a fee associated. Even as a business, you can't usually do this without jumping thru hoops and proving your business dealings in foreign countries. Most businesses who do this often will opt to using a payment processor service from a 3rd party which cuts checks in foreign currencies at a monthly and per check base. Your other option, which may be more feasible if you're planning on doing this often, would be to open a British bank account. But this can be difficult if not impossible due to the strict money laundering anti-fraud regulations. Many banks simply won't do it. But, you might try a few of the newer British banks like Tesco, Virgin and Metro.", "title": "" }, { "docid": "179073", "text": "Foreign stocks have two extra sources of risk attached to them; exchange rate and political. Exchange rate risk is obvious; if I buy a stock in a foreign currency and there is a currency movement that makes that investment worth less I lose money no matter what the stock does. This can be offset using exchange rate swaps. (This is ceteris paribus, of course; changes in exchange rate can give a comparative advantage to international and exporting companies that will improve the fundamentals and so increase the price of the stock relative to a local firm. The economics of the firms in particular are not explored in this answer as it would get too complicated and long if I did.) Political risk relates not only to the problems surrounding international politics such as a country deciding that foreign nationals may no longer own shares in their national industries or deciding to seize foreign nationals' assets as happens in some areas. Your home country may also decide to apply sanctions to the country in which you are invested thus making it impossible to get your money back even though the foreign country will allow you to redeem them or sell. Diplomatic relations and trade agreements tend to be difficult. There are further problems in lack of understanding of foreign countries' laws, tax code, customs etc. relating to investments and the necessity to find legal representation in a country you may never have visited if there are issues. There is also a hidden risk in that, as an individual investor, you are not likely to be reading the local financial news for that country regularly enough to spot company specific issues arising. By the time these issues get into international media its far too late as all of the local investors have sold out of their positions already. The risks are probably no different if you have the time to monitor international relations and the foreign country's news, and have FX swaps in place to counteract FX risk as the funds and investment banks do but as an individual investor the time required is not feasible.", "title": "" }, { "docid": "553133", "text": "\"A couple of thoughts and experiences (Germany/Italy): First of all, I recommend talking to the Belgian bank (and possibly to a Dutch bank of your choice). I have similar conditions for my German bank accounts. But even though they talk about it as salary account (\"\"Gehaltskonto\"\") all they really ask for is a monthly inflow of more than xxxx € - which can be satisfied with an automatic direct transfer (I have some money automatically circulating for this reason which \"\"earns\"\" about 4% p.a. by saving fees). In that case it may be a feasible way to have a Belgian and a Dutch bank account and set up some money circulation. Experiences working in Italy (some years ago, SEPA payments were kind of new and the debits weren't implemented then): My guess with your service providers is that they are allowed to offer you contracts that are bound to rather arbitrary payment conditions. After all, you probably can also get a prepaid phone or a contract with a bill that you can then pay by wire transfer - however, AFAIK they are allowed to offer discounts/ask fees for different payment methods. Just like there is no law that forces the store around your corner to accept credit cards or even large EUR denominations as long as they tell you so beforehand. AFAIK, there is EU regulation saying your bank isn't allowed to charge you more for wire transger to foreign country within the SEPA zone than a national wire transfer.\"", "title": "" }, { "docid": "202179", "text": "\"I think the key point that's making the other commenters misunderstand each other here is the concept of \"\"deductions\"\". I can only speak for the UK, but that's only a concept that business owners would understand in this country. For things like child credits or low income tax credits, we don't get paid them at the end of the tax year, but into our bank accounts every couple of weeks all year round. Therefore, we have nothing to \"\"deduct\"\". If we work for a company and have business expenses, then the company pays for them. If we make interest on our savings, the bank pays it for us. We make money at our jobs, and the employer works out what taxes and national insurance we owe, based on a tax code that the government works out for us annually (which we can challenge). To be fair, it's not like we're free from bureaucracy if we want to claim these benefits. There are often lots of forms if you want child benefit or disability allowances, for instance. We just apply as soon as we're eligible, rather than waiting to get a lump sum rebate. So it appears to be a very different system, and neither is inherently better than the other (though I'm personally glad I don't usually have to fill in a big tax return myself, which I only did one year when I was self employed). I'd be interested to know, since Google has let me down, which countries use the American system, and which the British or Czech.\"", "title": "" }, { "docid": "240628", "text": "Reddit doesn't have a ton of resources to offer you as you learn about where to invest, you want to start reading up on actual investing sites. You might start with Motley Fool, StockTwits, Seeking Alpha, Marketwatch, etc. I agree with hipster's take, if all countries are going to keep printing money and expanding their debts and craziness, gold has a bright future. Land, petroleum, commodities, and precious metals have an intrinsic worth that will still be there regardless of what currencies are doing, versus bonds which are merely promises to pay, which will be paid off in devalued money, or stocks which are just promises of future earnings. Think about spreading your risk in a few different places, one chunk here, one chunk there. Some people in the US now are big on dividend paying stocks in lieu of bonds which only pay a percent, which is negative return after inflation. Some people buy 'royalty trust' units, which throw off income from oil leases as dividends. You might want to park a portion in a different currency, but dollar funds aren't going to pay interest and Switzerland plans to keep devaluing its currency as people keep bidding the price up. I don't know if you are allowed to buy CEF, a bullion-backed fund out of Canada in your country, but that's one way to own gold &amp; silver. But with the instability out there, you might prefer a bit of the real thing stashed in a safe place. Or if you have a bit of family land, maybe just be sure you can pay the taxes to keep it; or pursue any other way to own 'real stuff' that will still be worth something after all hell breaks loose.", "title": "" }, { "docid": "115419", "text": "\"&gt; they want to lower the standards we have for goods and services Their avowed goal is \"\"regulatory coherence\"\" but its [not being done in a good way](http://www.ciel.org/Publications/ToxicPartnership_Mar2014.pdf), its an attempt to sneak through a [huge long long list](http://www.ttip2014.eu) of bad ideas that would not fly in any kind of light of day, and then make them permanent, with special [eternal entitlements](http://tpplegal.files.wordpress.com/2012/05/isds-domestic-legal-process-background-brief.pdf) for multinational corporations, so permanent that future elections can not change them, nor can states individually protect people, their laws would be preempted to the extent that unaccountable trade tribunals [can order huge fines against countries and states for merely doing their jobs](http://www.italaw.com/sites/default/files/case-documents/italaw3206.pdf), because they impinge upon new suddenly materialized \"\"rights\"\" as perceived by the trade agreements. Almost nobody knows they are doing this. often countries dont realize that they have lost their rights to determine their policies, and then countries usually lose. There are SO many problems I don't know where to begin. &gt; in part by opening up public services to private business? Privatization often goes badly. They are hiding that and portraying privatization as the only possible future. Well at the beginning, the prototypes FTAs, NAFTA and GATS mandated the privatization of most public services in countries that signed them, with services (everything you can't drop on your foot) especially some of the add on documents to GATS. That was in 1995. It contains a \"\"standstill\"\" (they all do) which said that countries could not change anything if it was a move back towards public ownership and control, in the case of services, they frame that as bad, as a theft from businesses.. So standstill typically says things like they can not create any new public services and [if there was any money involved in the market sector at all that it would have to be privatized](http://www.iatp.org/files/GATS_and_Public_Service_Systems.htm) in tiny steps. No going back to public services allowed. But of course, people dont know that and often don't believe it when told. For example, do you believe me when i tell you thats the reason US health care is so bad-? Can you see how and why they might lie about what they,, politicians, can do, can do about things because they want to win elections by promising things - like affordable health care- But also hide the ugly act [that they gave away the store](http://www.law.harvard.edu/programs/lwp/nafta.pdf) starting in 1995. The FTAs that we can read (the early ones) tried to do it by being undecipherable to non-experts- they are so complicated and ambiguous only a few people really know what they demanded, at least up until recently. Now they are top secret. Really secret. Only the 600 lobbyists have access. Now, a growing number of people, especially in Europe, seem to realize this is really scary and a red flag., but its not because the news was any help, its because of the net, the media - especially in the US, has been completely unhelpful. They dont cover this at all. TTIP is a huge controversy. But I have a feeling the worst one is TiSA, which has remained largely out of the news. Except for Wikileaks and the financial services chapter. Just one chapter is known. And its an old version. Now they want in TiSA to greatly [expand the scope of these FTAs to millions of service jobs](https://www.youtube.com/watch?v=2_pPqnbXpA4) in a huge number of countries. Countries want things, like the US wants to be able to charge more money for drugs and they want to force other countries to allow US companies into their markets, for example, insurance, or financial instruments, it seems that they are trying to deregulate banking when it should be re-regulated to avoid a repeat of the 2008 GFC. Another thing the US wants is to limit generic drugs and make it easier for companies to open factories, send contractors, etc. elsewhere. Its not always a good thing to open markets up to \"\"liberalisation\"\". In many cases, it could lead to substantial job losses, as it has in [Central America after CAFTA](http://citizen.typepad.com/eyesontrade/2014/08/central-america-crisis-belies-caftas-empty-promises.html).\"", "title": "" }, { "docid": "125424", "text": "erm... a) H1b applications went down over 90% in the last two years because the US does not offer anything better anymore (keep in mind, H1b means a Corp. vouchers for you and you can only stay as employee in the country, you can switch employer but you can't just start a startup or something. fired and no new employer? you get kicked out of the country. which also happens 6 years later no matter what because the visa only lasts 3+3 years and is a lottery so applying doesnt mean you actually get it. so why come in the first place?) b) H1b visa holders must be payed appropriate. c) if I can get hired by MS in the US, I can also work for a US office anywhere else, and they have plenty. d) H1b means you have either 4 years university possibly with degree or you can prove that you worked 3 years for each university year and have therefore a minimum of 12 years job experience in the field you're hired. again, if Microsoft, why in the US? pay in your own country is probably better. the whole worker visa system is doomed. they should give out IT greencards like Germany tried it many years ago to bring in foreign talent. a visa that is not chained to the employer that vouched for you but let's you open up a startup and stay for longer. h1b pretty much let's you stay in a country that takes taxes for you, you have to obey their laws but you get no benefits and 6 years later you get kicked out. if you want to come back after 6 years you have to stay out at least 1 years, then you're allowed to participate again in the yearly H1b lottery which means almost 2 years after you got kicked out you might win again and you can return to work for the company. seriously, would you like to be in that situation? building a life in a new country with a countdown attached to it? (I just left the US after 6 years on H1b) edit: btw. they are already charging 8 or 12k since 2012 per application. up from 1500 - one of the explanations why applications are down.", "title": "" }, { "docid": "405156", "text": "\"People are naturally pessimistic or optimistic. I am a pessimist, I have a anxiety disorder to prove. Tried to have a business, gave up when I realized I would have to borrow more money to keep on going. My dad on the other hand, he is eternal optimist. He was part of the 80es real estate bubble. It just was in his genes to believe that prizes keep on going up. And they might have, but there were factors at play that he could not foresee (falling of soviet union which influenced Finland). To me, bubbles are born because of 1 simple reason. Government backed loans. If governments would not bail out banks that lend money to speculators. There would not be bubbles. It is that simple. But then the economy would freeze, since banks would demand perfect guarantees before they would loan you a cent. One way to deal with that might be that central banks would naturally print money at a certain rate each year, knowing that a lot of that money will just burn in bad investments, basically forgiving banks for the bad loans they have made. Not too much to cause inflation, yet not too little to cause banks stop lending. This money would be simply printed off thin air. There would have to be a agreement on IMF level at what this \"\"burn rate\"\" could be to invidual countries. But since that burn rate could give an edge to a country that was allowed to print more, it would be very hard to come to an agreement how much each country could print. Or, there could be a international agreement that the money would printed this way only during recessions. Else we are stuck with bust and boom cycles, which are very destructive as I have witnessed first hand.\"", "title": "" }, { "docid": "295089", "text": "Some countries, like the United States, allow a mortgage interest tax deduction. This means the interest you pay on a mortgage, which is typically much more than half of the monthly payment at the beginning of a 25 year mortgage, is tax deductible, so you might get 33% or more of the interest back, and that effectively makes the interest rate significantly lower. Therefore you are borrowing the money really cheap. That makes MrChrister's answer even more appropriate.", "title": "" }, { "docid": "452275", "text": "Well, you're taking two companies who are overhauling their networks in a similar way (LTE) and combining resources... Combining Sprint's and Softbank's orders for phones and LTE equipment reduces overall cost per unit which allows both companies to offer better service and better devices for less. There is also the added advantage of capturing customers that travel between the US and Japan... Make it easier and cheaper to use one device in both countries. That's what they're aiming for.", "title": "" }, { "docid": "540437", "text": "Protect competition, not protect competitors. In a lot of cases in the tech world no one knows who the competitors is a few quarters/years down the road. Also, enforce regulations against regulation-arbitrage companies like Uber/Lyft, AirBnB, or reg-arb tech like ICO, all of which relied on regulatory leeways allowing them to crush existing companies that's been saddled w/ regulations. In countries where regulatory arbitrage doesnt exist these 'innovators' fail, e.g., Uber in South Korea.", "title": "" }, { "docid": "557550", "text": "First, currencies are not an investment; they are a medium of exchange; that is, you use currency to buy goods and services and/or investments. The goods and services you intend to buy in your retirement are presumably going to be bought in your country; to buy these you will need your country's currency. The investments you intend to buy now require the currency of whatever country they are located in. If you want to buy shares in Microsoft you need USD; if you want shares in BHP-Billiton you need AUD or GBP (It is traded on two exchanges), if you want property in Kuwait you need KWD and if you want bonds in your country you need IDR. When you sell these later to buy the goods and services you were saving for you need to convert from whatever currency you get for selling them into whatever currency you need to buy. When you invest you are taking on risk for which you expect to be compensated for - the higher the risk you take the better the returns had better be because there is always the chance that they will be negative, right down to losing it all if you are unlucky. There is no 100% safe investment; if you want to make sure you get full value for your money spend it all right now! If you invest overseas then, in addition to all the other investment risks, you are adding currency risk as well. That is, the risk that when you redeem your investments the overseas currency will have fallen relative you your currency. One of the best ways of mitigating risk is diversification; which allows the same return at a lower risk (or a higher return at the same risk). A pure equity portfolio is not diversified across asset classes (hopefully it is diversified across the equities). Equities are a high risk-high yield class; particularly in a developing economy like Indonesia. If you are very young with a decades long investment horizon this may be OK but even then, a diversified portfolio will probably offer better rewards at the same risk. Diversifying into local cash, bonds and property with a little foreign equities, bonds and property will serve you better than worrying about the strength of the IDR. Oh, and pay a professional for some real advice rather than listening to strangers on the internet.", "title": "" }, { "docid": "158185", "text": "The answer to your question doesn't depend on who you trade with but what country you live in. If you live outside of the US, you will have to pay tax on dividends... sometimes. This depends on the tax treaty that your country has with the US. Canada, Australia, UK and a few other countries have favorable tax treaties with the US that allow you to not be double taxed. You must look into the tax treaty that your home country has with the US to answer the question. Each country is different.", "title": "" }, { "docid": "454208", "text": "You can't currently avoid it. The reason the legislation was introduced was to prevent the big-name developers from setting up shop in a low-VAT country and selling apps to citizens of EU countries that would normally be paying a much higher VAT. You need to register for VAT and file quarterly nil-returns so that you get that money back. It's a hassle, but probably worth it just to recoup those funds. From an article in Kotaku from late 2014: You see, in the UK we have a rather sensible exemption on VAT for businesses that earn under £81,000 a year. This allows people to run small businesses - like making and selling games in your spare time, for instance - without the administrative nightmare of registering as a business and paying VAT on sales. Unfortunately, none of the other EU member states had an exemption like this, so when the new legislation was being put together, there was no exemption factored in. That means that if someone makes even £1 from selling something digital to another person in another EU country, they now have to be VAT registered in the UK AND they have to pay tax on that sale at whatever rate the buyer’s country of residence has set. That could be 25% in Sweden, 21% in the Netherlands, and so on. [...] There’s one piece of good news: even though anyone who sells digital stuff now has to be VAT-registered in the UK, they don’t actually have to pay VAT on sales to people in the UK if they earn less than £81,000 from it. (This concession was achieved earlier this month after extensive lobbying.) But they’ll still have to submit what’s called a “nil-return”, which is essentially a tax return with nothing on it, every quarter in order to use the VAT MOSS service. That’s a lot of paperwork. Obviously Brexit may have a significant impact on all this, so the rules might change. This is the official Google Link to how they've implemented this and for which countries it affects: https://support.google.com/googleplay/android-developer/answer/138000?hl=en Due to VAT laws in the European Union (EU), Google is responsible for determining, charging, and remitting VAT for all Google Play Store digital content purchases by EU customers. Google will send VAT for EU customers' digital content purchases to the appropriate authority. You don't need to calculate and send VAT separately for EU customers. Even if you're not located in the EU, this change in VAT laws will still apply.", "title": "" } ]
PLAIN-674
bergamottin
[ { "docid": "MED-5045", "text": "Helicobacter pylori (H. pylori) is one of the most widespread human pathogens, and plays major roles in chronic gastritis and gastric cancer. CD74 of gastric epithelial cells has recently been identified as an adhesion molecule to urease in H. pylori. In this study, we found that CD74 is highly expressed in a constitutive manner in NCI-N87 human gastric carcinoma cells at both the protein and mRNA levels as compared with Hs738St./Int fetal gastric cells. Subsequently, a novel cell-based ELISA able to rapidly screen the suppressive agents of CD74 expression was established. NCI-N87 cells were treated separately with 25 different food phytochemicals (4–100 µM) for 48 h and subjected to our novel assay. From those results, a citrus coumarin, bergamottin, was indicated to be the most promising compound with an LC50/IC50 value greater than 7.1, followed by luteolin (>5.4), nobiletin (>5.3), and quercetin (>5.1). Our findings suggest that these CD74 suppressants are unique candidates for preventing H. pylori adhesion and subsequent infection with reasonable action mechanisms.", "title": "Suppressive Effects of Selected Food Phytochemicals on CD74 Expression in NCI-N87 Gastric Carcinoma Cells" } ]
[ { "docid": "MED-3959", "text": "Context: Earlier age at menarche is associated with rapid infancy weight gain and childhood obesity. The role of hormone levels in mediating these associations is unclear. Objective: The aim of this study was to identify childhood hormone levels at age 8 yr that are associated with early menarche, independent of body size. Design, Settings, and Subjects: A total of 329 girls from a prospective United Kingdom birth cohort study provided blood samples at mean age 8.1 yr (range, 8.0–8.5) for hormone measurements and were followed longitudinally to establish age at menarche. Main Outcome Measures: Fasting plasma levels of IGF-I, androstenedione, dehydroepiandrosterone sulfate (DHEAS), leptin, insulin, IGF binding protein-1, and SHBG were measured. Age at menarche was reported by questionnaire and categorized as before 12.0, 12.0–13.0, or later than 13 yr. Results: Earlier menarche was associated with greater body weight, height, and body mass index at age 8 yr (all P-trend <0.001). Before adjustment for body size, earlier menarche was associated with higher levels of IGF-I, androstenedione, DHEAS, leptin, and fasting insulin, and with lower levels of IGF binding protein-1 and SHBG at age 8 yr (all P < 0.01). After adjustment for body mass index and height at age 8 yr, only IGF-I (P = 0.004), androstenedione (P = 0.01), and DHEAS (P = 0.01) remained associated with earlier menarche. Conclusions: Associations between higher levels of IGF-I and adrenal androgens at age 8 yr with earlier menarche, independent of body size, support functional roles of these hormones in regulating puberty timing in girls. Higher levels of these hormones reported in children who exhibited rapid weight gain during infancy may indicate their role in developmental pathways leading to earlier sexual maturation.", "title": "Higher Levels of IGF-I and Adrenal Androgens at Age 8 Years Are Associated with Earlier Age at Menarche in Girls" }, { "docid": "MED-933", "text": "A case of occult coeliac disease (CD) presenting with recurrent monoarthritis in a boy aged 11 years is reported. The case is unique due to the association of occult untreated CD and arthritis in childhood. Peripheral or axial arthritis as a first manifestation of occult CD has been described in adult patients, with an interval between the arthritis and CD of up to 15 years. In our case the interval between the appearance of arthritis and the diagnosis of CD was 2 years. The boy was asymptomatic for bowel disease and his nutritional status was normal. The diagnosis of CD was established using anti-gliadin (AGA) and anti-endomysium (EMA) antibody tests and was confirmed by small bowel biopsy. The introduction of a gluten-free diet resulted in the persistent remission of arthritis. As the treatment of CD-associated arthritis is based on dietary therapy, physicians should be alert to the possibility of occult CD in any child with arthritis of unclear origin.", "title": "Recurrent monoarthritis in an 11-year-old boy with occult coeliac disease. Successful and stable remission after gluten-free diet." }, { "docid": "MED-3988", "text": "Context: Two reports suggested that vitamin D2 is less effective than vitamin D3 in maintaining vitamin D status. Objective: Our objective was to determine whether vitamin D2 was less effective than vitamin D3 in maintaining serum 25-hydroxyvitamin D levels or increased the catabolism of 25-hydroxyvitamin D3. Subjects and Design: This was a randomized, placebo-controlled, double-blinded study of healthy adults ages 18–84 yr who received placebo, 1000 IU vitamin D3, 1000 IU vitamin D2, or 500 IU vitamin D2 plus 500 IU vitamin D3 daily for 11 wk at the end of the winter. Results: Sixty percent of the healthy adults were vitamin D deficient at the start of the study. The circulating levels of 25-hydroxyvitamin D (mean ± sd) increased to the same extent in the groups that received 1000 IU daily as vitamin D2 (baseline 16.9 ± 10.5 ng/ml; 11 wk 26.8 ± 9.6 ng/ml), vitamin D3 (baseline 19.6 ± 11.1 ng/ml; 11 wk 28.9 ± 11.0 ng/ml), or a combination of 500 IU vitamin D2 and 500 IU vitamin D3 (baseline 20.2 ± 10.4 ng/ml; 11 wk 28.4 ± 7.7 ng/ml). The 25-hydroxyvitamin D3 levels did not change in the group that received 1000 IU vitamin D2 daily. The 1000 IU dose of vitamin D2 or vitamin D3 did not raise 25-hydroxyvitamin D levels in vitamin D-deficient subjects above 30 ng/ml. Conclusion: A 1000 IU dose of vitamin D2 daily was as effective as 1000 IU vitamin D3 in maintaining serum 25-hydroxyvitamin D levels and did not negatively influence serum 25-hydroxyvitamin D3 levels. Therefore, vitamin D2 is equally as effective as vitamin D3 in maintaining 25-hydroxyvitamin D status.", "title": "Vitamin D2 Is as Effective as Vitamin D3 in Maintaining Circulating Concentrations of 25-Hydroxyvitamin D" }, { "docid": "MED-5107", "text": "Acne is caused by the action of dihydrotestosterone, derived from endogenous and exogenous precursors, likely acting synergistically with insulin-like growth factor-1. These sources and interactions are discussed. Both a mechanism of action and recommended dietary changes that limit ingestion and production of these hormones are proposed.", "title": "Diet and acne." }, { "docid": "MED-3567", "text": "In 2008, approximately 21.8 million persons aged ≥15 years sustained nonfatal, unintentional injuries, resulting in approximately $67.3 billion in lifetime medical costs. Information about where injuries occur is limited, but bathrooms commonly are believed to be a particularly hazardous location. To investigate this assumption, CDC analyzed data from a nationally representative sample of emergency departments (EDs) to describe the incidence and circumstances of nonfatal injuries in bathrooms (in any setting) among persons aged ≥15 years in the United States. This report describes the results of that investigation, which found that, based on 3,339 cases documented in the 2008 National Electronic Surveillance System All Injury Program (NEISS-AIP) database, an estimated 234,094 nonfatal bathroom injuries were treated in U.S. EDs. Injury rates increased with age, and most injuries (81.1%) were caused by falls. All persons, but especially older adults, should be aware of bathroom activities that are associated with a high risk for injury and of environmental modifications that might reduce that risk.", "title": "Nonfatal bathroom injuries among persons aged ≥15 years--United States, 2008." }, { "docid": "MED-4390", "text": "The medicinal properties of curcumin obtained from Curcuma longa L. cannot be utilised because of poor bioavailability due to its rapid metabolism in the liver and intestinal wall. In this study, the effect of combining piperine, a known inhibitor of hepatic and intestinal glucuronidation, was evaluated on the bioavailability of curcumin in rats and healthy human volunteers. When curcumin was given alone, in the dose 2 g/kg to rats, moderate serum concentrations were achieved over a period of 4 h. Concomitant administration of piperine 20 mg/kg increased the serum concentration of curcumin for a short period of 1-2 h post drug. Time to maximum was significantly increased (P < 0.02) while elimination half life and clearance significantly decreased (P < 0.02), and the bioavailability was increased by 154%. On the other hand in humans after a dose of 2 g curcumin alone, serum levels were either undetectable or very low. Concomitant administration of piperine 20 mg produced much higher concentrations from 0.25 to 1 h post drug (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h), the increase in bioavailability was 2000%. The study shows that in the dosages used, piperine enhances the serum concentration, extent of absorption and bioavailability of curcumin in both rats and humans with no adverse effects.", "title": "Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers." }, { "docid": "MED-4820", "text": "Background: Few prospective studies have examined cancer incidence among vegetarians. Methods: We studied 61 566 British men and women, comprising 32 403 meat eaters, 8562 non-meat eaters who did eat fish (‘fish eaters') and 20 601 vegetarians. After an average follow-up of 12.2 years, there were 3350 incident cancers of which 2204 were among meat eaters, 317 among fish eaters and 829 among vegetarians. Relative risks (RRs) were estimated by Cox regression, stratified by sex and recruitment protocol and adjusted for age, smoking, alcohol, body mass index, physical activity level and, for women only, parity and oral contraceptive use. Results: There was significant heterogeneity in cancer risk between groups for the following four cancer sites: stomach cancer, RRs (compared with meat eaters) of 0.29 (95% CI: 0.07–1.20) in fish eaters and 0.36 (0.16–0.78) in vegetarians, P for heterogeneity=0.007; ovarian cancer, RRs of 0.37 (0.18–0.77) in fish eaters and 0.69 (0.45–1.07) in vegetarians, P for heterogeneity=0.007; bladder cancer, RRs of 0.81 (0.36–1.81) in fish eaters and 0.47 (0.25–0.89) in vegetarians, P for heterogeneity=0.05; and cancers of the lymphatic and haematopoietic tissues, RRs of 0.85 (0.56–1.29) in fish eaters and 0.55 (0.39–0.78) in vegetarians, P for heterogeneity=0.002. The RRs for all malignant neoplasms were 0.82 (0.73–0.93) in fish eaters and 0.88 (0.81–0.96) in vegetarians (P for heterogeneity=0.001). Conclusion: The incidence of some cancers may be lower in fish eaters and vegetarians than in meat eaters.", "title": "Cancer incidence in British vegetarians" }, { "docid": "MED-2169", "text": "Norharman and harman are two heterocyclic beta-carboline (9H-pyrido[3,4-b]indole) alkaloids with biological and potential toxicological activity that appear in foodstuffs and environmental sources. To assess the occurrence and distribution of these compounds and to estimate the exposure levels based on the detected amounts, numerous samples of foodstuffs and cigarette smoke were analysed by solid-phase extraction and high-performance liquid chromatography-fluorescence. The levels found of beta-carbolines were highly variable. Low processed foodstuffs (i.e. milk, yoghurt, uncooked meats and fish) did not contain norharman and harman above the detection limit. Others, however, contained relatively high concentrations (at the tens of ng g(-1) or microg l(-1) level) depending on the processing conditions as, for example, 'well-done' cooked meat and fish. The highest amounts of norharman and harman were found in brewed coffee (29-207 microg l(-1)), sauces (soy sauce and Tabasco, among others; 4-252 microg l(-1)), 'well done' cooked meat and fish (57-160 ng g(-1)), toasted bread (42-160 ng g(-1)), and fermented alcoholic beverages (n.d.-41 mug l(-1)). beta-Carbolines also occurred in a high amount in the mainstream of cigarette smoke (207-2780 ng/cigarette), which is an important contributor to daily exposure to these compounds. Based on these results, it is concluded that the daily exposure to beta-carbolines in humans might be from tens to hundreds of micrograms, with cigarette smoke, coffee, certain seasonings, cooked foods and alcoholic beverages, in this order, being the major contributors. Many other foodstuffs might also contribute with minor amounts of norharman and harman. Foods and tobacco smoke might be potential contributors to the reported endogenous presence of beta-carbolines in humans.", "title": "Relative exposure to beta-carbolines norharman and harman from foods and tobacco smoke." }, { "docid": "MED-4408", "text": "The influence of protein oxidation, as measured by the dinitrophenylhydrazine (DNPH) method, on colour and texture changes during chill storage (2 degrees C, 12days) of cooked burger patties was studied. Extracts from arbutus-berries (Arbutus unedoL., AU), common hawthorns (Crataegus monogynaL., CM), dog roses (Rosa caninaL., RC) and elm-leaf blackberries (Rubus ulmifoliusSchott., RU) were prepared, added to burger patties (3% of total weight) and evaluated as inhibitors of protein oxidation and colour and texture changes. Negative (no added extract, C) and positive control (added quercetin; 230mg/kg, Q) groups were also considered. The significant increase of protein carbonyls during chill storage of control burger patties reflect the intense oxidative degradation of the muscle proteins. Concomitantly, an intense loss of redness and increase of hardness was found to take place in burger patties throughout refrigerated storage. Most fruit extracts as well as Q significantly reduced the formation of protein carbonyls and inhibited colour and texture deterioration during chill storage. Likely mechanisms through which protein oxidation could play a major role on colour and texture changes during chill storage of burger patties are discussed. Amongst the extracts, RC was most suitable for use as a functional ingredient in processed meats since it enhanced oxidative stability, colour and texture properties of burger patties with no apparent drawbacks. Copyright 2010 Elsevier Ltd. All rights reserved.", "title": "Protein oxidation in emulsified cooked burger patties with added fruit extracts: Influence on colour and texture deterioration during chill storage." }, { "docid": "MED-1394", "text": "BACKGROUND: Observational cohort studies and a secondary prevention trial have shown an inverse association between adherence to the Mediterranean diet and cardiovascular risk. We conducted a randomized trial of this diet pattern for the primary prevention of cardiovascular events. METHODS: In a multicenter trial in Spain, we randomly assigned participants who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly individual and group educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes). On the basis of the results of an interim analysis, the trial was stopped after a median follow-up of 4.8 years. RESULTS: A total of 7447 persons were enrolled (age range, 55 to 80 years); 57% were women. The two Mediterranean-diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses. A primary end-point event occurred in 288 participants. The multivariable-adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54 to 0.92) and 0.72 (95% CI, 0.54 to 0.96) for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events). No diet-related adverse effects were reported. CONCLUSIONS: Among persons at high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events. (Funded by the Spanish government's Instituto de Salud Carlos III and others; Controlled-Trials.com number, ISRCTN35739639.).", "title": "Primary prevention of cardiovascular disease with a Mediterranean diet." }, { "docid": "MED-3168", "text": "Legumes and the polyphenolic compounds present in them have gained a lot of interest due to their beneficial health implications. Dietary polyphenolic compounds, especially flavonoids, exert antioxidant properties and are potent inhibitors of xanthine oxidase (XO) activity. XO is the main contributor of free radicals during exercise but it is also involved in pathogenesis of several diseases such as vascular disorders, cancer and gout. In order to discover new natural, dietary XO inhibitors, some polyphenolic fractions and pure compounds isolated from two legume plant extracts were tested for their effects on XO activity. The fractions isolated from both Vicia faba and Lotus edulis plant extracts were potent inhibitors of XO with IC50 values range from 40–135 µg/mL and 55–260 µg/mL, respectively. All the pure polyphenolic compounds inhibited XO and their Ki values ranged from 13–767 µM. Ten of the compounds followed the non competitive inhibitory model whereas one of them was a competitive inhibitor. These findings indicate that flavonoid isolates from legume plant extracts are novel, natural XO inhibitors. Their mode of action is under investigation in order to examine their potential in drug design for diseases related to overwhelming XO action.", "title": "Flavonoid Glycosides Isolated from Unique Legume Plant Extracts as Novel Inhibitors of Xanthine Oxidase" }, { "docid": "MED-2346", "text": "Summary: Infection of humans with the nematode worm parasite Anisakis simplex was first described in the 1960s in association with the consumption of raw or undercooked fish. During the 1990s it was realized that even the ingestion of dead worms in food fish can cause severe hypersensitivity reactions, that these may be more prevalent than infection itself, and that this outcome could be associated with food preparations previously considered safe. Not only may allergic symptoms arise from infection by the parasites (“gastroallergic anisakiasis”), but true anaphylactic reactions can also occur following exposure to allergens from dead worms by food-borne, airborne, or skin contact routes. This review discusses A. simplex pathogenesis in humans, covering immune hypersensitivity reactions both in the context of a living infection and in terms of exposure to its allergens by other routes. Over the last 20 years, several studies have concentrated on A. simplex antigen characterization and innate as well as adaptive immune response to this parasite. Molecular characterization of Anisakis allergens and isolation of their encoding cDNAs is now an active field of research that should provide improved diagnostic tools in addition to tools with which to enhance our understanding of pathogenesis and controversial aspects of A. simplex allergy. We also discuss the potential relevance of parasite products such as allergens, proteinases, and proteinase inhibitors and the activation of basophils, eosinophils, and mast cells in the induction of A. simplex-related immune hypersensitivity states induced by exposure to the parasite, dead or alive.", "title": "Anisakis simplex: from Obscure Infectious Worm to Inducer of Immune Hypersensitivity" }, { "docid": "MED-4099", "text": "OBJECTIVE: A meta-analysis was performed on epidemiologic studies to assess the relation between β-glucan consumption from oats and from barley on blood cholesterol level, triglyceride/triacylglycerol (TGL/TAG) level, and blood glucose level (BGL) in humans. In addition, the effect of β-glucan on total cholesterol (TC) and BGL was translated into an empirical dose-response model. METHODS: Thirty research articles that evaluated the effect of different exposure levels of β-glucan on blood cholesterol and BGL were analyzed, yielding 126 clinical studies. RESULTS: There was a significant inverse relation in TC (-0.60 mmol/L, 95% confidence interval [CI] -0.85 to -0.34), low-density lipoprotein (-0.66 mmol/L, 95% CI -0.96 to -0.36), and TGL/TAG (-0.04 mmol/L, 95% CI -0.15 to 0.07) after consumption of β-glucan. In contrast, an increase in high-density lipoprotein cholesterol was noted (0.03 mmol/L, 95% CI -0.06 to 0.13) with the random-effect model. The analysis showed a significant change in BGL (-2.58 mmol/L, 95% CI -3.22 to -1.84) with high heterogeneity between (I(2) = 97%) and across (τ(2) = 5.88) the studies. The fixed-effect model showed a significant change in TC, low-density lipoprotein, and BGL, whereas it showed no significant changes in high-density lipoprotein and TGL/TAG. The dose-response model showed that a 3-g/d dose of oat or barley β-glucan was sufficient to decrease TC. CONCLUSION: Consumption of 3 g/d of oat or barley β-glucan is sufficient to decrease blood cholesterol, whereas the effect on BGL is still inconclusive, with high heterogeneity, and requires further clinical research studies with longer intervention periods. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Meta-analysis of the effect of β-glucan intake on blood cholesterol and glucose levels." }, { "docid": "MED-3718", "text": "The American Cancer Society (ACS) publishes Nutrition and Physical Activity Guidelines to serve as a foundation for its communication, policy, and community strategies and ultimately, to affect dietary and physical activity patterns among Americans. These Guidelines, published every 5 years, are developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and as such, they represent the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS Guidelines include recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or interferes with healthy behaviors. Community efforts are essential to create a social environment that promotes healthy food choices and physical activity. Therefore, this committee presents one key recommendation for community action to accompany the four recommendations for individual choices to reduce cancer risk. This recommendation for community action recognizes that a supportive social environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. The ACS Guidelines are consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes, as well as for general health promotion, as defined by the Department of Health and Human Services' 2005 Dietary Guidelines for Americans.", "title": "American Cancer Society Guidelines on Nutrition and Physical Activity for cancer prevention: reducing the risk of cancer with healthy food choices ..." }, { "docid": "MED-4383", "text": "OBJECTIVE: We investigated the relation between plasma carotenoids, retinol and tocopherol levels and ovarian cancer risk in Korean women. DESIGN: Hospital-based case-control study. SETTING: Six tertiary medical institutes in Korea. POPULATION: Forty-five epithelial ovarian cancers and 135 age-matched controls. METHODS: Preoperative plasma concentrations of beta-carotene, lycopene, zeaxanthin plus lutein, retinol, alpha-tocopherol, and gamma-tocopherol were measured by reverse-phase, gradient high-pressure liquid chromatography. MAIN OUTCOME MEASURES: Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated by tertiles to evaluate the effect of micronutrients on endometrial cancer risk after adjustment for body mass (BMI) index, menopause, parity, oral contraceptive use, smoking status, and alcohol consumption status. RESULTS: Women in the highest tertile for beta-carotene had 0.12-times the risk of ovarian cancer of in the lowest tertile (OR 0.12; 95%CI 0.04-0.36). Women with the highest tertiles of lycopene (OR 0.09; 95%CI 0.03-0.32), zeaxanthin/lutein (OR 0.21; 95%CI 0.09-0.52), retinol (OR 0.45; 95%CI 0.21-0.98), alpha-tocopherol (OR 0.23; 95%CI 0.10-0.53) and gamma-tocopherol (OR 0.28; 95%CI 0.11-0.70) had lower risk of ovarian cancer than women in the lowest tertiles. Results were consistent across strata of socio-epidemiologic factors. CONCLUSIONS: Micronutrients, specifically ss-carotene, lycopene, zeaxanthin, lutein, retinol, alpha-tocopherol, and gamma-tocopherol, may play a role in reducing the risk of ovarian cancer.", "title": "Plasma carotenoids, retinol and tocopherol levels and the risk of ovarian cancer." }, { "docid": "MED-1778", "text": "Objective To examine the relationship between dairy food intake and semen parameters Design Longitudinal study Setting Men attending academic medical center fertility clinic in Boston, MA Patients 155 men Interventions None Main Outcome Measures total sperm count, sperm concentration, progressive motility, and morphology Results Low-fat dairy intake was positively related to sperm concentration and progressive motility. On average, men in the highest quartile of intake (1.22–3.54 servings/day) had 33% (95% confidence interval (CI) 1, 55) higher sperm concentration and 9.3 (95%CI 1.4, 17.2) percentage units higher sperm motility than men in the lowest quartile of intake (≤0.28 servings/day). These associations were primarily explained by intake of low-fat milk. The corresponding results for low-fat milk were 30% (95%CI 1,51) higher sperm concentration and 8.7 (95%CI 3.0, 14.4) percentage units higher sperm motility. Cheese intake was associated with lower sperm concentration among ever smokers. In this group, men in the highest tertile of intake (0.82–2.43 servings/day) had 53.2% (95%CI 9.7, 75.7) lower sperm concentration than men in the lowest tertile of cheese intake (<0.43 servings/day). Conclusions Our findings suggest that low-fat dairy intake, particularly low-fat milk, is related to higher sperm concentration and progressive motility, while cheese intake to lower sperm concentration among past or current smokers.", "title": "Dairy intake and semen quality among men attending a fertility clinic" }, { "docid": "MED-717", "text": "OBJECTIVE: Fructose intake has increased considerably in the United States, primarily as a result of increased consumption of high-fructose corn syrup, fruits and juices, and crystalline fructose. The purpose was to determine how often fructose, in amounts commonly consumed, would result in malabsorption and/or symptoms in healthy persons. DESIGN: Fructose absorption was measured using 3-hour breath hydrogen tests and symptom scores were used to rate subjective responses for gas, borborygmus, abdominal pain, and loose stools. SUBJECTS/SETTING: The study included 15 normal, free-living volunteers from a medical center community and was performed in a gastrointestinal specialty clinic. INTERVENTION: Subjects consumed 25- and 50-g doses of crystalline fructose with water after an overnight fast on separate test days. MAIN OUTCOME MEASURES: Mean peak breath hydrogen, time of peak, area under the curve (AUC) for breath hydrogen and gastrointestinal symptoms were measured during a 3-hour period after subjects consumed both 25- and 50-g doses of fructose. STATISTICAL ANALYSES: Differences in mean breath hydrogen, AUC, and symptom scores between doses were analyzed using paired t tests. Correlations among peak breath hydrogen, AUC, and symptoms were also evaluated. RESULTS: More than half of the 15 adults tested showed evidence of fructose malabsorption after 25 g fructose and greater than two thirds showed malabsorption after 50 g fructose. AUC, representing overall breath hydrogen response, was significantly greater after the 50-g dose. Overall symptom scores were significantly greater than baseline after each dose, but scores were only marginally greater after 50 g than 25 g. Peak hydrogen levels and AUC were highly correlated, but neither was significantly related to symptoms. CONCLUSIONS: Fructose, in amounts commonly consumed, may result in mild gastrointestinal distress in normal people. Additional study is warranted to evaluate the response to fructose-glucose mixtures (as in high-fructose corn syrup) and fructose taken with food in both normal people and those with gastrointestinal dysfunction. Because breath hydrogen peaks occurred at 90 to 114 minutes and were highly correlated with 180-minute breath hydrogen AUC, the use of peak hydrogen measures may be considered to shorten the duration of the exam.", "title": "Fructose intake at current levels in the United States may cause gastrointestinal distress in normal adults." }, { "docid": "MED-3884", "text": "Microbes have evolved over 3.5 billion years and are arguably the most adaptable organisms on earth. Restricted genetically by their inability to reproduce sexually, bacteria have acquired several additional mechanisms by which to exchange genetic material horizontally. Such mechanisms have allowed bacteria to inhabit some of the most inhospitable environments on earth. It is thus hardly surprising that when faced with a barrage of inimical chemicals (antibiotics) they have responded with an equal and opposite force. This article compares and contrasts the evolution of antimicrobial resistance to beta-lactam antibiotics over the last 70 years in two bacterial species, namely Staphylococcus aureus, a highly evolved human pathogen, and Pseudomonas aeruginosa, an opportunistic nosocomial pathogen.", "title": "The 2009 Garrod lecture: the evolution of antimicrobial resistance: a Darwinian perspective." }, { "docid": "MED-2313", "text": "BACKGROUND: Chronic cutaneous complications such as pruritus are among the very frequent complaints of sulphur mustard (SM)-exposed patients. The present trial investigated the impact of curcumin on serum inflammatory biomarkers and their association with pruritus severity and quality of life (QoL). METHODS: This was a randomized, double-blind trial among 96 male Iranian veterans (age 37-59 y) who were suffering from chronic SM-induced pruritic skin lesions. Patients were randomly assigned to curcumin (1 g/d, n = 46) or placebo (n = 50) for four weeks. Serum concentrations of interleukins 6 (IL-6) and 8 (IL-8) together with high-sensitivity C-reactive protein (hs-CRP) and calcitonin gene-related peptide (CGRP) were measured at baseline and at the end of the trial. Assessment of pruritus severity was performed using the pruritus score and QoL using the Dermatology Life Quality Index (DLQI). RESULTS: Serum IL-8 and hs-CRP were significantly reduced in both groups but the magnitude of reduction was greater in the curcumin group (P < 0.001). Serum CGRP was only decreased in the curcumin group (P < 0.001). No significant change was observed in serum IL-6. There were significant correlations between CGRP and IL-6 changes (P = 0.011) and between DLQI and IL-8 changes (P = 0.026) in the curcumin group. In the curcumin group, changes in serum IL-8 concentrations were found as the significant predictor of DLQI scores (P = 0.026) but none of the independent variables could predict pruritus scores. CONCLUSIONS: Curcumin supplementation effectively mitigates inflammation in patients suffering from chronic SM-induced cutaneous complications. This anti-inflammatory effect might account for the observed pruritus alleviation and QoL improvement by this phytochemical.", "title": "A randomized controlled trial on the anti-inflammatory effects of curcumin in patients with chronic sulphur mustard-induced cutaneous complications." }, { "docid": "MED-1801", "text": "OBJECTIVE: In 1976, the Royal College of Physicians and the British Cardiac Society recommended eating less fatty red meat and more poultry instead because it was lean. However, the situation has changed since that time, with a striking increase in fat content of the standard broiler chicken. The aim of the present study was to report a snapshot of data on fat in chickens now sold to the public. DESIGN: Samples were obtained randomly between 2004 and 2008 from UK supermarkets, farm shops and a football club. The amount of chicken fat was estimated by emulsification and chloroform/methanol extraction. SETTING: Food sold in supermarkets and farms in England. SUBJECTS: Chicken samples. RESULTS: The fat energy exceeded that of protein. There has been a loss of n-3 fatty acids. The n-6:n-3 ratio was found to be as high as 9:1, as opposed to the recommendation of about 2:1. Moreover, the TAG level in the meat and whole bird mostly exceeded the proportion of phospholipids, which should be the higher for muscle function. The n-3 fatty acid docosapentaenoic acid (DPA, 22 : 5n-3) was in excess of DHA (22 : 6n-3). Previous analyses had, as usual for birds, more DHA than DPA. CONCLUSIONS: Traditional poultry and eggs were one of the few land-based sources of long-chain n-3 fatty acids, especially DHA, which is synthesized from its parent precursor in the green food chain. In view of the obesity epidemic, chickens that provide several times the fat energy compared with protein seem illogical. This type of chicken husbandry needs to be reviewed with regard to its implications for animal welfare and human nutrition.", "title": "Modern organic and broiler chickens sold for human consumption provide more energy from fat than protein." }, { "docid": "MED-863", "text": "Durian may inflict severe body injury when it drops from the tree. This case report describes a patient who presented with facial and penetrating eye injury when a ripe durian fruit dropped onto her face while harvesting the fruits under the tree. The authors emphasized the importance of facial and eye protective devices during durian fruit harvesting season.", "title": "Penetrating ocular injury by durian fruit." }, { "docid": "MED-5216", "text": "Vitamin A deficiency (VAD) has been recognized as a public-health issue in developing countries. Economic constraints, sociocultural limitations, insufficient dietary intake, and poor absorption leading to depleted vitamin A stores in the body have been regarded as potential determinants of the prevalence of VAD in South Asian developing countries. VAD is exacerbated by lack of education, poor sanitation, absence of new legislation and enforcement of existing food laws, and week monitoring and surveillance system. Several recent estimates confirmed higher morbidly and mortality rate among children and pregnant and non-pregnant women of childbearing age. Xerophthalmia is the leading cause of preventable childhood blindness with its earliest manifestations as night blindness and Bitot's spots, followed by blinding keratomalacia, all of which are the ocular manifestations of VAD. Children need additional vitamin A because they do not consume enough in their normal diet. There are three general ways for improving vitamin A status: supplementation, fortification, and dietary diversification. These approaches have not solved the problem in South Asian countries to the desired extent because of poor governmental support and supervision of vitamin A supplementation twice a year. An extensive review of the extant literature was carried out, and the data under various sections were identified by using a computerized bibliographic search via PubMed, Web of Science, and Google Scholar. All abstracts and full-text articles were examined, and the most relevant articles were selected for screening and inclusion in this review. Conclusively, high prevalence of VAD in South Asian developing countries leads to increased morbidity and mortality among infants, children, and pregnant women. Therefore, stern efforts are needed to address this issue of public-health significance at local and international level in lower- and middle-income countries of South Asia.", "title": "Prevalence of Vitamin A Deficiency in South Asia: Causes, Outcomes, and Possible Remedies" }, { "docid": "MED-1233", "text": "BACKGROUND AND PURPOSE: Fiber intake is associated with reduced stroke risk in prospective studies, but no meta-analysis has been published to date. METHODS: Multiple electronic databases were searched for healthy participant studies reporting fiber intake and incidence of first hemorrhagic or ischemic stroke, published between January 1990 and May 2012. RESULTS: Eight cohort studies from the United States, northern Europe, Australia, and Japan met inclusion criteria. Total dietary fiber intake was inversely associated with risk of hemorrhagic plus ischemic stroke, with some evidence of heterogeneity between studies (I(2); relative risk per 7 g/day, 0.93; 95% confidence interval, 0.88-0.98; I(2)=59%). Soluble fiber intake, per 4 g/day, was not associated with stroke risk reduction with evidence of low heterogeneity between studies, relative risk 0.94 (95% confidence interval, 0.88-1.01; I(2)=21%). There were few studies reporting stroke risk in relation to insoluble fiber or fiber from cereals, fruit, or vegetables. CONCLUSIONS: Greater dietary fiber intake is significantly associated with lower risk of first stroke. Overall, findings support dietary recommendations to increase intake of total dietary fiber. However, a paucity of data on fiber from different foods precludes conclusions regarding the association between fiber type and stroke. There is a need for future studies to focus on fiber type and to examine risk for ischemic and hemorrhagic strokes separately.", "title": "Dietary fiber intake and risk of first stroke: a systematic review and meta-analysis." }, { "docid": "MED-2336", "text": "Accumulated evidence shows that some phytochemicals provide beneficial effects for human health. Recently, a number of mechanistic studies have revealed that direct interactions between phytochemicals and functional proteins play significant roles in exhibiting their bioactivities. However, their binding selectivities to biological molecules are considered to be lower due to their small and simple structures. In this study, we found that zerumbone, a bioactive sesquiterpene, binds to numerous proteins with little selectivity. Similar to heat-denatured proteins, zerumbone-modified proteins were recognized by heat shock protein 90, a constitutive molecular chaperone, leading to heat shock factor 1-dependent heat shock protein induction in hepa1c1c7 mouse hepatoma cells. Furthermore, oral administration of this phytochemical up-regulated heat shock protein expressions in the livers of Sprague-Dawley rats. Interestingly, pretreatment with zerumbone conferred a thermoresistant phenotype to hepa1c1c7 cells as well as to the nematode Caenorhabditis elegans. It is also important to note that several phytochemicals with higher hydrophobicity or electrophilicity, including phenethyl isothiocyanate and curcumin, markedly induced heat shock proteins, whereas most of the tested nutrients did not. These results suggest that non-specific protein modifications by xenobiotic phytochemicals cause mild proteostress, thereby inducing heat shock response and leading to potentiation of protein quality control systems. We considered these bioactivities to be xenohormesis, an adaptation mechanism against xenobiotic chemical stresses. Heat shock response by phytochemicals may be a fundamental mechanism underlying their various bioactivities.", "title": "Non-Specific Protein Modifications by a Phytochemical Induce Heat Shock Response for Self-Defense" }, { "docid": "MED-3845", "text": "We previously demonstrated that high serum enterolactone levels are associated with a reduced incidence of breast cancer in healthy women. The present study was aimed at investigating whether a similar association might be found between serum enterolactone levels and the mortality of women with early breast cancer. The levels of enterolactone in cryopreserved serum aliquots obtained from 300 patients, operated on for breast cancer, were measured using a time-resolved fluoro-immunoassay. Levels were analyzed in respect to the risk of mortality following surgery. Cox proportional hazard regression models were used to check for prognostic features, to estimate hazard ratios for group comparisons and to test for the interaction on mortality hazards between the variables and enterolactone concentrations. The Fine and Gray competing risk proportional hazard regression model was used to predict the probabilities of breast cancer-related and breast cancer-unrelated mortalities. At a median follow-up time of 23 years (range 0.6-26.1), 180 patients died, 112 of whom died due to breast cancer-related events. An association between a decreased mortality risk and enterolactone levels ≥ 10 nmol/l was found in respect to both all-cause and breast cancer-specific mortality. The difference in mortality hazards was statistically significant, but it appeared to decrease and to lose significance after the first 10 years, though competing risk analysis showed that breast cancer-related mortality risk remained constantly lower in those patients with higher enterolactone levels. Our findings are consistent with those of most recent literature and provide further evidence that mammalian lignans might play an important role in reducing all-cause and cancer-specific mortality of the patients operated on for breast cancer.", "title": "Serum enterolactone levels and mortality outcome in women with early breast cancer: a retrospective cohort study." }, { "docid": "MED-962", "text": "Context: Hypovitaminosis D appears to be on the rise in young children, with implications for skeletal and overall health. Objective: The objective of the study was to compare the safety and efficacy of vitamin D2 daily, vitamin D2 weekly, and vitamin D3 daily, combined with supplemental calcium, in raising serum 25-hydroxyvitamin D [25(OH)D] and lowering PTH concentrations. Design: This was a 6-wk randomized controlled trial. Setting: The study was conducted at an urban pediatric clinic in Boston. Subjects: Forty otherwise healthy infants and toddlers with hypovitaminosis D [25(OH)D < 20 ng/ml] participated in the study. Interventions: Participants were assigned to one of three regimens: 2,000 IU oral vitamin D2 daily, 50,000 IU vitamin D2 weekly, or 2,000 IU vitamin D3 daily. Each was also prescribed elemental calcium (50 mg/kg·d). Infants received treatment for 6 wk. Main Outcome Measures: Before and after treatment, serum measurements of 25(OH)D, PTH, calcium, and alkaline phosphatase were taken. Results: All treatments approximately tripled the 25(OH)D concentration. Preplanned comparisons were nonsignificant: daily vitamin D2 vs. weekly vitamin D2 (12% difference in effect, P = 0.66) and daily D2 vs. daily D3 (7%, P = 0.82). The mean serum calcium change was small and similar in the three groups. There was no significant difference in PTH suppression. Conclusions: Short-term vitamin D2 2,000 IU daily, vitamin D2 50,000 IU weekly, or vitamin D3 2,000 IU daily yield equivalent outcomes in the treatment of hypovitaminosis D among young children. Therefore, pediatric providers can individualize the treatment regimen for a given patient to ensure compliance, given that no difference in efficacy or safety was noted among these three common treatment regimens.", "title": "Treatment of Hypovitaminosis D in Infants and Toddlers" }, { "docid": "MED-2156", "text": "BACKGROUND: Coffee is associated with a reduced risk of hepatocellular carcinoma in patients with chronic C hepatitis. This prospective trial was aimed at assessing the mechanisms underlying coffee-related protective effects. METHODS: Forty patients with chronic hepatitis C were randomized into two groups: the first consumed 4 cups of coffee/day for 30 days, while the second remained coffee \"abstinent\". At day 30, the groups were switched over for a second month. RESULTS: At baseline, aspartate aminotransferase and alanine aminotransferase were lower in patients drinking 3-5 (Group B) than 0-2 cups/day (Group A) (56 ± 6 vs 74 ± 11/60 ± 3 vs 73 ± 7 U/L p=0.05/p=0.04, respectively). HCV-RNA levels were significantly higher in Group B [(6.2 ± 1.5) × 10(5)vs (3.9 ± 1.0) × 10(5)UI/mL, p=0.05]. During coffee intake, 8-hydroxydeoxyguanosine and collagen levels were significantly lower than during abstinence (15 ± 3 vs 44 ± 16 8-hydroxydeoxyguanosine/10(5)deoxyguanosine, p=0.05 and 56 ± 9 vs 86 ± 21 ng/mL, p=0.04). Telomere length was significantly higher in patients during coffee intake (0.68 ± 0.06 vs 0.48 ± 0.04 Arbitrary Units, p=0.006). Telomere length and 8-hydroxydeoxyguanosine were inversely correlated. CONCLUSION: In chronic hepatitis C coffee consumption induces a reduction in oxidative damage, correlated with increased telomere length and apoptosis, with lower collagen synthesis, factors that probably mediate the protection exerted by coffee with respect to disease progression. Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.", "title": "Effects of coffee consumption in chronic hepatitis C: a randomized controlled trial." }, { "docid": "MED-5120", "text": "Human gammadeltaT lymphocytes are a subset of T cells and are a first line of defense against microbes and tumors. These gammadeltaT cells can be primed by nitrogen-containing bisphosphonates, and certain short-chain alkylamines. These primed gammadeltaT cells have an enhanced capacity to proliferate and to secrete cytokines upon ex vivo exposure to a wide variety of microbes and tumor cells. The largest dietary source of alkylamines is L-theanine, an amino acid unique to tea beverages that is catabolized to ethylamine. Supplementation of subjects with capsules containing L-theanine and catechins has recently been shown to decrease the incidence of cold and flu symptoms, while enhancing gammadeltaT cell function.", "title": "L-theanine intervention enhances human gammadeltaT lymphocyte function." }, { "docid": "MED-991", "text": "Background Cognitive impairment without dementia is associated with increased risk for disability, increased health care costs, and progression to dementia. There are no population-based prevalence estimates of this condition in the United States. Objective To estimate the prevalence of cognitive impairment without dementia in the United States and determine longitudinal cognitive and mortality outcomes. Design Longitudinal study from July 2001 to March 2005. Setting In-home assessment for cognitive impairment. Participants Participants in ADAMS (Aging, Demographics, and Memory Study) who were age 71 years or older drawn from the nationally representative HRS (Health and Retirement Study). Of 1770 selected individuals, 856 completed initial assessment, and of 241 selected individuals, 180 completed 16- to 18-month follow-up assessment. Measurements Assessments, including neuropsychological testing, neurologic examination, and clinical and medical history, were used to assign a diagnosis of normal cognition, cognitive impairment without dementia, or dementia. National prevalence rates were estimated by using a population-weighted sample. Results In 2002, an estimated 5.4 million people (22.2%) in the United States age 71 years or older had cognitive impairment without dementia. Prominent subtypes included prodromal Alzheimer disease (8.2%) and cerebrovascular disease (5.7%). Among participants who completed follow-up assessments, 11.7% with cognitive impairment without dementia progressed to dementia annually, whereas those with subtypes of prodromal Alzheimer disease and stroke progressed at annual rates of 17% to 20%. The annual death rate was 8% among those with cognitive impairment without dementia and almost 15% among those with cognitive impairment due to medical conditions. Limitations Only 56% of the nondeceased target sample completed the initial assessment. Population sampling weights were derived to adjust for at least some of the potential bias due to nonresponse and attrition. Conclusion Cognitive impairment without dementia is more prevalent in the United States than dementia, and its subtypes vary in prevalence and outcomes.", "title": "Prevalence of Cognitive Impairment without Dementia in the United States" }, { "docid": "MED-3467", "text": "The effects of antioxidant diet supplements on blood lactate concentration and on the aerobic and anaerobic thresholds and their adaptations to training were analysed. Fifteen amateur male athletes were randomly assigned to either a placebo group or an antioxidant-supplemented group (90 days supplementation with 500 mg x day(-1) of vitamin E and 30 mg x day(-1) of beta-carotene, and the last 15 days also with 1 g x day(-1) of vitamin C). Before and after the antioxidant supplements, the sportsmen performed a maximal exercise test on a cycle ergometer and maximal and submaximal physiological parameters were assessed together with blood lactate concentration. Maximal oxygen uptake (VO(2max)), maximal blood lactate concentration, and the maximal workload attained rose significantly in both groups after the 3 months of training. At the end of the study, maximal blood lactate concentration was lower in the group that took supplements than in the placebo group. The percentage of VO(2max) attained at the anaerobic threshold rose significantly in both groups after 3 months of training, although the final value in the supplemented group was higher than that in the placebo group. Antioxidant diet supplements induced lower increases in blood lactate concentration after a maximal exercise test and could improve the efficiency in which aerobic energy is obtained.", "title": "Antioxidant diet supplementation enhances aerobic performance in amateur sportsmen." } ]
128186
Down syndrome is a genetic mutation.
[ { "docid": "Down_syndrome", "text": "Down syndrome ( DS or DNS ) , also known as trisomy 21 , is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21 . It is typically associated with physical growth delays , characteristic facial features and mild to moderate intellectual disability . The average IQ of a young adult with Down syndrome is 50 , equivalent to the mental ability of an 8 - or 9-year-old child , but this can vary widely . The parents of the affected individual are typically genetically normal . The extra chromosome occurs by chance . The possibility increases from less than 0.1 % in 20-year-old mothers to 3 % in those age 45 . There is no known behavioral activity or environmental factor that changes the possibility . Down syndrome can be identified during pregnancy by prenatal screening followed by diagnostic testing or after birth by direct observation and genetic testing . Since the introduction of screening , pregnancies with the diagnosis are often terminated . Regular screening for health problems common in Down syndrome is recommended throughout the person 's life . There is no cure for Down syndrome . Education and proper care have been shown to improve quality of life . Some children with Down syndrome are educated in typical school classes , while others require more specialized education . Some individuals with Down syndrome graduate from high school and a few attend post-secondary education . In adulthood , about 20 % in the United States do paid work in some capacity with many requiring a sheltered work environment . Support in financial and legal matters is often needed . Life expectancy is around 50 to 60 years in the developed world with proper health care . Down syndrome is one of the most common chromosome abnormalities in humans . It occurs in about one per 1000 babies born each year . In 2015 , Down syndrome was present in 5.4 million individuals and resulted in 27,000 deaths down from 43,000 deaths in 1990 . It is named after John Langdon Down , the British doctor who fully described the syndrome in 1866 . Some aspects of the condition were described earlier by Jean-Étienne Dominique Esquirol in 1838 and Édouard Séguin in 1844 . In 1957 , the genetic cause of Down syndrome , an extra copy of chromosome 21 , was discovered .", "title": "" } ]
[ { "docid": "De_Barsy_syndrome", "text": "De Barsy syndrome is a rare autosomal recessive genetic disorder . Symptoms include cutis laxa ( loose hanging skin ) as well as other eye , musculoskeletal , and neurological abnormalities . It is usually progressive , manifesting side effects that can include clouded corneas , cataracts , short stature , dystonia , or progeria ( premature aging ) . It was first described in 1967 by De Barsy et al. and , as of 2011 , there have been 27 cases reported worldwide . The genes that cause De Barsy syndrome have not been identified yet , although several studies have narrowed down the symptoms ' cause . A study by Reversade et al. has shown that a mutation in PYCR1 , the genetic sequence that codes for mitochondrial enzymes that break down proline , are prevalent in cases of autosomal recessive cutis laxa ( ARCL ) , a condition very similar to De Barsy syndrome . A study by Leao-Teles et al. has shown that De Barsy syndrome may be related to mutations in ATP6V0A2 gene , known as ATP6V0A2-CDG by the new naming system . Alternative names for De Barsy syndrome include corneal clouding-cutis laxa-mental retardation , cutis laxa-growth deficiency syndrome , De Barsy -- Moens -- Diercks syndrome , and progeroid syndrome of De Barsy .", "title": "" }, { "docid": "Bohring–Opitz_syndrome", "text": "Bohring -- Opitz syndrome ( BOS ) is a medical syndrome characterised by characteristic craniofacial appearance , fixed contractures of the upper limbs , abnormal posture , feeding difficulties , intellectual disability , small size at birth , and failure to thrive . Some of these features are shared with other genetic syndromes . Genetically , de novo truncating mutations in ASXL1 have been shown to account for approximately 50 % of Bohring -- Opitz syndrome cases . Bohring-Opitz Syndrome is an extremely rare genetic syndrome . There are fewer than 60 cases in the world . This syndrome is diagnosed by genetic testing and is a mutation in the ASXL1 gene . The leading cause of death is respiratory infections . Children with BOS can have feeding difficulties , recurring respiratory infections , sleep apnea , developmental delay , failure to thrive , abnormal hair density and length , Wilm 's Tumors , brain abnormalities , silent aspiration , and the list goes on . To find out more about Bohring-Opitz Syndrome please visit Bohring-Opitz Syndrome Foundation.Inc , and Bohring-Opitz Syndrome Support . Bohring -- Opitz syndrome is sometimes also called Oberklaid -- Danks syndrome .", "title": "" }, { "docid": "RECQL4", "text": "ATP-dependent DNA helicase Q4 is an enzyme that in humans is encoded by the RECQL4 gene . Mutations in RECQL4 are associated with the autosomal recessive disease Rothmund-Thomson Syndrome , a disorder that has features of premature aging . In addition to the Rothmund-Thomson syndrome , RECQL4 mutations are also associated with RAPADILINO and Baller-Gerold syndromes . There are two types of Rothmund Thomson syndrome and it is Type 2 that occurs in patients carrying deleterious mutations in both copies of the RECQL4 gene . This condition is associated with a high risk of developing osteosarcoma ( malignant tumor of the bone ) . RECQL4 gets it name from being homologous ( sharing sequence ) with other members of the RecQ helicase family . Two other genetic diseases are due to mutations in other RECQ helicases . Bloom syndrome is associated with mutations in the BLM gene and Werner syndrome is associated with mutations in the WRN gene .", "title": "" }, { "docid": "Usher_syndrome", "text": "Usher syndrome , also known as Hallgren syndrome , Usher-Hallgren syndrome , retinitis pigmentosa-dysacusis syndrome , or dystrophia retinae dysacusis syndrome , is an extremely rare genetic disorder caused by a mutation in any one of at least 11 genes resulting in a combination of hearing loss and visual impairment . It is a leading cause of deafblindness and is at present incurable . Usher syndrome is classed into three subtypes according to onset and severity of symptoms . All three subtypes are caused by mutations in genes involved in the function of the inner ear and retina . These mutations are inherited in an autosomal recessive pattern .", "title": "" }, { "docid": "Cancer_syndrome", "text": "A cancer syndrome or family cancer syndrome is a genetic disorder in which inherited genetic mutations in one or more genes predispose the affected individuals to the development of cancers and may also cause the early onset of these cancers . Cancer syndromes often show not only a high lifetime risk of developing cancer , but also the development of multiple independent primary tumors . Many of these syndromes are caused by mutations in tumor suppressor genes , genes that are involved in protecting the cell from turning cancerous . Other genes that may be affected are DNA repair genes , oncogenes and genes involved in the production of blood vessels ( angiogenesis ) . Common examples of inherited cancer syndromes are hereditary breast-ovarian cancer syndrome and hereditary non-polyposis colon cancer ( Lynch syndrome ) .", "title": "" }, { "docid": "Roberts_syndrome", "text": "Roberts syndrome , or sometimes called pseudothalidomide syndrome , is an extremely rare genetic disorder that is characterized by mild to severe prenatal retardation or disruption of cell division , leading to malformation of the bones in the skull , face , arms , and legs . Roberts syndrome is also known by many other names , including : Hypomelia-Hypotrichosis-Facial Hemangioma Syndrome , SC Syndrome ( once thought to be an entirely separate disease ) , Pseudothalidomide Syndrome , Roberts-SC Phocomelia Syndrome , SC Phocomelia Syndrome , Appelt-Gerken-Lenz Syndrome , RBS , SC Pseudothalidomide Syndrome , and Tetraphocomelia-Cleft Palate Syndrome . It is a genetic disorder caused by the mutation of the ESCO2 gene on 8th chromosome . Named after John B. Roberts , who first described the syndrome in 1919 , it is one of the rarest autosomal recessive disorders , affecting approximately 150 known individuals . The Syndrome is both autosomal , in that there are equal numbers of copies of the gene in both males and females , and recessive , meaning the child must inherit the defective gene from both parents . The mutation causes cell division to occur slowly or unevenly , and the cells with abnormal genetic content die . Roberts syndrome can affect both males and females . Although the disorder is rare , the affected group is diverse . The mortality rate is high in severely affected individuals .", "title": "" }, { "docid": "Alström_syndrome", "text": "Alström syndrome , also called Alstrom-Halgren Syndrome , is a rare genetic disorder caused by mutations in the gene ALMS1 . It is among the rarest genetic disorders in the world , as currently it has only 266 reported cases in medical literature and over 501 known cases in 47 countries . It was first described by Carl-Henry Alström in Sweden in 1959 . Alstrom syndrome is sometimes confused with Bardet-Biedl syndrome , which has similar symptoms . Bardet-Biedl syndrome tends to have later onset in its symptoms . The likelihood of two carrier parents both passing the gene and therefore having a child affected by the syndrome is 25 % with each pregnancy . The likelihood of having a child who is only a carrier of the gene is 50 % with each pregnancy . The likelihood of a child receiving normal genes from both parents and being considered to be `` genetically '' normal is 25 % . The risk for carrying the gene is equivalent for both males and females . `` Alström syndrome ( AS ) is a rare autosomal recessive disease characterized by multiorgan dysfunction . The key features are childhood obesity , blindness due to congenital retinal dystrophy , and sensorineural hearing loss . Associated endocrinologic features include hyperinsulinemia , early-onset type 2 diabetes , and hypertriglyceridemia . '' Thus , AS shares several features with the common metabolic syndrome , namely obesity , hyperinsulinemia , and hypertriglyceridemia . Mutations in the ALMS1 gene have been found to be causative for AS with a total of 79 disease-causing mutations having been described . '' Prevalence estimates have ranged from 1 in 10,000 to fewer than 1 in 1,000,000 individuals in the general population .", "title": "" }, { "docid": "Epilepsy_syndromes", "text": "Cases of epilepsy may be organized into epilepsy syndromes by the specific features that are present . These features include the age at which seizures begin , the seizure types , and EEG findings , among others . Identifying an epilepsy syndrome is useful as it helps determine the underlying causes as well as what anti-seizure medication should be tried . The ability to categorize a case of epilepsy into a specific syndrome occurs more often with children since the onset of seizures is commonly early . Less serious examples are benign rolandic epilepsy ( 2.8 per 100,000 ) , childhood absence epilepsy ( 0.8 per 100,000 ) and juvenile myoclonic epilepsy ( 0.7 per 100,000 ) . Severe syndromes with diffuse brain dysfunction caused , at least partly , by some aspect of epilepsy , are also referred to as epileptic encephalopathies . These are associated with frequent seizures that are resistant to treatment and severe cognitive dysfunction , for instance Lennox-Gastaut syndrome and West syndrome . Epilepsies with onset in childhood are a complex group of diseases with a variety of causes and characteristics . Some people have no obvious underlying neurological problems or metabolic disturbances . They may be associated with variable degrees of intellectual disability , elements of autism , other mental disorders , and motor difficulties . Others have underlying inherited metabolic diseases , chromosomal abnormalities , specific eye , skin and nervous system features , or malformations of cortical development . Some of these epilepsies can be categorized into the traditional epilepsy syndromes . Furthermore , a variety of clinical syndromes exist of which the main feature is not epilepsy but which are associated with a higher risk of epilepsy . For instance between 1 and 10 % of those with Down syndrome and 90 % of those with Angelman syndrome have epilepsy . In general , genetics is believed to play an important role in epilepsies by a number of mechanisms . Simple and complex modes of inheritance have been identified for some of them . However , extensive screening has failed to identify many single rare gene variants of large effect . In the epileptic encephalopathies , de novo mutagenesis appear to be an important mechanism . De novo means that a child is affected , but the parents do not have the mutation . De novo mutations occur in eggs and sperms or at a very early stage of embryonic development . In Dravet syndrome a single affected gene was identified . Syndromes in which causes are not clearly identified are difficult to match with categories of the current classification of epilepsy . Categorization for these cases is made somewhat arbitrarily . The idiopathic ( unknown cause ) category of the 2011 classification includes syndromes in which the general clinical features and/or age specificity strongly point to a presumed genetic cause . Some childhood epilepsy syndromes are included in the unknown cause category in which the cause is presumed genetic , for instance benign rolandic epilepsy . Others are included in symptomatic despite a presumed genetic cause ( in at least in some cases ) , for instance Lennox-Gastaut syndrome . Clinical syndromes in which epilepsy is not the main feature ( e.g. Angelman syndrome ) were categorized symptomatic but it was argued to include these within the category idiopathic . Classification of epilepsies and particularly of epilepsy syndromes will change with advances in research .", "title": "" }, { "docid": "Malpuech_facial_clefting_syndrome", "text": "Malpuech facial clefting syndrome , also called Malpuech syndrome or Gypsy type facial clefting syndrome , is a rare congenital syndrome . It is characterized by facial clefting ( any type of cleft in the bones and tissues of the face , including a cleft lip and palate ) , a caudal appendage ( a `` human tail '' ) , growth deficiency , intellectual and developmental disability , and abnormalities of the renal system ( kidneys ) and the male genitalia . Abnormalities of the heart , and other skeletal malformations may also be present . The syndrome was initially described by Guilliaume Malpuech and associates in 1983 . It is thought to be genetically related to Juberg-Hayward syndrome . Malpuech syndrome has also been considered as part of a spectrum of congenital genetic disorders associated with similar facial , urogenital and skeletal anomalies . Termed `` 3MC syndrome '' , this proposed spectrum includes Malpuech , Michels and Mingarelli-Carnevale ( OSA ) syndromes . Mutations in the COLLEC11 and MASP1 genes are believed to be a cause of these syndromes . The incidence of Malpuech syndrome is unknown . The pattern of inheritance is autosomal recessive , which means a defective ( mutated ) gene associated with the syndrome is located on an autosome , and the syndrome occurs when two copies of this defective gene are inherited .", "title": "" }, { "docid": "Loeys–Dietz_syndrome", "text": "Loeys -- Dietz syndrome ( LDS ) is an autosomal dominant genetic connective tissue disorder . The disorder is marked by aneurysms in the aorta , often in children . The aorta may also undergo sudden dissection in the weakened layers of the wall of aorta . Aneurysms and dissections also can occur in arteries other than the aorta . Because aneurysms in children tend to rupture early , children are at greater risk for dying if the syndrome is not identified . Surgery to repair aortic aneurysms is essential for treatment . There are four types of the syndrome , labelled types I through IV , which are distinguished by their genetic cause . Type 1 , Type 2 , Type 3 , and Type 4 are caused by mutations in TGFBR1 , TGFBR2 , SMAD3 , and TGFB2 respectively . These four genes encoding transforming growth factors play a role in cell signaling that promotes growth and development of the body 's tissues . Mutations of these genes cause production of proteins without function . Although the disorder has an autosomal pattern of inheritance , this disorder results from a new gene mutation in 75 % of cases and occurs in people with no history of the disorder in their family . It has features similar to Marfan syndrome and Ehlers-Danlos syndrome . It was identified and characterized by pediatric geneticists Bart Loeys and Harry Dietz at Johns Hopkins University in 2005 .", "title": "" }, { "docid": "Heritability_of_autism", "text": "The heritability of autism is the proportion of differences in expression of autism that can be explained by genetic variation ; if the heritability of a condition is high , then the condition is considered to be primarily genetic . Autism has a strong genetic basis , although the genetics of autism is complex and it is unclear whether autism spectrum disorder ( ASD ) is explained more by multigene interactions or by rare mutations with major effects . Early studies of twins estimated the heritability of autism to be more than 90 % -- meaning that 90 % of the differences between autistic and non-autistic individuals was due to genetics . This may be an overestimate : new twin data and models with structural genetic variation are needed . When only one identical twin is autistic , the other often has learning or social disabilities . For adult siblings , the risk of having one or more features of the broader autism phenotype might be as high as 30 % , much higher than the risk in controls . Genetic linkage analysis has been inconclusive ; many association analyses have had inadequate power . For each autistic individual , mutations in more than one gene may be implicated . Mutations in different sets of genes may be involved in different autistic individuals . There may be significant interactions among mutations in several genes , or between the environment and mutated genes . By identifying genetic markers inherited with autism in family studies , numerous candidate genes have been located , most of which encode proteins involved in neural development and function . However , for most of the candidate genes , the actual mutations that increase the risk for autism have not been identified . Typically , autism can not be traced to a Mendelian ( single-gene ) mutation or to single chromosome abnormalities such as fragile X syndrome or 22q13 deletion syndrome . The large number of autistic individuals with unaffected family members may result from copy number variations ( CNVs ) -- spontaneous alterations in the genetic material during meiosis that delete or duplicate genetic material . Sporadic ( non-inherited ) cases have been examined to identify candidate genetic loci involved in autism . A substantial fraction of autism may be highly heritable but not inherited : that is , the mutation that causes the autism is not present in the parental genome . Although the fraction of autism traceable to a genetic cause may grow to 30 -- 40 % as the resolution of array CGH improves , several results in this area have been described incautiously , possibly misleading the public into thinking that a large proportion of autism is caused by CNVs and is detectable via array CGH , or that detecting CNVs is tantamount to a genetic diagnosis . The Autism Genome Project database contains genetic linkage and CNV data that connect autism to genetic loci and suggest that every human chromosome may be involved . It may be that using autism-related subphenotypes instead of the diagnosis of autism per se may be more useful in identifying susceptible loci .", "title": "" }, { "docid": "Nasodigitoacoustic_syndrome", "text": "Nasodigitoacoustic syndrome , also called Keipert syndrome , is a rare congenital syndrome first described by J.A. Keipert and colleagues in 1973 . The syndrome is characterized by a mishaped nose , broad thumbs and halluces ( the big toes ) , brachydactyly , sensorineural hearing loss , facial features such as hypertelorism ( unusually wide-set eyes ) , and developmental delay . It is believed to be inherited in an X-linked recessive manner , which means a genetic mutation causing the disorder is located on the X chromosome , and while two copies of the mutated gene must be inherited for a female to be born with the disorder , just one copy is sufficient to cause a male to be born with the disorder . Nasodigitoacoustic syndrome is likely caused by a mutated gene located on the X chromosome between positions Xq22 .2 -- q28 . The incidence of the syndrome has not been determined , but it is considered to affect less than 200,000 people in the United States , and no greater than 1 per 2,000 in Europe . It is similar to Keutel , Muenke , Rubinstein and Teunissen-Cremers syndrome .", "title": "" }, { "docid": "Crouzon_syndrome", "text": "Crouzon syndrome is an autosomal dominant genetic disorder known as a branchial arch syndrome . Specifically , this syndrome affects the first branchial ( or pharyngeal ) arch , which is the precursor of the maxilla and mandible . Since the branchial arches are important developmental features in a growing embryo , disturbances in their development create lasting and widespread effects . This syndrome is named after Octave Crouzon , a French physician who first described this disorder . He noted the affected patients were a mother and her daughter , implying a genetic basis . First called `` craniofacial dysostosis '' , the disorder was characterized by a number of clinical features . This syndrome is caused by a mutation in the fibroblast growth factor receptor II , located on chromosome 10 . Breaking down the name , `` craniofacial '' refers to the skull and face , and `` dysostosis '' refers to malformation of bone . Now known as Crouzon syndrome , the characteristics can be described by the rudimentary meanings of its former name . What occurs is that an infant 's skull and facial bones , while in development , fuse early or are unable to expand . Thus , normal bone growth can not occur . Fusion of different sutures leads to different patterns of growth of the skull . Examples include : trigonocephaly ( fusion of the metopic suture ) , brachycephaly ( fusion of the coronal suture ) , dolichocephaly ( fusion of the sagittal suture ) , plagiocephaly ( unilateral premature closure of lambdoid and coronal sutures ) , oxycephaly ( fusion of coronal and lambdoidal sutures ) , Kleeblattschaedel ( premature closure of all sutures ) .", "title": "" }, { "docid": "Gitelman_syndrome", "text": "Gitelman syndrome is an autosomal recessive kidney disorder characterized by low blood levels of potassium and magnesium , decreased excretion of calcium in the urine , and elevated blood pH. The disorder is caused by loss of function mutations of the thiazide-sensitive sodium-chloride symporter ( also known as NCC , NCCT , or TSC ) located in the distal convoluted tubule of the kidney . Gitelman syndrome was formerly considered a subset of Bartter syndrome until the distinct genetic and molecular bases of these disorders were identified . Bartter syndrome is also an autosomal recessive hypokalemic metabolic alkalosis , but it derives from a mutation to the NKCC2 found in the thick ascending limb of the loop of Henle .", "title": "" }, { "docid": "Floating–Harbor_syndrome", "text": "Floating -- Harbor syndrome , also known as Pelletier -- Leisti syndrome , is a rare disease with fewer than 50 cases described in the literature . It is usually diagnosed in early childhood and is characterized by the triad of proportionate short stature with delayed bone age , characteristic facial appearance , and delayed speech development . Although its cause is unknown , it is thought to result from genetic mutation , and diagnosis is established by the presence of a heterozygous SRCAP mutation in those with clinical findings of FHS .", "title": "" }, { "docid": "Rett_syndrome", "text": "Rett syndrome ( RTT ) is a rare genetic postnatal neurological disorder of the grey matter of the brain that almost exclusively affects females but has also been found in male patients . The clinical features include small hands and feet and a deceleration of the rate of head growth ( including microcephaly in some ) . Repetitive stereotyped hand movements , such as wringing and/or repeatedly putting hands into the mouth , are also noted . People with Rett syndrome are prone to gastrointestinal disorders and up to 80 % have seizures . They typically have no verbal skills , and about 50 % of affected individuals do not walk . Scoliosis , growth failure , and constipation are very common and can be problematic . The signs of this disorder are most easily confused with those of Angelman syndrome , cerebral palsy and autism . Rett syndrome occurs in approximately 1:10,000 live female births in all geographies , and across all ethnicities . The syndrome was first described by Austrian neurologist Andreas Rett in 1966 . While the disorder was identified scientifically , and could be reliably diagnosed , the causes remained unknown for decades . Huda Zoghbi demonstrated in 1999 that mutations in the gene MECP2 cause Rett syndrome . Prior to the discovery of a genetic cause , Rett syndrome had been arbitrarily designated as a pervasive developmental disorder by the Diagnostic and Statistical Manual of Mental Disorders ( DSM ) , together with the autism spectrum disorders . Some argued against this conclusive assignment because RTT resembles non-autistic disorders such as fragile X syndrome , tuberous sclerosis , or Down syndrome that exhibit autistic features coincidentally . After research proved the molecular mechanism , in 2013 the DSM-5 removed the syndrome altogether from classification as a mental disorder .", "title": "" }, { "docid": "Miller_syndrome", "text": "Miller syndrome is a genetic condition also known as the Genee -- Wiedemann syndrome , Wildervanck -- Smith syndrome , or postaxial acrofacial dystosis . The incidence of this condition is not known , but it is considered extremely rare . It is due to a mutation in the DHODH gene . Nothing is known of its pathogenesis .", "title": "" }, { "docid": "Progeroid_syndromes", "text": "Progeroid syndromes ( PS ) are a group of rare genetic disorders which mimic physiological aging , making affected individuals appear to be older than they are . The term progeroid syndrome does not necessarily imply progeria ( Hutchinson -- Gilford progeria syndrome ) , which is a specific type of progeroid syndrome . Progeroid means `` resembling premature aging '' , a definition that can apply to a broad range of diseases . Familial Alzheimer 's disease and familial Parkinson 's disease are two well-known accelerated-aging diseases that are more frequent in older individuals . They affect only one tissue and can be classified as unimodal progeroid syndromes . Segmental progeria , which is more frequently associated with the term progeroid syndrome , tends to affect multiple or all tissues while causing affected individuals to exhibit only some of the features associated with aging . All disorders within this group are thought to be monogenic , meaning they arise from mutations of a single gene . Most known PS are due to genetic mutations that lead to either defects in the DNA repair mechanism or defects in lamin A/C . Examples of PS include Werner syndrome ( WS ) , Bloom syndrome ( BS ) , Rothmund -- Thomson syndrome ( RTS ) , Cockayne syndrome ( CS ) , xeroderma pigmentosum ( XP ) , trichothiodystrophy ( TTD ) , combined xeroderma pigmentosum-Cockayne syndrome ( XP-CS ) , restrictive dermopathy ( RD ) , and Hutchinson -- Gilford progeria syndrome ( HGPS ) . Individuals with these disorders tend to have a reduced lifespan . Progeroid syndromes have been widely studied in the fields of aging , regeneration , stem cells , and cancer . The most widely studied of the progeroid syndromes are Werner syndrome and Hutchinson -- Gilford progeria , as they are seen to most resemble natural aging .", "title": "" }, { "docid": "Neonatal_onset_multisystem_inflammatory_disease", "text": "Neonatal onset multisystem inflammatory disease ( abbreviated NOMID , also known as chronic infantile neurologic cutaneous and articular syndrome , or CINCA ) is a rare genetic periodic fever syndrome which causes uncontrolled inflammation in multiple parts of the body starting in the newborn period . Symptoms include skin rashes , severe arthritis , and chronic meningitis leading to neurologic damage . It is one of the cryopyrin-associated periodic syndromes . NOMID can result from a mutation in the CIAS1 gene ( also known as NLRP3 gene ) , which helps control inflammation . Mutations in this gene also cause familial cold urticaria and Muckle -- Wells syndrome . NOMID has been successfully treated with the drug anakinra . This syndrome is also known as the Prieur -- Griscelli syndrome as it was first described by these authors in 1981 .", "title": "" }, { "docid": "Hydrolethalus_syndrome", "text": "Hydrolethalus syndrome ( less commonly referred to as Salonen-Herva-Norio syndrome ) is a rare genetic disorder that causes improper fetal development , resulting in birth defects and often stillbirth . It is associated with HYLS1 mutations .", "title": "" }, { "docid": "Congenital_chloride_diarrhea", "text": "Congenital chloride diarrhea ( CCD , also congenital chloridorrhea or Darrow Gamble syndrome ) is a genetic disorder due to an autosomal recessive mutation on chromosome 7 . The mutation is in downregulated-in-adenoma ( DRA ) , a gene that encodes a membrane protein of intestinal cells . The protein belongs to the solute carrier 26 family of membrane transport proteins . More than 20 mutations in the gene are known to date . A rare disease , CCD occurs in all parts of the world but is more common in some populations with genetic founder effects , most notably in Finland .", "title": "" }, { "docid": "Dnyandeo_Chopade", "text": "Dr. Dnyandeo Kisan Chopade is the founder president of Down 's Syndrome Care Association , India , which is a Non-Profit organization working for improving the quality of lives of people affected with Down 's syndrome . His leadership and tireless efforts in this filed for the past 13 years made him a well-known figure around the world especially for his contribution in the overall empowerment of people affected by Down 's Syndrome . He was born in a small village in Buldhana district in the state of Maharashtra in a poor family on 16 January 1967 to the farm labour parents . He self-supported his early education from the age of 10 . He did his medical graduation ( MBBS ) in 1990 , and post-graduation in Human Anatomy in 1995 from the reputed Government Medical College and Hospital , Nagpur . After doing job in various capacities as lecturer and Associate Professor in various Government medical colleges in India , between 1996 to 2002 , he started his medical practice as a medical geneticist at Nashik in the year 2003 . During this period he got trained in various aspects of medical genetics from number of reputed institutions like Saint John 's Medical College and Hospital , Bangalore ; Genetic department of Institute of Medical and Veterinary Sciences ( IMVS ) Adelaide , Australia and Grant Medical College , Mumbai . He has provided genetic health care services to thousands of patients suffering from the most neglected genetic diseases in India . His observation that people suffer mainly because of ignorance of the various genetic conditions made me start the ` Down 's Syndrome Care Association ' , India in the year 2006 . He was touched and moved by the suffering of the children born with the multidisabilty condition of Down 's Syndrome caused by the extra genetic material on chromosome 21 ( trisomy 21 ) . This led him to create the first parents support group of individuals with Down 's syndrome in the year 2006 . Since then , with the likeminded people , he has been providing support to the affected through various activities like free genetic counseling , parent empowerment programs , various therapies to the affected , health check-ups and special education at the Downs syndrome Activity Centre in Nashik . Currently , he is extending various services to the 600 families with a child having Down 's Syndrome . He is providing free genetic counseling to the parents in his clinic once a week ; running a free daily activity centre with all the therapies and special education ; celebrating World Down 's Days every year on 21 March since 2007 ; conducting free health check-up camps for Down 's Syndrome ; delivering public talk at various places , on radio and television and writing articles in various newspapers for public awareness ; creating self-sufficient parent support groups in various cities in Maharashtra , arranging the special exhibitions on Down 's Syndrome , `` Akashi Zep Ghe Re Pakhara '' . He has been associated with the Down 's Syndrome International ; Asia Pacific Down 's Syndrome Federation and Down 's Syndrome Federation of India for integrating the services at national and international levels . He has also written a book for parents , named Agantuk 21 , for effectively dealing with the condition in local language Marathi , which is in the process of publication . Inspired with the mission of empowering and enabling the individuals with Down 's Syndrome and their families , his future pan is to establish a national Down 's Syndrome Institute at Nashik , where all the facilities for dealing with the Down 's Syndrome issues at national level would be made available like preventing birth of the babies with Down 's Syndrome , counseling the prospective parents , health care , therapies , parent empowerment , special training for teachers , rehabilitation and research . He has also established a unique , state of the art museum , ` Museum Kohum ' at Nashik for creating public awareness about health in general and Down 's Syndrome with other genetic disorders in particular . School and college students and general public is getting highly benefitted through this museum . He has organized one national symposium for parents ' empowerment in Nashik in January 2014 and remained faculty at mainly national and international conferences , workshops and meetings . His work has been recognized through number of local , state and national awards . Important Awards Received : He has received a ` National Positive Health Hero Award ' in 2010 ; the prestigious ` Dr. Suresh Nadkarni Award ' by Maharashtra Indian Medical Association in 2011 , ` Dr. Vasantrao Gupte Award ' by Nashik Indian Medical Association , 2012 ; ` Social Service Award ' by the Rotary Club , 3030 , Nashik in 2013 and ` Purushsinh Award ' by the Lions Club in 2016 .", "title": "" }, { "docid": "22q13_deletion_syndrome", "text": "22q13 deletion syndrome ( spoken as twenty-two q one three , see Locus ( genetics ) ) is a genetic disorder caused by deletions or rearrangements on the q terminal end ( long arm ) of chromosome 22 . Any abnormal genetic variation in the q13 region that presents with significant manifestations ( phenotype ) typical of a terminal deletion may be diagnosed as 22q13 deletion syndrome . 22q13 deletion syndrome is often called Phelan-McDermid syndrome ( abbreviated PMS ) . There is disagreement among researchers as to the exact definition of 22q13 deletion syndrome . The Developmental Synaptopathies Consortium defines PMS as being caused by SHANK3 mutations , a definition that appears to exclude terminal deletions . The requirement to include SHANK3 in the definition is supported by many , but not by those who first described 22q13 deletion syndrome . A prototypical terminal deletion of 22q13 can be uncovered by karyotype analysis , but many terminal and interstitial deletions are too small . The availability of DNA microarray technology for revealing multiple genetic problems simultaneously has been the diagnostic tool of choice . The falling cost for whole exome sequencing and , eventually , whole genome sequencing , may replace DNA microarray technology for candidate evaluation . However , fluorescence in situ hybridization ( FISH ) tests remain valuable for diagnosing cases of mosaicism ( mosaic genetics ) and chromosomal rearrangements ( e.g. , ring chromosome , unbalanced chromosomal translocation ) . Although early researchers sought a monogenic ( single gene genetic disorder ) explanation , recent studies have not supported that hypothesis ( see Etiology , below ) .", "title": "" }, { "docid": "HUPRA_syndrome", "text": "HUPRA syndrome is a rare syndrome that was first described in 2010 in two infants of Palestinian origin from the same village in the Jerusalem area . One of the two infants ' parents were related . It was later described in a third infant from the same village , whose parents were not related . The acronym stands for Hyperuricemia , Pulmonary hypertension , Renal failure in infancy and Alkalosis . And it 's due to mutations in the mitochondrial SARS enzyme . It 's an autosomal recessive disease , that has a prevalence of less than one in a million . One in fifteen of the village 's inhabitants were found to carry the genetic mutation .", "title": "" }, { "docid": "Neuro-cardio-facial-cutaneous_syndromes", "text": "Neuro-cardio-facial-cutaneous-syndromes ( NCFC ) , ( also referred to as neuro-craniofacial-cardiac syndromes ) is a group of developmental disorders with a genetic ground , affecting the nervous system , circulatory system , ( cranio ) facial and cutaneous development . These four parts are the common denominator for the syndromes , but are mostly accompanied by disturbances in other parts of the body . The two most common syndromes under this `` umbrella '' are : Leopard syndrome ( LS ) and Noonan syndrome ( NS ) . Other members are Costello syndrome ( CS ) , cardio-facio-cutaneous syndrome ( CFC ) and Neurofibromatosis type I ( NF1 ) . Recently , it has been observed that NCFC syndromes result from de novo germline mutations that alter the Ras/Raf/Mek signal transduction pathway . These are called RASopathies . 1 percent of autistic children have either a loss or duplication in a region of Chromosome 16 that encompasses the gene for ERK 1 . Mutations within the ERK signal transduction pathway appears to be a common cause for NCFC syndromes . Some autistic children also have craniofacial and cardiac defects .", "title": "" }, { "docid": "Inherited_disorders_of_trafficking", "text": "Inherited disorders of trafficking ( IDT ) are a family of disorders that involve vesicular delivery of proteins . They were characterized in 1975 . CEDNIK Syndrome CEDNIK syndrome ( Cerebral Dysgenesis , Neuropathy , Ichthyosis and Keratoderma Syndrome ) is a rare inherited genetic skin condition ( Genodermatosis ) which has been associated with a loss-of-function mutation in SNAP29 ; SNAP29 is a member of the SNAP Receptor ( SNARE ) protein family . SNARE proteins assist with vesicle trafficking and are responsible for the fusion events between the membranes of vesicles and the membranes of their targets . There are two types of SNARE proteins , v-SNARE 's which are located on vesicle membranes , and t-SNARE 's that are located on target membranes . SNAP29 is a t-SNARE , and as a t-SNARE , this protein must form a complex with v-SNARE 's for fusion of vesicles and secretion of their load to occur . A mutation/deficiency in this protein which occurs in patients with CEDNIK syndrome results in an impaired maturation and secretion of lamellar granules -- these are vesicular structures derived from the Golgi . SNAP29 is necessary for proper epidermal differentiation . Mutations in SNAP29 result in problems with molecular trafficking and transport , and leads to CEDNIK syndrome .", "title": "" }, { "docid": "Angelman_syndrome", "text": "Angelman syndrome ( AS ) is a genetic disorder that mainly affects the nervous system . Symptoms include a small head and a specific facial appearance , severe intellectual disability , developmental disability , speech problems , balance and movement problems , seizures , and sleep problems . Children are usually happy in nature and have a particular interest in water . The symptoms generally become noticeable by a year of age . Angelman syndrome is typically due to a new mutation rather than one inherited from a person 's parents . Angelman syndrome is due to a lack of function of part of chromosome 15 inherited from a person 's mother . Most of the time , it is due to a deletion or mutation of the UBE3A gene on that chromosome . Occasionally , it is due to inheriting two copies of chromosome 15 from a person 's father and none from their mother . As the father 's versions are inactivated by a process known as genomic imprinting , no functional version of the gene remains . Diagnosis is based on symptoms and possibly genetic testing . No cure is available . Treatment is generally supportive in nature . Anti-seizure medications are used in those with seizures . Physical therapy and bracing may help with walking . Those affected have a nearly normal life expectancy . AS affects 1 in 12,000 to 20,000 people . Males and females are equally frequently affected . It is named after a British pediatrician , Harry Angelman , who first described the syndrome in 1965 . An older term , `` happy puppet syndrome '' , is generally considered pejorative . Prader -- Willi syndrome is a separate condition , caused by a similar loss of the father 's chromosome 15 .", "title": "" }, { "docid": "Setleis_syndrome", "text": "Setleis syndrome is a cutaneous condition characterized double upper and absent lower lashes . Setleis syndrome ( OMIM 227260 ) is an extremely rare inherited disorder that belongs to a group of diseases known as ectodermal dysplasias . Ectodermal dysplasias typically affect the hair , teeth , nails , and/or skin . Setleis syndrome is characterized by distinctive abnormalities of the facial area that may be apparent at birth ( congenital ) . Most affected infants have multiple , scar-like , circular depressions on both temples ( bitemporal ) . These marks closely resemble those made when forceps are used to assist delivery . The range and severity of symptoms may vary from case to case . Most cases of Setleis syndrome are thought to be inherited as an autosomal recessive genetic trait due to mutations in the TWIST2 gene . The differential diagnosis of Setleis syndrome includes X-linked focal dermal hypoplasia , or Goltz syndrome ; a syndrome of focal dermal hypoplasia , morning glory anomaly , and polymicrogyria ; incontinentia pigmenti ; oculocerebrocutaneous syndrome ; Rothmund-Thomson syndrome ; and MLS ( microphthalmia with linear skin defects ) syndrome caused by deletions or point mutations in the HCCS gene .", "title": "" }, { "docid": "Raine_syndrome", "text": "Raine syndrome ( RNS ) , also called osteosclerotic bone dysplasia , is a rare autosomal recessive congenital disorder characterized by craniofacial anomalies including microcephaly , noticeably low set ears , osteosclerosis , a cleft palate , gum hyperplasia , a hypoplastic nose , and eye proptosis . It is considered to be a lethal disease , and usually leads to death within a few hours of birth . However , a recent report describes two studies in which children with Raine Syndrome have lived to 8 and 11 years old , so it is currently proposed that there is a milder expression that the phenotype can take ( Simpson 2009 ) . It was first characterized in 1989 in a report that was published on an infant that had been born with an unknown syndrome , that later came to be called Raine Syndrome . The current research describes Raine Syndrome as a neonatal osteosclerotic bone dysplasia , indicated by its osteosclerotic symptoms that are seen in those suffering from the disease . It has been found that a mutation in the gene FAM20C is the cause of the Raine Syndrome phenotype . This microdeletion mutation leads to an unusual chromosome 7 arrangement . The milder phenotypes of Raine Syndrome , such as those described in Simpson 's 2007 report , suggest that Raine Syndrome resulting from missense mutations may not be as lethal as the other described mutations ( OMIM ) . This is supported by findings from Fradin et al. ( 2011 ) , who reported on children with missense mutations to FAM20C and lived to ages 1 and 4 years , relatively much longer than the life spans of the previously reported children . Simpson et al. 's ( 2007 ) report states that to date , effected individuals have had chromosome 7 uniparental isodisomy and a 7p telomeric microdeletion . They had abnormal chromosome 7 arrangements , with microdeletions of their D7S2477 and D7S1484 markers ( Simpson 2007 ) . Raine Syndrome appears to be an autosomal recessive disease . There are reports of recurrence in children born of the same parents , and an increased occurrence in children of closely related , genetically similar parents . Individuals with Raine Syndrome were either homozygous or compound heterozygous for the mutation of FAM20C . Also observed have been nonsynonomous mutation and splice-site changes ( Simpson et al. 2007 ) . FAM20C , located on chromosome 7p22 .3 , is an important molecule in bone development . Studies in mice have demonstrated its importance in the mineralization of bones in teeth in early development ( OMIM , Simpson et al. 2007 , Wang et al. 2010 ) . FAM20C stands for `` family with sequence similarity 20 , member C. '' It is also commonly referred to as DMP-4 . It is a Golgi-enriched fraction casein kinase and an extracellular serine/threonine protein kinase . It is 107,743 bases long , with 10 exons and 584 amino acids ( Weizmann Institute of Science ) .", "title": "" }, { "docid": "Bamforth–Lazarus_syndrome", "text": "Bamforth -- Lazarus syndrome is a genetic condition that results in thyroid dysgenesis . It is due to recessive mutations in forkhead/winged-helix domain transcription factor ( FKLH15 or TTF2 ) . It is associated with FOXE1 .", "title": "" } ]
118300
Splatoon 2 is the sequel of Splatoon.
[ { "docid": "Splatoon_2", "text": "Splatoon 2 is an upcoming third-person shooter video game developed and published by Nintendo for the Nintendo Switch . It is the sequel to the 2015 Wii U title , Splatoon , and is a team-based third-person shooter which is playable by up to eight players in online four-versus-four matches . The game was announced in January 2017 , and will be released worldwide in July 2017 .", "title": "" } ]
[ { "docid": "Splatoon", "text": "Splatoon is a third-person shooter video game developed and published by Nintendo for the Wii U , which released worldwide in May 2015 . The game centers around characters known as Inklings -- beings that can transform between humanoid and squid forms , and hide or swim through colored ink sprayed on surfaces using gun , bucket , or brush-based weaponry . Splatoon features several game modes , including 4-on-4 online multiplayer and a single player campaign . Splatoon was developed by Nintendo 's Entertainment Analysis & Development division . The game 's concept originated from having a competitive multiplayer ink-based territory control game , which was later expanded to include squid and the ability to swim through the ink . The idea was created by Shintaro Sato , a member of the Animal Crossing team , and was composed mostly of the younger employees of the company . Splatoon received positive reviews upon its unveiling and release , with critics praising Nintendo 's decision to enter the genre with a new franchise , the game 's overall style and presentation , gameplay mechanics , and its soundtrack . Criticism was directed at the exclusion of voice chat and private lobbies , the small number of multiplayer maps at launch , and issues with online matchmaking . Nintendo provided extensive post-release support for the game by adding new maps and weapons to the game , adding a feature to allow users to create private lobbies and holding time-limited events called `` Splatfests '' . Splatoon was awarded and nominated for several year-end accolades from several gaming publications . A sequel , Splatoon 2 , will be released for the Nintendo Switch in 2017 .", "title": "" }, { "docid": "Shiho_Fujii", "text": "is a Japanese video game music composer who works for Nintendo . She is best known for writing music for New Super Mario Bros. . Wii , The Legend of Zelda : Skyward Sword , Mario Kart 8 , and Splatoon .", "title": "" }, { "docid": "Inkling_(disambiguation)", "text": "Inkling is a US company Inkling may also refer to : Inklings , an Oxford literary discussion group . The inklings , the protagonists of the 2015 video game Splatoon The Inkling , album by Nels Cline Inkling ( programming language ) , programming language for AI and for training AI , from Bonsai .", "title": "" }, { "docid": "Ultra_Machine", "text": "The Ultra Machine is a batting toy made by Nintendo and designed by Gunpei Yokoi in 1967 . It is part of Nintendo 's Ultra toy series , which includes the Ultra Hand and the Ultra Scope . It launches soft balls that are to be hit with a bat . It sold over a million units . It was released elsewhere as the Slugger Mate . The Ultra Machine appears in both WarioWare , Inc. : Mega Microgame $ for the Game Boy Advance and WarioWare : Smooth Moves for the Wii , as a boss fight in the former and a regular microgame in the latter . It appears in some Mario Party games such as Mario Party 5 . It also makes an appearance as a piece of furniture in Animal Crossing : New Leaf for 3DS . The Ultra Machine also makes a major appearance in the 3DS game Rusty 's Real Deal Baseball . The game features characters with Ultra Machine shaped heads , and , in a few instances , flat out Ultra Machines . In the upcoming Splatoon 2 for the Nintendo Switch , one of the special weapons also resembles the Ultra Machine .", "title": "" }, { "docid": "2015_in_video_gaming", "text": "The year 2015 saw releases of numerous video games , including new installments for some well-received franchises , such as Anno , Assassin 's Creed , Batman : Arkham , Battlefield , Call of Duty , Disgaea , Dirt , Fallout , Fatal Frame , Five Nights at Freddy 's , Forza Motorsport , Guitar Hero , Halo , Heroes of Might and Magic , Hotline Miami , Just Cause , King 's Quest , Kirby , Magicka , Mario Party , Mario vs. Donkey Kong , Metal Gear , Minecraft , Mortal Kombat , Need for Speed , OlliOlli , Resident Evil , Rock Band , StarCraft , Star Wars : Battlefront , Tales , The Witcher , Tomb Raider , Tom Clancy 's Rainbow Six , Tony Hawk 's Pro Skater , Total War , Toy Soldiers , Xenoblade Chronicles , Yakuza and Yoshi . In addition , it saw the release of many new intellectual properties , including Dying Light , Evolve , Life Is Strange , Bloodborne , `` Until Dawn '' and Splatoon , and indie titles such as Her Story , Ori and the Blind Forest , Rocket League , and Undertale . Many awards went to games such as Bloodborne , The Witcher 3 : Wild Hunt , Metal Gear Solid V : The Phantom Pain , Fallout 4 , Rocket League , Ori and the Blind Forest and Rise of the Tomb Raider .", "title": "" }, { "docid": "IL-2", "text": "IL2 or IL-2 may refer to : Ilyushin Il-2 Shturmovik , a World War II era Soviet ground attack aircraft IL-2 Sturmovik ( video game series ) , a series of games named after the Ilyushin Il-2 aircraft IL-2 Sturmovik ( video game ) , a 2001 video game , the first in the series IL-2 Sturmovik : Forgotten Battles , a 2003 sequel to the IL-2 Sturmovik video game IL-2 Sturmovik : 1946 , a 2006 expansion pack for the IL-2 Sturmovik video game IL-2 Sturmovik : Birds of Prey , a 2009 sequel to the IL-2 Sturmovik video game IL-2 Sturmovik : Cliffs of Dover , a 2011 sequel to the original IL-2 Sturmovik video game IL-2 Sturmovik : Battle of Stalingrad , a 2013 sequel to the original IL-2 Sturmovik video game Interleukin 2 , a cytokine glycoprotein that stimulates the growth of T cell lymphocytes and provides other biochemical signaling to the immune system IL-2 receptor , a protein that binds and responds to interleukin 2 Illinois ' 2nd congressional district Illinois Route 2 , a north -- south state road in northern Illinois", "title": "" }, { "docid": "List_of_Bollywood_films_of_2013", "text": "2013 marked the completion of 100 years of Bollywood . It witnessed the release of multiple big-budget films in Bollywood including a number of sequels and quasi-sequels lined up . Some of the notable sequels were : Aashiqui 2 , Dhoom 3 , Grand Masti , Krrish 3 , Murder 3 , Once Upon a Time in Mumbai 2 , Race 2 , ( Saheb Biwi Aur Gangster Returns ) , Shootout at Wadala , Satya 2 and Yamla Pagla Deewana 2 .", "title": "" }, { "docid": "Ring_2", "text": "( 1999 ) , directed by Hideo Nakata , is the sequel to the Japanese horror film , Ring . Ring was originally a novel written by Koji Suzuki ; its sequel , Rasen ( a.k.a. Spiral ) , was also adapted into a film as the sequel to Ring . However , due to the poor response to Rasen , Ring 2 was made as a new sequel to Ring , not based on Suzuki 's works , and thus ultimately ignores the story of Rasen . Ring 2 takes place a couple of weeks after the first film , directly continuing the story and features most of the cast from Ring reprising their roles .", "title": "" }, { "docid": "Carnosaur_2", "text": "Carnosaur 2 is a 1995 low budget sequel to Carnosaur , and the second of the Carnosaur franchise . It has a similar plot to Aliens , about a team of scientists who go to a nuclear mining facility to investigate a possible meltdown and instead find a large number of cloned dinosaurs who have been hidden there after the events of the first film . Carnosaur 2 was followed by a direct sequel titled Carnosaur 3 : Primal Species , and an unofficial sequel titled Raptor .", "title": "" }, { "docid": "A_Christmas_Story_2", "text": "A Christmas Story 2 ( also known in the trailer as A Christmas Story 2 : Official Sequel ) is a 2012 film directed by Brian Levant and starring Braeden Lemasters . The film is a direct sequel to the 1983 film A Christmas Story , which ignores the events of the 1994 film My Summer Story . It was released straight to DVD on October 30 , 2012 . Although billed as an `` official sequel '' in the trailer , the film is not based on Jean Shepherd 's writings , instead relying on an original script by Nat Mauldin .", "title": "" }, { "docid": "Eating_out_(disambiguation)", "text": "Eating Out is a gay-themed American film . Eating Out may also refer to Eating Out ( film series ) Eating Out 2 : Sloppy Seconds , sequel to Eating Out Eating Out 3 : All You Can Eat , sequel to Eating Out 2 Eating Out 4 : Drama Camp , sequel to Eating Out 3 Eating Out 5 : The Open Weekend , sequel to Eating Out 4 `` Eating out '' , a slang term for performing cunnilingus `` Eating outside ( of the home ) , '' as in a restaurant", "title": "" }, { "docid": "SpellForce_2:_Shadow_Wars", "text": "SpellForce 2 : Shadow Wars is a video game which employs both real time strategy and role-playing elements , created by German game developers Phenomic . It is a sequel to their 2003 release SpellForce : The Order of Dawn and its two sequels , SpellForce : The Breath of Winter and SpellForce : Shadow of the Phoenix . SpellForce 2 : Shadow Wars was followed by SpellForce 2 : Dragon Storm and SpellForce 2 : Faith in Destiny , with a third sequel , SpellForce 2 : Demons of the Past , released by Nordic Games in January 2014 . In April 2017 Spellforce 2 : Shadow Wars and Spellforce 2 : Dragon Storm were released with an update engine and widescreen support as Spellforce 2 : Anniversary Edition . In October 2007 , SpellForce Universe Edition was released which contained all previous SpellForce games and expansion packs . SpellForce 2 : Shadow Wars requires the player to lead the main character and his band of heroes in forging new alliances to combat the invasion of the world . The game allows extensive co-operative campaigns for up to three players online or via a local area network .", "title": "" }, { "docid": "Rasen", "text": "is a sequel to the movie Ring . It is directed by Jōji Iida and is based on the novel Spiral by Kōji Suzuki . Ring and its sequel Rasen were released in Japan at the same time . The studio hoped this would increase revenues , because the Ring story was already a successful novel and television film . The two films shared a few cast members and had the same production team , but different directors and screenwriters ; Rasen was written and directed by Jōji Iida whereas Ring was written by Hiroshi Takahashi and directed by Hideo Nakata . After their release , Ring became an enormous success while Rasen floundered , quickly becoming the `` forgotten sequel '' . Takahashi and Nakata were later recruited to produce another sequel , Ring 2 , which replaced Rasen as the sequel to Ring , not based on Suzuki 's works , and thus ultimately ignores the story of Rasen . Sadako 3D and Sadako 3D 2 are sequels to Rasen , based on Kōji Suzuki 's 2012 follow-up novel S.", "title": "" }, { "docid": "Unriddle_2", "text": "Unriddle 2 ( simplified Chinese : 最火搭档 2 ) is a Singaporean Chinese drama which was telecast on Singapore 's free-to-air channel , MediaCorp Channel 8 . It made its debut on 5 March 2012 . This drama serial consists of 20 episodes , and was screened on every weekday night at 9:00 pm . In Malaysia , it will be broadcast on the ntv7 primetime drama slot at 10:00 pm around May . It is a sequel to Unriddle , one of the first sequels in Mediacorp dramas in nearly 10 years . The sequel is also noted for its much darker tone as compared to the first series .", "title": "" }, { "docid": "Sonic:_After_the_Sequel", "text": "Sonic : After the Sequel is a 2013 platform video game created by Brazilian student Felipe Daneluz ( LakeFeperd ) . It is an unofficial game based on the Sonic the Hedgehog series and set between the official games Sonic the Hedgehog 2 and Sonic the Hedgehog 3 . Daneluz 's second Sonic game , it follows Sonic : Before the Sequel , which was set after the original Sonic the Hedgehog . Like its predecessor , After the Sequel stars Sonic the Hedgehog and his sidekick Tails in a quest to retrieve the Chaos Emeralds from Doctor Eggman . After the Sequel was inspired by Sonic Heroes and other games both inside and outside the Sonic series , and it was developed with Sonic Worlds , an engine based in Multimedia Fusion 2 that reduces the amount of computer programming involved in game creation . It was released as a free download for Microsoft Windows personal computers . The game was very well received by video game journalists , who lauded its preservation of retro Sonic gameplay and its eclectic , 1990s-style soundtrack . The trilogy of Before the Sequel , After the Sequel , and their successor Sonic Chrono Adventure performed unusually well for fangames , having been downloaded 120,000 times by March 2014 .", "title": "" }, { "docid": "Dungeon_Travelers_2", "text": "is a dungeon crawler role-playing video game developed by Sting Entertainment . It is the sequel to To Heart 2 : Dungeon Travelers within the To Heart 2 franchise . Dungeon Travelers 2 was first released on March 28 , 2013 on the PlayStation Portable exclusively in Japan ; an enhanced remake for the PlayStation Vita was released in Japan on September 25 , 2014 , and later in North America and Europe in 2015 . A sequel game for the PlayStation Vita titled Dungeon Travelers 2-2 has been announced for a 2017 release in Japan .", "title": "" }, { "docid": "Walking_Tall", "text": "Walking Tall may refer to : Walking Tall ( 1973 film ) , a 1973 film Walking Tall Part 2 , ( a.k.a. . The Legend of Buford Pusser ) , a 1975 sequel to Walking Tall Walking Tall : Final Chapter , a 1977 sequel to Walking Tall Part 2 . A Real American Hero ( film ) , a 1978 made-for-television remake of Walking Tall ( 1973 ) . Walking Tall ( TV series ) , a 1981 television series adaptation of the films of the same name Walking Tall ( 2004 film ) , a remake of the 1973 film of the same name Walking Tall : The Payback , a 2007 sequel to the 2004 film Walking Tall Walking Tall : Lone Justice , a 2007 sequel to Walking Tall : The Payback", "title": "" }, { "docid": "Everblue_2", "text": "Everblue 2 is a scuba diving adventure game . It is the sequel to the game Everblue . Arika , the developers of both games , followed it with the spiritual sequel Endless Ocean , for the Wii .", "title": "" }, { "docid": "Shaman_King:_Master_of_Spirits_2", "text": "Shaman King : Master of Spirits 2 is the sequel to the Game Boy Advance game Shaman King : Master of Spirits that had been released in 2002 . Konami decided to make a sequel to this game , released on August 2 , 2005 , supposedly only for the United States and Europe .", "title": "" }, { "docid": "Tokyo_Xtreme_Racer_2", "text": "Tokyo Xtreme Racer 2 , known as Shutokō Battle 2 ( 首都高バトル 2 ) in Japan and Tokyo Highway Challenge 2 in Europe , is the sequel to Tokyo Xtreme Racer , which is also on the Sega Dreamcast . Tokyo Xtreme Racer 2 has been enhanced with better sound quality and graphics over its predecessor . The game managed to produce two more sequels . It is the last game in the series that was produced for Sega Dreamcast . Some of the game 's mechanics were implemented into Daytona USA 2001 .", "title": "" }, { "docid": "Jurassic_Park_2", "text": "Jurassic Park 2 may refer to : The Lost World , Michael Crichton 's sequel to the 1990 novel Jurassic Park The Lost World : Jurassic Park , the 1997 sequel to the 1993 film Jurassic Park Jurassic Park 2 : The Chaos Continues , a video game for the Super Nintendo Entertainment System", "title": "" }, { "docid": "Lego_Racers_2", "text": "Lego Racers 2 is a Lego-themed racing video game developed by Attention to Detail and published by Lego Software . It was first released in September 2001 for Microsoft Windows , PlayStation 2 and Game Boy Advance . It is the sequel to the 1999 game Lego Racers . This sequel was first revealed by The Lego Group on 20 August 2001 .", "title": "" }, { "docid": "Teen_Beach_2", "text": "Teen Beach 2 is a 2015 Disney Channel Original Movie and the sequel to the 2013 film Teen Beach Movie . The film premiered on Disney Channel on June 26 , 2015 . The film is the first sequel of a Disney Channel Original Movie in five years , the last being Camp Rock 2 : The Final Jam in 2010 .", "title": "" }, { "docid": "The_Detective_2", "text": "The Detective 2 is a 2011 Hong Kong thriller film directed by Oxide Pang and starring Aaron Kwok . It is the sequel to 2007 's The Detective . The film was followed by a sequel , Conspirators , released in 2013 .", "title": "" }, { "docid": "Clockwork_Knight_2", "text": "Clockwork Knight 2 , known in Japan as , is a side-scrolling platform video game developed and published by Sega for the Sega Saturn . It is the sequel to Clockwork Knight , a title also released for the Sega Saturn . A second sequel , the working titles for which included Clockwork Knight 3 : Pengin War and Clockwork Knight Puzzle , used gameplay similar to the Bomberman series , but never made it past the beta stage . Another sequel , titled Knight N ' Knight , was scheduled to appear on the GameCube , but never released .", "title": "" }, { "docid": "GOW2", "text": "GoW2 may refer to : God of War II , the sequel to the PlayStation 2 exclusive game God of War Gears of War 2 , the Xbox 360 exclusive sequel to the Xbox 360 and PC game Gears of War", "title": "" }, { "docid": "ATV_Offroad_Fury", "text": "ATV Offroad Fury is a PlayStation 2 racing game , released in 2001 . ATV Offroad Fury and its sequel ATV Offroad Fury 2 were developed by Rainbow Studios , whose work includes Splashdown , MX Unleashed , Motocross Madness , as well as its sequel , Motocross Madness 2 , and the later MX vs. ATV series .", "title": "" }, { "docid": "Another_Century's_Episode_2", "text": ", abbreviated as A.C.E. 2 , is a third-person mecha action video game produced by Banpresto and developed by From Software . It is the sequel to the popular 2005 game Another Century 's Episode . It was released for the PlayStation 2 on March 30 , 2006 . On November 29 , 2007 , Banpresto released A.C.E. 2 Special Vocal Edition as a follow-up to the heels of A.C.E. 2 '' 's sequel , Another Century 's Episode 3 : The Final '' . This version includes vocal theme songs for each of the featured animated series in the game .", "title": "" }, { "docid": "A_Turtle's_Tale_2:_Sammy's_Escape_from_Paradise", "text": "A Turtle 's Tale 2 : Sammy 's Escape from Paradise ( titled Sammy 's Great Escape in the UK ; Sammy 's avonturen 2 , literally `` Sammy 's adventures 2 '' ) is a 2012 English-language Belgian-French animated film sequel to the 2010 animated film A Turtle 's Tale : Sammy 's Adventures . The sequel features the voice talents of Kaitlyn Maher , Khary Payton and Carlos Alazraqui .", "title": "" }, { "docid": "Sports_Weekend:_As_Nasty_as_They_Wanna_Be,_Pt._2", "text": "Sports Weekend : As Nasty As They Wan na Be , Pt . 2 is the sixth album overall and fifth studio album by the 2 Live Crew ( released in 1991 ) and the sequel of As Nasty As They Wan na Be . A clean version was released later that same year titled Sports Weekend : As Clean As They Wan na Be Part II and was the sequel of As Clean As They Wan na Be . This would be the last studio album by all original members of the 2 Live Crew .", "title": "" } ]
41797
John Cusack was idolized by teens.
[ { "docid": "John_Cusack", "text": "John Paul Cusack ( -LSB- ˈkjuːsæk -RSB- , born June 28 , 1966 ) is an American actor , producer and screenwriter . He made one of his earliest film roles in the mid-1980s , before he starred in Cameron Crowe 's film Say Anything ... ( 1989 ) , for which he gained teen idol status . He was nominated for a Golden Globe Award for Best Actor -- Motion Picture Musical or Comedy for his performance in High Fidelity ( 2000 ) . Cusack starred in other films , including Grosse Pointe Blank ( 1997 ) , Being John Malkovich ( 1999 ) , 1408 ( 2007 ) , 2012 ( 2009 ) , Hot Tub Time Machine ( 2010 ) and The Raven ( 2012 ) .", "title": "" } ]
[ { "docid": "Teen_idol_(disambiguation)", "text": "A teen idol is a celebrity who is widely idolized by teenagers . Teen Idol may also refer to : Teen Idol ( novel ) , a 2004 novel by Meg Cabot '' Teen Idol ( Australian TV series ) , an Australian TV series Teen Idols , a pop punk group The Teen Idles , a hardcore band", "title": "" }, { "docid": "John_Cusack_(disambiguation)", "text": "John Cusack can refer to : John Paul Cusack , American actor , born 1966 John Cusack ( politician ) , Australian politician , 1868 -- 1956 John Cusack ( hurler ) , Irish hurler , active in the 1940s and 1950s John Bede Cusack , pseudonym John Beede , author , younger brother of Dymphna Cusack", "title": "" }, { "docid": "Teen_idol", "text": "A teen idol is a celebrity with a large teenage fan-base . Teen idols are generally young but not necessarily teenaged . Often teen idols are actors or singers , but some sports figures and even political figures also have an appeal to teenagers . Some teen idols began their careers as child actors , like Leif Garrett , Lindsay Lohan , Mary-Kate and Ashley Olsen , Raven-Symoné , Kenan Thompson , Kel Mitchell , Hilary Duff , as well as Shirley Temple . The idol 's popularity may be limited to teens , or may extend to all age groups . Many teen idols are targeted for adults for nostalgia purposes . There were teen idols before there were teen magazines , but idols have always been a permanent feature in magazines such as Seventeen , 16 magazine , Tiger Beat and Right On ! in the United States , and in similar magazines elsewhere . With the advent of television , teen idols were also promoted through programs such as American Bandstand , The Ed Sullivan Show , Soul Train and in the UK Top of the Pops . Today 's teen idols have spawned an entire industry of gossip magazines , television shows , YouTube , and whole television channels such as E! . Many American teen idols achieve `` cross-over '' success internationally ; however , this list is not limited to American artists alone with some people such as Japanese popstar Kusumi Koharu . In Asia , idols range from Japanese pop megastars Ayumi Hamasaki and Namie Amuro as well as Kana Nishino and Japanese music groups such as Momoiro Clover Z , Morning Musume , AKB48 , and Perfume and Johnny & Associates boy bands Arashi , NEWS , KAT-TUN , and Hey ! Say ! JUMP among others while Chinese pop icon Jay Chou and Jolin Tsai , music groups F4 and Lollipop F , and South Korean singers BoA and Rain and music groups TVXQ , 2PM , 2AM , Beast , Shinee , EXO , Super Junior , f ( x ) , 2NE1 , BIGBANG , Wonder Girls , BTS , T-ara , Kara and Girls ' Generation are examples . In Latin America , idols ranges from Mexican pop stars Thalía , Timbiriche , Lynda Thomas , Magneto , Puerto Rican born Mexican Luis Miguel , Puerto Rican singer Marc Anthony , and the very popular Puerto Rican boy band Menudo in the 1980s and 1990s , and Paty Cantú , Anahi , Belinda . Ha ^ Ash and RBD in the 2000s and 2010s . Besides , former Menudo member Ricky Martin , their chief rivals Los Chicos and former member Chayanne , Venezuelan actor and singer Guillermo Davila and more , to Argentina , where telenovela , Chiquititas , ushered in a new era of teen-idols for that country , including actors Benjamin Rojas , Felipe Colombo , Luisana Lopilato and Camila Bordonaba , who went on to form teen band Erreway , precursors to Mexican band RBD . In Spain , La Oreja de Van Gogh , Miguel Bose , Mecano and Hombres G all enjoyed teen-idol status . Even in the classical music field , a British-Chinese violinist Vanessa-Mae became the first `` teen idol '' in that category . In the past , young sports icons and Olympic athletes during their competitive times were considered teen idols such as Jean-Claude Killy , Peggy Fleming , Caitlyn Jenner , Joe Namath , Dorothy Hamill , Mark Spitz , Jim Craig , Nadia Comăneci , Mary Lou Retton , Michael Jordan , Dominique Moceanu , Michelle Kwan , Carly Patterson , Shawn Johnson , Nastia Liukin , Michelle Wie , Mia Hamm , Ryan Lochte , Michael Phelps , Missy Franklin , Katie Ledecky , Shaun White , Apolo Ohno , Simone Biles , Tom Daley , McKayla Maroney , and Gabby Douglas .", "title": "" }, { "docid": "Cusack_(surname)", "text": "Cusack is a surname . Notable people with the surname include : Ann Cusack , American actress , daughter of Dick Cusack Carmen Cusack , American musical theater actress and singer Catherine Cusack , Irish actress , daughter of Cyril Cusack Catherine Cusack ( politician ) , Australian politician Cyril Cusack , Irish actor Dick Cusack , American actor and filmmaker Donal Óg Cusack , Irish hurler Dymphna Cusack , Australian writer Joan Cusack , American actress , daughter of Dick Cusack John Cusack , American actor and writer , son of Dick Cusack John Cusack ( Australian politician ) Joyce Cusack , American politician Mary Frances Cusack , Irish nun and writer Michael Cusack , Irish teacher and founder of the Gaelic Athletic Association Niamh Cusack , Irish actress , daughter of Cyril Cusack Robert Cusack , Australian swimmer Sinéad Cusack , Irish actress , daughter of Cyril Cusack Sorcha Cusack , Irish actress , daughter of Cyril Cusack Thomas Cusack ( disambiguation )", "title": "" }, { "docid": "Better_Off_Dead_(film)", "text": "Better Off Dead is a 1985 American teen romantic comedy film starring John Cusack and written and directed by Savage Steve Holland . It tells the story of high school student Lane Myer who is suicidal after his girlfriend breaks up with him shortly before Christmas .", "title": "" }, { "docid": "Confessions_of_a_Teen_Idol", "text": "Confessions of a Teen Idol is an American reality series that began airing on VH1 on January 4 , 2009 and concluded on February 22 , 2009 . It ran for eight episodes . The series was hosted and produced by former teen idols Scott Baio and Jason Hervey . The show was filmed in the same house used to film The Real World : Hollywood .", "title": "" }, { "docid": "John_Cusack_(hurler)", "text": "John Cusack was an Irish hurler who played as a full-back for the Waterford senior team . Cusack , after an uneventful underage career , played for the senior team throughout the 1940s and the 1950s . During that time he won one All-Ireland medal and one Munster medal . At club level Cusack played with Rathgormack .", "title": "" }, { "docid": "Miss_Teen_USA_2016", "text": "Miss Teen USA 2016 , the 34th Miss Teen USA pageant , was held at The Venetian Theatre in Las Vegas , Nevada on July 30 , 2016 . Katherine Haik of Louisiana crowned her successor Karlie Hay of Texas , at the end of the event . The pageant was webcast on the Miss Universe website , Facebook page , and mobile app as well as on Xbox 360 and Xbox One consoles via Xbox Live . It was hosted by Miss USA 2015 Olivia Jordan and social media star Cody Johns , while American Idol winner Nick Fradiani performed . This is the first time that the state of Nevada hosted the pageant and the first Miss Teen USA pageant held in the United States since 2007 . It was also the final Miss Teen USA pageant to be streamed on Xbox 360 consoles .", "title": "" }, { "docid": "Teen_Idol_(Australian_TV_series)", "text": "Teen Idol is an Australian TV series .", "title": "" }, { "docid": "Teen_Idol_(novel)", "text": "Teen Idol was written by Meg Cabot and published in July 2004 in hardcover edition and in August 2005 in paperback edition .", "title": "" }, { "docid": "Teen_Beat", "text": "Teen Beat was an American magazine geared towards teenaged readers , published from 1967 -- c. 2007 . Over its history , the magazine had multiple teen idols on its cover , including John Travolta , David Cassidy , Menudo , Michael J. Fox , Debbie Gibson , the Coreys ( Feldman and Haim ) , Molly Ringwald , Tom Cruise , New Kids on the Block , Jonathan Taylor Thomas , Jonathan Brandis , and , more recently , Hanson , Ricky Martin , Leonardo DiCaprio , Backstreet Boys , * NSYNC , Hilary Duff , Amanda Lepore , Michael Jackson , Raven-Symoné and Lindsay Lohan , among many others .", "title": "" }, { "docid": "Idol_Show", "text": "Idol Show ( ; lit . Idol Corps , She Has Arrived ! ) , also called Idol Army , is a weekly Korean variety show on MBC Every 1 hosted by the nation 's most popular teen idol groups .", "title": "" }, { "docid": "Teen_Idols", "text": "The Teen Idols were a pop punk band originally from Nashville , Tennessee . They were formed in 1992 by Phillip Hill and originally broke up in 2003 . The band reunited in 2008 in Chicago , Illinois with a retooled lineup before breaking up again in 2010 .", "title": "" }, { "docid": "John_Cusack_(politician)", "text": "John Joseph Cusack ( 8 August 1868 -- 8 September 1956 ) was an Australian politician , coachbuilder and garage proprietor .", "title": "" }, { "docid": "High_Fidelity_(film)", "text": "High Fidelity is a 2000 American romantic comedy-drama film directed by Stephen Frears . It stars John Cusack , Iben Hjejle , Jack Black , Todd Louiso , and Lisa Bonet . The film is based on the 1995 British novel of the same name by Nick Hornby , with the setting moved from London to Chicago and the name of the lead character changed . After seeing the film , Hornby expressed his happiness with Cusack 's performance , saying that `` at times , it appears to be a film in which John Cusack reads my book '' .", "title": "" }, { "docid": "Thomas_Cusacke", "text": "Thomas Cusacke ( died c. 1496 ) was an Irish barrister and judge , who held the offices of Attorney General for Ireland and Lord Chief Justice of Ireland . He should not be confused with his much younger cousin Thomas Cusack , Lord Chancellor of Ireland , who was a child of about six when the elder Thomas died . Elrington Ball states that he belonged to a junior branch of the well-known landowning Cusack family of County Meath . He was thus a cousin of John Cusack of Cussington : John was the father of the Lord Chancellor , Thomas Cusack , and ancestor , through his granddaughter Catherine Colley ( née Catherine Cusack-Wellesley ) of the Duke of Wellington . Thomas is first heard of in London in 1472 where he was a law student : he went to London , in his own words : `` so as to thoroughly ground himself in the King 's law '' , and he was given a licence to import grain into Ireland . He was made Attorney General for Ireland in 1480 . Like nearly all the senior judges and lawyers in Ireland in that era he was a client of Gerald FitzGerald , 8th Earl of Kildare , who was almost all-powerful in Ireland for more than 30 years . Kildare and his faction made the mistake of supporting Lambert Simnel , pretender to the English Crown , who was decisively defeated at the Battle of Stoke Field in 1487 . The victorious King Henry VII was merciful to the Irish rebels ( as indeed he was to Simnel himself , who became an official of the Royal household ) . He issued a royal pardon for the great majority of them , including Cusacke , who became Lord Chief Justice in 1490 . Henry 's clemency had limits , and his strong suspicion that the Anglo-Irish nobility were aiding another pretender , Perkin Warbeck , led to Kildare 's temporary downfall in 1494 . The new Lord Deputy of Ireland , Sir Edward Poynings , undertook a general purge of the Irish judges , including Cusacke who was replaced by the eminent English lawyer Thomas Bowring . From 1496 onwards Kildare regained much of his influence , and some of his former allies on the bench returned to power , but no more is heard of Cusacke , which suggests that he had died sometime between 1494 and 1496 .", "title": "" }, { "docid": "Tommy_Sands_(American_singer)", "text": "Thomas Adrian `` Tommy '' Sands ( born August 27 , 1937 ) is an American pop music singer and actor . Working in show business as early as 1949 , Sands became an overnight sensation and instant teen idol when he appeared on Kraft Television Theater in January 1957 as `` The Singin ' Idol '' . The song from the show , `` Teen Age Crush '' , reached # 2 on the Billboard Hot 100 and # 1 on Cashbox .", "title": "" }, { "docid": "Bay_City_Rollers", "text": "The Bay City Rollers are a Scottish pop band whose popularity was highest in the mid 1970s . The British Hit Singles & Albums noted they were `` tartan teen sensations from Edinburgh '' , and were `` the first of many acts heralded as the ` biggest group since the Beatles ' and one of the most screamed-at teeny-bopper acts of the 1970s '' . For a relatively brief , but fervent period ( nicknamed `` Rollermania '' ) , they were worldwide teen idols . The group 's line-up had numerous changes over the years , but the classic line-up during its heyday included ; guitarists Eric Faulkner and Stuart John Wood , singer Les McKeown , bassist Alan Longmuir , and drummer Derek Longmuir .", "title": "" }, { "docid": "Dymphna_Cusack", "text": "Ellen Dymphna Cusack AM ( 21 September 1902 -- 19 October 1981 ) was an Australian author . Born in Wyalong , New South Wales , Cusack was educated at Saint Ursula 's College , Kingsgrove , and graduated from the University of Sydney with an honours degree in Arts and a diploma in Education . She worked as a teacher until she retired in 1944 for health reasons . Her illness was confirmed in 1978 as multiple sclerosis . Cusack wrote twelve novels ( two of which were collaborations ) , seven plays , three travel books , two children 's books and one non-fiction book . Her collaborative novels were Pioneers on Parade ( 1939 ) with Miles Franklin , and Come In Spinner ( 1951 ) with Florence James . The play Red Sky at Morning was filmed in 1944 , starring Peter Finch . The biography Caddie , the Story of a Barmaid , to which Cusack wrote an introduction and helped the author write , was produced as the film Caddie in 1976 . The novel Come In Spinner was produced as a television series by the Australian Broadcasting Corporation in 1989 , and broadcast in March 1990 . Her younger brother , John , was also an author , writing the war novel They Hosed Them Out under the pseudonym John Beede , which was first published in 1965 , republished in 2012 .", "title": "" }, { "docid": "Teen_Age_Idol", "text": "`` Teen Age Idol '' is a song written by Jack Lewis and performed by Rick Nelson . The song reached # 2 on the adult contemporary chart , # 5 on the Billboard Hot 100 , and # 39 in the UK in 1962 . The single 's B-side , `` I 've Got My Eyes on You ( And I Like What I See ) '' , reached # 105 on the Billboard chart . The song is ranked # 77 on Billboard magazine 's Top 100 songs of 1962 .", "title": "" }, { "docid": "Thomas_Cusack_(politician)", "text": "Thomas Cusack ( October 5 , 1858 in Kilrush , County Clare , Ireland -- November 19 , 1926 in Oak Park , Illinois ) was a pioneer and entrepreneur in the outdoor advertising industry and a politician , serving as a Democratic U.S. Representative from Illinois ' 4th District from 1899 to 1901 . Cusack emigrated with his family from Ireland to New York City in 1861 when he was a young boy . Shortly after the move , his parents died , leaving him and his younger brother orphaned . Cusack was raised by relatives in Chicago , where he received his education and learned how to paint , a skill that ultimately made him a very wealthy man . At the age of 17 , Cusack established his own sign painting business , the Thomas Cusack Company , in Chicago , Illinois , making him one of the pioneers in the field of outdoor advertising . The business soon grew to be very profitable , leasing over 100,000 billboards and advertising spaces and turning Cusack into a prosperous and influential Chicagoan . In addition to business savvy , Cusack had a strong sense of civic duty . In 1890 , Mayor of Chicago Hempstead Washburne appointed the `` billboard baron '' to a seat on the city 's school board . Cusack 's fervent support of public education drew the attention of progressive Illinois Governor John P. Altgeld , who invited Cusack to serve on his general staff . In 1898 , Cusack was elected to his first and only term in the United States Congress from the 4th District of Illinois . After his term , Cusack decided to return his attention primarily to his outdoor advertising business , which had grown considerably in size to more than one hundred offices with an annual revenue of over $ 20 million . Cusack was known for his fair labor practices and amicable relationships with his employees , and was most proud of the fact that , in a city known for labor strikes , his workers never walked off the job . In his day as a sign painter , Cusack remembered getting $ 8 a week in wages . By the time he sold his business to a New York banking syndicate in 1924 , he was paying his workers $ 10 to $ 15 a day . At the pinnacle of his success in business , Cusack bought the entire unincorporated town of Cascade , Colorado , at the Ute Pass in the Rocky Mountains . He hired architects and contractors to build a plush mansion nestled in the Ute Pass , which he named `` Marigreen Pines '' after his wife , Mary Green . Having lived through the Great Chicago Fire and experienced so many early losses in his life , Cusack built Marigreen Pines out of brick , marble and concrete to safeguard his family from harm . Marigreen Pines became a much loved mountain home for Cusack and his family , where he routinely and graciously hosted many friends and relatives , engaging them in lively conversation and debate . Thomas Cusack died on November 19 , 1926 , at the age of 68 . He is buried in Calvary Cemetery in Evanston , Illinois . In the 1970s , Cusack 's last surviving daughter donated Marigreen Pines to the Congregation of Holy Cross to serve as their novitiate .", "title": "" }, { "docid": "Piven_Theatre_Workshop", "text": "The Piven Theatre Workshop is located in Evanston , Illinois and was founded by Joyce and Byrne Piven . For over 30 years , it has existed both as a professional theatre company and a training center for children and adults . Famous alumni to come out of the program include Jeremy Piven , John Cusack , Joan Cusack , Ann Cusack , Aidan Quinn , Laurel Holloman , Lili Taylor , and Kate Walsh .", "title": "" }, { "docid": "Dick_Cusack", "text": "Richard John `` Dick '' Cusack ( August 29 , 1925 -- June 2 , 2003 ) was an American actor and filmmaker .", "title": "" }, { "docid": "Natural_Born_Teen_Top", "text": "Natural Born Teen Top is the sixth EP recorded and performed by the South Korean contemporary R&B idol group Teen Top . It was released digitally on June 22 , 2015 and physically on June 23 . The album was released in two versions and contains six tracks .", "title": "" }, { "docid": "Joan_Cusack", "text": "Joan Cusack ( -LSB- ˈkjuːsæk -RSB- , born October 11 , 1962 ) is an American actress . She received Academy Award nominations for Best Supporting Actress for her roles in the romantic comedy-drama Working Girl ( 1988 ) and the romantic comedy In & Out ( 1997 ) , as well as one Golden Globe nomination for her performance in the latter . She is also known as the voice of Jessie in the Toy Story franchise . Cusack was a cast member on the comedy sketch show Saturday Night Live from 1985 to 1986 . She starred on the Showtime hit drama/comedy Shameless as Sheila Gallagher ( née Jackson ) , a role for which she has received five consecutive Emmy Award nominations , winning for the first time in 2015 . She is the sister of actress Ann and actor John Cusack .", "title": "" }, { "docid": "War,_Inc.", "text": "War , Inc. is a 2008 American political action comedy film starring John Cusack and directed by Joshua Seftel . Cusack also co-wrote and produced the film .", "title": "" }, { "docid": "Nick_Cusack", "text": "Nicholas John Cusack ( born 24 December 1965 in Maltby , South Yorkshire ) is an English former footballer and , briefly , player-manager . He was for a time chairman of the Professional Footballers ' Association ( PFA ) .", "title": "" }, { "docid": "Tom_Jankiewicz", "text": "Thomas Anthony Jankiewicz ( September 8 , 1963 -- January 23 , 2013 ) was an American screenwriter . Jankiewicz was best known for penning the 1997 film , Grosse Pointe Blank , starring John Cusack , Minnie Driver , Alan Arkin , and Dan Aykroyd . Grosse Pointe Blank tells the story of an assassin , played by John Cusack , who returns to his hometown for his 10-year high school reunion .", "title": "" }, { "docid": "Cell_(film)", "text": "Cell is a 2016 American science fiction horror film based on the 2006 novel of the same name by Stephen King . The film is directed by Tod Williams , produced by John Cusack , with a screenplay by King and Adam Alleca . The film stars Cusack , Samuel L. Jackson , and Isabelle Fuhrman . The film was released on June 10 , 2016 to video on demand , prior to a limited release scheduled for July 8 , 2016 . Cell is the second film adaptation of a King story to co-star Cusack and Jackson , after 1408 ( 2007 ) . The film was panned by critics upon its release ; most criticized the film 's acting and plot .", "title": "" }, { "docid": "Japanese_youth_culture", "text": "Japanese youth culture is a style for the youth and teen . The youth culture include Japanese idol , visual kei , gothic lolita , Nagoya kei and gyaru . The cultures such as Japanese idol and visual kei began as youth culture in the Japan .", "title": "" } ]
197
CCL19 is a ligand for CCR7.
[ { "docid": "2177022", "text": "Chemokines orchestrate immune cell trafficking by eliciting either directed or random migration and by activating integrins in order to induce cell adhesion. Analyzing dendritic cell (DC) migration, we showed that these distinct cellular responses depended on the mode of chemokine presentation within tissues. The surface-immobilized form of the chemokine CCL21, the heparan sulfate-anchoring ligand of the CC-chemokine receptor 7 (CCR7), caused random movement of DCs that was confined to the chemokine-presenting surface because it triggered integrin-mediated adhesion. Upon direct contact with CCL21, DCs truncated the anchoring residues of CCL21, thereby releasing it from the solid phase. Soluble CCL21 functionally resembles the second CCR7 ligand, CCL19, which lacks anchoring residues and forms soluble gradients. Both soluble CCR7 ligands triggered chemotactic movement, but not surface adhesion. Adhesive random migration and directional steering cooperate to produce dynamic but spatially restricted locomotion patterns closely resembling the cellular dynamics observed in secondary lymphoid organs.", "title": "Immobilized chemokine fields and soluble chemokine gradients cooperatively shape migration patterns of dendritic cells." } ]
[ { "docid": "40590358", "text": "The pro-drug FTY720 is undergoing phase III clinical trials for prevention of allograft rejection. After phosphorylation, FTY720 targets the G protein-coupled-sphingosine-1-phosphate receptor 1 (S1PR1) on lymphocytes, thereby inhibiting their egress from lymphoid organs and their recirculation to inflammatory sites. Potential effects on dendritic cell (DC) trafficking have not been evaluated. Here, we demonstrate the expression of all five S1PR subtypes (S1PR1-5) by murine DCs. Administration of FTY720 to C57BL/10 mice markedly reduced circulating T and B lymphocytes within 24 h, but not blood-borne DCs, which were enhanced significantly for up to 96 h, while DCs in lymph nodes and spleen were reduced. Numbers of adoptively transferred, fluorochrome-labeled syngeneic or allogeneic DCs in blood were increased significantly in FTY720-treated animals, while donor-derived DCs and allostimulatory activity for host naïve T cells within the spleen were reduced. Administration of the selective S1PR1 agonist SEW2871 significantly enhanced circulating DC numbers. Flow analysis revealed that CD11b, CD31/PECAM-1, CD54/ICAM-1 and CCR7 expression on blood-borne DCs was downregulated following FTY720 administration. Transendothelial migration of FTY720-P-treated immature DCs to the CCR7 ligand CCL19 was reduced. These novel data suggest that modulation of DC trafficking by FTY720 may contribute to its immunosuppressive effects.", "title": "The sphingosine-1-phosphate receptor agonist FTY720 modulates dendritic cell trafficking in vivo." }, { "docid": "13778710", "text": "Chemokine-like receptor 1 (CMKLR1), also known as ChemR23, and chemokine (C-C motif) receptor-like 2 (CCRL2) are 7-transmembrane receptors that were cloned in the late 1990s based on their homology to known G-protein-coupled receptors. They were previously orphan receptors without any known biological roles; however, recent studies identified ligands for these receptors and their functions have begun to be unveiled. The plasma protein-derived chemoattractant chemerin is a ligand for CMKLR1 and activation of CMKLR1 with chemerin induces the migration of macrophages and dendritic cells (DCs) in vitro, suggesting a proinflammatory role. However, in vivo studies using CMKLR-deficient mice suggest an anti-inflammatory role for this receptor, possibly due to the recruitment of tolerogenic plasmacytoid DCs. Chemerin/CMKLR1 interaction also promotes adipogenesis and angiogenesis. The anti-inflammatory lipid mediator, resolving E1, is another CMKLR1 ligand and it inhibits leukocyte infiltration and proinflammatory gene expression. These divergent results suggest that CMKLR1 is a multifunctional receptor. The chemokine CCL5 and CCL19 are reported to bind to CCRL2. Like Duffy antigen for chemokine receptor (DARC), D6 and CCX-CKR, CCRL2 does not signal, but it constitutively recycles, potentially reducing local concentration of CCL5 and CCL19 and subsequent immune responses. Surprisingly, chemerin, a ligand for CMKLR1, is a ligand for CCRL2. CCRL2 binds chemerin and increases local chemerin concentration to efficiently present it to CMKLR1 on nearby cells, providing a link between CCRL2 and CMKLR1. Although these findings suggest an anti-inflammatory role, a recent study using CCRL2-deficient mice indicates a proinflammatory role; thus, CCRL2 may also be multifunctional. Further studies using CMKLR1- or CCRL2-deficient mice are needed to further define the role of these receptors in immune responses and other cellular processes.", "title": "Chemokine-like receptor 1 (CMKLR1) and chemokine (C-C motif) receptor-like 2 (CCRL2); two multifunctional receptors with unusual properties." }, { "docid": "25942757", "text": "The substantial importance of P-selectin glycoprotein ligand 1 (PSGL-1) in leukocyte trafficking has continued to emerge beyond its initial identification as a selectin ligand. PSGL-1 seemed to be a relatively simple molecule with an extracellular mucin domain extended as a flexible rod, teleologically consistent with its primary role in tethering leukocytes to endothelial selectins. The rolling interaction between leukocyte and endothelium mediated by this selectin-PSGL-1 interaction requires branched O-glycan extensions on specific PSGL-1 amino acid residues. In some cells, such as neutrophils, the glycosyltransferases involved in formation of the O-glycans are constitutively expressed, while in other cells, such as T cells, they are expressed only after appropriate activation. Thus, PSGL-1 supports leukocyte recruitment in both innate and adaptive arms of the immune response. A complex array of amino acids within the selectins engage multiple sugar residues of the branched O-glycans on PSGL-1 and provide the molecular interactions responsible for the velcro-like catch bonds that support leukocyte rolling. Such binding of PSGL-1 can also induce signaling events that influence cell phenotype and function. Scrutiny of PSGL-1 has revealed a better understanding of how it performs as a selectin ligand and yielded unexpected insights that extend its scope from supporting leukocyte rolling in inflammatory settings to homeostasis including stem cell homing to the thymus and mature T-cell homing to secondary lymphoid organs. PSGL-1 has been found to bind homeostatic chemokines CCL19 and CCL21 and to support the chemotactic response to these chemokines. Surprisingly, the O-glycan modifications of PSGL-1 that support rolling mediated by selectins in inflammatory conditions interfere with PSGL-1 binding to homeostatic chemokines and thereby limit responsiveness to the chemotactic cues used in steady state T-cell traffic. The multi-level influence of PSGL-1 on cell traffic in both inflammatory and steady state settings is therefore substantially determined by the orchestrated addition of O-glycans. However, central as specific O-glycosylation is to PSGL-1 function, in vivo regulation of PSGL-1 glycosylation in T cells remains poorly understood. It is our purpose herein to review what is known, and not known, of PSGL-1 glycosylation and to update understanding of PSGL-1 functional scope.", "title": "PSGL-1 function in immunity and steady state homeostasis." }, { "docid": "6123924", "text": "Immune tolerance and activation depend on precise control over the number and function of immunosuppressive Foxp3(+) regulatory T (T reg) cells, and the importance of IL-2 in maintaining tolerance and preventing autoimmunity is clear. However, the homeostatic requirement for IL-2 among specific populations of peripheral T reg cells remains poorly understood. We show that IL-2 selectively maintains a population of quiescent CD44(lo)CD62L(hi) T reg cells that gain access to paracrine IL-2 produced in the T cell zones of secondary lymphoid tissues due to their expression of the chemokine receptor CCR7. In contrast, CD44(hi)CD62L(lo)CCR7(lo) T reg cells that populate nonlymphoid tissues do not access IL-2-prevalent regions in vivo and are insensitive to IL-2 blockade; instead, their maintenance depends on continued signaling through the co-stimulatory receptor ICOS (inducible co-stimulator). Thus, we define a fundamental homeostatic subdivision in T reg cell populations based on their localization and provide an integrated framework for understanding how T reg cell abundance and function are controlled by unique signals in different tissue environments.", "title": "CCR7 provides localized access to IL-2 and defines homeostatically distinct regulatory T cell subsets" }, { "docid": "12100963", "text": "Memory/effector T cells efficiently migrate into extralymphoid tissues and sites of infection, providing immunosurveillance and a first line of defense against invading pathogens. Even though it is a potential means to regulate the size, quality, and duration of a tissue infiltrate, T cell egress from infected tissues is poorly understood. Using a mouse model of influenza A virus infection, we found that CD8 effector T cells egressed from the infected lung in a CCR7-dependent manner. In contrast, following antigen recognition, effector CD8 T cell egress decreased and CCR7 function was reduced in vivo and in vitro, indicating that the exit of CD8 T cells from infected tissues is tightly regulated. Our data suggest that the regulation of T cell egress is a mechanism to retain antigen-specific effectors at the site of infection to promote viral clearance, while decreasing the numbers of bystander T cells and preventing overt inflammation.", "title": "Tissue exit: a novel control point in the accumulation of antigen-specific CD8 T cells in the influenza a virus-infected lung." }, { "docid": "20148808", "text": "The mammalian gastrointestinal tract harbors a microbial community with metabolic activity critical for host health, including metabolites that can modulate effector functions of immune cells. Mice treated with vancomycin have an altered microbiome and metabolite profile, exhibit exacerbated T helper type 2 cell (Th2) responses, and are more susceptible to allergic lung inflammation. Here we show that dietary supplementation with short-chain fatty acids (SCFAs) ameliorates this enhanced asthma susceptibility by modulating the activity of T cells and dendritic cells (DCs). Dysbiotic mice treated with SCFAs have fewer interleukin-4 (IL4)-producing CD4+ T cells and decreased levels of circulating immunoglobulin E (IgE). In addition, DCs exposed to SCFAs activate T cells less robustly, are less motile in response to CCL19 in vitro, and exhibit a dampened ability to transport inhaled allergens to lung draining nodes. Our data thus demonstrate that gut dysbiosis can exacerbate allergic lung inflammation through both T cell- and DC-dependent mechanisms that are inhibited by SCFAs.", "title": "Microbiome-driven allergic lung inflammation is ameliorated by short-chain fatty acids" }, { "docid": "28644298", "text": "Epstein-Barr virus (EBV) latency III infection converts B lymphocytes into lymphoblastoid cell lines (LCLs) by expressing EBV nuclear and membrane proteins, EBNAs, and latent membrane proteins (LMPs), which regulate transcription through Notch and tumor necrosis factor receptor pathways. The role of NF-kappa B in LMP1 and overall EBV latency III transcriptional effects was investigated by treating LCLs with BAY11-7082 (BAY11). BAY11 rapidly and irreversibly inhibited NF-kappa B, decreased mitochondrial membrane potential, induced apoptosis, and altered LCL gene expression. BAY11 effects were similar to those of an NF-kappa B inhibitor, Delta N-I kappa B alpha, in effecting decreased JNK1 expression and in microarray analyses. More than 80% of array elements that decreased with Delta N-I kappa B alpha expression decreased with BAY11 treatment. Newly identified NF-kappa B-induced, LMP1-induced, and EBV-induced genes included pleckstrin, Jun-B, c-FLIP, CIP4, and I kappa B epsilon. Of 776 significantly changed array elements, 134 were fourfold upregulated in EBV latency III, and 74 were fourfold upregulated with LMP1 expression alone, whereas only 28 were more than fourfold downregulated by EBV latency III. EBV latency III-regulated gene products mediate cell migration (EBI2, CCR7, RGS1, RANTES, MIP1 alpha, MIP1 beta, CXCR5, and RGS13), antigen presentation (major histocompatibility complex proteins and JAW1), mitogen-activated protein kinase pathway (DUSP5 and p62Dok), and interferon (IFN) signaling (IFN-gamma R alpha, IRF-4, and STAT1). Comparison of EBV latency III LCL gene expression to immunoglobulin M (IgM)-stimulated B cells, germinal-center B cells, and germinal-center-derived lymphomas clustered LCLs with IgM-stimulated B cells separately from germinal-center cells or germinal-center lymphoma cells. Expression of IRF-2, AIM1, ASK1, SNF2L2, and components of IFN signaling pathways further distinguished EBV latency III-infected B cells from IgM-stimulated or germinal-center B cells.", "title": "Role of NF-kappa B in cell survival and transcription of latent membrane protein 1-expressing or Epstein-Barr virus latency III-infected cells." }, { "docid": "20690388", "text": "Natural killer (NK) cell activation is strictly regulated to ensure that healthy cells are preserved, but tumour-transformed or virus-infected cells are recognized and eliminated. To carry out this selective killing, NK cells have an ample repertoire of receptors on their surface. Signalling by inhibitory and activating receptors by interaction with their ligands will determine whether the NK cell becomes activated and kills the target cell. Here, we show reduced expression of NKp46, NKp30, DNAM-1, CD244 and CD94/NKG2C activating receptors on NK cells from acute myeloid leukaemia patients. This reduction may be induced by chronic exposure to their ligands on leukaemic blasts. The analysis of ligands for NK cell-activating receptors showed that leukaemic blasts from the majority of patients express ligands for NK cell-activating receptors. DNAM-1 ligands are frequently expressed on blasts, whereas the expression of the NKG2D ligand MICA/B is found in half of the patients and CD48, a ligand for CD244, in only one-fourth of the patients. The decreased expression of NK cell-activating receptors and/or the heterogeneous expression of ligands for major receptors on leukaemic blasts can lead to an inadequate tumour immunosurveillance by NK cells. A better knowledge of the activating receptor repertoire on NK cells and their putative ligands on blasts together with the possibility to modulate their expression will open new possibilities for the use of NK cells in immunotherapy against leukaemia.", "title": "Human NK cells in acute myeloid leukaemia patients: analysis of NK cell-activating receptors and their ligands" }, { "docid": "23938319", "text": "Retinoid receptors (RARs and RXRs) are ligand-activated transcription factors that regulate the transcription of target genes by recruiting coregulator complexes at cognate promoters. To understand the effects of heterodimerization and ligand binding on coactivator recruitment, we solved the crystal structure of the complex between the RARbeta/RXRalpha ligand-binding domain heterodimer, its 9-cis retinoic acid ligand, and an LXXLL-containing peptide (termed NR box 2) derived from the nuclear receptor interaction domain (NID) of the TRAP220 coactivator. In parallel, we measured the binding affinities of the isolated NR box 2 peptide or the full-length NID of the coactivator SRC-1 for retinoid receptors in the presence of various types of ligands. Our correlative analysis of three-dimensional structures and fluorescence data reveals that heterodimerization does not significantly alter the structure of individual subunits or their intrinsic capacity to interact with NR box 2. Similarly, we show that the ability of a protomer to recruit NR box 2 does not vary as a function of the ligand binding status of the partner receptor. In contrast, the strength of the overall association between the heterodimer and the full-length SRC-1 NID is dictated by the combinatorial action of RAR and RXR ligands, the simultaneous presence of the two receptor agonists being required for highest binding affinity. We identified an LXXLL peptide-driven mechanism by which the concerted reorientation of three phenylalanine side chains generates an \"aromatic clamp\" that locks the RXR activation helix H12 in the transcriptionally active conformation. Finally, we show how variations of helix H11-ligand interactions can alter the communication pathway linking helices H11, H12, and the connecting loop L11-12 to the coactivator-binding site. Together, our results reveal molecular and structural features that impact on the ligand-dependent interaction of the RAR/RXR heterodimer with nuclear receptor coactivators.", "title": "Characterization of the interaction between retinoic acid receptor/retinoid X receptor (RAR/RXR) heterodimers and transcriptional coactivators through structural and fluorescence anisotropy studies." }, { "docid": "12265561", "text": "The conformation of the ligand in complex with a macromolecular target can be studied by nuclear magnetic resonance (NMR) in solution for both tightly and weakly forming complexes. In the weak binding regime (k(off) > 10(4) Hz), the structure of the bound ligand is accessible also for very large complexes (>100 kDa), which are not amenable to NMR studies in the tight binding regime. Here I review the state-of-the-art NMR methodology used for screening ligands and for the structural investigation of bound ligand conformations, in both tight and weak binding regimes. The advantages and disadvantages of each approach are critically described. The NMR methodology used to investigate transiently forming complexes has expanded considerably in the past few years, opening new possibilities for a detailed description of ligand-target interactions. Novel methods for the determination of the bound ligand conformation, in particular transferred cross-correlated relaxation, are thoroughly reviewed, and their advantages with respect to established methodology are discussed, using the epothilone-tubulin complex as a primary example.", "title": "Ligand-target interactions: what can we learn from NMR?" }, { "docid": "10607877", "text": "Cell surface receptors have been extensively studied because they initiate and regulate signal transduction cascades leading to a variety of functional cellular outcomes. An important class of immune receptors (e.g., T-cell antigen receptors) whose ligands are anchored to the surfaces of other cells remain poorly understood. The mechanism by which ligand binding initiates receptor phosphorylation, a process termed \"receptor triggering\", remains controversial. Recently, direct measurements of the (two-dimensional) receptor-ligand complex lifetimes at cell-cell interface were found to be smaller than (three-dimensional) lifetimes in solution but the underlying mechanism is unknown. At the cell-cell interface, the receptor-ligand complex spans a short intermembrane distance (15 nm) compared to long surface molecules (LSMs) whose ectodomains span >40 nm and these LSMs include phosphatases (e.g., CD45) that dephosphorylate the receptor. It has been proposed that size-based segregation of LSMs from a receptor-ligand complex is a mechanism of receptor triggering but it is unclear whether the mechanochemistry supports such small-scale segregation. Here we present a nanometer-scale mathematical model that couples membrane elasticity with the compressional stiffness and lateral mobility of LSMs. We find robust supradiffusive segregation of LSMs from a single receptor-ligand complex. The model predicts that LSM redistribution will result in a time-dependent tension on the complex leading to a decreased two-dimensional lifetime. Interestingly, the model predicts a nonlinear relationship between the three- and two-dimensional lifetimes, which can enhance the ability of receptors to discriminate between similar ligands.", "title": "Mechanical modulation of receptor-ligand interactions at cell-cell interfaces." }, { "docid": "40383969", "text": "TGF-beta ligands stimulate diverse cellular differentiation and growth responses by signaling through type I and II receptors. Ligand antagonists, such as follistatin, block signaling and are essential regulators of physiological responses. Here we report the structure of activin A, a TGF-beta ligand, bound to the high-affinity antagonist follistatin. Two follistatin molecules encircle activin, neutralizing the ligand by burying one-third of its residues and its receptor binding sites. Previous studies have suggested that type I receptor binding would not be blocked by follistatin, but the crystal structure reveals that the follistatin N-terminal domain has an unexpected fold that mimics a universal type I receptor motif and occupies this receptor binding site. The formation of follistatin:BMP:type I receptor complexes can be explained by the stoichiometric and geometric arrangement of the activin:follistatin complex. The mode of ligand binding by follistatin has important implications for its ability to neutralize homo- and heterodimeric ligands of this growth factor family.", "title": "The structure of the follistatin:activin complex reveals antagonism of both type I and type II receptor binding." }, { "docid": "40963697", "text": "The family of tumor necrosis factor receptors (TNFRs) and their ligands form a regulatory signaling network that controls immune responses. Various members of this receptor family respond differently to the soluble and membrane-bound forms of their respective ligands. However, the determining factors and underlying molecular mechanisms of this diversity are not yet understood. Using an established system of chimeric TNFRs and novel ligand variants mimicking the bioactivity of membrane-bound TNF (mTNF), we demonstrate that the membrane-proximal extracellular stalk regions of TNFR1 and TNFR2 are crucial in controlling responsiveness to soluble TNF (sTNF). We show that the stalk region of TNFR2, in contrast to the corresponding part of TNFR1, efficiently inhibits both the receptor's enrichment/clustering in particular cell membrane regions and ligand-independent homotypic receptor preassembly, thereby preventing sTNF-induced, but not mTNF-induced, signaling. Thus, the stalk regions of the two TNFRs not only have implications for additional TNFR family members, but also provide potential targets for therapeutic intervention.", "title": "The tumor necrosis factor receptor stalk regions define responsiveness to soluble versus membrane-bound ligand." }, { "docid": "994800", "text": "T cell receptor (TCR) ligation is required for the extrathymic differentiation of forkhead box p3(+) (Foxp3(+)) regulatory T cells. Several lines of evidence indicate that weak TCR stimulation favors induction of Foxp3 in the periphery; however, it remains to be determined how TCR ligand potency influences this process. We characterized the density and affinity of TCR ligand favorable for Foxp3 induction and found that a low dose of a strong agonist resulted in maximal induction of Foxp3 in vivo. Initial Foxp3 induction by weak agonist peptide could be enhanced by disruption of TCR-peptide major histocompatibility complex (pMHC) interactions or alteration of peptide dose. However, time course experiments revealed that Foxp3-positive cells induced by weak agonist stimulation are deleted, along with their Foxp3-negative counterparts, whereas Foxp3-positive cells induced by low doses of the strong agonist persist. Our results suggest that, together, pMHC ligand potency, density, and duration of TCR interactions define a cumulative quantity of TCR stimulation that determines initial peripheral Foxp3 induction. However, in the persistence of induced Foxp3(+) T cells, TCR ligand potency and density are noninterchangeable factors that influence the route to peripheral tolerance.", "title": "TCR ligand density and affinity determine peripheral induction of Foxp3 in vivo" }, { "docid": "13868795", "text": "Ligation of the CD28 receptor on T cells provides a critical second signal alongside T cell receptor (TCR) ligation for naive T cell activation. Here, we discuss the expression, structure, and biochemistry of CD28 and its ligands. CD28 signals play a key role in many T cell processes, including cytoskeletal remodeling, production of cytokines, survival, and differentiation. CD28 ligation leads to unique epigenetic, transcriptional, and post-translational changes in T cells that cannot be recapitulated by TCR ligation alone. We discuss the function of CD28 and its ligands in both effector and regulatory T cells. CD28 is critical for regulatory T cell survival and the maintenance of immune homeostasis. We outline the roles that CD28 and its family members play in human disease and we review the clinical efficacy of drugs that block CD28 ligands. Despite the centrality of CD28 and its family members and ligands to immune function, many aspects of CD28 biology remain unclear. Translation of a basic understanding of CD28 function into immunomodulatory therapeutics has been uneven, with both successes and failures. Such real-world results might stem from multiple factors, including complex receptor-ligand interactions among CD28 family members, differences between the mouse and human CD28 families, and cell-type specific roles of CD28 family members.", "title": "CD28 Costimulation: From Mechanism to Therapy." }, { "docid": "2714623", "text": "How membrane receptors initiate signal transduction upon ligand binding is a matter of intense scrutiny. The T cell receptor complex (TCR-CD3) is composed of TCR alpha/beta ligand binding subunits bound to the CD3 subunits responsible for signal transduction. Although it has long been speculated that TCR-CD3 may undergo a conformational change, confirmation is still lacking. We present strong evidence that ligand engagement of TCR-CD3 induces a conformational change that exposes a proline-rich sequence in CD3 epsilon and results in recruitment of the adaptor protein Nck. This occurs earlier than and independently of tyrosine kinase activation. Finally, by interfering with Nck-CD3 epsilon association in vivo, we demonstrate that TCR-CD3 recruitment of Nck is critical for maturation of the immune synapse and for T cell activation.", "title": "Recruitment of Nck by CD3ϵ Reveals a Ligand-Induced Conformational Change Essential for T Cell Receptor Signaling and Synapse Formation" }, { "docid": "33499189", "text": "T cell receptor (TCR-CD3) triggering involves both receptor clustering and conformational changes at the cytoplasmic tails of the CD3 subunits. The mechanism by which TCRalphabeta ligand binding confers conformational changes to CD3 is unknown. By using well-defined ligands, we showed that induction of the conformational change requires both multivalent engagement and the mobility restriction of the TCR-CD3 imposed by the plasma membrane. The conformational change is elicited by cooperative rearrangements of two TCR-CD3 complexes and does not require accompanying changes in the structure of the TCRalphabeta ectodomains. This conformational change at CD3 reverts upon ligand dissociation and is required for T cell activation. Thus, our permissive geometry model provides a molecular mechanism that rationalizes how the information of ligand binding to TCRalphabeta is transmitted to the CD3 subunits and to the intracellular signaling machinery.", "title": "Full activation of the T cell receptor requires both clustering and conformational changes at CD3." }, { "docid": "7621534", "text": "Although chemokines are well established to function in immunity and endothelial cell activation and proliferation, a rapidly growing literature suggests that CXC Chemokine receptors CXCR3, CXCR4 and CXCR7 are critical in the development and progression of solid tumors. The effect of these chemokine receptors in tumorigenesis is mediated via interactions with shared ligands I-TAC (CXCL11) and SDF-1 (CXCL12). Over the last decade, CXCR4 has been extensively reported to be overexpressed in most human solid tumors and has earned considerable attention toward elucidating its role in cancer metastasis. To enrich the existing armamentarium of anti-cancerous agents, many inhibitors of CXCL12-CXCR4 axis have emerged as additional or alternative agents for neo-adjuvant treatments and even many of them are in preclinical and clinical stages of their development. However, the discovery of CXCR7 as another receptor for CXCL12 with rather high binding affinity and recent reports about its involvement in cancer progression, has questioned the potential of \"selective blockade\" of CXCR4 as cancer chemotherapeutics. Interestingly, CXCR7 can also bind another chemokine CXCL11, which is an established ligand for CXCR3. Recent reports have documented that CXCR3 and their ligands are overexpressed in different solid tumors and regulate tumor growth and metastasis. Therefore, it is important to consider the interactions and crosstalk between these three chemokine receptors and their ligand mediated signaling cascades for the development of effective anti-cancer therapies. Emerging evidence also indicates that these receptors are differentially expressed in tumor endothelial cells as well as in cancer stem cells, suggesting their direct role in regulating tumor angiogenesis and metastasis. In this review, we will focus on the signals mediated by this receptor trio via their shared ligands and their role in tumor growth and progression.", "title": "Chemokine receptor trio: CXCR3, CXCR4 and CXCR7 crosstalk via CXCL11 and CXCL12." }, { "docid": "13639330", "text": "Nuclear receptors undergo ligand-dependent conformational changes that are required for corepressor-coactivator exchange, but whether there is an actual requirement for specific epigenetic landmarks to impose ligand dependency for gene activation remains unknown. Here we report an unexpected and general strategy that is based on the requirement for specific cohorts of inhibitory histone methyltransferases (HMTs) to impose gene-specific gatekeeper functions that prevent unliganded nuclear receptors and other classes of regulated transcription factors from binding to their target gene promoters and causing constitutive gene activation in the absence of stimulating signals. This strategy, based at least in part on an HMT-dependent inhibitory histone code, imposes a requirement for specific histone demethylases, including LSD1, to permit ligand- and signal-dependent activation of regulated gene expression. These events link an inhibitory methylation component of the histone code to a broadly used strategy that circumvents pathological constitutive gene induction by physiologically regulated transcription factors.", "title": "Histone Methylation-Dependent Mechanisms Impose Ligand Dependency for Gene Activation by Nuclear Receptors" }, { "docid": "40760684", "text": "As ligand-regulated transcription factors, the nuclear hormone receptors are nearly ideal drug targets, with internal pockets that bind to hydrophobic, drug-like molecules and well-characterized ligand-induced conformational changes that recruit transcriptional coregulators to promoter elements. Yet, due to the multitude of genes under the control of a single receptor, the major challenge has been the identification of ligands with gene-selective actions, impacting disease outcomes through a narrow subset of target genes and not across their entire gene-regulatory repertoire. Here, we summarize the concepts and work to date underlying the development of steroidal and nonsteroidal receptor ligands, including the use of crystal structures, high-throughput screens, and rational design approaches for finding useful therapeutic molecules. Difficulties in finding selective receptor modulators require a more complete understanding of receptor interdomain communications, posttranslational modifications, and receptor-protein interactions that could be exploited for target gene selectivity.", "title": "Structural overview of the nuclear receptor superfamily: insights into physiology and therapeutics." }, { "docid": "7729656", "text": "Ionotropic glutamate receptors (iGluRs) constitute a family of ligand-gated ion channels that are essential for mediating fast synaptic transmission in the central nervous system. These receptors play an important role for the development and function of the nervous system, and are essential in learning and memory. However, iGluRs are also implicated in or have causal roles for several brain disorders, e.g. epilepsy, Alzheimer's disease, Parkinson's disease and schizophrenia. Their involvement in neurological diseases has stimulated widespread interest in their structure and function. Since the first publication in 1998 of the structure of a recombinant soluble protein comprising the ligand-binding domain of GluA2 extensive studies have afforded numerous crystal structures of wildtype and mutant proteins including different ligands. The structural information obtained combined with functional data have led to models for receptor activation and desensitization by agonists, inhibition by antagonists and block of desensitization by positive allosteric modulators. Furthermore, the structural and functional studies have formed a powerful platform for the design of new selective compounds.", "title": "Lessons from more than 80 structures of the GluA2 ligand-binding domain in complex with agonists, antagonists and allosteric modulators." }, { "docid": "40667066", "text": "Steroid hormones, thyroid hormones, retinoic acids, and vitamin D bind to their receptors, which are now called steroid/nuclear receptors, and liganded receptors translocate either intracellularly or intranuclearly and form large protein complexes with cofactors to induce or repress gene transcription. Therefore, steroid/nuclear receptors are ligand-dependent transcription factors. With the advent of green fluorescent protein (GFP) and its color variants, the subcellular distribution of many steroid/nuclear receptors has been found to be much more dynamic than previously thought, with some of the receptors shuttling between the cytoplasm and nucleus. Steroid/nuclear receptors can be divided into three categories based on their unliganded distribution: those that are primarily in the nucleus, those in the cytoplasm, and those with mixed cytoplasmic and nuclear distributions. However, in all cases, the addition of a ligand leads to almost complete nuclear translocation of the receptors. Hormonal stimulation induces intranuclear receptor distribution from a homogeneous pattern to a heterogeneous dot-like image. Ligand binding to steroid/nuclear receptors leads to the recruitment of many proteins including cofactors to provoke the redistribution of receptor complexes in the nucleus. This focal organization could involve more complex events than simple DNA binding sites for transcription. Protein activities and interactions of steroid/nuclear receptors can be imaged and localized in a single cell.", "title": "Subcellular steroid/nuclear receptor dynamics." }, { "docid": "18346333", "text": "Glutamate receptors mediate the majority of excitatory synaptic transmission in the CNS. The AMPA-subtype has rapid kinetics, with activation, deactivation and desensitization proceeding on the millisecond timescale or faster. Crystallographic, biochemical, and functional studies suggest that GluR2 Cys mutants which form intermolecular disulfide cross-links between the lower D2 lobes of the ligand binding cores can be trapped in a conformation that represents the desensitized state. We used multi-channel rapid perfusion techniques to examine the state dependence of cross-linking in these mutants. Under reducing conditions, both wild-type GluR2 and the G725C and S729C mutants have normal activation and desensitization kinetics, but the Cys mutants can be efficiently trapped in nonconducting states when oxidized. In contrast the I664C mutant is only partially inactivated under oxidizing conditions. For S729C, disulfide cross-links form rapidly when receptors are desensitized in the presence of glutamate, but receptors also become trapped at rest, in the absence of agonist. We assessed such spontaneous trapping in various conditions, including CNQX, a competitive antagonist; kainate, a weak partial agonist; or when desensitization was blocked by the L483Y mutation that stabilizes the D1 dimer interface. These experiments suggest that trapping in the absence of glutamate is due to two motions: Spontaneous breaking of the D1 dimer interface and hyperextension of the lower lobes of the ligand binding core. These data show that the glutamate binding domains are surprisingly mobile in the absence of ligand, which could influence receptor activity in the brain.", "title": "AMPA receptor ligand binding domain mobility revealed by functional cross linking." }, { "docid": "22134353", "text": "Natural killer (NK) cells are able to lyse infected and tumor cells while sparing healthy cells. Recognition of diseased cells by NK cells is governed by several activating and inhibitory receptors. We review numerous pathways that have been implicated in the regulation of self-ligands for activating receptors, including NKG2D, DNAM-1, LFA-1, NKp30, NKp44, NKp46, NKp65, and NKp80 found on NK cells and some T cells. Understanding how the regulation of self-encoded ligand expression is regulated may provide novel avenues for future therapeutic approaches to infections and cancer.", "title": "Regulation of self-ligands for activating natural killer cell receptors." }, { "docid": "14544564", "text": "Sterol-sensing nuclear receptors and insulin-like growth factor signaling play evolutionarily conserved roles in the control of aging. In the nematode Caenorhabditis elegans, bile acid-like steroid hormones known as dafachronic acids (DAs) influence longevity by binding to and regulating the activity of the conserved nuclear receptor DAF-12, and the insulin receptor (InsR) ortholog DAF-2 controls life span by inhibiting the FoxO transcription factor DAF-16. How the DA/DAF-12 pathway interacts with DAF-2/InsR signaling to control life span is poorly understood. Here we specifically investigated the roles of liganded and unliganded DAF-12 in life span control in the context of reduced DAF-2/InsR signaling. In animals with reduced daf-2/InsR activity, mutations that either reduce DA biosynthesis or fully abrogate DAF-12 activity shorten life span, suggesting that liganded DAF-12 promotes longevity. In animals with reduced DAF-2/InsR activity induced by daf-2/InsR RNAi, both liganded and unliganded DAF-12 promote longevity. However, in daf-2/InsR mutants, liganded and unliganded DAF-12 act in opposition to control life span. Thus, multiple DAF-12 activities influence life span in distinct ways in contexts of reduced DAF-2/InsR signaling. Our findings establish new roles for a conserved steroid signaling pathway in life span control and elucidate interactions among DA biosynthetic pathways, DAF-12, and DAF-2/InsR signaling in aging.", "title": "Influence of Steroid Hormone Signaling on Life Span Control by Caenorhabditis elegans Insulin-Like Signaling" }, { "docid": "8856690", "text": "The hormonal metabolite of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D), initiates biological responses via binding to the vitamin D receptor (VDR). When occupied by 1,25D, VDR interacts with the retinoid X receptor (RXR) to form a heterodimer that binds to vitamin D responsive elements in the region of genes directly controlled by 1,25D. By recruiting complexes of either coactivators or corepressors, ligand-activated VDR-RXR modulates the transcription of genes encoding proteins that promulgate the traditional functions of vitamin D, including signaling intestinal calcium and phosphate absorption to effect skeletal and calcium homeostasis. Thus, vitamin D action in a particular cell depends upon the metabolic production or delivery of sufficient concentrations of the 1,25D ligand, expression of adequate VDR and RXR coreceptor proteins, and cell-specific programming of transcriptional responses to regulate select genes that encode proteins that function in mediating the effects of vitamin D. For example, 1,25D induces RANKL, SPP1 (osteopontin), and BGP (osteocalcin) to govern bone mineral remodeling; TRPV6, CaBP9k, and claudin 2 to promote intestinal calcium absorption; and TRPV5, klotho, and Npt2c to regulate renal calcium and phosphate reabsorption. VDR appears to function unliganded by 1,25D in keratinocytes to drive mammalian hair cycling via regulation of genes such as CASP14, S100A8, SOSTDC1, and others affecting Wnt signaling. Finally, alternative, low-affinity, non-vitamin D VDR ligands, e.g., lithocholic acid, docosahexaenoic acid, and curcumin, have been reported. Combined alternative VDR ligand(s) and 1,25D/VDR control of gene expression may delay chronic disorders of aging such as osteoporosis, type 2 diabetes, cardiovascular disease, and cancer.", "title": "Molecular Mechanisms of Vitamin D Action" }, { "docid": "3127341", "text": "The glucagon-like peptide-1 receptor (GLP-1R) is a key physiological regulator of insulin secretion and a major therapeutic target for the treatment of type II diabetes. However, regulation of GLP-1R function is complex with multiple endogenous peptides that interact with the receptor, including full-length (1-37) and truncated (7-37) forms of GLP-1 that can exist in an amidated form (GLP-1(1-36)NH₂ and GLP-1(7-36)NH₂) and the related peptide oxyntomodulin. In addition, the GLP-1R possesses exogenous agonists, including exendin-4, and the allosteric modulator, compound 2 (6,7-dichloro-2-methylsulfonyl-3-tert-butylaminoquinoxaline). The complexity of this ligand-receptor system is further increased by the presence of several single nucleotide polymorphisms (SNPs) that are distributed across the receptor. We have investigated 10 GLP-1R SNPs, which were characterized in three physiologically relevant signaling pathways (cAMP accumulation, extracellular signal-regulated kinase 1/2 phosphorylation, and intracellular Ca²⁺ mobilization); ligand binding and cell surface receptor expression were also determined. We demonstrate both ligand- and pathway-specific effects for multiple SNPs, with the most dramatic effect observed for the Met¹⁴⁹ receptor variant. At the Met¹⁴⁹ variant, there was selective loss of peptide-induced responses across all pathways examined, but preservation of response to the small molecule compound 2. In contrast, at the Cys³³³ variant, peptide responses were preserved but there was attenuated response to compound 2. Strikingly, the loss of peptide function at the Met¹⁴⁹ receptor variant could be allosterically rescued by compound 2, providing proof-of-principle evidence that allosteric drugs could be used to treat patients with this loss of function variant.", "title": "Polymorphism and ligand dependent changes in human glucagon-like peptide-1 receptor (GLP-1R) function: allosteric rescue of loss of function mutation." }, { "docid": "16361581", "text": "Notch receptors expressed on hematopoietic stem cells interact with their ligands on bone marrow stromal cells and thereby control cell fate decisions and survival. We recently demonstrated that Notch signaling is involved in proliferation and survival of B cell-derived tumor cells of classic Hodgkin disease and described a novel mechanism for the oncogenic capacity of Notch. In this study we investigated whether Notch signaling is involved in the tight interactions between neoplastic plasma cells and their bone marrow microenvironment, which are essential for tumor cell growth in multiple myeloma (MM). Here we demonstrate that Notch receptors and their ligand Jagged1 are highly expressed in cultured and primary MM cells, whereas nonneoplastic counterparts show low to undetectable levels of Notch. Functional data indicate that ligand-induced Notch signaling is a growth factor for MM cells and suggest that these interactions contribute to myelomagenesis in vivo.", "title": "Jagged1-induced Notch signaling drives proliferation of multiple myeloma cells." }, { "docid": "28086354", "text": "Morphogenesis of the adult structures of holometabolous insects is regulated by ecdysteroids and juvenile hormones and involves cell-cell interactions mediated in part by the cell surface integrin receptors and their extracellular matrix (ECM) ligands. These adhesion molecules and their regulation by hormones are not well characterized. We describe the gene structure of a newly described ECM molecule, tenectin, and demonstrate that it is a hormonally regulated ECM protein required for proper morphogenesis of the adult wing and male genitalia. Tenectin's function as a new ligand of the PS2 integrins is demonstrated by both genetic interactions in the fly and by cell spreading and cell adhesion assays in cultured cells. Its interaction with the PS2 integrins is dependent on RGD and RGD-like motifs. Tenectin's function in looping morphogenesis in the development of the male genitalia led to experiments that demonstrate a role for PS integrins in the execution of left-right asymmetry.", "title": "Tenectin is a novel alphaPS2betaPS integrin ligand required for wing morphogenesis and male genital looping in Drosophila." }, { "docid": "12956194", "text": "Ligand-directed signal bias offers opportunities for sculpting molecular events, with the promise of better, safer therapeutics. Critical to the exploitation of signal bias is an understanding of the molecular events coupling ligand binding to intracellular signaling. Activation of class B G protein-coupled receptors is driven by interaction of the peptide N terminus with the receptor core. To understand how this drives signaling, we have used advanced analytical methods that enable separation of effects on pathway-specific signaling from those that modify agonist affinity and mapped the functional consequence of receptor modification onto three-dimensional models of a receptor-ligand complex. This yields molecular insights into the initiation of receptor activation and the mechanistic basis for biased agonism. Our data reveal that peptide agonists can engage different elements of the receptor extracellular face to achieve effector coupling and biased signaling providing a foundation for rational design of biased agonists.", "title": "The Extracellular Surface of the GLP-1 Receptor Is a Molecular Trigger for Biased Agonism" } ]
25606
Kristen Bell is American.
[ { "docid": "Kristen_Bell", "text": "Kristen Anne Bell ( born July 18 , 1980 ) is an American actress and singer . She began her acting career starring in stage productions and attended the Tisch School of Arts in New York . In 2001 , she made her Broadway debut as Becky Thatcher in The Adventures of Tom Sawyer and starred in the Broadway revival of The Crucible the following year . In 2004 , she had a supporting role in the film Spartan and received praise for her first leading performance in Gracie 's Choice . Bell gained critical acclaim for her first major role as the title character in the teen noir drama television series Veronica Mars ( 2004 -- 07 ) . For her performance she was awarded a Saturn Award for Best Actress on Television . She reprised the eponymous role in the 2014 film continuation of the series . During her time on Veronica Mars , Bell appeared as Mary Lane in the film Reefer Madness : The Movie Musical ( 2005 ) , a reprise of the role she had played in the New York musical upon which the film was based . In 2007 , Bell joined the cast of the sci-fi series Heroes , playing the character Elle Bishop , for which she was nominated for a Saturn Award . In 2008 , she had her breakout film role as the title character in Forgetting Sarah Marshall . She has since appeared in a number of comedy films , such as Couples Retreat ( 2009 ) , When in Rome ( 2010 ) , You Again ( 2010 ) , and The Boss ( 2016 ) . Bell garnered further recognition for voicing Princess Anna in the Disney film Frozen ( 2013 ) , the short film Frozen Fever ( 2015 ) , and the upcoming Frozen 2 . She also starred as the female lead on the Showtime series House of Lies . Since 2016 , she has starred in the main role of Eleanor Shellstrop on the NBC comedy series The Good Place . Bell married actor Dax Shepard in 2013 , with whom she has two daughters .", "title": "" } ]
[ { "docid": "Serious_Moonlight_(2009_film)", "text": "Serious Moonlight is a 2009 American black comedy film directed by Cheryl Hines and starring Meg Ryan , Timothy Hutton , Kristen Bell , and Justin Long . It was released by Magnolia Pictures on 4 December 2009 .", "title": "" }, { "docid": "The_Lifeguard", "text": "The Lifeguard is a 2013 American drama produced , written , and directed by Liz W. Garcia , and starring Kristen Bell and David Lambert . The film was released via video on demand on July 30 , 2013 , and received a limited release in theaters on August 30 .", "title": "" }, { "docid": "A_Bad_Moms_Christmas", "text": "A Bad Moms Christmas is an upcoming American Christmas black comedy film directed and written by Jon Lucas and Scott Moore . It is a sequel of the 2016 film Bad Moms . The film stars Mila Kunis , Kristen Bell , and Kathryn Hahn .", "title": "" }, { "docid": "Pulse_(2006_film)", "text": "Pulse is a 2006 American horror film and remake of the Japanese horror film , Kairo ; Pulse was written by Wes Craven and Ray Wright , and directed by Jim Sonzero . The film stars Kristen Bell , Ian Somerhalder , Christina Milian and a cameo by Brad Dourif .", "title": "" }, { "docid": "Spartan_(film)", "text": "Spartan is a 2004 American political thriller film written and directed by David Mamet . It features Val Kilmer , Derek Luke , Tia Texada , Ed O'Neill , William H. Macy , and Kristen Bell . It was released in the United States and Canada on 12 March 2004 .", "title": "" }, { "docid": "Veronica_Mars_(film)", "text": "Veronica Mars is a 2014 American neo-noir mystery comedy-drama film produced and directed by Rob Thomas , who co-wrote the script with Diane Ruggiero . It is a continuing film adaptation based on Thomas ' UPN/CW television series of the same name and stars Kristen Bell reprising her role as the title character . Its executive producers are Joel Silver , Bell , and Jenny Hinkey . Warner Bros. . Pictures opened the film in the United States in a limited release and through video on demand on March 14 , 2014 .", "title": "" }, { "docid": "For_the_First_Time_in_Forever", "text": "`` For the First Time in Forever '' is a song from Disney 's 2013 animated feature film Frozen , with music and lyrics composed by Kristen Anderson-Lopez and Robert Lopez . It is reprised later in the musical . Both versions are sung by sisters Princess Anna ( Kristen Bell ) and Queen Elsa ( Idina Menzel ) .", "title": "" }, { "docid": "When_in_Rome_(2010_film)", "text": "When in Rome is a 2010 American romantic comedy film directed by Mark Steven Johnson , co-written by Johnson , David Diamond and David Weissman . It stars Kristen Bell and Josh Duhamel . It was released by Touchstone Pictures in the United States on January 29 , 2010 .", "title": "" }, { "docid": "Frozen_Fever", "text": "Frozen Fever is a 2015 American computer-animated musical fantasy short film produced by Walt Disney Animation Studios and released by Walt Disney Pictures . It is a sequel to the 2013 feature film Frozen , and tells the story of Anna 's birthday party given by Elsa with the help of Kristoff , Sven , and Olaf . Chris Buck and Jennifer Lee again served as the directors with Kristen Bell , Idina Menzel , Jonathan Groff , and Josh Gad providing the lead voices . Production on Frozen Fever began in June 2014 and took six months to complete . The film debuted in theaters alongside Walt Disney Pictures ' Cinderella on March 13 , 2015 . It received positive reviews from critics , along with praise for its new song `` Making Today a Perfect Day '' by Kristen Anderson-Lopez and Robert Lopez .", "title": "" }, { "docid": "The_Boss_(2016_film)", "text": "The Boss is a 2016 American comedy film directed by Ben Falcone and written by Falcone , Melissa McCarthy and Steve Mallory . The film stars McCarthy , Kristen Bell , Ella Anderson , Tyler Labine , Kathy Bates , Annie Mumolo , Timothy Simons and Peter Dinklage . The film was released on April 8 , 2016 , by Universal Pictures .", "title": "" }, { "docid": "Lauralee_Bell", "text": "Lauralee Kristen Bell ( born December 22 , 1968 ) is an American soap opera actress . She was born in Chicago , Illinois , and attended The Latin School of Chicago . The daughter of soap opera creators William J. Bell and Lee Phillip Bell , and sister to Bill Bell , Jr. and Bradley Bell as well as sister-in-law to Maria Arena Bell and Colleen Bell , Lauralee was offered a bit role as a model , Christine `` Cricket '' Blair , on her parents ' show The Young and the Restless in 1983 and that became a contract role in 1986 . Over time , her character matured from a model into a legal aid lawyer . Her character also dropped the childish moniker `` Cricket '' , especially after her rival Phyllis ( Michelle Stafford ) turned it into a pun against her , calling her `` the Bug . '' In January 2005 , Bell asked to be released from her contract , and she appears only on a recurring basis . Lauralee married photographer Scott Martin on October 4 , 1997 . They have a son , Christian James Martin , born on January 17 , 2001 and a daughter , Samantha Lee Martin , born on October 28 , 2002 . In June 2007 , she reprised her role of Christine Blair for a short run on The Bold and the Beautiful . In July 2010 , she returned to The Young and the Restless in a recurring capacity . Lauralee co-owned a boutique , On Sunset , which closed in 2009 .", "title": "" }, { "docid": "Hit_and_Run_(2012_film)", "text": "Hit and Run is a 2012 American action comedy film written by Dax Shepard , with David Palmer and Shepard co-directing again ( their first film being Brother 's Justice in 2010 ) . The film stars Shepard and his now-wife Kristen Bell , with Kristin Chenoweth , Tom Arnold , and Bradley Cooper . It was released on August 22 , 2012 .", "title": "" }, { "docid": "How_to_Be_a_Latin_Lover", "text": "How to Be a Latin Lover is a 2017 American comedy film directed by Ken Marino , written by Chris Spain and Jon Zack and stars Eugenio Derbez , Salma Hayek , Rob Lowe , Kristen Bell , Raphael Alejandro , Raquel Welch and Rob Riggle . It was released on April 28 , 2017 by Pantelion Films and has grossed $ 50 million worldwide .", "title": "" }, { "docid": "Kristen_Dalton", "text": "Kristen Dalton may refer to : Kristen Dalton ( actress ) ( born 1966 ) , American actress Kristen Dalton ( Miss USA ) ( born 1986 ) , American beauty pageant titleholder", "title": "" }, { "docid": "Some_Girl(s)_(film)", "text": "Some Girl ( s ) is a 2013 American comedy film directed by Daisy von Scherler Mayer and written by Neil LaBute . It is based on the play of the same name , also written by LaBute . The film stars Adam Brody , Kristen Bell , Zoe Kazan , Mía Maestro , Jennifer Morrison and Emily Watson . The film was released on June 26 , 2013 , by Leeden Media .", "title": "" }, { "docid": "Green-Eyed_Monster_(Veronica_Mars)", "text": "`` Green-Eyed Monster '' is the fourth episode of the second season of the American television series Veronica Mars , and the twenty-sixth episode overall . Written by Dayna Lynne North and directed by Jason Bloom , the episode premiered on UPN on October 19 , 2005 . The series depicts the adventures of Veronica Mars ( Kristen Bell ) as she deals with life as a high school student while moonlighting as a private detective . In this episode , Veronica helps a woman named Julie ( Laura Bell Bundy ) find out whether her boyfriend , Collin ( Michael E. Rodgers ) , is cheating on her . Meanwhile , Nathan Woods ( Cress Williams ) shows up in Neptune and gives some new information regarding Alicia Fennel ( Erica Gimpel ) .", "title": "" }, { "docid": "Polish_Wedding", "text": "Polish Wedding is a 1998 American comedy-drama film written and directed by Theresa Connelly . It was screened at the Sundance Film Festival on January 16 , 1998 and Berlin International Film Festival on February 12 . It was released in the U.S. on July 17 . It takes place within the Polish American community of Hamtramck , Michigan -- the childhood home of director Theresa Connelly -- at some time between the 1950s and 1970s . Virtually all characters are Polish Americans , though the actors playing them are mostly of other ethnic origins . The film is also ( a then-unknown ) Kristen Bell 's film debut in her uncredited role .", "title": "" }, { "docid": "Elias_Tahan", "text": "Elias Tahan ( born September 11 , 1986 ) is an American photographer currently located in Los Angeles . Elias Tahan has been featured in publications such as Flaunt , Interview , and Nylon . His celebrity subjects include Jennifer Lopez , Malin Åkerman , Shirley Manson , Solange Knowles , Kristen Bell , Jena Malone , Nicole Richie , Ashley Tisdale , Rachael Leigh Cook , Sara Paxton , Shenae Grimes , Melanie Brown , and Shay Mitchell .", "title": "" }, { "docid": "Love_Is_an_Open_Door", "text": "`` Love Is an Open Door '' is a song written by Kristen Anderson-Lopez and Robert Lopez for Walt Disney Animation Studios 's 53rd animated feature film Frozen ( 2013 ) . Performed by Kristen Bell and Santino Fontana as Anna and Prince Hans respectively , `` Love Is an Open Door '' is a romantic duet which takes place during the first act of the film , when Anna meets Hans during the reception of her sister Elsa 's coronation . The song was intended by Lopez and Anderson-Lopez to `` feel like the perfect first date '' , inspired by the date depicted in the film The Karate Kid ( 1984 ) .", "title": "" }, { "docid": "Couples_Retreat", "text": "Couples Retreat is a 2009 American romantic comedy film directed by Peter Billingsley marking his directorial debut , and written by Jon Favreau , Vince Vaughn , Dana Fox , Curtis Hanson , and Greg Beeman . Vaughn and Favreau star with Jason Bateman , Faizon Love , Kristin Davis , Malin Åkerman , Kristen Bell , and Jean Reno . It was released on October 9 , 2009 , in the United States . The film was shot mostly on the French Polynesian island of Bora Bora . This film has been rated PG-13 .", "title": "" }, { "docid": "Locations_in_Veronica_Mars", "text": "Veronica Mars is an American television series created by Rob Thomas . The series premiered on September 22 , 2004 , during UPN 's last two years , and ended on May 22 , 2007 , after a season on UPN 's successor , The CW Television Network . Set in the fictional town of Neptune , the series starred Kristen Bell as the title character , a student who progressed from high school to college during the series while moonlighting as a private investigator under the wing of her detective father .", "title": "" }, { "docid": "Lost_Masterpieces_of_Pornography", "text": "Lost Masterpieces of Pornography is a 2010 short film written and directed by David Mamet , and starring Kristen Bell , Ed O'Neill and Ricky Jay . It was produced for Funny or Die .", "title": "" }, { "docid": "Text_Me_Merry_Christmas", "text": "`` Text Me Merry Christmas '' is a song performed by Straight No Chaser and Kristen Bell . It was written by Adam Schlesinger and David Javerbaum . The song was released on November 17 , 2014 .", "title": "" }, { "docid": "Kristen_Dalton_(actress)", "text": "Kristen Dalton ( born Kristen V. Hocking ; February 14 , 1973 ) is an American actress who has appeared in over 20 television shows .", "title": "" }, { "docid": "You_Think_You_Know_Somebody", "text": "`` You Think You Know Somebody '' is the fifth episode of the first season of the American mystery television series Veronica Mars . Written by Dayna Lynne North and directed by Nick Gomez , the episode premiered on UPN on October 26 , 2004 . The series depicts the adventures of Veronica Mars ( Kristen Bell ) as she deals with life as a high school student while moonlighting as a private detective . In this episode , Veronica goes on the case when her boyfriend Troy Vandegraff 's ( Aaron Ashmore ) car goes missing and finds out some unpleasant information in the process .", "title": "" }, { "docid": "Kristen_Heiss", "text": "Kristen Pritchett formerly Kristen Elizabeth Heiss ( born May 12 , 1987 ) is an American backstroke and freestyle swimmer . She is a 14-time collegiate All-American , Big 12 Conference swimmer of the year , 10-time Big 12 Champion , an Olympic Trials finalist , US National Team Member ( 2008-2010 ) , and won the 200 freestyle at the 2008 U.S. Open .", "title": "" }, { "docid": "Kristen_Walsh_Bellows", "text": "Kristen Walsh Bellows ( born Kristen Walsh , May 5 , 1982 ) is a retired American racquetball player . Wachtel 's highest women 's professional ranking was 4th , and she represented the USA on four occasions winning Women 's Singles at the 2005 Pan American Championships . She was a three-time collegiate champion , and a four-time World Junior champion .", "title": "" }, { "docid": "2013_CMT_Music_Awards", "text": "The 2013 CMT Music Awards is a music award ceremony that was held on June 5 , 2013 at the Bridgestone Arena in Nashville , Tennessee . CMT . The show was hosted by Kristen Bell and Jason Aldean .", "title": "" }, { "docid": "30th_Independent_Spirit_Awards", "text": "The 2014 Independent Spirit Awards announced its nominees on November 30 , 2014 . The winners were announced on February 21 , 2015 . The ceremony was hosted by Fred Armisen and Kristen Bell .", "title": "" }, { "docid": "Gracie's_Choice", "text": "Gracie 's Choice is a 2004 television movie that premiered on Lifetime , written by Joyce Eliason and directed by Peter Werner , and starring Ryan Britten , Kristen Bell , Anne Heche , Diane Ladd , and Kristin Fairlie .", "title": "" } ]
PLAIN-568
animal products
[ { "docid": "MED-3302", "text": "In November 2007 a novel neuropathy, immune-mediated polyradiculoneuropathy (IP), was identified among workers at a Minnesota swine abattoir where a unique compressed air technique was used to remove porcine brains. An epidemiologic investigation at another abattoir in Indiana that also uses this process was launched to evaluate workers self-reporting neurologic illness compatible with IP. A nested case-control study was performed to identify cases and risk factors. Six confirmed, one probable, and three possible IP cases were detected. IP cases were 28-52 years old, of Latino origin, and 62.5% female. Onset dates ranged from April 2005-December 2007; 60% were hospitalized. IP cases at this plant were similar in clinical presentation and exposure risks to those detected in Minnesota. Swine abattoirs using similar brain extraction methods should discontinue this process.", "title": "A clustering of immune-mediated polyradiculoneuropathy among swine abattoir workers exposed to aerosolized porcine brains, Indiana, United States." }, { "docid": "MED-1320", "text": "Context Because of a different degree of processing and nutrient contents, brown rice and white rice may have different effects on risk of type 2 diabetes. Objective To prospectively examine white rice and brown rice consumptions in relation to type 2 diabetes risk in US men and women aged 26–87 yr. Design and Setting The Health Professionals Follow-up Study (1986–2006) and the Nurses’ Health Study I (1984–2006) and II (1991–2005). Participants We prospectively ascertained diet, lifestyle practices, and disease status among 39,765 men and 157,463 women in these cohorts. All participants were free of diabetes, cardiovascular disease, and cancer at baseline. Intake of white rice, brown rice, other foods, and nutrients was assessed at baseline and updated every 2–4 years. Results During 3,318,196 person-years of follow-up, we documented 10,507 incident cases of type 2 diabetes. After multivariate adjustment for age and other lifestyle and dietary risk factors, higher intake of white rice was associated with a higher risk of type 2 diabetes. The pooled relative risk (95% confidence interval) of type 2 diabetes comparing ≥5 servings/week with <1 serving/month of white rice was 1.17 (1.02, 1.36). In contrast, high brown rice intake was associated with a lower risk of type 2 diabetes: The pooled multivariate relative risk (95% confidence interval) was 0.89 (0.81, 0.97) for ≥ 2 servings/week of brown rice as compared with <1 serving/month. We estimated that replacing 50 grams/day (cooked, equivalent to ⅓ serving/day) intake of white rice with the same amount of brown rice was associated with a 16% (95% confidence interval: 9%, 21%) lower risk of type 2 diabetes, whereas the same replacement with whole grains as a group was associated with a 36% (95% confidence interval: 30%, 42%) lower diabetes risk. Conclusions Substitution of whole grains, including brown rice, for white rice may lower risk of type 2 diabetes. These data support the recommendation that most carbohydrate intake should come from whole grains rather than refined grains to facilitate the prevention of type 2 diabetes.", "title": "White Rice, Brown Rice, and Risk of Type 2 Diabetes in US Men and Women" }, { "docid": "MED-2644", "text": "Alkylphenols are widely used as plastic additives and surfactants. We report the identification of an alkylphenol, nonylphenol, as an estrogenic substance released from plastic centrifuge tubes. This compound was extracted with methanol, purified by flash chromatography and reverse-phase high performance liquid chromatography, and identified by gas chromatography-mass spectrometry. Nonylphenol induced both cell proliferation and progesterone receptor in human estrogen-sensitive MCF7 breast tumor cells. Nonylphenol also triggered mitotic activity in rat endometrium; this result confirms the reliability of the MCF7 cell proliferation bioassay. The estrogenic properties of alkylphenols, specifically nonylphenols, indicate that the use of plasticware containing these chemicals in experimental and diagnostic tests may lead to spurious results, and these compounds as well as alkylphenol polyethoxylates may also be potentially harmful to exposed humans and the environment at large.", "title": "p-Nonyl-phenol: an estrogenic xenobiotic released from \"modified\" polystyrene." }, { "docid": "MED-3407", "text": "The Princeton Consensus (Expert Panel) Conference is a multispecialty collaborative tradition dedicated to optimizing sexual function and preserving cardiovascular health. The third Princeton Consensus met November 8 to 10, 2010, and had 2 primary objectives. The first objective focused on the evaluation and management of cardiovascular risk in men with erectile dysfunction (ED) and no known cardiovascular disease (CVD), with particular emphasis on identification of men with ED who may require additional cardiologic work-up. The second objective focused on reevaluation and modification of previous recommendations for evaluation of cardiac risk associated with sexual activity in men with known CVD. The Panel's recommendations build on those developed during the first and second Princeton Consensus Conferences, first emphasizing the use of exercise ability and stress testing to ensure that each man's cardiovascular health is consistent with the physical demands of sexual activity before prescribing treatment for ED, and second highlighting the link between ED and CVD, which may be asymptomatic and may benefit from cardiovascular risk reduction.", "title": "The Princeton III Consensus Recommendations for the Management of Erectile Dysfunction and Cardiovascular Disease" }, { "docid": "MED-2846", "text": "OBJECTIVE: A cross-sectional institutional-based study was undertaken to know the prevalence of Gestational Diabetes Mellitus (GDM) among Indian pregnant women. SUBJECTS AND METHODS: 325 pregnant women were screened for evidence of diabetes who were previously not known to be diabetic. They underwent 75 g, 2 hour, oral glucose tolerance test (OGTT). Chi-square test was done for statistically association of variables in GDM. RESULTS AND CONCLUSIONS: The results of this study indicate that bad obstetrics history, obese patient on high calorie diet especially non vegetarian diet with less physical activity are highly prone to develop GDM.", "title": "A hospital based study of prevalence of gestational diabetes mellitus in an urban population of India." }, { "docid": "MED-2652", "text": "The exposure to some chemicals can lead to hormone disrupting effects. Presently, much attention is focused on so-called xeno-estrogens, synthetic compounds that interact with hormone receptors causing a number of reactions that eventually lead to effects related to reproduction and development. The current study was initiated to investigate the presence of a number of such compounds in precipitation as a follow-up on a previous study in which pesticide concentrations in air and precipitation were determined. Rainwater samples were collected at about 50 locations in The Netherlands in a four week period. The samples were analysed for bisphenol-A, alkylphenols and alkylphenol ethoxylates, phthalates, flame retardants and synthetic musk compounds. The results clearly indicated the presence of these compounds in precipitation. The concentrations ranged from the low ng l(-1) range for flame retardants to several thousands of ng l(-1) for the phthalates. Bisphenol-A was found in 30% of the samples in concentrations up to 130 ng l(-1), while alkylphenols and alkylphenol ethoxylates were found in virtually all locations in concentrations up to 920 ng l(-1) for the individual compounds. Phthalates were by far the most abundant xeno-estrogens in the precipitation samples and were found in every sample. Di-isodecyl phthalate was found in a surprisingly high concentration of almost 100 000 ng l(-1). Polybrominated flame retardants were found in the low ng l(-1) range and generally in less than 20% of the samples. Noticeable was the finding of hexabromocyclododecane, a replacement for the polybrominted diphenyl ethers at one location in a concentration of almost 2000 ng l(-1). Finally, as expected, synthetic musk compounds were detected in almost all samples. This is especially true for the polycyclic musks HHCB and AHTN. Nitro musks were found, but only on a few locations. Kriging techniques were used to calculate precipitation concentrations in between actual sampling locations to produce contour plots for a number of compounds. These plots clearly show located emission sources for a number of compounds such as bisphenol-A, nonylphenol ethoxylate, phthalates and AHTN. On the contrary, the results for HHCB and some phthalates indicated diffuse emission patterns, probably as the result of the use of consumer products containing these compounds.", "title": "Xeno-estrogenic compounds in precipitation." }, { "docid": "MED-3053", "text": "BACKGROUND: The hypothalamus is the central homeostatic control region of the brain and, therefore, highly influenced by nutrients such as glucose and fat. Immediate and prolonged homeostatic effects of glucose ingestion have been well characterized. However, studies that used stimulation with fat have mainly investigated immediate perceptional processes. Besides homeostatic processes, the gustatory cortex, including parts of the insular cortex, is crucial for the processing of food items. OBJECTIVE: The aim of this study was to investigate the effect of high- compared with low-fat meals on the hypothalamus and the insular cortex. DESIGN: Eleven healthy men participated in a single-blinded, functional MRI study of high- and low-fat meals on 2 measurement days. Cerebral blood flow (CBF) was measured before and 30 and 120 min after intake of high- and low-fat yogurts. Hunger was rated and blood samples were taken before each CBF measurement. RESULTS: High-fat yogurt induced a pronounced decrease in CBF in the hypothalamus, and the corresponding CBF change correlated positively with the insulin change. Furthermore, insular activity increased after 120 min in the low-fat condition only. The CBF change in both regions correlated positively in the high-fat condition. CONCLUSIONS: The decrease in hypothalamic activity and the interaction with the insular cortex elicited by fat may contribute to an efficient energy homeostasis. Therefore, fat might be a modulator of homeostatic and gustatory brain regions and their interaction. This trial was registered at clinicaltrials.gov as NCT01516021.", "title": "Fat intake modulates cerebral blood flow in homeostatic and gustatory brain areas in humans." }, { "docid": "MED-4954", "text": "BACKGROUND To look at possible long-term risks from anabolic steroids and other xenobiotics in beef, we examined men's semen quality in relation to their mother's self-reported beef consumption during pregnancy. METHODS: The study was carried out in five US cities between 1999 and 2005. We used regression analyses to examine semen parameters in 387 partners of pregnant women in relation to the amount of beef their mothers reported eating while pregnant. Mothers' beef consumption was also analysed in relation to the son's history of previous subfertility. RESULTS Sperm concentration was inversely related to mothers' beef meals per week (P = 0.041). In sons of \"high beef consumers\" (>7 beef meals/week), sperm concentration was 24.3% lower (P = 0.014) and the proportion of men with sperm concentration below 20 x 10(6)/ml was three times higher (17.7 versus 5.7%, P = 0.002) than in men whose mothers ate less beef. A history of previous subfertility was also more frequent among sons of \"high beef consumers\" (P = 0.015). Sperm concentration was not significantly related to mother's consumption of other meat or to the man's consumption of any meat. CONCLUSIONS These data suggest that maternal beef consumption, and possibly xenobiotics in beef, may alter a man's testicular development in utero and adversely affect his reproductive capacity.", "title": "Semen quality of fertile US males in relation to their mothers' beef consumption during pregnancy." }, { "docid": "MED-1253", "text": "OBJECTIVES: To investigate the effect of replacing lean meat with a soy product, tofu, on serum lipoprotein concentrations. STUDY AND DESIGN: Randomized cross-over dietary intervention study. SUBJECTS: Forty-two free-living healthy males aged 35-62 y completed the dietary intervention. Three additional subjects were non-compliant and excluded prior to analysis. INTERVENTIONS: A diet containing lean meat (150 g/d) was compared with one with 290 g/d tofu in an isocaloric and isoprotein substitution. Both diet periods were 1 month, and fat intake was carefully controlled. RESULTS: Seven-day diet records showed the two diets were similar in energy, macronutrients and fibre. Total cholesterol (mean difference 0.23 mmol/l, 95% CI 0.02, 0.43; P=0.03) and triglycerides (mean difference 0.15 mmol/l, 95% CI 0.02, 0.31; P=0.017) were significantly lower on the tofu diet than the lean meat diet. However, HDL-C was also significantly lower on the tofu diet (mean difference 0.08 mmol/l, 95% CI 0.02, 0.14; P=0.01) although the LDL-C:HDL-C ratio was similar. CONCLUSION: The effect on HDL-C and the small LDL-C reduction differ from some other studies, where fat was often less controlled, and the comparison was of soy as textured protein or soymilk against casein. This suggests a differential effect of the various proteins compared to the soy may influence the findings. In practice, the replacement of meat with tofu would usually be associated with a decrease in saturated fat and an increase in polyunsaturated fat and this should enhance any small benefits due to the soy protein. SPONSOR: Deakin University with some contribution from a Commonwealth Department of Veterans Affairs research grant. European Journal of Clinical Nutrition (2000) 54, 14-19", "title": "Effects of soy as tofu vs meat on lipoprotein concentrations." }, { "docid": "MED-4033", "text": "Saturated fatty acids (SFAs) produce an inflammatory response. Hyperinflammation is now recognized as one of the key underlying etiologic factors in periodontal disease. The longitudinal relationship between dietary SFAs and periodontal disease in 264 Japanese individuals, aged 75 years, for whom data were available for the years 2003-2004, was investigated. SFA intake was assessed with a brief self-administered diet history questionnaire. Participants were classified by quartiles of SFA intake. Full-mouth periodontal status, measured as the clinical attachment level (CAL), was recorded at baseline and follow-up examinations. The number of teeth with a loss of CAL≥3 mm at any site over a year was calculated as 'periodontal disease events'. Poisson regression analysis was conducted, with dietary SFAs as the primary predictor of interest, to estimate their influence on periodontal disease events. High dietary SFA intake was significantly associated with a greater number of periodontal disease events among non-smokers. The multivariate adjusted relative risk (95% confidence intervals) in the 1st, 2nd, 3rd, and 4th quartiles of dietary SFAs was 1.00, 1.19 (0.72-1.97), 1.55 (0.95-2.52), and 1.92 (1.19-3.11), respectively. These findings suggest an independent association of dietary SFA intake to the progression of periodontal disease in older Japanese non-smokers. ABBREVIATIONS: saturated fatty acid (SFA); clinical attachment level (CAL); Toll-like receptor (TLR); lipopolysaccharide (LPS); brief self-administered diet history questionnaire (BDHQ); decayed, missing, and filled teeth (DMFT); clinical attachment level (CAL); body mass index (BMI); relative risk (RR); confidence intervals (CI); nuclear factor-kappa B (NF-κB).", "title": "Relationship between saturated fatty acids and periodontal disease." }, { "docid": "MED-4234", "text": "It has long been appreciated that a healthy lifestyle plays a critical role in cardiovascular health. It is now apparent that the same is true in the development of benign prostatic hyperplasia (BPH). Prospective cohort data originating from recently published randomized trials on the medical treatment of BPH and prevention of prostate cancer have been invaluable. A growing body of evidence suggests that exercise and the intake of specific macronutrients and micronutrients through regular diet play a beneficial role. Most strikingly, the magnitude of these effects is similar to medical therapies using alpha-blockers and 5-alpha-reductase inhibitors. The use of supplements for prostate disease is a multibillion dollar business in the United States, and supplements are more commonly prescribed than medical therapy in many countries. In contrast to consumption of micronutrients through regular diet, supplemental intake of micronutrients and phytotherapies currently lack evidence to support their efficacy.", "title": "Dietary patterns, supplement use, and the risk of benign prostatic hyperplasia." }, { "docid": "MED-4625", "text": "Arachidonic acid (ARA) is considered to be a minor contributor to the diet. Previous reports regarding the effect of ARA supplementation on the composition of long-chain polyunsaturated fatty acids (LCPUFA) in the blood of humans are extremely limited. In the present study, we conducted a crossover double-blind, placebo-control study. Twenty-three young Japanese women consumed one capsule containing triacylglycerol enriched with 80 mg ARA, equivalent to the amount in one egg, daily for 3 weeks. Blood samples were drawn before and after treatment periods, and the compositions of the LCPUFA in blood lipid fractions were measured. The supplementation of ARA increased the composition of ARA, but did not decrease the composition of n-3LCPUFA in erythrocyte phospholipids and plasma phospholipids, esterified cholesterol, and triacylglycerol. We found that dietary ARA increased the ARA level in all lipid fractions of the blood, even at a very low dose. (c) 2010 Elsevier Ltd. All rights reserved.", "title": "Low-dose arachidonic acid intake increases erythrocytes and plasma arachidonic acid in young women." }, { "docid": "MED-1990", "text": "BACKGROUND: The optimal target range for blood glucose in critically ill patients remains unclear. METHODS: Within 24 hours after admission to an intensive care unit (ICU), adults who were expected to require treatment in the ICU on 3 or more consecutive days were randomly assigned to undergo either intensive glucose control, with a target blood glucose range of 81 to 108 mg per deciliter (4.5 to 6.0 mmol per liter), or conventional glucose control, with a target of 180 mg or less per deciliter (10.0 mmol or less per liter). We defined the primary end point as death from any cause within 90 days after randomization. RESULTS: Of the 6104 patients who underwent randomization, 3054 were assigned to undergo intensive control and 3050 to undergo conventional control; data with regard to the primary outcome at day 90 were available for 3010 and 3012 patients, respectively. The two groups had similar characteristics at baseline. A total of 829 patients (27.5%) in the intensive-control group and 751 (24.9%) in the conventional-control group died (odds ratio for intensive control, 1.14; 95% confidence interval, 1.02 to 1.28; P=0.02). The treatment effect did not differ significantly between operative (surgical) patients and nonoperative (medical) patients (odds ratio for death in the intensive-control group, 1.31 and 1.07, respectively; P=0.10). Severe hypoglycemia (blood glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was reported in 206 of 3016 patients (6.8%) in the intensive-control group and 15 of 3014 (0.5%) in the conventional-control group (P<0.001). There was no significant difference between the two treatment groups in the median number of days in the ICU (P=0.84) or hospital (P=0.86) or the median number of days of mechanical ventilation (P=0.56) or renal-replacement therapy (P=0.39). CONCLUSIONS: In this large, international, randomized trial, we found that intensive glucose control increased mortality among adults in the ICU: a blood glucose target of 180 mg or less per deciliter resulted in lower mortality than did a target of 81 to 108 mg per deciliter. (ClinicalTrials.gov number, NCT00220987.) 2009 Massachusetts Medical Society", "title": "Intensive versus conventional glucose control in critically ill patients." }, { "docid": "MED-1958", "text": "Food, especially meat, milk, and fish, is the immediate source of almost all polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and dioxinlike compounds in the general population. To estimate intake of these highly toxic compounds, we performed congener-specific dioxin analyses for the first time on U.S. food for 18 dairy meat, and fish samples from a supermarket in upstate New York. 2,3,7,8 Tetrachlorodibenzo-p-dioxin (TCDD, \"dioxin\") toxic equivalents (TEqs) on a wet weight basis for the dairy products ranged for 0.04 to 0.7 ppt, meat TEqs ranged from 0.03 to 1.5 ppt, and fish TEqs ranged from 0.02 to 0.13 ppt. Previous human breast milk and infant formula analyses were used with the current preliminary food data to estimate a range of dioxin intake for Americans. Average daily food intake of TEqs for an adult weighing 65 kg was estimated to be between 0.3 and 3.0 pg/kg body weight, for a total of 18-192 pg TEq, using 1986 American consumption rates. Due to the relatively high level of PCDDs and PCDFs commonly found in human breast milk from American women and from women in other industrial countries, a nursing infant may consume an average of 35-53 pg TEq/kg body weight/day in its first year of life. This may be compared with the current U.S. EPA virtually safe dose of 0.006 pg TCDD/kg body weight per day over a 70-year lifetime based on an upper limit cancer risk of 10(-6), or the 10 pg/kg/day used by some European government agencies.", "title": "Congener-specific levels of dioxins and dibenzofurans in U.S. food and estimated daily dioxin toxic equivalent intake." }, { "docid": "MED-4324", "text": "BACKGROUND: Increasingly the potential harm from high cholesterol intake, and specifically from egg yolks, is considered insignificant. We therefore assessed total plaque area (TPA) in patients attending Canadian vascular prevention clinics to determine if the atherosclerosis burden, as a marker of arterial damage, was related to egg intake. To provide perspective on the magnitude of the effect, we also analysed the effect of smoking (pack-years). METHODS: Consecutive patients attending vascular prevention clinics at University Hospital had baseline measurement of TPA by duplex ultrasound, and filled out questionnaires regarding their lifestyle and medications, including pack-years of smoking, and the number of egg yolks consumed per week times the number of years consumed (egg-yolk years). RESULTS: Data were available in 1262 patients; mean (SD) age was 61.5 (14.8) years; 47% were women. Carotid plaque area increased linearly with age after age 40, but increased exponentially with pack-years of smoking and with egg-yolk years. Plaque area in patients consuming <2 eggs per week (n = 388) was 125 ± 129 mm(2), versus 132 ± 142 mm(2) in those consuming 3 or more eggs per week (n = 603); (p < 0.0001 after adjustment for age). In multiple regression, egg-yolk years remained significant after adjusting for coronary risk factors. INTERPRETATION: Our findings suggest that regular consumption of egg yolk should be avoided by persons at risk of cardiovascular disease. This hypothesis should be tested in a prospective study with more detailed information about diet, and other possible confounders such as exercise and waist circumference. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.", "title": "Egg yolk consumption and carotid plaque." }, { "docid": "MED-1252", "text": "The effect of substituting soy for animal protein in mixed diets was determined in young men with mildly elevated plasma cholesterol, 218 to 307 mg/dl. The diets were low in cholesterol, 200 mg/day, with 13 to 16% of energy as protein, 30 to 35% as fat, and a polyunsaturated to saturated fat ratio of 0.5. Of protein 65% was from either mixed animal proteins or isolated soy protein products made comparable by the addition of extracted animal fats. Fresh egg yolk was added to balance the cholesterol content of the diets. Proteins from grains and vegetables were identical in both menus and contributed about 35% of dietary protein. Twenty of 24 subjects decreased plasma cholesterol at the end of the protocol. Subjects were classified as responders or nonresponders as a function of greater or lesser than mean reduction in cholesterol for the groups. Mean decreases in plasma cholesterol, 16 and 13%, for responders in the animal and soy groups were significant, p less than 0.01 and 0.05, respectively. Responders in both groups had higher initial plasma cholesterol values than nonresponders. Although plasma high-density lipoprotein cholesterol decreased slightly, the high-density lipoprotein cholesterol to cholesterol ratio (high-density lipoprotein cholesterol/total cholesterol) remained constant for most individuals. The hypocholesterolemic effects were similar for both animal and soy protein (p less than 0.05) and fat (p less than 0.05) while on the experimental diet. All groups significantly decreased dietary cholesterol (p less than 0.001).", "title": "Determinants of hypocholesterolemic response to soy and animal protein-based diets." }, { "docid": "MED-1595", "text": "Hormones work in harmony in the body, and this status must be maintained to avoid metabolic disequilibrium and the subsequent illness. Besides, it has been reported that exogenous steroids (presence in the environment and food products) influence the development of several important illnesses in humans. Endogenous steroid hormones in food of animal origin are unavoidable as they occur naturally in these products. The presence of hormones in food has been connected with several human health problems. Bovine milk contains considerable quantities of hormones and it is of particular concern. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, based on hydroxylamine derivatisation, has been developed and validated for the quantification of six sex hormones in milk [pregnenolone (P₅), progesterone (P₄), estrone (E₁), testosterone (T), androstenedione (A) and dehydroepiandrosterone (DHEA)]. This method has been applied to real raw milk samples and the existence of differences between milk from pregnant and non-pregnant cows has been statistically confirmed. Basing on a revision of existing published data, it could be concluded that maximum daily intakes for hormones are not reached through milk ingestion. Although dairy products are an important source of hormones, other products of animal origin must be considered as well for intake calculations.", "title": "Development of an LC-MS/MS method to quantify sex hormones in bovine milk and influence of pregnancy in their levels." }, { "docid": "MED-2794", "text": "Turmeric, a plant rhizome that is often dried, ground and used as a cooking spice, has also been used medicinally for several thousand years. Curcumin, the phytochemical that gives turmeric its golden color, is responsible for most of the therapeutic effects of turmeric. In recent years curcumin has been studied for its effects on chronic diseases such as diabetes, Alzheimer's, and cancer. Though many researchers are investigating turmeric/curcumin in cancer therapy, there is little epidemiologic information on the effects of turmeric consumption. With limited availability of pharmacologic interventions in many areas of the world, use of turmeric in the diet may help to alleviate some of the disease burden through prevention. Here we provide a brief overview of turmeric consumption in different parts of the world, cancer rates in those regions, possible biochemical mechanisms by which turmeric acts and practical recommendations based on the information available.", "title": "Dietary turmeric potentially reduces the risk of cancer." }, { "docid": "MED-1963", "text": "In 1994, we analyzed 43 foodstuff samples from local supermarkets in southern Mississippi, USA, for PCDD/PCDF. 2,3,7,8-Cl4DD could be quantified in 31 of these samples. On a lipid basis, levels in meat (0.53-1.10 pg I-TEQ/g) and dairy products (0.42-1.10 pg I-TEQ/g) were slightly lower than those reported from other industrialized countries. While levels in dairy samples from the United States and Europe are comparable, there is a difference in the contribution of individual congeners to the I-TEQ: for example, in milk samples from Germany approximately 40% of the I-TEQ is due to the presence of 2,3, 4,7,8-Cl5DF while in the Mississippi samples this congener only contributes 16%. The highest concentrations of PCDD/PCDF in our study were detected in the farm-raised catfish (10.2-27.8 pg I-TEQ/g). A unique finding was that in addition to the 2,3,7,8-substituted PCDD/PCDF the catfish samples contained many non-2,3,7,8-substituted congeners. This is unusual because vertebrate animals selectively eliminate or metabolize the non-2,3,7,8-substituted congeners.", "title": "Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/PCDF) in food samples collected in southern Mississippi, USA." }, { "docid": "MED-3432", "text": "Men with the metabolic syndrome demonstrate an increased prevalence of erectile dysfunction (ED). In the present study, we tested the effect of a Mediterranean-style diet on ED in men with the metabolic syndrome. Men were identified in our database of subjects participating in controlled trials evaluating the effect of lifestyle changes and were included if they had a diagnosis of ED associated with a diagnosis of metabolic syndrome, complete follow-up in the study trial, and intervention focused mainly on dietary changes. Sixty-five men with the metabolic syndrome met the inclusion/exclusion criteria; 35 out of them were assigned to the Mediterranean-style diet and 30 to the control diet. After 2 years, men on the Mediterranean diet consumed more fruits, vegetables, nuts, whole grain, and olive oil as compared with men on the control diet. Endothelial function score and inflammatory markers (C-reactive protein) improved in the intervention group, but remained stable in the control group. There were 13 men in the intervention group and two in the control group (P=0.015) that reported an IIEF score of 22 or higher. Mediterranean-style diet rich in whole grain, fruits, vegetables, legumes, walnut, and olive oil might be effective per se in reducing the prevalence of ED in men with the metabolic syndrome.", "title": "Mediterranean diet improves erectile function in subjects with the metabolic syndrome." }, { "docid": "MED-3820", "text": "BACKGROUND: A single high-fat meal induces endothelial activation, which is associated with increased serum concentrations of inflammatory cytokines. OBJECTIVE: We compared the effect of 3 different meals on circulating concentrations of interleukin 8 (IL-8), interleukin 18 (IL-18), and adiponectin in healthy subjects and in patients with type 2 diabetes mellitus. DESIGN: Thirty patients with newly diagnosed type 2 diabetes and 30 matched, nondiabetic subjects received the following 3 isoenergetic (780 kcal) meals separated by 1-wk intervals: a high-fat meal; a high-carbohydrate, low-fiber (4.5 g) meal; and a high-carbohydrate, high-fiber meal in which refined-wheat flour was replaced with whole-wheat flour (16.8 g). We analyzed serum glucose and lipid variables and serum IL-8, IL-18, and adiponectin concentrations at baseline and at 2 and 4 h after ingestion of the meals. RESULTS: Compared with nondiabetic subjects, diabetic patients had higher fasting IL-8 (P < 0.05) and IL-18 (P < 0.01) concentrations and lower adiponectin concentrations (P < 0.01) at baseline. In both nondiabetic and diabetic subjects, IL-18 concentrations increased and adiponectin concentrations decreased (P < 0.05) from baseline concentrations after consumption of the high-fat meal. After consumption of the high-carbohydrate, high-fiber meal, serum IL-18 concentrations decreased from baseline concentrations (P < 0.05) in both nondiabetic and diabetic subjects; adiponectin concentrations decreased after the high-carbohydrate, low-fiber meal in diabetic patients. IL-8 concentrations did not change significantly after consumption of any of the 3 meals. CONCLUSIONS: This study provides evidence that circulating IL-18 and adiponectin concentrations are modulated by familiar foodstuffs in humans. Meal modulation of cytokines involved in atherogenesis may represent a safe strategy for ameliorating atherogenetic inflammatory activity in diabetic patients.", "title": "Meal modulation of circulating interleukin 18 and adiponectin concentrations in healthy subjects and in patients with type 2 diabetes mellitus." }, { "docid": "MED-3094", "text": "Sensory attributes of fully aged broiler breast fillets marinated in a 6% NaCl solution containing 2% sodium tripolyphosphate (2P), 2% citric acid (2C), 2% acetic acid (2A), 1% citric acid plus 1% phosphate solution (1C), or 1% acetic acid solution plus 1% phosphate (1A) were studied. A 6% NaCl (6S) solution with no additives was used as control. Oven-cooked samples (177C degrees oven; 75 degrees C internal temperature) were evaluated by a 9-member trained descriptive analysis sensory panel that rated the intensities of 26 different flavor and texture attributes using 15-point line scales. Data were analyzed using general linear model SAS procedures to determine significant differences (P < or = 0.05) in individual sensory attributes due to marinade treatment. All sensory attributes were scored in the low intensity range (1.5 to 5.0). Brothy, vinegar, and residual particles were the only individual attributes rated significantly different (P < or = 0.05) due to treatment. Multivariate analyses indicated that all sensory attributes formed 2 dimensions that explained 57% of variation in the data. The low intensity values for texture attributes indicated possible negative consequences due to phosphates, salt, and acids when used with fully aged fillets.", "title": "Descriptive sensory analysis of broiler breast fillets marinated in phosphate, salt, and acid solutions." }, { "docid": "MED-3878", "text": "Diet, nutritional status, and certain dietary supplements are postulated to influence the development and progression of prostate cancer. Angiogenesis and inflammation are central to tumor growth and progression, but the effect of diet on these processes remains uncertain. We explored changes in 50 plasma cytokines and angiogenic factors (CAFs) in 145 men with prostate cancer enrolled in a pre-operative, randomized controlled phase-II trial with four arms: control (usual diet); low-fat (LF) diet; flaxseed-supplemented (FS) diet; and flaxseed-supplemented, low-fat diet. The mean duration of dietary intervention was 30–31 days. Among the individual arms, the largest number of significant changes (baseline vs pre-operative follow-up) was observed in the LF arm, with 19 CAFs decreasing and one increasing (p<.05). Compared to the control arm, 6 CAFs—including pro-angiogenic factors (stromal-cell derived-1α and myeloid factors (granulocyte-colony-stimulating factor, macrophage colony-stimulating factor — all decreased in the LF arm compared to controls; 3 and 4 CAFs changed in the FS and FS+LF arms, respectively. Weight loss occurred in the LF arms and significantly correlated with VEGF decreases (P <0.001). The CAFs that changed in the LF arm are all known to be regulated by nuclear factor-kappa B (NF-κB), and a pathway analysis identified NF-κB as the most likely regulatory network associated with these changes in the LF arm, but not in the FS-containing arms. These results suggest that a low-fat diet without flaxseed may reduce levels of specific inflammatory cytokines and angiogenic factors and suggests that the NF-κB pathway may be a mediator of these changes.", "title": "Effect of Low-fat Diets on Plasma Levels of NFκB-regulated Inflammatory Cytokines and Angiogenic Factors in Men with Prostate Cancer" }, { "docid": "MED-4631", "text": "BACKGROUND: Patients with rheumatoid arthritis (RA) improve on a vegetarian diet or supplementation with fish oil. We investigated the effects of both dietary measures, alone and in combination, on inflammation, fatty acid composition of erythrocyte lipids, eicosanoids, and cytokine biosynthesis in patients with RA. METHODS: Sixty-eight patients with definitive RA were matched into two groups of 34 subjects each. One group was observed for 8 months on a normal western diet (WD) and the other on an anti-inflammatory diet (AID) providing an arachidonic acid intake of less than 90 mg/day. Patients in both groups were allocated to receive placebo or fish oil capsules (30 mg/kg body weight) for 3 months in a double-blind crossover study with a 2-month washout period between treatments. Clinical examination and routine laboratory findings were evaluated every month, and erythrocyte fatty acids, eicosanoids, and cytokines were evaluated before and after each 3-month experimental period. RESULTS: Sixty patients completed the study. In AID patients, but not in WD patients, the numbers of tender and swollen joints decreased by 14% during placebo treatment. In AID patients, as compared to WD patients, fish oil led to a significant reduction in the numbers of tender (28% vs 11%) and swollen (34% vs 22%) joints (P<0.01). Compared to baseline levels, higher enrichment of eicosapentaenoic acid in erythrocyte lipids (244% vs 217%) and lower formation of leukotriene B(4) (34% vs 8%, P>0.01), 11-dehydro-thromboxane B(2) (15% vs 10%, P<0.05), and prostaglandin metabolites (21% vs 16%, P<0.003) were found in AID patients, especially when fish oil was given during months 6-8 of the experiment. CONCLUSION: A diet low in arachidonic acid ameliorates clinical signs of inflammation in patients with RA and augments the beneficial effect of fish oil supplementation.", "title": "Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis." }, { "docid": "MED-2126", "text": "Increased protein supply by feeding cow-milk-based infant formula in comparison to lower protein content of human milk is a well-recognized major risk factor of childhood obesity. However, there is yet no conclusive biochemical concept explaining the mechanisms of formula-induced childhood obesity. It is the intention of this article to provide the biochemical link between leucine-mediated signalling of mammalian milk proteins and adipogenesis as well as early adipogenic programming. Leucine has been identified as the predominant signal transducer of mammalian milk, which stimulates the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1). Leucine thus functions as a maternal-neonatal relay for mTORC1-dependent neonatal β-cell proliferation and insulin secretion. The mTORC1 target S6K1 plays a pivotal role in stimulation of mesenchymal stem cells to differentiate into adipocytes and to induce insulin resistance. It is of most critical concern that infant formulas provide higher amounts of leucine in comparison to human milk. Exaggerated leucine-mediated mTORC1-S6K1 signalling induced by infant formulas may thus explain increased adipogenesis and generation of lifelong elevated adipocyte numbers. Attenuation of mTORC1 signalling of infant formula by leucine restriction to physiologic lower levels of human milk offers a great chance for the prevention of childhood obesity and obesity-related metabolic diseases.", "title": "Excessive Leucine-mTORC1-Signalling of Cow Milk-Based Infant Formula: The Missing Link to Understand Early Childhood Obesity" }, { "docid": "MED-4838", "text": "With a prevalence of 10-15% in adults in Europe and the USA, gallstones are the most common digestive disease needing admission to hospital in the West. The interplay between interprandial and postprandial physiological responses to endogenous and dietary lipids underscores the importance of coordinated hepatobiliary and gastrointestinal functions to prevent crystallisation and precipitation of excess biliary cholesterol. Indeed, identifying the metabolic and transcriptional pathways that drive the regulation of biliary lipid secretion has been a major achievement in the field. We highlight scientific advances in protein and gene regulation of cholesterol absorption, synthesis, and catabolism, and biliary lipid secretion with respect to the pathogenesis of cholesterol gallstone disease. We discuss the physical-chemical mechanisms of gallstone formation in bile and the active role of the gallbladder and the intestine. We also discuss gaps in our knowledge of the pathogenesis of gallstone formation and the potential for gene targeting in therapy.", "title": "Cholesterol gallstone disease." }, { "docid": "MED-4060", "text": "Heteroyclic aromatic amines (HAAs) are a class of hazardous chemicals that are receiving heightened attention as a risk factor for human cancer. HAAs arise during the cooking of meats, fish, and poultry, and several HAAs also occur in tobacco smoke condensate and diesel exhaust. Many HAAs are carcinogenic and induce tumors at multiple sites in rodents. A number of epidemiologic studies have reported that frequent consumption of well-done cooked meats containing HAAs can result in elevated risks for colon, prostate, and mammary cancers. Moreover, DNA adducts of HAAs have been detected in human tissues, demonstrating that HAAs induce genetic damage even though the concentrations of these compounds in cooked meats are generally in the low parts-per-billion (ppb) range. With recent improvements in sensitivity of mass spectrometry instrumentation, HAAs, their metabolites, and DNA adducts can be detected at trace amounts in biological fluids and tissues of humans. The incorporation of HAA biomarkers in epidemologic studies will help to clarify the role of these dietary genotoxicants in the etiology of human cancer.", "title": "Formation and biochemistry of carcinogenic heterocyclic aromatic amines in cooked meats." }, { "docid": "MED-1594", "text": "The estrogens estrone (E1), 17alpha-estradiol (E2alpha), 17beta-estradiol (E2beta), and estriol (E3) are natural sex hormones produced by humans and animals. In addition, there are some synthetic estrogens, such as 17alpha-ethinylestradiol (EE2), used for contraception purposes. These compounds are able to produce endocrine disruption in living organisms at nanogram-per-liter levels. In both humans and animals, estrogens are excreted in urine and feces, reaching the natural environment through discharge from sewage treatment plants (STP) and manure disposal units. In STPs, hormone removal depends on the type of treatment process and on different parameters such as the hydraulic and sludge retention times. Thus, hormone elimination rates vary from 0% to 90% in different STPs. Animals are also an important source of estrogens in the environment. Indeed, animals produce high concentrations of hormones which will end up in manure which is typically spread on land. Hence, waste-borne animal hormones may transfer these pollutants to the soil. The purpose of this review is to highlight the significance for both health and the environment of pollution by estrogens and critically review the existing knowledge on their fate and removal in different treatment processes. Relevant information on the microbial degradation of hormones and metabolic pathways is also included.", "title": "Occurrence, fate, and biodegradation of estrogens in sewage and manure." }, { "docid": "MED-2847", "text": "BACKGROUND: Women with gestational diabetes are at increased risk of developing type 2 diabetes, but the risk and time of onset have not been fully quantified. We therefore did a comprehensive systematic review and meta-analysis to assess the strength of association between these conditions and the effect of factors that might modify the risk. METHODS: We identified cohort studies in which women who had developed type 2 diabetes after gestational diabetes were followed up between Jan 1, 1960, and Jan 31, 2009, from Embase and Medline. 205 relevant reports were hand searched. We selected 20 studies that included 675 455 women and 10 859 type 2 diabetic events. We calculated and pooled unadjusted relative risks (RRs) with 95% CIs for each study using a random-effects model. Subgroups analysed were the number of cases of type 2 diabetes, ethnic origin, duration of follow-up, maternal age, body-mass index, and diagnostic criteria. FINDINGS: Women with gestational diabetes had an increased risk of developing type 2 diabetes compared with those who had a normoglycaemic pregnancy (RR 7.43, 95% CI 4.79-11.51). Although the largest study (659 164 women; 9502 cases of type 2 diabetes) had the largest RR (12.6, 95% CI 12.15-13.19), RRs were generally consistent among the subgroups assessed. INTERPRETATION: Increased awareness of the magnitude and timing of the risk of type 2 diabetes after gestational diabetes among patients and clinicians could provide an opportunity to test and use dietary, lifestyle, and pharmacological interventions that might prevent or delay the onset of type 2 diabetes in affected women. FUNDING: None.", "title": "Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis." }, { "docid": "MED-4634", "text": "OBJECTIVE: Since conventional food questionnaires are not precise in assessing the dietary fatty acids, the purpose of this study was to determine the relationship between the salivary fatty acid profile and the alimentary habits of two different groups in an attempt to develop a more reliable way to determine the lipidic intake. DESIGN: Twenty adults of both sexes, with mixed (M) or vegetarian (V) diets were studied. Data about the fat intake were obtained by means of a Food Frequency Questionnaire (FFQ) and the presence of the main salivary fatty acids was determined by gas chromatography. RESULTS: A greater salivary concentration of alpha-linolenic acid (18:3 n-3) (2.82) was found in V than in M subjects (1.65) (p = 0.001), whilst arachidonic acid (20:4 n-6) was lower in V (3.93) than in M (4.52) (p = 0.045). The same difference regarding arachidonic acid was observed in the dietary fatty acid intake, also showing a significant correlation between its dietary and salivary levels in vegetarian subjects. CONCLUSIONS: These results show that salivary arachidonic acid, relevant for their eicosanoid production related to the tumourigenesis process and cardiovascular diseases, is influenced by dietary fats.", "title": "Fatty acid profile of human saliva: a possible indicator of dietary fat intake." }, { "docid": "MED-4476", "text": "Total N-nitroso compounds (NOC) and NOC precursors (NOCP) were determined in extracts of food and tobacco products. Following Walters' method, NOC were decomposed to NO with refluxing HBr/HCl/HOAc/EtOAc and NO was measured by chemiluminescence. NOC were determined after sulfamic acid treatment to destroy nitrite, and NOCP were determined after treatment with 110 mM nitrite and then sulfamic acid. Analysis without HBr gave results < or =20% of those with HBr. This NOC method was efficient for nitrosamines but not nitrosoureas. The standard nitrosation for determining NOCP gave high yields for readily nitrosated amines, including 1-deoxy-1-fructosylvaline, but not for simple amines, dipeptides, and alkylureas. Mean NOC and NOCP results were (respectively, in micromol/kg of product) 5.5 and 2700 for frankfurters, 0.5 and 660 for fresh meat, 5.8 and 5800 for salted, dried fish, and 660 and 2900 for chewing tobacco (all for aqueous extracts) and 220 and 20000 nmol/cigarette for MeCN extracts of cigarette smoke filter pads.", "title": "Determination of total N-nitroso compounds and their precursors in frankfurters, fresh meat, dried salted fish, sauces, tobacco, and tobacco smoke ..." }, { "docid": "MED-4040", "text": "The consumption of cooked meat appears to predispose individuals to colonic cancer and heterocyclic aromatic amines (HA), formed during the cooking of meat, have been suggested as aetiological agents. Consumption of cruciferous vegetables is thought to protect against cancer. To study the effect of cruciferous vegetables on heterocyclic aromatic amine metabolism in man, a three-period, dietary intervention study has been carried out with 20 non-smoking Caucasian male subjects consuming cooked meat meals containing known amounts of these carcinogens. A high cruciferous vegetable diet (250 g each of Brussels sprouts and broccoli per day) was maintained during period 2 but such vegetables were excluded from periods 1 and 3. At the end of each period, subjects consumed a cooked meat meal and urinary excretion of the HA 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) was measured. Following a 12 day period of cruciferous vegetable consumption (period 2), induction of hepatic CYP1A2 activity was apparent from changes in the kinetics of caffeine metabolism. Excretion of MeIQx and PhIP in urine at the end of this period of the study was reduced by 23 and 21%, respectively, compared with period 1. This reduction in excretion is probably due to an increase in amine metabolism that might be expected given the observed increase in CYP1A2 activity, since this enzyme has been shown to be primarily responsible for the oxidative activation of MeIQx and PhIP in man. In period 2, urinary mutagenicity was increased relative to period 1 by 52 and 64% in the absence and presence, respectively, of a human liver microsomal activation system, yet no evidence was found of PhIP adduction to lymphocyte DNA, a potential biomarker of the activation process. After another 12 days without cruciferous vegetables (period 3 of the study), the kinetics of caffeine metabolism had returned to original values but excretion of MeIQx and PhIP was still reduced by 17 and 30%, respectively, and urinary mutagenicity (with metabolic activation) was still elevated compared with period 1. This prolonged response of amine metabolism to the cruciferous vegetable diet, shown especially with PhIP, suggests that enzyme systems other than CYP1A2 are involved and affected by a cruciferous vegetable diet.", "title": "Effect of cruciferous vegetable consumption on heterocyclic aromatic amine metabolism in man." }, { "docid": "MED-4643", "text": "Breast cancer incidence was monitored in a cohort of 20,341 California Seventh-day Adventist women who completed a detailed lifestyle questionnaire in 1976, and who were followed for 6 years. There were 215 histologically confirmed primary breast cancer detected among some 115,000 person-years of follow-up. Mean age at diagnosis was 66 years, indicating a primarily postmenopausal case series. Established risk factors for breast cancer showed strong relationships to risk in these data. Age at first live birth, maternal history of breast cancer, age at menopause, educational attainment, and obesity were all significantly related to risk. However, increasing consumption of high fat animal products was not associated with increased risk of breast cancer in a consistent fashion. Nor were childhood and early teenage dietary habits (vegetarian versus nonvegetarian) related to subsequent, adult risk of developing breast cancer. Also, a derived index of percent of calories from animal fat in the adult years was not significantly related to risk. These results persisted after simultaneously controlling for other, potentially confounding variables, utilizing Cox proportional hazard regression models.", "title": "Dietary habits and breast cancer incidence among Seventh-day Adventists." }, { "docid": "MED-4803", "text": "We investigated the prevalence of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) in 120 retail meat samples from 30 grocery stores in Baton Rouge, LA. S. aureus strains were recovered from 45.6% of pork samples and 20% of beef samples, whereas MRSA strains were isolated from six meat samples (five pork samples and one beef sample). The MRSA isolates were of two strain types (clones), one harboring Panton-Valentine leucocidin and belonging to pulsed-field gel electrophoresis type USA300 and the other one belonging to USA100.", "title": "Isolation and Characterization of Methicillin-Resistant Staphylococcus aureus Strains from Louisiana Retail Meats" }, { "docid": "MED-1584", "text": "Advances in assisted reproductive technology and increases in the proportion of maternities in older women have both contributed to the steep increase in the incidence of twin pregnancies since the 1980s. Maternal and perinatal complications are higher in twins than in singleton pregnancies. A significant proportion of perinatal mortality and morbidity among twins is due to the high incidence of preterm delivery and the added complication of twin-to-twin transfusion syndrome (TTTS) in monochorionic twins. Monochorionic twins also have a much higher rate of perinatal mortality than dichorionic twins, the greatest risk being before fetal viability (<24 weeks gestation). Early diagnosis of twins and their chorionicity, close fetal surveillance, particularly of monochorionic twins, and prompt therapeutic intervention in TTS are necessary to reduce perinatal mortality. Intrapartum management in the hospital setting with anaesthetic and neonatal facilities, as well as critical assessment of mode of delivery, have led to better outcomes. Ultrasonography is a valuable tool in the management of twin pregnancy. This chapter briefly summarises these topics, with a particular focus on recent literature.", "title": "Obstetric complications of twin pregnancies." }, { "docid": "MED-2905", "text": "Fish consumption during gestation can provide the fetus with long chain polyunsaturated fatty acids (LCPUFA) and other nutrients essential for growth and development of the brain. However, fish consumption also exposes the fetus to the neurotoxicant, methyl mercury (MeHg). We studied the association between these fetal exposures and early child development in the Seychelles Child Development Nutrition Study (SCDNS). Specifically, we examined a priori models of Ω-3 and Ω-6 LCPUFA measures in maternal serum to test the hypothesis that these LCPUFA families before or after adjusting for prenatal MeHg exposure would reveal associations with child development assessed by the BSID-II at ages 9 and 30 months. There were 229 children with complete outcome and covariate data available for analysis. At 9 months, the PDI was positively associated with total Ω-3 LCPUFA and negatively associated with the ratio of Ω-6/Ω-3 LCPUFA. These associations were stronger in models adjusted for prenatal MeHg exposure. Secondary models suggested that the MeHg effect at 9 months varied by the ratio of Ω-6/Ω-3 LCPUFA. There were no significant associations between LCPUFA measures and the PDI at 30 months. There were significant adverse associations, however, between prenatal MeHg and the 30 month PDI when the LCPUFA measures were included in the regression analysis. The BSID-II Mental Developmental Index (MDI) was not associated with any exposure variable. These data support the potential importance to child development of prenatal availability of Ω-3 LCPUFA present in fish and of LCPUFA in the overall diet. Furthermore, they indicate that the beneficial effects of LCPUFA can obscure the determination of adverse effects of prenatal MeHg exposure in longitudinal observational studies.", "title": "Associations of maternal long chain polyunsaturated fatty acids, methyl mercury, and infant development in the Seychelles Child Development Nutrition Study" }, { "docid": "MED-3567", "text": "In 2008, approximately 21.8 million persons aged ≥15 years sustained nonfatal, unintentional injuries, resulting in approximately $67.3 billion in lifetime medical costs. Information about where injuries occur is limited, but bathrooms commonly are believed to be a particularly hazardous location. To investigate this assumption, CDC analyzed data from a nationally representative sample of emergency departments (EDs) to describe the incidence and circumstances of nonfatal injuries in bathrooms (in any setting) among persons aged ≥15 years in the United States. This report describes the results of that investigation, which found that, based on 3,339 cases documented in the 2008 National Electronic Surveillance System All Injury Program (NEISS-AIP) database, an estimated 234,094 nonfatal bathroom injuries were treated in U.S. EDs. Injury rates increased with age, and most injuries (81.1%) were caused by falls. All persons, but especially older adults, should be aware of bathroom activities that are associated with a high risk for injury and of environmental modifications that might reduce that risk.", "title": "Nonfatal bathroom injuries among persons aged ≥15 years--United States, 2008." }, { "docid": "MED-3798", "text": "The Moos Menstrual Distress Questionnaire (MMDQ) was completed by thirty healthy premenopausal women randomized into one of two sets of weight-maintaining diets, those with a ratio of polyunsaturated to saturated fatty acids (P/S ratio) of 1.0 and those with a P/S ratio of 0.3. After a baseline interval of one menstrual cycle, both groups were fed a high fat diet (40% energy from fat) for four menstrual cycles per subject, followed by a similar interval on a low fat diet (20% energy from fat). There were no significant differences in self-reported menstrual symptoms between the two P/S groups. During both menses and the premenstrual week of the low fat dietary period there were significant decreases in self-reported symptoms associated with water retention. A decrease in symptoms in the group labelled \"arousal\" during the rest of the menstrual cycle was also reported.", "title": "Influence of dietary fat on self-reported menstrual symptoms." }, { "docid": "MED-1942", "text": "Curcumin, from the curry spice turmeric, has been shown to possess potent antioxidant and antiinflammatory properties and to reduce beta-amyloid and plaque burden in experimental studies, but epidemiologic evidence is lacking. The authors investigated the association between usual curry consumption level and cognitive function in elderly Asians. In a population-based cohort (n = 1,010) of nondemented elderly Asian subjects aged 60-93 years in 2003, the authors compared Mini-Mental State Examination (MMSE) scores for three categories of regular curry consumption, taking into account known sociodemographic, health, and behavioral correlates of MMSE performance. Those who consumed curry \"occasionally\" and \"often or very often\" had significantly better MMSE scores than did subjects who \"never or rarely\" consumed curry. The authors reported tentative evidence of better cognitive performance from curry consumption in nondemented elderly Asians, which should be confirmed in future studies.", "title": "Curry consumption and cognitive function in the elderly." }, { "docid": "MED-3585", "text": "The inhibitory effect of Old Coke, caffeine-free New Coke, New Coke, Diet Coke and Pepsi-Cola on human sperm motility was studied with a trans-membrane migration method. None of them could decrease sperm motility to less than 70% of control within one hour. A previous study which claimed a marked variation of spermicidal potencies among different formulations of Coca-Cola could not be confirmed. Even if cola has a spermicidal effect, its potency is relatively weak as compared with other well-known spermicidal agents.", "title": "The spermicidal potency of Coca-Cola and Pepsi-Cola." }, { "docid": "MED-3102", "text": "BACKGROUND: Halogenated aromatic hydrocarbons including dioxins and non-halogenated polycyclic aromatic hydrocarbons are ligands of an aryl hydrocarbon receptor (AhR) and stimulate its transformation. Exposure to these environmental contaminants occurs mainly through diet. Recent articles demonstrated that certain food factors regulate the AhR transformation and expression of downstream drug-metabolizing enzymes. OBJECTIVE: To explain the actions of these food factors on the AhR transformation, as the mechanisms underlying are not fully understood. METHODS: This review introduces recent articles that have demonstrated the molecular mechanisms by which food factors regulate the AhR transformation and downstream drug-metabolizing enzymes. RESULTS/CONCLUSION: The role of classical ligands including dioxins as agonists of the receptor is well documented. As to the food factors, they act as antagonists because they basically suppress the AhR transformation by different mechanisms. Moreover, the fate and metabolism of food factors are important to understand their mechanisms.", "title": "An update on the dietary ligands of the AhR." }, { "docid": "MED-3730", "text": "Dysplasia is a histologic precursor of esophageal squamous cell carcinoma (SCC). We previously showed that dietary freeze-dried, or lyophilized, strawberry powder inhibits N-nitrosomethylbenzylamine-induced SCC in the rat esophagus. On the basis of this observation, we conducted a randomized (noncomparative) phase II trial in China to investigate the effects of two doses of freeze-dried strawberries in patients with esophageal dysplastic lesions in a high-risk area for esophageal cancer. We randomly assigned 75 patients identified by endoscopy to have dysplastic esophageal premalignant lesions to receive freeze-dried strawberry powder at either 30 g/d (37 patients) or 60 g/d (38 patients) for six months; the powder was mixed with water and drunk. After six months, we assessed the changes in histologic grade of these lesions (primary endpoint) in a blinded fashion. The dose of 30 g/d, did not significantly affect histology or any other measured parameter. The dose of 60 g/d, however, reduced the histologic grade of dysplastic premalignant lesions in 29 (80.6%) of the 36 patients at this dose who were evaluated for histology (P < 0.0001). The strawberry powder was well tolerated, with no toxic effects or serious adverse events. Strawberries (60 g/d) also reduced protein expression levels of inducible nitric oxide synthase (iNOS) by 79.5% (P < 0.001), cyclooxygenase-2 (COX-2) by 62.9% (P < 0.001), phospho-nuclear factor kappa B (NFκB)-p65 (pNFκB-p65) by 62.6% (P < 0.001), and phospho-S6 (pS6) by 73.2% (P < 0.001). Freeze-dried strawberries (60 g/d) also significantly inhibited the Ki-67 labeling index by 37.9% (P = 0.023). Our present results indicate the potential of freeze-dried strawberry powder for preventing human esophageal cancer, supporting further clinical testing of this natural agent in this setting. ©2011 AACR.", "title": "Randomized phase II trial of lyophilized strawberries in patients with dysplastic precancerous lesions of the esophagus." }, { "docid": "MED-4759", "text": "The human serum Sex Hormone-Binding Globulin (SHBG) plays an important role in breast cancer pathophysiology and risk definition, since it regulates the bioavailable fraction of circulating estradiol. We here summarize data reported over the years concerning the involvement of SHBG and SHBG polymorphisms in the definition of breast cancer risk. We also report what is known about the direct action of SHBG in breast cancer cells, illustrating its interaction with these cells and the subsequent initiation of a specific intracellular pathway leading to cross-talk with the estradiol-activated pathway and, finally, to the inhibition of several effects of estradiol in breast cancer cells. In conclusion, as a result of its unique property of regulating the estrogen free fraction and cross-talking with the estradiol pathways, by inhibiting estradiol-induced breast cancer cell growth and proliferation, SHBG is associated with a reduced risk of developing the neoplasm after estrogen exposure. 2009 Elsevier Ireland Ltd. All rights reserved.", "title": "Sex Hormone-Binding Globulin (SHBG), estradiol and breast cancer." }, { "docid": "MED-4451", "text": "Research leading to the discovery of a series of mutagenic and carcinogenic heterocyclic amines (HCAs) was inspired by the idea that smoke produced during cooking of food, especially meat or fish, might be carcinogenic. More than ten kinds of HCAs, actually produced by cooking or heating of meat or fish, have now been isolated and their structures determined, most being previously unregistered compounds. They are highly mutagenic towards Salmonella typhimurium in the presence of S9 mix and are also mutagenic in vitro and in vivo toward mammalian cells. HCAs have now been chemically synthesized in quantity and subjected to long-term animal testing. When HCAs were fed in the diet, rodents developed cancers in many organs, including the colon, breast and prostate, and one HCA produced hepatomas in monkeys. The lesions exhibited alteration in genes including Apc, beta-catenin and Ha-ras, and these changes provide clues to the induction mechanisms. The HCAs are oxidized to hydroxyamino derivatives by cytochrome P450s, and further converted to ester forms by acetyltransferase and sulfotransferase. Eventually, they produce DNA adducts through the formation of N-C bonds at guanine bases. There are HCA-sensitive and resistant strains of rodents and a search for the responsible genes is now under way. While the content of HCAs in dishes consumed in ordinary life is low and not sufficient in itself to explain human cancer, the coexistence of many other mutagens/carcinogens of either autobiotic or xenobiotic type and the possibility that HCAs induce genomic instability and heightened sensitivity to tumor promoters suggest that avoidance of exposure to HCAs or reduction of HCAs' biological effects as far as possible are to be highly recommended. Usage of microwave ovens for cooking and supplementation of the diet, for example with soy-isoflavones, which have been found to suppress the occurrence of HCA-induced breast cancers, should be encouraged. Advice to the general public about how to reduce the carcinogenic load imposed by HCAs would be an important contribution to cancer prevention.", "title": "Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish." }, { "docid": "MED-3228", "text": "A precise understanding of the role of dietary protein in bone health has been evasive despite decades of research. It is known that a dietary acid load is harmful to bone, and sulfur-containing amino acids are metabolized to provide such an acid load. It is also known that protein elevates urine calcium loss. However, recent clinical studies and a meta-analysis have indicated either no effect or a modest benefit associated with higher protein intakes. These contradictory considerations may be explained by the existence of a two-faced relationship between protein and bone, with simultaneous positive and negative pathways. In opposition to the negative effects of dietary acid load, protein may exert positive effects related to improving calcium absorption, increasing insulin-like growth factor 1, or improving lean body mass, which, in turn, improves bone strength. Putative mechanisms behind these pathways are reviewed here, and some limitations in the historical literature as well as suggested measures to counter these in the future are identified. When positive and negative pathways are considered in tandem, protein may offer modest benefits to bone in the presence of adequate dietary calcium and acid-neutralizing fruits and vegetables. © 2011 International Life Sciences Institute.", "title": "Dietary protein and bone health: harmonizing conflicting theories." }, { "docid": "MED-2583", "text": "Inositol hexaphosphate (IP(6)), a naturally polyphosphorylated carbohydrate, has been reported to have significant in vivo and in vitro anticancer activity against numerous tumours, such as colon, prostate, breast, liver and rhabdomyosarcomas. To confirm this activity in haematological malignancies and to characterize some of the mechanisms of IP(6) action, we analysed its effects on human leukaemic cell lines and fresh chronic myelogenous leukaemia (CML) progenitor cells using a combined cellular and molecular approach. IP(6) had a dose-dependent cytotoxic effect on all of the evaluated cell lines, with accumulation in the G2M phase in two out of five cell lines tested. At the molecular level, cDNA microarray analysis after IP(6) exposure showed an extensive downmodulation of genes involved in transcription and cell cycle regulation and a coherent upregulation of cell cycle inhibitors. Furthermore, IP(6) treatment of fresh leukaemic samples of bone marrow CD34+ CML progenitor cells significantly inhibited granulocyte-macrophage colony-forming unit (CFU-GM) formation (P = 0.0062) in comparison to normal bone marrow specimens, which were not affected. No differentiating effect on HL60 cells was observed. Taken together, our results confirm the antiproliferative activity of IP(6) and suggest that it may have a specific antitumour effect also in chronic myeloid leukaemias, via active gene modulation.", "title": "Effect of inositol hexaphosphate (IP(6)) on human normal and leukaemic haematopoietic cells." }, { "docid": "MED-4691", "text": "Background: Age and certain lifestyle factors, including a higher body mass index and exposure to light at night, are related to lower circulating concentrations of melatonin—a hormone with probable cancer-protective properties. Although melatonin is a direct derivative of the essential amino acid tryptophan, little is known about the relation of diet with melatonin concentrations. Objective: The objective was to examine cross-sectional associations of various nutrients and dietary factors as well as food groups with creatinine-adjusted first morning urinary melatonin (6-sulfatoxymelatonin; aMT6s) concentrations. Design: Participants were 998 healthy women from 2 independent cohorts: the Nurses' Health Study (NHS; n = 585) and NHS II (n = 413). We computed least-squares mean hormone concentrations across categories of dietary variables, with adjustment for total energy intake, age, and other nondietary factors known to be associated with aMT6s concentrations. Results: In multivariate analyses, we found no significant associations between the intake of various nutrients, including tryptophan and urinary melatonin concentrations. A higher intake of meat, particularly red meat, was associated with lower concentrations of aMT6s (adjusted mean concentrations of aMT6s across increasing quartiles of red meat intake were 17.9, 17.0, 18.1, and 15.3 ng/mg creatinine; P for trend = 0.02). In contrast, neither poultry intake (including turkey) nor fish intake was associated with aMT6s concentrations. Conclusion: Although no specific nutrients were associated with altered concentrations of melatonin, our findings raise the possibility that several specific foods, including red meat, could affect cancer risk through the lowering of melatonin concentrations.", "title": "Dietary correlates of urinary 6-sulfatoxymelatonin concentrations in the Nurses' Health Study cohorts" }, { "docid": "MED-4353", "text": "We have compared the effects of dietary soy protein and casein in diets low in cholesterol (less than 100 mg/d) and in diets enriched in cholesterol (500 mg/d) to examine whether the level of cholesterol intake affects the response of plasma lipoproteins to dietary proteins of plant and animal origin. Normal men and women consumed formula diets containing 20% of calories as soy protein or casein, 27% as fat and 53% as carbohydrate in 2 crossover studies. The dietary periods lasted for 31 days and were separated by a month-long interim period on self-chosen food. Following an initial reduction of plasma total cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels on all diets, the plasma lipid and lipoprotein concentrations stabilized. On low-cholesterol diets the concentration of each of the major lipoprotein classes were similar during the soy and the casein dietary periods. On cholesterol-enriched diets, the concentration of LDL-C stabilized at a 16% lower level on soy protein than on the casein diet (p less than 0.02), while the concentration of high-density lipoprotein-cholesterol (HDL-C) was 16% higher (p less than 0.01). Since the difference in LDL-C (p less than 0.05) and in HDL-C (p less than 0.025) levels on casein and on soy protein diets were significantly greater on the high than on the low cholesterol intake, the findings indicate that the level of dietary cholesterol may determine whether plant and animal dietary proteins have similar or different effects on plasma LDL-C and HDL-C concentrations.", "title": "Effects of dietary proteins on plasma lipoprotein levels in normal subjects: interaction with dietary cholesterol." }, { "docid": "MED-1923", "text": "Relatively short telomere length may serve as a marker of accelerated aging, and shorter telomeres have been linked to chronic stress. Specific lifestyle behaviors that can mitigate the effects of stress might be associated with longer telomere lengths. Previous research suggests a link between behaviors that focus on the well-being of others, such as volunteering and caregiving, and overall health and longevity. We examined relative telomere length in a group of individuals experienced in Loving-Kindness Meditation (LKM), a practice derived from the Buddhist tradition which utilizes a focus on unselfish kindness and warmth towards all people, and control participants who had done no meditation. Blood was collected by venipuncture, and Genomic DNA was extracted from peripheral blood leukocytes. Quantitative real time PCR was used to measure relative telomere length (RTL) (Cawthon, 2002) in fifteen LKM practitioners and 22 control participants. There were no significant differences in age, gender, race, education, or exposure to trauma, but the control group had a higher mean body mass index (BMI) and lower rates of past depression. The LKM practitioners had longer RTL than controls at the trend level (p=.083); among women, the LKM practitioners had significantly longer RTL than controls, (p=.007), which remained significant even after controlling for BMI and past depression. Although limited by small sample size, these results offer the intriguing possibility that LKM practice, especially in women, might alter RTL, a biomarker associated with longevity. Copyright © 2013 Elsevier Inc. All rights reserved.", "title": "Loving-Kindness Meditation practice associated with longer telomeres in women." }, { "docid": "MED-3318", "text": "Smoking is an established risk factor for pancreatic cancer; however, detailed examination of the association of smoking intensity, smoking duration, and cumulative smoking dose with pancreatic cancer is limited. The authors analyzed pooled data from the international Pancreatic Cancer Cohort Consortium nested case-control study (1,481 cases, 1,539 controls). Odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression. Smoking intensity effects were examined with an excess odds ratio model that was linear in pack-years and exponential in cigarettes smoked per day and its square. When compared with never smokers, current smokers had a significantly elevated risk (odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.38, 2.26). Risk increased significantly with greater intensity (≥30 cigarettes/day: OR = 1.75, 95% CI: 1.27, 2.42), duration (≥50 years: OR = 2.13, 95% CI: 1.25, 3.62), and cumulative smoking dose (≥40 pack-years: OR = 1.78, 95% CI: 1.35, 2.34). Risk more than 15 years after smoking cessation was similar to that for never smokers. Estimates of excess odds ratio per pack-year declined with increasing intensity, suggesting greater risk for total exposure delivered at lower intensity for longer duration than for higher intensity for shorter duration. This finding and the decline in risk after smoking cessation suggest that smoking has a late-stage effect on pancreatic carcinogenesis.", "title": "Cigarette Smoking and Pancreatic Cancer: A Pooled Analysis From the Pancreatic Cancer Cohort Consortium" }, { "docid": "MED-2653", "text": "Human milk is the most important form of nourishment for newborn children. Its consumption is strongly recommended by health authorities also for other important advantages. Unfortunately, in the last three decades a great number of investigations have shown the occurrence of several environmental contaminants in human milk, especially those with lipophilic properties. This study investigates the presence of nonylphenol, octylphenol (OP), nonylphenol monoethoxylate (NP1EO) and two octylphenol ethoxylates (OPEOs) (namely OP1EO and OP2EO), in human breast milk of Italian women. NP was the contaminant found at the highest levels with mean concentrations of 32 ng/mL, about two orders of magnitude higher than OP (0.08 ng/mL), OP1EO (0.07 ng/mL) and OP2EO (0.16 ng/mL). In the group of study a positive correlation among fish consumption and levels of NP in the milk was observed, in accordance with the evidence that seafood represents one of the most important sources of exposure to this group of contaminants in Italy. On the basis of the concentrations found in the breast milk samples, a maximum NP daily intake of 3.94 microg/kg/day can be calculated, which is close to the Tolerable Daily Intake (TDI) of 5 microg/kg body weight (bw) proposed by the Danish Institute of Safety and Toxicology. In the cases of OP no TDI is available, but its intake is at least six orders of magnitude lower than the NOAEL of 10 mg/kg/day derived from a two generation study on rats.", "title": "Nonylphenol and octylphenol in human breast milk." }, { "docid": "MED-2679", "text": "Commercial aqueous wood-smoke flavouring induced significant increases in the 6-thioguanine resistance mutation frequency of TK6 human lymphoblasts at 0.1 microliter flavouring/ml of cell suspension. This corresponds to 6 micrograms/ml of dissolved 'solids' as determined by fully drying the aqueous flavouring in a vacuum desiccator. In AHH-1 human lymphoblasts, which contain a cytochrome P-450 monooxygenase system, mutations were induced at 0.3 microliter/ml, corresponding to 18 microliters/ml of dissolved 'solids'. The flavouring did not induce 8-azaguanine resistant mutations in Salmonella typhimurium at concentrations up to 1.5 microliter/ml. At higher concentrations the flavouring was toxic to bacteria. The flavouring did not induce lung adenomas or other tumours in newborn mice when injected ip with total doses of up to 26 microliters over a 3-wk period. Toxicity to the kidney, colon and rectum was observed in some mice at 15 wk of age.", "title": "Commercial hickory-smoke flavouring is a human lymphoblast mutagen but does not induce lung adenomas in newborn mice." }, { "docid": "MED-1160", "text": "Washing is the most practical way to remove pesticide residues in fruits and vegetables. Two commonly used kitchen dishwashing liquids (detergents) in Chinese market were tested for enhanced removal of chlorpyrifos (CHP) and chlorothalonil (CHT) in cherry tomatoes by soaking the cherry tomatoes in the detergent solutions. The critical micelle concentrations of detergent A and detergent B were about 250 mg L(-1) and 444 mg L(-1), respectively. Detergent A had a higher solubilizing ability for pesticides and hence washing effectiveness than detergent B. The apparent solubility of CHP increased with increasing detergent concentration, while that of CHT remained comparatively invariant independent of detergent concentration within the tested range. The apparent solubility of CHP was also consistently higher in solutions of both detergents as compared to CHT. Due probably to its lower logKow value, CHT was more readily washed off cherry tomatoes than CHP. In terms of washing, a duration of 10-20 min was sufficient for removal of pesticides on cherry tomatoes in distilled water and detergent solutions. The effectiveness of removing pesticides increased with increasing detergent concentration from 50 mg L(-1) to 5 g L(-1), with up to 80% CHT and 42% CHP removed. Multiple washing further increased pesticide removal. Adding 10% acetic acid to lower pH or increasing washing temperature favored pesticide removal, but 10% NaCl produced the shielding effect and substantially reduced the effectiveness of detergent A for pesticide removal. Copyright © 2013 Elsevier Ltd. All rights reserved.", "title": "Effectiveness of dishwashing liquids in removing chlorothalonil and chlorpyrifos residues from cherry tomatoes." }, { "docid": "MED-2786", "text": "Alzheimer's disease (AD) is the most common form of dementia. There is limited choice in modern therapeutics, and drugs available have limited success with multiple side effects in addition to high cost. Hence, newer and alternate treatment options are being explored for effective and safer therapeutic targets to address AD. Turmeric possesses multiple medicinal uses including treatment for AD. Curcuminoids, a mixture of curcumin, demethoxycurcumin, and bisdemethoxycurcumin, are vital constituents of turmeric. It is generally believed that curcumin is the most important constituent of the curcuminoid mixture that contributes to the pharmacological profile of parent curcuminoid mixture or turmeric. A careful literature study reveals that the other two constituents of the curcuminoid mixture also contribute significantly to the effectiveness of curcuminoids in AD. Therefore, it is emphasized in this review that each component of the curcuminoid mixture plays a distinct role in making curcuminoid mixture useful in AD, and hence, the curcuminoid mixture represents turmeric in its medicinal value better than curcumin alone. The progress in understanding the disease etiology demands a multiple-site-targeted therapy, and the curcuminoid mixture of all components, each with different merits, makes this mixture more promising in combating the challenging disease. Copyright © 2013 John Wiley & Sons, Ltd.", "title": "Therapeutic potential of turmeric in Alzheimer's disease: curcumin or curcuminoids?" }, { "docid": "MED-2396", "text": "Rates of type 2 diabetes mellitus (T2DM), both in the United States and worldwide, have been rising at an alarming rate over the last two decades. Because this disease is viewed as primarily being attributable to unhealthy lifestyle habits, a great deal of emphasis has been placed on encouraging increased exercise, better dietary habits, and weight loss. Recent studies reveal that the presence of several persistent organic pollutants (POPs) can confer greater risk for developing the disease than some of the established lifestyle risk factors. In fact, evidence suggests the hypothesis that obesity might only be a significant risk factor when adipose tissue contains high amounts of POPs. Chlorinated pesticides and polychlorinated biphenyls, in particular, have been strongly linked to the development of metabolic syndrome, insulin resistance, and T2DM. In addition to reviewing the evidence associating POPs to these conditions, this article explores the possible contribution of farmed Atlantic salmon - a significant and common dietary source of POPs - with blood sugar dysregulation conditions.", "title": "The role of persistent organic pollutants in the worldwide epidemic of type 2 diabetes mellitus and the possible connection to Farmed Atlantic Salm..." }, { "docid": "MED-3013", "text": "A 2002 analysis documented $54.9 billion in annual costs of environmentally mediated diseases in US children. However, few important changes in federal policy have been implemented to prevent exposures to toxic chemicals. We therefore updated and expanded the previous analysis and found that the costs of lead poisoning, prenatal methylmercury exposure, childhood cancer, asthma, intellectual disability, autism, and attention deficit hyperactivity disorder were $76.6 billion in 2008. To prevent further increases in these costs, efforts are needed to institute premarket testing of new chemicals; conduct toxicity testing on chemicals already in use; reduce lead-based paint hazards; and curb mercury emissions from coal-fired power plants.", "title": "Reducing the staggering costs of environmental disease in children, estimated at $76.6 billion in 2008." }, { "docid": "MED-3279", "text": "Various pesticides are being used to destabilize, perturb, or inhibit crucial biochemical and physiological targets related to metabolism, growth, development, nervous communication, or behavior in pestiferous organisms. Chitin is an eukaryotic extracellular aminosugar biopolymer, massively produced by most fungal systems and by invertebrates, notably arthropods. Being an integral supportive component in fungal cell wall, insect cuticle, and nematode egg shell, chitin has been considered as a selective target for pesticide action. Throughout the elaborate processes of chitin formation and deposition, only the polymerization events associated with the cell membrane compartment are so far available for chemical interference. Currently, the actinomycetes-derived nucleoside peptide fungicides such as the polyoxins and the insecticidal benzoylaryl ureas have reached commercial pesticide status. The polyoxins and other structurally-related antibiotics like nikkomycins are strong competitive inhibitors of the polymerizing enzyme chitin synthase. The exact biochemical lesion inflicted by the benzoylaryl ureas is still elusive, but a post-polymerization event, such as translocation of chitin chains across the cell membrane, is suggested. Hydrolytic degradation of the chitin polymer is essential for hyphal growth, branching, and septum formation in fungal systems as well as for the normal molting of arthropods. Recently, insect chitinase activity was strongly and specifically suppressed by allosamidin, an actimomycetes-derived metabolite. In part, the defense mechanism in plants against invasion of pathogens is associated with induced chitinases. Chitin, chitosan, and their oligomers are able to act as elicitors which induce enhanced levels of chitinases in various plants. Lectins which bind to N-acetyl-D-glucosamine strongly interfere with fungal and insect chitin synthases. Plant lectins with similar properties may be involved in plant-pathogen interaction inter alia by suppressing fungal invasion.", "title": "Chitin synthesis and degradation as targets for pesticide action." }, { "docid": "MED-2843", "text": "BACKGROUND: The risk of major congenital malformations (MCM) is increased in women with pregestational diabetes mellitus (PGDM). Whether this risk is increased in gestational diabetes mellitus (GDM) is still debated. The aim of this study was to perform a systematic review (and meta-analysis) of major congenital malformations in women with gestational diabetes versus a reference population. METHODS: We conducted a MEDLINE search (1 January 1995 to 31 December 2009) of original studies reporting data on major congenital malformations in women with gestational diabetes and a reference group. Information on pregestational diabetes was collected when available. Two investigators considered studies for inclusion and extracted data; discrepancies were solved by consensus. Meta-analysis tools were used to summarize results. MOOSE and PRISMA guidelines were followed. RESULTS: Two case control and 15 cohort studies were selected out of 3488 retrieved abstracts. A higher risk of major congenital malformations was observed in offspring of women with gestational diabetes with the following relative risk (RR)/odds ratios (OR) and 95% confidence intervals (CI): RR 1.16 (1.07-1.25) in cohort studies and OR 1.4 (1.22-1.62) in case control studies. Risk of major congenital malformations was much higher in offspring of women with PGDM than in those of the reference group: RR 2.66 (2.04-3.47) in cohort studies and OR 4.7 (3.01-6.95) in the single case control study providing information. CONCLUSION: There is a slightly higher risk of major congenital malformations in women with gestational diabetes than in the reference group. The contribution of women with overt hyperglycemia and other factors could not be ascertained. This risk, however, is much lower than in women with pregestational diabetes. Copyright © 2011 John Wiley & Sons, Ltd.", "title": "Major congenital malformations in women with gestational diabetes mellitus: a systematic review and meta-analysis." }, { "docid": "MED-4220", "text": "OBJECTIVE: Accumulating evidence indicates that prostate cancer is associated with high levels of serum IGF-I. This study was conducted to determine whether a low-fat diet and exercise (DE) intervention may modulate the IGF axis and reduce prostate cancer cell growth in vitro. METHODS: Fasting serum was obtained from 14 men (age 60 +/- 3 years) participating in an 11-day DE program and from eight similarly aged men who had followed the DE program for 14.2 +/- 1.7 years (long-term). Insulin, IGF-I, IGFBP-1, and IGFBP-3 were measured by ELISA, and serum was used to stimulate LNCaP cell growth in vitro. RESULTS: Serum IGF-I levels decreased by 20% while IGFBP-1 increased by 53% after 11-day DE. In the long-term group, IGF-I was 55% lower, while IGFBP-1 was 150% higher relative to baseline. Serum insulin decreased by 25% after 11-day DE and was 68% lower in the long-term group, relative to baseline. No changes in serum IGFBP-3 were observed. Serum-stimulated LNCaP cell growth was reduced by 30% in post-11-day serum and by 44% in long-term serum relative to baseline. LNCaP cells incubated with post-DE serum showed increased apoptosis/ necrosis, compared to baseline. CONCLUSIONS: A low-fat diet and exercise intervention induces in-vivo changes in the circulating IGF axis and is associated with reduced growth and enhanced apoptosis/necrosis of LNCaP tumor cells in vitro.", "title": "Effect of diet and exercise on serum insulin, IGF-I, and IGFBP-1 levels and growth of LNCaP cells in vitro (United States)." }, { "docid": "MED-4233", "text": "OBJECTIVES: Dietary fat and fiber affect hormonal levels and may influence cancer progression. Flaxseed is a rich source of lignan and omega-3 fatty acids and may thwart prostate cancer. The potential effects of flaxseed may be enhanced with concomitant fat restriction. We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet could affect the biomarkers of prostatic neoplasia. METHODS: Twenty-five patients with prostate cancer who were awaiting prostatectomy were instructed on a low-fat (20% of kilocalories or less), flaxseed-supplemented (30 g/day) diet. The baseline and follow-up levels of prostate-specific antigen, testosterone, free androgen index, and total serum cholesterol were determined. The tumors of diet-treated patients were compared with those of historic cases (matched by age, race, prostate-specific antigen level at diagnosis, and biopsy Gleason sum) with respect to apoptosis (terminal deoxynucleotidyl transferase [TdT]-mediated dUTP-biotin nick end-labeling [TUNEL]) and proliferation (MIB-1). RESULTS: The average duration on the diet was 34 days (range 21 to 77), during which time significant decreases were observed in total serum cholesterol (201 +/- 39 mg/dL to 174 +/- 42 mg/dL), total testosterone (422 +/- 122 ng/dL to 360 +/- 128 ng/dL), and free androgen index (36.3% +/- 18.9% to 29.3% +/- 16.8%) (all P <0.05). The baseline and follow-up levels of prostate-specific antigen were 8.1 +/- 5.2 ng/mL and 8.5 +/- 7.7 ng/mL, respectively, for the entire sample (P = 0.58); however, among men with Gleason sums of 6 or less (n = 19), the PSA values were 7.1 +/- 3.9 ng/mL and 6.4 +/- 4.1 ng/mL (P = 0.10). The mean proliferation index was 7.4 +/- 7.8 for the historic controls versus 5.0 +/- 4.9 for the diet-treated patients (P = 0.05). The distribution of the apoptotic indexes differed significantly (P = 0.01) between groups, with most historic controls exhibiting TUNEL categorical scores of 0; diet-treated patients largely exhibited scores of 1. Both the proliferation rate and apoptosis were significantly associated with the number of days on the diet (P = 0.049 and P = 0.017, respectively). CONCLUSIONS: These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect prostate cancer biology and associated biomarkers. Further study is needed to determine the benefit of this dietary regimen as either a complementary or preventive therapy.", "title": "Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal l..." }, { "docid": "MED-2109", "text": "Thirty-nine newborn infants with severe persistent pulmonary hypertension and respiratory failure who met criteria for 85% likelihood of dying were enrolled in a randomized trial in which extracorporeal membrane oxygenation (ECMO) therapy was compared with conventional medical therapy (CMT). In phase I, 4 of 10 babies in the CMT group died and 9 of 9 babies in the ECMO group survived. Randomization was halted after the fourth CMT death, as planned before initiating the study, and the next 20 babies were treated with ECMO (phase II). Of the 20, 19 survived. All three treatment groups (CMT and ECMO in phase I and ECMO, phase II) were comparable in severity of illness and mechanical ventilator support. The overall survival of ECMO-treated infants was 97% (28 of 29) compared with 60% (6 of 10) in the CMT group (P less than .05).", "title": "Extracorporeal membrane oxygenation and conventional medical therapy in neonates with persistent pulmonary hypertension of the newborn: a prospecti..." }, { "docid": "MED-4027", "text": "Objectives To study the dietary behavior and knowledge about dental erosion and self-reported symptoms that can be related to dental erosion among Chinese adults in Hong Kong. Methods Chinese adults aged 25-45 years were randomly selected from a list of registered telephone numbers generated by computer. A telephone survey was administered to obtain information on demographic characteristics, dietary habits, dental visits, and knowledge of and presence of self-reported symptoms that can be related to dental erosion. Results A total of 520 participants were interviewed (response rate, 75%; sampling error, ± 4.4%) and their mean age was 37. Most respondents (79%) had ever had caries, and about two thirds (64%) attended dental check-ups at least once a year. Respondents had a mean of 5.4 meals per day and 36% had at least 6 meals per day. Fruit (89%) and lemon tea/water (41%) were the most commonly consumed acidic food and beverage. When asked if they ever noticed changes in their teeth, most respondents (92%) said they had experienced change that can be related to erosion. However, many (71%) had never heard about dental erosion and 53% mixed up dental erosion with dental caries. Conclusion Hong Kong Chinese adults have frequent intake of food and many have experienced symptoms that can be related to dental erosion. Their level of awareness of and knowledge about dental erosion is generally low, despite most of them have regular dental check-ups. Dental health education is essential to help the public understand dental erosion and its damaging effects.", "title": "Dietary behavior and knowledge of dental erosion among Chinese adults" }, { "docid": "MED-1605", "text": "The Family Smoking Prevention and Tobacco Control Act gives the Food and Drug Administration power to regulate tobacco products. This commentary calls for immediate regulation of the carcinogenic tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N’-nitrosonornicotine (NNN) in cigarette tobacco as a logical path to cancer prevention. NNK and NNN, powerful carcinogens in laboratory animals, have been evaluated as “carcinogenic to humans” by the International Agency for Research on Cancer. NNK and NNN are present in the tobacco of virtually all marketed cigarettes; levels in cigarette smoke are directly proportional to the amounts in tobacco. The NNK metabolite NNAL, itself a strong carcinogen, is present in the urine of smokers and non-smokers exposed to secondhand smoke. Some of the highest levels of NNK and NNN are found in U.S. products. It is well established that factors such as choice of tobacco blend, agricultural conditions, and processing methods influence levels of NNK and NNN in cigarette tobacco and cigarette smoke. Therefore, it is time to control these factors and produce cigarettes with 100 ppb or less each of NNK and NNN in tobacco, which would result in an approximate 15-20 fold reduction of these carcinogens in the mainstream smoke of popular cigarettes sold in the United States.", "title": "It is time to regulate carcinogenic tobacco-specific nitrosamines in cigarette tobacco" }, { "docid": "MED-4481", "text": "The aim of this study was to investigate whether dietary fat and meat intakes are associated with reflux esophagitis (RE), Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). In this all-Ireland case-control study, dietary intake data was collected using a food frequency questionnaire in 219 RE patients, 220 BE patients, 224 EAC patients, and 256 frequency-matched controls between 2002 and 2005. Unconditional multiple logistic regression analysis was used to examine the association between dietary variables and disease risk using quartiles of intake, to attain odds ratios (OR) and 95% confidence intervals (95%CI), while adjusting for potential confounders. Patients in the highest quartile of total fat intake had a higher risk of RE (OR=3.54; 95%CI=1.32–9.46) and EAC (OR=5.44; 95%CI=2.08–14.27). A higher risk of RE and EAC was also reported for patients in the highest quartile of saturated fat intake (OR=2.79; 95%CI=1.11–7.04; OR=2.41; 95%CI=1.14–5.08, respectively) and monounsaturated fat intake (OR=2.63; 95%CI=1.01–6.86; OR=5.35; 95%CI=2.14–13.34, respectively). Patients in the highest quartile of fresh red meat intake had a higher risk of EAC (OR=3.15; 95%CI=1.38–7.20). Patients in the highest category of processed meat intake had a higher risk of RE (OR=4.67; 95%CI=1.71–12.74). No consistent associations were seen for BE with either fat or meat intakes. Further studies, investigating the association between dietary fat and food sources of fat are needed to confirm these results.", "title": "Dietary fat and meat intakes and risk of reflux esophagitis, Barrett’s esophagus and esophageal adenocarcinoma" }, { "docid": "MED-3054", "text": "The relationship between overeating, substance abuse and (behavioral) addiction is controversial. Medically established forms of addiction so far pertain to substance use disorders only. But the preliminary Diagnostic and Statistical Manual for Mental Disorders V (DSM V) suggests replacing the previous category 'Substance-Related Disorders' with 'Addiction and Related Disorders', thus for the first time allowing the diagnosis of behavioral addictions. In the past psychiatrists and psychologists have been reluctant to systematically delineate and classify the term behavioral addiction. However, there is a broad overlap between chemical and behavioral addiction including phenomenological, therapeutic, genetic, and neurobiological aspects. It is of interest to point out that the hormone leptin in itself has a pronounced effect on the reward system, thus suggesting an indirect link between overeating and 'chemical' addiction. Thus, leptin-deficient individuals could be classified as fulfilling criteria for food addiction. In our overview we first review psychological findings in chemical (substance-based) and subsequently in behavioral addiction to analyze the overlap. We discuss the diagnostic validity of food addiction, which in theory can be chemically and/or behaviorally based. Copyright © 2012 S. Karger GmbH, Freiburg.", "title": "Does food addiction exist? A phenomenological discussion based on the psychiatric classification of substance-related disorders and addiction." }, { "docid": "MED-2650", "text": "Over the last 40 years there have been constant reports concerning environmental chemicals with hormone-like effects in wildlife. An endocrine disruptor is an exogenous substance that causes adverse health effects in an intact organism or its progeny, secondary to changes in endocrine function. Endocrine disruptors of widely diverse chemical structures that have oestrogenic properties are known as oestrogenic xenobiotics or xenoestrogens. Some of these substances, such as phytoestrogens and mycoestrogens, can come from diet or from the environment. Although the oestrogenic activity of these substances is weaker than that of oestradiol, new chemicals with endocrine disrupting potential continue to be discovered, inadvertent forms of exposure are constantly being identified, and there is increasing concern about cumulative effects. Studies in the 1960s and 1970s characterized the oestrogenicity of a number of industrial compounds and the pesticides o,p-DDT, kepone, methoxychlor, phenolic derivatives and polychlorinated biphenyls (PCBs). In the last 5 years, several environmental chemicals have been added to the list of xenoestrogens, including the pesticides toxaphene, dieldrin and endosulphan, and several different compounds used in the food industry, antioxidants such a t-butylhydroxyanisole; plasticizers such as benzylbutylphthalate and 4-OH-alkylphenols; and substances used in dental restorations, such as bisphenol-A. The relevance of these newly discovered endocrine disruptors to human health is now starting to emerge. The few studies that have investigated their effect in humans point in the same direction: if there is indeed an association between exposure to substances with hormone-disruptive activity and certain disorders of endocrine organs, the incidence of such disorders would be greater in areas where exposure to agents with this activity is high. A closer scrutiny is required to determine whether these newly discovered endocrine disrupting chemicals contribute, together with oestrogenic pesticides, to the exposure of humans to xenoestrogens.", "title": "Inadvertent exposure to xenoestrogens." }, { "docid": "MED-5116", "text": "BACKGROUND: Laboratory research and a growing number of epidemiologic studies have provided evidence for a reduced risk of breast cancer associated with dietary intake of certain classes of flavonoids. However, the effects of flavonoids on survival are not known. In a population-based cohort of breast cancer patients, we investigated whether dietary flavonoid intake before diagnosis is associated with subsequent survival. METHODS: Women ages 25 to 98 years who were newly diagnosed with a first primary invasive breast cancer between August 1, 1996, and July 31, 1997, and participated in a population-based, case-control study (n=1,210) were followed for vital status through December 31, 2002. At the case-control interview conducted shortly after diagnosis, respondents completed a FFQ that assessed dietary intake in the previous 12 months. All-cause mortality (n=173 deaths) and breast cancer-specific mortality (n=113 deaths) were determined through the National Death Index. RESULTS: Reduced hazard ratios [age- and energy-adjusted hazard ratio (95% confidence interval)] for all-cause mortality were observed among premenopausal and postmenopausal women for the highest quintile of intake, compared with the lowest, for flavones [0.63 (0.41-0.96)], isoflavones [0.52 (0.33-0.82)], and anthocyanidins [0.64 (0.42-0.98)]. No significant trends in risk were observed. Results were similar for breast cancer-specific mortality only. CONCLUSION: Mortality may be reduced in association with high levels of dietary flavones and isoflavones among postmenopausal U.S. breast cancer patients. Larger studies are needed to confirm our findings.", "title": "Dietary flavonoid intake and breast cancer survival among women on Long Island." }, { "docid": "MED-2502", "text": "Dietary restriction (DR) without malnutrition is widely regarded to be a universal mechanism for prolonging lifespan. It is generally believed that the benefits of DR arise from eating fewer calories (termed caloric restriction, CR). Here we argue that, rather than calories, the key determinant of the relationship between diet and longevity is the balance of protein to non-protein energy ingested. This ratio affects not only lifespan, but also total energy intake, metabolism, immunity and the likelihood of developing obesity and associated metabolic disorders. Among various possible mechanisms linking macronutrient balance to lifespan, the nexus between the TOR and AMPK signaling pathways is emerging as a central coordinator.", "title": "Macronutrient balance and lifespan" }, { "docid": "MED-4035", "text": "The aim of the present in situ study was to evaluate the effect of different periods of intra-oral remineralisation on the susceptibility of softened dentin to toothbrushing abrasion. Groups of 6 human dentin specimens (A-F) were recessed in the buccal aspects of intra-oral appliances which were worn for 21 days by 11 volunteers. The samples were demineralised twice a day extra-orally in the acidic beverage Sprite Light (pH 2.9) for 90 s. Subsequently, the dentin specimens were brushed at different times. Specimen A was brushed immediately after demineralisation. Specimens B-E were brushed after the intra-oral appliances had been worn for various periods in the mouth: specimen B for 10 min, C for 20 min, D for 30 min and E for 60 min. Specimen F was not brushed (control). After 21 days, dentin wear was measured with a profilometer. The following values (means +/- standard deviation) were recorded (microm): A, 23.6 +/- 16.7; B, 37.9 +/- 29.7; C, 31.8 +/- 26.5; D, 18.5 +/- 10.5; E, 15.3 +/- 11.6; F, 12.6 +/- 6.7. There was a statistically significantly increased dentin loss for groups A, B and C as compared to the controls (U test: p < 0.05). However, after intra-oral periods of 30 and 60 min, wear was not significantly higher than in unbrushed controls. It is concluded that for protection of dentin surfaces at least 30 min should elapse before toothbrushing after an erosive attack. Copyright 2004 S. Karger AG, Basel", "title": "Brushing abrasion of softened and remineralised dentin: an in situ study." }, { "docid": "MED-1401", "text": "The link between iron intake as well as body iron stores and coronary heart disease (CHD) has been contentiously debated, and the epidemiologic evidence is inconsistent. We aimed to quantitatively summarize the literature on the association between dietary iron intake/body iron stores and CHD risk by conducting a meta-analysis of prospective cohort studies. PubMed was used to find studies published through June 2013 in peer-reviewed journals. Embase or a hand search of relevant articles was used to obtain additional articles. The pooled RRs of CHD incidence and mortality with 95% CIs were calculated by using either a random-effects or fixed-effects model, as appropriate. Twenty-one eligible studies (32 cohorts) including 292,454 participants with an average of 10.2 y of follow-up were included. Heme iron was found to be positively associated with CHD incidence (RR: 1.57; 95% CI: 1.28, 1.94), whereas total iron was inversely associated (RR: 0.85; 95% CI: 0.73, 0.999). Neither heme-iron nor total iron intakes were significantly associated with CHD mortality. Both transferrin saturation and serum iron were inversely related to CHD incidence [RR (95% CI): 0.76 (0.66, 0.88) and 0.68 (0.56, 0.82), respectively], but only transferrin saturation was inversely associated with CHD mortality (RR: 0.85; 95% CI: 0.73, 0.99). In conclusion, total iron intake and serum iron concentrations were inversely associated with CHD incidence, but heme iron intake was positively related to CHD incidence. Elevated serum transferrin saturation concentration was inversely associated with both CHD incidence and mortality. Future research is needed to establish the causal relation and to elucidate potential mechanisms.", "title": "Dietary Iron Intake and Body Iron Stores Are Associated with Risk of Coronary Heart Disease in a Meta-Analysis of Prospective Cohort Studies" }, { "docid": "MED-3052", "text": "Drug addiction and obesity appear to share several properties. Both can be defined as disorders in which the saliency of a specific type of reward (food or drug) becomes exaggerated relative to, and at the expense of others rewards. Both drugs and food have powerful reinforcing effects, which are in part mediated by abrupt dopamine increases in the brain reward centres. The abrupt dopamine increases, in vulnerable individuals, can override the brain's homeostatic control mechanisms. These parallels have generated interest in understanding the shared vulnerabilities between addiction and obesity. Predictably, they also engendered a heated debate. Specifically, brain imaging studies are beginning to uncover common features between these two conditions and delineate some of the overlapping brain circuits whose dysfunctions may underlie the observed deficits. The combined results suggest that both obese and drug-addicted individuals suffer from impairments in dopaminergic pathways that regulate neuronal systems associated not only with reward sensitivity and incentive motivation, but also with conditioning, self-control, stress reactivity and interoceptive awareness. In parallel, studies are also delineating differences between them that centre on the key role that peripheral signals involved with homeostatic control exert on food intake. Here, we focus on the shared neurobiological substrates of obesity and addiction. © 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.", "title": "Obesity and addiction: neurobiological overlaps." }, { "docid": "MED-4349", "text": "Inflammation is a pathological condition underlying a number of diseases including cardiovascular diseases, cancer, and chronic inflammatory diseases. In addition, healthy, obese subjects also express markers of inflammation in their blood. Diet provides a variety of nutrients as well as non-nutritive bioactive constituents which modulate immunomodulatory and inflammatory processes. Epidemiological data suggest that dietary patterns strongly affect inflammatory processes. Primarily the intake of fruit and vegetables as well as of whole wheat is inversely associated with the risk of inflammation. In addition to observational studies there are also data from human intervention studies suggesting an anti-inflammatory potential of these plant foods. At the level of bioactive compounds occurring in plant foods, primarily carotenoids and flavonoids seem to modulate inflammatory as well as immunological processes. In conclusion, there is convincing evidence that plant foods and non-nutritive constituents associated with these foods modulate immunological and inflammatory processes. By means of anti-inflammatory activities a plant-based diet may contribute to the lower risk of cardiovascular diseases and cancer. A high intake of vegetables, fruit, and whole wheat as recommended by all international nutrition authorities provides a wide spectrum of bioactive compounds at health-promoting concentrations.", "title": "Anti-inflammatory effects of plant-based foods and of their constituents." }, { "docid": "MED-4753", "text": "BACKGROUND: Modern genetically improved dairy cows continue to lactate throughout almost the entire pregnancy. Therefore, recent commercial cow's milk contains large amounts of estrogens and progesterone. With regard to the exposure of prepubertal children to exogenous estrogens, the authors are particularly concerned about commercial milk produced from pregnant cows. The purpose of the present study was therefore to examine concentrations of serum and urine sex hormones after the intake of cow milk. METHODS: Subjects were seven men, six prepubertal children, and five women. The men and children drank 600 mL/m(2) of cow milk. Urine samples were collected 1 h before the milk intake and four times every hour after intake. In men the serum samples were obtained before and 15, 30, 45, 60, 90 and 120 min after milk intake. Women drank 500 mL of cow's milk every night for 21 days beginning on the first day of the second menstruation. In three successive menstrual cycles, the day of ovulation was examined using an ovulation checker. RESULTS: After the intake of cow milk, serum estrone (E1) and progesterone concentrations significantly increased, and serum luteinizing hormone, follicle-stimulating hormone and testosterone significantly decreased in men. Urine concentrations of E1, estradiol, estriol and pregnanediol significantly increased in all adults and children. In four out of five women, ovulation occurred during the milk intake, and the timing of ovulation was similar among the three menstrual cycles. CONCLUSIONS: The present data on men and children indicate that estrogens in milk were absorbed, and gonadotropin secretion was suppressed, followed by a decrease in testosterone secretion. Sexual maturation of prepubertal children could be affected by the ordinary intake of cow milk.", "title": "Exposure to exogenous estrogen through intake of commercial milk produced from pregnant cows." }, { "docid": "MED-2654", "text": "4-Nonylphenols (NPs) are common products of biodegradation of a widely used group of nonionic surfactants, the nonylphenol ethoxylates (NPEs). These compounds are known to be persistent, toxic, and estrogen active. There is a worldwide scientific and public discussion on the potential consequences of human long term dietary exposure to such endocrine disrupters. Despite numerous determinations of NPs in environmental samples no systematical reports exist relating to concentrations of NPs in food. We analyzed NPs in 60 different foodstuff commercially available in Germany. The results indicate that NPs are ubiquitous in food. The concentrations of NPs on a fresh weight basis varied between 0.1 and 19.4 microg/kg regardless of the fat content of the foodstuff. Based on data on German food consumption rates and these first analyses of NPs in food, the daily intake for an adult was calculated to be 7.5 microg/day NPs. For infants exclusively fed with breast milk or infant formulas daily intakes of 0.2 microg/day and 1.4 microg/day NPs, respectively, can be estimated.", "title": "Endocrine disrupting nonylphenols are ubiquitous in food." }, { "docid": "MED-4795", "text": "Forty-one children with a variety of gastrointestinal complaints were diagnosed with Clostridium difficile infections as part of a routine screen over 3 years. The infection had not been suspected prior to the screen. Each child responded to treatment with metronidazole with resolution of their symptoms. These data suggest that community-associated C difficile is increasing and may produce atypical disease and lead to misdiagnosis.", "title": "Increasing incidence of community-associated atypical Clostridium difficile disease in children." }, { "docid": "MED-2378", "text": "Background Polyunsaturated fatty acids (PUFA) have beneficial effects on cardiovascular risk, although the mechanisms are incompletely understood. In a previous article, we showed significant reductions in low-density lipoprotein cholesterol and several markers of inflammation with increasing intake of alpha-linolenic acid (ALA) from walnuts and flax. Objective To examine effects of ALA on cardiovascular responses to acute stress, flow-mediated dilation (FMD) of the brachial artery, and blood concentrations of endothelin-1 and arginine-vasopressin (AVP). Design Using a randomized, crossover study design, cardiovascular responses to acute stress were assessed in 20 hypercholesterolemic subjects, a subset of whom also underwent FMD testing (n = 12). Participants were fed an average American diet (AAD) and 2 experimental diets that varied in the amount of ALA and linoleic acid (LA) that they contained. The AAD provided 8.7% energy from PUFA (7.7% LA, 0.8% ALA). On the LA diet, saturated fat was reduced, and PUFA from walnuts and walnut oil provided 16.4% of energy (12.6% LA, 3.6% ALA). On the ALA diet, walnuts, walnut oil, and flax oil provided 17% energy from PUFA (10.5% LA, 6.5% ALA). Results The ALA and LA diets significantly reduced diastolic blood pressure (−2 to −3 mm Hg) and total peripheral resistance (−4%), and this effect was evident at rest and during stress (main effect of diet, p < 0.02). FMD increased (+34%) on the diet containing additional ALA. AVP also increased by 20%, and endothelin-1 was unchanged. Conclusions These results suggest novel mechanisms for the cardioprotective effects of walnuts and flax, and further work is needed to identify the bioactives responsible for these effects.", "title": "Effects of Diets High in Walnuts and Flax Oil on Hemodynamic Responses to Stress and Vascular Endothelial Function" }, { "docid": "MED-3422", "text": "In the present study, we tested the effect of a Mediterranean-style diet on sexual function in women with the metabolic syndrome. Women were identified in our database of subjects participating in controlled trials evaluating the effect of lifestyle changes and were included if they had a diagnosis of female sexual dysfunction (FSD) associated with a diagnosis of metabolic syndrome, a complete follow-up in the study trial and an intervention focused mainly on dietary changes. Fifty-nine women met the inclusion/exclusion criteria; 31 out of them were assigned to the Mediterranean-style diet and 28 to the control diet. After 2 years, women on the Mediterranean diet consumed more fruits, vegetables, nuts, whole grain and olive oil as compared with the women on the control diet. Female sexual function index (FSFI) improved in the intervention group, from a mean basal value of 19.7+/-3.1 to a mean post-treatment value of 26.1+/-4.1 (P=0.01), and remained stable in the control group. C-reactive protein (CRP) levels were significantly reduced in the intervention group (P<0.02). No single sexual domain (desire, arousal, lubrication, orgasm, satisfaction, pain) was significantly ameliorated by the dietary treatment, suggesting that the whole female sexuality may find benefit from lifestyle changes. A Mediterranean-style diet might be effective in ameliorating sexual function in women with metabolic syndrome.", "title": "Mediterranean diet improves sexual function in women with the metabolic syndrome." }, { "docid": "MED-5192", "text": "High dietary intakes of calcium and dairy products have been hypothesized to enhance prostate cancer risk, but available prospective data regarding these associations are inconsistent. We examined dietary intakes of calcium and dairy products in relation to risk of prostate cancer in the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study, a cohort of 29,133 male smokers aged 50-69 years at study entry. Dietary intake was assessed at baseline using a validated 276-item food use questionnaire. Cox proportional hazards regression was used to adjust for known or suspected risk factors for prostate cancer. During 17 years of follow-up, we ascertained 1,267 incident cases of prostate cancer. High versus low intake of dietary calcium was associated with a marked increase in prostate cancer risk. The multivariate relative risk (RR) of prostate cancer for > or =2,000 mg/day compared to <1,000 mg/day of calcium intake was 1.63 (95% confidence interval (CI), 1.27-2.10; p trend < 0.0001). Total dairy intake was also positively associated with risk of prostate cancer. The multivariate RR of prostate cancer comparing extreme quintiles of intake was 1.26 (95% CI, 1.04-1.51; p trend = 0.03). However, no association with total dairy intake remained after we adjusted for calcium (p trend = 0.17). Findings were similar by stage and grade of prostate cancer. The results from this large prospective study suggest that intake of calcium or some related component contained in dairy foods is associated with increased prostate cancer risk.", "title": "A prospective study of dietary calcium, dairy products and prostate cancer risk (Finland)." }, { "docid": "MED-1330", "text": "AIMS: To systematically review trends in diabetes mellitus (DM) prevalence in adults in China over the last 10 years and to identify the determinants of these trends. METHODS: A systematic search was conducted for studies published between 2000 and 2010. Studies reporting DM prevalence were included if they met the pre-determined criteria. The prevalence estimates and reported determinants of these studies were compared. RESULTS: Twenty-five manuscripts, reporting on 22 studies, were selected for inclusion in the review. There has been an increase in DM prevalence from 2.6% to 9.7% in China over the past decade. DM prevalence is strongly associated with age and is higher in urban residents compared with rural populations. Some studies found a difference in DM prevalence between males and females, but this finding was not consistent. Other commonly reported associations with DM included family history, obesity and hypertension. CONCLUSION: Over the period of 2000-2010, we identify a significant increase in DM prevalence at the national level. It is important for all levels of government to develop more effective strategies to prevent and manage this rising diabetes epidemic. There is also an important need for more large-scale studies of diabetes in the western and central regions of China. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.", "title": "Diabetes prevalence and determinants in adults in China mainland from 2000 to 2010: a systematic review." }, { "docid": "MED-3445", "text": "A population-based case-control interview study was designed to test the hypothesis that dietary iodine or the consumption of goitrogenic vegetables increases the risk of thyroid cancer. A total of 191 histologically confirmed cases (64 percent female) and 441 matched controls from five ethnic groups in Hawaii were available for analysis. Among women, intake of seafood (especially shellfish), harm ha (a fermented fish sauce), and dietary iodine were associated with an increased risk of cancer, whereas consumption of goitrogenic (primarily cruciferous) vegetables was associated with a decreased risk. Non-dietary risk factors included miscarriage (especially at first pregnancy), use of fertility drugs, family history of thyroid disease, obesity, and work as a farm laborer. The odds ratio for the combined effect of a high iodine intake and a first-pregnancy miscarriage was 4.8 (95 percent confidence interval [CI] = 1.2-19.2); and for high iodine intake and use of fertility drugs 7.3 (95 percent CI = 1.5-34.5). Among men, positive associations were found for obesity, work as a farm laborer, and a past history of benign thyroid disease. Although this study identified several dietary and non-dietary risk factors for thyroid cancer, it could not fully explain the exceptionally high incidence rates among Filipino women in Hawaii.", "title": "An epidemiologic study of thyroid cancer in Hawaii." }, { "docid": "MED-3884", "text": "Microbes have evolved over 3.5 billion years and are arguably the most adaptable organisms on earth. Restricted genetically by their inability to reproduce sexually, bacteria have acquired several additional mechanisms by which to exchange genetic material horizontally. Such mechanisms have allowed bacteria to inhabit some of the most inhospitable environments on earth. It is thus hardly surprising that when faced with a barrage of inimical chemicals (antibiotics) they have responded with an equal and opposite force. This article compares and contrasts the evolution of antimicrobial resistance to beta-lactam antibiotics over the last 70 years in two bacterial species, namely Staphylococcus aureus, a highly evolved human pathogen, and Pseudomonas aeruginosa, an opportunistic nosocomial pathogen.", "title": "The 2009 Garrod lecture: the evolution of antimicrobial resistance: a Darwinian perspective." }, { "docid": "MED-1409", "text": "This study compares the prevalence of coronary heart disease (CHD), risk factors (RF), and cardiovascular diseases (CVD) among Cretan men from a rural area examined in 1960 and 1991. The study population consisted of 148 men in 1960 and 42 men in 1991 of the same age group (fifty-five to fifty-nine years old) and from the same rural area. All men had a complete examination of the cardiovascular system and a resting electrocardiogram (ECG). Systolic BP (SBP) > or = 140 mmHg was found in 42.6% of the subjects in 1960 and in 45.2% in 1991 (NS). Diastolic BP > or = 95 mmHG was found in 14.9% of the subjects in 1960 as opposed to 33.3% in 1991 (P < 0.02). Total serum cholesterol (TSCH) > or = 260 mg/dL approximately 6.7 mmol/L) was found in 12.8% of the subjects in 1960 and in 28.6% in 1991 (P < 0.01). Heavy smokers ( > or = 20 cigarettes/daily) were 27.0% in 1960 as compared with 35.7% in 1991 (:NS); 5.4% of the subjects in 1960 had light physical activity (PA) as compared with 14.3% in 1991 (P < 0.01); 74.7% of the subjects were farmers in 1960 as compared with 43.6% in 1991 (P < 0.1). The prevalence of CHD was 0.7% in 1960 as compared with 9.5% in 1991 (P < 0.001). Hypertensive heart disease was found in 3.4% of the subjects in 1960 and 4.8% in 1991 (NS). The prevalence of all major CVD was much higher in 1991 (19.1%) as compared with 1960 (8.8%) (P < 0.01). In conclusion, the prevalence of CHD RF and CVD was much higher in 1991 than in 1960 for Cretan men of the same age group. This higher prevalence seems to be related to dietary and life-style changes that have taken place in Crete during the last thirty years.", "title": "Changing prevalence of coronary heart disease risk factors and cardiovascular diseases in men of a rural area of Crete from 1960 to 1991." }, { "docid": "MED-4069", "text": "To examine whether meat intake modifies breast-cancer risk, a case-control study was conducted in Uruguay. Dietary patterns were assessed in detail (for cases, before diagnosis or symptoms occurred) using a food frequency questionnaire involving 64 food items, which allowed total energy intake to be calculated. Nutrient residuals were calculated through regression analysis. After adjustment for potential confounders (which included family history of breast cancer, menopausal status, body-mass index, total energy and total alcohol intake), an increased risk associated with consumption of total meat intake, red meat intake, total fat and saturated fat intake was observed. The strongest effect was observed for red meat intake (OR 4.2, 95% CL 2.3-7.7) for consumption in the upper quartile, after controlling for protein and fat intake. This suggests an independent effect for meat. Since experimental studies have shown a strong effect of heterocyclic amines in rat mammary carcinogenesis, further studies should be performed in human epidemiology, perhaps using biomarkers of heterocyclic amine exposure.", "title": "Meat, fat and risk of breast cancer: a case-control study from Uruguay." }, { "docid": "MED-4590", "text": "Increased oxidative stress contributes to the decline in cognitive performance during normal aging and in neurodegenerative conditions such as Alzheimer's disease. Dietary supplementation with fruits and vegetables that are high in antioxidant potential have in some cases compensated for oxidative stress. Herein, we examined whether apple juice could alleviate the neurotoxic consequences of exposure of cultured neuronal cells to amyloid-beta (Abeta), since at least a portion of the neurotoxicity of Abeta is due to oxidative stress. Apple juice concentrate (AJC; 70 degree brix) was diluted into culture medium of SH-SY-5Y human neuroblastoma cells that had been differentiated for 7 days with 5 microM retinoic acid concurrent with the addition of 20 microM Abeta. AJC prevented the increased generation of reactive oxygen species (ROS) normally induced by Abeta treatment under these conditions. AJC also prevented Abeta-induced calcium influx and apoptosis, each of which results in part due to increased ROS. These findings suggest that the antioxidant potential of apple products can prevent Abeta-induced oxidative damage.", "title": "Apple juice prevents oxidative stress induced by amyloid-beta in culture." }, { "docid": "MED-5061", "text": "Bovine leukemia virus (BLV) is an oncogenic retrovirus that commonly infects cattle and causes B cell leukosis in 1-5% of infected cattle. BLV-infected cells are present in marketed beef and dairy products. In the decade after the discovery of BLV in 1969, studies using agar gel immunodiffusion and complement fixation assays failed to find antibodies to BLV in human sera. This led to the prevailing opinion that exposure of humans to BLV and/or the potential for infection are not significant and therefore the virus is not a public health hazard. We reexamined this issue using more sensitive immunological techniques available today. Using immunoblotting to test the sera of 257 humans for antibodies of four isotypes (IgG1, IgM, IgA, and IgG4) to the BLV capsid antigen (p24), we detected at least one antibody isotype reactive with BLV in 74% of the human sera tested. The specificity of the reactivity was strongly suggested by competition studies and by ruling out cross-reacting antibodies to other chronic human viruses. Our results suggest that antibodies reactive with the BLV capsid antigen may serve as a biomarker for exposure to BLV and this exposure may be widespread. The results do not necessarily mean that humans are actually infected with BLV; the antibodies could be a response to heat-denatured BLV antigens consumed in food. They do, however, suggest that further studies in this area could be important.", "title": "Humans have antibodies reactive with Bovine leukemia virus." }, { "docid": "MED-2352", "text": "BACKGROUND: Carbohydrate-specific IgE antibodies present on nonprimate mammalian proteins were incriminated recently in delayed meat anaphylaxis. The aim of this study was to explore whether anaphylaxis to mammalian kidney is also associated with galactose-α-1,3-galactose (αGal)-specific IgE. METHODS: Fourteen patients with anaphylaxis to pork or beef kidney underwent prick tests to meat and kidney. Some patients also underwent skin tests to Erbitux(®) (cetuximab). IgE antibodies to αGal, swine urine proteins, beef and pork meat, serum albumin proteins, cat, and rFel d 1 were measured by ImmunoCAP(®). The αGal levels were estimated in meats and kidney by ELISA inhibition assay. Cross-reactivity between αGal and pork kidney was studied with the ImmunoCAP(®) inhibition assay. RESULTS: Among the 14 patients, 12 presented with anaphylactic shock. Reactions occurred within 2 h from exposure in 67% of patients. Associated risk factors were observed in 10 cases, and alcohol was the main cofactor. Three patients underwent an oral challenge to pork kidney, and anaphylaxis occurred after ingestion of small quantities (1-2 g). Prick tests to kidney were positive in 54% of patients. All tested patients showed positive skin tests to Erbitux(®). All patients tested positive for IgE to αGal, with levels ranging from 0.4 to 294 kU/l. IgE binding to αGal was inhibited by raw pork kidney extract (mean, 77%; range, 55-87%), which showed a high amount of αGal determinants. CONCLUSIONS: Pork or beef kidney anaphylaxis is related to αGal IgE. Its peculiar severity could be due to an elevated content of αGal epitopes in kidney. © 2012 John Wiley & Sons A/S.", "title": "Anaphylaxis to pork kidney is related to IgE antibodies specific for galactose-alpha-1,3-galactose." }, { "docid": "MED-2356", "text": "Background In 2009, we reported a novel form of delayed anaphylaxis to red meat, which is related to serum IgE antibodies to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal). Most of these patients had tolerated meat for many years previously. The implication is that some exposure in adult life had stimulated the production of these IgE antibodies. Objectives To investigate possible causes of this IgE antibody response, focusing on evidence related to tick bites, which are common in the region where these reactions occur. Methods Serum assays were carried out using biotinylated proteins and extracts bound to a streptavidin ImmunoCAP. Results Prospective studies on IgE antibodies in three subjects following tick bites showed an increase in IgE to alpha-gal of twenty-fold or greater. Other evidence included i) a strong correlation between histories of tick bites and IgE to alpha-gal (χ2=26.8, p<0.001), ii) evidence that these IgE antibodies are common in areas where the tick Amblyomma americanum is common, and iii) a significant correlation between IgE antibodies to alpha-gal and IgE antibodies to proteins derived from A. americanum (rs=0.75, p<0.001). Conclusion The results presented here provide evidence that tick bites are a cause, or possibly the only cause, of IgE specific for alpha-gal in this area of the United States. Both the number of subjects becoming sensitized and the titer of IgE antibodies to alpha-gal are striking. Here we report the first example of a response to an ectoparasite giving rise to an important form of food allergy.", "title": "The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose" }, { "docid": "MED-2574", "text": "Inositol hexaphosphate (IP(6)) is a naturally occurring polyphosphorylated carbohydrate, abundantly present in many plant sources and in certain high-fiber diets, such as cereals and legumes. In addition to being found in plants, IP(6) is contained in almost all mammalian cells, although in much smaller amounts, where it is important in regulating vital cellular functions such as signal transduction, cell proliferation, and differentiation. For a long time IP(6) has been recognized as a natural antioxidant. Recently IP(6) has received much attention for its role in cancer prevention and control of experimental tumor growth, progression, and metastasis. In addition, IP(6) possesses other significant benefits for human health, such as the ability to enhance immune system, prevent pathological calcification and kidney stone formation, lower elevated serum cholesterol, and reduce pathological platelet activity. In this review we show the efficacy and discuss some of the molecular mechanisms that govern the action of this dietary agent. Exogenously administered IP(6) is rapidly taken up into cells and dephosphorylated to lower inositol phosphates, which further affect signal transduction pathways resulting in cell cycle arrest. A striking anticancer action of IP(6) was demonstrated in different experimental models. In addition to reducing cell proliferation, IP(6) also induces differentiation of malignant cells. Enhanced immunity and antioxidant properties also contribute to tumor cell destruction. Preliminary studies in humans show that IP(6) and inositol, the precursor molecule of IP(6), appear to enhance the anticancer effect of conventional chemotherapy, control cancer metastases, and improve quality of life. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP(6) + inositol holds great promise in our strategies for cancer prevention and therapy. There is clearly enough evidence to justify the initiation of full-scale clinical trials in humans.", "title": "Protection against cancer by dietary IP6 and inositol." }, { "docid": "MED-1136", "text": "1. Studies were carried out on six normal male subjects to determine the short-term effect of increasing the dietary consumption of animal protein on the urinary risk factors for stone-formation, namely, volume, pH, calcium oxalate, uric acid and glycosaminoglycans. 2. An increase of 34 g/day of animal protein in the diet significantly increased urinary calcium (23%) and oxalate (24%). Total urinary nitrogen increased by an average of 368 mmol/day. The accompanying increase in dietary purine (11 mmol of purine nitrogen/day) caused a 48% increase in the excretion of uric acid. 3. The overall relative probability of forming stones, calculated from a combination of the risk factors, was markedly increased (250%) throughout the period of high animal protein ingestion.", "title": "The effect of high animal protein intake on the risk of calcium stone-formation in the urinary tract." }, { "docid": "MED-3817", "text": "Background: Putrescine, spermidine, and spermine are the polyamines required for human cell growth. The inhibition of ornithine decarboxylase (ODC), which is the rate-limiting enzyme of polyamine biosynthesis, decreases tumor growth and the development of colorectal adenomas. A database was developed to estimate dietary polyamine exposure and relate exposure to health outcomes. Objective: We hypothesized that high polyamine intake would increase risk of colorectal adenoma and that the allelic variation at ODC G>A +316 would modify the association. Design: Polyamine exposure was estimated in subjects pooled (n = 1164) from the control arms of 2 randomized trials for colorectal adenoma prevention [Wheat Bran Fiber low-fiber diet arm (n = 585) and Ursodeoxycholic Acid placebo arm (n = 579)] by using baseline food-frequency questionnaire data. All subjects had to have a diagnosis of colorectal adenoma to be eligible for the trial. Results: A dietary intake of polyamines above the median amount in the study population was associated with 39% increased risk of colorectal adenoma at follow-up (adjusted OR: 1.39; 95% CI: 1.06, 1.83) in the pooled sample. In addition, younger participants (OR: 1.94; 95% CI: 1.23, 3.08), women (OR: 2.43; 95% CI: 1.48, 4.00), and ODC GG genotype carriers (OR: 1.59; 95% CI: 1.00, 2.53) had significantly increased odds of colorectal adenoma if they consumed above-median polyamine amounts. Conclusions: This study showed a role for dietary polyamines in colorectal adenoma risk. Corroboration of these findings would confirm a previously unrecognized, modifiable dietary risk factor for colorectal adenoma.", "title": "Dietary polyamine intake and risk of colorectal adenomatous polyps" }, { "docid": "MED-4826", "text": "A role of diet and nutrition in pancreatic carcinogenesis has been suggested, but the association between selected macronutrients, fatty acids, cholesterol and pancreatic cancer remains controversial. We analysed data from a hospital-based case-control study conducted in Italy between 1991 and 2008, including 326 cases (174 men and 152 women) with incident pancreatic cancer, and 652 controls (348 men and 304 women) frequency-matched to cases by sex, age and study centre. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multiple logistic regression models conditioned on age, sex and study centre, and adjusted for year of interview, education, tobacco smoking, history of diabetes and energy intake. A positive association was found for animal proteins (OR=1.85 for the highest versus the lowest quintile of intake; 95% CI: 1.15-2.96; p for trend=0.039), whereas a negative association was observed for sugars (OR=0.52; 95% CI: 0.31-0.86; p for trend=0.003). Non-significant negative associations emerged for vegetable proteins (OR=0.69) and polyunsaturated fatty acids (OR=0.67). In conclusion, a diet poor in animal proteins and rich in sugars (mainly derived from fruit) appears to have a beneficial effect on pancreatic cancer risk. Copyright (c) 2009 Elsevier Ltd. All rights reserved.", "title": "Macronutrients, fatty acids, cholesterol and pancreatic cancer." }, { "docid": "MED-3245", "text": "Cruciferous vegetables, tomato sauce, and legumes have been associated with reduced risk of incident advanced prostate cancer. In vitro and animal studies suggest these foods may inhibit progression of prostate cancer, but there are limited data in men. Therefore, we prospectively examined whether intake of total vegetables, and specifically cruciferous vegetables, tomato sauce, and legumes, after diagnosis reduce risk of prostate cancer progression among 1,560 men diagnosed with non-metastatic prostate cancer and participating in the Cancer of the Prostate Strategic Urologic Research Endeavor, a United States prostate cancer registry. As a secondary analysis, we also examined other vegetable sub-groups, total fruit, and subgroups of fruits. The participants were diagnosed primarily at community-based clinics and followed from 2004–2009. We assessed vegetable and fruit intake via a semi-quantitative food frequency questionnaire, and ascertained prostate cancer outcomes via urologist report and medical records. We observed 134 events of progression (53 biochemical recurrences, 71 secondary treatments likely due to recurrence, six bone metastases, four prostate cancer deaths) during 3,171 person-yrs. Men in the fourth quartile of post-diagnostic cruciferous vegetable intake had a statistically significant 59% decreased risk of prostate cancer progression compared to men in the lowest quartile (hazard ratio (HR): 0.41; 95% confidence interval (CI): 0.22, 0.76; p-trend: 0.003). No other vegetable or fruit group was statistically significantly associated with risk of prostate cancer progression. In conclusion, cruciferous vegetable intake after diagnosis may reduce risk of prostate cancer progression.", "title": "Vegetable and fruit intake after diagnosis and risk of prostate cancer progression" }, { "docid": "MED-1137", "text": "The lifetime prevalence of kidney stones is around 10 % and incidence rates are increasing. Diet may be an important determinant of kidney stone development. Our objective was to investigate the association between diet and kidney stone risk in a population with a wide range of diets. This association was examined among 51,336 participants in the Oxford arm of the European Prospective Investigation into Cancer and Nutrition using data from Hospital Episode Statistics in England and Scottish Morbidity Records. In the cohort, 303 participants attended hospital with a new kidney stone episode. Cox proportional hazards regression was performed to calculate hazard ratios (HR) and their 95 % confidence intervals (95 % CI). Compared to those with high intake of meat (>100 g/day), the HR estimates for moderate meat-eaters (50-99 g/day), low meat-eaters (<50 g/day), fish-eaters and vegetarians were 0.80 (95 % CI 0.57-1.11), 0.52 (95 % CI 0.35-0.8), 0.73 (95 % CI 0.48-1.11) and 0.69 (95 % CI 0.48-0.98), respectively. High intakes of fresh fruit, fibre from wholegrain cereals and magnesium were also associated with a lower risk of kidney stone formation. A high intake of zinc was associated with a higher risk. In conclusion, vegetarians have a lower risk of developing kidney stones compared with those who eat a high meat diet. This information may be important to advise the public about prevention of kidney stone formation.", "title": "Diet and risk of kidney stones in the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)." }, { "docid": "MED-3249", "text": "144 multiple sclerosis patients took a low-fat diet for 34 years. For each of three categories of neurological disability (minimum, moderate, severe) patients who adhered to the prescribed diet (less than or equal to 20 g fat/day) showed significantly less deterioration and much lower death rates than did those who consumed more fat than prescribed (greater than 20 g fat/day). The greatest benefit was seen in those with minimum disability at the start of the trial; in this group, when those who died from non-MS diseases were excluded from the analysis, 95% survived and remained physically active.", "title": "Effect of low saturated fat diet in early and late cases of multiple sclerosis." }, { "docid": "MED-3046", "text": "Tobacco smoking is the most frequent form of substance abuse. Several studies have shown that the addictive action of nicotine is mediated by the mesolimbic dopamine system. This system is implicated in reward processing. In order to better understand the relationship between nicotine addiction and reward in humans, we investigated differences between smokers and nonsmokers in the activation of brain regions involved in processing reward information. Using [H2(15O)] positron emission tomography (PET), we measured regional cerebral blood flow (rCBF) in healthy smokers and nonsmokers while they performed a prelearned, pattern-recognition task. We compared two conditions involving nonmonetary reinforcement or monetary reward with a baseline condition in which nonsense feedback was presented. With monetary reward, we found activation in the frontal and orbitofrontal cortex, occipital cortex, cingulate gyrus, cerebellum, and midbrain in both groups. Additionally, monetary reward activated typical dopaminergic regions such as the striatum in nonsmokers but not in smokers. We found a similar pattern of activation associated with nonmonetary reinforcement in nonsmokers, whereas activation was found in smokers only in the cerebellum. The different patterns of activation suggest that the brains of smokers react in a different way to reward than those of nonsmokers. This difference involves in particular the regions of the dopaminergic system including the striatum. In principle these observations could be interpreted either as a consequence of tobacco use or as a primitive condition of the brain that led people to smoke. Supported by related nonimaging studies, we interpret these differences as a consequence of tobacco smoking, even if a short-term effect of smoking prior to the experiment cannot be excluded.", "title": "Changes in brain activation associated with reward processing in smokers and nonsmokers. A positron emission tomography study." }, { "docid": "MED-1986", "text": "BACKGROUND: Overweight in adults is associated with increased morbidity and mortality. In contrast, the long-term effect of overweight in adolescence on morbidity and mortality is not known. METHODS: We studied the relation between overweight and morbidity and mortality in 508 lean or overweight adolescents 13 to 18 years old who participated in the Harvard Growth Study of 1922 to 1935. Overweight adolescents were defined as those with a body-mass index that on two occasions was greater than the 75th percentile in subjects of the same age and sex in a large national survey. Lean adolescents were defined as those with a body-mass index between the 25th and 50th percentiles. Subjects who were still alive were interviewed in 1988 to obtain information about their medical history, weight, functional capacity, and other risk factors. For those who had died, information on the cause of death was obtained from death certificates. RESULTS: Overweight in adolescent subjects was associated with an increased risk of mortality from all causes and disease-specific mortality among men, but not among women. The relative risks among men were 1.8 (95 percent confidence interval, 1.2 to 2.7; P = 0.004) for mortality from all causes and 2.3 (95 percent confidence interval, 1.4 to 4.1; P = 0.002) for mortality from coronary heart disease. The risk of morbidity from coronary heart disease and atherosclerosis was increased among men and women who had been overweight in adolescence. The risk of colorectal cancer and gout was increased among men and the risk of arthritis was increased among women who had been overweight in adolescence. Overweight in adolescence was a more powerful predictor of these risks than overweight in adulthood. CONCLUSIONS: Overweight in adolescence predicted a broad range of adverse health effects that were independent of adult weight after 55 years of follow-up.", "title": "Long-term morbidity and mortality of overweight adolescents. A follow-up of the Harvard Growth Study of 1922 to 1935." }, { "docid": "MED-4642", "text": "The role of diet in breast cancer (BC) risk is unclear. Fiber could reduce BC risk, through the enterohepatic circulation of estrogens. We examined the relationship between diet and sex hormones in postmenopausal women with or without BC. Thirty-one postmenopausal women (10 omnivores, 11 vegetarians, and 10 BC omnivores) were recruited. Dietary records (5 days) and hormone levels (3 days) were evaluated on 4 occasions over 1 yr. Vegetarians showed a lower fat/fiber ratio, a higher intake of total and cereal fiber (g/d)/body weight (kg), a significantly lower level of plasma estrone-sulfate, estradiol, free-estradiol, free-testosterone, and ring D oxygenated estrogens, and a significantly higher level of sex-hormone-binding-globulin than BC subjects. Fiber was consumed in slightly larger amounts by omnivores than by BC subjects. Omnivores had significantly lower plasma testosterone and estrone-sulfate but higher sex-hormone-binding-globulin than BC subjects. No difference was found for the urinary 16-oxygenated estrogens. However, the 2-MeO-E1/2-OH-E1 ratio was significantly lower in omnivores than in BC group. This ratio is positively associated with the fat/fiber ratio. In conclusion, testosterone may contribute to causing alterations in the levels of catechol estrogens and 16-oxygenated estrogens. The fat/fiber ratio appears to be useful in evaluating dietary effects on estrogen metabolism.", "title": "Diets and hormonal levels in postmenopausal women with or without breast cancer." }, { "docid": "MED-4589", "text": "Understanding mechanisms associated with flavonoid neuroprotection is complicated by the lack of information on their ability to enter the CNS. This study examined naringenin and quercetin permeability across the blood-brain barrier (BBB), using in vitro (ECV304/C6 coculture) and in situ (rat) models. We report measurable permeabilities (P(app)) for both flavonoids across the in vitro BBB model, consistent with their lipophilicity. Both flavonoids showed measurable in situ BBB permeability. The rates of uptake (K(in)) into the right cerebral hemisphere were 0.145 and 0.019 ml min(-1) g(-1) for naringenin and quercetin, respectively. Quercetin K(in) was comparable to that of colchicine (0.006 ml min(-1) g(-1)), a substrate for P-glycoprotein (P-gp). Preadministration of the P-gp inhibitor PSC833 or GF120918 (10 mg/kg body wt) significantly increased colchicine K(in), but only GF120918 (able to inhibit breast cancer resistance protein, BCRP) affected K(in) for quercetin. Naringenin K(in) was not affected. The influence of efflux transporters on flavonoid permeability at the BBB was further studied using MDCK-MDR1 and immortalized rat brain endothelial cells (RBE4). Colchicine, quercetin, and naringenin all showed measurable accumulation (distribution volume, V(d) (microl/mg protein)) in both cell types. The V(d) for colchicine increased significantly in both cell lines following coincubation with either PSC833 (25 microM) or GF120918 (25 microM). Both inhibitors also caused an increase in naringenin V(d); by contrast only GF120918 coincubation significantly increased quercetin V(d). In conclusion, the results demonstrate that flavonoids are able to traverse the BBB in vivo. However, the permeability of certain flavonoids in vivo is influenced by their lipophilicity and interactions with efflux transporters.", "title": "Flavonoid permeability across an in situ model of the blood-brain barrier." }, { "docid": "MED-2215", "text": "We investigated the relationship between animal product consumption and evidence of dementia in two cohort substudies. The first enrolled 272 California residents matched for age, sex, and zip code (1 vegan, 1 lacto-ovo-vegetarian, and 2 'heavy' meat eaters in each of 68 quartets). This design ensured a wide range of dietary exposure. The second included 2,984 unmatched subjects who resided within the Loma Linda, California area. All subjects were enrolled in the Adventist Health Study. The matched subjects who ate meat (including poultry and fish) were more than twice as likely to become demented as their vegetarian counterparts (relative risk 2.18, p = 0.065) and the discrepancy was further widened (relative risk 2.99, p = 0.048) when past meat consumption was taken into account. There was no significant difference in the incidence of dementia in the vegetarian versus meat-eating unmatched subjects. There was no obvious explanation for the difference between the two substudies, although the power of the unmatched sub-study to detect an effect of 'heavy' meat consumption was unexpectedly limited. There was a trend towards delayed onset of dementia in vegetarians in both substudies.", "title": "The incidence of dementia and intake of animal products: preliminary findings from the Adventist Health Study." }, { "docid": "MED-4053", "text": "Heterocyclic amines (HCAs), potent mutagens and a risk factor for human cancers, are produced in meats cooked at high temperature. The aim of this study was to determine the HCA content in cooked meat products (beef, chicken, pork, fish) prepared by various cooking methods (pan frying, oven broiling, and oven baking at 170 to 230°C) that are preferred by U.S. meat consumers. The primary HCAs in these samples were PhIP (2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine) (1.49-10.89ng/g), MeIQx (2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline) (not detected-4.0ng/g), and DiMeIQx (2-amino-3,4,8-trimethyl-imidazo [4,5-f]quinoxaline) (not detected-3.57ng/g). Type and content of HCAs in cooked meat samples were highly dependent on cooking conditions. The total HCA content in well-done meat was 3.5 times higher than that of medium-rare meat. Fried pork (13.91ng/g) had higher levels of total HCAs than fried beef (8.92ng/g) and fried chicken (7.00ng/g). Among the samples, fried bacon contained the highest total HCA content (17.59ng/g). Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Occurrence of heterocyclic amines in cooked meat products." }, { "docid": "MED-1374", "text": "The Mediterranean diet has been linked to a number of health benefits, including reduced mortality risk and lower incidence of cardiovascular disease. Definitions of the Mediterranean diet vary across some settings, and scores are increasingly being employed to define Mediterranean diet adherence in epidemiological studies. Some components of the Mediterranean diet overlap with other healthy dietary patterns, whereas other aspects are unique to the Mediterranean diet. In this forum article, we asked clinicians and researchers with an interest in the effect of diet on health to describe what constitutes a Mediterranean diet in different geographical settings, and how we can study the health benefits of this dietary pattern.", "title": "Definitions and potential health benefits of the Mediterranean diet: views from experts around the world" }, { "docid": "MED-2559", "text": "Inositol hexaphosphate (IP6) has anti-cancer properties, but recently other extracellular functions have been observed for IP6, including enhancing superoxide production and phagocytosis by neutrophils in the presence of microbial stimuli. This study investigated other inflammatory functions of IP6 on adherent neutrophils. The effect of IP6 on the release of IL-8, tumour necrosis factor (TNF-alpha) and IL-6 by neutrophils attached to either plastic or laminin for up to 6 hours in response to stimulation with lipopolysaccharide or N-formyl-Met-Leu-Phe (fMLP) was investigated. An increase in IL-8 secretion by stimulated cells occurred in the presence of IP6. The incubation of cells attached to laminin with IP6 alone (100-250 BM) did not effect cell morphology, but in the presence of 10(-7) M fMLP altered cell shape. A direct effect of IP6 on cell function was to trigger a sustained assembly of F-actin. Thus, exposure of neutrophils to low levels of IP6 appears to modulate selective neutrophil functions.", "title": "Effect of IP6 on human neutrophil cytokine production and cell morphology." }, { "docid": "MED-4342", "text": "OBJECTIVES: Diet composition has long been suspected to contribute to inflammatory bowel disease (IBD), but has not been thoroughly assessed, and has been assessed only in retrospective studies that are prone to recall bias. The aim of the present study was to evaluate the role of dietary macronutrients in the etiology of IBD in a large prospective cohort. METHODS: The Etude Épidémiologique des femmes de la Mutuelle Générale de l'Education Nationale cohort consists of women living in France, aged 40-65 years, and free of major diseases at inclusion. A self-administered questionnaire was used to record dietary habits at baseline. Questionnaires on disease occurrence and lifestyle factors were completed every 24 months. IBDs were assessed in each questionnaire until June 2005, and subsequently validated using clinical and pathological criteria. We estimated the association between nutrients or foods and IBD using Cox proportional hazards models adjusted for energy intake. RESULTS: Among 67,581 participants (705,445 person-years, mean follow-up since completion of the baseline dietary questionnaire 10.4 years), we validated 77 incident IBD cases. High total protein intake, specifically animal protein, was associated with a significantly increased risk of IBD, (hazards ratio for the third vs. first tertile and 95% confidence interval being 3.31 and 1.41-7.77 (P trend=0.007), and 3.03 and 1.45-6.34 (P trend=0.005) for total and animal protein, respectively). Among sources of animal protein, high consumption of meat or fish but not of eggs or dairy products was associated with IBD risk. CONCLUSIONS: High protein intake is associated with an increased risk of incident IBD in French middle-aged women.", "title": "Animal protein intake and risk of inflammatory bowel disease: The E3N prospective study." }, { "docid": "MED-4520", "text": "Evidence suggests that endothelial dysfunction is on the causal pathway for both atherogenesis and destabilization of established plaques. In this review, the role of flow-mediated dilatation (FMD) as a non-invasive method to assess endothelial function is discussed. Technical modifications and development of analysis software have significantly improved the variability of the method. Following a strict standardized protocol enables reproducible measurements to be achieved and export of the technique from specialized laboratories to population studies and multicentre settings. Endothelial function assessed by FMD has been shown to be affected by cardiovascular risk factors, to be related to structural arterial disease and to cardiovascular outcome, validating its use for studying the pathophysiology of arterial disease. Numerous studies have also demonstrated that it is responsive to physiological and pharmacological interventions. Flow-mediated dilatation provides unique opportunities in drug development programmes to assess an early rapidly responsive signal of risk or benefit, complementing endpoints of structural arterial disease and cardiovascular outcomes that take much longer and are more expensive.", "title": "Assessment of atherosclerosis: the role of flow-mediated dilatation." }, { "docid": "MED-4406", "text": "Objective To investigate longitudinal associations between community-level gasoline price and physical activity (PA). Method In the Coronary Artery Risk Development in Young Adults study, 5,115 black and white participants aged 18–30 at baseline 1985–86 were recruited from four U.S. cities (Birmingham, Chicago, Minneapolis and Oakland) and followed over time. We used data from 3 follow-up exams: 1992–93, 1995–96, and 2000–01, when the participants were located across 48 states. From questionnaire data, a total PA score was summarized in exercise units (EU) based on intensity and frequency of 13 PA categories. Using Geographic Information Systems, participants’ residential locations were linked to county-level inflation-adjusted gasoline price data collected by the Council for Community & Economic Research. We used a random-effect longitudinal regression model to examine associations between time-varying gasoline price and time-varying PA, controlling for age, race, gender, baseline study center, and time-varying education, marital status, household income, county cost of living, county bus fare, census block-group poverty, and urbanicity. Results Holding all control variables constant, a 25-cent increase in inflation-adjusted gasoline price was significantly associated with an increase of 9.9 EU in total PA (95%CI: 0.8–19.1). Conclusion Rising prices of gasoline may be associated with an unintended increase in leisure PA.", "title": "Longitudinal trends in gasoline price and physical activity: The CARDIA study" }, { "docid": "MED-1606", "text": "Background: Plant-based and fiber-rich diets high in vegetables, fruit, and whole grains are recommended to prevent cancer and chronic conditions associated with renal cell carcinoma (RCC), such as obesity, hypertension, and diabetes. Diet may play a role in the etiology of RCC directly and/or indirectly. Objective: In a large prospective cohort of US men and women, we comprehensively investigated dietary intake and food sources of fiber in relation to RCC risk. Design: Participants of the NIH-AARP Diet and Health Study (n = 491,841) completed a self-administered questionnaire of demographics, diet, lifestyle, and medical history. Over 9 (mean) years of follow-up we identified 1816 incident cases of RCC. HRs and 95% CIs were estimated within quintiles by using multivariable Cox proportional hazards regression. Results: Total dietary fiber intake was associated with a significant 15–20% lower risk of RCC in the 2 highest quintiles compared with the lowest (P-trend = 0.005). Intakes of legumes, whole grains, and cruciferous vegetables were also associated with a 16–18% reduced risk of RCC. Conversely, refined grain intake was positively associated with RCC risk in a comparison of quintile 5 with quintile 1 (HR: 1.19; 95% CI: 1.02, 1.39; P-trend = 0.04). The inverse association between fiber intake and RCC was consistent among participants who never smoked, had a body mass index [BMI (in kg/m2)] <30, and did not report a history of diabetes or hypertension. Conclusions: Intake of fiber and fiber-rich plant foods was associated with a significantly lower risk of RCC in this large US cohort. This trial was registered at clinicaltrials.gov as NCT00340015.", "title": "Intake of fiber and fiber-rich plant foods is associated with a lower risk of renal cell carcinoma in a large US cohort" }, { "docid": "MED-2658", "text": "The prevalence of allergic diseases has increased in recent decades. Allergic diseases, particularly asthma, are complex diseases with strong gene-environment interactions. Epidemiological studies have identified a variety of risk factors for the development of allergic diseases. Among them, endocrine-disrupting chemicals (EDCs) play an important role in triggering or exacerbating these diseases. 4-Nonylphenol (NP) and 4-octylphenol (OP)--two major alkylphenols--have been recognized as common toxic and xenobiotic endocrine disrupters. Due to their low solubility, high hydrophobicity, and low estrogenic activity, they tend to accumulate in the human body and may be associated with the adverse effects of allergic diseases. Recently, new evidence has supported the importance of alkylphenols in the in vitro allergic response. This review focuses on the effects of alkylphenols on several key cell types in the context of allergic inflammation. Copyright © 2012. Published by Elsevier B.V.", "title": "Alkylphenols--potential modulators of the allergic response." }, { "docid": "MED-2511", "text": "Residents of Okinawa, the southernmost prefecture of Japan, are known for their long average life expectancy, high numbers of centenarians, and accompanying low risk of age-associated diseases. Much of the longevity advantage in Okinawa is thought to be related to a healthy lifestyle, particularly the traditional diet, which is low in calories yet nutritionally dense, especially with regard to phytonutrients in the form of antioxidants and flavonoids. Research suggests that diets associated with a reduced risk of chronic diseases are similar to the traditional Okinawan diet, that is, vegetable and fruit heavy (therefore phytonutrient and antioxidant rich) but reduced in meat, refined grains, saturated fat, sugar, salt, and full-fat dairy products. Many of the characteristics of the diet in Okinawa are shared with other healthy dietary patterns, such as the traditional Mediterranean diet or the modern DASH (Dietary Approaches to Stop Hypertension) diet. Features such as the low levels of saturated fat, high antioxidant intake, and low glycemic load in these diets are likely contributing to a decreased risk for cardiovascular disease, some cancers, and other chronic diseases through multiple mechanisms, including reduced oxidative stress. A comparison of the nutrient profiles of the three dietary patterns shows that the traditional Okinawan diet is the lowest in fat intake, particularly in terms of saturated fat, and highest in carbohydrate intake, in keeping with the very high intake of antioxidant-rich yet calorie-poor orange-yellow root vegetables, such as sweet potatoes, and green leafy vegetables. Deeper analyses of the individual components of the Okinawan diet reveal that many of the traditional foods, herbs, or spices consumed on a regular basis could be labeled \"functional foods\" and, indeed, are currently being explored for their potential health-enhancing properties.", "title": "The Okinawan diet: health implications of a low-calorie, nutrient-dense, antioxidant-rich dietary pattern low in glycemic load." }, { "docid": "MED-1575", "text": "Background Epithelial barrier function is impaired in Crohn's disease. Aim To define the underlying cellular mechanisms with special attention to tight junctions. Methods Biopsy specimens from the sigmoid colon of patients with mild to moderately active or inactive Crohn's disease were studied in Ussing chambers, and barrier function was determined by impedance analysis and conductance scanning. Tight junction structure was analysed by freeze fracture electron microscopy, and tight junction proteins were investigated immunohistochemically by confocal laser scanning microscopy and quantified in immunoblots. Epithelial apoptosis was analysed in terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick‐end labelling and 4′,6‐diamidino‐2‐phenylindole staining. Results Patients with active Crohn's disease showed an impaired intestinal barrier function as indicated by a distinct reduction in epithelial resistance. As distribution of conductivity was even, focal epithelial lesions (eg, microerosions) did not contribute to barrier dysfunction. Instead, freeze fracture electron microscopy analysis showed reduced and discontinuous tight junction strands. Occludin and the sealing tight junction proteins claudin 5 and claudin 8 were downregulated and redistributed off the tight junction, whereas the pore‐forming tight junctions protein claudin 2 was strongly upregulated, which constitute the molecular basis of tight junction changes. Other claudins were unchanged (claudins 1, 4 and 7) or not detectable in sigmoid colon (claudins 11, 12, 14, 15 and 16). Claudin 2 upregulation was less pronounced in active Crohn's disease compared with active ulcerative colitis and was inducible by tumour necrosis factor α. As a second source of impaired barrier function, epithelial apoptosis was distinctly increased in active Crohn's disease (mean (SD) 5.2 (0.5)% v 1.9 (0.2)% in control). By contrast, barrier function, tight junction proteins and apoptosis were unaffected in Crohn's disease in remission. Conclusion Upregulation of pore‐forming claudin 2 and downregulation and redistribution of sealing claudins 5 and 8 lead to altered tight junction structure and pronounced barrier dysfunction already in mild to moderately active Crohn's disease.", "title": "Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease" }, { "docid": "MED-4305", "text": "Influence of diet composition on mood during weight-reducing diets was studied in healthy young women of normal weight. A broad range of macronutrient intake was achieved by means of divergent dietary instructions for the composition of a 1,000 kcal per day diet adhered to for six weeks. Global mood during the last three weeks of the diet was significantly better in the \"vegetarian\" than in the \"mixed\" diet group. During this time a significant correlation was observed between relative carbohydrate intake and global mood (r = -0.74; p less than 0.01) and between the ratio of plasma tryptophan to other large neutral amino acids (a predictor of tryptophan flow into brain) and global mood (r = -0.52; p less than 0.05). Results suggest that group differences are related to differences in carbohydrate intake. It is hypothesized that impairment of central serotonergic function due to reduced tryptophan availability can prompt mood deterioration in situations of relatively low carbohydrate intake.", "title": "Macronutrient intake, plasma large neutral amino acids and mood during weight-reducing diets." }, { "docid": "MED-4756", "text": "BACKGROUND/OBJECTIVES: Little is known about nutritional factors that influence circulating concentrations of steroid hormones, which are consistently associated with risk of breast cancer for postmenopausal women. We aimed to investigate the association between consumption of animal products and the plasma concentrations of steroid hormones and sex hormone-binding globulin (SHBG). SUBJECTS/METHODS: Cross-sectional analysis was conducted on plasma from 766 naturally postmenopausal women. We measured plasma concentrations of steroid hormones and SHBG, and estimated dietary intakes using a 121-item food frequency questionnaire. Log-transformed values of hormone concentrations were regressed on quartiles of intake of meat and dairy products among food items, and fats, proteins and cholesterol among nutrient intake. RESULTS: Total red and fresh red meat consumption was negatively associated with SHBG levels (P for trend=0.04 and <0.01, respectively). Mean SHBG concentrations were approximately 8% and 13% lower for women in the highest quartile compared with the lowest quartile of total red and fresh red meat consumption, respectively. Positive associations were observed between dairy product consumption and total and free estradiol concentrations (P for trend=0.02 and 0.03, respectively). Mean concentrations of total and free estradiol were 15 and 14% higher for women in the highest quartile of dairy product consumption than for those in the lowest quartile, respectively. No associations were observed with consumption of processed meat, chicken, fish, eggs, cholesterol, fats or protein. CONCLUSIONS: Our study suggests that greater consumption of total red and fresh red meat and dairy products might influence circulating concentrations of SHBG and estradiol, respectively. Confirmation and further investigation is required.", "title": "Consumption of animal products, their nutrient components and postmenopausal circulating steroid hormone concentrations." }, { "docid": "MED-3791", "text": "Experimental and epidemiological evidence suggest that a diet with dietary fat as low as 20% of kcal may be necessary to reduce the risk of breast cancer. Two groups of women, postmenopausal women treated for breast cancer and premenopausal women with cystic breast disease accompanied by cyclical mastaligia, participated in an intervention program to determine the feasibility of such a low-fat diet. After 3 mo of intervention both groups were consuming a low-fat diet; in the premenopausal groups serum estrogen levels decreased in response to the fat reduction. Other nutrition-education programs in research institutions, restaurants, and schools are attempting to influence the public's knowledge and behavior regarding the importance of dietary fat reduction.", "title": "Recommendations for the prevention of chronic disease: the application for breast disease." }, { "docid": "MED-2256", "text": "Previous analyses at the European scale have shown that cadmium and lead concentrations in mosses are primarily determined by the total deposition of these metals. Further analyses in the current study show that Spearman rank correlations between the concentration in mosses and the deposition modelled by the European Monitoring and Evaluation Programme (EMEP) are country and metal-specific. Significant positive correlations were found for about two thirds or more of the participating countries in 1990, 1995, 2000 and 2005 (except for Cd in 1990). Correlations were often not significant and sometimes negative in countries where mosses were only sampled in a relatively small number of EMEP grids. Correlations frequently improved when only data for EMEP grids with at least three moss sampling sites per grid were included. It was concluded that spatial patterns and temporal trends agree reasonably well between lead and cadmium concentrations in mosses and modelled atmospheric deposition. Copyright © 2012 Elsevier Ltd. All rights reserved.", "title": "Country-specific correlations across Europe between modelled atmospheric cadmium and lead deposition and concentrations in mosses." }, { "docid": "MED-4587", "text": "A polyphenol-rich (P-R) juice drink was developed as a potential approach to increase intake of dietary polyphenols. Analysis of the beverage by HPLC with PDA, fluorescence, and MS detection facilitated the identification/partial identification of 40 flavonoids and related phenolic compounds. The main constituents were (-)-epigallocatechin and other green tea flavan-3-ols, phloretin-2'-O-glucoside, gallic acid, hesperetin-7-O-rutinoside, 5-O-caffeoylquinic acid, and procyanidins, with trace levels of several flavonols and purple grape juice anthocyanins also being present. Healthy human subjects (n = 10) consumed 350 mL of the P-R juice drink, after which plasma and urine samples were collected over a 0-24 h period. HPLC-MS analysis identified 13 metabolites in plasma and a further 20 in urine. Qualitatively, the profiles of the glucuronide, sulfated, and methylated metabolites were very similar to those detected in earlier investigations when the main components in the juice drink were consumed separately in feeding studies with coffee, green tea, orange juice, and apple cider.", "title": "Identification of metabolites in human plasma and urine after consumption of a polyphenol-rich juice drink." }, { "docid": "MED-4799", "text": "To determine the presence of Clostridium difficile, we sampled cooked and uncooked meat products sold in Tucson, Arizona. Forty-two percent contained toxigenic C. difficile strains (either ribotype 078/toxinotype V [73%] or 027/toxinotype III [NAP1 or NAP1-related; 27%]). These findings indicate that food products may play a role in interspecies C. difficile transmission.", "title": "Clostridium difficile in Retail Meat Products, USA, 2007" }, { "docid": "MED-3929", "text": "Objective: To prospectively examine whether higher intakes of total flavonoids and their subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones, and polymers) were associated with a lower risk of developing Parkinson disease (PD). Methods: In the current analysis, we included 49,281 men in the Health Professional Follow-up Study and 80,336 women from the Nurses' Health Study. Five major sources of flavonoid-rich foods (tea, berry fruits, apples, red wine, and orange/orange juice) were also examined. Flavonoid intake was assessed using an updated food composition database and a validated food frequency questionnaire. Results: We identified 805 participants (438 men and 367 women) who developed PD during 20–22 years of follow-up. In men, after adjusting for multiple confounders, participants in the highest quintile of total flavonoids had a 40%lower PD risk than those in the lowest quintile (hazard ratio [HR] = 0.60; 95% confidence interval 0.43, 0.83; p trend = 0.001). No significant relationship was observed in women (p trend = 0.62) or in pooled analyses (p trend = 0.23). In the pooled analyses for the subclasses, intakes of anthocyanins and a rich dietary source, berries, were significantly associated with a lower PD risk (HR comparing 2 extreme intake quintiles were 0.76 for anthocyanins and 0.77 for berries, respectively; p trend < 0.02 for both). Conclusions: Our findings suggest that intake of some flavonoids may reduce PD risk, particularly in men, but a protective effect of other constituents of plant foods cannot be excluded.", "title": "Habitual intake of dietary flavonoids and risk of Parkinson disease" }, { "docid": "MED-2278", "text": "OBJECTIVES: To investigate the anti-inflammatory and anti-oxidative effects of anthocyanins from cherries on Freund's adjuvant-induced arthritis (AIA) in rats. METHODS: Arthritis was induced intradermally by injection with 0.1 mL of complete Freund's adjuvant (CFA) into the right hind footpad of male Sprague Dawley (SD) rats. Anthocyanins at 40, 20 and 10 mg/kg (body weight) were administered orally to the treated rats for 28 days after the injection. Tumour necrosis factor-alpha (TNFalpha) in serum and prostaglandin E2 (PGE2) in paws were assayed by radioimmunoassay (RIA), and anti-oxidative effects was assayed by measuring total anti-oxidative capacity (T-AOC), superoxide dismutase (SOD) and malondialdehyde (MDA) in serum. RESULTS: Anthocyanins at 40 mg/kg significantly decreased the levels of TNFalpha in serum and PGE2 in paws, simultaneously improving the anti-oxidative status of AIA. We found that at this dosage T-AOC was potentized, the activity of SOD increased and the level of MDA in serum decreased. However, anthocyanins at 20 and 10 mg/kg had less effect on the inflammatory factors and anti-oxidative capacity of AIA. CONCLUSIONS: Anthocyanins have potential anti-inflammatory and anti-oxidative effects on AIA.", "title": "Anti-inflammatory and anti-oxidative effects of cherries on Freund's adjuvant-induced arthritis in rats." }, { "docid": "MED-1616", "text": "The role of very-low-carbohydrate ketogenic diets (VLCKD) in the long-term management of obesity is not well established. The present meta-analysis aimed to investigate whether individuals assigned to a VLCKD (i.e. a diet with no more than 50 g carbohydrates/d) achieve better long-term body weight and cardiovascular risk factor management when compared with individuals assigned to a conventional low-fat diet (LFD; i.e. a restricted-energy diet with less than 30% of energy from fat). Through August 2012, MEDLINE, CENTRAL, ScienceDirect,Scopus, LILACS, SciELO, ClinicalTrials.gov and grey literature databases were searched, using no date or language restrictions, for randomised controlled trials that assigned adults to a VLCKD or a LFD, with 12 months or more of follow-up. The primary outcome was bodyweight. The secondary outcomes were TAG, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), systolic and diastolic blood pressure,glucose, insulin, HbA1c and C-reactive protein levels. A total of thirteen studies met the inclusion/exclusion criteria. In the overall analysis,five outcomes revealed significant results. Individuals assigned to a VLCKD showed decreased body weight (weighted mean difference 20·91 (95% CI 21·65, 20·17) kg, 1415 patients), TAG (weighted mean difference 20·18 (95% CI 20·27, 20·08) mmol/l, 1258 patients)and diastolic blood pressure (weighted mean difference 21·43 (95% CI 22·49, 20·37) mmHg, 1298 patients) while increased HDL-C(weighted mean difference 0·09 (95% CI 0·06, 0·12) mmol/l, 1257 patients) and LDL-C (weighted mean difference 0·12 (95% CI 0·04,0·2) mmol/l, 1255 patients). Individuals assigned to a VLCKD achieve a greater weight loss than those assigned to a LFD in the longterm; hence, a VLCKD may be an alternative tool against obesity.", "title": "Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials." }, { "docid": "MED-3417", "text": "The aim of this work is to assess the association between vasculogenic erectile dysfunction (ED) and coronary artery disease in men above the age of 40 y. The study included 40 patients above 40 y of age with vasculogenic ED of more than 3 months duration. A dynamic duplex study after intracavernosal injection of a bimix solution (60 mg papaverine + 2 mg phentolamine mesylate) was carried out using a color ultrasound machine. The patients underwent a stress ECG test, carried out on a motor-driven treadmill according to the 'Bruce Protocol'. A total of 12 patients were diagnosed with positive ischemic heart disease (IHD). Their mean peak systolic velocity (PSV) was PSV = 19.58 cm/s. In all, patients were diagnosed with negative IHD; their mean PSV was 36.21 cm/s. A statistically significant difference was observed between patients with positive IHD and patients with negative IHD regarding PSV (P = 0.003). The sensitivity of a PSV of less than 35 cm/s in predicting IHD was 50% with a specificity of 100%. Positive predictive value for abnormal stress ECG to predict a PSV of less than 35 cm/s was 100%. In conclusion, the PSV of cavernosal arteries is a reliable measure for predicting IHD in patients with vasculogenic ED. Patients with a PSV of less than 35 cm/s should be referred for cardiologic assessment as they carry a real risk of having silent IHD.", "title": "Correlation between penile duplex findings and stress electrocardiography in men with erectile dysfunction." }, { "docid": "MED-4846", "text": "The effects of a strict uncooked vegan diet on serum lipid and sterol concentrations were studied in patients with rheumatoid arthritis. The subjects were randomized into a vegan diet group (n 16), who consumed a vegan diet for 2-3 months, or into a control group (n 13), who continued their usual omnivorous diets. Serum total and LDL-cholesterol and -phospholipid concentrations were significantly decreased by the vegan diet. The levels of serum cholestanol and lathosterol also decreased, but serum cholestanol:total cholesterol and lathosterol:total cholesterol did not change. The effect of a vegan diet on serum plant sterols was divergent as the concentration of campesterol decreased while that of sitosterol increased. This effect resulted in a significantly greater sitosterol:campesterol value in the vegan diet group than in the control group (1.48 (SD 0.39) v. 0.72 (SD 0.14); P < 0.001). A higher concentration of campesterol compared with sitosterol is normal in omnivorous subjects and can be explained by lower absorption and esterification rates of sitosterol. Our results suggest that a strict uncooked vegan diet changes the relative absorption rates of these sterols and/or their biliary clearance.", "title": "Divergent changes in serum sterols during a strict uncooked vegan diet in patients with rheumatoid arthritis." }, { "docid": "MED-1987", "text": "OBJECTIVE: Over the last 3 decades, the prevalence of childhood obesity has increased dramatically in North America, ushering in a variety of health problems, including type 2 diabetes mellitus (T2DM), which previously was not typically seen until much later in life. This technical report describes, in detail, the procedures undertaken to develop the recommendations given in the accompanying clinical practice guideline, \"Management of Type 2 Diabetes Mellitus in Children and Adolescents,\" and provides in-depth information about the rationale for the recommendations and the studies used to make the clinical practice guideline's recommendations. METHODS: A primary literature search was conducted relating to the treatment of T2DM in children and adolescents, and a secondary literature search was conducted relating to the screening and treatment of T2DM's comorbidities in children and adolescents. Inclusion criteria were prospectively and unanimously agreed on by members of the committee. An article was eligible for inclusion if it addressed treatment (primary search) or 1 of 4 comorbidities (secondary search) of T2DM, was published in 1990 or later, was written in English, and included an abstract. Only primary research inquiries were considered; review articles were considered if they included primary data or opinion. The research population had to constitute children and/or adolescents with an existing diagnosis of T2DM; studies of adult patients were considered if at least 10% of the study population was younger than 35 years. All retrieved titles, abstracts, and articles were reviewed by the consulting epidemiologist. RESULTS: Thousands of articles were retrieved and considered in both searches on the basis of the aforementioned criteria. From those, in the primary search, 199 abstracts were identified for possible inclusion, 58 of which were retained for systematic review. Five of these studies were classified as grade A studies, 1 as grade B, 20 as grade C, and 32 as grade D. Articles regarding treatment of T2DM selected for inclusion were divided into 4 major subcategories on the basis of type of treatment being discussed: (1) medical treatments (32 studies); (2) nonmedical treatments (9 studies); (3) provider behaviors (8 studies); and (4) social issues (9 studies). From the secondary search, an additional 336 abstracts relating to comorbidities were identified for possible inclusion, of which 26 were retained for systematic review. These articles included the following: 1 systematic review of literature regarding comorbidities of T2DM in adolescents; 5 expert opinions presenting global recommendations not based on evidence; 5 cohort studies reporting natural history of disease and comorbidities; 3 with specific attention to comorbidity patterns in specific ethnic groups (case-control, cohort, and clinical report using adult literature); 3 reporting an association between microalbuminuria and retinopathy (2 case-control, 1 cohort); 3 reporting the prevalence of nephropathy (cohort); 1 reporting peripheral vascular disease (case series); 2 discussing retinopathy (1 case-control, 1 position statement); and 3 addressing hyperlipidemia (American Heart Association position statement on cardiovascular risks; American Diabetes Association consensus statement; case series). A breakdown of grade of recommendation shows no grade A studies, 10 grade B studies, 6 grade C studies, and 10 grade D studies. With regard to screening and treatment recommendations for comorbidities, data in children are scarce, and the available literature is conflicting. Therapeutic recommendations for hypertension, dyslipidemia, retinopathy, microalbuminuria, and depression were summarized from expert guideline documents and are presented in detail in the guideline. The references are provided, but the committee did not independently assess the supporting evidence. Screening tools are provided in the Supplemental Information.", "title": "Management of type 2 diabetes mellitus in children and adolescents." }, { "docid": "MED-4556", "text": "Tolerable upper intake levels (ULs) set by the Institute of Medicine (IOM) are important, in part because they are used for estimating the percentage of the population at potential risk of adverse effects from excessive nutrient intake. The IOM did not set ULs for trans fat, saturated fat, and cholesterol because any intake level above 0% of energy increased LDL cholesterol concentration and these three food components are unavoidable in ordinary diets. The purpose of the analysis presented in this review was to evaluate clinical trial and prospective observational data that were not previously considered for setting a UL with the aim of determining whether the current UL model could be used for saturated fat, trans fat, and cholesterol. The results of this analysis confirm the limitations of the risk assessment model for setting ULs because of its inability to identify a UL for food components, such as cholesterol, that lack an intake threshold associated with increased chronic disease risk. © 2011 International Life Sciences Institute.", "title": "Tolerable upper intake levels for trans fat, saturated fat, and cholesterol." }, { "docid": "MED-4727", "text": "The objective of this study was to estimate the intake of organic tin compounds from foodstuffs in a Finnish market basket. The study was conducted by collecting 13 market baskets from supermarkets and market places in the city of Kuopio, eastern Finland. Altogether 115 different food items were bought. In each basket, foodstuffs were mixed in proportion to their consumption and analysed by GC/MS for seven organic tin compounds (mono-, di-, and tributyltin, mono-, di-, and triphenyltin, and dioctyltin). Organotin compounds were detected in only four baskets, with the fish basket containing the largest number of different organotins. The European Food Safety Authority has established a tolerable daily intake of 250 ng kg(-1) body weight for the sum of dibutyltin, tributyltin, triphenyltin and dioctyltin. According to this study, the daily intake of these compounds was 2.47 ng kg(-1) body weight, of which 81% originated from the fish basket. This exposure is only 1% of the tolerable daily intake and poses negligible risk to the average consumer. However, for consumers eating large quantities of fish from contaminated areas, the intake may be much higher.", "title": "Dietary intake of organotin compounds in Finland: a market-basket study." }, { "docid": "MED-5060", "text": "Objective To assess the association between animal exposures and non-Hodgkin lymphoma (NHL). Methods Exposure data were collected from 1,591 cases and 2,515 controls during in-person interviews in a population-based case-control study of NHL in the San Francisco Bay Area. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for potential confounders. Results Pet owners had a reduced risk of NHL (OR=0.71,CI=0.52 –0.97) and diffuse large-cell and immunoblastic large-cell (DLCL;OR=0.58,CI=0.39 –0.87) compared with those who never had owned a pet. Ever having owned dogs and/or cats was associated with reduced risk of all NHL (OR=0.71,CI=0.54–0.94) and of DLCL (OR=0.60,CI=0.42–0.86). Longer duration of cat ownership (p-trend=0.008), dog ownership (p-trend=0.04), and dog and/or cat ownership (p-trend =0.004) was inversely associated with risk of NHL. Ownership of pets other than cats and dogs was associated with a reduced risk of NHL (OR=0.64,CI=0.55–0.74) and DLCL (OR=0.58,CI=0.47 –0.71). Exposure to cattle for ≥5 years was associated with an increased risk of NHL (OR=1.6,CI=1.0–2.5) as was exposure to pigs for all NHL (OR=1.8,CI=1.2–2.6) and for DLCL (OR=2.0,CI=1.2–3.4). Conclusions The association between animal exposure and NHL warrants further investigation in pooled analyses.", "title": "Domestic and farm-animal exposures and risk of non-Hodgkin lymphoma in a population-based study in the San Francisco Bay Area" }, { "docid": "MED-2845", "text": "OBJECTIVE: Epidemiological studies suggest that high body iron stores are associated with insulin resistance and type 2 diabetes. The aim of this study was to evaluate the association between dietary intake of iron and the risk of type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort study within the Nurses' Health Study. We followed 85,031 healthy women aged 34-59 years from 1980 to 2000. Dietary data were collected every 4 years, and data on medical history and lifestyle factors were updated biennially. RESULTS: During the 20 years of follow-up, we documented 4,599 incident cases of type 2 diabetes. We found no association between total, dietary, supplemental, or nonheme iron and the risk of type 2 diabetes. However, heme iron intake (derived from animal products) was positively associated with risk; relative risks (RRs) across increasing quintiles of cumulative intake were 1.00, 1.08 (95% CI 0.97-1.19), 1.20 (1.09-1.33), 1.27 (1.14-1.41), and 1.28 (1.14-1.45) (P(trend) < 0.0001) after controlling for age, BMI, and other nondietary and dietary risk factors. In addition, when we modeled heme iron in seven categories, the multivariate RR comparing women who consumed > or =2.25 mg/day and those with intake <0.75 mg/day was 1.52 (1.22-1.88). The association between heme iron and the risk of diabetes was significant in both overweight and lean women. CONCLUSIONS: This large cohort study suggests that higher heme iron intake is associated with a significantly increased risk of type 2 diabetes.", "title": "Iron intake and the risk of type 2 diabetes in women: a prospective cohort study." }, { "docid": "MED-4757", "text": "The purpose of the present study was to investigate the sex hormonal and metabolic profiles in vegetarians and compare these with the profiles in omnivores. The design of the present study was cross-sectional. The study sample of pre- and post-menopausal women included forty-one omnivores and twenty-one vegetarians. Thereafter we determined: (1) plasma sex hormones, (2) fasting insulin, NEFA as well as apo-A and apo-B, (3) BMI, (4) a dietary profile (3 d dietary records), (5) physical activity and (6) total faecal excretion per 72 h and total urinary excretion per 72 h. Vegetarians showed higher levels of sex hormone-binding globulin (SHBG), apo-A, total faecal excretion per 72 h and total fibre intake as well as lower levels of apo-B, free oestradiol, free testosterone, dehydroepiandrosterone sulfate (DHEA-s) and BMI. Interestingly, after controlling for BMI, significant differences between groups still persisted except for apo-B. Moreover, stepwise regression analysis showed that total fibre intake explained 15.2 % of the variation in SHBG in our cohort, which accounted for the greatest source of unique variance. Results of the present study indicate that pre- and post-menopausal vegetarians present higher concentrations of SHBG, which could be explained, in part, by higher levels of fibre intake. This may explain, at least in part, the lower risk of developing type 2 diabetes.", "title": "Comparison of sex hormonal and metabolic profiles between omnivores and vegetarians in pre- and post-menopausal women." }, { "docid": "MED-2259", "text": "Mean blood cadmium (B-Cd) concentrations are two- to threefold higher in smokers than in nonsmokers. The basis for this phenomenon is not well understood. We conducted a detailed, multifaceted study of cadmium exposure in smokers. Groups were older smokers (62±4 years, n = 25, 20% male) and nonsmokers (62±3 years, n = 16, 31% male). Each subject's cigarettes were machine smoked, generating individually paired measures of inhaled cadmium (I-Cd) versus B-Cd; I-Cd and B-Cd were each evaluated three times, at monthly intervals. Urine cadmium (U-Cd) was analyzed for comparison. In four smokers, a duplicate-diet study was conducted, along with a kinetic study of plasma cadmium versus B-Cd. Female smokers had a mean B-Cd of 1.21ng Cd/ml, with a nearly 10-fold range (0.29-2.74ng Cd/ml); nonsmokers had a lower mean B-Cd, 0.35ng Cd/ml (p < 0.05), and narrower range (0.20-0.61ng Cd/ml). Means and ranges for males were similar. Estimates of cadmium amounts inhaled daily for our subjects smoking ≥ 20 cigarettes/day were far less than the 15 µg Cd reported to be ingested daily via diet. This I-Cd amount was too low to alone explain the 3.5-fold elevation of B-Cd in our smokers, even assuming greater cadmium absorption via lungs than gastrointestinal tract; cadmium accumulated in smokers' lungs may provide the added cadmium. Finally, B-Cd appeared to be linearly related to I-Cd values in 75% of smokers, whereas 25% had far higher B-Cd, implying a possible heterogeneity among smokers regarding circulating cadmium concentrations and potentially cadmium toxicity.", "title": "Cadmium intake and systemic exposure in postmenopausal women and age-matched men who smoke cigarettes." }, { "docid": "MED-3701", "text": "Estrogen synthesized in situ plays a more important role in breast cancer cell proliferation than does circulating estrogen. Aromatase is the enzyme that converts androgen to estrogen and is expressed at a higher level in breast cancer tissue than in surrounding noncancer tissue. A promising route of chemoprevention against breast cancer may be through the suppression of in situ estrogen formation using aromatase inhibitors. A diet high in fruits and vegetables may reduce the incidence of breast cancer, because they contain phytochemicals that can act as aromatase inhibitors. In our previous studies, we found that grapes and wine contain potent phytochemicals that can inhibit aromatase. We show that red wine was more effective than white wine in suppressing aromatase activity. Interestingly, our results from white wine studies suggest a weak inductive effect of alcohol on aromatase activity. On the other hand, the potent effect of anti-aromatase chemicals in red wine overcomes the weak inductive effect of alcohol in wine. Several purification procedures were performed on whole red wine to separate active aromatase inhibitors from non-active compounds. These techniques included liquid-liquid extraction, silica gel chromatography, various solid phase extraction (SPE) columns, and high performance liquid chromatography. An active Pinot Noir red wine SPE C18 column fraction (20% acetonitrile:water) was more effective than complete Pinot Noir wine in suppressing aromatase assay. This red wine extract was further analyzed in a transgenic mouse model in which aromatase was over-expressed in mammary tissue. Our gavaged red wine extract completely abrogated aromatase-induced hyperplasia and other neoplastic changes in mammary tissue. These results suggest that red wine or red wine extract may be a chemopreventive diet supplement for postmenopausal women who have a high risk of breast cancer. Further research is underway to purify and characterize the active compounds in red wine that are responsible for the inhibition of aromatase.", "title": "Anti-aromatase chemicals in red wine." }, { "docid": "MED-4976", "text": "Airborne cooking by-products from frying beef (hamburgers), pork (bacon strips) and soybean-based food (tempeh burgers) were collected, extracted, tested for mutagenicity and chemically analysed. The fumes generated by frying pork and beef were mutagenic, with 4900 and 1300 revertants/g of food cooked, respectively. No mutagenicity was detected in fumes from frying tempeh burgers. Bacon fried to a well-done but non-charred state was eight times more mutagenic in a microsuspension Ames/Salmonella test (TA98 with S-9) than hamburgers and about 350 times more mutagenic than tempeh burgers. Among food samples cooked to a well-done, non-charred state, bacon strips had almost 15-fold more mass (109.5 ng/g) than that of the beef, whereas no heterocyclic amine (HCA) was detected in the fried tempeh burgers. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was the most abundant HCA, followed by 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx). No 2-amino-9H-pyrido[2,3-b]indole (A alpha C) was detected in the food samples fried at about 200 degrees C, although it was present in the collected airborne products. The total amounts of HCAs in the smoke condensates were 3 ng/g from fried bacon, 0.37 ng/g from fried beef and 0.177 ng/g from fried soy-based food. This study indicates that cooks are potentially exposed to relatively high levels of airborne mutagens and carcinogens and that long-term sampling inside restaurants and kitchens may be warranted in order to assess the potential risk of prolonged exposure.", "title": "Airborne mutagens produced by frying beef, pork and a soy-based food." }, { "docid": "MED-1770", "text": "Oestrogens govern reproductive functions in vertebrates, and are present in all animal tissues. The theoretical maximum daily intake (TMDI) of oestradiol-17beta by consumption of cattle meat is calculated to be 4.3 ng. Following the use of oestradiol-containing growth-promoting agents, TMDI is increased by a factor of 4.6 to 20 ng oestradiol-17beta, assuming that single dosage and 'good animal husbandry' are observed. Pork and poultry probably contain similar amounts of oestrogens as untreated cattle. The mean concentration of oestradiol-17beta in whole milk is estimated at 6.4 pg/ml. Scarce data available on eggs report up to 200 pg/g oestradiol-17beta. The risk evaluation of oestrogenic growth-promoting agents is limited by analytical uncertainties. Residues of oestradiol-17alpha and the importance of oestrogen conjugates are widely unknown. The performance of mass spectrometry still needs to be improved for confirmation of oestrogen concentrations in most food. At present, the potential relevance of oestradiol acyl esters, the actual daily production rate of oestradiol in prepubertal children, and the role of oestradiol metabolites in cancer are obscure. The presence of different cytoplasmic oestrogen receptor subtypes and potential oestradiol effects in non-reproductive functions require further examination.", "title": "Possible health impact of animal oestrogens in food." }, { "docid": "MED-2411", "text": "The relationship between omega-3 polyunsaturated fatty acids (n-3 PUFA) from seafood (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) or plant (alpha-linolenic acid, ALA) sources and risk of type 2 diabetes mellitus (DM) remains unclear. We systematically searched multiple literature databases through June 2011 to identify prospective studies examining relations of dietary n-3 PUFA, dietary fish and/or seafood, and circulating n-3 PUFA biomarkers with incidence of DM. Data were independently extracted in duplicate by 2 investigators, including multivariate-adjusted relative risk (RR) estimates and corresponding 95% CIs. Generalized least-squares trend estimation was used to assess dose-response relationships, with pooled summary estimates calculated by both fixed-effect and random-effect models. From 288 identified abstracts, 16 studies met inclusion criteria, including 18 separate cohorts comprising 540,184 individuals and 25,670 cases of incident DM. Consumption of fish and/or seafood was not significantly associated with DM (n=13 studies; RR per 100g/d=1.12, 95% CI=0.94, 1.34); nor were consumption of EPA+DHA (n=16 cohorts; RR per 250mg/d=1.04, 95% CI=0.97, 1.10) or circulating levels of EPA+DHA biomarkers (n=5 cohorts; RR per 3% of total fatty acids=0.94, 95% CI=0.75, 1.17). Both dietary ALA (n=7 studies; RR per 0.5g/d=0.93, 95% CI=0.83, 1.04) and circulating ALA biomarker levels (n=6 studies; RR per 0.1% of total fatty acid=0.90, 95% CI=0.80, 1.00, P=0.06) were associated with non-significant trend towards lower risk of DM. Substantial heterogeneity (I2~80%) was observed among studies of fish/seafood or EPA+DHA and DM; moderate heterogeneity (<55%) was seen for dietary and biomarker ALA and DM. In unadjusted meta-regressions, study location (Asia vs. North America/Europe), mean BMI, and duration of follow-up each modified the association between fish/seafood and EPA+DHA consumption and DM risk (P-Interaction ≤ 0.02 each). We had limited statistical power to determine the independent effect of these sources of heterogeneity due to their high collinearity. The overall pooled findings do not support either major harms or benefits of fish/seafood or EPA+DHA on development of DM, and suggest that ALA may be associated with modestly lower risk. Reasons for potential heterogeneity of effects, which could include true biologic heterogeneity, publication bias, or chance, deserve further investigation.", "title": "Omega-3 Fatty Acids and incident Type 2 Diabetes: A Systematic Review and Meta-Analysis" }, { "docid": "MED-4216", "text": "High levels of insulin-like growth factor 1 (IGF-1) are associated with increased risk of prostate cancer, whereas increased levels of some of its binding proteins (IGFBPs) seem to be protective. High intakes of dietary protein, especially animal and soy protein, appear to increase IGF-1. However, soy isoflavones have demonstrated anti-proliferative and apoptotic effects both in vitro and in vivo. We evaluated dietary intakes of total protein and soy isoflavones in relation to the IGF axis in prostate cancer patients making comprehensive lifestyle changes including a very low-fat vegan diet supplemented with soy protein (58 g/day). After one year, intervention group patients reported significantly higher intakes of dietary protein and soy isoflavones compared to usual-care controls (P < 0.001). IGF-1 increased significantly in both groups, whereas IGFBP-1 rose in the experimental group only (P < 0.01). Increases in vegetable protein over one year were associated with increases in IGFBP-1 among intervention group patients (P < 0.05). These results suggest that dietary protein and soy isoflavones, in the context of comprehensive lifestyle changes, may not significantly alter IGF-1. However, given the recent literature indicating that high intake of protein rich in essential amino acids (animal or soy protein) may increase IGF-1, it may be prudent for men with early stage prostate cancer not to exceed dietary protein recommendations.", "title": "Relationship of dietary protein and soy isoflavones to serum IGF-1 and IGF binding proteins in the Prostate Cancer Lifestyle Trial." }, { "docid": "MED-1527", "text": "Importance Some evidence suggests vegetarian dietary patterns may be associated with reduced mortality, but the relationship is not well established. Objective To evaluate the association between vegetarian dietary patterns and mortality. Design Prospective cohort study; mortality analysis by Cox proportional hazards regression, controlling for important demographic and lifestyle confounders. Setting Adventist Health Study 2 (AHS-2), a large North American cohort. Participants A total of 96 469 Seventh-day Adventist men and women recruited between 2002 and 2007, from which an analytic sample of 73 308 participants remained after exclusions. Exposures Diet was assessed at baseline by a quantitative food frequency questionnaire and categorized into 5 dietary patterns: nonvegetarian, semi-vegetarian, pesco-vegetarian, lacto-ovo–vegetarian, and vegan. Main Outcome and Measure The relationship between vegetarian dietary patterns and all-cause and cause-specific mortality; deaths through 2009 were identified from the National Death Index. Results There were 2570 deaths among 73 308 participants during a mean follow-up time of 5.79 years. The mortality rate was 6.05 (95% CI, 5.82–6.29) deaths per 1000 person-years. The adjusted hazard ratio (HR) for all-cause mortality in all vegetarians combined vs non-vegetarians was 0.88 (95% CI, 0.80–0.97). The adjusted HR for all-cause mortality in vegans was 0.85 (95% CI, 0.73–1.01); in lacto-ovo–vegetarians, 0.91 (95% CI, 0.82–1.00); in pesco-vegetarians, 0.81 (95% CI, 0.69–0.94); and in semi-vegetarians, 0.92 (95% CI, 0.75–1.13) compared with nonvegetarians. Significant associations with vegetarian diets were detected for cardiovascular mortality, noncardiovascular noncancer mortality, renal mortality, and endocrine mortality. Associations in men were larger and more often significant than were those in women. Conclusions and Relevance Vegetarian diets are associated with lower all-cause mortality and with some reductions in cause-specific mortality. Results appeared to be more robust in males. These favorable associations should be considered carefully by those offering dietary guidance.", "title": "Vegetarian Dietary Patterns and Mortality in Adventist Health Study 2" }, { "docid": "MED-2694", "text": "Lipid peroxidation (LPO) product accumulation in human tissues is a major cause of tissular and cellular dysfunction that plays a major role in ageing and most age-related and oxidative stress-related diseases. The current evidence for the implication of LPO in pathological processes is discussed in this review. New data and literature review are provided evaluating the role of LPO in the pathophysiology of ageing and classically oxidative stress-linked diseases, such as neurodegenerative diseases, diabetes and atherosclerosis (the main cause of cardiovascular complications). Striking evidences implicating LPO in foetal vascular dysfunction occurring in pre-eclampsia, in renal and liver diseases, as well as their role as cause and consequence to cancer development are addressed.", "title": "Pathological aspects of lipid peroxidation." }, { "docid": "MED-3599", "text": "The dietary intake of industrially-produced trans fatty acids (IP-TFA) was estimated for the US population (aged 2 years or more), children (aged 2-5 years) and teenage boys (aged 13-18 years) using the 2003-2006 National Health and Nutrition Examination Survey (NHANES) food consumption database, market share information and trans fat levels based on label survey data and analytical data for packaged and in-store purchased foods. For fast foods, a Monte Carlo model was used to estimate IP-TFA intake. Further, the intake of trans fat was also estimated using trans fat levels reported in the US Department of Agriculture (USDA) National Nutrient Database for Standard Reference, Release 22 (SR 22, 2009) and the 2003-2006 NHANES food consumption database. The cumulative intake of IP-TFA was estimated to be 1.3 g per person per day (g/p/d) at the mean for the US population. Based on this estimate, the mean dietary intake of IP-TFA has decreased significantly from that cited in the 2003 US Food and Drug Administration (FDA) final rule that established labelling requirements for trans fat (4.6 g/p/d for adults). Although the overall intake of IP-TFA has decreased as a result of the implementation of labelling requirements, individuals with certain dietary habits may still consume high levels of IP-TFA if certain brands or types of food products are frequently chosen.", "title": "Updated estimate of trans fat intake by the US population." }, { "docid": "MED-1915", "text": "Background Psychological stress is suggested to accelerate the rate of biological aging. We investigated whether work-related exhaustion, an indicator of prolonged work stress, is associated with accelerated biological aging, as indicated by shorter leukocyte telomeres, that is, the DNA-protein complexes that cap chromosomal ends in cells. Methods We used data from a representative sample of the Finnish working-age population, the Health 2000 Study. Our sample consisted of 2911 men and women aged 30–64. Work-related exhaustion was assessed using the Maslach Burnout Inventory - General Survey. We determined relative leukocyte telomere length using a quantitative real-time polymerase chain reaction (PCR) -based method. Results After adjustment for age and sex, individuals with severe exhaustion had leukocyte telomeres on average 0.043 relative units shorter (standard error of the mean 0.016) than those with no exhaustion (p = 0.009). The association between exhaustion and relative telomere length remained significant after additional adjustment for marital and socioeconomic status, smoking, body mass index, and morbidities (adjusted difference 0.044 relative units, standard error of the mean 0.017, p = 0.008). Conclusions These data suggest that work-related exhaustion is related to the acceleration of the rate of biological aging. This hypothesis awaits confirmation in a prospective study measuring changes in relative telomere length over time.", "title": "Work-Related Exhaustion and Telomere Length: A Population-Based Study" }, { "docid": "MED-3822", "text": "Only a limited number of studies on cellulite have been published in the international literature and many of them reach somewhat antithetical conclusions. Consequently, it is not yet possible to reconcile the extreme differences of opinion which have lingered on for years concerning the nature of this disorder, as well as its origin and even the most basic aspects of its histopathological classification. It does not even have a recognized name: in fact, the term 'cellulitis' is used in scientific English to indicate a spreading gangrenous infection of the subcutaneous cellular tissue. The other terms used from time to time [panniculitis, lipodystrophy, edematofibrosclerotic panniculitis (EFP), liposclerosis, lipoedema, etc.] have quite different morphological and pathogenetic connotations in general. Over the last few decades, three major conflicting theories have emerged in relation to the ethiopathogenesis of cellulite. These indicate, respectively, the following causes: 1. Oedema caused by excessive hydrophilia of the intercellular matrix. 2. A homeostatic alteration on a regional microcirculatory level; this pathogenetic theory is summarized in a synthetic and self-explanatory denomination: EFP. 3. A peculiar anatomical conformation of the subcutaneous tissue of women, different from male morphology. These theories must all now be updated in the light of recent advances on the sophisticated and composite physiopathology of the adipose organ - which acts not only as a control device which regulates the systematic equilibrium of energy and modulates the food intake and the metabolism of other tissue substrate through a multiple glandular secretion of hormones and parahormones.", "title": "Cellulite: nature and aetiopathogenesis." }, { "docid": "MED-4024", "text": "We reviewed data from six cohort studies and approximately 40 case-control studies on the relation between selected aspects of diet and the risk of oral and pharyngeal cancer. Fruit and vegetables were inversely related to the risk: the pooled relative risk (RR) for high vegetable consumption was 0.65 from three cohort studies on upper aerodigestive tract cancers and 0.52 from 18 case-control studies of oral and pharyngeal cancer; corresponding RRs for high fruit consumption were 0.78 and 0.55. beta-carotene, vitamin C and selected flavonoids have been inversely related to the risk, but it is difficult to disentangle their potential effect from that of fruit and vegetables. Whole grain, but not refined grain, intake was also favorably related to oral cancer risk. The results were not consistent with reference to other foods beverages, and nutrients, but it is now possible to exclude a strong relation between these foods and oral and pharyngeal cancer risk. In western countries, selected aspects of diet may account for 20-25% of oral and pharyngeal cancer, and the population attributable risk increases to 85-95% when tobacco and alcohol consumption are also considered.", "title": "Dietary factors and oral and pharyngeal cancer risk." }, { "docid": "MED-4679", "text": "OBJECTIVES The objective of this study was to describe the assessment methods and maturation status for a multisite cohort of girls at baseline recruitment and at ages 7 and 8 years. METHODS The method for pubertal maturation staging was developed collaboratively across 3 sites. Girls at ages 6 to 8 years were recruited at 3 sites: East Harlem, New York; greater Cincinnati metropolitan area; and San Francisco Bay area, California. Baseline characteristics were obtained through interviews with caregivers and anthropometric measurements by trained examiners; breast stage 2 was defined as onset of pubertal maturation. The κ statistic was used to evaluate agreement between master trainers and examiners. Logistic regression models were used to identify factors that are associated with pubertal maturation and linear regression models to examine factors that are associated with height velocity. RESULTS The baseline cohort included 1239 girls. The proportion of girls who had attained breast stage 2 varied by age, race/ethnicity, BMI percentile, and site. At 7 years, 10.4% of white, 23.4% of black non-Hispanic, and 14.9% of Hispanic girls had attained breast stage ≥2; at 8 years, 18.3%, 42.9%, and 30.9%, respectively, had attained breast stage ≥2. The prime determinant of height velocity was pubertal status. CONCLUSIONS In this multisite study, there was substantial agreement regarding pubertal staging between examiners across sites. The proportion of girls who had breast development at ages 7 and 8 years, particularly among white girls, is greater than that reported from studies of girls who were born 10 to 30 years earlier.", "title": "Pubertal Assessment Method and Baseline Characteristics in a Mixed Longitudinal Study of Girls" }, { "docid": "MED-1319", "text": "A comprehensive ecologic survey of dietary, life-style, and mortality characteristics of 65 counties in rural China showed that diets are substantially richer in foods of plant origin when compared with diets consumed in the more industrialized, Western societies. Mean intakes of animal protein (about one-tenth of the mean intake in the United States as energy percent), total fat (14.5% of energy), and dietary fiber (33.3 g/d) reflected a substantial preference for foods of plant origin. Mean plasma cholesterol concentration, at approximately 3.23-3.49 mmol/L, corresponds to this dietary life-style. The principal hypothesis under investigation in this paper is that chronic degenerative diseases are prevented by an aggregate effect of nutrients and nutrient-intake amounts that are commonly supplied by foods of plant origin. The breadth and consistency of evidence for this hypothesis was investigated with multiple intake-biomarker-disease associations, which were appropriately adjusted. There appears to be no threshold of plant-food enrichment or minimization of fat intake beyond which further disease prevention does not occur. These findings suggest that even small intakes of foods of animal origin are associated with significant increases in plasma cholesterol concentrations, which are associated, in turn, with significant increases in chronic degenerative disease mortality rates.", "title": "Diet and chronic degenerative diseases: perspectives from China." }, { "docid": "MED-2579", "text": "There are now extensive scientific data suggesting the potential role of dietary and non-dietary phytochemicals in the prevention and control of prostate cancer (PCA) growth and progression. PCA is a disease of elderly male populations with a relatively slower rate of growth and progression as compared to most other cancers and, therefore, is a candidate disease for preventive intervention. Overall, PCA growth and progression involve aberrant mitogenic and survival signaling and deregulated cell cycle progression, accompanied by gradual accumulation of genetic and epigenetic changes over a period of years. Several mechanisms, including overexpression of growth, survival and angiogenic factors and their receptors, together with a loss/decrease of tumor suppressor p53, retinoblastoma and cyclin-dependent kinase inhibitor, have been implicated in PCA growth and progression. Therefore, phytochemicals targeting these molecular events could have a promising role in PCA prevention and/or therapy. Inositol hexaphosphate (IP6) is a major constituent of most cereals, legumes, nuts, oil seeds and soybean. Taken orally as an over-the-counter dietary/nutrient supplement, and is recognised as offering several health benefits without any known toxicity. In vitro anticancer efficacy of IP6 has been observed in many human, mouse and rat prostate cancer cells. Completed studies also show that oral feeding of IP6 inhibits human PCA xenograft growth in nude mice without toxicity. In a recently completed pilot study, we observed similar preventive effects of IP6 on prostate tumorigenesis in the TRAMP model. Mechanistic studies indicate that IP6 targets mitogenic and survival signaling, as well as cell cycle progression, in PCA cells. IP6 is also shown to target molecular events associated with angiogenesis. Moreover, IP6 has pleiotropic molecular targets for its overall efficacy against PCA and, therefore, could be a suitable candidate agent for preventive intervention of this malignancy in humans.", "title": "Prostate cancer and inositol hexaphosphate: efficacy and mechanisms." }, { "docid": "MED-2381", "text": "The inverse association of nut consumption and risk markers of coronary heart disease (lipids) has sparked the interest of the scientific and lay community. The objective of this study was to conduct a systematic review to investigate the effects of nuts on the lipid profile. Medline and Web of Science databases were searched from the start of the database to August 2004 and supplemented by cross-checking reference lists of relevant publications. Human intervention trials with the objective of investigating independent effects of nuts on lipid concentrations were included. From the literature search, 415 publications were screened and 23 studies were included. These papers received a rating based upon the methodology as it appeared in the publication. No formal statistical analysis was performed due to the large differences in study designs of the dietary intervention trials. The results of 3 almond (50-100 g/d), 2 peanut (35-68 g/d), 1 pecan nut (72 g/d), and 4 walnut (40-84 g/d) studies showed decreases in total cholesterol between 2 and 16% and LDL cholesterol between 2 and 19% compared with subjects consuming control diets. Consumption of macadamia nuts (50-100 g/d) produced less convincing results. In conclusion, consumption of approximately 50-100 g (approximately 1.5-3.5 servings) of nuts > or = 5 times/wk as part of a heart-healthy diet with total fat content (high in mono- and/or polyunsaturated fatty acids) of approximately 35% of energy may significantly decrease total cholesterol and LDL cholesterol in normo- and hyperlipidemic individuals.", "title": "A systematic review of the effects of nuts on blood lipid profiles in humans." }, { "docid": "MED-4600", "text": "Enough solid evidence now exists to offer women several fundamental strategies for healthy eating. They include emphasizing healthful unsaturated fats, whole grains, good protein “packages,” and fruits and vegetables; limiting consumption of trans and saturated fats, highly refined grains, and sugary beverages; and taking a multivitamin with folic acid and extra vitamin D as a nutritional safety net. A diet based on these principles is healthy through virtually all life stages, from young adulthood through planning for pregnancy, pregnancy, and on into old age.", "title": "Essentials of Healthy Eating: A Guide" }, { "docid": "MED-4694", "text": "OBJECTIVE: Observational data, though sparse and based on small studies with limited ability to control for known breast cancer risk factors, support a lower risk of breast cancer in blind women compared to sighted women. Mechanisms influenced by ocular light perception, such as melatonin or circadian synchronization, are thought to account for this lower risk. METHODS: To evaluate whether blind women with no perception of light (NPL) have a lower prevalence of breast cancer compared to blind women with light perception (LP), we surveyed a cohort of 1,392 blind women living in North America (66 breast cancer cases). RESULTS: In multivariate-logistic regression models controlling for breast cancer risk factors, women with NPL had a significantly lower prevalence of breast cancer than women with LP (odds ratio, 0.43; 95% confidence interval, 0.21-0.85). We observed little difference in these associations when restricting to postmenopausal women, non-shift workers or when excluding women diagnosed with breast cancer within 2 or 4 years of onset of blindness. Blind women with NPL appear to have a lower risk of breast cancer, compared to blind women with LP. More research is needed to elucidate the impact of LP on circadian coordination and melatonin production in the blind and how these factors may relate to breast cancer risk.", "title": "Total visual blindness is protective against breast cancer." }, { "docid": "MED-2705", "text": "Atherosclerosis may result partly from processes that occur following food consumption and that involve oxidized lipids in chylomicrons. We investigated reactions that could occur in the acidic pH of the stomach and accelerate the generation of lipid hydroperoxides and co-oxidation of dietary constituents. The ability of dietary polyphenols to invert catalysis from pro-oxidation to antioxidation was examined. The acidic pH of gastric fluid amplified lipid peroxidation catalyzed by metmyoglobin or iron ions. Metmyoglobin catalyzed peroxidation of edible oil, resulting in 8-fold increase of hydroperoxide concentration. The incubation of heated muscle tissue in simulated gastric fluid for 2 h enhanced hydroperoxides accumulation by 6-fold to 1200 microM. In the presence of catechin or red wine polyphenols, metmyoglobin catalyzed the breakdown of hydroperoxides to zero, totally preventing lipid peroxidation and beta-carotene cooxidation. We suggest that human gastric fluid may be an excellent medium for enhancing the oxidation of lipids and other dietary constituents. The results indicate the potentially harmful effects of oxidized fats intake in the presence of endogenous catalysts found in foods, and the major benefit of including in the meal plant dietary antioxidants.", "title": "The stomach as a bioreactor: dietary lipid peroxidation in the gastric fluid and the effects of plant-derived antioxidants." }, { "docid": "MED-4632", "text": "Vegetarians have an apparent diminished risk for the development of ischemic coronary heart disease. This may be secondary to dietary effects of plasma lipids and lipoproteins, but platelets, which may also play a role, have also been observed to have aberrant functions in vegetarians. We measured plasma lipid and lipoprotein levels, platelet function, platelet fatty acid levels, and platelet active prostaglandins in ten strict vegetarians (vegans), 15 lactovegetarians, and 25 age- and sex-matched omnivorous controls. The most striking observations were a highly significant rise in platelet linoleic acid concentration and a decline in platelet arachidonic acid concentration in both vegetarian subgroups as compared with omnivorous controls. Serum thromboxane and prostacyclin levels as well as results of platelet aggregation studies did not differ among the groups tested. Cholesterol levels were significantly lower in both vegetarian groups as compared with controls, but plasma high- and low-density lipoprotein levels were lower only in the vegan subgroup as compared with omnivores. If diet produces these changes in platelet fatty acid and plasma lipid levels it may contribute to the decreased risk of coronary heart disease and possibly atherosclerosis in vegetarians.", "title": "The effect of vegetarian diets on plasma lipid and platelet levels." }, { "docid": "MED-3001", "text": "Over the last three decades, the concept of Western disease has become well established. Medicine has approached this group of diseases by searching for new cures but has achieved relatively little success. We argue that medicine should now accept the failure of this strategy and place a major emphasis on prevention. The key objective is to change the climate of opinion so that prevention is taken seriously by the general population. The chief activity should be a wide ranging public education campaign so as to persuade people to live a healthier lifestyle. Medicine will require restructuring in order to carry out this work. Medical education needs to be reformed so that medical students receive the necessary training. This must be done as part of an integrated approach in which government, industry and medical research all play a major role. Governments should use taxation and subsidies in areas such as food and tobacco so as to shift consumption patterns towards healthier products. Governments must also tighten laws on tobacco sales and advertising, support health education, and improve food labelling. Industry must be made far more responsive to the health needs of the population. This should be done both by public education, so as to alter demand, and by government action. Medical research should change its emphasis from studying the detailed mechanisms of disease (\"complex research\") to studying the role of lifestyle factors (\"simple research\").", "title": "Towards a new system of health: the challenge of Western disease." }, { "docid": "MED-2497", "text": "The birth cohort BraMat (n = 205; a sub-cohort of the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health) was established to study whether prenatal exposure to toxicants from the maternal diet affects immunological health outcomes in children. We here report on the environmental pollutants polychlorinated biphenyls (PCBs) and dioxins, as well as acrylamide generated in food during heat treatment. The frequency of common infections, eczema or itchiness, and periods of more than 10 days of dry cough, chest tightness or wheeze (called wheeze) in the children during the first year of life was assessed by questionnaire data (n = 195). Prenatal dietary exposure to the toxicants was estimated using a validated food frequency questionnaire from MoBa. Prenatal exposure to PCBs and dioxins was found to be associated with increased risk of wheeze and exanthema subitum, and also with increased frequency of upper respiratory tract infections. We found no associations between prenatal exposure to acrylamide and the health outcomes investigated. Our results suggest that prenatal dietary exposure to dioxins and PCBs may increase the risk of wheeze and infectious diseases during the first year of life. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Prenatal exposure to polychlorinated biphenyls and dioxins is associated with increased risk of wheeze and infections in infants." }, { "docid": "MED-1528", "text": "A vegetarian diet generally includes plenty of vegetables and fruits, which are rich in phytochemicals, antioxidants, fiber, magnesium, vitamins C and E, Fe³⁺, folic acid and n-6 polyunsaturated fatty acid (PUFA), and is low in cholesterol, total fat and saturated fatty acid, sodium, Fe²⁺, zinc, vitamin A, B₁₂ and D, and especially n-3 PUFA. Mortality from all-cause, ischemic heart disease, and circulatory and cerebrovascular diseases was significantly lower in vegetarians than in omnivorous populations. Compared with omnivores, the incidence of cancer and type 2 diabetes was also significantly lower in vegetarians. However, vegetarians have a number of increased risk factors for non-communicable diseases such as increased plasma homocysteine, mean platelet volume and platelet aggregability compared with omnivores, which are associated with low intake of vitamin B₁₂ and n-3 PUFA. Based on the present data, it would seem appropriate for vegetarians to carefully design their diet, specifically focusing on increasing their intake of vitamin B₁₂ and n-3 PUFA to further reduce already low mortality and morbidity from non-communicable diseases. © 2013 Society of Chemical Industry.", "title": "Effect of the vegetarian diet on non-communicable diseases." }, { "docid": "MED-1930", "text": "BACKGROUND/OBJECTIVES: Shorter leukocyte telomere length (LTL) is associated with several chronic diseases, but only a few studies have assessed the association between dietary factors and LTL. Our objective was to study the association between fats, fruits, vegetables and LTL in a cross-sectional study design. We hypothesized that intakes of fruits and vegetables would be positively associated with LTL and that intakes of fats, and especially saturated fatty acids (SFAs), would be negatively associated with LTL. SUBJECTS/METHODS: LTL was measured by quantitative real-time polymerase chain reaction in 1942 men and women aged 57-70 years from the Helsinki Birth Cohort Study. We assessed the whole diet by a validated semiquantitative 128-item food-frequency questionnaire. RESULTS: In general, there were only a few significant results. However, total fat and SFA intake (P=0.04 and 0.01, respectively) were inversely associated with LTL in men adjusting for age and energy intake. In women, vegetable intake was positively associated with LTL (P=0.05). Men consuming the most butter and least fruits had significantly shorter telomeres than those consuming the lowest amounts of butter and highest amounts of fruits (P=0.05). We found no association between LTL and body mass index, waist-hip ratio, smoking, physical activity or educational attainment. CONCLUSIONS: In this cross-sectional study of elderly men and women, there were only a few statistically significant effects of diet, but in general they support the hypothesis that fat and vegetable intakes were associated with LTL.", "title": "Leukocyte telomere length and its relation to food and nutrient intake in an elderly population." }, { "docid": "MED-4740", "text": "The US Environmental Protection Agency's 2004 Dioxin Reassessment included a characterization of background exposures to dioxin-like compounds, including an estimate of an average background intake dose and an average background body burden. These quantities were derived from data generated in the mid-1990s. Studies conducted in the 2000s were gathered in an attempt to update the estimates generated by the Reassessment. While these studies suggest declines in the average background dose and body burden, a precise quantification of this decline, much less a conclusion that a decline has indeed occurred, cannot be made because of the inconsistency of study design and data sources, and the treatment of non-detects in the generation of congener average concentrations. The average background intake of the Reassessment was 61.0 pg TEQ/day, and using more current data, the average background intake was 40.6 pg TEQ/day. The average body burden from the surveys in the mid-1990s was 22.9 pg TEQ/g lipid weight (pg/g lwt). More recent blood concentration data, from NHANES 2001/2, suggest an adult average at 21.7 pg/g TEQ lwt. These TEQ values include the 17 dioxin and furan congeners and 3 coplanar PCBs, and were generated substituting ND=(1/2)DL or ND=DL/sq rt (2). Results are provided for ND=0 and analyses conducted to evaluate the impacts of this substitution. A more detailed examination of beef and pork data from similarly designed national statistical surveys show that declines in pork are statistically significant while the beef concentrations appeared to have remained constant between the time periods.", "title": "Evaluation of background exposures of Americans to dioxin-like compounds in the 1990s and the 2000s." }, { "docid": "MED-1541", "text": "We propose the hypothesis that a vegetarian diet reduces the risk of developing diabetes. Findings that have generated this hypothesis are from a population of 25,698 adult White Seventh-day Adventists identified in 1960. During 21 years of follow-up, the risk of diabetes as an underlying cause of death in Adventists was approximately one-half the risk for all US Whites. Within the male Adventist population, vegetarians had a substantially lower risk than non-vegetarians of diabetes as an underlying or contributing cause of death. Within both the male and female Adventist populations, the prevalence of self-reported diabetes also was lower in vegetarians than in non-vegetarians. The associations observed between diabetes and meat consumption were apparently not due to confounding by over- or under-weight, other selected dietary factors, or physical activity. All of the associations between meat consumption and diabetes were stronger in males than in females.", "title": "Does a vegetarian diet reduce the occurrence of diabetes?" }, { "docid": "MED-4733", "text": "OBJECTIVES: Mercury and most of its compounds are extremely toxic and should be handled with care. It can be inhaled and absorbed through the skin and mucous membranes. The most toxic forms of mercury are its organic compounds such as dimethylmercury and methylmercury. Fish have a natural tendency to accumulate mercury. Methylmercury is produced by microbial methylation of inorganic mercury in water sediment then it infiltrates the food chain and it consequently accumulates in fish. Fish are the main source of methylmercury in human food. Mercury is transferred into a hair; and this can be than used to monitor the long-term exposure to mercury. The content of mercury in hair depends on the frequency of fish consumption. The aim of our study was to compare mercury content in the hair of children that had various amounts of fish consumption (increased or reduced). DESIGN: Total mercury content in hair was determined by direct method of cold vapors using an AMA 245 analyzer. A total of 174 hair samples from the children (9-17 years old) were analyzed. In this study, the following localities were compared: Neratovice (n=42), Jeseníky (n=44), Prague (n=59) in Czech Republic and Olsztyn in Poland (n=29). Every sample was accompanied with questionnaire about age, gender, regions, amalgam fillings and fish consumption. RESULTS: We did not find a correlation between the content of mercury in hair with age, gender or amalgam fillings. We did find a correlation between fish consumption and the amount of mercury found in the hair samples. CONCLUSION: The amount of mercury in hair increases with more frequent consumption of freshwater and marine fish.", "title": "Mercury in human hair as an indicator of the fish consumption." }, { "docid": "MED-3446", "text": "Seaweed and soy foods are consumed daily in Japan, where breast cancer rates for postmenopausal women are significantly lower than in the West. Likely mechanisms include differences in diet, especially soy consumption, and estrogen metabolism. Fifteen healthy postmenopausal women participated in this double-blind trial of seaweed supplementation with soy challenge. Participants were randomized to 7 wk of either 5 g/d seaweed (Alaria) or placebo (maltodextrin). During wk 7, participants also consumed a daily soy protein isolate (2 mg isoflavones/kg body weight). After a 3-wk washout period, participants were crossed over to the alternate supplement schedule. There was an inverse correlation between seaweed dose (mg/kg body weight) and serum estradiol (E2) (seaweed-placebo = y = -2.29 x dose + 172.3; r = -0.70; P = 0.003), [corrected] which was linear across the range of weights. Soy supplementation increased urinary daidzein, glycitein, genistein, and O-desmethylangolensin (P = 0.0001) and decreased matairesinol and enterolactone (P < 0.05). Soy and seaweed plus soy (SeaSoy) increased urinary excretion of 2-hydroxyestrogen (2-OHE) (P = 0.0001) and the ratio of 2-OHE:16alpha-hydroxyestrone (16alphaOHE(1)) (P = 0.01). For the 5 equol excretors, soy increased urinary equol excretion (P = 0.0001); the combination of SeaSoy further increased equol excretion by 58% (P = 0.0001). Equol producers also had a 315% increase in 2:16 ratio (P = 0.001) with SeaSoy. Seaweed favorably alters estrogen and phytoestrogen metabolism and these changes likely include modulation of colonic bacteria.", "title": "Dietary seaweed modifies estrogen and phytoestrogen metabolism in healthy postmenopausal women." }, { "docid": "MED-3797", "text": "A double blind crossover trial of the prolactin inhibitor bromocriptine in painful benign breast disease is reported. Twenty-nine women with cyclical mastalgia and 11 with non-cyclical pain were treated with bromocriptine, 5 mg daily, and placebo over six menstrual cycels. Assessment of response to treatment was made by a linear analogue system and clinical examination together with plasma prolactin estimations. Bromocriptine produced a significant improvement in breast symptoms and a significant fall in prolactin levels in the cyclical pain group, but had no effect in the non-cyclical group. These results suggest that bromocriptine offers a new and effective approach in the management of cyclical breast pain.", "title": "A double blind trial of the prolactin inhibitor bromocriptine in painful benign breast disease." }, { "docid": "MED-3880", "text": "A common approach to reducing microbial contamination has been the implementation of a Hazard Analysis and Critical Control Point (HACCP) program to prevent or reduce contamination during production. One example is the Pathogen Reduction HACCP program implemented by the U.S. Department of Agriculture's Food Safety and Inspection Service (FSIS). This program consisted of a staged implementation between 1996 and 2000 to reduce microbial contamination on meat and poultry products. Of the commodities regulated by FSIS, one of the largest observed reductions was for Salmonella contamination on broiler chicken carcasses. Nevertheless, how this reduction might have influenced the total number of salmonellosis cases in the United States has not been assessed. This study incorporates information from public health surveillance and surveys of the poultry slaughter industry into a model that estimates the number of broiler-related salmonellosis cases through time. The model estimates that-following the 56% reduction in the proportion of contaminated broiler carcasses observed between 1995 and 2000-approximately 190,000 fewer annual salmonellosis cases (attributed to broilers) occurred in 2000 compared with 1995. The uncertainty bounds for this estimate range from approximately 37,000 to 500,000 illnesses. Estimated illnesses prevented, due to the more modest reduction in contamination of 13% between 2000 and 2007, were not statistically significant. An analysis relating the necessary magnitude of change in contamination required for detection via human surveillance also is provided.", "title": "Estimating changes in public health following implementation of hazard analysis and critical control point in the United States broiler slaughter i..." }, { "docid": "MED-1612", "text": "Type II diabetic subjects were given 50 g protein, 50 g glucose, or 50 g glucose with 50 g protein as a single meal in random sequence. The plasma glucose and insulin response was determined over the subsequent 5 h. The plasma glucose area above the baseline following a glucose meal was reduced 34% when protein was given with the glucose. When protein was given alone, the glucose concentration remained stable for 2 h and then declined. The insulin area following glucose was only modestly greater than with a protein meal (97 +/- 35, 83 +/- 19 microU X h/ml, respectively). When glucose was given with protein, the mean insulin area was considerably greater than when glucose or protein was given alone (247 +/- 33 microU X h/ml). When various amounts of protein were given with 50 g glucose, the insulin area response was essentially first order. Subsequently, subjects were given 50 g glucose or 50 g glucose with 50 g protein as two meals 4 h apart in random sequence. The insulin areas were not significantly different for each meal but were higher when protein + glucose was given. After the second glucose meal the plasma glucose area was 33% less than after the first meal. Following the second glucose + protein meal the plasma glucose area was markedly reduced, being only 7% as large as after the first meal. These data indicate that protein given with glucose will increase insulin secretion and reduce the plasma glucose rise in at least some type II diabetic persons.", "title": "Effect of protein ingestion on the glucose and insulin response to a standardized oral glucose load." }, { "docid": "MED-2505", "text": "BACKGROUND: Relative risk estimates suggest that effective implementation of behaviors commonly advocated in preventive medicine should increase life expectancy, although there is little direct evidence. OBJECTIVE: To test the hypothesis that choices regarding diet, exercise, and smoking influence life expectancy. METHODS: A total of 34 192 California Seventh-Day Adventists (75% of those eligible) were enrolled in a cohort and followed up from 1976 to 1988. A mailed questionnaire provided dietary and other exposure information at study baseline. Mortality for all subjects was ascertained by matching to state death tapes and the National Death Index. RESULTS: California Adventists have higher life expectancies at the age of 30 years than other white Californians by 7.28 years (95% confidence interval, 6.59-7.97 years) in men and by 4.42 years (95% confidence interval, 3.96-4.88 years) in women, giving them perhaps the highest life expectancy of any formally described population. Commonly observed combinations of diet, exercise, body mass index, past smoking habits, and hormone replacement therapy (in women) can account for differences of up to 10 years of life expectancy among Adventists. A comparison of life expectancy when these factors take high-risk compared with low-risk values shows independent effects that vary between 1.06 and 2.74 years for different variables. The effect of each variable is assessed with all others at either medium- or high-risk levels. CONCLUSIONS: Choices regarding diet, exercise, cigarette smoking, body weight, and hormone replacement therapy, in combination, appear to change life expectancy by many years. The longevity experience of Adventists probably demonstrates the beneficial effects of more optimal behaviors.", "title": "Ten years of life: Is it a matter of choice?" }, { "docid": "MED-4750", "text": "Androgenic steroids always exist in different animal tissues at trace level, with significant numbers of interfering compounds, which makes their determination difficult. To solve some of the problems in quantification of the natural steroids in those tissues, a new GC-MS method was developed in this study. By using a surrogate analyte approach, which was developed in the authors' previous studies, and extensive sample preparation procedure, which successfully eliminates many of the interfering compounds and resulting in a cleaner extract, accuracy, precision, sensitivity and selectivity of the method for the determination of steroids in complex matrices such as meat, liver and testis were improved. By aid of this method, the levels of androgens in different tissues of Iranian native cross-breed bulls and male sheep were determined. According to the results obtained in the present study, although the androgenic profile (contents and ratios of precursors and metabolites to the main hormones) is similar between the same tissues of both animals, the total androgenic content of each tissue is higher in the bull than the same tissue in male sheep. In addition, in both animals higher amount of androgens were found in liver in comparison with meat and testis.", "title": "Assessment of endogenous androgen levels in meat, liver and testis of Iranian native cross-breed male sheep and bull by gas chromatography-mass spe..." }, { "docid": "MED-1597", "text": "Background Detection of estrogens in the environment has raised concerns in recent years because of their potential to affect both wildlife and humans. Objectives We compared exposures to prescribed and naturally occurring estrogens in drinking water to exposures to naturally occurring background levels of estrogens in the diet of children and adults and to four independently derived acceptable daily intakes (ADIs) to determine whether drinking water intakes are larger or smaller than dietary intake or ADIs. Methods We used the Pharmaceutical Assessment and Transport Evaluation (PhATE) model to predict concentrations of estrogens potentially present in drinking water. Predicted drinking water concentrations were combined with default water intake rates to estimate drinking water exposures. Predicted drinking water intakes were compared to dietary intakes and also to ADIs. We present comparisons for individual estrogens as well as combined estrogens. Results In the analysis we estimated that a child’s exposures to individual prescribed estrogens in drinking water are 730–480,000 times lower (depending upon estrogen type) than exposure to background levels of naturally occurring estrogens in milk. A child’s exposure to total estrogens in drinking water (prescribed and naturally occurring) is about 150 times lower than exposure from milk. Adult margins of exposure (MOEs) based on total dietary exposure are about 2 times smaller than those for children. Margins of safety (MOSs) for an adult’s exposure to total prescribed estrogens in drinking water vary from about 135 to > 17,000, depending on ADI. MOSs for exposure to total estrogens in drinking water are about 2 times lower than MOSs for prescribed estrogens. Depending on the ADI that is used, MOSs for young children range from 28 to 5,120 for total estrogens (including both prescribed and naturally occurring sources) in drinking water. Conclusions The consistently large MOEs and MOSs strongly suggest that prescribed and total estrogens that may potentially be present in drinking water in the United States are not causing adverse effects in U.S. residents, including sensitive subpopulations.", "title": "An Assessment of Potential Exposure and Risk from Estrogens in Drinking Water" }, { "docid": "MED-1531", "text": "Observational and ecological studies are generally used to determine the presence of effect of cancer risk-modifying factors. Researchers generally agree that environmental factors such as smoking, alcohol consumption, poor diet, lack of physical activity, and low serum 25-hdyroxyvitamin D levels are important cancer risk factors. This ecological study used age-adjusted incidence rates for 21 cancers for 157 countries (87 with high-quality data) in 2008 with respect to dietary supply and other factors, including per capita gross domestic product, life expectancy, lung cancer incidence rate (an index for smoking), and latitude (an index for solar ultraviolet-B doses). The factors found to correlate strongly with multiple types of cancer were lung cancer (direct correlation with 12 types of cancer), energy derived from animal products (direct correlation with 12 types of cancer, inverse with two), latitude (direct correlation with six types, inverse correlation with three), and per capita gross national product (five types). Life expectancy and sweeteners directly correlated with three cancers, animal fat with two, and alcohol with one. Consumption of animal products correlated with cancer incidence with a lag time of 15–25 years. Types of cancer which correlated strongly with animal product consumption, tended to correlate weakly with latitude; this occurred for 11 cancers for the entire set of countries. Regression results were somewhat different for the 87 high-quality country data set and the 157-country set. Single-country ecological studies have inversely correlated nearly all of these cancers with solar ultraviolet-B doses. These results can provide guidance for prevention of cancer.", "title": "A Multicountry Ecological Study of Cancer Incidence Rates in 2008 with Respect to Various Risk-Modifying Factors" }, { "docid": "MED-1960", "text": "Nine catfish fillets, three catfish nuggets, two feed samples, and one pond sediment were analyzed for PCDD, PCDF, and PCB. Farm-raised catfish from Mississippi, Alabama, and Arkansas contained significant levels of 2,3,7,8-substituted PCDD and PCDF. In addition, a large number of non-2,3,7,8-substituted congeners were present in all samples. The catfish fillets and catfish nuggets also contained high concentrations of dioxin-like PCB, as well as a number of non-dioxin-like PCB. The TEQ based on PCDD and PCDF ranged from 9.5 to 43.0 pg/g lipid and the TEQ based on PCB ranged from 0.45 to 4.9 pg/g lipid for all catfish samples. The dioxin-like PCB contributed 4-16% to the total TEQ (PCDD/PCDF/PCB) for the catfish samples. The major source for the PCDD, PCDF, and PCB appears to be from feed and not from pond sediment. Immunoreactive CYP1A protein was elevated 2.5 fold in the pond-raised catfish compared to the aquarium-raised one. The results of this study suggest that the PCDD/PCDF are more important than the PCB in the CYP1A induction.", "title": "PCDD, PCDF, and PCB in farm-raised catfish from southeast United States--concentrations, sources, and CYP1A induction." }, { "docid": "MED-1574", "text": "Crohn's disease (CD) is associated with intestinal dysbiosis evidenced by an altered microbiome forming thick biofilms on the epithelium. Additionally, adherent-invasive E. coli (AIEC) strains are frequently isolated from ileal lesions of CD patients indicating a potential role for these strains in disease pathogenesis. The composition and characteristics of the host microbiome are influenced by environmental factors, particularly diet. Polysaccharides added to food as emulsifiers, stabilizers or bulking agents have been linked to bacteria-associated intestinal disorders. The escalating consumption of polysaccharides in Western diets parallels an increased incidence of CD during the latter 20th century. In this study, the effect of a polysaccharide panel on adhesiveness of the CD-associated AIEC strain LF82 was analyzed to determine if these food additives promote disease-associated bacterial phenotypes. Maltodextrin (MDX), a polysaccharide derived from starch hydrolysis, markedly enhanced LF82 specific biofilm formation. Biofilm formation of multiple other E. coli strains was also promoted by MDX. MDX-induced E. coli biofilm formation was independent of polysaccharide chain length indicating a requirement for MDX metabolism. MDX exposure induced type I pili expression, which was required for MDX-enhanced biofilm formation. MDX also increased bacterial adhesion to human intestinal epithelial cell monolayers in a mechanism dependent on type 1 pili and independent of the cellular receptor CEACAM6, suggesting a novel mechanism of epithelial cell adhesion. Analysis of mucosa-associated bacteria from individuals with and without CD showed increased prevalence of malX, a gene essential for MDX metabolism, uniquely in the ileum of CD patients. These findings demonstrate that the ubiquitous dietary component MDX enhances E. coli adhesion and suggests a mechanism by which Western diets rich in specific polysaccharides may promote dysbiosis of gut microbes and contribute to disease susceptibility.", "title": "Crohn's Disease-Associated Adherent-Invasive Escherichia coli Adhesion Is Enhanced by Exposure to the Ubiquitous Dietary Polysaccharide Maltodextrin" }, { "docid": "MED-2677", "text": "Population differences in age-related diseases and cancer could stem from differences in diet. To characterize DNA strand-breaking activities in selected foods/beverages, flavorings, and some of their constituent chemicals, we used p53R cells, a cellular assay sensitive to such breaks. Substances testing positive included reference chemicals: quinacrine (peak response, 51X) and etoposide (33X); flavonoids: EGCG (19X), curcumin (12X), apigenin (9X), and quercetin (7X); beverages: chamomile (11X), green (21X), and black tea (26X) and coffee (3 to 29X); and liquid smoke (4 to 28X). Damage occurred at dietary concentrations: etoposide near 5 μg/ml produced responses similar to a 1:1000 dilution of liquid smoke, a 1:20 dilution of coffee, and a 1:5 dilution of tea. Pyrogallol-related chemicals and tannins are present in dietary sources and individually produced strong activity: pyrogallol (30X), 3-methoxycatechol (25X), gallic acid (21X), and 1,2,4-benzenetriol (21X). From structure-activity relationships, high activities depended on specific orientations of hydroxyls on the benzene ring. Responses accompanied cellular signals characteristic of DNA breaks such as H2AX phosphorylation. Breaks were also directly detected by comet assay. Cellular toxicological effects of foods and flavorings could guide epidemiologic and experimental studies of potential disease risks from DNA strand-breaking chemicals in diets.", "title": "Biological Clues to Potent DNA-Damaging Activities in Food and Flavoring" }, { "docid": "MED-3886", "text": "The treatment of bacterial infections is increasingly complicated by the ability of bacteria to develop resistance to antimicrobial agents. Antimicrobial agents are often categorized according to their principal mechanism of action. Mechanisms include interference with cell wall synthesis (e.g., beta-lactams and glycopeptide agents), inhibition of protein synthesis (macrolides and tetracyclines), interference with nucleic acid synthesis (fluoroquinolones and rifampin), inhibition of a metabolic pathway (trimethoprim-sulfamethoxazole), and disruption of bacterial membrane structure (polymyxins and daptomycin). Bacteria may be intrinsically resistant to > or =1 class of antimicrobial agents, or may acquire resistance by de novo mutation or via the acquisition of resistance genes from other organisms. Acquired resistance genes may enable a bacterium to produce enzymes that destroy the antibacterial drug, to express efflux systems that prevent the drug from reaching its intracellular target, to modify the drug's target site, or to produce an alternative metabolic pathway that bypasses the action of the drug. Acquisition of new genetic material by antimicrobial-susceptible bacteria from resistant strains of bacteria may occur through conjugation, transformation, or transduction, with transposons often facilitating the incorporation of the multiple resistance genes into the host's genome or plasmids. Use of antibacterial agents creates selective pressure for the emergence of resistant strains. Herein 3 case histories-one involving Escherichia coli resistance to third-generation cephalosporins, another focusing on the emergence of vancomycin-resistant Staphylococcus aureus, and a third detailing multidrug resistance in Pseudomonas aeruginosa--are reviewed to illustrate the varied ways in which resistant bacteria develop.", "title": "Mechanisms of antimicrobial resistance in bacteria." }, { "docid": "MED-1956", "text": "The U.S. Food and Drug Administration (FDA) terminated the use of ball clay from a mine in Mississippi as an additive in animal feed after discovering nanogram per gram concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). The FDA collected chicken eggs and farm-raised catfish in affected areas and throughout the remaining continental United States to assess levels of 2,3,7,8-TCDD. A new method using quadrupole ion storage tandem-in-time mass spectrometry (QISTMS) measured the 2,3,7,8-TCDD levels in 42 catfish fillet composites, 3 Tilapia fillet composites, 46 chicken egg samples, and 6 chicken feeds. Six catfish composites and 20 egg samples had 2,3,7,8-TCDD concentrations significantly above 1.0 pg/g wet weight of fillet or whole egg. Farm-raised catfish not exposed to feed containing ball clay had a mean 2,3,7,8-TCDD concentration of 0.12 pg/g. The TCDD isomer pattern in ball clay differed from the TCDD isomer pattern in a fly ash sample and from the \"chick edema factor\" TCDD pattern in a sample of reference toxic fat used as a feed ingredient in the 1950s.", "title": "Elevated TCDD in chicken eggs and farm-raised catfish fed a diet with ball clay from a Southern United States mine." }, { "docid": "MED-3305", "text": "BACKGROUND AND AIM: The occurrence of malignant pleural mesothelioma (MPM) has been reported among population groups with no documented professional exposure to asbestos fibres living in different geographic areas. This paper reviews existing data related to non occupational MPM including its occurrence in the province of Catania (Sicily, Italy). METHODS: An electronic search of literature related to non occupational MPM was performed including the year 2005. RESULTS: Non occupational MPM in subjects living in areas contaminated by a variety of asbestos and non asbestos fibres has been well documented through a number of epidemiologic studies including cases series, case-control studies, and a cohort study. In addition, the observation of familial clustering of MPM, suggests that genetic factors may play a role in the pathogenesis of this malignancy. The epidemiological evidence also suggests that MPM may occur as a result of the interaction between environmental carcinogens, genetic factors, and virus infection. CONCLUSION: It is likely that genetic predisposition and non-occupational exposure to low doses of asbestos and asbestos-like fibres may concur to the development of malignant mesothelioma. However, additional epidemiological and laboratory studies are needed to further understand the relationship between environmental exposure and individual susceptibility to this malignancy.", "title": "Non-occupational malignant pleural mesothelioma due to asbestos and non-asbestos fibres." }, { "docid": "MED-3783", "text": "Fish odour syndrome (trimethylaminuria) is a metabolic syndrome caused by abnormal excretion of trimethylamine in the breath, urine, sweat, saliva and vaginal secretions. Trimethylamine is derived from the intestinal bacterial degradation of foods rich in choline and carnitine and is normally oxidised by the liver to odourless trimethylamine N-oxide which is then excreted in the urine. Impaired oxidation of trimethylamine is thought to be the cause of the fish odour syndrome and is responsible for the smell of rotting fish. Certain foods rich in choline exacerbate the condition and the patients have a variety of psychological problems. Recognition of the condition is important as dietary adjustments reduce the excretion of trimethylamine and may reduce the odour. Occasionally, a short course of metronidazole, neomycin and lactulose may suppress production of trimethylamine by reducing the activity of gut microflora. Keywords: fish odour syndrome; trimethylaminuria", "title": "Fish odour syndrome" }, { "docid": "MED-4055", "text": "Heterocyclic amines (HCAs) are formed when meat products such as beef, chicken, pork and fish are cooked at high temperatures. The most abundant HCA found in the human diet is 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP). PhIP causes mammary carcinomas in female rats and mice, and is associated with an increased risk of developing colon, breast, and prostate cancer in humans. PhIP is metabolized by cytochrome P-450s producing N-OH-PhIP. The N-OH-PhIP can be esterified by phase II enzymes forming an arylnitrenium ion that binds to DNA causing adducts. Furthermore, N-OH-PhIP may be reduced by cytochrome b5 reductase producing superoxide anions and hydroxyl radicals causing DNA strand breaks. Diallyl sulfide (DAS) has been shown to prevent cancer in several animal models, presumably by metabolic modulation. We hypothesize that PhIP produces reactive oxygen species causing DNA strand breaks and that DAS will inhibit the formation of PhIP induced DNA strand breaks. To test this hypothesis we treated normal breast epithelial (MCF-10A) cells with PhIP, DAS and a combination of PhIP and DAS. The detection of lipid peroxides was used as a surrogate for ROS. Lipid peroxides were detected using a PeroxiDetect kit (Sigma). PhIP increased the production of lipid peroxides and DAS decreased the PhIP-induced peroxidation by 47%. To determine if PhIP causes DNA strand breaks in MCF-10A cells, cells were treated for 3, 6, 9, and 24 h with PhIP (100 microM), DAS (100 microM) and a combination of PhIP (100 microM) and DAS (100 microM). DNA strand breaks were evaluated using the Comet assay. PhIP produced DNA strand breaks in a dose- and time-dependent fashion. We have shown that DAS inhibits PhIP-induced DNA strand breaks by inhibiting the production of reactive oxygen species. Therefore, we propose that DAS can prevent PhIP-induced breast cancer.", "title": "Diallyl sulfide inhibits PhIP-induced DNA strand breaks in normal human breast epithelial cells." }, { "docid": "MED-1576", "text": "OBJECTIVES: The incidence of inflammatory bowel disease (IBD) is increasing. Dietary factors such as the spread of the \"Western\" diet, high in fat and protein but low in fruits and vegetables, may be associated with the increase. Although many studies have evaluated the association between diet and IBD risk, there has been no systematic review. METHODS: We performed a systematic review using guideline-recommended methodology to evaluate the association between pre-illness intake of nutrients (fats, carbohydrates, protein) and food groups (fruits, vegetables, meats) and the risk of subsequent IBD diagnosis. Eligible studies were identified via structured keyword searches in PubMed and Google Scholar and manual searches. RESULTS: Nineteen studies were included, encompassing 2,609 IBD patients (1,269 Crohn's disease (CD) and 1,340 ulcerative colitis (UC) patients) and over 4,000 controls. Studies reported a positive association between high intake of saturated fats, monounsaturated fatty acids, total polyunsaturated fatty acids (PUFAs), total omega-3 fatty acids, omega-6 fatty acids, mono- and disaccharides, and meat and increased subsequent CD risk. Studies reported a negative association between dietary fiber and fruits and subsequent CD risk. High intakes of total fats, total PUFAs, omega-6 fatty acids, and meat were associated with an increased risk of UC. High vegetable intake was associated with a decreased risk of UC. CONCLUSIONS: High dietary intakes of total fats, PUFAs, omega-6 fatty acids, and meat were associated with an increased risk of CD and UC. High fiber and fruit intakes were associated with decreased CD risk, and high vegetable intake was associated with decreased UC risk.", "title": "Dietary intake and risk of developing inflammatory bowel disease: a systematic review of the literature." }, { "docid": "MED-2593", "text": "Background Prospective studies in non-Mediterranean populations have consistently related increasing nut consumption to lower coronary heart disease mortality. A small protective effect on all-cause and cancer mortality has also been suggested. To examine the association between frequency of nut consumption and mortality in individuals at high cardiovascular risk from Spain, a Mediterranean country with a relatively high average nut intake per person. Methods We evaluated 7,216 men and women aged 55 to 80 years randomized to 1 of 3 interventions (Mediterranean diets supplemented with nuts or olive oil and control diet) in the PREDIMED (‘PREvención con DIeta MEDiterránea’) study. Nut consumption was assessed at baseline and mortality was ascertained by medical records and linkage to the National Death Index. Multivariable-adjusted Cox regression and multivariable analyses with generalized estimating equation models were used to assess the association between yearly repeated measurements of nut consumption and mortality. Results During a median follow-up of 4.8 years, 323 total deaths, 81 cardiovascular deaths and 130 cancer deaths occurred. Nut consumption was associated with a significantly reduced risk of all-cause mortality (P for trend <0.05, all). Compared to non-consumers, subjects consuming nuts >3 servings/week (32% of the cohort) had a 39% lower mortality risk (hazard ratio (HR) 0.61; 95% CI 0.45 to 0.83). A similar protective effect against cardiovascular and cancer mortality was observed. Participants allocated to the Mediterranean diet with nuts group who consumed nuts >3 servings/week at baseline had the lowest total mortality risk (HR 0.37; 95% CI 0.22 to 0.66). Conclusions Increased frequency of nut consumption was associated with a significantly reduced risk of mortality in a Mediterranean population at high cardiovascular risk. Please see related commentary: http://www.biomedcentral.com/1741-7015/11/165. Trial registration Clinicaltrials.gov. International Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005.", "title": "Frequency of nut consumption and mortality risk in the PREDIMED nutrition intervention trial" }, { "docid": "MED-4626", "text": "Chicken meat with reduced concentration of arachidonic acid (AA) and reduced ratio between omega-6 and omega-3 fatty acids has potential health benefits because a reduction in AA intake dampens prostanoid signaling, and the proportion between omega-6 and omega-3 fatty acids is too high in our diet. Analyses for fatty acid determination are expensive, and finding the optimal number of analyses to give reliable results is a challenge. The objective of the present study was i) to analyse the intraclass correlation of different fatty acids in five meat samples, of one gram each, within the same chicken thigh, and ii) to study individual variations in the concentrations of a range of fatty acids and the ratio between omega-6 and omega-3 fatty acid concentrations among fifteen chickens. Fifteen newly hatched broilers were fed a wheat-based diet containing 4% rapeseed oil and 1% linseed oil for three weeks. Five muscle samples from the mid location of the thigh of each chicken were analysed for fatty acid composition. The intraclass correlation (sample correlation within the same animal) was 0.85-0.98 for the ratios of total omega-6 to total omega-3 fatty acids and of AA to eicosapentaenoic acid (EPA). This indicates that when studying these fatty acid ratios, one sample of one gram per animal is sufficient. However, due to the high individual variation between chicken for these ratios, a relatively high number of animals (minimum 15) are required to obtain a sufficiently high power to reveal significant effects of experimental factors (e.g. feeding regimes). The present experiment resulted in meat with a favorable concentration ratio between omega-6 and omega-3 fatty acids. The AA concentration varied from 1.5 to 2.8 g/100 g total fatty acids in thigh muscle in the fifteen broilers, and the ratio between AA and EPA concentrations ranged from 2.3 to 3.9. These differences among the birds may be due to genetic variance that can be exploited by breeding for lower AA concentration and/or a more favorable AA/EPA ratio to produce meat with health benefits.", "title": "Individual variation and intraclass correlation in arachidonic acid and eicosapentaenoic acid in chicken muscle" }, { "docid": "MED-1936", "text": "BACKGROUND: The underlying molecular mechanisms of the vasculoprotective effects of physical exercise are incompletely understood. Telomere erosion is a central component of aging, and telomere-associated proteins regulate cellular senescence and survival. This study examines the effects of exercising on vascular telomere biology and endothelial apoptosis in mice and the effects of long-term endurance training on telomere biology in humans. METHODS AND RESULTS: C57/Bl6 mice were randomized to voluntary running or no running wheel conditions for 3 weeks. Exercise upregulated telomerase activity in the thoracic aorta and in circulating mononuclear cells compared with sedentary controls, increased vascular expression of telomere repeat-binding factor 2 and Ku70, and reduced the expression of vascular apoptosis regulators such as cell-cycle-checkpoint kinase 2, p16, and p53. Mice preconditioned by voluntary running exhibited a marked reduction in lipopolysaccharide-induced aortic endothelial apoptosis. Transgenic mouse studies showed that endothelial nitric oxide synthase and telomerase reverse transcriptase synergize to confer endothelial stress resistance after physical activity. To test the significance of these data in humans, telomere biology in circulating leukocytes of young and middle-aged track and field athletes was analyzed. Peripheral blood leukocytes isolated from endurance athletes showed increased telomerase activity, expression of telomere-stabilizing proteins, and downregulation of cell-cycle inhibitors compared with untrained individuals. Long-term endurance training was associated with reduced leukocyte telomere erosion compared with untrained controls. CONCLUSIONS: Physical activity regulates telomere-stabilizing proteins in mice and in humans and thereby protects from stress-induced vascular apoptosis.", "title": "Physical exercise prevents cellular senescence in circulating leukocytes and in the vessel wall." }, { "docid": "MED-2765", "text": "To prevent or delay the occurrence of chronic diseases, scientific bodies from the cardiologic and oncologic disciplines have made recommendations regarding the daily dietary intake of certain macro- and micronutrients. This study assessed the knowledge of a random population of 2,305 individuals comprising members of the public, health care workers, university graduate students, and health club attendees. Segments of this population might be expected to have a greater understanding and ability to implement these dietary recommendations. We found that over 90% of the participants were unaware of the recommendations for calcium, salt, vitamin A, and fiber, and the fiber content in a high fiber cereal. Approximately 80% of the participants were unaware of the recommendations regarding fat intake and could not calculate the fat content of a food product. Almost half of the study population took a vitamin pill daily. Of the subjects who were aware of the correct unit measurement for vitamin A (IU), almost 25% of gave a response that exceeded the recommended daily intake. A majority of this study population were unaware of the dietary recommendations regarding the prevention of cardiovascular events and cancer. Subgroups of this study population that might be expected to have more information regarding these recommendations (i.e., having higher education or being a health care professional) did not display a satisfactory level of knowledge. To further compound the problems of adhering to the recommended guidelines, the labeling of many food products is misleading. The recommendations on dietary intake and the information on food product content must be transmitted to the public in a form that allows for ready application when purchasing and consuming food.", "title": "The value of current nutrition information." }, { "docid": "MED-4736", "text": "OBJECTIVE: Few biomarkers for dietary intake of various food groups have been established. The aim of the present study was to explore whether selenium (Se), iodine, mercury (Hg) or arsenic may serve as a biomarker for total fish and seafood intake in addition to the traditionally used n-3 fatty acids EPA and DHA. DESIGN: Intake of fish and seafood estimated by an FFQ was compared with intake assessed by a 4 d weighed food diary and with biomarkers in blood and urine. SETTING: Validation study in the Norwegian Mother and Child Cohort Study (MoBa). SUBJECTS: One hundred and nineteen women. RESULTS: Total fish/seafood intake (median 39 g/d) calculated with the MoBa FFQ was comparable to intake calculated by the food diary (median 30 g/d, rS = 0.37, P < 0.001). Erythrocyte DHA and blood Hg, Se and arsenic concentrations were positively correlated with intake of fish and seafood, but the association for DHA was weakened by the widespread use of supplements. The main finding was the consistent positive association between the intake of fish/seafood and blood arsenic concentration. In multivariate analyses, blood arsenic was associated with blood Hg and fish and seafood intake. In these models, arsenic turned out to be the best indicator of intake of fish and seafood, both totally and in subgroups of fish/seafood intake. CONCLUSIONS: While DHA reflected the intake of fatty fish and n-3 PUFA supplements, blood arsenic concentration also reflected the intake of lean fish and seafood. Blood arsenic appears to be a useful biomarker for total fish and seafood intake.", "title": "Exploration of biomarkers for total fish intake in pregnant Norwegian women." }, { "docid": "MED-3012", "text": "The fish ingredient N3-docosahexaenoic acid 22:6 n-3 (DHA) stimulates brain development. On the other hand methylmercury (MeHg) in fish disturbs the developing central nervous system. In this Context the IQ score in children is considered as an aggregate measure of in utero brain development. To determine the effect of DHA exposure on prenatal neurodevelopment the maternal DHA intake during pregnancy was compared with its epidemiologically observed effect on the IQ score of children. For MeHg the maternal intake was converted into its accumulation in the maternal body. The maternal body burden then was compared with its epidemiologically observed relationship with the IQ score. Taking the MeHg and DHA content of 33 fish species the net effect of these compounds on the IQ score was quantified. For most fish species the adverse effect of MeHg on the IQ score exceeded the beneficial effect of DHA. In the case of long-living predators a negative effect up to 10 points on the IQ score was found. The results of this study indicate that food interventions aiming at the beneficial effects of fish consumption should focus on fish species with a high DHA content, while avoiding fish species with a high MeHg content. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Fish consumption during child bearing age: a quantitative risk-benefit analysis on neurodevelopment." }, { "docid": "MED-1922", "text": "In the past decade, the growing field of telomere science has opened exciting new avenues for understanding the cellular and molecular substrates of stress and stress-related aging processes ver the lifespan. Shorter telomere length is associated with advancing chronological age and also increased disease morbidity and mortality. Emerging studies suggest that stress accelerates the erosion of telomeres from very early in life and possibly even influences the initial (newborn) setting of telomere length. In this review, we highlight recent empirical evidence linking stress and mental illnesses at various times across the lifespan with telomere erosion. We first present findings in the developmental programming of telomere biology linking prenatal stress to newborn and adult telomere length. We then present findings linking exposure to childhood trauma and to certain mental disorders with telomere shortening. Last, we review studies that characterize the relationship between related health-risk behaviors with telomere shortening over the lifespan, and how this process may further buffer the negative effects of stress on telomeres. A better understanding of the mechanisms that govern and regulate telomere biology throughout the lifespan may inform our understanding of etiology and the long-term consequences of stress and mental illnesses on aging processes in diverse populations and settings.", "title": "Stress and Telomere Biology: A Lifespan Perspective" }, { "docid": "MED-4115", "text": "Cui and associates show that healthy individuals have natural autoantibodies (NAAs) specific for myeloperoxidase, proteinase 3, and glomerular basement membrane (GBM) with the same specificity as anti-neutrophil cytoplasmic antibodies and anti-GBM antibodies that are pathogenic. Although Ehrlich proposed horror autotoxicus and Burnet envisioned elimination of forbidden clones, NAAs are present in all healthy individuals and play beneficial homeostatic roles. Pathogenic autoimmunity is dysregulation of natural homeostatic autoimmunity rather than onset of a previously absent self-recognition.", "title": "The rise and fall of horror autotoxicus and forbidden clones." }, { "docid": "MED-3086", "text": "Campylobacter spp. are responsible for a large number of the bacterial food poisoning cases worldwide. Despite being sensitive to oxygen and nutritionally fastidious, Campylobacter spp. are able to survive in food processing environments and reach consumers in sufficient numbers to cause disease. To investigate Campylobacter persistence on processed chicken, exudates from chickens produced for consumer sale were collected and sterilized. Two types of exudates from chicken products were collected: enhanced, where a marinade was added to the chickens during processing, and nonenhanced, where no additives were added during processing. Exudates from enhanced chicken products examined in this study contained a mixture of polyphosphates. Exudate samples were inoculated with Campylobacter jejuni or Campylobacter coli strains and incubated under a range of environmental conditions, and viable bacteria present in the resultant cultures were enumerated. When incubated at 42°C in a microaerobic environment, exudates from enhanced chicken products resulted in increased survival of C. jejuni and C. coli compared with that in nonenhanced exudates in the range of <1 to >4 log CFU/ml. Under more relevant food storage conditions (4°C and normal atmosphere), the exudates from enhanced chicken products also demonstrated improved Campylobacter survival compared with that in nonenhanced exudates. Polyphosphates present in the enhanced exudates were determined to be largely responsible for the improved survival observed when the two types of exudates were compared. Therefore, polyphosphates used to enhance chicken quality aid in sustaining the numbers of Campylobacter bacteria, increasing the opportunity for disease via cross-contamination or improperly cooked poultry.", "title": "Effects of Polyphosphate Additives on Campylobacter Survival in Processed Chicken Exudates" }, { "docid": "MED-1998", "text": "The growing epidemic of type 2 diabetes is one of the leading causes of premature morbidity and mortality worldwide, mainly due to the micro- and macrovascular complications associated with the disease. A growing body of evidence suggests that although the risk of developing complications is greater with glucose levels beyond the established threshold for diagnosis--increasing in parallel with rising hyperglycemia-individuals with glucose levels in the prediabetic range are already at increased risk. Early intervention, ideally as soon as abnormalities in glucose homeostasis are detected, is of great importance to minimize the burden of the disease. However, as the early stages of the disease are asymptomatic, diagnosing prediabetes and early overt type 2 diabetes is challenging. The aim of this article is to discuss these challenges, the benefits of early intervention--with emphasis on the prevention trials showing that progression to type 2 diabetes can be delayed by addressing prediabetes--and the existing evidence-based guidelines that have been drawn to optimize the standards of care at the prediabetes and overt type 2 diabetes stages. Copyright © 2013. Published by Elsevier Inc.", "title": "The early treatment of type 2 diabetes." }, { "docid": "MED-3093", "text": "BACKGROUND: Dietary intake of phosphorus is derived largely from protein sources and is a critical determinant of phosphorus balance in patients with chronic kidney disease. Information about the phosphorus content of prepared foods generally is unavailable, but it is believed to contribute significantly to the phosphorus burden of patients with chronic kidney disease. DESIGN: Analysis of dietary components. SETTING: We measured the phosphorus content of 44 food products, including 30 refrigerated or frozen precooked meat, poultry, and fish items, generally national brands. OUTCOMES: Measured and reported phosphorus content of foods. MEASUREMENTS: Phosphorus by using Association of Analytical Communities official method 984.27; protein by using Association of Analytical Communities official method 990.03. RESULTS: We found that the ratio of phosphorus to protein content in these items ranged from 6.1 to 21.5 mg of phosphorus per 1 g of protein. The mean ratio in the 19 food products with a label listing phosphorus as an additive was 14.6 mg/g compared with 9.0 mg/g in the 11 items without listed phosphorus. The phosphorus content of only 1 precooked food product was available in a widely used dietary database. LIMITATIONS: Results cannot be extrapolated to other products. Manufacturers also may alter the phosphorus content of foods at any time. Protein content was not directly measured for all foods. CONCLUSION: Better reporting of phosphorus content of foods by manufacturers could result in improved dietary phosphorus control without risk of protein malnutrition.", "title": "Dietary phosphorus restriction in dialysis patients: potential impact of processed meat, poultry, and fish products as protein sources." }, { "docid": "MED-4094", "text": "BACKGROUND: Evidence from case-control studies suggest that dietary fiber may be inversely related to breast cancer risk, but it is unclear if this is supported by prospective data. We conducted a systematic review and meta-analysis of the evidence from prospective studies. METHODS: PubMed was searched for prospective studies of fiber intake and breast cancer risk until 31st August 2011. Random effects models were used to estimate summary relative risks (RRs). RESULTS: Sixteen prospective studies were included. The summary RR for the highest versus the lowest intake was 0.93 [95% confidence interval (CI) 0.89-0.98, I(2) = 0%] for dietary fiber, 0.95 (95% CI 0.86-1.06, I(2) = 4%) for fruit fiber, 0.99 (95% CI 0.92-1.07, I(2) = 1%) for vegetable fiber, 0.96 (95% CI 0.90-1.02, I(2) = 5%) for cereal fiber, 0.91 (95% CI 0.84-0.99, I(2) = 7%) for soluble fiber and 0.95 (95% CI 0.89-1.02, I(2) = 0%) for insoluble fiber. The summary RR per 10 g/day of dietary fiber was 0.95 (95% CI 0.91-0.98, I(2) = 0%, P(heterogeneity) = 0.82). In stratified analyses, the inverse association was only observed among studies with a large range (≥13 g/day) or high level of intake (≥25 g/day). CONCLUSION: In this meta-analysis of prospective studies, there was an inverse association between dietary fiber intake and breast cancer risk.", "title": "Dietary fiber and breast cancer risk: a systematic review and meta-analysis of prospective studies." }, { "docid": "MED-3193", "text": "Background Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8). Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.", "title": "11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma" }, { "docid": "MED-4801", "text": "Until recently, reports on methicillin-resistant Staphylococcus aureus (MRSA) in food production animals were mainly limited to occasional detections in dairy cattle mastitis. However, since 2005 a MRSA clone, CC398, has been reported colonizing pigs, veal calves and broiler chickens and infecting dairy cows. Many aspects of its prevalence in pigs remain unclear. In other livestock, colonizing capacity and reservoir status still require elucidation. MRSA CC398 has also been detected in meat, but, as for other MRSA, the risk this poses is somewhat unclear. Currently, the most worrying aspect of MRSA CC398 appears to be its capacity to spread to humans. This might complicate MRSA control measures in human healthcare, urging research into risk factors and transmission routes. Although infections with MRSA CC398 are much less reported than carriage, more investigation into its pathogenic potential is required. Moreover, the origin and evolution of this clone remain unknown.", "title": "Methicillin-resistant Staphylococcus aureus (MRSA) in food production animals." }, { "docid": "MED-4824", "text": "In Japan, the number of patients with both chronic pancreatitis (CP) and pancreatic cancer (PC) is increasing. A nationwide survey on CP revealed that the total number of patients treated for CP in Japan in 2002 was estimated as 45,200 (95% confidence interval, 35,600-54,700), and 20,137 patients died of PC in 2002. Alcoholic pancreatitis was the most common type of pancreatitis (67.5 %). Cigarette smoking was an independent and significant risk factor for CP. The risks of pancreatic and nonpancreatic cancers increased in the course of CP. While alcohol consumption may increase the risk of PC via CP, smoking was important as a risk factor for both CP and PC. The increasing incidence of PC was closely related to the increasing intake of animal fat. Lifestyle in patients with CP appeared to be the same as that in patients with PC. Environmental factors such as lifestyle in combination with genetic factors may increase the risk for both CP and PC. Therefore, changing and improving lifestyle habits such as drinking, smoking and nutrition may reduce the risks for both CP and PC.", "title": "4. Chronic pancreatitis and pancreatic cancer, lifestyle-related diseases." }, { "docid": "MED-2400", "text": "The early effects of 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) exposure in the population involved in the Seveso, Italy, incident in 1976, have been examined in numerous studies. Chloracne was the only effect linked with sufficient certainty to dioxin exposure. The possible long-term consequences were investigated with mortality and cancer incidence studies. Mortality and morbidity findings during the 20-year period following the accident showed increased risk from lymphoemopoietic neoplasm, digestive system cancer (rectum in males, and biliary tract among females, in particular) and respiratory system cancer (lung, among males). In the incidence analyses, also thyroid gland and pleura cancer appeared suggestively increased. Soft tissue sarcomas showed an increase in the largest, yet least exposed, exposure sub-cohort. Several hypotheses associating non-cancer effects with dioxin exposure were corroborated by findings in the Seveso population: this was the case with cardiovascular effects (possibly linked to both chemical exposure and stressful disaster experience), endocrine effects (diabetes among females) and reproductive effects: exposure of men to TCDD was linked to a lowered male/female sex ratio in their offspring. The results of many Seveso studies point to possible gender effects, in accordance with animal models. Notwithstanding the acknowledged study limitations (lack of individual exposure markers, short latency, and small population size for certain cancer types), results of previous experimental and epidemiological studies, along with mechanistic knowledge on dioxin toxicity, support the hypotheses that the observed excesses might be associated with dioxin exposure. The mortality and cancer incidence follow-up of the Seveso cohort are continuing.", "title": "Short- and long-term morbidity and mortality in the population exposed to dioxin after the \"Seveso accident\"." }, { "docid": "MED-4742", "text": "Anisakis simplex has been recognized as an important cause of disease in humans and as a food-borne allergen source. Actually, this food-borne parasite was recently identified as an emerging food safety risk. An A. simplex -specific primer-probe system based on a real-time polymerase chain reaction (PCR) detection assay has been successfully optimized and validated with seafood samples. In addition, a DNA extraction procedure has been optimized to detect the presence of the nematode in food samples. The assay is a very reliable, specific, and sensitive methodology to detect the presence of traces of this parasite in seafood products, including highly processed samples. As a result, 13 sequences of cytochrome c oxidase II gene were obtained and scrutinized to calculate intra- and interspecific variabilities of 0 and 35-67%, respectively. Finally, an efficiency of 2.07 +/- 0.14 of the assay was calculated, and a limit of detection of 40 ppm parasite in 25 g of sample was also optimized. Actually, the presence of this parasite in several seafood products has been demonstrated, enforcing the necessity of a design for a good manufacturing practice protocol for the processing industry to minimize the presence of this parasite as a food-borne allergen source in seafood products.", "title": "Evaluation of a real-time polymerase chain reaction (PCR) assay for detection of anisakis simplex parasite as a food-borne allergen source in seafo..." }, { "docid": "MED-2519", "text": "To date, the only intervention that has consistently been shown to slow the rate of aging, and to increase mean and maximum lifespan in short-lived species, is life-long calorie restriction. It is yet unclear whether long-term calorie restriction in longer lived species (i.e. primates and humans) will have a similar effect. In humans, several studies investigating short-term calorie restriction or \"weight loss\" programs suggest beneficial outcomes on parameters of cardiovascular disease. Studies on long-term calorie restriction are performed on a self-selected group of human subjects and show similar effects. However, few studies are currently investigating the quality of life and potential pitfalls of long-term calorie restriction in humans. It is likely that some of the physiological and psychological effects of caloric restriction that occur in animals may impact the human life very differently. For certain, calorie restriction has a plethora of health benefits in mammals, such as a reduction in age-related diseases such as cancer. However, despite the \"magic\" of CR, this intervention in humans may present itself with a number of health concerns, which may not be applicable to or impact the life of experimental animals, but may do so in humans. These potential pitfalls and \"side effects\" are not clearly addressed in the literature and will be a focus of this review.", "title": "Caloric restriction in humans: potential pitfalls and health concerns." }, { "docid": "MED-1331", "text": "Many changes in diet and in physical activity are occurring simultaneously in the developing world. These diet shifts include large increases in energy density, in the proportion of the population consuming a high fat diet and in animal product intake. Animal source foods (ASF) play a major role in these diet shifts. This article documents the large shifts in the composition of diets and obesity across the developing world and notes that these changes are accelerating. Using China as a case study, evidence of the speeding up of this process is presented in descriptive and more rigorous dynamic longitudinal analysis. The implications of these changes for dietary and obesity patterns and cardiovascular disease are great. Indeed, developing countries are at a point where the prevalence of obesity is greater than that of undernutrition and concerns related to intake of saturated fat and energy imbalance must be considered more seriously by the agriculture sector. Current agriculture development policy in many developing countries focuses on livestock promotion and does not consider the potential adverse health consequences of this strategy. Although linkages between ASF intake and obesity cannot be established as clearly as they are for high ASF intakes, heart disease and cancer, the potential adverse health effects linked with an increased ASF intake should no longer be ignored.", "title": "Dynamics of the nutrition transition toward the animal foods sector in China and its implications: a worried perspective." }, { "docid": "MED-4850", "text": "Plants are rich natural sources of antioxidants in addition to other nutrients. Interventions and cross sectional studies on subjects consuming uncooked vegan diet called living food (LF) have been carried out. We have clarified the efficacy of LF in rheumatoid diseases as an example of a health problem where inflammation is one of the main concerns. LF is an uncooked vegan diet and consists of berries, fruits, vegetables and roots, nuts, germinated seeds and sprouts, i.e. rich sources of carotenoids, vitamins C and E. The subjects eating LF showed highly increased levels of beta and alfa carotenes, lycopen and lutein in their sera. Also the increases of vitamin C and vitamin E (adjusted to cholesterol) were statistically significant. As the berry intake was 3-fold compared to controls the intake of polyphenolic compounds like quercetin, myricetin and kaempherol was much higher than in the omnivorous controls. The LF diet is rich in fibre, substrate of lignan production, and the urinary excretion of polyphenols like enterodiol and enterolactone as well as secoisolaricirecinol were much increased in subjects eating LF. The shift of fibromyalgic subjects to LF resulted in a decrease of their joint stiffness and pain as well as an improvement of their self-experienced health. The rheumatoid arthritis patients eating the LF diet also reported similar positive responses and the objective measures supported this finding. The improvement of rheumatoid arthritis was significantly correlated with the day-to-day fluctuation of subjective symptoms. In conclusion the rheumatoid patients subjectively benefited from the vegan diet rich in antioxidants, lactobacilli and fibre, and this was also seen in objective measures.", "title": "Antioxidants in vegan diet and rheumatic disorders." }, { "docid": "MED-2659", "text": "U.S. and European regulators and researchers disagree over risks of a common class of surfactants.", "title": "European bans on surfactant trigger transatlantic debate." }, { "docid": "MED-2263", "text": "BACKGROUND: Chronic dietary cadmium (Cd) exposure results in kidney dysfunction and decrease in bone mineral density. OBJECTIVE: To determine and compare the bioavailability of Cd from vegetable and animal-based foods. MATERIAL AND METHOD: Caco-2 cells were exposed to Cd in boiled pig kidney, ark shell, kale, raw kale, mixed boiled pig kidney with raw kale and CdCl2 after in vitro digestion. Then cellular Cd uptake from the digests and reference CdCl2 solution was measured by atomic absorption spectrometry. RESULTS: Cd bioavailability from animal-based foods was higher than that from vegetable-based foods. In addition, raw kale exhibited an inhibitory effect on Cd bioavailability when mixed with boiled pig kidney. However Cd in kale was increasingly absorbed after boiling. CONCLUSION: Cd binding to different molecular species, other food components in vegetable and animal-based foods, food combination, as well as cooking processes influenced the uptake of dietary Cd. A relative bioavailability factor accounted for the food matrix might be necessary for exposure assessment and consequently for estimation and prevention of the risk of dietary Cd.", "title": "Cadmium bioavailability from vegetable and animal-based foods assessed with in vitro digestion/caco-2 cell model." }, { "docid": "MED-2749", "text": "Noroviruses are the leading cause of foodborne illness in the United States. To better guide interventions, we analyzed 2,922 foodborne disease outbreaks for which norovirus was the suspected or confirmed cause, which had been reported to the Foodborne Disease Outbreak Surveillance System of the Centers for Disease Control and Prevention during 2001–2008. On average, 365 foodborne norovirus outbreaks were reported annually, resulting in an estimated 10,324 illnesses, 1,247 health care provider visits, 156 hospitalizations, and 1 death. In 364 outbreaks attributed to a single commodity, leafy vegetables (33%), fruits/nuts (16%), and mollusks (13%) were implicated most commonly. Infected food handlers were the source of 53% of outbreaks and may have contributed to 82% of outbreaks. Most foods were likely contaminated during preparation and service, except for mollusks, and occasionally, produce was contaminated during production and processing. Interventions to reduce the frequency of foodborne norovirus outbreaks should focus on food workers and production of produce and shellfish.", "title": "Epidemiology of Foodborne Norovirus Outbreaks, United States, 2001–2008" }, { "docid": "MED-4821", "text": "The relation between diet, lifestyle, and acute myeloid leukemia was assessed in a US cohort of 491,163 persons from the NIH–AARP Diet and Health Study (1995–2003). A total of 338 incident cases of acute myeloid leukemia were ascertained. Multivariate Cox models were utilized to estimate hazard ratios and 95% confidence intervals. Compared with those for never smokers, hazard ratios were 1.29 (95% confidence interval: 0.95, 1.75), 1.79 (95% confidence interval: 1.32, 2.42), 2.42 (95% confidence interval: 1.63, 3.57), and 2.29 (85% confidence interval: 1.38, 3.79) for former smokers who smoked ≤1 or >1 pack/day and for current smokers who smoked ≤1 or >1 pack/day, respectively. Higher meat intake was associated with an increased risk of acute myeloid leukemia (hazard ratio = 1.45, 95% confidence interval: 1.02, 2.07 for the fifth vs. first quintile; P for trend = 0.06); however, there were no clear effects of meat-cooking method or doneness level. Individuals who did not drink coffee appeared to have a higher risk of acute myeloid leukemia than those who drank various quantities of coffee. Neither fruit nor vegetable intake was associated with acute myeloid leukemia. This large prospective study identified smoking and meat intake as risk factors for acute myeloid leukemia.", "title": "Diet, Lifestyle, and Acute Myeloid Leukemia in the NIH–AARP Cohort" }, { "docid": "MED-2577", "text": "A case-control study probing the role of diet on the incidence of colorectal cancer was undertaken in Athens, Greece, in a population characterized by ethnic homogeneity but substantial heterogeneity with respect to dietary habits. The case series consisted of 100 consecutive patients with histologically confirmed colorectal cancer admitted to two large hospitals of Athens during a 16-month period; the control series consisted of orthopaedic patients, admitted to the same hospitals during the same time period, individually matched to the index cases by age and sex. Dietary histories concerning the frequency of consumption (per month or per week) of about 80 food items were obtained by the same interviewer. Cases reported significantly less frequent consumption of vegetables (particularly beets, spinach, lettuce and cabbage) and, independently, significantly more frequent consumption of meat (notably lamb and beef). Between the two extremes (high-vegetable, low-meat diet versus high-meat, low-vegetable diet) a risk ratio of about 8 appears to exist, sufficient (in size and direction) to explain a substantial part of the international variation in the incidence of colorectal cancer. Significant associations were not found with beer or other alcoholic beverages, and significant interactions were not noted with respect to age, sex and anatomic localization (colon vs. rectum).", "title": "Diet and colorectal cancer: a case-control study in Greece." }, { "docid": "MED-2851", "text": "OBJECTIVE Higher heme iron intake is associated with increased type 2 diabetes risk. However, no previous study has evaluated gestational diabetes mellitus (GDM) risk in relation to heme iron intake during pregnancy. We investigated associations of maternal preconceptional and early pregnancy heme and nonheme iron intake with subsequent GDM risk. RESEARCH DESIGN AND METHODS We conducted a prospective cohort study of 3,158 pregnant women. A food frequency questionnaire was used to assess maternal diet. Multivariable generalized linear regression models were used to derive estimates of relative risks (RRs) and 95% CIs. RESULTS Approximately 5.0% of the cohort developed GDM (n = 158). Heme iron intake was positively and significantly associated with GDM risk (Ptrend = 0.04). After adjusting for confounders, women reporting the highest heme iron intake levels (≥1.52 vs. <0.48 mg per day) experienced a 3.31-fold–increased GDM risk (95% CI 1.02–10.72). In fully adjusted models, we noted that a 1-mg per day increase in heme iron was associated with a 51% increased GDM risk (RR 1.51 [95% CI 0.99–2.36]). Nonheme iron was inversely, though not statistically significantly, associated with GDM risk, and the corresponding RRs were 1.00, 0.83, 0.62, and 0.61 across quartiles of nonheme iron intake (Ptrend = 0.08). CONCLUSIONS High levels of dietary heme iron intake during the preconceptional and early pregnancy period may be associated with increased GDM risk. Associations of GDM risk with dietary nonheme iron intake are less clear. Confirmation of these findings by future studies is warranted.", "title": "Gestational Diabetes Mellitus in Relation to Maternal Dietary Heme Iron and Nonheme Iron Intake" }, { "docid": "MED-4031", "text": "INTRODUCTION: High low-density lipoproteins (LDL) cholesterol is one of the major risk factors for cardiovascular disease. In recent years, some evidence has been presented that periodontitis, an infectious inflammatory condition of the periodontium, is associated with an increased risk of cardiovascular disease. To further elucidate this association, we have studied the levels of LDL cholesterol, a known risk marker for cardiovascular disease, in a periodontally-diseased group. METHODS: The levels of serum LDL cholesterol in 47 subjects with mild to severe (clinical attachment loss equal to or greater than 1 mm) chronic generalized (at least 30% of teeth affected) periodontitis with the mean age of 42.21 ± 1.46 years were measured and compared with those obtained from 42 age (39.83 ± 0.94) and sex matched controls. Both groups were free from systemic illnesses. RESULTS: The mean serum LDL cholesterol in periodontitis patients was found to be significantly higher (P < 0.001) as compared to that of the controls. The mean clinical attachment loss was positively correlated with serum LDL cholesterol (P < 0.01) and gingival index (P<0.05). The frequency of persons with pathologic values of LDL cholesterol was significantly higher in periodontitis patients compared with that of the controls. CONCLUSIONS: These results showed that high serum LDL cholesterol may be associated with periodontitis in healthy people. However, it is unclear whether periodontitis causes an increase in the levels of serum LDL or an increased LDL is a risk factor for both periodontitis and cardiovascular disease.", "title": "Association of serum LDL cholesterol level with periodontitis among patients visiting a tertiary-care hospital." }, { "docid": "MED-4553", "text": "Alzheimer's disease (AD) is the most common dementing disorder of late life. Although there might be various different triggering events in the early stages of the disease, they seem to converge on a few characteristic final pathways in the late stages, characterized by inflammation and neurodegeneration. In this review, we put forward the hypothesis that advanced glycation end products (AGEs) and their precursors, including methylglyoxal, are both biomarkers and causative agents (\"gerontotoxins\") characteristic for this disorder. Accumulation of AGEs is a normal feature of aging, but is accelerated in AD, where AGEs can be detected in amyloid plaques and neurofibrillary tangles. AGE modification may explain many of the neuropathological and biochemical features of AD such as extensive protein cross-linking, inflammation, oxidative stress and neuronal cell death. We suggest that methylglyoxal is one of the major carbonyl species responsible for the formation of AGEs. We propose that one promising pharmacological approach to prevent the formation of AGEs would be to lower the methylglyoxal concentration. This can be achieved, for example, by decreasing the concentration of methylglyoxal precursors such as d-glyceraldehyde-3-phosphate by allowing a higher flux through the pentose phosphate pathway or by increasing methylglyoxal detoxification through the glyoxalase system. Alternatively, methylglyoxal could be scavenged by various types of carbonyl scavengers. Copyright © 2010 Elsevier Inc. All rights reserved.", "title": "Advanced glycation end products as biomarkers and gerontotoxins - A basis to explore methylglyoxal-lowering agents for Alzheimer's disease?" }, { "docid": "MED-1598", "text": "Cigarette smoking remains a significant health threat for smokers and nonsmokers alike. Secondhand smoke (SHS) is intrinsically more toxic than directly inhaled smoke. Recently, a new threat has been discovered – Thirdhand smoke (THS) – the accumulation of SHS on surfaces that ages with time, becoming progressively more toxic. THS is a potential health threat to children, spouses of smokers and workers in environments where smoking is or has been allowed. The goal of this study is to investigate the effects of THS on liver, lung, skin healing, and behavior, using an animal model exposed to THS under conditions that mimic exposure of humans. THS-exposed mice show alterations in multiple organ systems and excrete levels of NNAL (a tobacco-specific carcinogen biomarker) similar to those found in children exposed to SHS (and consequently to THS). In liver, THS leads to increased lipid levels and non-alcoholic fatty liver disease, a precursor to cirrhosis and cancer and a potential contributor to cardiovascular disease. In lung, THS stimulates excess collagen production and high levels of inflammatory cytokines, suggesting propensity for fibrosis with implications for inflammation-induced diseases such as chronic obstructive pulmonary disease and asthma. In wounded skin, healing in THS-exposed mice has many characteristics of the poor healing of surgical incisions observed in human smokers. Lastly, behavioral tests show that THS-exposed mice become hyperactive. The latter data, combined with emerging associated behavioral problems in children exposed to SHS/THS, suggest that, with prolonged exposure, they may be at significant risk for developing more severe neurological disorders. These results provide a basis for studies on the toxic effects of THS in humans and inform potential regulatory policies to prevent involuntary exposure to THS.", "title": "Cigarette Smoke Toxins Deposited on Surfaces: Implications for Human Health" }, { "docid": "MED-1157", "text": "In 1997 this laboratory initiated a research program with the objective of examining the effect that rinsing of produce with tap water would have on pesticide residues. Samples were obtained from local markets and/or grown at our experimental farm. Because approximately 35% of produce from retail sources contains pesticide residues, growing and treating produce at an experimental farm had the advantage that all such samples contain pesticide residues. Pesticides were applied under normal field conditions to a variety of food crops and the vegetation was allowed to undergo natural weathering prior to harvest. The resulting samples contained field-incurred or \"field-fortified\" residues. This experimental design was employed to mimic as closely as possible real world samples. Crops were treated, harvested, and divided into equal subsamples. One subsample was processed unwashed, whereas the other was rinsed under tap water. The extraction and analysis method used was a multi-residue method developed in our laboratory. Twelve pesticides were included in this study: the fungicides captan, chlorothalonil, iprodione, and vinclozolin; and the insecticides endosulfan, permethrin, methoxychlor, malathion, diazinon, chlorpyrifos, bifenthrin, and DDE (a soil metabolite of DDT). Statistical analysis of the data using the Wilcoxon signed-rank test showed that rinsing removed residues for nine of the twelve pesticides studied. Residues of vinclozolin, bifenthrin, and chlorpyrifos were not reduced. The rinsability of a pesticide is not correlated with its water solubility.", "title": "Reduction of pesticide residues on produce by rinsing." }, { "docid": "MED-4023", "text": "INTRODUCTION: The aim of the study was to determine the potential relation between vegetarian diet and tooth erosion and abrasion. MATERIAL/METHODS: The examination included 46 vegetarians and the same number in the control group. Clinical research was carried out in order to detect the presence of abrasive and erosive changes and the level of hygiene in oral cavities. The questionnaire survey concerned dietary and hygienic habits. Statistical analysis of the data was conducted with Chi-square test and Mann-Whitney U test. The relations between following a vegetarian diet and the occurrence of non-carious cavities was tested with models of logistic regression. RESULTS: Tooth erosion was present among 39.1% of vegetarians and 23.9% of controls, while abrasion appeared among 26.1% and 10.9%, respectively, and the differences were statistically insignificant. The distribution of the changes was similar in both groups. Among vegetarians, significantly more frequent consumption of sour products (predominantly raw vegetables and fruit and tomatoes) was observed. The level of oral hygiene and hygienic habits were similar in both groups. The analysis of statistical regression did not reveal any relations between following a vegetarian diet and the occurrence of tooth erosion and abrasion. DISCUSSION: The results did not reveal any direct influence of vegetarian diet on the occurrence of erosive and abrasive changes. However, in the vegetarian group, more frequent consumption of some sour products and more commonly used horizontal brushing method were observed, with a slightly higher occurrence of non-carious cavities. Further research is required to obtain unambiguous conclusions.", "title": "Assessment of the influence of vegetarian diet on the occurrence of erosive and abrasive cavities in hard tooth tissues." }, { "docid": "MED-3216", "text": "Increasing dietary protein results in an increase in urinary calcium. Despite over 80 y of research, the source of the additional urinary calcium remains unclear. Because most calcium balance studies found little effect of dietary protein on intestinal calcium absorption, it was assumed that the skeleton was the source of the calcium. The hypothesis was that the high endogenous acid load generated by a protein-rich diet would increase bone resorption and skeletal fracture. However, there are no definitive nutrition intervention studies that show a detrimental effect of a high protein diet on the skeleton and the hypothesis remains unproven. Recent studies from our laboratory demonstrate that dietary protein affects intestinal calcium absorption. We conducted a series of short-term nutrition intervention trials in healthy adults where dietary protein was adjusted to either low, medium or high. The highest protein diet resulted in hypercalciuria with no change in serum parathyroid hormone. Surprisingly, within 4 d, the low protein diet induced secondary hyperparathyroidism that persisted for 2 wk. The secondary hyperparathyroidism induced by the low protein diet was attributed to a reduction in intestinal calcium absorption (as assessed by dual stable calcium isotopes). The long-term consequences of these low protein-induced changes in calcium metabolism are not known, but they could be detrimental to skeletal health. Several recent epidemiological studies demonstrate reduced bone density and increased rates of bone loss in individuals habitually consuming low protein diets. Therefore, studies are needed to determine whether low protein intakes directly affect rates of bone resorption, bone formation or both.", "title": "Low protein intake: the impact on calcium and bone homeostasis in humans." }, { "docid": "MED-3315", "text": "PURPOSE: To test the hypothesis that exposure to poultry oncogenic viruses that widely occurs occupationally in poultry workers and in the general population, may be associated with increased risks of deaths from liver and pancreatic cancers, and to identify new risk factors. METHODS: A pilot case-cohort study of both cancers within a combined cohort of 30,411 highly exposed poultry workers and 16,408 control subjects was conducted, and risk assessed by logistic regression odds ratios (OR) and proportional hazards risk ratios. RESULTS: New occupational findings were recorded respectively for pancreatic/liver cancers, for slaughtering of poultry (OR = 8.9, 95% confidence interval [CI]: 2.7-29.3)/OR = 9.1, 95% CI: 1.9-42.9); catching of live chickens (OR = 3.6, 95% CI: 1.2-10.9)/OR = 1.0, 95% CI: 0.1-8.5); killing other types of animals for food (OR = 4.8, 95% CI: 1.5-16.6)/OR = 2.0, 95% CI: 0.2-18.2), and ever worked on a pig raising farm (OR = 3.0, 95% CI: 1.0-8.2) for pancreatic cancer only. New non-occupational findings for liver cancer were for receiving immunization with yellow fever vaccine (OR = 8.7, 95% CI: 1.0-76.3); and vaccination with typhoid vaccine (OR = 6.3, 95% CI: 1.1-37.4). The study also confirmed previously reported risk factors for both diseases. CONCLUSIONS: This study provides preliminary evidence that exposure to poultry oncogenic viruses may possibly be associated with the occurrence of liver and pancreatic cancers. Case-control studies nested within occupational cohorts of highly exposed subjects of sufficient statistical power may provide an efficient and valid method of investigating/confirming these findings. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "A pilot case-cohort study of liver and pancreatic cancers in poultry workers." }, { "docid": "MED-3358", "text": "BACKGROUND & AIMS: Taste sensitivity to fatty acids influences food ingestion and may regulate fat intake and body weight status. Fatty acids are detected via homologous receptors within the mouth and gastrointestinal (GI) tract, where attenuated sensitivity may be associated with greater fat intake and BMI. This study aimed to extend observations surrounding fatty acid taste, specifically the types of foods consumed and dietary behaviours that may be associated with fatty acid taste sensitivity. METHODS: 51 subjects (41 female; BMI, 21.4 ± 0.46 kg/m², age, 20 ± 0.52 yrs, 10 male; BMI, 23.6 ± 1.4 kg/m², age, 22 ± 1 yrs) were screened for oral sensitivity to oleic acid (3.8 mM) using triplicate sensory evaluations, and classified as hypersensitive; (3/3 correct identifications), or hyposensitive, (<3/3). Fat-taste perception (using sensory-matched custards made with 0, 2, 6, 10% oil), recent diet (4-day diet record) and food habits and behaviours (food habits and behaviours questionnaire) were also established. RESULTS: 75% (n = 38) of subjects were classified as hyposensitive to oleic acid and these subjects differed from those who were classified as hypersensitive. Hyposensitive subjects consumed significantly more energy, fat, saturated fat, fatty foods (butter, meat, dairy), had greater BMI and were less perceptive of small changes in the fat content of custard (all P < 0.05), compared to hypersensitive subjects. CONCLUSION: An inability to perceive low concentrations of fatty acids in foods was associated with greater consumption of fatty foods, specifically butter, meat, dairy, and increasing BMI. 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.", "title": "Oral sensitivity to oleic acid is associated with fat intake and body mass index." }, { "docid": "MED-3227", "text": "Although high-protein diets induce hypercalciuria in humans, the source of the additional urinary calcium remains unclear. One hypothesis is that the high endogenous acid load of a high-protein diet is partially buffered by bone, leading to increased skeletal resorption and hypercalciuria. We used dual stable calcium isotopes to quantify the effect of a high-protein diet on calcium kinetics in women. The study consisted of 2 wk of a lead-in, well-balanced diet followed by 10 d of an experimental diet containing either moderate (1.0 g/kg) or high (2.1 g/kg) protein. Thirteen healthy women received both levels of protein in random order. Intestinal calcium absorption increased during the high-protein diet in comparison with the moderate (26.2 +/- 1.9% vs. 18.5 +/- 1.6%, P < 0.0001, mean +/- sem) as did urinary calcium (5.23 +/- 0.37 vs. 3.57 +/- 0.35 mmol/d, P < 0.0001, mean +/- sem). The high-protein diet caused a significant reduction in the fraction of urinary calcium of bone origin and a nonsignificant trend toward a reduction in the rate of bone turnover. There were no protein-induced effects on net bone balance. These data directly demonstrate that, at least in the short term, high-protein diets are not detrimental to bone.", "title": "The impact of dietary protein on calcium absorption and kinetic measures of bone turnover in women." }, { "docid": "MED-4766", "text": "The aetiology of obesity is multifactorial. An understanding of the contributions of various causal factors is essential for the proper management of obesity. Although it is primarily thought of as a condition brought on by lifestyle choices, recent evidence shows there is a link between obesity and viral infections. Numerous animal models have documented an increased body weight and a number of physiologic changes, including increased insulin sensitivity, increased glucose uptake and decreased leptin secretion that contribute to an increase in body fat in adenovirus-36 infection. Other viral agents associated with increasing obesity in animals included canine distemper virus, rous-associated virus 7, scrapie, Borna disease virus, SMAM-1 and other adenoviruses. This review attempted to determine if viral infection is a possible cause of obesity. Also, this paper discussed mechanisms by which viruses might produce obesity. Based on the evidence presented in this paper, it can be concluded that a link between obesity and viral infections cannot be ruled out. Further epidemiologic studies are needed to establish a causal link between the two, and determine if these results can be used in future management and prevention of obesity.", "title": "Viral obesity: fact or fiction?" }, { "docid": "MED-2647", "text": "Continuing evidence of the feminising effects of xenoestrogens on a range of wildlife species increases the need to assess the human health risk of these estrogen mimics. We have estimated the exposure of New Zealand males, females and young men to a range of naturally occurring and synthetic xenoestrogens found in food. Only estrogenic compounds that act by interaction with the estrogen receptor have been included. Theoretical plasma estrogen activity levels were derived from estrogen exposure estimates and estrogenic potency data. Theoretical plasma levels were compared with published data for specific xenoestrogens. There was surprisingly close agreement. Xenoestrogenicity from dietary intake was almost equally attributed to naturally occurring and synthetic xenoestrogens. Relative contributions for a male, for example were isoflavones (genistein and daidzein) (36%) and bisphenol A (34%) with smaller contributions from alkyl phenols (18%) and the flavonoids (phloretin and kaempferol) (12%). It is suggested that dietary xenoestrogens might have a pharmacological effect on New Zealand males and postmenopausal women, but are unlikely to be significant for pre-menopausal women.", "title": "Dietary exposure to xenoestrogens in New Zealand." }, { "docid": "MED-2250", "text": "Chronic low-level cadmium (Cd) exposure is linked to kidney and cardiovascular disease, fractures, and cancer. Diet and smoking are primary sources of exposure in the general population. We analyzed urinary Cd in NHANES 1999-2008 to determine whether levels declined significantly over the decade for U.S. children, teens, and adults (nonsmokers and smokers) and, if so, factors influencing the decline(s). For each subpopulation, we modeled log urinary Cd using variable-threshold censored multiple regression. Models included individual-level covariates (age, gender, BMI, income, race/ethnicity/country of origin, education, survey period), smoking, housing (home age, water source, filter use), and diet (supplement use; 24-h calorie, fat, protein, micronutrient, and Cd-containing food intakes), creatinine, and survey year variables. Geometric mean urinary Cd (ng/mL) declined 20-25% in these subpopulations, and the regressions showed statistically significant declines in later years for teens and adults. While certain covariates were significantly associated with Cd by subpopulation (creatinine; age; BMI; race/ethnicity/origin; education; smokers in the home; serum cotinine; 24-h fat, Mg, Fe intakes; use of dietary supplements), they did not help explain the declines. Instead, unidentified time-related factors appeared responsible. Despite the declines, millions of Americans remain potentially at risk of adverse outcomes associated with low-level Cd exposure.", "title": "Urinary cadmium in the 1999-2008 U.S. National Health and Nutrition Examination Survey (NHANES)." }, { "docid": "MED-1948", "text": "Over the last ten years curcumin has been reported to be effective against a wide variety of diseases and is characterized as having anti-carcinogenic, hepatoprotective, thrombosuppressive, cardioprotective, anti-arthritic, and anti-infectious properties. Recent studies performed in both vertebrate and invertebrate models have been conducted to determine whether curcumin was also neuroprotective. The efficacy of curcumin in several pre-clinical trials for neurodegenerative diseases has created considerable excitement mainly due to its lack of toxicity and low cost. This suggests that curcumin could be a worthy candidate for nutraceutical intervention. Since aging is a common risk factor for neurodegenerative diseases, it is possible that some compounds that target aging mechanisms could also prevent these kinds of diseases. One potential mechanism to explain several of the general health benefits associated with curcumin is that it may prevent aging-associated changes in cellular proteins that lead to protein insolubility and aggregation. This loss in protein homeostasis is associated with several age-related diseases. Recently, curcumin has been found to help maintain protein homeostasis and extend lifespan in the model invertebrate Caenorhabditis elegans. Here, we review the evidence from several animal models that curcumin improves healthspan by preventing or delaying the onset of various neurodegenerative diseases.", "title": "Curcumin and neurodegenerative diseases" }, { "docid": "MED-3352", "text": "The popularity of low- and reduced-fat foods has increased as consumers seek to decrease their energy consumption. Fat replacers may be used in fat-reduced products to maintain their sensory properties. However, these ingredients have been largely formulated to replicate nongustatory properties of fats to foods and have only achieved moderate success. There is increasing evidence that fats also activate the taste system and uniquely evoke responses that may influence product acceptance. Work supporting a taste component of fat has prompted questions about whether fat constitutes an additional \"primary\" or \"basic\" taste quality. This review briefly summarizes this evidence, focusing on human studies, when possible. Effective stimuli, possible receptors, and physiological changes due to oral fat exposure are discussed. Some studies suggest that there are fatty acid tasters and nontasters and if verified could have implications for targeted product development. © 2011 Institute of Food Technologists®", "title": "Are free fatty acids effective taste stimuli in humans? Presented at the symposium \"The Taste for Fat: New Discoveries on the Role of Fat in Sensor..." }, { "docid": "MED-2853", "text": "Background Two criteria based on a 2 h 75 g OGTT are being used for the diagnosis of gestational diabetes (GDM), those recommended over the years by the World Health Organization (WHO), and those recently recommended by the International Association for Diabetes in Pregnancy Study Group (IADPSG), the latter generated in the HAPO study and based on pregnancy outcomes. Our aim is to systematically review the evidence for the associations between GDM (according to these criteria) and adverse outcomes. Methods We searched relevant studies in MEDLINE, EMBASE, LILACS, the Cochrane Library, CINHAL, WHO-Afro library, IMSEAR, EMCAT, IMEMR and WPRIM. We included cohort studies permitting the evaluation of GDM diagnosed by WHO and or IADPSG criteria against adverse maternal and perinatal outcomes in untreated women. Only studies with universal application of a 75 g OGTT were included. Relative risks (RRs) and their 95% confidence intervals (CI) were obtained for each study. We combined study results using a random-effects model. Inconsistency across studies was defined by an inconsistency index (I2) > 50%. Results Data were extracted from eight studies, totaling 44,829 women. Greater risk of adverse outcomes was observed for both diagnostic criteria. When using the WHO criteria, consistent associations were seen for macrosomia (RR = 1.81; 95%CI 1.47-2.22; p < 0.001); large for gestational age (RR = 1.53; 95%CI 1.39-1.69; p < 0.001); perinatal mortality (RR = 1.55; 95% CI 0.88-2.73; p = 0.13); preeclampsia (RR = 1.69; 95%CI 1.31-2.18; p < 0.001); and cesarean delivery (RR = 1.37;95%CI 1.24-1.51; p < 0.001). Less data were available for the IADPSG criteria, and associations were inconsistent across studies (I2 ≥ 73%). Magnitudes of RRs and their 95%CIs were 1.73 (1.28-2.35; p = 0.001) for large for gestational age; 1.71 (1.38-2.13; p < 0.001) for preeclampsia; and 1.23 (1.01-1.51; p = 0.04) for cesarean delivery. Excluding either the HAPO or the EBDG studies minimally altered these associations, but the RRs seen for the IADPSG criteria were reduced after excluding HAPO. Conclusions The WHO and the IADPSG criteria for GDM identified women at a small increased risk for adverse pregnancy outcomes. Associations were of similar magnitude for both criteria. However, high inconsistency was seen for those with the IADPSG criteria. Full evaluation of the latter in settings other than HAPO requires additional studies.", "title": "Gestational diabetes and pregnancy outcomes - a systematic review of the World Health Organization (WHO) and the International Association of Diabetes in Pregnancy Study Groups (IADPSG) diagnostic criteria" }, { "docid": "MED-3572", "text": "Chemotherapeutic options to treat tuberculosis are severely restricted by the intrinsic resistance of Mycobacterium tuberculosis to the majority of clinically applied antibiotics. Such resistance is partially provided by the low permeability of their unique cell envelope. Here we describe a complementary system that coordinates resistance to drugs that have penetrated the envelope, allowing mycobacteria to tolerate diverse classes of antibiotics that inhibit cytoplasmic targets. This system depends on whiB7, a gene that pathogenic Mycobacterium shares with Streptomyces, a phylogenetically related genus known as the source of diverse antibiotics. In M. tuberculosis, whiB7 is induced by subinhibitory concentrations of antibiotics (erythromycin, tetracycline, and streptomycin) and whiB7 null mutants (Streptomyces and Mycobacterium) are hypersusceptible to antibiotics in vitro. M. tuberculosis is also antibiotic sensitive within a monocyte model system. In addition to antibiotics, whiB7 is induced by exposure to fatty acids that pathogenic Mycobacterium species may accumulate internally or encounter within eukaryotic hosts during infection. Gene expression profiling analyses demonstrate that whiB7 transcription determines drug resistance by activating expression of a regulon including genes involved in ribosomal protection and antibiotic efflux. Components of the whiB7 system may serve as attractive targets for the identification of inhibitors that render M. tuberculosis or multidrug-resistant derivatives more antibiotic-sensitive.", "title": "Ancestral antibiotic resistance in Mycobacterium tuberculosis" }, { "docid": "MED-5196", "text": "The authors prospectively investigated the association between dairy intake and risk of Parkinson’s disease among 57,689 men and 73,175 women from the Cancer Prevention Study II Nutrition Cohort from the American Cancer Society. A total of 250 men and 138 women with Parkinson’s disease were identified during the follow-up (1992–2001). Dairy consumption was positively associated with the risk of Parkinson’s disease: compared with the lowest intake quintile, the corresponding relative risks (RRs) for quintiles 2–5 were 1.4, 1.4, 1.4, and 1.6 (95 percent confidence interval (CI): 1.1–2.2; p for trend=0.05). A higher risk among dairy consumers was found in both men and women, although the association in women appeared non-linear. The meta-analysis of all prospective studies confirmed a moderately elevated risk of Parkinson’s disease among individuals with high dairy consumption: the RRs between extreme intake categories were 1.6 (95 percent CI: 1.3–2.0) for men and women combined, 1.8 for men (95 percent CI: 1.4–2.4), and 1.3 for women (95 percent CI: 0.8–2.1). These data suggest that dairy consumption may increase the risk of Parkinson’s disease, particularly in men. More studies are needed to further examine these findings and to explore the underlying mechanisms.", "title": "Dairy products and risk of Parkinson’s disease" }, { "docid": "MED-1992", "text": "Summary Prediabetes (or “intermediate hyperglycaemia”), based on glycaemic parameters above normal but below diabetes thresholds is a high risk state for diabetes with an annualized conversion rate of 5%–10%; with similar proportion converting back to normoglycaemia. The prevalence of prediabetes is increasing worldwide and it is projected that >470 million people will have prediabetes in 2030. Prediabetes is associated with the simultaneous presence of insulin resistance and β-cell dysfunction, abnormalities that start before glucose changes are detectable. Observational evidence shows associations of prediabetes with early forms of nephropathy, chronic kidney disease, small fibre neuropathy, diabetic retinopathy, and increased risk of macrovascular disease. Multifactorial risk scores could optimize the estimation of diabetes risk using non-invasive parameters and blood-based metabolic traits in addition to glycaemic values. For prediabetic individuals, lifestyle modification is the cornerstone of diabetes prevention with evidence of a 40%–70% relative risk reduction. Accumulating data also suggests potential benefits from pharmacotherapy.", "title": "Prediabetes: A high-risk state for developing diabetes" }, { "docid": "MED-1326", "text": "BACKGROUND: Because of the rapid change in lifestyle in China, there is concern that diabetes may become epidemic. We conducted a national study from June 2007 through May 2008 to estimate the prevalence of diabetes among Chinese adults. METHODS: A nationally representative sample of 46,239 adults, 20 years of age or older, from 14 provinces and municipalities participated in the study. After an overnight fast, participants underwent an oral glucose-tolerance test, and fasting and 2-hour glucose levels were measured to identify undiagnosed diabetes and prediabetes (i.e., impaired fasting glucose or impaired glucose tolerance). Previously diagnosed diabetes was determined on the basis of self-report. RESULTS: The age-standardized prevalences of total diabetes (which included both previously diagnosed diabetes and previously undiagnosed diabetes) and prediabetes were 9.7% (10.6% among men and 8.8% among women) and 15.5% (16.1% among men and 14.9% among women), respectively, accounting for 92.4 million adults with diabetes (50.2 million men and 42.2 million women) and 148.2 million adults with prediabetes (76.1 million men and 72.1 million women). The prevalence of diabetes increased with increasing age (3.2%, 11.5%, and 20.4% among persons who were 20 to 39, 40 to 59, and > or = 60 years of age, respectively) and with increasing weight (4.5%, 7.6%, 12.8%, and 18.5% among persons with a body-mass index [the weight in kilograms divided by the square of the height in meters] of < 18.5, 18.5 to 24.9, 25.0 to 29.9, and > or = 30.0, respectively). The prevalence of diabetes was higher among urban residents than among rural residents (11.4% vs. 8.2%). The prevalence of isolated impaired glucose tolerance was higher than that of isolated impaired fasting glucose (11.0% vs. 3.2% among men and 10.9% vs. 2.2% among women). CONCLUSIONS: These results indicate that diabetes has become a major public health problem in China and that strategies aimed at the prevention and treatment of diabetes are needed. 2010 Massachusetts Medical Society", "title": "Prevalence of diabetes among men and women in China." }, { "docid": "MED-2917", "text": "The effect of alternative dietary habits and prolonged lactation on the nutrient and contaminant concentrations in human milk was studied. The study sample consisted of mothers on macrobiotic diets, containing little or no diary products and meat, at 2-3 months postpartum (n = 9) and 9-13 months postpartum (n = 12), and mothers on omnivorous diets at 2-3 months postpartum (n = 10). Protein and zinc concentrations in breast-milk from macrobiotic mothers decreased with stage of lactation. After adjustment for stage of lactation, milk from macrobiotic mothers contained less calcium, magnesium and saturated fatty acids C15:0-C20:0, and more polyunsaturated fatty acids. Observed tendencies for lower protein and fat and higher lactose concentrations in the macrobiotic group were not statistically significant. Concentrations of vitamin B12, HCB and polychlorinated biphenyls (PCB 118, PCB 138, PCB 153 and PCB 180) were lower in the macrobiotic group. After adjustment for confounding variables, meat and fish consumption, but not dairy products, contributed to vitamin B12 concentrations. Meat and diary products strongly contributed to breast-milk concentrations of dieldrin and PCBs, fish to PCB 118, and smoking to DDT and dieldrin. Our findings suggest that breast-milk contamination could be reduced by abstinence from smoking and a moderate intake of animal products. However, risk of nutritional deficiencies rules out complete avoidance of meat, fish or diary products. Quantitative research on the effects of a reduced consumption of animal products, as well as smoking, on breast-milk contamination is warranted.", "title": "Nutrients and contaminants in human milk from mothers on macrobiotic and omnivorous diets." }, { "docid": "MED-2460", "text": "BACKGROUND: Elevated oxidative stress and impaired antioxidant defences are increasingly recognised features of asthma. Carotenoids are potent dietary antioxidants that may protect against asthma by reducing oxidative damage. OBJECTIVES: This study aimed firstly, to characterise circulating and airway levels of carotenoids in asthma compared to healthy controls, in relation to dietary intake. Secondly, the study aimed to test whether airway lycopene defences can be improved using oral supplements. METHODS: Induced sputum and peripheral blood samples were collected from subjects with asthma (n = 15) and healthy controls (n = 16). Dietary carotenoid intakes were estimated using the 24-hour recall method and analysed using a modified version of the Foodworks 210 Nutrient Calculation Software. Another group of healthy controls (n = 9) were supplemented with 20 mg/day lycopene for 4 weeks. Carotenoids (beta-carotene, lycopene, alpha-carotene, beta-cryptoxanthin, lutein/zeaxanthin) were measured by HPLC. RESULTS: Despite similar dietary intake, whole blood levels of total carotenoids, lycopene, lutein, beta-cryptoxanthin, alpha-carotene and beta-carotene were significantly lower in asthma than controls. However, there were no differences in plasma or sputum carotenoid levels. Induced sputum carotenoid levels were significantly lower than plasma and whole blood levels, but correlated strongly with plasma levels (r = 0.798, p < 0.001). Although there were no overall increases in either plasma or sputum lycopene levels following supplementation, changes in airway lycopene levels correlated with changes in plasma levels (r = 0.908, p < 0.002). CONCLUSIONS: Whole blood, but not plasma or sputum, carotenoid levels are deficient in asthma. Plasma carotenoid levels reflect airway carotenoid levels and when plasma levels are improved using oral supplements this is reflected in the airways.", "title": "Airway and circulating levels of carotenoids in asthma and healthy controls." }, { "docid": "MED-4758", "text": "AIM: To examine the relation between meat intake and diabetes occurrence in adults. METHODS: In a prospective cohort study we examined the relation between diet and incident diabetes recorded among 8,401 cohort members (ages 45-88 years) of the Adventist Mortality Study and Adventist Health Study (California, USA) who were non-diabetic at baseline. During the 17-year follow-up, we identified 543 incident diabetes cases. RESULTS: (1) Subjects who were weekly consumers of all meats were 29% (OR = 1.29; 95% CI 1.08, 1.55) more likely (relative to zero meat intake) to develop diabetes. (2) Subjects who consumed any processed meats (salted fish and frankfurters) were 38% (OR = 1.38; 95% CI 1.05-1.82) more likely to develop diabetes. (3) Long-term adherence (over a 17-year interval) to a diet that included at least weekly meat intake was associated with a 74% increase (OR = 1.74; 95% CI 1.36-2.22) in odds of diabetes relative to long-term adherence to a vegetarian diet (zero meat intake). Further analyses indicated that some of this risk may be attributable to obesity and/or weight gain--both of which were strong risk factors in this cohort. It is noteworthy that even after control for weight and weight change, weekly meat intake remained an important risk factor (OR = 1.38; 95% CI 1.06-1.68) for diabetes [corrected]. CONCLUSIONS: Our findings raise the possibility that meat intake, particularly processed meats, is a dietary risk factor for diabetes. 2008 S. Karger AG, Basel.", "title": "Meats, processed meats, obesity, weight gain and occurrence of diabetes among adults: findings from Adventist Health Studies." }, { "docid": "MED-2367", "text": "Naturally developing xenospecific Abs are well-documented barriers to xenograft transplantation in humans, but whether analogous xenoreactive T cell immunity develops is not known. We used an enzyme-linked immunospot assay to determine the frequency and cytokine profiles of xenoreactive PBLs from a panel of human volunteers. Because naive T cells produce only IL-2 in short term culture, IFN-gamma production by this approach is a measure of a memory immune response. Stimulation of human PBLs or purified T lymphocytes with stimulator cells from inbred swine revealed a high frequency of IFN-gamma producers with 5-fold fewer IL-2 producers. In contrast, lymphocytes obtained from neonatal umbilical cord blood contained swine-specific IL-2 producers but few IFN-gamma producers, which is what one would expect to find with a naive phenotype. Moreover, PBLs from adults with a history of abstention from pork consumption responded to swine cells with a significantly lower frequency of IFN-gamma producers than PBLs from adults with unrestricted diets did, suggesting that pork consumption may result in priming of swine-specific T cell immunity. Our findings provide the first evidence for naturally occurring xenospecific T cell immunity in humans. The detected strength of this memory response suggests that it will present a formidable barrier to transplantation of swine organs.", "title": "Naturally developing memory T cell xenoreactivity to swine antigens in human peripheral blood lymphocytes." }, { "docid": "MED-3320", "text": "OBJECTIVES: Reticuloendotheliosis viruses (REV) are a group of retroviruses like avian leukosis/sarcoma viruses (ALSV) that naturally infect and cause cancers in chickens. We recently found that ALSV antibody levels were associated with job tasks in the poultry industry. The objectives of this study are to examine whether a similar association can be found with REV antibody levels and to examine the correlation between REV and ALSV antibody levels. METHODS: Relative risk was estimated comparing REV antibody levels of 45 poultry workers with those of 44 controls. The expected mean antibody level was predicted for the association with employment by a generalized linear model. Correlation coefficient was measured between ALSV and REV antibody levels. RESULTS: REV antibody levels were significantly higher in poultry workers than in control subjects and were associated with gender and employment conditions, especially employment duration. The relative risk was significantly higher for some job categories. A significant correlation was observed between REV and ALSV antibody levels, which was strong among poultry workers, but weak among the control subjects. CONCLUSION: Antibody levels can be validly used to identify certain job tasks associated with high risk of exposure to REV in the workplace, and the practical implication is recommendations for protection at these job tasks. Importantly, in situations where there is exposure to multiple pathogens in the workplace, the analysis of antibody levels of one pathogen may sufficiently represent exposure to the other correlated pathogens. This suggested exposure assessment may hold true for pathogens with a similar route of transmission.", "title": "Industrial hygiene assessment of reticuloendotheliosis viruses exposure in the poultry industry." }, { "docid": "MED-3545", "text": "Background Omnivorous diets are high in arachidonic acid (AA) compared to vegetarian diets. Research shows that high intakes of AA promote changes in brain that can disturb mood. Omnivores who eat fish regularly increase their intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), fats that oppose the negative effects of AA in vivo. In a recent cross-sectional study, omnivores reported significantly worse mood than vegetarians despite higher intakes of EPA and DHA. This study investigated the impact of restricting meat, fish, and poultry on mood. Findings Thirty-nine omnivores were randomly assigned to a control group consuming meat, fish, and poultry daily (OMN); a group consuming fish 3-4 times weekly but avoiding meat and poultry (FISH), or a vegetarian group avoiding meat, fish, and poultry (VEG). At baseline and after two weeks, participants completed a food frequency questionnaire, the Profile of Mood States questionnaire and the Depression Anxiety and Stress Scales. After the diet intervention, VEG participants reduced their EPA, DHA, and AA intakes, while FISH participants increased their EPA and DHA intakes. Mood scores were unchanged for OMN or FISH participants, but several mood scores for VEG participants improved significantly after two weeks. Conclusions Restricting meat, fish, and poultry improved some domains of short-term mood state in modern omnivores. To our knowledge, this is the first trial to examine the impact of restricting meat, fish, and poultry on mood state in omnivores.", "title": "Restriction of meat, fish, and poultry in omnivores improves mood: A pilot randomized controlled trial" }, { "docid": "MED-4515", "text": "BACKGROUND: Low-carbohydrate, high-animal protein diets, which are advocated for weight loss, may not promote the desired reduction in low-density lipoprotein cholesterol (LDL-C) concentration. The effect of exchanging the animal proteins and fats for those of vegetable origin has not been tested. Our objective was to determine the effect on weight loss and LDL-C concentration of a low-carbohydrate diet high in vegetable proteins from gluten, soy, nuts, fruits, vegetables, cereals, and vegetable oils compared with a high-carbohydrate diet based on low-fat dairy and whole grain products. METHODS: A total of 47 overweight hyperlipidemic men and women consumed either (1) a low-carbohydrate (26% of total calories), high-vegetable protein (31% from gluten, soy, nuts, fruit, vegetables, and cereals), and vegetable oil (43%) plant-based diet or (2) a high-carbohydrate lacto-ovo vegetarian diet (58% carbohydrate, 16% protein, and 25% fat) for 4 weeks each in a parallel study design. The study food was provided at 60% of calorie requirements. RESULTS: Of the 47 subjects, 44 (94%) (test, n = 22 [92%]; control, n = 22 [96%]) completed the study. Weight loss was similar for both diets (approximately 4.0 kg). However, reductions in LDL-C concentration and total cholesterol-HDL-C and apolipoprotein B-apolipoprotein AI ratios were greater for the low-carbohydrate compared with the high-carbohydrate diet (-8.1% [P = .002], -8.7% [P = .004], and -9.6% [P = .001], respectively). Reductions in systolic and diastolic blood pressure were also seen (-1.9% [P = .052] and -2.4% [P = .02], respectively). CONCLUSION: A low-carbohydrate plant-based diet has lipid-lowering advantages over a high-carbohydrate, low-fat weight-loss diet in improving heart disease risk factors not seen with conventional low-fat diets with animal products.", "title": "The effect of a plant-based low-carbohydrate (\"Eco-Atkins\") diet on body weight and blood lipid concentrations in hyperlipidemic subjects." }, { "docid": "MED-4719", "text": "Among the many known health benefits of tea catechins count anti-inflammatory and neuroprotective activities, as well as effects on the regulation of food intake. Here we address cannabimimetic bioactivity of catechin derivatives occurring in tea leaves as a possible cellular effector of these functionalities. Competitive radioligand binding assays using recombinant human cannabinoid receptors expressed in Chem-1 and CHO cells identified (-)-epigallocatechin-3-O-gallate, EGCG (K(i)=33.6 microM), (-)-epigallocatechin, EGC (K(i)=35.7 microM), and (-)-epicatechin-3-O-gallate, ECG (K(i)=47.3 microM) as ligands with moderate affinity for type 1 cannabinoid receptors, CB1. Binding to CB2 was weaker with inhibition constants exceeding 50 microM for EGC and ECG. The epimers (+)-catechin and (-)-epicatechin exhibited negligible affinities for both CB1 and CB2. It can be concluded that central nervous cannabinoid receptors may be targeted by selected tea catechins but signaling via peripheral type receptors is less likely to play a major role in vivo.", "title": "Tea catechins' affinity for human cannabinoid receptors." }, { "docid": "MED-2496", "text": "Persistent organic pollutants (POPs) exert harmful effects on cognitive, endocrine and immune functions and bioaccumulate in the environment and human tissues. The aim of this study was to investigate the body burden of several POPs in the adult population (n=246) and their association to diet and other lifestyle factors in a Swedish national survey. Serum concentrations of several polychlorinated biphenyls (PCBs), and the pesticides hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH), chlordane compounds and dichlorodiphenyldichloroethylene (DDE) were determined by liquid-liquid extraction, silica column cleanup and gas chromatography high resolution mass spectrometry. Diet was assessed using 4-day food records and complementary dietary and lifestyle factors by questionnaire. Fish intake was additionally assessed by plasma fatty acid composition. Clustering of the compounds revealed that PCBs were separated into two clusters, one including low-chlorinated PCB 28 and 52, and the other high-chlorinated mono- and di-ortho PCBs, suggesting similarities and dissimilarities in exposure sources and possibly also toxicokinetics. Men had 24% and 32% higher levels of PCB 138-180 and chlordane compounds, respectively, compared with women. This may partly be explained by elimination of the POPs among women reporting a history of breastfeeding. The proportion of very long-chain n-3 fatty acids in plasma were positively correlated with the pollutants: r=0.24 (PCB 28), r=0.33 (PCB 118), r=0.35 (PCB 138-180), r=0.29 (HCB), r=0.18 (β-HCH), r=0.34 (chlordane compounds), r=0.34 (p,p'-DDE), p≤0.005. Individuals consuming fatty Baltic fish≥1 time per months had 45% higher serum levels of PCB 118 compared with non-consumers. Levels of PCB 28 were associated with the age of the residential building. To conclude, the population-distributed approach of surveying dietary habits, lifestyle factors and POP body burdens, made it possible to identify personal characteristics associated with the POP body burdens in Sweden. Copyright © 2012 Elsevier Ltd. All rights reserved.", "title": "Fish intake and breastfeeding time are associated with serum concentrations of organochlorines in a Swedish population." }, { "docid": "MED-3055", "text": "Both drug addiction and obesity can be defined as disorders in which the saliency value of one type of reward (drugs and food, respectively) becomes abnormally enhanced relative to, and at the expense of others. This model is consistent with the fact that both drugs and food have powerful reinforcing effects-partly mediated by dopamine increases in the limbic system-that, under certain circumstances or in vulnerable individuals, could overwhelm the brain's homeostatic control mechanisms. Such parallels have generated significant interest in understanding the shared vulnerabilities and trajectories between addiction and obesity. Now, brain imaging discoveries have started to uncover common features between these two conditions and to delineate some of the overlapping brain circuits whose dysfunctions may explain stereotypic and related behavioral deficits in human subjects. These results suggest that both obese and drug-addicted individuals suffer from impairments in dopaminergic pathways that regulate neuronal systems associated not only with reward sensitivity and incentive motivation, but also with conditioning (memory/learning), impulse control (behavioural inhibition), stress reactivity, and interoceptive awareness. Here, we integrate findings predominantly derived from positron emission tomography that shed light on the role of dopamine in drug addiction and in obesity, and propose an updated working model to help identify treatment strategies that may benefit both of these conditions.", "title": "Food and drug reward: overlapping circuits in human obesity and addiction." }, { "docid": "MED-4804", "text": "BACKGROUND: Alcohol-based hand rubs (ABHRs) are an effective means of decreasing the transmission of bacterial pathogens. Alcohol is not effective against Clostridium difficile spores. We examined the retention of C. difficile spores on the hands of volunteers after ABHR use and the subsequent transfer of these spores through physical contact. METHODS: Nontoxigenic C. difficile spores were spread on the bare palms of 10 volunteers. Use of 3 ABHRs and chlorhexidine soap-and-water washing were compared with plain water rubbing alone for removal of C. difficile spores. Palmar cultures were performed before and after hand decontamination by means of a plate stamping method. Transferability of C. difficile after application of ABHR was tested by having each volunteer shake hands with an uninoculated volunteer. RESULTS: Plain water rubbing reduced palmar culture counts by a mean (+/- standard deviation [SD]) of 1.57 +/- 0.11 log10 colony-forming units (CFU) per cm2, and this value was set as the zero point for the other products. Compared with water washing, chlorhexidine soap washing reduced spore counts by a mean (+/- SD) of 0.89 +/- 0.34 log10 CFU per cm2; among the ABHRs, Isagel accounted for a reduction of 0.11 +/- 0.20 log10 CFU per cm2 (P = .005), Endure for a reduction of 0.37 +/- 0.42 log10 CFU per cm2 (P = .010), and Purell for a reduction of 0.14 +/- 0.33 log10 CFU per cm2 (P = .005). There were no statistically significant differences between the reductions achieved by the ABHRs; only Endure had a reduction statistically different from that for water control rubbing (P = .040). After ABHR use, handshaking transferred a mean of 30% of the residual C. difficile spores to the hands of recipients. CONCLUSIONS: Hand washing with soap and water is significantly more effective at removing C. difficile spores from the hands of volunteers than are ABHRs. Residual spores are readily transferred by a handshake after use of ABHR.", "title": "Effectiveness of alcohol-based hand rubs for removal of Clostridium difficile spores from hands." }, { "docid": "MED-4690", "text": "Physiological and pharmacological blood concentrations of melatonin inhibit tumorigenesis in a variety of in vivo and in vitro experimental models of neoplasia. Evidence indicates that melatonin's anticancer effects are exerted via inhibition of cell proliferation and a stimulation of differentiation and apoptosis. A new mechanism by which physiological and pharmacological blood levels of melatonin inhibit cancer growth in vivois via a melatonin-induced suppression of tumor linoleic acid (LA) uptake and its metabolism to the important mitogenic signaling molecule 13-hydroxyoctadecadienoic acid (13-HODE). Melatonin suppresses cAMP formation and inhibits tumor uptake of LA and its metabolism to 13-HODE via a melatonin receptor-mediated mechanism in both tissue-isolated rat hepatoma 7288 CTC and human breast cancer xenografts. It has been postulated that in industrialized societies, light at night, by suppressing melatonin production, poses a new risk for the development of breast cancer and, perhaps, other cancers as well. In support of this hypothesis, light during darkness suppresses nocturnal melatonin production and stimulates the LA metabolism and growth of rat hepatoma and human breast cancer xenografts. Nocturnal dietary supplementation with melatonin, at levels contained in a melatonin-rich diet, inhibits rat hepatoma growth via the mechanisms described above. The nocturnal melatonin signal organizes tumor metabolism and growth within circadian time structure that can be further reinforced by appropriately timed melatonin supplementation. Dietary melatonin supplementation working in concert with the endogenous melatonin signal has the potential to be a new preventive/therapeutic strategy to optimize the host/cancer balance in favor of host survival and quality of life.", "title": "Putting cancer to sleep at night: the neuroendocrine/circadian melatonin signal." }, { "docid": "MED-1765", "text": "Inhibition of cholesterol biosynthesis by hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors could, in theory, adversely affect male gonadal function because cholesterol is a precursor of steroid hormones. The objective of this randomized double-blind trial was to compare the effects of simvastatin, pravastatin, and placebo on gonadal testosterone production and spermatogenesis. After a 6-week placebo and lipid-lowering diet run-in period, 159 male patients aged 21 to 55 years with type IIa or IIb hypercholesterolemia, low-density lipoprotein (LDL) cholesterol between 145 and 240 mg/dL, and normal basal levels of testosterone were randomly assigned to treatment with simvastatin 20 mg (n = 40), simvastatin 40 mg (n = 41), pravastatin 40 mg (n = 39), or placebo (n = 39) once daily. After 24 weeks of treatment, mean total cholesterol levels were decreased 24% to 27% and mean LDL cholesterol was decreased 30% to 34% in the 3 active-treatment groups (P < .001 for all comparisons to placebo). At 24 weeks, there were no statistically significant differences between the placebo group and any of the active-treatment groups for the change from baseline in testosterone, human chorionic gonadotropin (hCG)stimulated testosterone, free testosterone index, follicle-stimulating hormone (FSH), luteinizing hormone (LH), or sex hormone-binding globulin (SHBG). Moreover, there were no statistically significant differences at week 12 or week 24 for the change from baseline in sperm concentration, ejaculate volume, or sperm motility for any active treatment relative to placebo. Both simvastatin and pravastatin were well tolerated. In summary, we found no evidence for clinically meaningful effects of simvastatin or pravastatin on gonadal testosterone production, testosterone reserve, or multiple parameters of semen quality.", "title": "Effects of simvastatin and pravastatin on gonadal function in male hypercholesterolemic patients." }, { "docid": "MED-3233", "text": "Our objective in this study was to determine the effects of a high-protein and high-potential renal acid load (PRAL) diet on calcium (Ca) absorption and retention and markers of bone metabolism. In a randomized crossover design, 16 postmenopausal women consumed 2 diets: 1 with low protein and low PRAL (LPLP; total protein: 61 g/d; PRAL: -48 mEq/d) and 1 with high protein and high PRAL (HPHP; total protein: 118 g/d; PRAL: 33 mEq/d) for 7 wk each separated by a 1-wk break. Ca absorption was measured by whole body scintillation counting of radio-labeled (47)Ca. Compared with the LPLP diet, the HPHP diet increased participants' serum IGF-I concentrations (P < 0.0001), decreased serum intact PTH concentrations (P < 0.001), and increased fractional (47)Ca absorption (mean ± pooled SD: 22.3 vs. 26.5 ± 5.4%; P < 0.05) and urinary Ca excretion (156 vs. 203 ± 63 mg/d; P = 0.005). The net difference between the amount of Ca absorbed and excreted in urine did not differ between 2 diet periods (55 vs. 28 ± 51 mg/d). The dietary treatments did not affect other markers of bone metabolism. In summary, a diet high in protein and PRAL increases the fractional absorption of dietary Ca, which partially compensates for increased urinary Ca, in postmenopausal women. The increased IGF-I and decreased PTH concentrations in serum, with no change in biomarkers of bone resorption or formation, indicate a high-protein diet has no adverse effects on bone health.", "title": "A diet high in meat protein and potential renal acid load increases fractional calcium absorption and urinary calcium excretion without affecting m..." }, { "docid": "MED-3373", "text": "Objectives. We considered the relationship between an urban adult population's fruit and vegetable consumption and several selected social and psychological processes, beneficial aesthetic experiences, and garden participation. Methods. We conducted a population-based survey representing 436 residents across 58 block groups in Denver, Colorado, from 2006 to 2007. We used multilevel statistical models to evaluate the survey data. Results. Neighborhood aesthetics, social involvement, and community garden participation were significantly associated with fruit and vegetable intake. Community gardeners consumed fruits and vegetables 5.7 times per day, compared with home gardeners (4.6 times per day) and nongardeners (3.9 times per day). Moreover, 56% of community gardeners met national recommendations to consume fruits and vegetables at least 5 times per day, compared with 37% of home gardeners and 25% of nongardeners. Conclusions. Our study results shed light on neighborhood processes that affect food-related behaviors and provides insights about the potential of community gardens to affect these behaviors. The qualities intrinsic to community gardens make them a unique intervention that can narrow the divide between people and the places where food is grown and increase local opportunities to eat better.", "title": "The Influence of Social Involvement, Neighborhood Aesthetics, and Community Garden Participation on Fruit and Vegetable Consumption" }, { "docid": "MED-2374", "text": "OBJECTIVES: To assess the dose-response relationship between egg consumption and the risk of cardiovascular diseases (CVD) and diabetes. METHODS: We systematically searched MEDLINE database through December 2012. Fixed- or random-effects model was used to pool the relative risks (RRs) and their 95% confidence intervals (CIs). Subgroup analyses was performed to explore the potential sources of heterogeneity. Weighted linear regression model was used to estimate the dose-response relationship. RESULTS: Fourteen studies involving 320,778 subjects were included. The pooled RRs of the risk of CVD, CVD for separated diabetes patients, and diabetes for the highest vs lowest egg intake were 1.19 (95% CI 1.02-1.38), 1.83 (95% CI 1.42-2.37), 1.68 (95% CI 1.41-2.00), respectively. For each 4/week increment in egg intake, the RRs of the risk for CVD, CVD for separated diabetes patients, diabetes was 1.06 (95% CI 1.03-1.10), 1.40 (95% CI 1.25-1.57), 1.29 (95% CI 1.21-1.37), respectively. Subgroup analyses showed that population in other western countries have increased CVD than ones in USA (RR 2.00, 95% CI 1.14 to 3.51 vs 1.13, 95% CI 0.98 to 1.30, P = 0.02 for subgroup difference). CONCLUSIONS: Our study suggests that there is a dose-response positive association between egg consumption and the risk of CVD and diabetes. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.", "title": "Egg consumption and risk of cardiovascular diseases and diabetes: a meta-analysis." }, { "docid": "MED-4251", "text": "Obesity is a global public health issue. Although the etiology of this global epidemic is multifactorial, most sufferers would be delighted to find a relatively effortless way to lose weight. Herbal \"weight loss pills\" can fit the bill. The authors systematically review the scientific evidence concerning various weight loss agents that are available over the counter or in food stores. The review provides a starting point to make informed choices among nutraceutical agents promoted for weight loss, as well as advice for incorporating healthy alternatives in the diet.", "title": "Nutraceutical supplements for weight loss: a systematic review." }, { "docid": "MED-2110", "text": "Almost all types of newborn respiratory failure are reversible. However, supportive treatment (oxygen and positive airway pressure) can damage the lung, and newborn respiratory failure remains a major cause of morbidity and death in infants. Prolonged extracorporeal membrane oxygenation (ECMO) provides life support while allowing the lung to \"rest.\" We have used ECMO in 45 moribund newborn infants; 25 survived. Neonatologists referred patients who were unresponsive to maximal therapy. The right atrium and aortic arch were cannulated via the jugular vein and carotid artery. Heparin was infused continuously to main activated clotting time at 200 to 300 seconds. Airway oxygenation and pressure were reduced to low levels. Primary diagnoses were hyaline membrane disease, 14 (6 survived, 8 died); meconium aspiration, 22 (15 survived, 7 died); persistent fetal circulation including diaphragmatic hernia, 5 (3 survived, 2 died); and sepsis, 4 (1 survived, 3 died). Growth, development, and brain and lung function are normal in 20 of 25 survivors. ECMO decreased newborn respiratory failure mortality and morbidity rates in this phase I trial. A controlled randomized study is underway. The results suggest that ECMO may be effective in older patients if used before irreversible lung damage occurs.", "title": "Extracorporeal membrane oxygenation for newborn respiratory failure: forty-five cases." }, { "docid": "MED-3789", "text": "Background: Meat, milk, and eggs have been inconsistently associated with the risk of advanced prostate cancer. These foods are sources of choline—a nutrient that may affect prostate cancer progression through cell membrane function and one-carbon metabolism. No study has examined dietary choline and the risk of lethal prostate cancer. Objective: Our objective was to examine whether dietary choline, choline-containing compounds, and betaine (a choline metabolite) increase the risk of lethal prostate cancer. Design: We prospectively examined the intake of these nutrients and the risk of lethal prostate cancer among 47,896 men in the Health Professionals Follow-Up Study. In a case-only survival analysis, we examined the postdiagnostic intake of these nutrients and the risk of lethal prostate cancer among 4282 men with an initial diagnosis of nonmetastatic disease during follow-up. Diet was assessed with a validated questionnaire 6 times during 22 y of follow-up. Results: In the incidence analysis, we observed 695 lethal prostate cancers during 879,627 person-years. Men in the highest quintile of choline intake had a 70% increased risk of lethal prostate cancer (HR: 1.70; 95% CI: 1.18, 2.45; P-trend = 0.005). In the case-only survival analysis, we observed 271 lethal cases during 33,679 person-years. Postdiagnostic choline intake was not statistically significantly associated with the risk of lethal prostate cancer (HR for quintile 5 compared with quintile 1: 1.69; 95% CI: 0.93, 3.09; P-trend = 0.20). Conclusion: Of the 47,896 men in our study population, choline intake was associated with an increased risk of lethal prostate cancer.", "title": "Choline intake and risk of lethal prostate cancer: incidence and survival" }, { "docid": "MED-3598", "text": "Trans-fatty acids (TFA) have adverse effects on blood lipids, but whether TFA from different sources are associated with risk of CVD remains unresolved. The objective of the present study was to evaluate the association between TFA intake from partially hydrogenated vegetable oils (PHVO), partially hydrogenated fish oils (PHFO) and ruminant fat (rTFA) and risks of death of CVD, CHD, cerebrovascular diseases and sudden death in the Norwegian Counties Study, a population-based cohort study. Between 1974 and 1988, participants were examined for up to three times. Fat intake was assessed with a semi-quantitative FFQ. A total of 71,464 men and women were followed up through 2007. Hazard ratios (HR) and 95 % CI were estimated with Cox regression. Energy from TFA was compared to energy from all other sources, carbohydrates or unsaturated cis-fatty acids with different multivariable models. During follow-up, 3870 subjects died of CVD, 2383 of CHD, 732 of cerebrovascular diseases and 243 of sudden death. Significant risks, comparing highest to lowest intake category, were found for: TFA from PHVO and CHD (HR 1.23 (95 % CI 1.00, 1.50)) and cerebrovascular diseases (HR 0.65 (95 % CI 0.45, 0.94)); TFA from PHFO and CVD (HR 1.14 (95 % CI 1.03, 1.26)) and cerebrovascular diseases (HR 1.32 (95 % CI 1.04, 1.69)); and rTFA intake and CVD (HR 1.30 (95 % CI 1.05, 1.61)), CHD (HR 1.50 (95 % CI 1.11, 2.03)) and sudden death (HR 2.73 (95 % CI 1.19, 6.25)) in women. These associations with rTFA intake were not significant in men (P interaction ≥ 0.01). The present study supports that TFA intake, irrespective of source, increases CVD risk. Whether TFA from PHVO decreases risk of cerebrovascular diseases warrants further investigation.", "title": "A prospective study of intake of trans-fatty acids from ruminant fat, partially hydrogenated vegetable oils, and marine oils and mortality from CVD." }, { "docid": "MED-1403", "text": "Background Several epidemiological studies have observed an increased risk of type 2 diabetes mellitus (T2DM) among subjects with a higher consumption of red and processed meat. Heme iron intake has been directly associated with a higher risk of T2DM in healthy adult Chinese and U.S populations. The objective of the present study was to evaluate the association between heme iron intake and the incidence of T2DM in a Mediterranean population at high cardiovascular risk. Methods We assessed a subset of participants in the PREDIMED trial as an observational cohort, followed up for a maximum of eight years. We initially included 1073 non-diabetic subjects (57.1% women) aged 67.3 ± 6.0 years, at high cardiovascular risk. Diet was assessed at the study baseline using a validated, semi-quantitative food frequency questionnaire. Results During the follow-up period 131 diabetics were newly diagnosed. The risk of developing T2DM was assessed using baseline heme iron intake and proportional hazard models, first unadjusted, then adjusted for energy, and finally adjusted for dietary, anthropometric, socio-demographic and lifestyle variables. Significant direct associations with the incidence of T2DM were found for heme iron (Hazard Ratio [HR] 1.30, 95% confidence interval [CI], 1.02 to 1.66). Secondarily, we have also observed that coffee (HR:0.93, 95% CI, 0.89 to 0.98) and alcoholic beverages (HR: 1.02, 95% CI, 1.01 to 1.04) were also found to reduce and increase the risk of T2DM, respectively. Conclusion High dietary intake of heme iron was associated with an increased risk of developing T2DM in a Mediterranean population at high cardiovascular risk. Trial registration Identifier: ISRCTN35739639.", "title": "Heme iron intake and risk of new-onset diabetes in a Mediterranean population at high risk of cardiovascular disease: an observational cohort analysis" }, { "docid": "MED-2748", "text": "The consumption of fresh produce is frequently associated with outbreaks of human norovirus (hNoV) disease. To prevent the contamination of fresh produce with hNoV, knowledge of the possible introduction sources of the viruses, such as water, is needed to be able to implement appropriate and efficient preventive measures. Contaminated water used to reconstitute pesticides could be a relevant source of infectious hNoV, determined by the initial level of virus contamination and the persistence of these viruses in reconstituted pesticides. We studied the persistence of hNoV GI.4, hNoV GII.4 and murine norovirus (MNV-1), the only culturable norovirus, in eight different pesticides after 0 and 2h. Virus concentrations were determined by reverse transcriptase PCR, and infectivity of MNV-1 was determined by endpoint dilutions followed by maximum likelihood estimations. MNV-1 was found to remain infectious in seven of the eight tested pesticides at the highest concentration applied in practice. In the presence of the insecticide Vertimec, MNV-1 infectivity decreased rapidly with a 1.9 log(10)-unit reduction at timepoint T(0). Also, the concentration of NoV GI.4 RNA decreased considerably with a 1.7 log(10)-unit reduction; whereas the detected PCR fragment of hNoV GII.4 remained stable. Assuming a similar persistence of infectious MNV-1 and hNoV we can conclude that water containing hNoV used to dilute pesticides may be an important source of infectious hNoV in fresh produce chains. The application of pesticides may therefore not only be a chemical hazard, but also a microbiological hazard for public health. The inclusion of antiviral substances in reconstituted pesticides may be appropriate to reduce the virological health risk posed by the application of pesticides. Copyright © 2012 Elsevier B.V. All rights reserved.", "title": "Persistence of human norovirus in reconstituted pesticides--pesticide application as a possible source of viruses in fresh produce chains." }, { "docid": "MED-4825", "text": "Pancreatic cancer kills more than 250,000 people each year worldwide and has a poor prognosis. The aim of this article is to critically review the epidemiologic evidence for exposures that may either increase or decrease the risk. A Medline search was performed for epidemiologic studies and reviews published up to April 2007. Consistent evidence of a positive association was found for family history and cigarette smoking. Many studies documented a positive association with diabetes mellitus and chronic pancreatitis, although the etiologic mechanisms are unclear. Other associations were detected, but the results were either inconsistent or from few studies. These included positive associations with red meat, sugar, fat, body mass index, gallstones, and Helicobacter pylori, and protective effects of increasing parity, dietary folate, aspirin, and statins. There was no evidence linking alcohol or coffee consumption with an increased risk of pancreatic cancer. The associations with many exposures need to be clarified from further epidemiologic work in which there is both precise measurement of risk factors, adjustment for potential confounders, and, for dietary studies, information recorded on the method of food preparation and pattern of consumption. Such work is important to reduce the incidence of this fatal disease.", "title": "Pancreatic cancer: a review of the evidence on causation." }, { "docid": "MED-1530", "text": "BACKGROUND: Prospective cohort studies have examined mortality and overall cancer incidence among vegetarians, but the results have been inconclusive. AIMS: The objective of the present meta-analysis was to investigate cardiovascular disease mortality and cancer incidence among vegetarians and nonvegetarians. METHODS: Medline, EMBASE and Web Of Science databases were searched for cohort studies published from inception to September 2011. Studies were included if they contained the relative risk (RR) and corresponding 95% CI. Participants were from the UK, Germany, California, USA, the Netherlands and Japan. RESULTS: Seven studies with a total of 124,706 participants were included in this analysis. All-cause mortality in vegetarians was 9% lower than in nonvegetarians (RR = 0.91; 95% CI, 0.66-1.16). The mortality from ischemic heart disease was significantly lower in vegetarians than in nonvegetarians (RR = 0.71; 95% CI, 0.56-0.87). We observed a 16% lower mortality from circulatory diseases (RR = 0.84; 95% CI, 0.54-1.14) and a 12% lower mortality from cerebrovascular disease (RR = 0.88; 95% CI, 0.70-1.06) in vegetarians compared with nonvegetarians. Vegetarians had a significantly lower cancer incidence than nonvegetarians (RR = 0.82; 95% CI, 0.67-0.97). CONCLUSIONS: Our results suggest that vegetarians have a significantly lower ischemic heart disease mortality (29%) and overall cancer incidence (18%) than nonvegetarians. Copyright © 2012 S. Karger AG, Basel.", "title": "Cardiovascular disease mortality and cancer incidence in vegetarians: a meta-analysis and systematic review." }, { "docid": "MED-1449", "text": "Amid soaring health spending, there is growing interest in workplace disease prevention and wellness programs to improve health and lower costs. In a critical meta-analysis of the literature on costs and savings associated with such programs, we found that medical costs fall by about $3.27 for every dollar spent on wellness programs and that absenteeism costs fall by about $2.73 for every dollar spent. Although further exploration of the mechanisms at work and broader applicability of the findings is needed, this return on investment suggests that the wider adoption of such programs could prove beneficial for budgets and productivity as well as health outcomes.", "title": "Workplace wellness programs can generate savings." }, { "docid": "MED-2921", "text": "Background: Methylmercury (MeHg) is a known neuro-toxicant. Emerging evidence indicates it may have adverse effects on the neuro-logic and other body systems at common low levels of exposure. Impacts of MeHg exposure could vary by individual susceptibility or be confounded by bene-ficial nutrients in fish containing MeHg. Despite its global relevance, synthesis of the available literature on low-level MeHg exposure has been limited. Objectives: We undertook a synthesis of the current knowledge on the human health effects of low-level MeHg exposure to provide a basis for future research efforts, risk assessment, and exposure remediation policies worldwide. Data sources and extraction: We reviewed the published literature for original human epidemio-logic research articles that reported a direct biomarker of mercury exposure. To focus on high-quality studies and those specifically on low mercury exposure, we excluded case series, as well as studies of populations with unusually high fish consumption (e.g., the Seychelles), marine mammal consumption (e.g., the Faroe Islands, circumpolar, and other indigenous populations), or consumption of highly contaminated fish (e.g., gold-mining regions in the Amazon). Data synthesis: Recent evidence raises the possibility of effects of low-level MeHg exposure on fetal growth among susceptible subgroups and on infant growth in the first 2 years of life. Low-level effects of MeHg on neuro-logic outcomes may differ by age, sex, and timing of exposure. No clear pattern has been observed for cardio-vascular disease (CVD) risk across populations or for specific CVD end points. For the few studies evaluating immunologic effects associated with MeHg, results have been inconsistent. Conclusions: Studies targeted at identifying potential mechanisms of low-level MeHg effects and characterizing individual susceptibility, sexual dimorphism, and non-linearity in dose response would help guide future prevention, policy, and regulatory efforts surrounding MeHg exposure.", "title": "Evidence on the Human Health Effects of Low-Level Methylmercury Exposure" }, { "docid": "MED-2382", "text": "BACKGROUND: Allergy to peanuts and tree nuts (TNs) is the leading cause of fatal allergic reactions in the United States, and the prevalence appears to be increasing. OBJECTIVES: We sought to determine the US prevalence of self-reported peanut, TN, and sesame allergy in 2008 and compare results with comparable surveys conducted in 1997 and 2002. METHODS: A nationwide, cross-sectional, random telephone survey for peanut and TN allergy was conducted with a previously used questionnaire, with additional questions about sesame. RESULTS: A total of 5,300 households (13,534 subjects) were surveyed (participation rate, 42% vs 52% in 2002 and 67% in 1997). Peanut allergy, TN allergy, or both was reported by 1.4% of subjects (95% CI, 1.2% to 1.6%) compared with 1.2% in 2002 and 1.4% in 1997. For adults, the prevalence was 1.3% (95% CI, 1.1% to 1.6%), which was not significantly different from prior surveys. However, the prevalence of peanut or TN allergy for children younger than 18 years was 2.1% (95% CI, 1.6% to 2.7%) compared with 1.2% in 2002 (P = .007) and 0.6% in 1997 (P < .001). The prevalence of peanut allergy in children in 2008 was 1.4% (95% CI, 1.0% to 1.9%) compared with 0.8% in 2002 (P = not significant) and 0.4% in 1997 (P < .0001). The prevalence of childhood TN allergy increased significantly across the survey waves (1.1% in 2008, 0.5% in 2002, and 0.2% in 1997). Sesame allergy was reported by 0.1% (95% CI, 0.0% to 0.2%). CONCLUSIONS: Although caution is required in comparing surveys, peanut allergy, TN allergy, or both continue to be reported by more than 1% of the US population (eg, >3 million subjects) and appear to be increasingly reported among children over the past decade. Sesame allergy is reported much less commonly. Copyright (c) 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.", "title": "US prevalence of self-reported peanut, tree nut, and sesame allergy: 11-year follow-up." }, { "docid": "MED-1600", "text": "Over the past 10years there has been ongoing development of curing processes with natural ingredients designed to meet consumer demand and regulatory requirements for natural and organic processed meats. Initially, these processes utilized celery concentrates with a high nitrate content combined with a nitrate-reducing starter culture. Subsequent advances included celery concentrates with the nitrate converted to nitrite by suppliers. Further, as questions developed concerning reduced concentration of preservatives and the microbiological safety of these processed meats, additional advances have resulted in a wide variety of ingredients and processes designed to provide supplementary antimicrobial effects for improved product safety. Copyright © 2012 Elsevier Ltd. All rights reserved.", "title": "Beyond celery and starter culture: advances in natural/organic curing processes in the United States." }, { "docid": "MED-3248", "text": "OBJECTIVE: To examine the relation between retinal artery disease and cerebral small-vessel disease (SVD). METHODS: In a prospective cohort of patients with symptomatic atherosclerotic disease, the authors performed retinal photographs and brain MRI. Two ophthalmologists, not aware of the MR results, independently assessed retinal arterial narrowing, crossings, sclerosis, and tortuosity according to standard scoring lists. Two observers independently assessed white matter lesions (WML) and lacunar infarcts on the MR images. Lesions were considered abnormal only when both ophthalmologists or MR raters agreed. Cerebral SVD was defined as the presence of WML or lacunar infarcts. RESULTS: In 179 patients, retinal photographs and brain MRI were performed. Of the 108 patients with MR signs of SVD, 92% had at least one retinal vascular abnormality; of the 71 patients without SVD, 77% had retinal pathology (p < 0.01). All types of retinal vascular pathology occurred more frequently in patients with SVD, but only retinal arterial narrowing and sclerosis differed significantly. In the 109 normotensive patients, the presence of any retinal vascular change correlated with signs of SVD (p = 0.01). CONCLUSION: Pathologic changes in the retinal arteries parallel changes in the small cerebral arteries that cause WML and lacunes, both in hypertensive and in normotensive patients.", "title": "Retinal arterial changes correlate with cerebral small-vessel disease." }, { "docid": "MED-2660", "text": "BACKGROUND: Rapid socioeconomic development in Japan since the beginning of the Seven Countries Study in 1958 has brought remarkable changes in lifestyle and dietary patterns. We investigated the relationship between time trends in nutrient intake and serum cholesterol levels in a Japanese cohort of the Seven Countries Study, in Tanushimaru, a typical farming town on Kyushu Island. METHODS: Subjects totaled 628 in 1958, 539 in 1977, 602 in 1982, 752 in 1989, and 402 in 1999, and all of the subjects were men aged 40-64 years. Eating patterns were evaluated by 24-hour dietary recall from 1958 through 1989, and by a food frequency questionnaire in 1999. We also measured serum cholesterol levels in each health examination. RESULTS: The total daily energy intake decreased from 2837 kcal in 1958 to 2202 kcal in 1999. The carbohydrate intake in percentage of total daily energy intake decreased markedly, from 84% in 1958 to 62% in 1999, in contrast to large increases during this period in protein intake (from 11% to 18%) and fat intake (from 5% to 20%). In proportion to the dramatic change in protein and fat intake, serum cholesterol levels showed large increases (from 152.5mg/dl to 194.2 mg/ dL). CONCLUSIONS: In spite of such big dietary changes toward a westernized diet, the incidence of coronary artery disease in a rural Japanese area remains low. However, careful surveillance is needed in the future because of the remarkably increasing intake of fats, especially saturated fatty acids.", "title": "Trends in nutritional intake and serum cholesterol levels over 40 years in Tanushimaru, Japanese men." }, { "docid": "MED-1257", "text": "Meat protein is associated with an increase in risk of heart disease. Recent data have shown that meat protein appeared to be associated with weight gain over 6.5 years, with 1 kg of weight increase per 125 g of meat per day. In the Nurses' Health Study, diets low in red meat, containing nuts, low-fat dairy, poultry, or fish, were associated with a 13% to 30% lower risk of CHD compared with diets high in meat. Low-carbohydrate diets high in animal protein were associated with a 23% higher total mortality rate whereas low-carbohydrate diets high in vegetable protein were associated with a 20% lower total mortality rate. Recent soy interventions have been assessed by the American Heart Association and found to be associated with only small reductions in LDL cholesterol. Although dairy intake has been associated with a lower weight and lower insulin resistance and metabolic syndrome, the only long-term (6 months) dairy intervention performed so far has shown no effects on these parameters.", "title": "Protein and coronary heart disease: the role of different protein sources." }, { "docid": "MED-1917", "text": "The telomere length is an indicator of biologic aging, and shorter telomeres have been associated with coronary artery calcium (CAC), a validated indicator of coronary atherosclerosis. It is unclear, however, whether healthy lifestyle behaviors affect the relation between telomere length and CAC. In a sample of subjects aged 40 to 64 years with no previous diagnosis of coronary heart disease, stroke, diabetes mellitus, or cancer (n = 318), healthy lifestyle behaviors of greater fruit and vegetable consumption, lower meat consumption, exercise, being at a healthy weight, and the presence of social support were examined to determine whether they attenuated the association between a shorter telomere length and the presence of CAC. Logistic regression analyses controlling for age, gender, race/ethnicity, and Framingham risk score revealed that the relation between having shorter telomeres and the presence of CAC was attenuated in the presence of high social support, low meat consumption, and high fruit and vegetable consumption. Those with shorter telomeres and these characteristics were not significantly different from those with longer telomeres. Conversely, the subjects with shorter telomeres and less healthy lifestyles had a significantly increased risk of the presence of CAC: low fruit and vegetable consumption (odds ratio 3.30, 95% confidence interval 1.61 to 6.75), high meat consumption (odds ratio 3.33, 95% confidence interval 1.54 to 7.20), and low social support (odds ratio 2.58, 95% confidence interval 1.24 to 5.37). Stratification by gender yielded similar results for men; however, among women, only fruit and vegetable consumption attenuated the shorter telomere length and CAC relation. In conclusion, the results of the present study suggest that being involved in healthy lifestyle behaviors might attenuate the association between shorter telomere length and coronary atherosclerosis, as identified using CAC. 2010 Elsevier Inc. All rights reserved.", "title": "Effect of healthy lifestyle behaviors on the association between leukocyte telomere length and coronary artery calcium." }, { "docid": "MED-3294", "text": "In the past two decades or so, a number of viruses have emerged in the global swine population. Some, such as porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2), cause economically important diseases in pigs, whereas others such as porcine torque teno virus (TTV), now known as Torque teno sus virus (TTSuV), porcine bocavirus (PBoV) and related novel parvoviruses, porcine kobuvirus, porcine toroviruses (PToV) and porcine lymphotropic herpesviruses (PLHV), are mostly subclinical in swine herds. Although some emerging swine viruses such as swine hepatitis E virus (swine HEV), porcine endogenous retrovirus (PERV) and porcine sapovirus (porcine SaV) may have a limited clinical implication in swine health, they do pose a potential public health concern in humans due to zoonotic (swine HEV) or potential zoonotic (porcine SaV) and xenozoonotic (PERV, PLHV) risks. Other emerging viruses such as Nipah virus, Bungowannah virus and Menangle virus not only cause diseases in pigs but some also pose important zoonotic threat to humans. This article focuses on emerging and re-emerging swine viruses that have a limited or uncertain clinical and economic impact on pig health. The transmission, epidemiology and pathogenic potential of these viruses are discussed. In addition, the two economically important emerging viruses, PRRSV and PCV2, are also briefly discussed to identify important knowledge gaps. © 2012 Blackwell Verlag GmbH.", "title": "Emerging and re-emerging swine viruses." }, { "docid": "MED-2364", "text": "We have recently demonstrated that both antibodies to Gal alpha(1,3)Gal, and the Gal alpha(1,3)Gal binding lectin (IB4), bind a synthetic peptide (DAHWESWL), there being a similar recognition of carbohydrate and peptide structures. We now report that the anti-Gal alpha(1,3)Gal antibodies and IB4 lectin also react with peptides encoded by mucin genes (MUC 1, 3, 4)-sequences known to be rich in serine, threonine and proline. This activity was demonstrated (1) by the ability of mucin derived peptides to block the reaction of anti-Gal alpha(1,3)Gal antibodies and IB4 lectin with a Gal alpha(1,3)Gal+ pig endothelial cell line; the reactions were specific and did not occur with a random peptide containing the same sequences or with other mucin peptides; (2) by the fact that anti-mucin1 antibodies could react with the Gal alpha(1,3)Gal expressed after transfection of COS cells (Gal alpha(1,3)Gal-,Muc1-) with cDNA encoding the pig alpha, 3galactosyltransferase; and (3) that the IB4 lectin and anti-Gal alpha(1,3)Gal antibodies could react with mucin 1 found on the surface of human breast cancer cells. Thus natural occurring anti-Gal alpha(1,3)Gal antibodies found in all human serum can react with self (Muc1) peptides expressed in large amounts on the surface of tumour cells but not on normal cells. The findings are of interest and serve to explain the previously reported findings that human cells can, at times, express Gal alpha(1,3)Gal; such expression is an artefact, the reaction is due to the phenomenon described herein, i.e. that anti-Gal alpha(1,3)Gal antibodies react with mucin peptides.", "title": "Natural human anti-Gal alpha(1,3)Gal antibodies react with human mucin peptides." }, { "docid": "MED-3353", "text": "Skin blood perfusion and oxygenation depends upon cardiovascular, hormonal and circulatory health in humans and provides socio-sexual signals of underlying physiology, dominance and reproductive status in some primates. We allowed participants to manipulate colour calibrated facial photographs along empirically-measured oxygenated and deoxygenated blood colour axes both separately and simultaneously, to optimise healthy appearance. Participants increased skin blood colour, particularly oxygenated, above basal levels to optimise healthy appearance. We show, therefore, that skin blood perfusion and oxygenation influence perceived health in a way that may be important to mate choice.", "title": "Skin Blood Perfusion and Oxygenation Colour Affect Perceived Human Health" }, { "docid": "MED-3095", "text": "Campylobacter spp. are nutritionally fastidious organisms that are sensitive to normal atmospheric oxygen levels and lack homologues of common cold shock genes. At first glance, these bacteria seem ill equipped to persist within food products under processing and storage conditions; however, they survive in numbers sufficient to cause the largest number of foodborne bacterial disease annually. A mechanism proposed to play a role in Campylobacter survival is the addition of polyphosphate-containing marinades during poultry processing. Campylobacter jejuni and Campylobacter coli strains incubated in chicken exudates collected from poultry treated with a marinade demonstrated considerable survival advantages (1 to 4 log CFU/ml) over the same strains incubated in chicken exudate from untreated birds. Polyphosphates, which constitute a large portion of the commercial poultry marinades, were shown to account for a majority of the observed influence of the marinades on Campylobacter survival. When six different food grade polyphosphates (disodium pyrophosphate, tetrasodium pyrophosphate, pentasodium triphosphate, sodium polyphosphate, monosodium phosphate, and trisodium phosphate) were utilized to compare the survival of Campylobacter strains in chicken exudate, significant differences were observed with regard to Campylobacter survival between the different polyphosphates. It was then determined that the addition of polyphosphates to chicken exudate increased the pH of the exudate, with the more sodiated polyphosphates increasing the pH to a greater degree than the less sodiated polyphosphates. It was confirmed that the change in pH mediated by polyphosphates is responsible for the observed increases in Campylobacter survival.", "title": "Effects of polyphosphate additives on the pH of processed chicken exudates and the survival of Campylobacter." }, { "docid": "MED-3034", "text": "In the 1970s several states in the Great Lakes region became concerned about mercury contamination in lakes and rivers and were the first to issue local fish consumption advisories. In 2001, the Food and Drug Administration (FDA) advised pregnant women, nursing mothers, young children, and women who may become pregnant not to consume shark, swordfish, king mackerel, and tilefish and recommended that these women not exceed 12 ounces of other fish per week. In 2004, FDA reissued this advice jointly with the U.S. Environmental Protection Agency (EPA) and modified it slightly to provide information about consumption of canned tuna and more details about consumption of recreationally caught fish. Though several studies have examined consumers' awareness of the joint FDA and EPA advisory as well as different state advisories, few used representative data. We examined the changes in awareness and knowledge of mercury as a problem in fish using the pooled nationally representative 2001 and 2006 Food Safety Surveys (FSS) with sample sizes of 4482 in 2001 and 2275 in 2006. Our results indicated an increase in consumers' awareness of mercury as a problem in fish (69% in 2001 to 80% in 2006, p<.001). In our regression models, we found that in both years, parents having children less than 5 years of age were more aware of mercury in fish and knowledgeable about the information contained in the national advisories about mercury in fish (p<.01) than other adults. In both 2001 and 2006, women of childbearing age (aged 18-45) were less aware and knowledgeable about this information than other women. However, women of all age groups had larger gains in awareness and knowledge than their male counterparts during this time. Participants' race, education, income, region, fish preparation experiences, having a foodborne illness in the past year, and risk perceptions about the safety of food were significant predictors of their awareness and knowledge. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Awareness and knowledge of methylmercury in fish in the United States." }, { "docid": "MED-3722", "text": "BACKGROUND: The role of dietary habits on esophageal cancer risk has been rarely considered in terms of dietary patterns. PATIENTS AND METHODS: We analyzed data from an Italian case-control study, including 304 cases with squamous cell carcinoma of the esophagus and 743 hospital controls. Dietary habits were evaluated using a food frequency questionnaire. A posteriori dietary patterns were identified through principal component factor analysis performed on 28 selected nutrients. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained from multiple logistic regression models applied on quartiles of factor scores, adjusting for potential confounding variables. RESULTS: We identified five major dietary patterns, named 'animal products and related components', 'vitamins and fiber', 'starch-rich', 'other polyunsaturated fatty acids and vitamin D', and 'other fats'. The 'animal products and related components' pattern was positively related to esophageal cancer (OR = 1.64, 95% CI:1.06-2.55, for the highest versus the lowest quartile of factor scores category). The 'vitamins and fiber' (OR = 0.50, 95% CI: 0.32-0.78) and the 'other polyunsaturated fatty acids and vitamin D' (OR = 0.48, 95% CI: 0.31-0.74) were inversely related to esophageal cancer. No significant association was observed for the other patterns. CONCLUSION: Our findings suggest that a diet rich in foods from animal origin and poor in foods containing vitamins and fiber increase esophageal cancer risk.", "title": "Dietary patterns and the risk of esophageal cancer." }, { "docid": "MED-3021", "text": "The hair-to-blood ratio and biological half-life of methylmercury in a one-compartment model seem to differ between past and recent studies. To reevaluate them, 27 healthy volunteers were exposed to methylmercury at the provisional tolerable weekly intake (3.4 µg/kg body weight/week) for adults through fish consumption for 14 weeks, followed by a 15-week washout period after the cessation of exposure. Blood was collected every 1 or 2 weeks, and hair was cut every 4 weeks. Total mercury (T-Hg) concentrations were analyzed in blood and hair. The T-Hg levels of blood and hair changed with time (p < 0.001). The mean concentrations increased from 6.7 ng/g at week 0 to 26.9 ng/g at week 14 in blood, and from 2.3 to 8.8 µg/g in hair. The mean hair-to-blood ratio after the adjustment for the time lag from blood to hair was 344 ± 54 (S.D.) for the entire period. The half-lives of T-Hg were calculated from raw data to be 94 ± 23 days for blood and 102 ± 31 days for hair, but the half-lives recalculated after subtracting the background levels from the raw data were 57 ± 18 and 64 ± 22 days, respectively. In conclusion, the hair-to-blood ratio of methylmercury, based on past studies, appears to be underestimated in light of recent studies. The crude half-life may be preferred rather than the recalculated one because of the practicability and uncertainties of the background level, though the latter half-life may approximate the conventional one.", "title": "Hair-to-blood ratio and biological half-life of mercury: experimental study of methylmercury exposure through fish consumption in humans." }, { "docid": "MED-3371", "text": "Background: The overconsumption of energy-dense foods leads to excessive energy intakes. The substitution of low-energy-dense vegetables for foods higher in energy density can help decrease energy intakes but may be difficult to implement if individuals dislike the taste of vegetables. Objective: We investigated whether incorporating puréed vegetables to decrease the energy density of entrées at multiple meals reduced daily energy intakes and increased daily vegetable intakes. Design: In this crossover study, 20 men and 21 women ate ad libitum breakfast, lunch, and dinner in the laboratory once a week for 3 wk. Across conditions, entrées at meals varied in energy density from standard versions (100% condition) to reduced versions (85% and 75% conditions) by the covert incorporation of 3 or 4.5 times the amount of puréed vegetables. Entrées were accompanied by unmanipulated side dishes. Participants rated their hunger and fullness before and after meals. Results: Subjects consumed a consistent weight of foods across conditions of energy density; thus, the daily energy intake significantly decreased by 202 ± 60 kcal in the 85% condition (P < 0.001) and by 357 ± 47 kcal in the 75% condition (P < 0.0001). Daily vegetable consumption significantly increased from 270 ± 17 g of vegetables in the 100% condition to 487 ± 25 g of vegetables in the 75% condition (P < 0.0001). Despite the decreased energy intake, ratings of hunger and fullness did not significantly differ across conditions. Entrées were rated as similar in palatability across conditions. Conclusions: Large amounts of puréed vegetables can be incorporated into various foods to decrease the energy density. This strategy can lead to substantial reductions in energy intakes and increases in vegetable intakes. This trial was registered at clinicaltrials.gov as NCT01165086.", "title": "Hidden vegetables: an effective strategy to reduce energy intake and increase vegetable intake in adults" }, { "docid": "MED-4807", "text": "To determine the presence of Shiga toxin-producing Escherichia coli (STEC) and other potentially diarrheagenic E. coli strains in retail meats, 7,258 E. coli isolates collected by the U.S. National Antimicrobial Resistance Monitoring System (NARMS) retail meat program from 2002 to 2007 were screened for Shiga toxin genes. In addition, 1,275 of the E. coli isolates recovered in 2006 were examined for virulence genes specific for other diarrheagenic E. coli strains. Seventeen isolates (16 from ground beef and 1 from a pork chop) were positive for stx genes, including 5 positive for both stx1 and stx2, 2 positive for stx1, and 10 positive for stx2. The 17 STEC strains belonged to 10 serotypes: O83:H8, O8:H16, O15:H16, O15:H17, O88:H38, ONT:H51, ONT:H2, ONT:H10, ONT:H7, and ONT:H46. None of the STEC isolates contained eae, whereas seven carried enterohemorrhagic E. coli (EHEC) hlyA. All except one STEC isolate exhibited toxic effects on Vero cells. DNA sequence analysis showed that the stx2 genes from five STEC isolates encoded mucus-activatable Stx2d. Subtyping of the 17 STEC isolates by pulsed-field gel electrophoresis (PFGE) yielded 14 distinct restriction patterns. Among the 1,275 isolates from 2006, 11 atypical enteropathogenic E. coli (EPEC) isolates were identified in addition to 3 STEC isolates. This study demonstrated that retail meats, mainly ground beef, were contaminated with diverse STEC strains. The presence of atypical EPEC strains in retail meat is also of concern due to their potential to cause human infections.", "title": "Presence and Characterization of Shiga Toxin-Producing Escherichia coli and Other Potentially Diarrheagenic E. coli Strains in Retail Meats" }, { "docid": "MED-2675", "text": "Although products of pyrolysis are often cytotoxic and mutagenic, the relationship between the type of material pyrolysed and the toxicity of the resulting pyrolysis products is poorly understood. The objective of this study was to evaluate and compare the cytotoxicity and mutagenicity of several types of common pyrolysis products. The cytotoxicity and mutagenicity of these products were assessed by using neutral red uptake and Ames mutagenicity assays, respectively. The biological activities of four liquid smoke food flavourings (LSF) were compared with two other pyrolysis-derived materials; cigarette smoke condensate (CSC) and a wood smoke condensate (WSC). Results indicated all of the mixtures exhibited a concentration-dependent cytotoxic response. The CSC and WSC were less cytotoxic than three of the LSFs, but more cytotoxic than one of the brands. The CSC was mutagenic in two Salmonella strains; however, none of the LSFs or WSC was mutagenic using TA98, and only three of the LSFs were positive with TA100. The six pyrolysis-derived materials evaluated in this study showed differing patterns and magnitudes of cytotoxicity and mutagenicity. These results indicate that the cytotoxicity and mutagenicity of complex mixtures derived from pyrolysis products are affected by the type of material pyrolysed and/or the method used to prepare the mixture. The cytotoxic potential of some commercial smoke flavourings is greater than cigarette smoke condensate and several of the food flavourings are mutagenic in one Salmonella strain.", "title": "Comparison of the cytotoxic and mutagenic potential of liquid smoke food flavourings, cigarette smoke condensate and wood smoke condensate." }, { "docid": "MED-4808", "text": "BACKGROUND: Extraintestinal Escherichia coli infections are associated with specialized extraintestinal pathogenic E. coli (ExPEC) strains and, increasingly, with antimicrobial resistance. The food supply may disseminate ExPEC and antimicrobial-resistant E. coli. METHODS: In a prospective survey of 1648 diverse food items from 10 retail markets in the Minneapolis-St. Paul area during 2001-2003, selective cultures and disk-diffusion assays for the isolation and characterization of antimicrobial-resistant E. coli and polymerase chain reaction-based assays and O serotyping to define ExPEC-associated traits were performed. RESULTS: E. coli contamination exhibited a prevalence gradient from miscellaneous foods (9%), through beef or pork (69%), to poultry (92%; P<.001). Among E. coli-positive samples, similar prevalence gradients were detected for antimicrobial resistance (27%, 85%, and 94% of samples, respectively; P<.001) and ExPEC contamination (4%, 19%, and 46%, respectively; P<.001). By multivariate analysis, beef or pork and poultry from natural-food stores exhibited reduced risks of E. coli contamination and antimicrobial resistance. Indirect evidence suggested on-farm selection of resistance. Four food-source ExPEC isolates (from pea pods, turkey parts, ground pork, and vegetable dip) closely resembled selected human clinical isolates by O antigen and genomic profile. CONCLUSIONS: Retail foods may be an important vehicle for community-wide dissemination of antimicrobial-resistant E. coli and ExPEC, which may represent a newly recognized group of medically significant foodborne pathogens.", "title": "Antimicrobial-resistant and extraintestinal pathogenic Escherichia coli in retail foods." }, { "docid": "MED-1773", "text": "STUDY QUESTION Is increased consumption of dairy foods associated with lower semen quality? SUMMARY ANSWER We found that intake of full-fat dairy was inversely related to sperm motility and morphology. These associations were driven primarily by intake of cheese and were independent of overall dietary patterns. WHAT IS KNOWN ALREADY It has been suggested that environmental estrogens could be responsible for the putative secular decline in sperm counts. Dairy foods contain large amounts of estrogens. While some studies have suggested dairy as a possible contributing factor for decreased semen quality, this finding has not been consistent across studies. STUDY DESIGN, SIZE, DURATION The Rochester Young Men's Study (n = 189) was a cross-sectional study conducted between 2009 and 2010 at the University of Rochester. PARTICIPANTS/MATERIALS, SETTING, METHODS Men aged 18–22 years were included in this analysis. Diet was assessed via food frequency questionnaire. Linear regression was used to analyze the relation between dairy intake and conventional semen quality parameters (total sperm count, sperm concentration, progressive motility, morphology and ejaculate volume) adjusting for age, abstinence time, race, smoking status, body mass index, recruitment period, moderate-to-intense exercise, TV watching and total calorie intake. MAIN RESULTS AND THE ROLE OF CHANCE Total dairy food intake was inversely related to sperm morphology (P-trend = 0.004). This association was mostly driven by intake of full-fat dairy foods. The adjusted difference (95% confidence interval) in normal sperm morphology percent was −3.2% (−4.5 to −1.8) between men in the upper half and those in the lower half of full-fat dairy intake (P < 0.0001), while the equivalent contrast for low-fat dairy intake was less pronounced [−1.3% (−2.7 to −0.07; P= 0.06)]. Full-fat dairy intake was also associated with significantly lower percent progressively motile sperm (P= 0.05). LIMITATIONS, REASONS FOR CAUTION As it was a cross-sectional study, causal inference is limited. WIDER IMPLICATIONS OF THE FINDINGS Further research is needed to prove a causal link between a high consumption of full-fat dairy foods and detrimental effects on semen quality. If verified our findings would mean that intake of full-fat dairy foods should be considered in attempts to explain secular trends in semen quality and that men trying to have children should restrict their intake. STUDY FUNDING/COMPETING INTEREST(S) European Union Seventh Framework Program (Environment), ‘Developmental Effects of Environment on Reproductive Health’ (DEER) grant 212844. Grant P30 {\"type\":\"entrez-nucleotide\",\"attrs\":{\"text\":\"DK046200\",\"term_id\":\"187635970\",\"term_text\":\"DK046200\"}}DK046200 and Ruth L. Kirschstein National Research Service Award T32 DK007703-16 from the National Institutes of Health. None of the authors has any conflicts of interest to declare.", "title": "Dairy food intake in relation to semen quality and reproductive hormone levels among physically active young men" }, { "docid": "MED-1763", "text": "The current trends of increasing incidences of testis, breast and prostate cancers are poorly understood, although it is assumed that sex hormones play a role. Disrupted sex hormone action is also believed to be involved in the increased occurrence of genital abnormalities among newborn boys and precocious puberty in girls. In this article, recent literature on sex steroid levels and their physiological roles during childhood is reviewed. It is concluded that (i) circulating levels of estradiol in prepubertal children are lower than originally claimed; (ii) children are extremely sensitive to estradiol and may respond with increased growth and/or breast development even at serum levels below the current detection limits; (iii) no threshold has been established, below which no hormonal effects can be seen in children exposed to exogenous steroids or endocrine disruptors; (iv) changes in hormone levels during fetal and prepubertal development may have severe effects in adult life and (v) the daily production rates of sex steroids in children estimated by the Food and Drug Administration in 1999 and still used in risk assessments are highly overestimated and should be revised. Because no lower threshold for estrogenic action has been established, caution should be taken to avoid unnecessary exposure of fetuses and children to exogenous sex steroids and endocrine disruptors, even at very low levels.", "title": "The sensitivity of the child to sex steroids: possible impact of exogenous estrogens." }, { "docid": "MED-4802", "text": "Background Recent research has demonstrated that many swine and swine farmers in the Netherlands and Canada are colonized with MRSA. However, no studies to date have investigated carriage of MRSA among swine and swine farmers in the United States (U.S.). Methods We sampled the nares of 299 swine and 20 workers from two different production systems in Iowa and Illinois, comprising approximately 87,000 live animals. MRSA isolates were typed by pulsed field gel electrophoresis (PFGE) using SmaI and EagI restriction enzymes, and by multi locus sequence typing (MLST). PCR was used to determine SCCmec type and presence of the pvl gene. Results In this pilot study, overall MRSA prevalence in swine was 49% (147/299) and 45% (9/20) in workers. The prevalence of MRSA carriage among production system A's swine varied by age, ranging from 36% (11/30) in adult swine to 100% (60/60) of animals aged 9 and 12 weeks. The prevalence among production system A's workers was 64% (9/14). MRSA was not isolated from production system B's swine or workers. Isolates examined were not typeable by PFGE when SmaI was used, but digestion with EagI revealed that the isolates were clonal and were not related to common human types in Iowa (USA100, USA300, and USA400). MLST documented that the isolates were ST398. Conclusions These results show that colonization of swine by MRSA was very common on one swine production system in the midwestern U.S., suggesting that agricultural animals could become an important reservoir for this bacterium. MRSA strain ST398 was the only strain documented on this farm. Further studies are examining carriage rates on additional farms.", "title": "Methicillin-Resistant Staphylococcus aureus (MRSA) Strain ST398 Is Present in Midwestern U.S. Swine and Swine Workers" }, { "docid": "MED-1332", "text": "Background The definition of incident type 2 diabetes varies across studies; hence, the actual incidence of type 2 diabetes in Japan is unclear. Here, we reviewed the various definitions of incident type 2 diabetes used in previous epidemiologic studies and estimated the diabetes incidence rate in Japan. Methods We searched for related literature in the MEDLINE, EMBASE, and Ichushi databases through September 2012. Two reviewers selected studies that evaluated incident type 2 diabetes in the Japanese population. Results From 1824 relevant articles, we included 33 studies with 386,803 participants. The follow-up period ranged from 2.3 to 14 years and the studies were initiated between 1980 and 2003. The random-effects model indicated that the pooled incidence rate of diabetes was 8.8 (95% confidence interval, 7.4–10.4) per 1000 person-years. We observed a high degree of heterogeneity in the results (I2 = 99.2%; p < 0.001), with incidence rates ranging from 2.3 to 52.6 per 1000 person-years. Three studies based their definition of incident type 2 diabetes on self-reports only, 10 on laboratory data only, and 20 on self-reports and laboratory data. Compared with studies defining diabetes using laboratory data (n = 30; pooled incidence rate = 9.6; 95% confidence interval = 8.3–11.1), studies based on self-reports alone tended to show a lower incidence rate (n = 3; pooled incidence rate = 4.0; 95% confidence interval = 3.2–5.0; p for interaction < 0.001). However, stratified analyses could not entirely explain the heterogeneity in the results. Conclusions Our systematic review and meta-analysis indicated the presence of a high degree of heterogeneity, which suggests that there is a considerable amount of uncertainty regarding the incidence of type 2 diabetes in Japan. They also suggested that laboratory data may be important for the accurate estimation of the incidence of type 2 diabetes.", "title": "Incidence of Type 2 Diabetes in Japan: A Systematic Review and Meta-Analysis" }, { "docid": "MED-3782", "text": "Red and processed meat may increase risk of advanced prostate cancer. Data on post-diagnostic diet and prostate cancer are sparse, but post-diagnostic intake of poultry with skin and eggs may increase risk of disease progression. Therefore, we prospectively examined total, unprocessed, and processed red meat, poultry, and eggs in relation to risk of lethal prostate cancer (e.g. men without cancer at baseline who developed distant organ metastases or died from prostate cancer during follow-up) among 27, 607 men followed from 1994–2008. We also performed a case-only survival analysis to examine post-diagnostic consumption of these foods and risk of lethal prostate cancer among the 3,127 men initially diagnosed with non-metastatic prostate cancer during follow-up. In the incidence analysis, we observed 199 events during 306,715 person-years. Men who consumed 2.5 or more eggs per week had an 81% increased risk of lethal prostate cancer compared to men who consumed less than 0.5 eggs per week (HR: 1.81; 95% confidence interval (CI): 1.13, 2.89; p-trend: 0.01). In the case-only survival analysis, we observed 123 events during 19,354 person-years. There were suggestive, but not statistically significant, positive associations between post-diagnostic poultry (HR ≥3.5 vs. <1.5 servings per week: 1.69; 95%CI: 0.96, 2.99; p-trend: 0.07) and post-diagnostic processed red meat (HR ≥3 vs. <0.5 servings per week: 1.45; 95%CI: 0.73, 2.87; p-trend: 0.08) and risk of progression of localized prostate cancer to lethal disease. In conclusion, consumption of eggs may increase risk of developing a lethal-form of prostate cancer among healthy men.", "title": "Egg, red meat, and poultry intake and risk of lethal prostate cancer in the prostate specific antigen-era: incidence and survival" }, { "docid": "MED-1558", "text": "Dietary fat and its effects on health and disease has attracted interest for research and Public Health. Since the 1980s many bodies and organizations have published recommendations regarding fat intake. In this paper different sets of recommendations are analyzed following a systematic review process to examine dietary reference intakes, nutritional goals and dietary guidelines for fat and fatty acids. A literature search was conducted in relevant literature databases along a search for suitable grey literature reports. Documents were included if they reported information on either recommended intake levels or dietary reference values or nutritional objectives or dietary guidelines regarding fat and/or fatty acids and/or cholesterol intake or if reported background information on the process followed to produce the recommendations. There is no standard approach for deriving nutrient recommendations. Recommendations vary between countries regarding the levels of intake advised, the process followed to set the recommendations. Recommendations on fat intake share similar figures regarding total fat intake, saturated fats and trans fats. Many sets do not include a recommendation about cholesterol intake. Most recent documents provide advice regarding specific n-3 fatty acids. Despite efforts to develop evidence based nutrient recommendations and dietary guidelines that may contribute to enhance health, there are still many gaps in research. It would be desirable that all bodies concerned remain transparent about the development of dietary recommendations. In order to achieve this, the type of evidence selected to base the recommendations should be specified and ranked. Regular updates of such recommendations should be planned.", "title": "Recommended dietary reference intakes, nutritional goals and dietary guidelines for fat and fatty acids: a systematic review." }, { "docid": "MED-5176", "text": "A flaxseed lignan extract containing 33% secoisolariciresinol diglucoside (SDG) was evaluated for its ability to alleviate lower urinary tract symptoms (LUTS) in 87 subjects with benign prostatic hyperplasia (BPH). A randomized, double-blind, placebo-controlled clinical trial with repeated measurements was conducted over a 4-month period using treatment dosages of 0 (placebo), 300, or 600 mg/day SDG. After 4 months of treatment, 78 of the 87 subjects completed the study. For the 0, 300, and 600 mg/day SDG groups, respectively, the International Prostate Symptom Score (IPSS) decreased -3.67 +/- 1.56, -7.33 +/- 1.18, and -6.88 +/- 1.43 (mean +/- SE, P = .100, < .001, and < .001 compared to baseline), the Quality of Life score (QOL score) improved by -0.71 +/- 0.23, -1.48 +/- 0.24, and -1.75 +/- 0.25 (mean +/- SE, P = .163 and .012 compared to placebo and P = .103, < .001, and < .001 compared to baseline), and the number of subjects whose LUTS grade changed from \"moderate/severe\" to \"mild\" increased by three, six, and 10 (P = .188, .032, and .012 compared to baseline). Maximum urinary flows insignificantly increased 0.43 +/- 1.57, 1.86 +/- 1.08, and 2.7 +/- 1.93 mL/second (mean +/- SE, no statistical significance reached), and postvoiding urine volume decreased insignificantly by -29.4 +/- 20.46, -19.2 +/- 16.91, and -55.62 +/- 36.45 mL (mean +/- SE, no statistical significance reached). Plasma concentrations of secoisolariciresinol (SECO), enterodiol (ED), and enterolactone (EL) were significantly raised after the supplementation. The observed decreases in IPSS and QOL score were correlated with the concentrations of plasma total lignans, SECO, ED, and EL. In conclusion, dietary flaxseed lignan extract appreciably improves LUTS in BPH subjects, and the therapeutic efficacy appeared comparable to that of commonly used intervention agents of alpha1A-adrenoceptor blockers and 5alpha-reductase inhibitors.", "title": "Effects of dietary flaxseed lignan extract on symptoms of benign prostatic hyperplasia." }, { "docid": "MED-4805", "text": "Colibacillosis appears to be of increasing significance in layer flocks, but there have been no studies of the risk factors associated with outbreaks. This study aimed to investigate the possible associations between risk factors of non-infectious nature and outbreaks of mortality due to colibacillosis in flocks of caged layer hens. Information on management, biosecurity measures and housing conditions was collected in 20 flocks suffering from the disease and in 20 clinically healthy control flocks. The data were processed using multiple logistic regression. The statistical analysis demonstrated that an increase in the distance to the nearest poultry farm by 1 km was associated with a six-fold decreased risk of an outbreak of colibacillosis (odds ratio=0.16). Furthermore, a 1 l increase in cage volume per hen was associated with a 33% decrease in the risk of an outbreak (odds ratio=0.75). It was concluded that the distance between poultry farms and the hen density in the cages are important risk factors for outbreaks of colibacillosis in flocks of layer hens.", "title": "Risk factors associated with colibacillosis outbreaks in caged layer flocks." }, { "docid": "MED-1918", "text": "BACKGROUND: Telomerase activity is a predictor of long-term cellular viability, which decreases with chronic psychological distress (Epel et al., 2004). Buddhist traditions claim that meditation decreases psychological distress and promotes well-being (e.g., Dalai Lama and Cutler, 2009). Therefore, we investigated the effects of a 3-month meditation retreat on telomerase activity and two major contributors to the experience of stress: Perceived Control (associated with decreased stress) and Neuroticism (associated with increased subjective distress). We used mediation models to test whether changes in Perceived Control and Neuroticism explained meditation retreat effects on telomerase activity. In addition, we investigated whether two qualities developed by meditative practice, increased Mindfulness and Purpose in Life, accounted for retreat-related changes in the two stress-related variables and in telomerase activity. METHODS: Retreat participants (n=30) meditated for ∼6 h daily for 3 months and were compared with a wait-list control group (n=30) matched for age, sex, body mass index, and prior meditation experience. Retreat participants received instruction in concentrative meditation techniques and complementary practices used to cultivate benevolent states of mind (Wallace, 2006). Psychological measures were assessed pre- and post-retreat. Peripheral blood mononuclear cell samples were collected post-retreat for telomerase activity. Because there were clear, a priori hypotheses, 1-tailed significance criteria were used throughout. RESULTS: Telomerase activity was significantly greater in retreat participants than in controls at the end of the retreat (p<0.05). Increases in Perceived Control, decreases in Neuroticism, and increases in both Mindfulness and Purpose in Life were greater in the retreat group (p<0.01). Mediation analyses indicated that the effect of the retreat on telomerase was mediated by increased Perceived Control and decreased Neuroticism. In turn, changes in Perceived Control and Neuroticism were both partially mediated by increased Mindfulness and Purpose in Life. Additionally, increases in Purpose in Life directly mediated the telomerase group difference, whereas increases in Mindfulness did not. CONCLUSIONS: This is the first study to link meditation and positive psychological change with telomerase activity. Although we did not measure baseline telomerase activity, the data suggest that increases in perceived control and decreases in negative affectivity contributed to an increase in telomerase activity, with implications for telomere length and immune cell longevity. Further, Purpose in Life is influenced by meditative practice and directly affects both perceived control and negative emotionality, affecting telomerase activity directly as well as indirectly. Copyright © 2010 Elsevier Ltd. All rights reserved.", "title": "Intensive meditation training, immune cell telomerase activity, and psychological mediators." }, { "docid": "MED-2257", "text": "Background Low-level environmental cadmium exposure and neurotoxicity has not been well studied in adults. Our goal was to evaluate associations between neurocognitive exam scores and a biomarker of cumulative cadmium exposure among adults in the Third National Health and Nutrition Examination Survey (NHANES III). Methods NHANES III is a nationally representative cross-sectional survey of the U.S. population conducted between 1988 and 1994. We analyzed data from a subset of participants, age 20–59, who participated in a computer-based neurocognitive evaluation. There were four outcome measures: the Simple Reaction Time Test (SRTT: visual motor speed), the Symbol Digit Substitution Test (SDST: attention/perception), the Serial Digit Learning Test (SDLT) trials-to-criterion, and the SDLT total-error-score (SDLT-tests: learning recall/short-term memory). We fit multivariable-adjusted models to estimate associations between urinary cadmium concentrations and test scores. Results 5662 participants underwent neurocognitive screening, and 5572 (98%) of these had a urinary cadmium level available. Prior to multivariable-adjustment, higher urinary cadmium concentration was associated with worse performance in each of the 4 outcomes. After multivariable-adjustment most of these relationships were not significant, and age was the most influential variable in reducing the association magnitudes. However among never-smokers with no known occupational cadmium exposure the relationship between urinary cadmium and SDST score (attention/perception) was significant: a 1 μg/L increase in urinary cadmium corresponded to a 1.93% (95%CI: 0.05, 3.81) decrement in performance. Conclusions These results suggest that higher cumulative cadmium exposure in adults may be related to subtly decreased performance in tasks requiring attention and perception, particularly among those adults whose cadmium exposure is primarily though diet (no smoking or work based cadmium exposure). This association was observed among exposure levels that have been considered to be without adverse effects and these levels are common in U.S. adults. Thus further research into the potential neurocognitive effects of cadmium exposure is warranted. Because cumulative cadmium exposure may mediate some of the effects of age and smoking on cognition, adjusting for these variables may result in the underestimation of associations with cumulative cadmium exposure. Prospective studies that include never-smokers and non-occupationally exposed individuals are needed to clarify these issues.", "title": "Associations between cadmium exposure and neurocognitive test scores in a cross-sectional study of US adults" }, { "docid": "MED-1448", "text": "OBJECTIVE: To quantify per capita and aggregate medical expenditures and the value of lost productivity, including absenteeism and presenteeism, because of overweight, and grade I, II, and III obesity among U.S. employees. METHODS: Cross-sectional analysis of the 2006 Medical Expenditure Panel Survey and the 2008 National Health and Wellness Survey. RESULTS: Among men, estimates range from -$322 for overweight to $6087 for grade III obese men. For women, estimates range from $797 for overweight to $6694 for grade III. In aggregate, the annual cost attributable to obesity among full-time employees is $73.1 billion. Individuals with a body mass index >35 represent 37% of the obese population but are responsible for 61% of excess costs. CONCLUSIONS: Successful efforts to reduce the prevalence of obesity, especially among those with a body mass index >35, could result in significant savings to employers.", "title": "The costs of obesity in the workplace." }, { "docid": "MED-1996", "text": "Until recently, the majority of cases of diabetes mellitus among children and adolescents were immune-mediated type 1a diabetes. Obesity has led to a dramatic increase in the incidence of type 2 diabetes (T2DM) among children and adolescents over the past 2 decades. Obesity is strongly associated with insulin resistance, which, when coupled with relative insulin deficiency, leads to the development of overt T2DM. Children and adolescents with T2DM may experience the microvascular and macrovascular complications of this disease at younger ages than individuals who develop diabetes in adulthood, including atherosclerotic cardiovascular disease, stroke, myocardial infarction, and sudden death; renal insufficiency and chronic renal failure; limb-threatening neuropathy and vasculopathy; and retinopathy leading to blindness. Health care professionals are advised to perform the appropriate screening in children at risk for T2DM, diagnose the condition as early as possible, and provide rigorous management of the disease.", "title": "Childhood obesity and type 2 diabetes mellitus." }, { "docid": "MED-3887", "text": "Summary: Antimicrobials are valuable therapeutics whose efficacy is seriously compromised by the emergence and spread of antimicrobial resistance. The provision of antibiotics to food animals encompasses a wide variety of nontherapeutic purposes that include growth promotion. The concern over resistance emergence and spread to people by nontherapeutic use of antimicrobials has led to conflicted practices and opinions. Considerable evidence supported the removal of nontherapeutic antimicrobials (NTAs) in Europe, based on the “precautionary principle.” Still, concrete scientific evidence of the favorable versus unfavorable consequences of NTAs is not clear to all stakeholders. Substantial data show elevated antibiotic resistance in bacteria associated with animals fed NTAs and their food products. This resistance spreads to other animals and humans—directly by contact and indirectly via the food chain, water, air, and manured and sludge-fertilized soils. Modern genetic techniques are making advances in deciphering the ecological impact of NTAs, but modeling efforts are thwarted by deficits in key knowledge of microbial and antibiotic loads at each stage of the transmission chain. Still, the substantial and expanding volume of evidence reporting animal-to-human spread of resistant bacteria, including that arising from use of NTAs, supports eliminating NTA use in order to reduce the growing environmental load of resistance genes.", "title": "Food Animals and Antimicrobials: Impacts on Human Health" }, { "docid": "MED-4752", "text": "A potent link to dairy seems to exist for three hormone-responsive glands. Acne, breast cancer and prostate cancer have all been linked epidemiologically to dairy intake. Although mechanisms postulated here remain to be accurately defined, the likely link involves Insulin-like Growth Factor-1 as a general stimulant, synergized by the steroid hormones present in milk. The IGF-1 may be either absorbed from milk, or stimulated by its ingestion, or both. The 5alpha-reduced compound 5alpha-pregnanedione (5α-P) present in milk is a direct precursor of dihydrotestosterone and may act through that pathway in prostate cancer, but 5α-P has also recently been shown to be capable of inducing estrogen receptors in breast cancer cells, upregulating cancer cells' sensitivity to estrogen. The introduction of exogenous hormones and growth factors into tissues that have not evolved defensive feedback inhibition of their corresponding endogenous sources is postulated as a direct stimulatory threat to these organ systems, whether for hyperplasia or neoplasia.", "title": "Acne, dairy and cancer" }, { "docid": "MED-3243", "text": "OBJECTIVES: Considerable evidence has shown that diet can affect both the incidence and the progression of prostate cancer. The objective of this study was to determine whether men in this situation could make a change to a diet emphasizing plant-based foods and fish and to examine the effect on quality of life (QOL) and prostate-specific antigen (PSA) velocity. METHODS: A total of 36 men and their partners were randomly assigned to attend a series of 11 dietary and cooking classes that also integrated mindfulness practice as a support in making the change or a wait-list control group. Assessments were made of dietary intake, QOL, and PSA at baseline, after intervention (11 weeks), and 3 months after intervention. RESULTS: The intervention group showed significant reductions in the consumption of saturated fat and increased consumption of vegetable proteins with accompanying reductions in animal proteins, including dairy products. They also showed increased QOL. Although no significant change was found in the rate of PSA increase between the two groups, the mean PSA doubling time for the intervention group was substantially longer at the 3-month follow-up visit than that of the controls. CONCLUSIONS: Men with a increasing PSA level after primary treatment were able to make a change to a prostate-healthy diet, accompanied by increases in QOL. No significant difference was found in the log PSA slope between the two groups; however, the PSA doubling time increased substantially in the intervention group compared with that in the controls. Future trials should examine the effect of the prostate-healthy diet with a larger sample of men for a longer period.", "title": "A dietary intervention for recurrent prostate cancer after definitive primary treatment: results of a randomized pilot trial." }, { "docid": "MED-3317", "text": "Twenty-four patients, all of whom were exposed to aerosolized porcine brain tissue through work-place environment (abattoir), developed a syndrome of immune-mediated polyradiculoneuropathy; three also had central nervous system manifestations (transverse myelitis, meningoencephalitis, and aseptic meningitis). Patients had characteristic electrophysiological findings of very distal and proximal conduction slowing (prolonged distal and F-wave latencies, regions where the blood-nerve barrier is the most permeable) and all patients' serum contained a novel IgG immunofluorescence pattern. Nerve pathology, when available, showed mild changes of segmental demyelination, axonal degeneration, and inflammatory changes. Patients had meaningful improvement of symptoms and electrophysiologic findings with immune therapy and with removal of exposure to aerosolized brain tissue. We postulate that this outbreak is an auto-immune polyradiculoneuropathy triggered by occupational exposure to multiple aerosolized porcine neural tissue antigens that result in neural damage where the blood-nerve barrier is the least robust. © 2011 Peripheral Nerve Society.", "title": "Auto-immune polyradiculoneuropathy and a novel IgG biomarker in workers exposed to aerosolized porcine brain." }, { "docid": "MED-2671", "text": "Microbiology of meats has been a subject of great concern in food science and public health in recent years. Although many articles have been devoted to the microbiology of beef, pork, and poultry meats, much less has been written about microbiology of lamb meat and even less on restructured lamb meat. This article presents data on microbiology and shelf-life of fresh lamb meat; restructured meat products, restructured lamb meat products, bacteriology of restructured meat products, and important foodborne pathogens such as Salmonella, Escherichia coli O157:H7, and Listeria monocytogenes in meats and lamb meats. Also, the potential use of sodium and potassium lactates to control foodborne pathogens in meats and restructured lamb meat is reviewed This article should be of interest to all meat scientists, food scientists, and public health microbiologists who are concerned with the safety of meats in general and lamb meat in particular.", "title": "Microbiology of fresh and restructured lamb meat: a review." }, { "docid": "MED-3885", "text": "The treatment of bacterial infections is increasingly complicated by the ability of bacteria to develop resistance to antimicrobial agents. Antimicrobial agents are often categorized according to their principal mechanism of action. Mechanisms include interference with cell wall synthesis (eg, beta-lactams and glycopeptide agents), inhibition of protein synthesis (macrolides and tetracyclines), interference with nucleic acid synthesis (fluoroquinolones and rifampin), inhibition of a metabolic pathway (trimethoprim-sulfamethoxazole), and disruption of bacterial membrane structure (polymyxins and daptomycin). Bacteria may be intrinsically resistant to > or =1 class of antimicrobial agents, or may acquire resistance by de novo mutation or via the acquisition of resistance genes from other organisms. Acquired resistance genes may enable a bacterium to produce enzymes that destroy the antibacterial drug, to express efflux systems that prevent the drug from reaching its intracellular target, to modify the drug's target site, or to produce an alternative metabolic pathway that bypasses the action of the drug. Acquisition of new genetic material by antimicrobial-susceptible bacteria from resistant strains of bacteria may occur through conjugation, transformation, or transduction, with transposons often facilitating the incorporation of the multiple resistance genes into the host's genome or plasmids. Use of antibacterial agents creates selective pressure for the emergence of resistant strains. Herein 3 case histories-one involving Escherichia coli resistance to third-generation cephalosporins, another focusing on the emergence of vancomycin-resistant Staphylococcus aureus, and a third detailing multidrug resistance in Pseudomonas aeruginosa-are reviewed to illustrate the varied ways in which resistant bacteria develop.", "title": "Mechanisms of antimicrobial resistance in bacteria." }, { "docid": "MED-3800", "text": "OBJECTIVE: To review the current management of women with breast pain. OPTIONS: The effect of various treatment modes and health practices, including medications, was considered for the management of both cyclical and noncyclical breast pain. OUTCOMES: Effective and timely management of the woman with breast pain and improved quality of life. EVIDENCE: A literature search was performed to identify reports published in English between 1975 and July 2003 using MEDLINE and Cochrane Database of Systematic Reviews. VALUES: Levels of evidence, as outlined, have been determined using the criteria outlined by the Canadian Task Force on the Periodic Health Examination. Participants were the principal authors: a clinical dietitian, a surgeon oncologist, and a nurse. BENEFITS, HARMS, AND COSTS: Utilizing the information will increase knowledge, enabling a consistent approach, which will reduce the number of ineffective interventions and ensure appropriate use medications. VALIDATION: Comparison has been made with management protocols in the literature, but no clinical guidelines have been located. No formal clinical testing has taken place. SPONSOR: The Society of Obstetricians and Gynaecologists of Canada (SOGC). Work on these guidelines was initiated by team members to fill a need for practice guidelines at Winnipeg Regional Health Authority Breast Health Centre, Winnipeg, MB. RECOMMENDATIONS: 1. Education and reassurance is an integral part of the management of mastalgia and should be the first-line treatment. (II-1 A) 2. The use of a well-fitting bra that provides good support should be considered for the relief of cyclical and noncyclical mastalgia. (II-3 B) 3. A change in dose, formulation, or scheduling should be considered for women on HRT. HRT may be discontinued if appropriate. (III C) 4. Women with breast pain should not be advised to reduce caffeine intake. (1 E) 5. Vitamin E should not be considered for the treatment of mastalgia. (1 E) 6. There is presently insufficient evidence to recommend the use of evening primrose oil (EPO) in the treatment of breast pain. (II-2 C) 7. Flaxseed should be considered as a first-line treatment for cyclical mastalgia. (I A) 8. Topical non-steroidal anti-inflammatory gel, such as diclofenac 2% in pluronic lethicin organogel, should be considered for pain control for localized treatment of mastalgia. (I A) 9. Tamoxifen 10 mg daily or danazol 200 mg daily should be considered when first-line treatments are ineffective. (I A) 10. Mastectomy or partial mastectomy should not be considered an effective treatment for mastalgia. (III E).", "title": "Mastalgia." }, { "docid": "MED-3892", "text": "Mathematical models that estimate the proportion of foodborne illnesses attributable to food commodities at specific points in the food chain may be useful to risk managers and policy makers to formulate public health goals, prioritize interventions, and document the effectiveness of mitigations aimed at reducing illness. Using human surveillance data on laboratory-confirmed Salmonella infections from the Centers for Disease Control and Prevention and Salmonella testing data from U.S. Department of Agriculture Food Safety and Inspection Service's regulatory programs, we developed a point-of-processing foodborne illness attribution model by adapting the Hald Salmonella Bayesian source attribution model. Key model outputs include estimates of the relative proportions of domestically acquired sporadic human Salmonella infections resulting from contamination of raw meat, poultry, and egg products processed in the United States from 1998 through 2003. The current model estimates the relative contribution of chicken (48%), ground beef (28%), turkey (17%), egg products (6%), intact beef (1%), and pork (<1%) across 109 Salmonella serotypes found in food commodities at point of processing. While interpretation of the attribution estimates is constrained by data inputs, the adapted model shows promise and may serve as a basis for a common approach to attribution of human salmonellosis and food safety decision-making in more than one country.", "title": "Application of Bayesian Techniques to Model the Burden of Human Salmonellosis Attributable to U.S. Food Commodities at the Point of Processing: Adaptation of a Danish Model" }, { "docid": "MED-3799", "text": "Modifiable factors, including diet, might alter breast cancer risk. We used the WHI Dietary Modification (DM) trial to test the effect of the intervention on risk of benign proliferative breast disease, a condition associated with increased risk of and considered to be on the pathway to invasive breast cancer. The WHI DM trial was a randomized, controlled, primary prevention trial conducted in 40 US clinical centers from 1993–2005. 48,835 postmenopausal women, aged 50–79 years, without prior breast cancer, were enrolled. Participants were randomly assigned to the DM intervention group or to the comparison group. The intervention was designed to reduce total dietary fat intake to 20% of total energy intake, and to increase fruit and vegetable intake to ≥5 servings/day and intake of grain products to ≥6 servings/day, but resulted in smaller, albeit significant changes in practice. Participants had biennial mammograms and regular clinical breast exams. We identified women who reported breast biopsies free of cancer, obtained the histologic sections, and subjected them to standardized central review. During follow-up (average, 7.7 years), 570 incident cases of benign proliferative breast disease were ascertained in the intervention group and 793 in the comparison group. The hazard ratio for the association between DM and benign proliferative breast disease was 1.09 (95%CI, 0.98–1.23). Risk varied by levels of baseline total vitamin D intake but it varied little by levels of other baseline variables. These results suggest that a modest reduction in fat intake and increase in fruit, vegetable, and grain intake does not alter the risk of benign proliferative breast disease.", "title": "Low-fat dietary pattern and risk of benign proliferative breast disease: a randomized, controlled dietary modification trial" }, { "docid": "MED-1406", "text": "The relation between dietary magnesium intake and cardiovascular disease (CVD) or mortality was evaluated in several prospective studies, but few of them have assessed the risk of all-cause mortality, which has never been evaluated in Mediterranean adults at high cardiovascular risk. The aim of this study was to assess the association between magnesium intake and CVD and mortality risk in a Mediterranean population at high cardiovascular risk with high average magnesium intake. The present study included 7216 men and women aged 55-80 y from the PREDIMED (Prevención con Dieta Mediterránea) study, a randomized clinical trial. Participants were assigned to 1 of 2 Mediterranean diets (supplemented with nuts or olive oil) or to a control diet (advice on a low-fat diet). Mortality was ascertained by linkage to the National Death Index and medical records. We fitted multivariable-adjusted Cox regressions to assess associations between baseline energy-adjusted tertiles of magnesium intake and relative risk of CVD and mortality. Multivariable analyses with generalized estimating equation models were used to assess the associations between yearly repeated measurements of magnesium intake and mortality. After a median follow-up of 4.8 y, 323 total deaths, 81 cardiovascular deaths, 130 cancer deaths, and 277 cardiovascular events occurred. Energy-adjusted baseline magnesium intake was inversely associated with cardiovascular, cancer, and all-cause mortality. Compared with lower consumers, individuals in the highest tertile of magnesium intake had a 34% reduction in mortality risk (HR: 0.66; 95% CI: 0.45, 0.95; P < 0.01). Dietary magnesium intake was inversely associated with mortality risk in Mediterranean individuals at high risk of CVD. This trial was registered at controlled-trials.com as ISRCTN35739639.", "title": "Dietary magnesium intake is inversely associated with mortality in adults at high cardiovascular disease risk." }, { "docid": "MED-2354", "text": "A new natural anti-alpha-galactosyl IgG antibody (anti-Gal) was found to be present in high titer in the serum of every normal individual studied. The antibody was isolated by affinity chromatography on a melibiose-Sepharose column. The reactivity of the antibody was assessed by its interaction with alpha-galactosyl residues on rabbit erythrocytes (RabRBC). The specificity was determined by inhibition experiments with various carbohydrates. The anti-Gal interacts with alpha-galactosyl residues, possibly on glycolipids of human RBC (HuRBC), after removal of membrane proteins by treatment with pronase. In addition, the anti-Gal bind specifically to normal and pathologically senescent HuRBC, suggesting a physiological role for this natural antibody in the aging of RBC. The ubiquitous presence of anti-Gal in high titers throughout life implies a constant antigenic stimulation. In addition to the theoretical interest in the antibody, the study of the anti-Gal reactivity seems to bear immunodiagnostic significance. Decrease in the antibody titer was found to reflect humoral immunodeficiency disorders.", "title": "A unique natural human IgG antibody with anti-alpha-galactosyl specificity" }, { "docid": "MED-3544", "text": "Whole-body PET-scan studies in brains of tobacco smokers have shown a decrease in monoamine oxidase (MAO) activity, which reverts to control level when they quit smoking. The observed decrease in MAO activity in smokers is presumably due to their exposure to tobacco constituents that possess MAO-inhibiting properties. The inhibition of MAO activity seems, however, not to be a unique feature of tobacco smoking as subjects with Type II alcoholism have been reported to show a similar decrease in MAO activity that reverses when they cease to use alcohol. The present review summarizes the data on MAO-inhibiting tobacco constituents and explains that the decrease in MAO activity observed in alcoholics is probably due to concomitant tobacco use. It is concluded that the inhibition of MAO by constituents contained in tobacco and tobacco smoke, enhances the addiction induced by tobacco smoking.", "title": "Contribution of monoamine oxidase (MAO) inhibition to tobacco and alcohol addiction." }, { "docid": "MED-2221", "text": "Context: In 1954 the tobacco industry paid to publish the “Frank Statement to Cigarette Smokers” in hundreds of U.S. newspapers. It stated that the public's health was the industry's concern above all others and promised a variety of good-faith changes. What followed were decades of deceit and actions that cost millions of lives. In the hope that the food history will be written differently, this article both highlights important lessons that can be learned from the tobacco experience and recommends actions for the food industry. Methods: A review and analysis of empirical and historical evidence pertaining to tobacco and food industry practices, messages, and strategies to influence public opinion, legislation and regulation, litigation, and the conduct of science. Findings: The tobacco industry had a playbook, a script, that emphasized personal responsibility, paying scientists who delivered research that instilled doubt, criticizing the “junk” science that found harms associated with smoking, making self-regulatory pledges, lobbying with massive resources to stifle government action, introducing “safer” products, and simultaneously manipulating and denying both the addictive nature of their products and their marketing to children. The script of the food industry is both similar to and different from the tobacco industry script. Conclusions: Food is obviously different from tobacco, and the food industry differs from tobacco companies in important ways, but there also are significant similarities in the actions that these industries have taken in response to concern that their products cause harm. Because obesity is now a major global problem, the world cannot afford a repeat of the tobacco history, in which industry talks about the moral high ground but does not occupy it.", "title": "The Perils of Ignoring History: Big Tobacco Played Dirty and Millions Died. How Similar Is Big Food?" }, { "docid": "MED-2136", "text": "Prostate cancer (PCa) is dependent on androgen receptor signaling and aberrations of the PI3K-Akt-mTORC1 pathway mediating excessive and sustained growth signaling. The nutrient-sensitive kinase mTORC1 is upregulated in nearly 100% of advanced human PCas. Oncogenic mTORC1 signaling activates key subsets of mRNAs that cooperate in distinct steps of PCa initiation and progression. Epidemiological evidence points to increased dairy protein consumption as a major dietary risk factor for the development of PCa. mTORC1 is a master regulator of protein synthesis, lipid synthesis and autophagy pathways that couple nutrient sensing to cell growth and cancer. This review provides evidence that PCa initiation and progression are promoted by cow´s milk, but not human milk, stimulation of mTORC1 signaling. Mammalian milk is presented as an endocrine signaling system, which activates mTORC1, promotes cell growth and proliferation and suppresses autophagy. Naturally, milk-mediated mTORC1 signaling is restricted only to the postnatal growth phase of mammals. However, persistent consumption of cow´s milk proteins in humans provide highly insulinotropic branched-chain amino acids (BCAAs) provided by milk´s fast hydrolysable whey proteins, which elevate postprandial plasma insulin levels, and increase hepatic IGF-1 plasma concentrations by casein-derived amino acids. BCAAs, insulin and IGF-1 are pivotal activating signals of mTORC1. Increased cow´s milk protein-mediated mTORC1 signaling along with constant exposure to commercial cow´s milk estrogens derived from pregnant cows may explain the observed association between high dairy consumption and increased risk of PCa in Westernized societies. As well-balanced mTORC1-signaling plays an important role in appropriate prostate morphogenesis and differentiation, exaggerated mTORC1-signaling by high cow´s milk consumption predominantly during critical growth phases of prostate development and differentiation may exert long-term adverse effects on prostate health. Attenuation of mTORC1 signaling by contemporary Paleolithic diets and restriction of dairy protein intake, especially during mTORC1-dependent phases of prostate development and differentiation, may offer protection from the most common dairy-promoted cancer in men of Western societies.", "title": "The impact of cow's milk-mediated mTORC1-signaling in the initiation and progression of prostate cancer" }, { "docid": "MED-2394", "text": "Background One of the outcomes positively associated with dioxin exposure in humans is type 2 diabetes. Objectives This study was conducted in order to find the molecular biological evidence for the diabetogenic action of dioxin in adipose samples from Vietnam veterans. Methods We obtained 313 adipose tissue samples both from Vietnam veterans who were exposed to dioxin (Operation Ranch Hand) and from comparison veterans who served in Southeast Asia with no record of dioxin exposure. We conducted quantitative reverse-transcribed polymerase chain reaction studies on selected marker mRNAs from these samples. Results We found the most sensitive and reliable molecular indicator of dioxin-induced diabetes to be the ratio of mRNA of glucose transporter 4 (GLUT4) and nuclear transcription factor kappa B (NFκB), a marker of inflammation. This ratio showed significant correlations to serum dioxin residues and to fasting glucose among those in the Ranch Hand group and, surprisingly, even in the comparison group, who have low levels of dioxin comparable to the general public. Such a correlation in the comparison group was particularly significant among those with known risk factors such as obesity and family history of diabetes. Conclusions These results show that the GLUT4:NFκB ratio is a reliable marker for the diabetogenic action of dioxin, particularly at very low exposure levels that are not much higher than those found in the general public, implying a need to address current exposure levels.", "title": "Molecular Epidemiologic Evidence for Diabetogenic Effects of Dioxin Exposure in U.S. Air Force Veterans of the Vietnam War" }, { "docid": "MED-3443", "text": "Incidence of the metabolic syndrome is increasing worldwide, with notable exceptions of some Asian countries where seaweeds are commonly consumed. 13 men (mean age 47.4+/-9.9 yr) and 14 women (average age 45.6+/-12.2 yr) with at least one symptom of the metabolic syndrome were recruited in Quito Ecuador to a randomized double-blinded placebo-controlled trial. Subjects were assigned to either Group 1 (1 m placebo, followed by 1 m 4 g/d seaweed [Undaria pinnatifida]) or Group 2 (1 m of 4 g/d seaweed, followed by 1 m of 6 g/d of seaweed). Blood pressure, weight, waist circumference, inflammation biomarkers, and lipids were measured monthly. Repeated measures analysis of variance with Tukey's multiple comparison tests were used for statistical analysis. In Group 2, systolic blood pressure decreased 10.5 mmHg after a month of 6 g/d seaweed (95% CI: 4.1, 16.8 mmHg; p<0.05), primarily in subjects with high-normal baseline blood pressure. Waist circumference changed only for women participants, with a 2.4 cm decrease in Group 1 after treatment with placebo (95% CI: 1.0, 3.7 cm; p<0.01). In Group 2, women had a mean decrease of 2.1 cm after 4 g/d (95% CI: 0.4, 3.7 cm; p<0.05) and a further 1.8 cm decrease after 1 m 6 g/d seaweed (95 % CI: 0.1, 3.4, p<0.05). No other changes were observed. Consumption of 4 to 6 g/d seaweed, typical for most people in Japan, may be associated with low metabolic syndrome prevalence.", "title": "Could dietary seaweed reverse the metabolic syndrome?" }, { "docid": "MED-2498", "text": "Dietary restriction (DR) and reduced growth factor signaling both elevate resistance to oxidative stress, reduce macromolecular damage, and increase lifespan in model organisms. In rodents, both DR and decreased growth factor signaling reduce the incidence of tumors and slow down cognitive decline and aging. DR reduces cancer and cardiovascular disease and mortality in monkeys, and reduces metabolic traits associated with diabetes, cardiovascular disease and cancer in humans. Neoplasias and diabetes are also rare in humans with loss of function mutations in the growth hormone receptor. DR and reduced growth factor signaling may thus slow aging by similar, evolutionarily conserved, mechanisms. We review these conserved anti-aging pathways in model organisms, discuss their link to disease prevention in mammals, and consider the negative side effects that might hinder interventions intended to extend healthy lifespan in humans.", "title": "Dietary Restriction, Growth Factors and Aging: from yeast to humans" }, { "docid": "MED-1450", "text": "Background/objectives: To determine the effects of a low-fat plant-based diet program on anthropometric and biochemical measures in a multicenter corporate setting. Subjects/methods: Employees from 10 sites of a major US company with body mass index ⩾25 kg/m2 and/or previous diagnosis of type 2 diabetes were randomized to either follow a low-fat vegan diet, with weekly group support and work cafeteria options available, or make no diet changes for 18 weeks. Dietary intake, body weight, plasma lipid concentrations, blood pressure and glycated hemoglobin (HbA1C) were determined at baseline and 18 weeks. Results: Mean body weight fell 2.9 kg and 0.06 kg in the intervention and control groups, respectively (P<0.001). Total and low-density lipoprotein (LDL) cholesterol fell 8.0 and 8.1 mg/dl in the intervention group and 0.01 and 0.9 mg/dl in the control group (P<0.01). HbA1C fell 0.6 percentage point and 0.08 percentage point in the intervention and control group, respectively (P<0.01). Among study completers, mean changes in body weight were −4.3 kg and −0.08 kg in the intervention and control groups, respectively (P<0.001). Total and LDL cholesterol fell 13.7 and 13.0 mg/dl in the intervention group and 1.3 and 1.7 mg/dl in the control group (P<0.001). HbA1C levels decreased 0.7 percentage point and 0.1 percentage point in the intervention and control group, respectively (P<0.01). Conclusions: An 18-week dietary intervention using a low-fat plant-based diet in a corporate setting improves body weight, plasma lipids, and, in individuals with diabetes, glycemic control.", "title": "A multicenter randomized controlled trial of a plant-based nutrition program to reduce body weight and cardiovascular risk in the corporate setting: the GEICO study" }, { "docid": "MED-2572", "text": "In traditional cultures, balancing health with a balanced lifestyle was a core belief. The diseases of modern civilization were rare. Indigenous people have patterns of illness very different from Western civilization; yet, they rapidly develop diseases once exposed to Western foods and lifestyles. Food and medicine were interwoven. All cultures used special or functional foods to prevent disease. Food could be used at different times either as food or medicine. Foods, cultivation, and cooking methods maximized community health and well-being. With methods passed down through generations, cooking processes were utilized that enhanced mineral and nutrient bioavailability. This article focuses on what researchers observed about the food traditions of indigenous people, their disease patterns, the use of specific foods, and the environmental factors that affect people who still eat traditional foods.", "title": "Traditional non-Western diets." }, { "docid": "MED-3351", "text": "Based on evidence that the color red elicits avoidance motivation across contexts (Mehta & Zhu, 2009), two studies investigated the effect of the color red on snack food and soft drink consumption. In line with our hypothesis, participants drank less from a red labeled cup than from a blue labeled cup (Study 1), and ate less snack food from a red plate than from a blue or white plate (Study 2). The results suggest that red functions as a subtle stop signal that works outside of focused awareness and thereby reduces incidental food and drink intake. Copyright © 2012 Elsevier Ltd. All rights reserved.", "title": "The color red reduces snack food and soft drink intake." }, { "docid": "MED-3591", "text": "Background In recent decades, young men in some industrialized areas have reportedly experienced a decrease in semen quality. Objective We examined effects of perinatal dioxin exposure on sperm quality and reproductive hormones. Methods We investigated sperm quality and hormone concentrations in 39 sons (mean age, 22.5 years) born between 1977 and 1984 to mothers exposed to dioxin after the accident in Seveso, Italy (1976), and 58 comparisons (mean age, 24.6 years) born to mothers exposed only to background dioxin. Maternal dioxin levels at conception were extrapolated from the concentrations measured in 1976 serum samples. Results The 21 breast-fed sons whose exposed mothers had a median serum dioxin concentration as low as 19 ppt at conception had lower sperm concentration (36.3 vs. 86.3 million/mL; p = 0.002), total count (116.9 vs. 231.1; p = 0.02), progressive motility (35.8 vs. 44.2%; p = 0.03), and total motile count (38.7 vs. 98 million; p = 0.01) than did the 36 breast-fed comparisons. The 18 formula-fed exposed and the 22 formula-fed and 36 breast-fed comparisons (maternal dioxin background 10 ppt at conception) had no sperm-related differences. Follicle-stimulating hormone was higher in the breast-fed exposed group than in the breast-fed comparisons (4.1 vs. 2.63 IU/L; p = 0.03) or the formula-fed exposed (4.1 vs. 2.6 IU/L; p = 0.04), and inhibin B was lower (breast-fed exposed group, 70.2; breast-fed comparisons, 101.8 pg/mL, p = 0.01; formula-fed exposed, 99.9 pg/mL, p = 0.02). Conclusions In utero and lactational exposure of children to relatively low dioxin doses can permanently reduce sperm quality.", "title": "Perinatal Exposure to Low Doses of Dioxin Can Permanently Impair Human Semen Quality" }, { "docid": "MED-1602", "text": "Background: Nitrate and nitrite are present in many foods and are precursors of N-nitroso compounds, known animal carcinogens and potential human carcinogens. We prospectively investigated the association between nitrate and nitrite intake from dietary sources and risk of renal cell carcinoma (RCC) overall and clear cell and papillary histological subtypes in the NIH-AARP Diet and Health Study. Methods: Nitrate and nitrite intakes were estimated from a 124-item food frequency questionnaire. Over a mean follow-up of 9 years, we identified 1816 RCC cases (n=498, clear cell; n=115, papillary cell) among 491 841 participants. Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Individuals in the highest quintile of nitrite intake from animal sources compared with those in the lowest quintile, had an increased risk of total RCC and clear cell subtype (HR=1.28, 95% CI, 1.10–1.49 and HR=1.68, 95% CI, 1.25–2.27, respectively). Nitrite from processed meats and other animal sources were associated with increased clear cell adenocarcinoma risk (HR=1.33, 95% CI, 1.01–1.76 and HR=1.78, 95% CI, 1.34–2.36, respectively). We found no association for nitrite intake from plant sources or nitrate intake overall. Conclusion: Our findings suggest that nitrite from animal sources may increase the risk of RCC, particularly clear cell adenocarcinomas.", "title": "Dietary intake of nitrate and nitrite and risk of renal cell carcinoma in the NIH-AARP Diet and Health Study" }, { "docid": "MED-3589", "text": "OBJECTIVE: To compare dietary habits in normospermic and oligoasthenoteratospermic patients attending a reproductive assisted clinic. DESIGN: An observational, analytical case-control study. SETTING: Private fertility clinics. PATIENT(S): Thirty men with poor semen quality (cases) and 31 normospermic control couples attending our fertility clinics. INTERVENTION(S): We recorded dietary habits and food consumption using a food frequency questionnaire adapted to meet specific study objectives. Analysis of semen parameters, hormone levels, Y microdeletions, and karyotypes were also carried out. MAIN OUTCOME MEASURE(S): Frequency of intake food items were registered in a scale with nine categories ranging from no consumption to repeated daily consumption. RESULT(S): Controls had a higher intake of skimmed milk, shellfish, tomatoes, and lettuce, and cases consumed more yogurt, meat products, and potatoes. In the logistic regression model cases had lower intake of lettuce and tomatoes, fruits (apricots and peaches), and significantly higher intake of dairy and meat processed products. CONCLUSION(S): Frequent intake of lipophilic foods like meat products or milk may negatively affect semen quality in humans, whereas some fruits or vegetables may maintain or improve semen quality.", "title": "Food intake and its relationship with semen quality: a case-control study." }, { "docid": "MED-4167", "text": "Antibiotic entry into the water environment has been of growing concern. However, few investigations have been performed to examine the potential for indirect human exposure to environmental antibiotic residues. We evaluated the contribution of drinking water and major food consumption to inadvertent intake of antibiotic residues among general human population in Korea. We estimated daily human intake of six antibiotics, i.e., sulfamethazine (SMZ), sulfamethoxazole (SMX), sulfathiazole (STZ), trimethoprim (TMP), enrofloxacin (EFX), and roxithromycin (RTM), by measuring the concentrations of the antibiotics and their major metabolites in urine from general population in Korea (n=541). In addition, we measured antibiotics from source water of drinking water as well as in tap water samples, and surveyed water consumption rates among the study population. To assess the contribution of dietary factor, we also surveyed consumption pattern for several major foods which are suspected of antibiotics residue. SMZ, Sulfamethazine-N4-acetyl (SMZ-N4), TMP, EFX, ciprofloxacin (CFX), and RTM were detected up to 448, 6210, 11,900, 6970, 32,400, and 151pg/ml in the urine samples, respectively. Estimates of daily intake of major antibiotics did not appear to be related with consumption of drinking water although antibiotics were frequently detected in source waters (10-67ng/l). Consumption of several foods correlated significantly with urinary excretion of several antibiotics. Daily intake estimates of EFX and CFX were associated with consumption of beef, pork, and dairy products; those of SMZ and TMP associated with pork and dairy products; and that of TMP related with raw fish. Daily antibiotics intake estimates however did not exceed the acceptable daily intake levels. Copyright 2010 Elsevier Inc. All rights reserved.", "title": "Influence of water and food consumption on inadvertent antibiotics intake among general population." }, { "docid": "MED-5239", "text": "Epidemiological evidence points to increased dairy and meat consumption, staples of the Western diet, as major risk factors for the development of type 2 diabetes (T2D). This paper presents a new concept and comprehensive review of leucine-mediated cell signaling explaining the pathogenesis of T2D and obesity by leucine-induced over-stimulation of mammalian target of rapamycin complex 1 (mTORC1). mTORC1, a pivotal nutrient-sensitive kinase, promotes growth and cell proliferation in response to glucose, energy, growth factors and amino acids. Dairy proteins and meat stimulate insulin/insulin-like growth factor 1 signaling and provide high amounts of leucine, a primary and independent stimulator for mTORC1 activation. The downstream target of mTORC1, the kinase S6K1, induces insulin resistance by phosphorylation of insulin receptor substrate-1, thereby increasing the metabolic burden of β-cells. Moreover, leucine-mediated mTORC1-S6K1-signaling plays an important role in adipogenesis, thus increasing the risk of obesity-mediated insulin resistance. High consumption of leucine-rich proteins explains exaggerated mTORC1-dependent insulin secretion, increased β-cell growth and β-cell proliferation promoting an early onset of replicative β-cell senescence with subsequent β-cell apoptosis. Disturbances of β-cell mass regulation with increased β-cell proliferation and apoptosis as well as insulin resistance are hallmarks of T2D, which are all associated with hyperactivation of mTORC1. In contrast, the anti-diabetic drug metformin antagonizes leucine-mediated mTORC1 signaling. Plant-derived polyphenols and flavonoids are identified as natural inhibitors of mTORC1 and exert anti-diabetic and anti-obesity effects. Furthermore, bariatric surgery in obesity reduces increased plasma levels of leucine and other branched-chain amino acids. Attenuation of leucine-mediated mTORC1 signaling by defining appropriate upper limits of the daily intake of leucine-rich animal and dairy proteins may offer a great chance for the prevention of T2D and obesity, as well as other epidemic diseases of civilization with increased mTORC1 signaling, especially cancer and neurodegenerative diseases, which are frequently associated with T2D.", "title": "Leucine signaling in the pathogenesis of type 2 diabetes and obesity" }, { "docid": "MED-2260", "text": "Faecal elimination of lead and cadmium in 16 subjects who changed from a mixed diet to a lactovegetarian diet has been studied. The faecal weight increased significantly following the change to the vegetarian diet, partly because of increased water content. There was a large inter-individual variation in faecal elimination of lead and cadmium during both the mixed-diet period (range 14 to 118, median 31 micrograms Pb/day; range 4.5 to 21, median 12 micrograms Cd/day) and the vegetarian diet period (range 19 to 136, median 42 micrograms Pb/day; range 6.1 to 24, median 14 micrograms Cd/day). There was a tendency towards increased faecal elimination of lead and cadmium following the change to the vegetarian diet, but the differences were not statistically significant.", "title": "Faecal elimination of lead and cadmium in subjects on a mixed and a lactovegetarian diet." }, { "docid": "MED-3925", "text": "This study describes how foods rich in fisetin and hexacosanol added to a strict diet reversed most symptoms of Parkinson's disease (PD) in one patient. This is a case report involving outpatient care. The subject was a dietitian diagnosed with idiopathic PD in 2000 at the age of 53 years old, with a history of exposure to neurotoxins and no family history of PD. A basic diet started in 2000 consisted of predominantly fruits, vegetables, 100% whole grains, extra virgin olive oil, nuts, seeds, nonfat milk products, tea, coffee, spices, small amounts of dark chocolate, and less than 25 g of animal fat daily. The basic diet alone failed to prevent decline due to PD. In 2009, the basic diet was enhanced with a good dietary source of both fisetin and hexacosanol. Six months after the patient started the enhanced diet rich in fisetin and hexacosanol, a clinically significant improvement in symptoms was noted; the patient's attending neurologist reported that the clinical presentation of cogwheel rigidity, micrographia, bradykinesia, dystonia, constricted arm swing with gait, hypomimia, and retropulsion appeared to be resolved. The only worsening of symptoms occurred when the diet was not followed precisely. Little improvement in tremor or seborrhea was observed. The clinical improvement has persisted to date. To the best of our knowledge, this is the first case where adjunctive diet therapy resulted in a significant reduction of symptoms of PD without changing the type or increasing the amount of medications.", "title": "A diet low in animal fat and rich in N-hexacosanol and fisetin is effective in reducing symptoms of Parkinson's disease." }, { "docid": "MED-2844", "text": "OBJECTIVE It is important to identify modifiable factors that may lower gestational diabetes mellitus (GDM) risk. Dietary iron is of particular interest given that iron is a strong prooxidant, and high body iron levels can damage pancreatic β-cell function and impair glucose metabolism. The current study is to determine if prepregnancy dietary and supplemental iron intakes are associated with the risk of GDM. RESEARCH DESIGN AND METHODS A prospective study was conducted among 13,475 women who reported a singleton pregnancy between 1991 and 2001 in the Nurses’ Health Study II. A total of 867 incident GDM cases were reported. Pooled logistic regression was used to estimate the relative risk (RR) of GDM by quintiles of iron intake controlling for dietary and nondietary risk factors. RESULTS Dietary heme iron intake was positively and significantly associated with GDM risk. After adjusting for age, BMI, and other risk factors, RRs (95% CIs) across increasing quintiles of heme iron were 1.0 (reference), 1.11 (0.87–1.43), 1.31 (1.03–1.68), 1.51 (1.17–1.93), and 1.58 (1.21–2.08), respectively (P for linear trend 0.0001). The multivariate adjusted RR for GDM associated with every 0.5-mg per day of increase in intake was 1.22 (1.10–1.36). No significant associations were observed between total dietary, nonheme, or supplemental iron intake and GDM risk. CONCLUSIONS These findings suggest that higher prepregnancy intake of dietary heme iron is associated with an increased GDM risk.", "title": "A Prospective Study of Prepregnancy Dietary Iron Intake and Risk for Gestational Diabetes Mellitus" }, { "docid": "MED-1586", "text": "Women with a multiple pregnancy face greater risks for themselves and their infants than women pregnant with one child. Pre-pregnancy care should focus on avoiding multiple pregnancy. Early prenatal care centres on determining chorionicity and screening for fetal anomalies, with later care focusing on the presentation, prediction and management of preterm birth, and intrauterine growth restriction. The optimal timing and mode of birth are the focus of current multicentre, randomised, controlled trials. However, the data from such trials on care for women with a multiple pregnancy are limited. Many areas of care require better-quality information, including when using assisted reproductive techniques, the optimal number of embryos to be transferred, care after the diagnosis of chorionicity, and the benefits of specialised multiple pregnancy clinics. Better-quality information is required to inform clinical practice for women with complications of multiple pregnancy, including monoamniotic twin pregnancy, treatment of twin-to-twin transfusion syndrome, and care following single intrauterine fetal death.", "title": "Evidence-based care of women with a multiple pregnancy." }, { "docid": "MED-3586", "text": "BACKGROUND The objective of this study was to examine the relation between dietary fats and semen quality parameters. METHODS Data from 99 men with complete dietary and semen quality data were analyzed. Fatty acid levels in sperm and seminal plasma were measured using gas chromatography in a subgroup of men (n = 23). Linear regression was used to determine associations while adjusting for potential confounders. RESULTS Men were primarily Caucasian (89%) with a mean (SD) age of 36.4 (5.3) years; 71% were overweight or obese; and 67% were never smokers. Higher total fat intake was negatively related to total sperm count and concentration. Men in the highest third of total fat intake had 43% (95% confidence interval (CI): 62–14%) lower total sperm count and 38% (95% CI: 58–10%) lower sperm concentration than men in the lowest third (Ptrend = 0.01). This association was driven by intake of saturated fats. Levels of saturated fatty acids in sperm were also negatively related to sperm concentration (r= −0.53), but saturated fat intake was unrelated to sperm levels (r = 0.09). Higher intake of omega-3 polyunsaturated fats was related to a more favorable sperm morphology. Men in the highest third of omega-3 fatty acids had 1.9% (0.4–3.5%) higher normal morphology than men in the lowest third (Ptrend = 0.02). CONCLUSIONS In this preliminary cross-sectional study, high intake of saturated fats was negatively related to sperm concentration whereas higher intake of omega-3 fats was positively related to sperm morphology. Further, studies with larger samples are now required to confirm these findings.", "title": "Dietary fat and semen quality among men attending a fertility clinic" }, { "docid": "MED-3354", "text": "The luminance contrast between facial features and facial skin is greater in women than in men, and women's use of make-up enhances this contrast. In black-and-white photographs, increased luminance contrast enhances femininity and attractiveness in women's faces, but reduces masculinity and attractiveness in men's faces. In Caucasians, much of the contrast between the lips and facial skin is in redness. Red lips have been considered attractive in women in geographically and temporally diverse cultures, possibly because they mimic vasodilation associated with sexual arousal. Here, we investigate the effects of lip luminance and colour contrast on the attractiveness and sex typicality (masculinity/femininity) of human faces. In a Caucasian sample, we allowed participants to manipulate the colour of the lips in colour-calibrated face photographs along CIELab L* (light--dark), a* (red--green), and b* (yellow--blue) axes to enhance apparent attractiveness and sex typicality. Participants increased redness contrast to enhance femininity and attractiveness of female faces, but reduced redness contrast to enhance masculinity of men's faces. Lip blueness was reduced more in female than male faces. Increased lightness contrast enhanced the attractiveness of both sexes, and had little effect on perceptions of sex typicality. The association between lip colour contrast and attractiveness in women's faces may be attributable to its association with oxygenated blood perfusion indicating oestrogen levels, sexual arousal, and cardiac and respiratory health.", "title": "Lip colour affects perceived sex typicality and attractiveness of human faces." }, { "docid": "MED-1774", "text": "This study measured 21 persistent, bioaccumulative, and toxic (PBT) pollutants in the US milk supply. Since milk fat is likely to be among the highest dietary sources of exposure to PBTs, it is important to understand their levels in this food. Nationwide samples were collected from 45 dairy plants in July of 2000 and again in January 2001. The levels of all chemicals in the chlorobenzene, pesticide and other halogenated organic groups were determined to be below their detection limits in all samples. National averages were computed for 11 chemicals or chemical groups found above the detection limits. The national average CDD/CDF and PCB TEQ concentrations were 14.30 and 8.64 pg/l, respectively, for a total of 22.94 pg/l. These levels are about half the values found in a similar study conducted in 1996. If this difference is in fact indicative of declining milk levels and assuming exposure levels from nondairy pathways have remained the same over this time period, this would result in an overall decrease in adult background dioxin exposure of 14%. Six PAHs were detected with national averages ranging from 40 to 777 ng/l. Cadmium concentrations ranged from 150 to 870 ng/l with a national average of 360 ng/l. Lead concentrations were consistently higher than those of cadmium, ranging from 630 to 1950 ng/l with a national average of 830 ng/l. PAHs showed the strongest seasonal/geographic differences, with higher levels in winter than summer, north than south and east than west. Average adult daily intakes from total milk fat ingestion were computed for all detected compounds and compared to total intakes from all pathways: CDD/CDF/PCB TEQs: 8 vs. 55 pg/day, PAHs: 0.6 vs. 3 micro g/day, lead: 0.14 vs. 4-6 micro g/day, and cadmium: 0.06 vs. 30 micro g/day.", "title": "A national survey of persistent, bioaccumulative, and toxic (PBT) pollutants in the United States milk supply." }, { "docid": "MED-4877", "text": "BACKGROUND: Telomeres are protective DNA-protein complexes at the end of linear chromosomes that promote chromosomal stability. Telomere shortness in human beings is emerging as a prognostic marker of disease risk, progression, and premature mortality in many types of cancer, including breast, prostate, colorectal, bladder, head and neck, lung, and renal cell. Telomere shortening is counteracted by the cellular enzyme telomerase. Lifestyle factors known to promote cancer and cardiovascular disease might also adversely affect telomerase function. However, previous studies have not addressed whether improvements in nutrition and lifestyle are associated with increases in telomerase activity. We aimed to assess whether 3 months of intensive lifestyle changes increased telomerase activity in peripheral blood mononuclear cells (PBMC). METHODS: 30 men with biopsy-diagnosed low-risk prostate cancer were asked to make comprehensive lifestyle changes. The primary endpoint was telomerase enzymatic activity per viable cell, measured at baseline and after 3 months. 24 patients had sufficient PBMCs needed for longitudinal analysis. This study is registered on the ClinicalTrials.gov website, number NCT00739791. FINDINGS: PBMC telomerase activity expressed as natural logarithms increased from 2.00 (SD 0.44) to 2.22 (SD 0.49; p=0.031). Raw values of telomerase increased from 8.05 (SD 3.50) standard arbitrary units to 10.38 (SD 6.01) standard arbitrary units. The increases in telomerase activity were significantly associated with decreases in low-density lipoprotein (LDL) cholesterol (r=-0.36, p=0.041) and decreases in psychological distress (r=-0.35, p=0.047). INTERPRETATION: Comprehensive lifestyle changes significantly increase telomerase activity and consequently telomere maintenance capacity in human immune-system cells. Given this finding and the pilot nature of this study, we report these increases in telomerase activity as a significant association rather than inferring causation. Larger randomised controlled trials are warranted to confirm the findings of this study.", "title": "Increased telomerase activity and comprehensive lifestyle changes: a pilot study." }, { "docid": "MED-3096", "text": "Background and objectives: Uncooked meat and poultry products are commonly enhanced by food processors using phosphate salts. The addition of potassium and phosphorus to these foods has been recognized but not quantified. Design, setting, participants, & measurements: We measured the phosphorus, potassium, and protein content of 36 uncooked meat and poultry products: Phosphorus using the Association of Analytical Communities (AOAC) official method 984.27, potassium using AOAC official method 985.01, and protein using AOAC official method 990.03. Results: Products that reported the use of additives had an average phosphate-protein ratio 28% higher than additive free products; the content ranged up to almost 100% higher. Potassium content in foods with additives varied widely; additive free products all contained <387 mg/100 g, whereas five of the 25 products with additives contained at least 692 mg/100 g (maximum 930 mg/100 g). Most but not all foods with phosphate and potassium additives reported the additives (unquantified) on the labeling; eight of 25 enhanced products did not list the additives. The results cannot be applied to other products. The composition of the food additives used by food processors may change over time. Conclusions: Uncooked meat and poultry products that are enhanced may contain additives that increase phosphorus and potassium content by as much as almost two- and three-fold, respectively; this modification may not be discernible from inspection of the food label.", "title": "Original Articles: Phosphorus and Potassium Content of Enhanced Meat and Poultry Products: Implications for Patients Who Receive Dialysis" }, { "docid": "MED-1795", "text": "Objective To determine whether individual fruits are differentially associated with risk of type 2 diabetes. Design Prospective longitudinal cohort study. Setting Health professionals in the United States. Participants 66 105 women from the Nurses’ Health Study (1984-2008), 85 104 women from the Nurses’ Health Study II (1991-2009), and 36 173 men from the Health Professionals Follow-up Study (1986-2008) who were free of major chronic diseases at baseline in these studies. Main outcome measure Incident cases of type 2 diabetes, identified through self report and confirmed by supplementary questionnaires. Results During 3 464 641 person years of follow-up, 12 198 participants developed type 2 diabetes. After adjustment for personal, lifestyle, and dietary risk factors of diabetes, the pooled hazard ratio of type 2 diabetes for every three servings/week of total whole fruit consumption was 0.98 (95% confidence interval 0.96 to 0.99). With mutual adjustment of individual fruits, the pooled hazard ratios of type 2 diabetes for every three servings/week were 0.74 (0.66 to 0.83) for blueberries, 0.88 (0.83 to 0.93) for grapes and raisins, 0.89 (0.79 to 1.01) for prunes, 0.93 (0.90 to 0.96) for apples and pears, 0.95 (0.91 to 0.98) for bananas, 0.95 (0.91 to 0.99) for grapefruit, 0.97 (0.92 to 1.02) for peaches, plums, and apricots, 0.99 (0.95 to 1.03) for oranges, 1.03 (0.96 to 1.10) for strawberries, and 1.10 (1.02 to 1.18) for cantaloupe. The pooled hazard ratio for the same increment in fruit juice consumption was 1.08 (1.05 to 1.11). The associations with risk of type 2 diabetes differed significantly among individual fruits (P<0.001 in all cohorts). Conclusion Our findings suggest the presence of heterogeneity in the associations between individual fruit consumption and risk of type 2 diabetes. Greater consumption of specific whole fruits, particularly blueberries, grapes, and apples, is significantly associated with a lower risk of type 2 diabetes, whereas greater consumption of fruit juice is associated with a higher risk.", "title": "Fruit consumption and risk of type 2 diabetes: results from three prospective longitudinal cohort studies" }, { "docid": "MED-5197", "text": "BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs) are carcinogens formed in or on the surface of well-done meat, cooked at high temperature. METHODS: We estimated breast cancer risk in relation to intake of cooked meat in a population-based, case-control study (1508 cases and 1556 controls) conducted in Long Island, NY from 1996 to 1997. Lifetime intakes of grilled or barbecued and smoked meats were derived from the interviewer-administered questionnaire data. Dietary intakes of PAH and HCA were derived from the self-administered modified Block food frequency questionnaire of intake 1 year before reference date. Unconditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Modest increased risk was observed among postmenopausal, but not premenopausal, women consuming the most grilled or barbecued and smoked meats over the life course (OR = 1.47; CI = 1.12-1.92 for highest vs. lowest tertile of intake). Postmenopausal women with low fruit and vegetable intake, but high lifetime intake of grilled or barbecued and smoked meats, had a higher OR of 1.74 (CI = 1.20-2.50). No associations were observed with the food frequency questionnaire-derived intake measures of PAHs and HCAs, with the possible exception of benzo(alpha)pyrene from meat among postmenopausal women whose tumors were positive for both estrogen receptors and progesterone receptors (OR = 1.47; CI = 0.99-2.19). CONCLUSIONS: These results support the accumulating evidence that consumption of meats cooked by methods that promote carcinogen formation may increase risk of postmenopausal breast cancer.", "title": "Cooked meat and risk of breast cancer--lifetime versus recent dietary intake." }, { "docid": "MED-1919", "text": "Telomerases constitute a group of specialized ribonucleoprotein enzymes that remediate chromosomal shrinkage resulting from the “end-replication” problem. Defects in telomere length regulation are associated with several diseases as well as with aging and cancer. Despite significant progress in understanding the roles of telomerase, the complete structure of the human telomerase enzyme bound to telomeric DNA remains elusive, with the detailed molecular mechanism of telomere elongation still unknown. By application of computational methods for distant homology detection, comparative modeling, and molecular docking, guided by available experimental data, we have generated a three-dimensional structural model of a partial telomerase elongation complex composed of three essential protein domains bound to a single-stranded telomeric DNA sequence in the form of a heteroduplex with the template region of the human RNA subunit, TER. This model provides a structural mechanism for the processivity of telomerase and offers new insights into elongation. We conclude that the RNA∶DNA heteroduplex is constrained by the telomerase TEN domain through repeated extension cycles and that the TEN domain controls the process by moving the template ahead one base at a time by translation and rotation of the double helix. The RNA region directly following the template can bind complementarily to the newly synthesized telomeric DNA, while the template itself is reused in the telomerase active site during the next reaction cycle. This first structural model of the human telomerase enzyme provides many details of the molecular mechanism of telomerase and immediately provides an important target for rational drug design.", "title": "Human telomerase model shows the role of the TEN domain in advancing the double helix for the next polymerization step" }, { "docid": "MED-2376", "text": "Endothelial dysfunction is considered an important prognostic factor in atherosclerosis. To determine the long-term association of brachial artery flow-mediated dilation (FMD) and adverse cardiovascular (CV) events in healthy subjects, we prospectively assessed brachial FMD in 618 consecutive healthy subjects with no apparent heart disease, 387 men (63%), and mean age 54 ± 11 years. After overnight fasting and discontinuation of all medications for ≥12 hours, FMD was assessed using high-resolution linear array ultrasound. Subjects were divided into 2 groups: FMD ≤11.3% (n = 309) and >11.3% (n = 309), where 11.3% is the median FMD, and were comparable regarding CV risk factors, lipoproteins, fasting glucose, C-reactive protein, concomitant medications, and Framingham 10-year risk score. In a mean clinical follow-up of 4.6 ± 1.8 years, the composite CV events (all-cause mortality, nonfatal myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting, and percutaneous coronary interventions) were significantly more common in subjects with FMD ≤11.3% rather than >11.3% (15.2% vs 1.2%, p = 0.0001, respectively). Univariate analysis demonstrated that the median FMD significantly predicted CV events (odds ratio 2.78, 95% CI 1.35 to 5.71, p <0.001). Multivariate analysis, controlling for traditional CV risk factors, demonstrated that median FMD was the best independent predictor of long-term CV adverse events (odds ratio 2.93, 95% CI 1.28 to 6.68, p <0.001). In conclusion, brachial artery median FMD independently predicts long-term adverse CV events in healthy subjects with no apparent heart disease in addition to those derived from traditional risk factor assessment. Copyright © 2014 Elsevier Inc. All rights reserved.", "title": "Usefulness of brachial artery flow-mediated dilation to predict long-term cardiovascular events in subjects without heart disease." }, { "docid": "MED-3933", "text": "In this study, the effects of a diet rich in insoluble fiber (DRIF) on motor disability and the peripheral pharmacokinetics of orally administered L-dopa in Parkinsonian patients with marked constipation are analyzed. We found a useful effect of a DRIF on plasma L-dopa concentration and motor function. The greatest effect on the plasma L-dopa levels was found early (at 30 and 60 min) after oral administration. There was a relationship between the improvement of constipation and the higher bioavailability of L-dopa. DRIF can be a coadjuvant treatment in patients with Parkinson's disease.", "title": "Clinical and pharmacokinetic effects of a diet rich in insoluble fiber on Parkinson disease." }, { "docid": "MED-5189", "text": "Recent case-control studies suggested that dairy product consumption is an important risk factor for testicular cancer. We examined the association between consumption of dairy products, especially milk, milk fat, and galactose, and testicular cancer in a population-based case-control study including 269 case and 797 controls (response proportions of 76% and 46%, respectively). Dietary history was assessed by food frequency questions for the index persons and through their mothers including diet 1 year before interview and diet at age 17 years. We used conditional logistic regression to calculate odds ratios as estimates of the relative risk (RR), 95% confidence intervals (95% CI), and to control for social status and height. The RR of testicular cancer was 1.37 (95% CI, 1.12-1.68) per additional 20 servings of milk per month (each 200 mL) in adolescence. This elevated overall risk was mainly due to an increased risk for seminoma (RR, 1.66; 95% CI, 1.30-2.12) per additional 20 milk servings per month. The RR for seminoma was 1.30 (95% CI, 1.15-1.48) for each additional 200 g milk fat per month and was 2.01 (95% CI, 1.41-2.86) for each additional 200 g galactose per month during adolescence. Our results suggest that milk fat and/or galactose may explain the association between milk and dairy product consumption and seminomatous testicular cancer.", "title": "Adolescent milk fat and galactose consumption and testicular germ cell cancer." }, { "docid": "MED-1926", "text": "OBJECTIVE: It has been reported that women benefit from the maintenance of telomere length by estrogen. Exercise may favorably influence telomere length, although results are inconsistent regarding the duration and type of exercise and the cell type used to measure telomere length. The purpose of this study was to investigate the relationship between habitual physical exercise and telomere length in peripheral blood mononuclear cells (PBMCs) in postmenopausal women. Postmenopausal women were chosen as study participants because they are typically estrogen deficient. METHODS: This experimental-control, cross-sectional study included 44 healthy, nondiabetic, nonsmoking, postmenopausal women. Habitual exercisers and sedentary participants were matched for age and body mass index. Body weight, height, blood pressure, and waist and hip circumference were measured. Mitochondrial DNA copy number and telomere length in PBMCs were determined, and biochemical tests were performed. Habitual physical exercise was defined as combined aerobic and resistance exercise performed for at least 60 minutes per session more than three times a week for more than 12 months. RESULTS: The mean age of all participants was 58.11 ± 6.84 years, and participants in the habitual exercise group had been exercising more than three times per week for an average of 19.23 ± 5.15 months. Serum triglyceride levels (P = 0.01), fasting insulin concentrations (P < 0.01), and homeostasis model assessment of insulin resistance (P < 0.01) were significantly lower and high-density lipoprotein cholesterol levels (P < 0.01), circulating adiponectin (P < 0.01), mitochondrial DNA copy number (P < 0.01), and telomere length (P < 0.01) were significantly higher in the habitual exercise group than in the sedentary group. In a stepwise multiple regression analysis, habitual exercise (β = 0.522, P < 0.01) and adiponectin levels (β = 0.139, P = 0.03) were the independent factors associated with the telomere length of PBMCs in postmenopausal women. CONCLUSIONS: Habitual physical exercise is associated with greater telomere length in postmenopausal women. This finding suggests that habitual physical exercise in postmenopausal women may reduce telomere attrition.", "title": "Habitual physical exercise has beneficial effects on telomere length in postmenopausal women." }, { "docid": "MED-2365", "text": "Twenty-five patients living in a tick-endemic region of Sydney, New South Wales developed red meat allergy after experiencing large local reactions to tick bites. This represents a potentially novel cross-reaction between an arthropod and a food protein. (MJA 2009; 190: 510-511).", "title": "An association between tick bite reactions and red meat allergy in humans." }, { "docid": "MED-3307", "text": "OBJECTIVE: workers in slaughterhouses and processing plants that handle pigs, and pork butchers/meatcutters have been little studied for health risks associated with employment, in spite of the fact that they are potentially exposed to oncogenic and non-oncogenic transmissible agents and chemical carcinogens at work. We report here on an update of mortality in 510 workers employed in abattoirs and processing plants that almost exclusively handled pigs and pork products. METHODS: standardized mortality ratios (SMRs) were estimated for the cohort as a whole, and in subgroups defined by race and sex, using the corresponding US general population mortality rates for comparison. Study subjects were followed up from January 1950 to December 2006, during which time 45% of them died. RESULTS: mortality was significantly increased overall in the cohort. A statistically significant excess of deaths was observed for colon and lung cancers in the entire cohort, SMR=2.7 (95% CI, 1.2-5.1), SMR=1.8 (95% CI, 1.1-2.7), respectively. Significant SMRs in the cohort as a whole were also observed for senile and pre-senile psychotic conditions (SMR=5.1, 95% CI, 1.4-13.1), and pneumonia (SMR=2.6, 95% CI, 1.3-4.8). An observed excess of subarachnoid hemorrhage was seen mainly in whites (SMR=10.1, 95% CI, 1.2-36.3). There was a suggestion of an excess of deaths from ischemic heart disease also, but the elevated SMR was confined to men and was not statistically significant. CONCLUSION: this study confirms the excess occurrence of lung and colon cancers, and stroke previously reported in this occupational group. New findings are the excess of risk for senile and pre-senile psychotic conditions and pneumonia, which together with the excess of colon cancer appear specific for pig/pork workers, as they were not evident in much larger studies of workers in abattoirs and processing plants handling cattle and sheep. However, caution should be exercised in interpreting these findings, since some of them could have occurred by chance, resulting from our examination of a large number of causes of death in multiple study subgroups. For the moment, the significance of these findings remains unknown until they are confirmed in larger studies of adequate statistical power. Studies that will take into account possible occupational and non-occupational confounding factors are needed. Copyright © 2011. Published by Elsevier Inc.", "title": "Mortality in workers employed in pig abattoirs and processing plants." }, { "docid": "MED-3280", "text": "Conventional chemotherapies have showed their limits, notably for patients with advanced cancer. New therapeutic strategies must be identified, and the metabolic abnormalities of cancer cells offer such opportunities. Many human cancer cell lines and primary tumors have absolute requirements for methionine, an essential amino acid. In contrast, normal cells are relatively resistant to exogenous methionine restriction. The biochemical mechanism for methionine dependency has been studied extensively, but the fundamental mechanism remains unclear. A number of investigators have attempted to exploit the methionine dependence of tumors for therapeutic effects in vivo. To reduce in vivo methionine in plasma and tumours, dietary and pharmacological treatments have been used. Methionine-free diet or methionine-deprived total parenteral nutrition causes regression of a variety of animal tumours. Alternatively, methionine depletion was achieved by the use of methioninase. This enzyme specifically degrades methionine and inhibits tumour growth in preclinical models. Because of potential toxicity and quality of life problems, prolonged methionine restriction with diet or with methioninase is not suitable for clinical use. Methionine restriction may find greater application in association with various chemotherapeutic agents. Several preclinical studies have demonstrated synergy between methionine restriction and various cytotoxic chemotherapy drugs. The experimental results accumulated during the last three decades suggest that methionine restriction can become an additional cancer therapeutic strategy, notably in association with chemotherapy.", "title": "Methionine dependency and cancer treatment." }, { "docid": "MED-4689", "text": "Background A plant-based diet protects against chronic oxidative stress-related diseases. Dietary plants contain variable chemical families and amounts of antioxidants. It has been hypothesized that plant antioxidants may contribute to the beneficial health effects of dietary plants. Our objective was to develop a comprehensive food database consisting of the total antioxidant content of typical foods as well as other dietary items such as traditional medicine plants, herbs and spices and dietary supplements. This database is intended for use in a wide range of nutritional research, from in vitro and cell and animal studies, to clinical trials and nutritional epidemiological studies. Methods We procured samples from countries worldwide and assayed the samples for their total antioxidant content using a modified version of the FRAP assay. Results and sample information (such as country of origin, product and/or brand name) were registered for each individual food sample and constitute the Antioxidant Food Table. Results The results demonstrate that there are several thousand-fold differences in antioxidant content of foods. Spices, herbs and supplements include the most antioxidant rich products in our study, some exceptionally high. Berries, fruits, nuts, chocolate, vegetables and products thereof constitute common foods and beverages with high antioxidant values. Conclusions This database is to our best knowledge the most comprehensive Antioxidant Food Database published and it shows that plant-based foods introduce significantly more antioxidants into human diet than non-plant foods. Because of the large variations observed between otherwise comparable food samples the study emphasizes the importance of using a comprehensive database combined with a detailed system for food registration in clinical and epidemiological studies. The present antioxidant database is therefore an essential research tool to further elucidate the potential health effects of phytochemical antioxidants in diet.", "title": "The total antioxidant content of more than 3100 foods, beverages, spices, herbs and supplements used worldwide" }, { "docid": "MED-2255", "text": "Background Diet is a major source of cadmium intake among the non-smoking general population. Recent studies have determined that cadmium exposure may produce adverse health effects at lower exposure levels than previously predicted. We conducted a meta-analysis to combine and analyze the results of previous studies that have investigated the association of dietary cadmium intake and cancer risk. Methods We searched PubMed, EMBASE, and MEDLINE database for case-control and cohort studies that assessed the association of dietary cadmium intake and cancer risk. We performed a meta-analysis using eight eligible studies to summarize the data and summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a random effects model. Results Overall, dietary cadmium intake showed no statistically significant association with cancer risk (RR = 1.10; 95% CI: 0.99–1.22, for highest vs. lowest dietary cadmium group). However, there was strong evidence of heterogeneity, and subgroup analyses were conducted using the study design, geographical location, and cancer type. In subgroup analyses, the positive associations between dietary cadmium intake and cancer risk were observed among studies with Western populations (RR = 1.15; 95% CI: 1.08–1.23) and studies investigating some hormone-related cancers (prostate, breast, and endometrial cancers). Conclusion Our analysis found a positive association between dietary cadmium intake and cancer risk among studies conducted in Western countries, particularly with hormone-related cancers. Additional experimental and epidemiological studies are required to verify our findings.", "title": "Dietary Cadmium Intake and the Risk of Cancer: A Meta-Analysis" }, { "docid": "MED-1532", "text": "Although substantial nutrition transition, characterized by an increased intake of energy, animal fat, and red meats, has occurred during the last several decades in East Asia, few studies have systematically evaluated temporal trends in cancer incidence or mortality among populations in this area. Therefore, we sought to investigate this question with tremendous public health implications. Data on mortality rates of cancers of the breast, colon, prostate, esophagus, and stomach for China (1988-2000), Hong Kong (1960-2006), Japan (1950-2006), Korea (1985-2006), and Singapore (1963-2006) were obtained from WHO. Joinpoint regression was used to investigate trends in mortality of these cancers. A remarkable increase in mortality rates of breast, colon, and prostate cancers and a precipitous decrease in those of esophageal and stomach cancers have been observed in selected countries (except breast cancer in Hong Kong) during the study periods. For example, the annual percentage increase in breast cancer mortality was 5.5% (95% confidence interval: 3.8, 7.3%) for the period 1985-1993 in Korea, and mortality rates for prostate cancer significantly increased by 3.2% (95% confidence interval: 3.0, 3.3%) per year from 1958 to 1993 in Japan. These changes in cancer mortality lagged ∼ 10 years behind the inception of the nutrition transition toward a westernized diet in selected countries or regions. There have been striking changes in mortality rates of breast, colon, prostate, esophageal, and stomach cancers in East Asia during the last several decades, which may be at least in part attributable to the concurrent nutrition transition.", "title": "Trends in mortality from cancers of the breast, colon, prostate, esophagus, and stomach in East Asia: role of nutrition transition." }, { "docid": "MED-3540", "text": "The 1950s saw the clinical introduction of the first two specifically antidepressant drugs: iproniazid, a monoamine-oxidase inhibitor that had been used in the treatment of tuberculosis, and imipramine, the first drug in the tricyclic antidepressant family. Iproniazid and imipramine made two fundamental contributions to the development of psychiatry: one of a social-health nature, consisting in an authentic change in the psychiatric care of depressive patients; and the other of a purely pharmacological nature, since these agents have constituted an indispensable research tool for neurobiology and psychopharmacology, permitting, among other things, the postulation of the first aetiopathogenic hypotheses of depressive disorders. The clinical introduction of fluoxetine, a selective serotonin reuptake inhibitor, in the late 1980s, once again revolutionized therapy for depression, opening the way for new families of antidepressants. The present work reviews, from a historical perspective, the entire process that led to the discovery of these drugs, as well as their contribution to the development of the neuroscientific disciplines. However, all of these antidepressants, like the rest of those currently available for clinical practice, share the same action mechanism, which involves the modulation of monoaminergic neurotransmission at a synaptic level, so that the future of antidepressant therapy would seem to revolve around the search for extraneuronal non-aminergic mechanisms or mechanisms that modulate the intraneuronal biochemical pathways.", "title": "Monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today." }, { "docid": "MED-4693", "text": "Background Breast cancer incidence is increasing globally for largely unknown reasons. The possibility that a portion of the breast cancer burden might be explained by the introduction and increasing use of electricity to light the night was suggested >20 years ago. Methods The theory is based on nocturnal light-induced disruption of circadian rhythms, notably reduction of melatonin synthesis. It has formed the basis for a series of predictions including that non-day shift work would increase risk, blind women would be at lower risk, long sleep duration would lower risk and community nighttime light level would co-distribute with breast cancer incidence on the population level. Results Accumulation of epidemiological evidence has accelerated in recent years, reflected in an International Agency for Research on Cancer (IARC) classification of shift work as a probable human carcinogen (2A). There is also a strong rodent model in support of the light-at-night (LAN) idea. Conclusion If a consensus eventually emerges that LAN does increase risk, then the mechanisms for the effect are important to elucidate for intervention and mitigation. The basic understanding of phototransduction for the circadian system, and of the molecular genetics of circadian rhythm generation are both advancing rapidly, and will provide for the development of lighting technologies at home and at work that minimize circadian disruption, while maintaining visual efficiency and aesthetics. In the interim, there are strategies now available to reduce the potential for circadian disruption, which include extending the daily dark period, appreciate nocturnal awakening in the dark, using dim red light for nighttime necessities, and unless recommended by a physician, not taking melatonin tablets.", "title": "Light-at-night, circadian disruption and breast cancer: assessment of existing evidence" }, { "docid": "MED-2395", "text": "OBJECTIVE: Low-level exposure to some persistent organic pollutants (POPs) has recently become a focus because of their possible link with the risk of diabetes. RESEARCH DESIGN AND METHODS: Cross-sectional associations of the serum concentrations of POPs with diabetes prevalence were investigated in 2,016 adult participants in the National Health and Nutrition Examination Survey 1999-2002. Six POPs (2,2',4,4',5,5'-hexachlorobiphenyl, 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin, 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin, oxychlordane, p,p'-dichlorodiphenyltrichloroethane, and trans-nonachlor) were selected, because they were detectable in >or=80% of participants. RESULTS: Compared with subjects with serum concentrations below the limit of detection, after adjustment for age, sex, race and ethnicity, poverty income ratio, BMI, and waist circumference, diabetes prevalence was strongly positively associated with lipid-adjusted serum concentrations of all six POPs. When the participants were classified according to the sum of category numbers of the six POPs, adjusted odds ratios were 1.0, 14.0, 14.7, 38.3, and 37.7 (P for trend < 0.001). The association was consistent in stratified analyses and stronger in younger participants, Mexican Americans, and obese individuals. CONCLUSIONS: There were striking dose-response relations between serum concentrations of six selected POPs and the prevalence of diabetes. The strong graded association could offer a compelling challenge to future epidemiologic and toxicological research.", "title": "A strong dose-response relation between serum concentrations of persistent organic pollutants and diabetes: results from the National Health and Ex..." }, { "docid": "MED-1577", "text": "Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disorder of the brain caused by a ubiquitous polyomavirus, JC virus. PML is almost always associated with some underlying immunosuppression and acquired immune deficiency syndrome has been the most common predisposing disorder. Recently, different pharmacological agents have been demonstrated to increase the risk of PML. Therapies that predispose people to PML can be classified into three categories: therapies that uniquely increase the risk for the disorder, such as the monoclonal antibodies natalizumab and efalizumab; therapies that appear to increase the risk in individuals already at risk of PML due to pre-existing conditions, such as rituximab and mycophenolate mofetil; and therapies with a mechanism of action that might suggest a potential for increased PML risk and/or with which rare cases of PML have been observed. Unlike the latter two classes, therapeutic agents uniquely increasing the risk of PML are associated with a much greater prevalence of the disorder and a latent interval from the time of drug initiation to the development of PML. PML development with pharmacological agents has provided new insight into the pathogenesis of this devastating disorder. This review focuses on the risks of PML with multiple pharmacological agents, the proposed pathogenesis with these agents, and potential risk mitigation strategies.", "title": "Treatment-related progressive multifocal leukoencephalopathy: current understanding and future steps" }, { "docid": "MED-1405", "text": "Background Polyphenols may lower the risk of cardiovascular disease (CVD) and other chronic diseases due to their antioxidant and anti-inflammatory properties, as well as their beneficial effects on blood pressure, lipids and insulin resistance. However, no previous epidemiological studies have evaluated the relationship between the intake of total polyphenols intake and polyphenol subclasses with overall mortality. Our aim was to evaluate whether polyphenol intake is associated with all-cause mortality in subjects at high cardiovascular risk. Methods We used data from the PREDIMED study, a 7,447-participant, parallel-group, randomized, multicenter, controlled five-year feeding trial aimed at assessing the effects of the Mediterranean Diet in primary prevention of cardiovascular disease. Polyphenol intake was calculated by matching food consumption data from repeated food frequency questionnaires (FFQ) with the Phenol-Explorer database on the polyphenol content of each reported food. Hazard ratios (HR) and 95% confidence intervals (CI) between polyphenol intake and mortality were estimated using time-dependent Cox proportional hazard models. Results Over an average of 4.8 years of follow-up, we observed 327 deaths. After multivariate adjustment, we found a 37% relative reduction in all-cause mortality comparing the highest versus the lowest quintiles of total polyphenol intake (hazard ratio (HR) = 0.63; 95% CI 0.41 to 0.97; P for trend = 0.12). Among the polyphenol subclasses, stilbenes and lignans were significantly associated with reduced all-cause mortality (HR =0.48; 95% CI 0.25 to 0.91; P for trend = 0.04 and HR = 0.60; 95% CI 0.37 to 0.97; P for trend = 0.03, respectively), with no significant associations apparent in the rest (flavonoids or phenolic acids). Conclusions Among high-risk subjects, those who reported a high polyphenol intake, especially of stilbenes and lignans, showed a reduced risk of overall mortality compared to those with lower intakes. These results may be useful to determine optimal polyphenol intake or specific food sources of polyphenols that may reduce the risk of all-cause mortality. Clinical trial registration ISRCTN35739639.", "title": "Polyphenol intake and mortality risk: a re-analysis of the PREDIMED trial" }, { "docid": "MED-3059", "text": "AIMS: In animals, intracerebroventricular glucose and fructose have opposing effects on appetite and weight regulation. In humans, functional brain magnetic resonance imaging (fMRI) studies during glucose ingestion or infusion have demonstrated suppression of hypothalamic signalling, but no studies have compared the effects of glucose and fructose. We therefore sought to determine if the brain response differed to glucose vs. fructose in humans independently of the ingestive process. METHODS: Nine healthy, normal weight subjects underwent blood oxygenation level dependent (BOLD) fMRI measurements during either intravenous (IV) glucose (0.3 mg/kg), fructose (0.3 mg/kg) or saline, administered over 2 min in a randomized, double-blind, crossover study. Blood was sampled every 5 min during a baseline period and following infusion for 60 min in total for glucose, fructose, lactate and insulin levels. RESULTS: No significant brain BOLD signal changes were detected in response to IV saline. BOLD signal in the cortical control areas increased during glucose infusion (p = 0.002), corresponding with increased plasma glucose and insulin levels. In contrast, BOLD signal decreased in the cortical control areas during fructose infusion (p = 0.006), corresponding with increases of plasma fructose and lactate. Neither glucose nor fructose infusions significantly altered BOLD signal in the hypothalamus. CONCLUSION: In normal weight humans, cortical responses as assessed by BOLD fMRI to infused glucose are opposite to those of fructose. Differential brain responses to these sugars and their metabolites may provide insight into the neurologic basis for dysregulation of food intake during high dietary fructose intake. © 2011 Blackwell Publishing Ltd.", "title": "Brain functional magnetic resonance imaging response to glucose and fructose infusions in humans." }, { "docid": "MED-3425", "text": "OBJECTIVES: We examined whether common coronary heart disease (CHD) risk factors measured in mid-life predict erectile dysfunction (ED) 25 years later. BACKGROUND: Retrospective and cross-sectional studies have suggested that ED is associated with classic CHD risk factors, but few prospective studies have studied these associations. METHODS: In this prospective study of community-dwelling men age 30 to 69 years, seven classic CHD risk factors (age, smoking, hypertension, diabetes, hypercholesterolemia, hypertriglyceridemia, and obesity) were assessed from 1972 to 1974. In 1998, after an average follow-up of 25 years, surviving male participants were asked to complete the International Index of Erectile Function (IIEF-5), which allows stratification of ED into five groups. RESULTS: Sixty-eight percent of the surviving men returned, and 60% completed the IIEF-5 questionnaire. Respondents had more favorable levels of all heart disease risk factors at baseline than non-respondents. At baseline, the average age of the 570 ED study participants was 46 years; at follow-up, their average age was 72 years. Mean age, body mass index, cholesterol, and triglycerides were each significantly associated with an increased risk of ED. Cigarette smoking was marginally more common in those with severe/complete ED, as compared with those without ED. Blood pressure and fasting blood glucose were not significantly associated with ED, likely due to selective mortality. CONCLUSIONS: Improving CHD risk factors in mid-life may decrease the risk of ED as well as CHD. Erectile dysfunction should be included as an outcome in clinical trials of lipid-lowering agents and lifestyle modifications.", "title": "Heart disease risk factors predict erectile dysfunction 25 years later: the Rancho Bernardo Study." }, { "docid": "MED-1256", "text": "BACKGROUND: Limited consumption of red meat, including beef, is one of many often-suggested strategies to reduce the risk of coronary heart disease (CHD). However, the role that beef consumption specifically plays in promoting adverse changes in the cardiovascular risk factor profile is unclear. OBJECTIVE: A meta-analysis of randomized, controlled, clinical trials (RCTs) was conducted to evaluate the effects of beef, independent of other red and processed meats, compared with poultry and/or fish consumption, on lipoprotein lipids. METHODS: RCTs published from 1950 to 2010 were considered for inclusion. Studies were included if they reported fasting lipoprotein lipid changes after beef and poultry/fish consumption by subjects free of chronic disease. A total of 124 RCTs were identified, and 8 studies involving 406 subjects met the prespecified entry criteria and were included in the analysis. RESULTS: Relative to the baseline diet, mean ± standard error changes (in mg/dL) after beef versus poultry/fish consumption, respectively, were -8.1 ± 2.8 vs. -6.2 ± 3.1 for total cholesterol (P = .630), -8.2 ± 4.2 vs. -8.9 ± 4.4 for low-density lipoprotein cholesterol (P = .905), -2.3 ± 1.0 vs. -1.9 ± 0.8 for high-density lipoprotein cholesterol (P = .762), and -8.1 ± 3.6 vs. -12.9 ± 4.0 mg/dL for triacylglycerols (P = .367). CONCLUSION: Changes in the fasting lipid profile were not significantly different with beef consumption compared with those with poultry and/or fish consumption. Inclusion of lean beef in the diet increases the variety of available food choices, which may improve long-term adherence with dietary recommendations for lipid management. Copyright © 2012 National Lipid Association. Published by Elsevier Inc. All rights reserved.", "title": "A meta-analysis of randomized controlled trials that compare the lipid effects of beef versus poultry and/or fish consumption." }, { "docid": "MED-3744", "text": "Consumption of fruits and vegetables has been associated with reduced risk of chronic diseases such as cardiovascular disease and cancer. Phytochemicals, especially phenolics, in fruits and vegetables are suggested to be the major bioactive compounds for the health benefits. However, the phenolic contents and their antioxidant activities in fruits and vegetables were underestimated in the literature, because bound phenolics were not included. This study was designed to investigate the profiles of total phenolics, including both soluble free and bound forms in common fruits, by applying solvent extraction, base digestion, and solid-phase extraction methods. Cranberry had the highest total phenolic content, followed by apple, red grape, strawberry, pineapple, banana, peach, lemon, orange, pear, and grapefruit. Total antioxidant activity was measured using the TOSC assay. Cranberry had the highest total antioxidant activity (177.0 +/- 4.3 micromol of vitamin C equiv/g of fruit), followed by apple, red grape, strawberry, peach, lemon, pear, banana, orange, grapefruit, and pineapple. Antiproliferation activities were also studied in vitro using HepG(2) human liver-cancer cells, and cranberry showed the highest inhibitory effect with an EC(50) of 14.5 +/- 0.5 mg/mL, followed by lemon, apple, strawberry, red grape, banana, grapefruit, and peach. A bioactivity index (BI) for dietary cancer prevention is proposed to provide a new alternative biomarker for future epidemiological studies in dietary cancer prevention and health promotion.", "title": "Antioxidant and antiproliferative activities of common fruits." }, { "docid": "MED-4072", "text": "It was the aim of this study to examine the association of the consumption of meat in general, meat prepared by different cooking methods and the dietary intake of heterocyclic aromatic amines (HCA) with the level of DNA adducts in the breast tissue of women undergoing reduction mammoplasty. Dietary intake of meat and HCA were assessed via questionnaire in 44 women undergoing reduction mammoplasty. DNA adduct analysis in breast tissue was performed by (32)P-postlabelling analysis. Spearman rank correlation coefficients (r) were calculated to examine the association of meat consumption and dietary HCA intake with tissue DNA adduct levels. A median DNA adduct level of 18.45 (interquartile range 12.81-25.65) per 10(9) nucleotides in breast tissue was observed; median HCA intake was 40.43 ng/day (interquartile range 19.55-102.33 ng/day). Total HCA intake (r = 0.33, P = 0.03), consumption of fried meat (r = 0.39, P = 0.01), beef (r = 0.32, P = 0.03) and processed meat (r = 0.51, P = 0.0004) were statistically significantly correlated with the level of DNA adducts in breast tissue. The detected DNA adducts could not be confirmed to be specific HCA-derived DNA adducts by comparison with external standards, using the (32)P-postlabelling assay. We observed strong correlations of dietary HCA intake and consumption of fried and processed meat with DNA adduct levels in breast tissue of 44 women. Since the detected DNA adducts were not necessarily specific only for HCA, it is possible that HCA intake is a surrogate of other genotoxic substances, such as polycyclic aromatic hydrocarbons, in meat prepared at high temperatures.", "title": "Dietary intake of meat and meat-derived heterocyclic aromatic amines and their correlation with DNA adducts in female breast tissue." }, { "docid": "MED-2493", "text": "There is now compelling evidence that developmental exposure to chemicals from our environment contributes to disease later in life, with animal models supporting this concept in reproductive, metabolic, and neurodegenerative diseases. In contrast, data regarding how developmental exposures impact the susceptibility of the immune system to functional alterations later in life are surprisingly scant. Given that the immune system forms an integrated network that detects and destroys invading pathogens and cancer cells, it provides the body’s first line of defense. Thus, the consequences of early-life exposures that reduce immune function are profound. This review summarizes available data for pollutants such as cigarette smoke and dioxin-like compounds, which consistently support the idea that developmental exposures critically impact the immune system. These findings suggest that exposure to common chemicals from our daily environment represent overlooked contributors to the fact that infectious diseases remain among the top five causes of death worldwide.", "title": "Environmental toxicants and the developing immune system: a missing link in the global battle against infectious disease?" }, { "docid": "MED-3444", "text": "Research on the relationship between iodine exposure and thyroid cancer risk is limited, and the findings are inconclusive. In most studies, fish/shellfish consumption has been used as a proxy measure of iodine exposure. The present study extends this research by quantifying dietary iodine exposure as well as incorporating a biomarker of long-term (1 year) exposure, i.e., from toenail clippings. This study is conducted in a multiethnic population with a wide variation in thyroid cancer incidence rates and substantial diversity in exposure. Women, ages 20-74, residing in the San Francisco Bay Area and diagnosed with thyroid cancer between 1995 and 1998 (1992-1998 for Asian women) were compared with women selected from the general population via random digit dialing. Interviews were conducted in six languages with 608 cases and 558 controls. The established risk factors for thyroid cancer were found to increase risk in this population: radiation to the head/neck [odds ratio (OR), 2.3; 95% confidence interval (CI), 0.97-5.5]; history of goiter/nodules (OR, 3.7; 95% CI, 2.5-5.6); and a family history of proliferative thyroid disease (OR, 2.5; 95% CI, 1.6-3.8). Contrary to our hypothesis, increased dietary iodine, most likely related to the use of multivitamin pills, was associated with a reduced risk of papillary thyroid cancer. This risk reduction was observed in \"low-risk\" women (i.e., women without any of the three established risk factors noted above; OR, 0.53; 95% CI, 0.33-0.85) but not in \"high-risk\" women, among whom a slight elevation in risk was seen (OR, 1.4; 95% CI, 0.56-3.4). However, no association with risk was observed in either group when the biomarker of exposure was evaluated. In addition, no ethnic differences in risk were observed. The authors conclude that iodine exposure appears to have, at most, a weak effect on the risk of papillary thyroid cancer.", "title": "Iodine and thyroid cancer risk among women in a multiethnic population: the Bay Area Thyroid Cancer Study." }, { "docid": "MED-1944", "text": "OBJECTIVE: To determine overall and age-specific incidence rates of AD in a rural, population-based cohort in Ballabgarh, India, and to compare them with those of a reference US population in the Monongahela Valley of Pennsylvania. METHODS: A 2-year, prospective, epidemiologic study of subjects aged > or =55 years utilizing repeated cognitive and functional ability screening, followed by standardized clinical evaluation using the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for the diagnosis, and the Clinical Dementia Rating scale for the staging, of dementia and AD. RESULTS: Incidence rates per 1000 person-years for AD with CDR > or =0.5 were 3.24 (95% CI: 1.48-6.14) for those aged > or =65 years and 1.74 (95% CI: 0.84-3.20) for those aged > or =55 years. Standardized against the age distribution of the 1990 US Census, the overall incidence rate in those aged > or =65 years was 4.7 per 1000 person-years, substantially lower than the corresponding rate of 17.5 per 1000 person-years in the Monongahela Valley. CONCLUSION: These are the first AD incidence rates to be reported from the Indian subcontinent, and they appear to be among the lowest ever reported. However, the relatively short duration of follow-up, cultural factors, and other potential confounders suggest caution in interpreting this finding.", "title": "Incidence of Alzheimer's disease in a rural community in India: the Indo-US study." }, { "docid": "MED-4843", "text": "We have previously reported that significant improvement may be obtained in rheumatoid arthritis patients by fasting followed by a vegetarian diet for one year. The present study was carried out to examine to what extent biochemical and immunological variables changed during the clinical trial of fasting and vegetarian diet. For the patients who were randomised to the vegetarian diet there was a significant decrease in platelet count, leukocyte count, calprotectin, total IgG, IgM rheumatoid factor (RF), C3-activation products, and the complement components C3 and C4 after one month of treatment. None of the measured parameters changed significantly during this period in the group of omnivores. The course of 14 of 15 measured variables favored the vegetarians compared with the omnivores, but the difference was only significant for leukocyte count, IgM RF, and the complement components C3 and C4. Most of the laboratory variables declined considerably in the vegetarians who improved according to clinical variables, indicating a substantial reduction in inflammatory activity. The leukocyte count, however, decreased in the vegetarians irrespective of the clinical results. Thus, the decline in leukocyte count may be attributed to vegetarian diet per se and not to the reduction in disease activity. The results of the present study are in accordance with the findings from the clinical trial, namely that dietary treatment can reduce the disease activity in some patients with rheumatoid arthritis.", "title": "Changes in laboratory variables in rheumatoid arthritis patients during a trial of fasting and one-year vegetarian diet." }, { "docid": "MED-1529", "text": "BACKGROUND: Few previous prospective studies have examined differences in incident ischemic heart disease (IHD) risk between vegetarians and nonvegetarians. OBJECTIVE: The objective was to examine the association of a vegetarian diet with risk of incident (nonfatal and fatal) IHD. DESIGN: A total of 44,561 men and women living in England and Scotland who were enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Oxford study, of whom 34% consumed a vegetarian diet at baseline, were part of the analysis. Incident cases of IHD were identified through linkage with hospital records and death certificates. Serum lipids and blood pressure measurements were available for 1519 non cases, who were matched to IHD cases by sex and age. IHD risk by vegetarian status was estimated by using multivariate Cox proportional hazards models. RESULTS: After an average follow-up of 11.6 y, there were 1235 IHD cases (1066 hospital admissions and 169 deaths). Compared with nonvegetarians, vegetarians had a lower mean BMI [in kg/m(2); -1.2 (95% CI: -1.3, -1.1)], non-HDL-cholesterol concentration [-0.45 (95% CI: -0.60, -0.30) mmol/L], and systolic blood pressure [-3.3 (95% CI: -5.9, -0.7) mm Hg]. Vegetarians had a 32% lower risk (HR: 0.68; 95% CI: 0.58, 0.81) of IHD than did nonvegetarians, which was only slightly attenuated after adjustment for BMI and did not differ materially by sex, age, BMI, smoking, or the presence of IHD risk factors. CONCLUSION: Consuming a vegetarian diet was associated with lower IHD risk, a finding that is probably mediated by differences in non-HDL cholesterol, and systolic blood pressure.", "title": "Risk of hospitalization or death from ischemic heart disease among British vegetarians and nonvegetarians: results from the EPIC-Oxford cohort study." }, { "docid": "MED-1328", "text": "BACKGROUND: In 2010, overweight and obesity were estimated to cause 3·4 million deaths, 3·9% of years of life lost, and 3·8% of disability-adjusted life-years (DALYs) worldwide. The rise in obesity has led to widespread calls for regular monitoring of changes in overweight and obesity prevalence in all populations. Comparable, up-to-date information about levels and trends is essential to quantify population health effects and to prompt decision makers to prioritise action. We estimate the global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013. METHODS: We systematically identified surveys, reports, and published studies (n=1769) that included data for height and weight, both through physical measurements and self-reports. We used mixed effects linear regression to correct for bias in self-reports. We obtained data for prevalence of obesity and overweight by age, sex, country, and year (n=19,244) with a spatiotemporal Gaussian process regression model to estimate prevalence with 95% uncertainty intervals (UIs). FINDINGS: Worldwide, the proportion of adults with a body-mass index (BMI) of 25 kg/m(2) or greater increased between 1980 and 2013 from 28·8% (95% UI 28·4-29·3) to 36·9% (36·3-37·4) in men, and from 29·8% (29·3-30·2) to 38·0% (37·5-38·5) in women. Prevalence has increased substantially in children and adolescents in developed countries; 23·8% (22·9-24·7) of boys and 22·6% (21·7-23·6) of girls were overweight or obese in 2013. The prevalence of overweight and obesity has also increased in children and adolescents in developing countries, from 8·1% (7·7-8·6) to 12·9% (12·3-13·5) in 2013 for boys and from 8·4% (8·1-8·8) to 13·4% (13·0-13·9) in girls. In adults, estimated prevalence of obesity exceeded 50% in men in Tonga and in women in Kuwait, Kiribati, Federated States of Micronesia, Libya, Qatar, Tonga, and Samoa. Since 2006, the increase in adult obesity in developed countries has slowed down. INTERPRETATION: Because of the established health risks and substantial increases in prevalence, obesity has become a major global health challenge. Not only is obesity increasing, but no national success stories have been reported in the past 33 years. Urgent global action and leadership is needed to help countries to more effectively intervene. FUNDING: Bill & Melinda Gates Foundation. Copyright © 2014 Elsevier Ltd. All rights reserved.", "title": "Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global B..." }, { "docid": "MED-3597", "text": "Background Dietary trans fatty acids (dTFA) are primarily synthetic compounds that have been introduced only recently; little is known about their behavioral effects. dTFA inhibit production of omega-3 fatty acids, which experimentally have been shown to reduce aggression. Potential behavioral effects of dTFA merit investigation. We sought to determine whether dTFA are associated with aggression/irritability. Methodolgy/Prinicpal Findings We capitalized on baseline dietary and behavioral assessments in an existing clinical trial to analyze the relationship of dTFA to aggression. Of 1,018 broadly sampled baseline subjects, the 945 adult men and women who brought a completed dietary survey to their baseline visit are the target of this analysis. Subjects (seen 1999–2004) were not on lipid medications, and were without LDL-cholesterol extremes, diabetes, HIV, cancer or heart disease. Outcomes assessed adverse behaviors with impact on others: Overt Aggression Scale Modified-aggression subscale (primary behavioral endpoint); Life History of Aggression; Conflict Tactics Scale; and self-rated impatience and irritability. The association of dTFA to aggression was analyzed via regression and ordinal logit, unadjusted and adjusted for potential confounders (sex, age, education, alcohol, and smoking). Additional analyses stratified on sex, age, and ethnicity, and examined the prospective association. Greater dTFA were strongly significantly associated with greater aggression, with dTFA more consistently predictive than other assessed aggression predictors. The relationship was upheld with adjustment for confounders, was preserved across sex, age, and ethnicity strata, and held cross-sectionally and prospectively. Conclusions/Significance This study provides the first evidence linking dTFA with behavioral irritability and aggression. While confounding is always a concern in observational studies, factors including strength and consistency of association, biological gradient, temporality, and biological plausibility add weight to the prospect of a causal connection. Our results may have relevance to public policy determinations regarding dietary trans fats. Clinicaltrials.gov # NCT00330980", "title": "Trans Fat Consumption and Aggression" }, { "docid": "MED-4680", "text": "OBJECTIVE: To investigate associations between dietary intakes throughout childhood and age at menarche, a possible indicator of future risk of disease, in a contemporary cohort of British girls. DESIGN: Diet was assessed by FFQ at 3 and 7 years of age, and by a 3 d unweighed food diary at 10 years. Age at menarche was categorised as before or after 12 years 8 months, a point close to the median age in this cohort. SETTING: Bristol, South-West England. SUBJECTS: Girls (n 3298) participating in the Avon Longitudinal Study of Parents and Children. RESULTS: Higher energy intakes at 10 years were positively associated with the early occurrence of menarche, but this association was removed on adjusting for body size. Total and animal protein intakes at 3 and 7 years were positively associated with age at menarche ≤12 years 8 months (adjusted OR for a 1 sd increase in protein at 7 years: 1·14 (95 % CI 1·04, 1·26)). Higher PUFA intakes at 3 and 7 years were also positively associated with early occurrence of menarche. Meat intake at 3 and 7 years was strongly positively associated with reaching menarche by 12 years 8 months (OR for menarche in the highest v. lowest category of meat consumption at 7 years: 1·75 (95 % CI 1·25, 2·44)). CONCLUSIONS: These data suggest that higher intakes of protein and meat in early to mid-childhood may lead to earlier menarche. This may have implications for the lifetime risk of breast cancer and osteoporosis.", "title": "Diet throughout childhood and age at menarche in a contemporary cohort of British girls." }, { "docid": "MED-4230", "text": "PURPOSE OF REVIEW: Although age, genetics, and sex steroid hormones play prominent roles in the cause of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS), recent epidemiological studies suggest that modifiable lifestyle factors also contribute substantially to the pathogenesis of these conditions. RECENT FINDINGS: Lifestyle and metabolic factors associated with significantly increased risks of benign prostatic hyperplasia and lower urinary tract symptoms include obesity, diabetes, and meat and fat consumption. Factors associated with decreased risks include physical activity, moderate alcohol intake, and vegetable consumption. Factors for which no clear risk patterns have emerged include lipids and smoking. Randomized clinical trials of lifestyle alterations - such as weight loss, exercise, and diet - for the prevention or treatment of benign prostatic hyperplasia and lower urinary tract symptoms have yet to be performed. SUMMARY: Lifestyle factors present a novel opportunity for the prevention and treatment of benign prostatic hyperplasia and lower urinary tract symptoms. Although clinical trials of lifestyle modifications have not yet been undertaken, promotion of healthy lifestyle alternatives within the context of standard benign prostatic hyperplasia and lower urinary tract symptoms treatment algorithms is potentially beneficial.", "title": "Lifestyle factors, benign prostatic hyperplasia, and lower urinary tract symptoms." }, { "docid": "MED-1329", "text": "White rice-based foods, which are high in refined carbohydrates, are widely consumed in China. A case-control study was conducted to investigate the association between white rice-based food consumption and the risk of ischemic stroke in the southern Chinese population. Information on diet and lifestyle was obtained from 374 incident ischemic stroke patients and 464 hospital-based controls. Logistic regression analyses were performed to assess the effects of rice-based foods on stroke risk. The mean weekly intake of rice foods appeared to be significantly higher in cases than in controls. Increased consumptions of cooked rice, congee, and rice noodle were associated with a higher risk for ischemic stroke after controlling for confounding factors. The corresponding adjusted odds ratios (with 95% confidence intervals) for the highest versus lowest intake level were 2.73 (1.31-5.69), 2.93 (1.68-5.13), and 2.03 (1.40-2.94), with significant dose-response relationships observed. The results provide evidence of a positive association between habitual rice food consumption and the risk of ischemic stroke in Chinese adults. Copyright © 2010 National Stroke Association. Published by Elsevier Inc. All rights reserved.", "title": "White rice-based food consumption and ischemic stroke risk: a case-control study in southern China." }, { "docid": "MED-3244", "text": "Diet may represent a modifiable prostate cancer (CaP) risk factor, but a vegetable-based prostate-healthy diet is a major change for most men. We used a ratio of animal:vegetable proteins (A:V ratio) to evaluate whether a comprehensive dietary change was self-sustaining following completion of 11 weekly dietary and cooking classes that integrated mindfulness training (MT). Thirty-six men with recurring CaP were randomized to the intervention or wait-list control. Assessments were at baseline, three months and six months. Of the 17 men randomized to the intervention, 14 completed the requirements. Nineteen were randomized to control and 17 completed requirements. Compared to controls, a significant post-intervention (3 months) decrease in A:V ratio in the intervention group (p=.01) was self-maintained 3 months post-intervention (p=0.049). At each assessment, the A:V ratio was correlated with lycopene, fiber, saturated fat, and dietary cholesterol; four dietary components linked to clinically relevant outcomes in CaP. Change in A:V ratio was also significantly correlated with changes in fiber, saturated fat and dietary cholesterol intake. Participants reported regular MT practice and there was a significant correlation between MT practice and changes in both initiation and maintenance of the change in the A:V ratio. These pilot results provide encouraging evidence for the feasibility of a dietary program that includes MT in supporting dietary change for men with recurrent CaP and invite further study to explore the possible role of MT as a means of supporting both initiation of dietary changes and maintenance of those changes over time.", "title": "A Novel Measure of Dietary Change in a Prostate Cancer Dietary Program Incorporating Mindfulness Training" }, { "docid": "MED-4382", "text": "BACKGROUND: Age-related cataract is a major cause of morbidity. Previous studies of diet and cataract risk have focused on specific nutrients or healthy eating indexes but not on identifiable dietary groups such as vegetarians. OBJECTIVE: We investigated the association between diet and cataract risk in a population that has a wide range of diets and includes a high proportion of vegetarians. DESIGN: We used Cox proportional hazards regression to study cataract risk in relation to baseline dietary and lifestyle characteristics of 27,670 self-reported nondiabetic participants aged ≥40 y at recruitment in the Oxford (United Kingdom) arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Oxford) by using data from the Hospital Episode Statistics in England and Scottish Morbidity Records. RESULTS: There was a strong relation between cataract risk and diet group, with a progressive decrease in risk of cataract in high meat eaters to low meat eaters, fish eaters (participants who ate fish but not meat), vegetarians, and vegans. After multivariable adjustment, incidence rate ratios (95% CIs) for moderate meat eaters (50-99 g meat/d), low meat eaters (<50 g meat/d), fish eaters, vegetarians, and vegans compared with high-meat eaters (≥100 g meat/d) were 0.96 (0.84, 1.11), 0.85 (0.72, 0.99), 0.79 (0.65, 0.97), 0.70 (0.58, 0.84), and 0.60 (0.38, 0.96), respectively (P < 0.001 for heterogeneity). Associations between cataract risk and intakes of selected nutrients and foods generally reflected the strong association with diet group. CONCLUSION: Vegetarians were at lower risk of cataract than were meat eaters in this cohort of health-conscious British residents.", "title": "Diet, vegetarianism, and cataract risk." }, { "docid": "MED-2578", "text": "The incidence of colonic cancer differs widely between various human populations. It has been suggested that dietary fiber content is of utmost importance and is inversely related to the occurrence of colonic cancer. However, high-fiber diets are not always correlated with low frequency of colonic cancer, suggesting the involvement of additional dietary constituents. Inositol hexaphosphate (phytic acid) is an abundant plant seed component present in many, but not all, fiber-rich diets. The authors have found that phytic acid is a potent inhibitor of iron-mediated generation of the hazardous oxidant, hydroxyl radical. Herein, the authors propose that inhibition of intracolonic hydroxyl radical generation, via the chelation of reactive iron by phytic acid, may help explain the suppression of colonic carcinogenesis and other inflammatory bowel diseases by diets rich in phytic acid.", "title": "Dietary suppression of colonic cancer. Fiber or phytate?" }, { "docid": "MED-1603", "text": "BACKGROUND: A growing body of evidence shows that secondhand cigarette smoke undergoes numerous chemical changes after it is released into the air: it can adsorb to indoor surfaces, desorb back into the air and undergo chemical changes as it ages. OBJECTIVES: To test the effects of aging on the concentration of polycyclic aromatic hydrocarbons (PAHs), nicotine and tobacco-specific nitrosamines in cigarette smoke. METHODS: We generated sidestream and mainstream cigarette smoke with a smoking machine, diluted it with conditioned filtered air, and passed it through a 6 m(3) flow reactor with air exchange rates that matched normal residential air exchange rates. We tested the effects of 60 min aging on the concentration of 16 PAHs, nicotine, cotinine and tobacco-specific nitrosamines. We also measured sorption and deposition of nicotine, cotinine and tobacco-specific nitrosamines on materials placed within the flow reactor. RESULTS: We observed mass losses of 62% for PAHs, 72%, for nicotine, 79% for N-nitrosonornicotine and 80% for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Extraction of cotton cloth exposed to smoke yielded nicotine and NNK. The ratio of NNK:nicotine on the exposed cloth was 10-fold higher than that in aerosol samples. CONCLUSIONS: Our data suggest that the majority of the PAHs, nicotine, cotinine and tobacco-specific nitrosamines that are released during smoking in homes and public places deposit on room surfaces. These data give an estimate of the potential for accumulation of carcinogens in thirdhand cigarette smoke. Exposure to PAHs and tobacco-specific nitrosamines, through dermal absorption and inhalation of contaminated dust, may contribute to smoking-attributable morbidity and mortality.", "title": "Thirdhand cigarette smoke in an experimental chamber: evidence of surface deposition of nicotine, nitrosamines and polycyclic aromatic hydrocarbons..." }, { "docid": "MED-1581", "text": "Crohn's disease is a life-long idiopathic inflammatory disease which affects the entire gastrointestinal tract and occasionally extra-intestinal organs. CD is thought to result from complex interactions between environmental factors, the gut microbes, and the genetic background and the immune system of the host. In the last decades research on these pathogenetic components, and especially on mucosal immunity, has led to the development of biologic agents and therapeutic strategies that have improved dramatically the treatment of CD but we are still far away from curing the disease. If there is a treatment for CD that will probably evolve through methodical steps towards integrating research on all the components involved in the pathogenesis of CD. This holistic and global approach may aid at unravelling the mysteries of CD and developing novel agents and therapeutic strategies which by targeting multiple pathogenetic pathways and at different stages of disease may lead hopefully to cure. Copyright © 2014 Elsevier Ltd. All rights reserved.", "title": "When can we cure Crohn's?" }, { "docid": "MED-3423", "text": "INTRODUCTION: There are no reported studies assessing the relation between diet and sexual function in women with diabetes. AIM: In the present study, we explored the relation between consumption of a Mediterranean-type diet and sexual function in a population of type 2 diabetic women. METHODS: Patients with type 2 diabetes were enrolled if they had a diagnosis of type 2 diabetes for at least six months but less than 10 years, age 35-70 years, body mass index (BMI) of 24 or higher, HbA1c of 6.5% or higher, treatment with diet or oral drugs. All diabetic patients were invited to complete a food-frequency questionnaire and self-report measures of sexual function. A total of 595 (90.2%) of the 659 women completed both questionnaires and were analyzed in the present study. MAIN OUTCOME MEASURES: Adherence to a Mediterranean diet was assessed by a 9-point scale that incorporated the salient characteristics of this diet (range of scores, 0-9, with higher scores indicating greater adherence). The Female Sexual Function Index (FSFI) was used for assessing the key dimensions of female sexual function. RESULTS: Diabetic women with the highest scores (6-9) had lower BMI, waist circumference, and waist-to-hip ratio, a lower prevalence of depression, obesity and metabolic syndrome, a higher level of physical activity, and better glucose and lipid profiles than the diabetic women who scored <3 points on the scale. The proportion of sexually active women showed a significant increase across tertiles of adherence to Mediterranean diet (from 54.2% to 65.1%, P = 0.01). Based on the FSFI cutoff score for female sexual dysfunction (FSD) of 23, women with the highest score of adherence had a lower prevalence of sexual dysfunction as compared with women of lower tertiles (47.6%, 53.9%, and 57.8%, higher, middle, and lower tertile, respectively, P = 0.01). These associations remained significant after adjustment for many potential confounders. CONCLUSIONS: In women with type 2 diabetes, greater adherence to Mediterranean diet is associated with a lower prevalence of FSD.", "title": "Adherence to Mediterranean diet and sexual function in women with type 2 diabetes." }, { "docid": "MED-4630", "text": "Arachidonic acid (AA)-derived eicosanoids belong to a complex family of lipid mediators that regulate a wide variety of physiological responses and pathological processes. They are produced by various cell types through distinct enzymatic pathways and act on target cells via specific G-protein-coupled receptors. Although originally recognized for their capacity to elicit biological responses such as vascular homeostasis, protection of the gastric mucosa and platelet aggregation, eicosanoids are now understood to regulate immunopathological processes ranging from inflammatory responses to chronic tissue remodelling, cancer, asthma, rheumatoid arthritis and autoimmune disorders. Here, we review the major properties of eicosanoids and their expanding roles in biology and medicine.", "title": "Arachidonic-acid-derived eicosanoids: roles in biology and immunopathology." }, { "docid": "MED-3000", "text": "An increased risk for colorectal cancer has been consistently reported for long-time consumption of cooked and processed red meat. This has frequently been attributed to chemical carcinogens arising during the cooking process of meat. Long-time fish or poultry consumption apparently does not increase the risk, although similar or higher concentrations of chemical carcinogens were recorded in their preparation for consumption. The geographic epidemiology of colorectal cancer seems to correspond to regions with a high rate of beef consumption. Countries with a virtual absence of beef in the diet (India) or where preferably lamb or goat meat is consumed (several Arabic countries) reveal low rates of colorectal cancer. In China, pork consumption has a long tradition, with an intermediate colorectal cancer rate. In Japan and Korea, large scale beef and pork imports started after World War II or after the Korean War. A steep rise in colorectal cancer incidence was noted after 1970 in Japan and 1990 in Korea. The consumption of undercooked beef (e.g., shabu-shabu, Korean yukhoe and Japanese yukke) became very popular in both countries. The available data are compatible with the interpretation that a specific beef factor, suspected to be one or more thermoresistant potentially oncogenic bovine viruses (e.g., polyoma-, papilloma- or possibly single-stranded DNA viruses) may contaminate beef preparations and lead to latent infections in the colorectal tract. Preceding, concomitant or subsequent exposure to chemical carcinogens arising during cooking procedures should result in increased risk for colorectal cancer synergistic with these infections. Copyright © 2011 UICC.", "title": "Red meat consumption and cancer: reasons to suspect involvement of bovine infectious factors in colorectal cancer." }, { "docid": "MED-3441", "text": "As modern lifestyles and new feeding habits settle in the world, noncommunicable diseases (NCDs) have evolved to be major causes of disability in developing as well as developed countries. As a concomitant effect, there is a growing interest in natural, healthy food and an increasing awareness of risk factors and determinants of disease. This chapter describes some nutritional facts about seaweeds, which have been used as food since ancient times in China, Japan, Egypt, and India and comments on the potential utilization of marine algae as functional foods. This concept and the description of metabolic syndrome are used as a basis to comprehension of seaweeds against two dreadful illnesses of our times: high blood pressure and cancer. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Marine edible algae as disease preventers." }, { "docid": "MED-4738", "text": "BACKGROUND: Isothiocyanates (ITCs), hydrolysis products from glucosinolates, are a family of biologically active compounds originating from cruciferous vegetables. Many ITCs are assumed to have cancer preventive effects and to further evaluate these potential health effects, reliable biomarkers of ITC exposure are needed. AIM OF THE STUDY: In this study we investigated the ability of urinary ITC excretion to reflect a low or high daily intake of cruciferous vegetables. METHODS: The design was a controlled human crossover study (n = 6). Subjects consumed a self-restricted glucosinolate-free diet 48 h before the study-day where a basic diet supplemented with 80 or 350 g of mixed cruciferous vegetables was consumed. All urine was collected in intervals during the 48 h period after ingestion of the cruciferous vegetables. Total ITC in the cruciferous mixture and total ITC and their metabolites in urine was quantified as the cyclocondensation product of 1,2-bezenedithiol by high performance liquid chromatography. RESULTS: The total urinary excretion of ITCs correlated significantly with the two doses of ITC from diets with high or low cruciferous content (r (s )= 0.90, P < 0.01). The fraction of urinary ITC excreted was 69.02 +/- 11.57% and 74.53 +/- 8.39% of the amounts ingested for 80 and 350 g cruciferous vegetables, respectively. CONCLUSION: The results in this study indicate that the urinary excretion of ITCs, measured by use of the cyclocondesation reaction, is a useful and precise tool that may be used as a biomarker of ITC exposure in population based studies.", "title": "Urinary excretion of total isothiocyanates from cruciferous vegetables shows high dose-response relationship and may be a useful biomarker for isot..." }, { "docid": "MED-1333", "text": "New epidemiology confirms that glucose intolerance is a risk factor for pancreatic cancer, and that this association cannot be accounted for by an adverse impact of early pancreatic cancer on beta cell function. Previous reports indicate that risk for pancreatic cancer is increased in adult-onset diabetics. Since streptozotocin diabetes inhibits carcinogen-mediated induction of pancreatic cancer in hamsters, the most reasonable interpretation of these findings is that insulin (or some other beta cell product) acts as a promoter for pancreatic carcinogenesis. This view is consistent with a report that human pancreatic adenocarcinomas express insulin receptors that can stimulate mitosis; an additional possibility is that high insulin levels indirectly promote pancreatic carcinogenesis by boosting effective IGF-I activity via hepatic actions. In international ecologic epidemiology, pancreatic cancer rates correlate tightly with dietary intake of animal products; this may reflect the fact that vegan diets are associated with low diurnal insulin secretion. There is also suggestive evidence that macrobiotic vegan diets, which are low in glycemic index, may increase mean survival time in pancreatic cancer. However, other types of diets associated with decreased postprandial insulin response, such as high-protein diets or 'Mediterranean' diets high in oleic acid, may also have the potential for pancreatic cancer prevention. The huge increases of age-adjusted pancreatic cancer mortality in Japan and among African-Americans during the last century imply that pancreatic cancer is substantially preventable; a low-insulin-response diet coupled with exercise training, weight control, and smoking avoidance, commendable for a great many other reasons, may slash pancreatic cancer mortality dramatically. Copyright 2001 Harcourt Publishers Ltd.", "title": "Insulin secretion as a determinant of pancreatic cancer risk." }, { "docid": "MED-3732", "text": "Background Endoscopic submucosal dissection (ESD) is an advanced technique of therapeutic endoscopy alternative to endoscopic mucosal resection (EMR) for superficial gastrointestinal neoplasms >2 cm. ESD allows for the direct dissection of the submucosa and large lesions can be resected en bloc. ESD is not limited by resection size, increases histologically complete resection rates and may reduce the local recurrence. Nevertheless, the technique is time-consuming, technically demanding and associated with a high complication rate. To reduce the risk of complications, different devices and technical advances have been proposed with conflicting results and, still, ESD en bloc resections of huge lesions are associated with increased complications. Case Presentation We successfully used a combined ESD/EMR technique for huge rectal laterally spreading tumors (LSTs). ESD was used for circumferential resection of 2/3 of the lesion followed by piecemeal resection (2-3 pieces) of the central part of the tumour. In all three patients we obtained the complete dissection of the polyp and the complete histological evaluation in absence of complications and recurrence at 6 months' follow up. Conclusions In the treatment of rectal LSTs, the combined treatment - ESD/EMR resection may be considered a suitable therapeutic option, indicated in selected cases as an alternative to surgery, in which the two techniques are neither reliable nor safe separately. However, to confirm our results, larger trials with longer follow up are required together with improvement of the technique and of the technical devices.", "title": "Rectal laterally spreading tumors successfully treated in two steps by endoscopic submucosal dissection and endoscopic mucosal resection" }, { "docid": "MED-2722", "text": "Background Obesity and physical inactivity are associated with several chronic conditions, increased medical care costs, and premature death. Methods We used the Behavioral Risk Factor Surveillance System (BRFSS), a state-based random-digit telephone survey that covers the majority of United States counties, and the National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of the US civilian noninstitutionalized population. About 3.7 million adults aged 20 years or older participated in the BRFSS from 2000 to 2011, and 30,000 adults aged 20 or older participated in NHANES from 1999 to 2010. We calculated body mass index (BMI) from self-reported weight and height in the BRFSS and adjusted for self-reporting bias using NHANES. We calculated self-reported physical activity—both any physical activity and physical activity meeting recommended levels—from self-reported data in the BRFSS. We used validated small area estimation methods to generate estimates of obesity and physical activity prevalence for each county annually for 2001 to 2011. Results Our results showed an increase in the prevalence of sufficient physical activity from 2001 to 2009. Levels were generally higher in men than in women, but increases were greater in women than men. Counties in Kentucky, Florida, Georgia, and California reported the largest gains. This increase in level of activity was matched by an increase in obesity in almost all counties during the same time period. There was a low correlation between level of physical activity and obesity in US counties. From 2001 to 2009, controlling for changes in poverty, unemployment, number of doctors per 100,000 population, percent rural, and baseline levels of obesity, for every 1 percentage point increase in physical activity prevalence, obesity prevalence was 0.11 percentage points lower. Conclusions Our study showed that increased physical activity alone has a small impact on obesity prevalence at the county level in the US. Indeed, the rise in physical activity levels will have a positive independent impact on the health of Americans as it will reduce the burden of cardiovascular diseases and diabetes. Other changes such as reduction in caloric intake are likely needed to curb the obesity epidemic and its burden.", "title": "Prevalence of physical activity and obesity in US counties, 2001–2011: a road map for action" }, { "docid": "MED-2907", "text": "Background: Diverse perspectives have influenced fish consumption choices. Objectives: We summarized the issue of fish consumption choice from toxicological, nutritional, ecological, and economic points of view; identified areas of overlap and disagreement among these viewpoints; and reviewed effects of previous fish consumption advisories. Methods: We reviewed published scientific literature, public health guidelines, and advisories related to fish consumption, focusing on advisories targeted at U.S. populations. However, our conclusions apply to groups having similar fish consumption patterns. Discussion: There are many possible combinations of matters related to fish consumption, but few, if any, fish consumption patterns optimize all domains. Fish provides a rich source of protein and other nutrients, but because of contamination by methylmercury and other toxicants, higher fish intake often leads to greater toxicant exposure. Furthermore, stocks of wild fish are not adequate to meet the nutrient demands of the growing world population, and fish consumption choices also have a broad economic impact on the fishing industry. Most guidance does not account for ecological and economic impacts of different fish consumption choices. Conclusion: Despite the relative lack of information integrating the health, ecological, and economic impacts of different fish choices, clear and simple guidance is necessary to effect desired changes. Thus, more comprehensive advice can be developed to describe the multiple impacts of fish consumption. In addition, policy and fishery management inter-ventions will be necessary to ensure long-term availability of fish as an important source of human nutrition.", "title": "Which Fish Should I Eat? Perspectives Influencing Fish Consumption Choices" }, { "docid": "MED-3785", "text": "PURPOSE: Components of one-carbon metabolism are believed to influence cancer development with suggested mechanisms, including DNA methylation and DNA repair mechanisms. However, few prospective studies have investigated one-carbon metabolism in relation to prostate cancer risk, and the results have been conflicting. The aim of this study was to do a comprehensive investigation of the components of one-carbon metabolism in relation to prostate cancer risk. A panel of seven circulating B vitamins and related metabolites was selected, most of which have not been studied before. MATERIALS AND METHODS: We analyzed plasma concentrations of betaine, choline, cysteine, methionine, methylmalonic acid (MMA), vitamin B2, and vitamin B6 in 561 cases and 1,034 controls matched for age and recruitment date, nested within the population-based Northern Sweden Health and Disease Cohort. Relative risks of prostate cancer were estimated by conditional logistic regression. RESULTS: Positive associations with prostate cancer risk were observed for choline and vitamin B2, and an inverse association was observed for MMA. The relative risks for a doubling in concentrations were 1.46 [95% confidence interval (95% CI), 1.04-2.05; P(trend) = 0.03] for choline, 1.11 (95% CI, 1.00-1.23; P(trend) = 0.04) for vitamin B2, and 0.78 (95% CI, 0.63-0.97; P(trend) = 0.03) for MMA. Concentrations of betaine, cysteine, methionine, and vitamin B6 were not associated with prostate cancer risk. CONCLUSION: The results of this large prospective study suggest that elevated plasma concentrations of choline and vitamin B2 may be associated with an increased risk of prostate cancer. These novel findings support a role of one-carbon metabolism in prostate cancer etiology and warrant further investigation.", "title": "One-carbon metabolism and prostate cancer risk: prospective investigation of seven circulating B vitamins and metabolites." }, { "docid": "MED-2407", "text": "Background Persistent organic pollutants (POPs) are hazardous chemicals omnipresent in our food chain, which have been internationally regulated to ensure public health. Initially described for their potency to affect reproduction and promote cancer, recent studies have highlighted an unexpected implication of POPs in the development of metabolic diseases like type 2 diabetes and obesity. Based on this novel knowledge, this article aims at stimulating discussion and evaluating the effectiveness of current POP legislation to protect humans against the risk of metabolic diseases. Furthermore, the regulation of POPs in animal food products in the European Union (EU) is addressed, with a special focus on marine food since it may represent a major source of POP exposure to humans. Discussion There is mounting scientific evidence showing that current POP risk assessment and regulation cannot effectively protect humans against metabolic disorders. Better regulatory control of POPs in dietary products should be of high public health priority. Summary The general population is exposed to sufficient POPs, both in term of concentration and diversity, to induce metabolic disorders. This situation should attract the greatest attention from the public health and governmental authorities.", "title": "Public health concern behind the exposure to persistent organic pollutants and the risk of metabolic diseases" }, { "docid": "MED-2261", "text": "Seven zinc-containing dietary supplements were analyzed for zinc (Zn) and cadmium (Cd) by inductively coupled plasma/mass spectrometry (ICP/MS). Cadmium was detected in all samples; however, the amount of Cd per 15 mg Zn (the daily US Recommended Dietary Allowance) varied by over 37-fold (0.039 to 1.46 micrograms Cd/15 mg Zn). Supplements with Zn in the form of a gluconate consistently contained the lowest amounts of Cd. Because Cd is a non-essential potentially toxic element for humans, its concentration in nutritional supplements should be minimized and possibly regulated by government-established standards.", "title": "Cadmium in zinc-containing mineral supplements." }, { "docid": "MED-3860", "text": "Purpose Evaluate the hypothesis that relation of breast cancer associated with dietary fiber intakes varies by type of fiber, menopausal, and the tumor’s hormone receptor status. Methods A case-control study of female breast cancer was conducted in Connecticut. A total of 557 incident breast cancer cases and 536 age frequency-matched controls were included in the analysis. Information on dietary intakes was collected through in-person interviews with a semi-quantitative food frequency questionnaire and was converted into nutrient intakes. Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression. Results Among pre-menopausal women, higher intake of soluble fiber (highest versus lowest quartile of intake) was associated with a significantly reduced risk of breast cancer (OR = 0.38, 95% CI, 0.15–0.97, Ptrend = 0.08). When further restricted to pre-menopausal women with ER− tumors, the adjusted OR for the highest quartile of intake was 0.15 (95% CI, 0.03–0.69, Ptrend = 0.02) for soluble fiber intake. Among post-menopausal women, no reduced risk of breast cancer was observed for either soluble or insoluble fiber intakes or among ER+ or ER− tumor groups. Conclusions The results from this study show that dietary soluble fiber intake is associated with a significantly reduced risk of ER− breast cancer among pre-menopausal women. Additional studies with larger sample size are needed to confirm these results.", "title": "Dietary fiber intake and risk of breast cancer by menopausal and estrogen receptor status" }, { "docid": "MED-1378", "text": "Longevity is a very complex phenomenon, because many environmental, behavioral, socio-demographic and dietary factors influence the physiological pathways of aging and life-expectancy. Nutrition has been recognized to have an important impact on overall mortality and morbidity; and its role in extending life expectancy has been the object of extensive scientific research. This paper reviews the pathophysiological mechanisms that potentially link aging with diet and the scientific evidence supporting the anti-aging effect of the traditional Mediterranean diet, as well as of some specific foods. The diet and several of its components have additionally been shown to have beneficial effects on the co-morbidities typical of elderly populations. Furthermore, the epigenetic effects of diet on the aging process - through calorie restriction and the consumption of foods like red wine, orange juice, probiotics and prebiotics - have attracted scientific interest. Some, such as dark chocolate, red wine, nuts, beans, avocados are being promoted as anti-aging foods, due to their anti-oxidative and anti-inflammatory properties. Finally, an important moderator in the relationship between diet, longevity and human health remains the socio-economic status of individual, as a healthy diet, due to its higher cost, is closely related to higher financial and educational status. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.", "title": "Longevity and diet. Myth or pragmatism?" }, { "docid": "MED-3350", "text": "Normotensive adults on low-sodium, weight-loss, and control diets recorded preferences and perceived saltiness for sodium chloride (NaCl) added to cream soup at intervals over 1 yr. Reduction in sodium intake and excretion accompanied a shift in preference toward less salt: preferred concentrations by ad libitum salting declined from 0.72% at the onset to 0.33% NaCl at week 24; hedonic scores for high concentrations of NaCl decreased significantly while scores for low concentrations increased. After 3 mo of sodium restriction, NaCl preferences readjusted to a lower level: ad libitum additions of NaCl were similar after 13, 24, and 52 wk. Less hedonic variation was observed among controls than among Na-restricted groups. The weight-loss group showed increased liking for mid-range NaCl levels. Mechanisms underlying preference changes, including physiological, behavioral, and context effects, may provide insights into maintenance of low-sodium diets for treatment and prevention of hypertension.", "title": "Effect of dietary sodium restriction on taste responses to sodium chloride: a longitudinal study." }, { "docid": "MED-1932", "text": "There is increasing interest in discovering mechanisms that mediate the effects of childhood stress on late-life disease morbidity and mortality. Previous studies have suggested one potential mechanism linking stress to cellular aging, disease and mortality in humans: telomere erosion. We examined telomere erosion in relation to children’s exposure to violence, a salient early-life stressor, which has known long-term consequences for well-being and is a major public-health and social-welfare problem. In the first prospective-longitudinal study with repeated telomere measurements in children while they experienced stress, we tested the hypothesis that childhood violence exposure would accelerate telomere erosion from age 5 to age 10 years. Violence was assessed as exposure to maternal domestic violence, frequent bullying victimization and physical maltreatment by an adult. Participants were 236 children (49% females; 42% with one or more violence exposures) recruited from the Environmental-Risk Longitudinal Twin Study, a nationally representative 1994–1995 birth cohort. Each child’s mean relative telomere length was measured simultaneously in baseline and follow-up DNA samples, using the quantitative PCR method for T/S ratio (the ratio of telomere repeat copy numbers to single-copy gene numbers). Compared with their counterparts, the children who experienced two or more kinds of violence exposure showed significantly more telomere erosion between age-5 baseline and age-10 follow-up measurements, even after adjusting for sex, socioeconomic status and body mass index (B = −0.052, s.e. = 0.021, P = 0.015). This finding provides support for a mechanism linking cumulative childhood stress to telomere maintenance, observed already at a young age, with potential impact for life-long health.", "title": "Exposure to violence during childhood is associated with telomere erosion from 5 to 10 years of age: a longitudinal study" }, { "docid": "MED-4057", "text": "BACKGROUND: Heterocyclic amines, mutagens formed in meats cooked at high temperatures, have been demonstrated as mammary carcinogens in animals. We conducted a nested, case-control study among 41836 cohort members of the Iowa Women's Health Study to evaluate the potential role of heterocyclic amines and intake of well-done meat in the risk for human breast cancer. METHODS: A questionnaire was mailed to individuals in the cohort who had breast cancer diagnosed during the period from 1992 through 1994 and a random sample of cancer-free cohort members to obtain information on usual intake of meats and on meat preparation practices. Color photographs showing various doneness levels of hamburger, beefsteak, and bacon were included. Multivariate analysis was performed on data from 273 case subjects and 657 control subjects who completed the survey. RESULTS: A dose-response relationship was found between doneness levels of meat consumed and breast cancer risk. The adjusted odds ratios (ORs) for very well-done meat versus rare or medium-done meat were 1.54 (95% confidence interval [CI]=0.96-2.47) for hamburger, 2.21 (95% CI=1.30-3.77) for beef steak, and 1.64 (95% CI=0.92-2.93) for bacon. Women who consumed these three meats consistently very well done had a 4.62 times higher risk (95% CI=1.36-15.70) than that of women who consumed the meats rare or medium done. Risk of breast cancer was also elevated with increasing intake of well-done to very well-done meat. CONCLUSIONS: Consumption of well-done meats and, thus, exposures to heterocyclic amines (or other compounds) formed during high-temperature cooking may play an important role in the risk of breast cancer.", "title": "Well-done meat intake and the risk of breast cancer." }, { "docid": "MED-3821", "text": "Reducing the concentration of polyamines (spermine, spermidine, and putrescine) in the body pool may slow the cancer process. Because dietary spermine, spermidine, and putrescine contribute to the body pool of polyamines, quantifying them in the diet is important. Limited information about polyamine content of food is available, especially for diets in the United States. This brief report describes the development of a polyamine database linked to the Fred Hutchinson Cancer Center food frequency questionnaire (FFQ). Values for spermine, spermidine, and putrescine were calculated and reported per serving size (nmol/serving). Of the foods from the database that were evaluated, fresh and frozen corn contain the highest levels of putrescine (560,000 nmol/serving and 902,880 nmol/serving) and spermidine (137,682 nmol/serving and 221,111 nmol/serving), and green pea soup contains the highest concentration of spermine (36,988 nmol/serving). The polyamine database and FFQ were tested with a convenience sample (n=165). Average daily polyamine intakes from the sample were: 159,133 nmol/day putrescine, 54,697 nmol/day spermidine, and 35,698 nmol/day spermine. Orange and grapefruit juices contributed the greatest amount of putrescine (44,441 nmol/day) to the diet. Green peas contributed the greatest amount of spermidine (3,283 nmol/day) and ground meat contributed the greatest amount of spermine (2,186 nmol/day). Development of this database linked to an FFQ provides a means of estimating polyamine intake and contributes to investigations relating polyamines to cancer.", "title": "Development of a Polyamine Database for Assessing Dietary Intake" }, { "docid": "MED-3590", "text": "Male reproductive disorders that are of interest from an environmental point of view include sexual dysfunction, infertility, cryptorchidism, hypospadias and testicular cancer. Several reports suggest declining sperm counts and increase of these reproductive disorders in some areas during some time periods past 50 years. Except for testicular cancer this evidence is circumstantial and needs cautious interpretation. However, the male germ line is one of the most sensitive tissues to the damaging effects of ionizing radiation, radiant heat and a number of known toxicants. So far occupational hazards are the best documented risk factors for impaired male reproductive function and include physical exposures (radiant heat, ionizing radiation, high frequency electromagnetic radiation), chemical exposures (some solvents as carbon disulfide and ethylene glycol ethers, some pesticides as dibromochloropropane, ethylendibromide and DDT/DDE, some heavy metals as inorganic lead and mercury) and work processes such as metal welding. Improved working conditions in affluent countries have dramatically decreased known hazardous workplace exposures, but millions of workers in less affluent countries are at risk from reproductive toxicants. New data show that environmental low-level exposure to biopersistent pollutants in the diet may pose a risk to people in all parts of the world. For other toxicants the evidence is only suggestive and further evaluation is needed before conclusions can be drawn. Whether compounds as phthalates, bisphenol A and boron that are present in a large number of industrial and consumer products entails a risk remains to be established. The same applies to psychosocial stressors and use of mobile phones. Finally, there are data indicating a particular vulnerability of the fetal testis to toxicants—for instance maternal tobacco smoking. Time has come where male reproductive toxicity should be addressed form entirely new angles including exposures very early in life.", "title": "Male reproductive organs are at risk from environmental hazards" }, { "docid": "MED-2570", "text": "The functional properties, including antioxidant and chemopreventative capacities as well as the inhibitory effects on angiotensin-converting enzyme (ACE), α-glucosidase and pancreatic lipase, of three Australian-grown faba bean genotypes (Nura, Rossa and TF(Ic*As)*483/13) were investigated using an array of in vitro assays. Chromatograms of on-line post column derivatisation assay coupled with HPLC revealed the existence of active phenolics (hump) in the coloured genotypes, which was lacking in the white-coloured breeding line, TF(Ic*As)*483/13. Roasting reduced the phenolic content, and diminished antioxidant activity by 10-40 % as measured by the reagent-based assays (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and oxygen radical absorbance capacity) in all genotypes. Cell culture-based antioxidant activity assay (cellular antioxidant activity) showed an increase of activity in the coloured genotypes after roasting. Faba bean extracts demonstrated cellular protection ability against H₂O₂-induced DNA damage (assessed using RAW264.7 cells), and inhibited the proliferation of all human cancer cell lines (BL13, AGS, Hep G2 and HT-29) evaluated. However, the effect of faba bean extracts on the non-transformed human cells (CCD-18Co) was negligible. Flow cytometric analyses showed that faba bean extracts successfully induced apoptosis of HL-60 (acute promyelocytic leukaemia) cells. The faba bean extracts also exhibited ACE, α-glucosidase and pancreatic lipase inhibitory activities. Overall, extracts from Nura (buff-coloured) and Rossa (red-coloured) were comparable, while TF(Ic*As)*483/13 (white-coloured) contained the lowest phenolic content and exhibited the least antioxidant and enzyme inhibition activities. These results are important to promote the utilisation of faba beans in human diets for various health benefits.", "title": "In vitro investigations of the potential health benefits of Australian-grown faba beans (Vicia faba L.): chemopreventative capacity and inhibitory ..." }, { "docid": "MED-2517", "text": "Many experts in the biology of ageing believe that pharmacological interventions to slow ageing are a matter of ‘when’ rather than ‘if’. A leading target for such interventions is the nutrient response pathway defined by the mechanistic target of rapamycin (mTOR). Inhibition of this pathway extends lifespan in model organisms and confers protection against a growing list of age-related pathologies. Characterized inhibitors of this pathway are already clinically approved, and others are under development. Although adverse side effects currently preclude use in otherwise healthy individuals, drugs that target the mTOR pathway could one day become widely used to slow ageing and reduce age-related pathologies in humans.", "title": "mTOR is a key modulator of ageing and age-related disease" }, { "docid": "MED-2212", "text": "With the republication of Grant (18), the first paper providing epidemiologic evidence linking diet to the development of Alzheimer's disease (AD), it is an appropriate time to review the findings and hypotheses therein in light of the subsequent literature. The main findings, that dietary fat and energy in old age are high risk factors, while fish and cereals are risk-reduction factors, have been supported in various recent epidemiologic studies. Diet contributes to the development of AD through modulating oxidative stress and inflammation, which is also linked to oxidative stress, but may also arise from series 2 prostaglandins. Thus, as one ages, dietary modifications and additional supplements designed to reduce free radical production and inflammation provide a significant measure of reduction in risk for the development of AD.", "title": "Dietary links to Alzheimer's disease: 1999 update." }, { "docid": "MED-4831", "text": "Dyslipidemia is a primary risk factor for cardiovascular disease, peripheral vascular disease, and stroke. Current guidelines recommend diet as first-line therapy for patients with elevated plasma cholesterol concentrations. However, what constitutes an optimal dietary regimen remains a matter of controversy. Large prospective trials have demonstrated that populations following plant-based diets, particularly vegetarian and vegan diets, are at lower risk for ischemic heart disease mortality. The investigators therefore reviewed the published scientific research to determine the effectiveness of plant-based diets in modifying plasma lipid concentrations. Twenty-seven randomized controlled and observational trials were included. Of the 4 types of plant-based diets considered, interventions testing a combination diet (a vegetarian or vegan diet combined with nuts, soy, and/or fiber) demonstrated the greatest effects (up to 35% plasma low-density lipoprotein cholesterol reduction), followed by vegan and ovolactovegetarian diets. Interventions allowing small amounts of lean meat demonstrated less dramatic reductions in total cholesterol and low-density lipoprotein levels. In conclusion, plant-based dietary interventions are effective in lowering plasma cholesterol concentrations.", "title": "Effects of plant-based diets on plasma lipids." }, { "docid": "MED-1929", "text": "BACKGROUND This study examined the effects of brief daily yogic meditation on mental health, cognitive functioning, and immune cell telomerase activity in family dementia caregivers with mild depressive symptoms. METHODS Thirty-nine family dementia caregivers (mean age 60.3 years old (SD=10.2)) were randomized to practicing Kirtan Kriya or listening to relaxation music for 12 minutes per day for eight weeks. The severity of depressive symptoms, mental and cognitive functioning were assessed at baseline and follow-up. Telomerase activity in peripheral blood mononuclear cells (PMBC) was examined in peripheral PBMC pre- and post-intervention. RESULTS The meditation group showed significantly lower levels of depressive symptoms and greater improvement in mental health and cognitive functioning compared to the relaxation group. In the meditation group, 65.2% showed 50% improvement on the Hamilton Depression Rating scale and 52% of the participants showed 50% improvement on the Mental Health Composite Summary score (MCS) of the SF-36 scale; compared to 31.2% and 19% respectively in the relaxation group (pp<0.05). The meditation group showed 43% improvement in telomerase activity compared to 3.7% in the relaxation group (p=0.05). CONCLUSION This pilot study found that brief daily meditation practices by family dementia caregivers can lead to improved mental and cognitive functioning, and lower levels of depressive symptoms. This improvement is accompanied by an increase in telomerase activity suggesting improvement in stress-induced cellular aging. These results need to be confirmed in a larger sample.", "title": "A pilot study of yogic meditation for family dementia caregivers with depressive symptoms: Effects on mental health, cognition, and telomerase activity" }, { "docid": "MED-4168", "text": "Diet is purported to be means of exposure to many environmental contaminants. The purpose of this study is to understand the influence of dietary change on the levels of exposure to several environmental chemicals - in particular, antibiotics and phthalates. For this purpose, we examined the extent to which short-term changes in diet influenced the inadvertent exposure levels to these chemicals in an adult population. We recruited participants (n=25) of a five-day 'Temple Stay' program in Korea and collected urine samples before and after the program. We also conducted a questionnaire survey on participants' dietary patterns prior to their participation. During the program, participants followed the daily routines of Buddhist monks and maintained a vegetarian diet. Urinary levels of three antibiotics and their major metabolites, metabolites of four major phthalates, and malondialdehyde (MDA) as an oxidative stress biomarker were analyzed. The frequency and levels of detection for antibiotics and phthalates noticeably decreased during the program. Urinary MDA levels were significantly lower than before program participation (0.16 versus 0.27mg/g creatinine). Although the exposure to target compounds might be influenced by other behavioral patterns, these results suggest that even short-term changes in dietary behavior may significantly decrease inadvertent exposure to antibiotics and phthalates and hence may reduce oxidative stress levels. Copyright 2010 Elsevier Inc. All rights reserved.", "title": "Influence of a five-day vegetarian diet on urinary levels of antibiotics and phthalate metabolites: a pilot study with \"Temple Stay\" participants." }, { "docid": "MED-4117", "text": "Breast cancer is a complex disease. Its aetiology is multifactorial, its period of development can span decades, and its clinical course is highly variable. Evaluation of the role of the immune response in either the development or control of breast cancer is also complex. Nevertheless, there is substantial information that in this disease, the immune response is not a host defence reaction and may even serve to facilitate cancer development. This evidence comes from a variety of sources including clinical-pathological investigations in women that show a correlation between the intensity of lymphocytic infiltration into the tumour mass with poor prognosis, studies in breast cancer patients that demonstrate a similar correlation between delayed hypersensitivity reactivity or in vitro assays of immune reactivity to tumour cell membranes or non-specific antigens and poor prognosis, and analyses of cancer incidence in chronically immunosuppressed, kidney transplant recipients who develop an unexpectedly low incidence of breast cancer. The overall conclusions from these human studies are corroborated by observations in mouse mammary tumour models that also demonstrate immune enhancement of breast cell proliferation in vitro and of breast cancer development in vivo. Potential mechanisms for these effects include production, by inflammatory cell infiltrates, of direct or indirect modulators of breast cell growth, e.g. cytokines, peptide or steroid hormones, enzymes involved in steroid metabolism, as well as of antibodies to growth factors or their receptors. These immune facilitatory mechanisms must be overcome if immune-based therapies are to be applied successfully in breast cancer.", "title": "Immunological enhancement of breast cancer." }, { "docid": "MED-2910", "text": "Hit Reaction Time latencies (HRT) in the Continuous Performance Test (CPT) measure the speed of visual information processing. The latencies may involve different neuropsychological functions depending on the time from test initiation, i.e., first orientation, learning and habituation, then cognitive processing and focused attention, and finally sustained attention as the dominant demand. Prenatal methylmercury exposure is associated with increased reaction time (RT) latencies. We therefore examined the association of methylmercury exposure with the average HRT at age 14 years at three different time intervals after test initiation. A total of 878 adolescents (87% of birth cohort members) completed the CPT. The RT latencies were recorded for 10 minutes, with visual targets presented at 1000 ms intervals. After confounder adjustment, regression coefficients showed that CPT-RT outcomes differed in their associations with exposure biomarkers of prenatal methylmercury exposure: During the first two minutes, the average HRT was weakly associated with methylmercury (beta (SE) for a ten-fold increase in exposure, (3.41 (2.06)), was strongly for the 3-to-6 minute interval (6.10 (2.18)), and the strongest during 7–10 minutes after test initiation (7.64 (2.39)). This pattern was unchanged when simple reaction time and finger tapping speed were included in the models as covariates. Postnatal methylmercury exposures did not affect the outcomes. Thus, these findings suggest that sustained attention as a neuropsychological domain is particularly vulnerable to developmental methylmercury exposure, indicating probable underlying dysfunction of the frontal lobes. When using CPT data as a possible measure of neurotoxicity, test results should therefore be analyzed in regard to time from test initiation and not as overall average reaction times.", "title": "Sensitivity of Continuous Performance Test (CPT) at Age 14 Years to Developmental Methylmercury Exposure" }, { "docid": "MED-1957", "text": "One combined catfish feed sample from Arkansas, USA, and its eight ingredients were analyzed for PCDDs and PCDFs. One of the ingredients, soybean meal, was highly contaminated by PCDDs, especially the toxic 2,3,7,8-substituted congeners, e.g., 7.3 pg/g dry weight or 370 pg/g lipid for the 2,3,7,8-tetra CDD. The I-TEQ value for the soybean meal was 11.4 pg/g dry weight or 576 pg/g fat. The corresponding values for the combined catfish feed concentrations were approximately 3 times lower. The congener pattern, the congener profile and the ratio sigma PCDDs/sigma PCDFs for the soybean meal were quite unique. We are not aware of any environmental sample or technical product with similar characteristics. As a result, natural formation of the PCDDs found in the soybean meal cannot be ruled out.", "title": "PCDD and PCDF contamination in catfish feed from Arkansas, USA." }, { "docid": "MED-4261", "text": "BACKGROUND: Meat intake may be related to weight gain because of its high energy and fat content. Some observational studies have shown that meat consumption is positively associated with weight gain, but intervention studies have shown mixed results. OBJECTIVE: Our objective was to assess the association between consumption of total meat, red meat, poultry, and processed meat and weight gain after 5 y of follow-up, on average, in the large European population who participated in the European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home and Obesity (EPIC-PANACEA) project. DESIGN: A total of 103,455 men and 270,348 women aged 25-70 y were recruited between 1992 and 2000 in 10 European countries. Diet was assessed at baseline with the use of country-specific validated questionnaires. A dietary calibration study was conducted in a representative subsample of the cohort. Weight and height were measured at baseline and self-reported at follow-up in most centers. Associations between energy from meat (kcal/d) and annual weight change (g/y) were assessed with the use of linear mixed models, controlled for age, sex, total energy intake, physical activity, dietary patterns, and other potential confounders. RESULTS: Total meat consumption was positively associated with weight gain in men and women, in normal-weight and overweight subjects, and in smokers and nonsmokers. With adjustment for estimated energy intake, an increase in meat intake of 250 g/d (eg, one steak at approximately 450 kcal) would lead to a 2-kg higher weight gain after 5 y (95% CI: 1.5, 2.7 kg). Positive associations were observed for red meat, poultry, and processed meat. CONCLUSION: Our results suggest that a decrease in meat consumption may improve weight management.", "title": "Meat consumption and prospective weight change in participants of the EPIC-PANACEA study." }, { "docid": "MED-1921", "text": "Dietary factors, including dietary fat, may affect the biological aging process, as reflected by the shortening of telomere length (TL), by affecting levels of oxidative stress and inflammatory responses. We examined the direct relations of total and types of dietary fats and fat-rich foods to peripheral leukocyte TL. In 4029 apparently healthy postmenopausal women who participated in the Women’s Health Initiative, intakes of total fat, individual fatty acids, and fat-rich foods were assessed by a questionnaire. TL was measured by quantitative polymerase chain reaction. Intake of short-to-medium-chain saturated fatty acids (SMSFAs; aliphatic tails of ≤12 carbons) was inversely associated with TL. Compared with participants in other quartiles of SMSFA intake, women who were in the highest quartile (median: 1.29% of energy) had shorter TLs [mean: 4.00 kb (95% CI: 3.89, 4.11 kb)], whereas women in the lowest quartile of intake (median: 0.29% of energy) had longer TLs [mean: 4.13 kb (95% CI: 4.03, 4.24 kb); P-trend = 0.046]. Except for lauric acid, all other individual SMSFAs were inversely associated with TL (P < 0.05). In isoenergetic substitution models, the substitution of 1% of energy from SMSFAs with any other energy source was associated with 119 bp longer TLs (95% CI: 21, 216 bp). Intakes of nonskim milk, butter, and whole-milk cheese (major sources of SMSFAs) were all inversely associated with TL. No significant associations were found with long-chain saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids. In conclusion, we found that higher intakes of SMSFAs and SMSFA-rich foods were associated with shorter peripheral leukocyte TL among postmenopausal women. These findings suggest the potential roles of SMSFAs in the rate of biological aging.", "title": "Intake of Small-to-Medium-Chain Saturated Fatty Acids Is Associated with Peripheral Leukocyte Telomere Length in Postmenopausal Women" }, { "docid": "MED-1579", "text": "Crohn's disease is an autoimmune disorder that affects nearly 1.4 million Americans. The etiology of Crohn's disease is not completely understood, however, research has suggested a genetic link. There is currently no known cure for Crohn's disease and, as a result, most government-funded research is being conducted to increase the quality of life of afflicted patients (i.e. reducing chronic inflammation and alleviating growth impairment in pediatric patients). A number of treatment options are available including an alpha-4 integrin inhibitor and several TNF-alpha inhibitors. Furthermore, research is being conducted on several alternative treatment options to help understand exactly which cellular mechanisms (i.e. inducing apoptosis in leukocytes) are required for clinical efficacy. This review seeks to chronicle the current available treatment options for patients affected by Crohn's disease to aid in understanding potential cellular mechanistic requirements for an efficacious drug, and shed light on potential options for future treatment. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.", "title": "Crohn's disease: a review of treatment options and current research." }, { "docid": "MED-2115", "text": "Dietary PUFA, mainly those of the n-3 family, are known to play essential roles in the maintenance of energy balance and in the reduction of body fat deposition through the upregulation of mitochondrial uncoupling that is the main source of reactive oxygen species. We hypothesized that rat supplementation with raw donkey's milk (DM), characterized by low-fat content and higher n3:n6 ratio, may affect energy balance, lipid metabolism, and prooxidant status as compared to animals treated with cow's milk. In the present study, the effects of drinking raw DM (for 4 weeks) on energy balance, lipid metabolism, antiinflammatory, and antioxidant/detoxifying defences was compared to that produced by rat intake of an iso-energetic amount of raw cow's milk. The hypolipidemic effect produced by DM paralleled with the enhanced mitochondrial activity/proton leakage and with the increased activity or expression of mitochondrial markers namely, carnitine palmitoyl transferase and uncoupling protein 2. The association of decreased energy efficiency with reduced proinflammatory signs (TNF-α and LPS levels) with the significant increase antioxidant (total thiols) and detoxifying enzyme activities (glutathione-S-transferase NADH quinone oxidoreductase) in DM-treated animals, indicated that beneficial effects were attributable, at least in part, to the activation of nuclear factor 2 erythroid-related factor 2 pathway. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.", "title": "Diet supplementation with donkey milk upregulates liver mitochondrial uncoupling, reduces energy efficiency and improves antioxidant and antiinflam..." }, { "docid": "MED-3027", "text": "Background Some persistent environmental chemicals are suspected of causing an increased risk of type 2 diabetes mellitus, a disease particularly common after age 70. This concern was examined in a cross-sectional study of elderly subjects in a population with elevated contaminant exposures from seafood species high in the food chain. Methods Clinical examinations of 713 Faroese residents aged 70-74 years (64% of eligible population) included fasting plasma concentrations of glucose and insulin, and glycosylated hemoglobin. Lifetime exposure to persistent environmental chemicals from pilot whale and other traditional food was estimated from a dietary questionnaire and by analysis of blood samples for polychlorinated biphenyls (PCBs) and related food contaminants. Results Septuagenarians with type 2 diabetes or impaired fasting glycemia tended to have higher PCB concentrations and higher past intake of traditional foods, especially during childhood and adolescence. In non-diabetic subjects, the fasting insulin concentration decreased by 7% (95% CI= −12% to −2%) for each doubling of the PCB concentration after adjustment for sex and body mass index at age 20. Conversely, the fasting glucose concentration increased by 6% (−1% to 13%) for each doubling in PCB. Similar associations were seen in subjects without impaired fasting glycemia, while further adjustment for current body mass index and lipid metabolism parameters attenuated some of the associations. Conclusions Impaired insulin secretion appears to constitute an important part of the type 2 diabetes pathogenesis associated with exposure to persistent lipophilic food contaminants.", "title": "Marine Food Pollutants as a Risk Factor for Hypoinsulinemia and Type 2 Diabetes" }, { "docid": "MED-3088", "text": "Elevated serum phosphorus is a major, preventable etiologic factor associated with the increased cardiovascular morbidity and mortality of dialysis patients. An important determinant of serum phosphorus is the dietary intake of this mineral; this makes dietary restriction of phosphorus a cornerstone for the prevention and treatment of hyperphosphatemia. The average daily dietary intake of phosphorus is about 1550 mg for males and 1000 mg for females. In general, foods high in protein are also high in phosphorus. These figures, however, are changing as phosphates are currently being added to a large number of processed foods including meats, cheeses, dressings, beverages, and bakery products. As a result, and depending on the food choices, such additives may increase the phosphorus intake by as a much as 1 g/day. Moreover, nutrient composition tables usually do not include the phosphorus from these additives, resulting in an underestimate of the dietary intake of phosphorus in our patients. Our goal is to convey an understanding of the phosphorus content of the current American diet to better equip nephrologists in their attempt to control hyperphosphatemia.", "title": "Hidden sources of phosphorus in the typical American diet: does it matter in nephrology?" }, { "docid": "MED-3983", "text": "This study was aimed at determining the molecular epidemiology of rabies virus (RABV) circulating in Vietnam. Intra vitam samples (saliva and cerebrospinal fluid) were collected from 31 patients who were believed to have rabies and were admitted to hospitals in northern provinces of Vietnam. Brain samples were collected from 176 sick or furious rabid dogs from all over the country. The human and canine samples were subjected to reverse transcription-polymerase chain reaction analysis. The findings showed that 23 patients tested positive for RABV. Interestingly, 5 rabies patients did not have any history of dog or cat bites, but they had an experience of butchering dogs or cats, or consuming their meat. RABV was also detected in 2 of the 100 sick dogs from slaughterhouses. Molecular epidemiological analysis of 27 RABV strains showed that these viruses could be classified into two groups. The RABVs classified into Group 1 were distributed throughout Vietnam and had sequence similarity with the strains from China, Thailand, Malaysia, and the Philippines. However, the RABVs classified into Group 2 were only found in the northern provinces of Vietnam and showed high sequence similarity with the strain from southern China. This finding suggested the recent influx of Group 2 RABVs between Vietnam and China across the border. Although the incidence of rabies due to circulating RABVs in slaughterhouses is less common than that due to dog bite, the national program for rabies control and prevention in Vietnam should include monitoring of the health of dogs meant for human consumption and vaccination for workers at dog slaughterhouses. Further, monitoring of and research on the circulating RABVs in dog markets may help to determine the cause of rabies and control the spread of rabies in slaughterhouses in Vietnam.", "title": "Molecular epidemiology of rabies virus in Vietnam (2006-2009)." }, { "docid": "MED-4748", "text": "BACKGROUND: Adrenarche is the increase in adrenal androgen (AA) production starting in childhood. Until now, it has been unknown whether or not nutritional factors modulate adrenarche. OBJECTIVE: The objective was to examine whether body composition and certain dietary intakes are associated with AA production in children after accounting for urinary indicators of major adrenarche-related steroidogenic enzymes. DESIGN: Androgen and glucocorticoid metabolites were profiled by gas chromatography-mass spectrometry in 24-h urine samples of 137 healthy prepubertal children aged 3-12 y, for whom birth characteristics, growth velocity data, and 3-d weighed-diet record information were available. Associations of the sum of C19 metabolites (reflecting daily AA secretion) with nutritional factors [fat mass (FM), fat-free mass (FFM), nutrient intakes, glycemic index, and glycemic load] and AA-relevant estimates of steroidogenic enzyme were examined in stepwise multiple regression models adjusted for age, sex, urine volume, and total energy intake. Enzyme activity estimates were calculated by using specific urinary steroid metabolite ratios. RESULTS: Of the nutrition-relevant predictors, FM (P < 0.0001) explained most of the variation of AA secretion (R(2) = 5%). Animal protein intake was also positively associated with AA secretion (P < 0.05), which explained 1% of its variation. FFM (P = 0.1) and total protein intake (P = 0.05) showed positive trends. The difference in daily AA secretion between the lowest and highest quartile of FM was comparable to that between the lowest and highest estimated activity of one of the major steroidogenic enzymes. CONCLUSIONS: Body fat mass may relevantly influence prepubertal adrenarchal androgen status. In addition, animal protein intake may also make a small contribution to AA secretion in children.", "title": "Body fat and animal protein intakes are associated with adrenal androgen secretion in children." }, { "docid": "MED-2648", "text": "The aim of this study was to compare results obtained by eight different short-term assays of estrogenlike actions of chemicals conducted in 10 different laboratories in five countries. Twenty chemicals were selected to represent direct-acting estrogens, compounds with estrogenic metabolites, estrogenic antagonists, and a known cytotoxic agent. Also included in the test panel were 17beta++-estradiol as a positive control and ethanol as solvent control. The test compounds were coded before distribution. Test methods included direct binding to the estrogen receptor (ER), proliferation of MCF-7 cells, transient reporter gene expression in MCF-7 cells, reporter gene expression in yeast strains stably transfected with the human ER and an estrogen-responsive reporter gene, and vitellogenin production in juvenile rainbow trout. 17beta-Estradiol, 17alpha-ethynyl estradiol, and diethylstilbestrol induced a strong estrogenic response in all test systems. Colchicine caused cytotoxicity only. Bisphenol A induced an estrogenic response in all assays. The results obtained for the remaining test compounds--tamoxifen, ICI 182.780, testosterone, bisphenol A dimethacrylate, 4-n-octylphenol, 4-n-nonylphenol, nonylphenol dodecylethoxylate, butylbenzylphthalate, dibutylphthalate, methoxychlor, o,p'-DDT, p,p'-DDE, endosulfan, chlomequat chloride, and ethanol--varied among the assays. The results demonstrate that careful standardization is necessary to obtain a reasonable degree of reproducibility. Also, similar methods vary in their sensitivity to estrogenic compounds. Thus, short-term tests are useful for screening purposes, but the methods must be further validated by additional interlaboratory and interassay comparisons to document the reliability of the methods.", "title": "Comparison of Short-Term Estrogenicity Tests for Identification of Hormone-Disrupting Chemicals" }, { "docid": "MED-3242", "text": "Previous studies have suggested that dietary factors may be important in the development of bladder cancer. We examined macronutrient intake in relation to risk of urothelial cell carcinoma among 469,339 men and women in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by sex, age at recruitment and centre and further adjusted for smoking status and duration, body mass index and total energy intake. After an average of 11.3 years of follow-up, 1,416 new cases of urothelial cell carcinoma were identified. After allowing for measurement error, a 3% increase in the consumption of energy intake from animal protein was associated with a 15% higher risk (95% confidence interval [CI]: 3-30%; p(trend) = 0.01) and a 2% increase in energy from plant protein intake was associated with a 23% lower risk (95% CI: 36-7%, p(trend) = 0.006). Dietary intake of fat, carbohydrate, fibre or calcium was not associated with risk. These findings suggest that animal and/or plant protein may affect the risk of urothelial cell carcinoma, and examination of these associations in other studies is needed. Copyright © 2012 UICC.", "title": "Macronutrient intake and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition." }, { "docid": "MED-1607", "text": "Background: As sodium, potassium and fluid intake are related to hypertension, an established risk factor for renal cell cancer (RCC), they may be independent risk factors for RCC. Methods: The Netherlands Cohort Study (NLCS) with case-cohort design included 120 852 participants aged 55–69 years. At baseline, diet and lifestyle were assessed with questionnaires. After 17.3 years of follow-up, 485 RCC cases and 4438 subcohort members were available for analyses. Results: Sodium intake increased RCC risk (P-trend=0.03), whereas fluid and potassium intake did not. For high sodium and low fluid intake, the RCC risk additionally increased (P-interaction=0.02). Conclusion: Sodium intake is a potential risk factor for RCC, particularly if fluid consumption is low.", "title": "Long-term dietary sodium, potassium and fluid intake; exploring potential novel risk factors for renal cell cancer in the Netherlands Cohort Study on diet and cancer" }, { "docid": "MED-4258", "text": "The objective of the present study was to assess animal and plant protein intakes in the Belgian population and to examine their relationship with overweight and obesity (OB). The subjects participated in the Belgian National Food Consumption Survey conducted in 2004. Food consumption was assessed by using two non-consecutive 24 h dietary recalls. About 3083 participants ( ≥ 15 years of age; 1546 males, 1537 females) provided completed dietary information. Animal protein intake (47 g/d) contributed more to total protein intakes of 72 g/d than plant protein intake, which accounted for 25 g/d. Meat and meat products were the main contributors to total animal protein intakes (53 %), whereas cereals and cereal products contributed most to plant protein intake (54 %). Males had higher animal and plant protein intakes than females (P < 0·001). Legume and soya protein intakes were low in the whole population (0·101 and 0·174 g/d, respectively). In males, animal protein intake was positively associated with BMI (β = 0·013; P = 0·001) and waist circumference (WC; β = 0·041; P = 0·002). Both in males and females, plant protein intake was inversely associated with BMI (males: β = - 0·036; P < 0·001; females: β = - 0·046; P = 0·001) and WC (male: β = - 0·137; P < 0·001; female: β = - 0·096; P = 0·024). In conclusion, plant protein intakes were lower than animal protein intakes among a representative sample of the Belgian population and decreased with age. Associations with anthropometric data indicated that plant proteins could offer a protective effect in the prevention of overweight and OB in the Belgian population.", "title": "Plant and animal protein intake and its association with overweight and obesity among the Belgian population." }, { "docid": "MED-1991", "text": "The objective of this article is to review the epidemiologic literature examining the role of plant foods and plant-based diets in the prevention of childhood obesity. Available data suggest a protective effect of ready-to-eat cereal on risk of obesity, although prospective studies are still needed. Studies on fruit and vegetables; grains other than cereal; high-protein foods, including beans, legumes, and soy; fiber; and plant-based dietary patterns are inconsistent or generally null. The evidence base is limited, and most studies are fraught with methodologic limitations, including cross-sectional design, inadequate adjustment for potential confounders, and lack of consideration of reporting errors, stage of growth, and genetic influences. Well-designed prospective studies are needed. The lack of evidence showing an association between plant-based diets and childhood obesity does not mean that such diets should not be encouraged. Plant foods are highlighted in the Dietary Guidelines for Americans, and children do not meet the current recommendations for most plant foods. Although the advice to consume a plant-based, low-energy-dense diet is sound, ethical questions arise concerning the relatively high price of these diets in the United States and the way in which such diets are perceived in other parts of the world. Reducing the burden of childhood obesity, eliminating health disparities, and preventing the further spread of the disease around the globe will require not only policy interventions to ensure that plant foods are affordable and accessible to children of all income levels but also awareness of sociocultural norms that affect consumption.", "title": "Plant foods and plant-based diets: protective against childhood obesity?" }, { "docid": "MED-1934", "text": "Objective Investigate the effects of 12 months of dietary weight loss and/or aerobic exercise on leukocyte telomere length in postmenopausal women. Design and Methods 439 overweight or obese women (50–75 y) were randomized to: i) dietary weight loss (N=118); ii) aerobic exercise (N=117), iii) diet + exercise (N=117), or iv) control (N=87). The diet intervention was a group-based program with a 10% weight loss goal. The exercise intervention was 45 mins/day, 5 days/week of moderate-to-vigorous aerobic activity. Fasting blood samples were taken at baseline and 12 months. DNA was extracted from isolated leukocytes and telomere length was measured by quantitative-polymerase chain reaction (qPCR). Mean changes were compared between groups (intent-to-treat) using generalized estimating equations. Results Baseline telomere length was inversely associated with age (r=−0.12 p<0.01) and positively associated with maximal oxygen uptake (r=0.11, p=0.03), but not with BMI or %body fat. Change in telomere length was inversely correlated with baseline telomere length (r=−0.47, p<0.0001). No significant difference in leukocyte telomere length was detected in any intervention group compared to controls, nor was the magnitude of weight loss associated with telomere length at 12 months. Conclusions Twelve-months of dietary weight loss and exercise did not change telomere length in postmenopausal women.", "title": "Independent and Combined Effects of Dietary Weight Loss and Exercise on Leukocyte Telomere Length in Postmenopausal Women" }, { "docid": "MED-2676", "text": "Smokehouse smoke, which is used for flavouring meat products, was investigated for its mutagenic activity in the Salmonella typhimurium assay. We were chiefly concerned with the fractions free of polycyclic aromatic hydrocarbons but containing phenol compounds, which are responsible for the preservative and aromatizing properties of the smoke. The most abundantly occurring phenol compounds (phenol, cresols, 2,4-dimethylphenol, brenzcatechine, syringol, eugenol, vanilline and guaiacol) gave negative results when they were tested for mutagenicity at five concentrations up to 5000 micrograms/plate, with and without S-9 mix, using five strains of S. typhimurium. Even when phenol was further investigated in a variety of test conditions, no induction of his+ revertants was observed. When smokehouse smoke was condensed and fractionated the majority of the various phenolic fractions also gave negative results when tested at five concentrations using five strains of S. typhimurium. However there was a slight increase in the number of revertants in a few cases. The presence in the phenolic fractions of very small amounts of mutagenic impurities, the nature of which needs further investigation, cannot be excluded. These results support the further development of non-hazardous smoke-aroma preparations, based on the phenolic components of smokehouse smoke.", "title": "Mutagenicity testing in the Salmonella typhimurium assay of phenolic compounds and phenolic fractions obtained from smokehouse smoke condensates." }, { "docid": "MED-4822", "text": "Objective We examined the associations between sweets, sweetened and unsweetened beverages, and sugars and pancreatic cancer risk. Methods We conducted a population-based case–control study (532 cases, 1,701 controls) and used multivariate logistic regression models to calculate odds ratios (OR) and 95% confidence intervals (CI). Because associations were often different by sex, we present results for men and women combined and separately. Results Among men, greater intakes of total and specific sweets were associated with pancreatic cancer risk (total sweets: OR = 1.9, 95% CI: 1.0, 3.6; sweet condiments: OR = 1.9, 95% CI: 1.2, 3.1; chocolate candy: OR = 2.4, 95% CI: 1.1, 5.0; other mixed candy bars: OR = 3.3, 95% CI: 1.5, 7.3 for 1 + servings/day versus none/rarely). Sweets were not consistently associated with risk among women. Sweetened beverages were not associated with increased pancreatic cancer risk. In contrast, low-calorie soft drinks were associated with increased risk among men only; while other low-/non-caloric beverages (e.g., coffee, tea, and water) were unassociated with risk. Of the three sugars assessed (lactose, fructose, and sucrose), only the milk sugar lactose was associated with pancreatic cancer risk (OR = 2.0, 95% CI: 1.5, 2.7 comparing extreme quartiles). Conclusion These results provide limited support for the hypothesis that sweets or sugars increase pancreatic cancer risk.", "title": "Sweets, sweetened beverages, and risk of pancreatic cancer in a large population-based case–control study" }, { "docid": "MED-4848", "text": "We have previously reported that a significant improvement can be obtained in rheumatoid arthritis patients by fasting followed by an individually adjusted vegetarian diet for one year. The patients who changed their diet could be divided into diet responders and diet nonresponders. After the clinical trial the patients were free to change diet or medication and after approximately one year they were asked to attend a new clinical examination. We compared the change from baseline (i.e. at the time of study entry) to the time of the follow-up examination for diet responders, diet nonresponders and controls who ate an omnivorous diet. The following variables favoured diet responders: pain score, duration of morning stiffness, Stanford Health Assessment Questionnaire index, number of tender joints, Ritchie's articular index, number of swollen joints, ESR and platelet count [corrected]. The difference between the three groups were significant for all the clinical variables, except for grip strength. There was no significant difference between the groups with regard to laboratory or anthropometric variables. At the time of the follow-up examination all diet responders but only half of the diet nonresponders still followed a diet. Our findings indicate that a group of patients with rheumatoid arthritis benefit from dietary manipulations and that the improvement can be sustained through a two-year period.", "title": "Vegetarian diet for patients with rheumatoid arthritis--status: two years after introduction of the diet." }, { "docid": "MED-2254", "text": "The aim of this study was to estimate the dietary cadmium (Cd) intake of the Belgian adult population, to compare this dietary Cd exposure to the tolerable weekly intake (TWI) recently established by the European Food Safety Authority (EFSA) and to determine the major food groups that contribute to dietary Cd exposure in Belgium. Food consumption data were derived from the 2004 Belgian food consumption survey (two 24 h recalls, 3083 participants). Cadmium concentrations in food items (n = 4000) were gathered from the control program of the Belgian Federal Agency for the Safety of the Food Chain for the period 2006-2008. Dietary intake per individual was calculated from consumption data and median Cd concentrations. The population mean, median and 95th percentile of the dietary intake values were 0.98, 0.85 and 2.02 µg kg⁻¹ body weight per week respectively. Two percent of the Belgian adult population has a dietary Cd intake above the recent TWI of 2.5 µg kg⁻¹ body weight established by EFSA in 2009. Cereal products and potatoes contribute for more than 60% to Cd intake.", "title": "Dietary cadmium intake by the Belgian adult population." }, { "docid": "MED-4049", "text": "More than 85% of breast cancers are sporadic and attributable to long-term exposure to environmental carcinogens, such as those in the diet, through a multistep disease process progressing from non-cancerous to premalignant and malignant stages. The chemical carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is one of the most abundant heterocyclic amines found in high-temperature cooked meats and is recognized as a mammary carcinogen. However, the PhIP’s mechanism of action in breast cell carcinogenesis is not clear. Here, we demonstrated, for the first time, that cumulative exposures to PhIP at physiologically achievable, pico to nanomolar concentrations effectively induced progressive carcinogenesis of human breast epithelial MCF10A cells from a non-cancerous stage to premalignant and malignant stages in a dose- and exposure-dependent manner. Progressive carcinogenesis was measured by increasingly- acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth, acinar-conformational disruption, proliferation, migration, invasion, tumorigenicity with metastasis and increased stem-like cell populations. These biological changes were accompanied by biochemical and molecular changes, including upregulated H-Ras gene expression, extracellular signal-regulated kinase (ERK) pathway activation, Nox-1 expression, reactive oxygen species (ROS) elevation, increased HIF-1α, Sp1, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2, MMP-9, aldehyde dehydrogenase activity and reduced E-cadherin. The Ras-ERK-Nox-ROS pathway played an important role in not only initiation but also maintenance of cellular carcinogenesis induced by PhIP. Using biological, biochemical and molecular changes as targeted endpoints, we identified that the green tea catechin components epicatechin-3-gallate and epigallocatechin-3-gallate, at non-cytotoxic doses, were capable of suppressing PhIP-induced cellular carcinogenesis and tumorigenicity.", "title": "Intervention of human breast cell carcinogenesis chronically induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine" }, { "docid": "MED-3273", "text": "Recent studies confirm that dietary methionine restriction increases both mean and maximal lifespan in rats and mice, achieving \"aging retardant\" effects very similar to those of caloric restriction, including a suppression of mitochondrial superoxide generation. Although voluntary caloric restriction is never likely to gain much popularity as a pro-longevity strategy for humans, it may be more feasible to achieve moderate methionine restriction, in light of the fact that vegan diets tend to be relatively low in this amino acid. Plant proteins - especially those derived from legumes or nuts - tend to be lower in methionine than animal proteins. Furthermore, the total protein content of vegan diets, as a function of calorie content, tends to be lower than that of omnivore diets, and plant protein has somewhat lower bioavailability than animal protein. Whole-food vegan diets that moderate bean and soy intake, while including ample amounts of fruit and wine or beer, can be quite low in methionine, while supplying abundant nutrition for health (assuming concurrent B12 supplementation). Furthermore, low-fat vegan diets, coupled with exercise training, can be expected to promote longevity by decreasing systemic levels of insulin and free IGF-I; the latter effect would be amplified by methionine restriction - though it is not clear whether IGF-I down-regulation is the sole basis for the impact of low-methionine diets on longevity in rodents.", "title": "The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy." }, { "docid": "MED-3359", "text": "Background Fruit and vegetable consumption and ingestion of carotenoids have been found to be associated with human skin-color (yellowness) in a recent cross-sectional study. This carotenoid-based coloration contributes beneficially to the appearance of health in humans and is held to be a sexually selected cue of condition in other species. Methodology and Principal Findings Here we investigate the effects of fruit and vegetable consumption on skin-color longitudinally to determine the magnitude and duration of diet change required to change skin-color perceptibly. Diet and skin-color were recorded at baseline and after three and six weeks, in a group of 35 individuals who were without makeup, self-tanning agents and/or recent intensive UV exposure. Six-week changes in fruit and vegetable consumption were significantly correlated with changes in skin redness and yellowness over this period, and diet-linked skin reflectance changes were significantly associated with the spectral absorption of carotenoids and not melanin. We also used psychophysical methods to investigate the minimum color change required to confer perceptibly healthier and more attractive skin-coloration. Modest dietary changes are required to enhance apparent health (2.91 portions per day) and attractiveness (3.30 portions). Conclusions Increased fruit and vegetable consumption confers measurable and perceptibly beneficial effects on Caucasian skin appearance within six weeks. This effect could potentially be used as a motivational tool in dietary intervention.", "title": "You Are What You Eat: Within-Subject Increases in Fruit and Vegetable Consumption Confer Beneficial Skin-Color Changes" }, { "docid": "MED-2656", "text": "The aim of previous research into the causes of allergic diseases, including asthma was mostly to identify potential risk factors in the environment. No major risk factors have been identified, however. Over the past 10 years, focus has, therefore, more been directed towards protective factors that could enhance the development of tolerance to allergens which were previously encountered early in life, but are now lost in modern affluent societies. In particular, the role of childhood infections has been discussed, but so far these studies have not been conclusive. Recent epidemiological studies and experimental research suggest that the microbial environment and exposure to microbial products in infancy modifies immune responses and enhances the development of tolerance to ubiquitous allergens. The intestinal microflora may play a particular role in this respect, as it is the major external driving force in the maturation of the immune system after birth, and animal experiments have shown it to be a prerequisite for normal development of oral tolerance. Recent studies have shown differences in the composition of the microflora between healthy and allergic infants in countries with a high and low prevalence of allergies and between healthy and allergic infants within such countries. These differences are apparent within the first week of life and thus precede clinical symptoms. The use of live microorganisms that might be beneficial to health has a long tradition and the safety is well documented. Very recently, several prospective intervention studies, modifying the gut flora from birth have yielded encouraging results and may suggest a new mode of primary prevention of allergy in the future.", "title": "Effects of intestinal microflora and the environment on the development of asthma and allergy." }, { "docid": "MED-1334", "text": "By 2002, China’s prevalence of overweight and obesity among adults was 18.9 percent and 2.9 percent, respectively. The Chinese traditional diet has been replaced by the “Western diet” and major declines in all phases of activity and increased sedentary activity as the main reasons explaining the rapid increase in overweight and obesity, bring major economic and health costs. The Nutrition Improvement Work Management Approach was released in 2010. Overweight and obesity prevention-related policies were added to national planning for disease prevention and control. The Guidelines for Prevention and Control of Overweight and Obesity of Chinese Adults and the School-age Children and Teenagers Overweight and Obesity Prevention and Control Guidelines in China were promulgated in 2003 and 2007, respectively. Few education programs have been implemented. Selected academic intervention research projects dominate with a focus on reducing child obesity and promoting healthier diets; increasing physical activity and reducing sedentary time; and facilitating changes in family, school, social, and cultural environments. Intervention samples are small and have not addressed the increasing rates of obesity throughout the entire population. Government provision of effective policy measures, multisectoral cooperation and increasing corporate social responsibility are keys to curb the trend toward overweight and obesity in China.", "title": "Program and Policy Options for Preventing Obesity in China" }, { "docid": "MED-2384", "text": "BACKGROUND: Tree nuts, particularly almonds, walnuts, and pistachios, have been shown to possess cardioprotective effects. However, there is little information on the effects of hazelnut consumption on cardiovascular risk markers. METHODS: The antiatherogenic effect of hazelnut before and after consumption in hypercholesterolemic subjects was investigated. Twenty-one hypercholesterolemic volunteers (18 men and 3 women) were recruited in a double control sandwich model intervention study with a single group and three isoenergetic diet periods. These were control diet I (4 weeks), hazelnut-enriched diet (4 weeks; hazelnut contributing 18%-20% of the total daily energy intake), and control diet period II (4 weeks). The cardiovascular risk biomarkers such as endothelial function, using flow-mediated dilation (FMD) technique, low-density lipoprotein (LDL) oxidation products and inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 (sVCAM-1) as well as lipids and lipoprotein levels were monitored. RESULTS: Consumption of a hazelnut-enriched diet significantly improved FMD (56.6%), total cholesterol (-7.8%), triacylglycerol (-7.3%), LDL-cholesterol (-6.17%), and high-density lipoprotein cholesterol (6.07%) compared with the control diet I. Oxidized-LDL, hs-CRP, and sVCAM-1 levels were significantly lower in the group ingesting a hazelnut-enriched diet compared with the control diets I and II. Modest correlations between sVCAM-1 and FMD and between sVCAM-1 and hs-CRP were observed (r = -0.49, P < .025; r = 0.66, P < .001, respectively). CONCLUSION: Hazelnut-enriched diets may exert antiatherogenic effect by improving endothelial function, preventing LDL oxidation, and inflammatory markers, in addition to their lipid and lipoprotein-lowering effects. These beneficial effects appeared to be reversible after 4 weeks on a hazelnut-free diet. Therefore, hazelnut may be incorporated into daily diet without change in total caloric intake for sustained health benefit. Copyright © 2013 National Lipid Association. All rights reserved.", "title": "Hazelnut-enriched diet improves cardiovascular risk biomarkers beyond a lipid-lowering effect in hypercholesterolemic subjects." }, { "docid": "MED-3087", "text": "Sixty random samples of bulk farm milk, market milk, locally manufactured processed cheese, and milk powder were collected to be analyzed for aluminum (Al) concentration using graphite furnace atomic absorption spectrometry (GFAAS). The results were compared with provisional acceptable permissible limits (PAPLs). The maximum estimated dietary intake (MEDI) of Al for the examined samples was calculated. In addition, an experimental study was conducted to determine the possible leaching of Al from cookware in milk during boiling. The obtained results showed that Al concentration in examined bulk farm milk samples was found to be negligible. In contrast, market milk revealed higher concentration, 65.0% of the examined samples were above the PAPLs. The results revealed significant difference of Al concentration among them. The Al levels in processed cheese wrapped in Al foil were significantly higher than those found in samples packed in glass containers with a significant difference of Al concentration between them. Also, 20% of the examined milk powder samples exceeded the PAPLs (0.01 to 0.4 mg/kg). The MEDI for Al in bulk farm milk, control market milk, market milk boiled in Al cookware, market milk boiled in stainless-steel cookware, processed cheese wrapped in Al foil, processed cheese packed in glass containers, and milk powder were calculated as 3.0%, 61.0%, 63.0%, 61.0%, 428.0%, 220.0%, and 166.0% from \"PTDI,\" respectively. The results of the experimental study showed no marked significant differences of Al concentration between market milk (control group) and those boiled in Al cookware, as well as to those boiled in stainless-steel cookware. PRACTICAL APPLICATION:   The results of the present study indicate that Al level in milk kept in Al containers and dairy products packed in Al foil is beyond the permissible limits, suggesting health hazard. Therefore, all milk cans should be constructed of stainless steel, prevent the entrance of tap water into milk, and the processed cheese should be packed in glass containers and not wrapped in Al foil. Leaching of Al increased to a significant percent more during storage than during boiling, so milk should be kept in stainless steel or glass containers in the refrigerator.", "title": "Prevalence and public health significance of aluminum residues in milk and some dairy products." }, { "docid": "MED-4352", "text": "Changes in the concentration and composition of serum VLDL, LDL, and HDL were studied in rabbits transferred from Chow diets to cholesterol-free, semipurified diets containing casein or isolated soy protein. During the first week on the casein diet, there was a marked increase in LDL-cholesterol and these higher levels were maintained during the subsequent 3 weeks of the study. Similar but less marked changes were obtained with the soy protein diet. When the percent composition of the particles was determined, both VLDL and LDL had a higher proportion of cholesterol. Turnover studies indicated that the FCRs for radiolabelled VLDL and LDL were reduced in casein-fed animals compared to those fed soy protein. The elevated LDL levels in casein-fed rabbits were primarily due to a reduction in receptor-mediated catabolism of LDL-apo B. Receptor-independent removal in the two groups was similar. These studies show that the hypercholesterolemia in casein-fed rabbits, compared to those fed soy protein, is associated with cholesterol enrichment of LDL and impaired receptor-dependent removal of LDL-apo B.", "title": "Effects of dietary protein on composition and metabolism of plasma lipoproteins in rabbits." }, { "docid": "MED-3535", "text": "Cherries, and in particular sweet cherries, are a nutritionally dense food rich in anthocyanins, quercetin, hydroxycinnamates, potassium, fiber, vitamin C, carotenoids, and melatonin. UV concentration, degree of ripeness, postharvest storage conditions, and processing, each can significantly alter the amounts of nutrients and bioactive components. These constituent nutrients and bioactive food components support the potential preventive health benefits of cherry intake in relation to cancer, cardiovascular disease, diabetes, inflammatory diseases, and Alzheimer's disease. Mechanistically, cherries exhibit relatively high antioxidant activity, low glycemic response, COX 1 and 2 enzyme inhibition, and other anti-carcinogenic effects in vitro and in animal experiments. Well-designed cherry feeding studies are needed to further substantiate any health benefits in humans.", "title": "Cherries and health: a review." }, { "docid": "MED-4769", "text": "Excessive fat accumulation has been observed in the field in chickens infected with adenovirus. In the present study this has been verified under experimental conditions. Chickens inoculated with adenovirus showed lesser weight gain but excessive adiposity compared to normal control chickens. These changes could not be explained by variation in food consumption. Chickens acquiring adenovirus naturally from the inoculated group showed similar adiposity. Serum cholesterol and triglyceride levels of inoculated and naturally infected chickens were significantly lower compared to those of the control group. Such an association between adenovirus infection and adiposity has been shown, probably, for the first time, which might help in further understanding of the complex problem of obesity.", "title": "Effect of adenovirus infection on adiposity in chicken." }, { "docid": "MED-3876", "text": "BACKGROUND: Chinese men have lower incidences of prostate cancer compared to men from Europe and North America. Asians consume large quantities of soya, a rich source of isoflavanoids phyto-oestrogens and have high plasma and urinary levels of these compounds. The mammalian lignans, enterolactone and enterodiol, are another group of weak plant oestrogens and are derived from seeds, cereals and grains. Vegetarians have high plasma and urinary concentrations of lignans. METHODS: The concentrations lignans and isoflavonic phyto-oestrogens were determined by gas chromatography-mass spectrometry (GC-MS) in plasma and prostatic fluid from Portuguese, Chinese and British men consuming their traditional diets. RESULTS: In prostatic fluid the mean concentrations of enterolactone were 31, 162 and 20.3 ng/ml for Hong Kong, Portugal and Britain respectively. Very high levels of enterolactone (> 600 ng/ml) were observed in the prostatic fluid of some of the men from Portugal. High concentrations of equol (3270 ng/ml) and daidzein (532 ng/ml) were found in a sample of prostatic fluid from Hong Kong. Higher mean levels of daidzein were observed in prostatic fluid from Hong Kong at 70 ng/ml, compared to 4.6 and 11.3 ng/ml in samples from Portugal and Britain respectively. Mean levels of daidzein were higher in the plasma samples from Hong Kong (31.3 ng/ml) compared to those from Portugal (1.3 ng/ml) and Britain (8.2 ng/ml). In general, the mean plasma concentrations of enterolactone from the three centres were similar, at 6.2, 3.9 and 3.9 ng/ml in samples from Hong Kong Portugal and Britain respectively. CONCLUSIONS: Higher concentrations of the isoflavanoid phyto-oestrogens, daidzein and equol, were found in the plasma and prostatic fluid of men from Hong Kong compared to those from Britain and Portugal. However, the levels of the lignan, enterolactone, were very much higher in prostatic fluid of Portuguese men. Isoflavanoids and lignans have many interesting properties and may, in part, be responsible for lower incidences of prostate cancer in men from Asia and also some Mediterranean countries. The isoflavanoids from soya, which are present in high concentrations in the prostatic fluid of Asian men, may be protective against prostate disease.", "title": "Lignans and isoflavonoids in plasma and prostatic fluid in men: samples from Portugal, Hong Kong, and the United Kingdom." }, { "docid": "MED-2513", "text": "Over the last several years, new evidence has kept pouring in about the remarkable effect of caloric restriction (CR) on the conspicuous bedfellows- aging and cancer. Through the use of various animal models, it is now well established that by reducing calorie intake one can not only increase life span but, also, lower the risk of various age related diseases such as cancer. Cancer cells are believed to be more dependent on glycolysis for their energy requirements than normal cells and, therefore, can be easily targeted by alteration in the energy-metabolic pathways, a hallmark of CR. Apart from inhibiting the growth of transplantable tumors, CR has been also shown to inhibit the development of spontaneous, radiation, and chemically induced tumors. The question regarding the potentiality of the anti-tumor effect of CR in humans has been in part answered by the resistance of a cohort of women, who had suffered from anorexia in their early life, to breast cancer. However, human research on the beneficial effect of CR is still at an early stage and needs further validation. Though the complete mechanism of the anti-tumor effect of CR is far from clear, the plausible involvement of nutrient sensing pathways or IGF-1 pathways proposed for its anti-aging action cannot be overruled. In fact, cancer cell lines, mutant for proteins involved in IGF-1 pathways, failed to respond to CR. In addition, CR decreases the levels of many growth factors, anabolic hormones, inflammatory cytokines, and oxidative markers that are deregulated in several cancers. In this review, we discuss the anti-tumor effect of CR, describing experiments done in vitro in tumor models and in vivo in mouse models in which the tumor was induced by means of radiation or chemical exposure, expressing oncogenes or deleting tumor suppression genes. We also discuss the proposed mechanisms of CR anti-tumor action. Lastly, we argue the necessity of gene expression studies in cancerous versus normal cells upon CR.", "title": "Insights into the beneficial effect of caloric/ dietary restriction for a healthy and prolonged life" }, { "docid": "MED-2217", "text": "OBJECTIVE: To determine the prevalence of AD and other dementias in a rural elderly Hindi-speaking population in Ballabgarh in northern India. DESIGN: The authors performed a community survey of a cohort of 5,126 individuals aged 55 years and older, 73.3% of whom were illiterate. Hindi cognitive and functional screening instruments, developed for and validated in this population, were used to screen the cohort. A total of 536 subjects (10.5%) who met operational criteria for cognitive and functional impairment and a random sample of 270 unimpaired control subjects (5.3%) underwent standardized clinical assessment for dementia using the Diagnostic and Statistical Manual of Mental Disorders-fourth edition diagnostic criteria, the Clinical Dementia Rating Scale (CDR), and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable and possible AD. RESULTS: We found an overall prevalence rate of 0.84% (95% CI, 0.61 to 1.13) for all dementias with a CDR score of at least 0.5 in the population aged 55 years and older, and an overall prevalence rate of 1.36% (95% CI, 0.96 to 1.88) in the population aged 65 years and older. The overall prevalence rate for AD was 0.62% (95% CI, 0.43 to 0.88) in the population aged 55+ and 1.07% (95% CI, 0.72 to 1.53) in the population aged 65+. Greater age was associated significantly with higher prevalence of both AD and all dementias, but neither gender nor literacy was associated with prevalence. CONCLUSIONS: In this population, the prevalence of AD and other dementias was low, increased with age, and was not associated with gender or literacy. Possible explanations include low overall life expectancy, short survival with the disease, and low age-specific incidence potentially due to differences in the underlying distribution of risk and protective factors compared with populations with higher prevalence.", "title": "Prevalence of Alzheimer's disease and other dementias in rural India: the Indo-US study." }, { "docid": "MED-3794", "text": "OBJECTIVE: To test the hypothesis that a low-fat, vegetarian diet reduces dysmenorrhea and premenstrual symptoms by its effect on serum sex-hormone binding globulin concentration and estrogen activity. METHODS: In a crossover design, 33 women followed a low-fat, vegetarian diet for two menstrual cycles. For two additional cycles, they followed their customary diet while taking a supplement placebo pill. Dietary intake, serum sex-hormone binding globulin concentration, body weight, pain duration and intensity, and premenstrual symptoms were assessed during each study phase. RESULTS: Mean (+/- standard deviation [SD]) serum sex-hormone binding globulin concentration was higher during the diet phase (46.7 +/- 23.6 nmol/L) than during the supplement phase (39.3 +/- 19.8 nmol/L, P < .001). Mean (+/- SD) body weight was lower during the diet (66.1 +/- 11.3 kg) compared with the supplement phase (67.9 +/- 12.1 kg, P < .001). Mean dysmenorrhea duration fell significantly from baseline (3.9 +/- 1.7 days) to diet phase (2.7 +/- 1.9 days) compared with change from baseline to supplement phase (3.6 +/- 1.7 days, P < .01). Pain intensity fell significantly during the diet phase, compared with baseline, for the worst, second-worst, and third-worst days, and mean durations of premenstrual concentration, behavioral change, and water retention symptoms were reduced significantly, compared with the supplement phase. CONCLUSION: A low-fat vegetarian diet was associated with increased serum sex-hormone binding globulin concentration and reductions in body weight, dysmenorrhea duration and intensity, and premenstrual symptom duration. The symptom effects might be mediated by dietary influences on estrogen activity.", "title": "Diet and sex-hormone binding globulin, dysmenorrhea, and premenstrual symptoms." }, { "docid": "MED-4741", "text": "BACKGROUND: Previous studies have suggested that egg consumption may increase the risk of colorectal cancer and some other cancers. However, the evidence is still limited. To further explore the association between egg intake and cancer risk we conducted a case-control study of 11 cancer sites in Uruguay between 1996 and 2004, including 3,539 cancer cases and 2,032 hospital controls. RESULTS: In the multivariable model with adjustment for age, sex (when applicable), residence, education, income, interviewer, smoking, alcohol intake, intake of fruits and vegetables, grains, dairy products, fatty foods, meat, energy intake and BMI, there was a significant increase in the odds of cancers of the oral cavity and pharynx (OR= 2.02, 95% CI: 1.19-3.44), upper aerodigestive tract (OR= 1.67, 95% CI: 1.17-2.37), colorectum (OR= 1.64, 95% CI: 1.02-2.63), lung (OR= 1.59, 95% CI: 1.10-2.29), breast (OR= 2.86, 95% CI: 1.66-4.92), prostate (OR= 1.89, 95% CI: 1.15-3.10), bladder (OR= 2.23, 95% CI: 1.30-3.83) and all cancer sites combined (OR= 1.71, 95% CI: 1.35-2.17) with a high vs low egg intake. CONCLUSIONS: We found an association between higher intake of eggs and increased risk of several cancers. Further prospective studies of these associations are warranted.", "title": "Egg consumption and the risk of cancer: a multisite case-control study in Uruguay." }, { "docid": "MED-2571", "text": "Background Prospective, randomized, pilot clinical study was conducted to evaluate the beneficial effects of inositol hexaphosphate (IP6) + Inositol in breast cancer patients treated with adjuvant therapy. Patients and methods Patients with invasive ductal breast cancer where polychemotherapy was indicated were monitored in the period from 2005-2007. Fourteen patients in the same stage of ductal invasive breast cancer were involved in the study, divided in two randomized groups. One group was subjected to take IP6 + Inositol while the other group was taking placebo. In both groups of patients the same laboratory parameters were monitored. When the treatment was finished, all patients have filled questionnaires QLQ C30 and QLQ-BR23 to determine the quality of life. Results Patients receiving chemotherapy, along with IP6 + Inositol did not have cytopenia, drop in leukocyte and platelet counts. Red blood cell counts and tumor markers were unaltered in both groups. However, patients who took IP6 + Inositol had significantly better quality of life (p = 0.05) and functional status (p = 0.0003) and were able to perform their daily activities. Conclusion IP6 + Inositol as an adjunctive therapy is valuable help in ameliorating the side effects and preserving quality of life among the patients treated with chemotherapy.", "title": "Efficacy of IP6 + inositol in the treatment of breast cancer patients receiving chemotherapy: prospective, randomized, pilot clinical study" }, { "docid": "MED-3281", "text": "INTRODUCTION: Amino acid auxotrophy or the metabolic defect which renders cancer incapable of surviving under amino acid depleted conditions is being exploited and explored as a therapeutic against cancer. Early clinical data on asparagine- and arginine-depleting drugs have demonstrated low toxicity and efficacy in melanoma, hepatocellular carcinoma and acute lymphoblastic leukemia. Methionine auxotrophy is a novel niche currently under exploration for targeting certain cancers. AREAS COVERED: In this review we explore the discovery of methionine auxotrophy followed by in vitro, in vivo and patient data on targeting cancer with methionine depletion. We end with a small discussion on bioengineering, pegylation and red blood cell encapsulation as mechanisms for decreasing immunogenicity of methionine-depleting drugs. We hope to provide a platform for future pharmacology, toxicology and cytotoxicity studies with methionine depletion therapy and drugs. EXPERT OPINION: Although methionine auxotrophy seems as a viable target, extensive research addressing normal versus cancer cell toxicity needs to be conducted. Further research also needs to be conducted into the molecular mechanism associated with methionine depletion therapy. Finally, novel methods need to be developed to decrease the immunogenicity of methionine-depleting drugs, a current issue with protein therapeutics.", "title": "Targeting methionine auxotrophy in cancer: discovery & exploration." }, { "docid": "MED-1318", "text": "BACKGROUND: Rice consumption has been associated with risk of type 2 diabetes, but its relation with cardiovascular disease (CVD) is limited. OBJECTIVE: We examined the association between rice consumption and risk of CVD incidence and mortality in a Japanese population. DESIGN: This was a prospective study in 91,223 Japanese men and women aged 40-69 y in whom rice consumption was determined and updated from 3 self-administered food-frequency questionnaires, each 5 y apart. Follow-up for incidence was from 1990 to 2009 in cohort I and 1993 to 2007 in cohort II and for mortality was from 1990 to 2009 in cohort I and 1993 to 2009 in cohort II. HRs and 95% CIs of CVD incidence and mortality were calculated according to quintiles of cumulative average rice consumption. RESULTS: In 15-18 y of follow-up, we ascertained 4395 incident cases of stroke, 1088 incident cases of ischemic heart disease (IHD), and 2705 deaths from CVD. Rice consumption was not associated with risk of incident stroke or IHD; the multivariable HR (95% CI) in the highest compared with lowest rice consumption quintiles was 1.01 (0.90, 1.14) for total stroke and 1.08 (0.84, 1.38) for IHD. Similarly, there was no association between rice consumption and risk of mortality from CVD; the HR (95% CI) for mortality from total CVD was 0.97 (0.84, 1.13). There were no interactions with sex or effect modifications by body mass index for any endpoint. CONCLUSION: Rice consumption is not associated with risk of CVD morbidity or mortality. © 2014 American Society for Nutrition.", "title": "Rice consumption is not associated with risk of cardiovascular disease morbidity or mortality in Japanese men and women: a large population-based, ..." }, { "docid": "MED-3696", "text": "The authors assessed the association between moderate alcohol consumption and breast cancer risk in the Women's Health Study (United States, 1992-2004). During an average of 10 years of follow-up, 1,484 cases of total breast cancer (1,190 invasive and 294 in situ) were documented among 38,454 women who, at baseline, were free of cancer and cardiovascular disease and provided detailed dietary information, including alcohol consumption, for the preceding 12 months. Higher alcohol consumption was associated with a modest increase in breast cancer risk; the multivariable relative risks for > or =30 g/day of alcohol vs. none were 1.32 (95% confidence interval (CI): 0.96, 1.82) for total breast cancer and 1.43 (95% CI: 1.02, 2.02) for invasive breast cancer. An increased risk was limited to estrogen receptor (ER)- and progesterone receptor (PR)-positive tumors; the multivariable relative risks for an increment of 10 g/day of alcohol were 1.11 (95% CI: 1.03, 1.20) for ER+PR+ tumors (804 cases), 1.00 (95% CI: 0.81, 1.24) for ER+PR- tumors (125 cases), and 0.99 (95% CI: 0.82, 1.20) for ER-PR- tumors (167 cases). The association also seemed strongest among those taking postmenopausal hormones currently, but the test for interaction was not significant. The findings from this prospective study suggest that moderate alcohol consumption increases breast cancer risk.", "title": "Alcohol consumption and breast cancer risk in the Women's Health Study." }, { "docid": "MED-4028", "text": "This paper aims to provide dental health professionals with practical advice to pass on to patients about diet and dental health. Sugars are the most important dietary factor contributing to dental caries. Different foods carry different dental health risks; those containing non-milk, extrinsic sugars are potentially the most damaging. In the UK, sugared soft drinks and confectionery contribute approximately 50% to total intake of non-milk extrinsic sugars. Patients should be encouraged to reduce the frequency of intake of sugary foods. Intake of acidic foods and drinks contributes to dental erosion and consumption of such foods should also be limited. Dietary advice to dental patients should be positive and personalized if possible and can be in line with dietary recommendations for general health. These are to increase the consumption of starchy staple foods (eg bread, potatoes and unsweetened cereals), vegetables and fruit and to reduce the consumption of sugary and fatty foods.", "title": "Dietary advice in dental practice." }, { "docid": "MED-3874", "text": "Background Prostate cancer affects one-out-of-six men during their lifetime. Dietary factors are postulated to influence the development and progression of prostate cancer. Low-fat diets and flaxseed supplementation may offer potentially protective strategies. Methods We undertook a multi-site, randomized controlled trial to test the effects of low-fat and/or flaxseed-supplemented diets on the biology of the prostate and other biomarkers. Prostate cancer patients (n=161) scheduled at least 21 days before prostatectomy were randomly assigned to one of the following arms: 1) control (usual diet); 2) flaxseed-supplemented diet (30 g/day); 2) low-fat diet (<20% total energy); or 4) flaxseed-supplemented, low-fat diet. Blood was drawn at baseline and prior to surgery and analyzed for prostate specific antigen (PSA), sex hormone binding globulin, testosterone, insulin-like growth factor-1 and binding protein-3, c-reactive protein, and total and low density lipoprotein cholesterol. Tumors were assessed for proliferation (Ki-67, the primary endpoint) and apoptosis. Results Men were on protocol an average of 30 days. Proliferation rates were significantly lower (P < 0.002) among men assigned to the flaxseed arms. Median Ki-67 positive cells/total nuclei ratios (x100) were 1.66 (flaxseed-supplemented diet) and 1.50 (flaxseed-supplemented, low-fat diet) vs. 3.23 (control) and 2.56 (low-fat diet). No differences were observed between arms with regard to side effects, apoptosis, and most serological endpoints; however, men on low-fat diets experienced significant decreases in serum cholesterol (P=0.048). Conclusions Findings suggest that flaxseed is safe, and associated with biologic alterations that may be protective for prostate cancer. Data also further support low-fat diets to manage serum cholesterol.", "title": "Flaxseed Supplementation (not Dietary Fat Restriction) Reduces Prostate Cancer Proliferation Rates in Men Presurgery" }, { "docid": "MED-3588", "text": "Background Many studies have examined whether caffeine, alcohol, or specific beverages containing these affect fertility in women. However most of these studies have retrospectively collected information on alcohol and caffeine intake, making the results susceptible to biases. Methods We followed 18,555 married women without a history of infertility for 8 years as they attempted to become (or became) pregnant. Diet was measured twice during this period and prospectively related to the incidence of ovulatory disorder infertility. Results There were 438 incident report of ovulatory disorder infertility during follow-up. Intakes of alcohol and caffeine were unrelated to the risk of ovulatory disorder infertility. The multivariate-adjusted relative risk (RR), 95% confidence interval (CI), P for trend comparing the highest to lowest categories of intake were 1.11 (0.76–1.64; 0.78) for alcohol and 0.86 (0.61–1.20; 0.44) for total caffeine. However, intake of caffeinated soft drinks was positively related to ovulatory disorder infertility. The multivariate-adjusted RR 95% CI, and P for trend comparing the highest to lowest categories of caffeinated soft drink consumption were 1.47 (1.09–1.98; 0.01). Similar associations were observed for noncaffeinated, sugared, diet and total soft drinks. Conclusions Our findings do not support the hypothesis that alcohol and caffeine impair ovulation to the point of decreasing fertility. The association between soft drinks and ovulatory disorder infertility appears not to be attributable to their caffeine or sugar content, and deserves further investigation.", "title": "Caffeinated and alcoholic beverage intake in relation to ovulatory disorder infertility" }, { "docid": "MED-3197", "text": "Background: A Step I diet with lean beef compared with lean white meat both decrease LDL cholesterol. To our knowledge, no studies have evaluated a low–saturated fatty acid (SFA) (<7% calories) diet that contains lean beef. Objective: We studied the effect on LDL cholesterol of cholesterol-lowering diets with varying amounts of lean beef [ie, Dietary Approaches to Stop Hypertension (DASH): 28 g beef/d; Beef in an Optimal Lean Diet (BOLD): 113 g beef/d; and Beef in an Optimal Lean Diet plus additional protein (BOLD+): 153 g beef/d] compared with that of a healthy American diet (HAD). Design: Thirty-six hypercholesterolemic participants (with LDL-cholesterol concentrations >2.8 mmol/L) were randomly assigned to consume each of the 4 diets (HAD: 33% total fat, 12% SFA, 17% protein, and 20 g beef/d), DASH (27% total fat, 6% SFA, 18% protein, and 28 g beef/d), BOLD (28% total fat, 6% SFA, 19% protein, and 113 g beef/d), and BOLD+ (28% total fat, 6% SFA, 27% protein, and 153 g beef/d) for 5 wk. Results: There was a decrease in total cholesterol (TC) and LDL-cholesterol concentrations (P < 0.05) after consumption of the DASH (−0.49 ± 0.11 and −0.37 ± 0.09 mmol/L, respectively), BOLD (−0.48 ± 0.10 and −0.35 ± 0.9 mmol/L, respectively), and BOLD+ (−0.50 ± 0.10 and −0.345 ± 0.09 mmol/L, respectively) diets compared with after consumption of the HAD (−0.22 ± 0.10 and −0.14 ± 0.10 mmol/L, respectively). Apolipoprotein A-I, C-III, and C-III bound to apolipoprotein A1 particles decreased after BOLD and BOLD+ diets compared with after the HAD, and there was a greater decrease in apolipoprotein B after consumption of the BOLD+ diet than after consumption of the HAD (P < 0.05 for both). LDL cholesterol and TC decreased after consumption of the DASH, BOLD, and BOLD+ diets when the baseline C-reactive protein (CRP) concentration was <1 mg/L; LDL cholesterol and TC decreased when baseline CRP concentration was >1 mg/L with the BOLD and BOLD+ diets. Conclusions: Low-SFA, heart-healthy dietary patterns that contain lean beef elicit favorable effects on cardiovascular disease (CVD) lipid and lipoprotein risk factors that are comparable to those elicited by a DASH dietary pattern. These results, in conjunction with the beneficial effects on apolipoprotein CVD risk factors after consumption of the BOLD and BOLD+ diets, which were greater with the BOLD+ diet, provide support for including lean beef in a heart-healthy dietary pattern. This trial was registered at clinicaltrials.gov as NCT00937898.", "title": "Beef in an Optimal Lean Diet study: effects on lipids, lipoproteins, and apolipoproteins" }, { "docid": "MED-4050", "text": "Green tea is a commonly consumed beverage in Asia and has been suggested to have anti-inflammatory and possible anti-carcinogenic properties in laboratory studies. We sought to examine the association between green tea consumption and risk of breast cancer incidence or recurrence, using all available epidemiologic evidence to date. We conducted a systematic search of five databases and performed a meta-analysis of studies of breast cancer risk and recurrence published between 1998 and 2009, encompassing 5,617 cases of breast cancer. Summary relative risks (RR) were calculated using a fixed effects model, and tests of heterogeneity across combined studies were conducted. We identified two studies of breast cancer recurrence and seven studies of breast cancer incidence. Increased green tea consumption (more than three cups a day) was inversely associated with breast cancer recurrence (Pooled RR = 0.73, 95% CI: 0.56-0.96). An analysis of case-control studies of breast cancer incidence suggested an inverse association with a pooled RR of 0.81 (95% CI: 0.75, 0.88) while no association was found among cohort studies of breast cancer incidence. Combining all studies of breast cancer incidence resulted in significant heterogeneity. Available epidemiologic evidence supports the hypothesis that increased green tea consumption may be inversely associated with risk of breast cancer recurrence. The association between green tea consumption and breast cancer incidence remains unclear based on the current evidence.", "title": "Green tea consumption and breast cancer risk or recurrence: a meta-analysis." }, { "docid": "MED-4751", "text": "The continued increase in incidence of some hormone-related cancers worldwide is of great concern. Although estrogen-like substances in the environment were blamed for this increase, the possible role of endogenous estrogens from food has not been widely discussed. We are particularly concerned about cows' milk, which contains a considerable quantity of estrogens. When we name cows' milk as one of the important routes of human exposure to estrogens, the general response of Western people is that \"man has been drinking cows' milk for around 2000 years without apparent harm.\" However, the milk that we are now consuming is quite different from that consumed 100 years ago. Unlike their pasture-fed counterparts of 100 years ago, modern dairy cows are usually pregnant and continue to lactate during the latter half of pregnancy, when the concentration of estrogens in blood, and hence in milk, increases. The correlation of incidence and mortality rates with environmental variables in worldwide countries provides useful clues to the etiology of cancer. In this study, we correlated incidence rates for breast, ovarian, and corpus uteri cancers (1993-97 from Cancer Incidence in Five Continents) with food intake (1961-97 from FAOSTAT) in 40 countries. Meat was most closely correlated with the breast cancer incidence (r=0.827), followed by milk (0.817) and cheese (0.751). Stepwise multiple-regression analysis (SMRA) identified meat as the factor contributing most greatly to the incidence of breast cancer ([R]=0.862). Milk was most closely correlated with the incidence of ovarian cancer (r=0.779), followed by animal fats (0.717) and cheese (0.697). SMRA revealed that milk plus cheese make the greatest contribution to the incidence of ovarian cancer ([R]=0.767). Milk was most closely correlated with corpus uteri cancer (r=0.814), followed by cheese (0.787). SMRA revealed that milk plus cheese make the most significant contribution to the incidence of corpus uteri cancer ([R]=0.861). In conclusion, increased consumption of animal-derived food may have adverse effects on the development of hormone-dependent cancers. Among dietary risk factors, we are most concerned with milk and dairy products, because the milk we drink today is produced from pregnant cows, in which estrogen and progesterone levels are markedly elevated.", "title": "The possible role of female sex hormones in milk from pregnant cows in the development of breast, ovarian and corpus uteri cancers." }, { "docid": "MED-3044", "text": "OBJECTIVE: Cocaine-related cues have been hypothesized to perpetuate drug abuse by inducing a craving response that prompts drug-seeking behavior. However, the mechanisms, underlying neuroanatomy, and specificity of this neuroanatomy are not yet fully understood. METHOD: To address these issues, experienced cocaine users (N=17) and comparison subjects (N=14) underwent functional magnetic resonance imaging while viewing three separate films that portrayed 1 ) individuals smoking crack cocaine, 2) outdoor nature scenes, and 3) explicit sexual content. Candidate craving sites were identified as those that showed significant activation in the cocaine users when viewing the cocaine film. These sites were then required to show significantly greater activation when contrasted with comparison subjects viewing the cocaine film (population specificity) and cocaine users viewing the nature film (content specificity). RESULTS: Brain regions that satisfied these criteria were largely left lateralized and included the frontal lobe (medial and middle frontal gyri, bilateral inferior frontal gyrus), parietal lobe (bilateral inferior parietal lobule), insula, and limbic lobe (anterior and posterior cingulate gyrus). Of the 13 regions identified as putative craving sites, just three (anterior cingulate, right inferior parietal lobule, and the caudate/lateral dorsal nucleus) showed significantly greater activation during the cocaine film than during the sex film in the cocaine users, which suggests that cocaine cues activated similar neuroanatomical substrates as naturally evocative stimuli in the cocaine users. Finally, contrary to the effects of the cocaine film, cocaine users showed a smaller response than the comparison subjects to the sex film. CONCLUSIONS: These data suggest that cocaine craving is not associated with a dedicated and unique neuroanatomical circuitry; instead, unique to the cocaine user is the ability of learned, drug-related cues to produce brain activation comparable to that seen with nondrug evocative stimuli in healthy comparison subjects.", "title": "Cue-induced cocaine craving: neuroanatomical specificity for drug users and drug stimuli." }, { "docid": "MED-1258", "text": "Reductions in low-density lipoprotein-cholesterol (LDL-C) result from diets containing almonds, or diets that are either low in saturated fat or high in viscous fibers, soy proteins, or plant sterols. We have therefore combined all of these interventions in a single diet (portfolio diet) to determine whether cholesterol reductions could be achieved of similar magnitude to those reported in recent statin trials which reduced cardiovascular events. Twenty-five hyperlipidemic subjects consumed either a portfolio diet (n=13), very low in saturated fat and high in plant sterols (1.2 g/1,000 kcal), soy protein (16.2 g/1,000 kcal), viscous fibers (8.3 g/1,000 kcal), and almonds (16.6 g/1,000 kcal), or a low-saturated fat diet (n=12) based on whole-wheat cereals and low-fat dairy foods. Fasting blood, blood pressure, and body weight were obtained at weeks 0, 2, and 4 of each phase. LDL-C was reduced by 12.1% +/- 2.4% (P<.001) on the low-fat diet and by 35.0% +/- 3.1% (P<.001) on the portfolio diet, which also reduced the ratio of LDL-C to high-density lipoprotein-cholesterol (HDL-C) significantly (30.0% +/- 3.5%; P<.001). The reductions in LDL-C and the LDL:HDL-C ratio were both significantly lower on the portfolio diet than on the control diet (P<.001 and P<.001, respectively). Mean weight loss was similar on test and control diets (1.0 kg and 0.9 kg, respectively). No difference was seen in blood pressure, HDL-C, serum triglycerides, lipoprotein(a) [Lp(a)], or homocysteine concentrations between diets. Combining a number of foods and food components in a single dietary portfolio may lower LDL-C similarly to statins and so increase the potential effectiveness of dietary therapy.", "title": "The effect of combining plant sterols, soy protein, viscous fibers, and almonds in treating hypercholesterolemia." }, { "docid": "MED-2584", "text": "In a 6-year prospective study, the authors examined the relation between diet and incident colon cancer among 32,051 non-Hispanic white cohort members of the Adventist Health Study (California, 1976-1982) who, at baseline, had no documented or reported history of cancer. The risk of colon cancer was determined from proportional hazards regression with adjustment for age and other covariates. The authors found a positive association with total meat intake (risk ratio (RR) for > or =1 time/week vs. no meat intake = 1.85, 95% confidence interval (CI) 1.19-2.87; p for trend = 0.01) and, among subjects who favored specific types of meat, positive associations with red meat intake (RR for > or =1 time/week vs. no red meat intake = 1.90, 95% CI 1.16-3.11; p for trend = 0.02) and white meat intake (RR for > or =1 time/week vs. no white meat intake = 3.29, 95% CI 1.60-6.75; p for trend = 0.006). An inverse association with legume intake (RR for >2 times/week vs. <1 time/week = 0.53, 95% CI 0.33-0.86; p for trend = 0.03) was observed. Among men, a positive association with body mass index was observed (relative to the RR for tertile III (>25.6 kg/m2) vs. tertile I (<22.5 kg/m2) = 2.63, 95% CI 1.12-6.13; p for trend = 0.05). A complex relation was identified whereby subjects exhibiting a high red meat intake, a low legume intake, and a high body mass experienced a more than threefold elevation in risk relative to all other patterns based on these variables. This pattern of putative risk factors would likely contribute to increases in both insulin resistance (high body mass, high red meat intake) and glycemic load (low legume intake), a synergism that, if causal, implicates hyperinsulinemic exposure in colon carcinogenesis. The overall findings from this cohort identify both red meat intake and white meat intake as important dietary risk factors for colon cancer and raise the possibility that the risk due to red meat intake reflects a more complex etiology.", "title": "Dietary risk factors for colon cancer in a low-risk population." }, { "docid": "MED-2379", "text": "Objectives Metabolic syndrome is a precursor of diabetes and cardiovascular disease (CVD). Walnut ingestion has been shown to reduce CVD risk indices in diabetes. This randomized controlled crossover trial was performed to investigate the effects of daily walnut consumption on endothelial function and other biomarkers of cardiac risk in a population of overweight individuals with visceral adiposity. Methods Forty-six overweight adults (average age, 57.4 years; 28 women, 18 men) with elevated waist circumference and 1 or more additional signs of metabolic syndrome were randomly assigned to two 8-week sequences of walnut-enriched ad libitum diet and ad libitum diet without walnuts, which were separated by a 4-week washout period. The primary outcome measure was the change in flow-mediated vasodilation (FMD) of the brachial artery. Secondary measures included serum lipid panel, fasting glucose and insulin, Homeostasis Model Assessment–Insulin Resistance values, blood pressure, and anthropometric measures. Results FMD improved significantly from baseline when subjects consumed a walnut-enriched diet as compared with the control diet (1.4% ± 2.4% versus 0.3% ± 1.5%; p = 0.019). Beneficial trends in systolic blood pressure reduction were seen, and maintenance of the baseline anthropometric values was also observed. Other measures were unaltered. Conclusion Daily ingestion of 56 g of walnuts improves endothelial function in overweight adults with visceral adiposity. The addition of walnuts to the diet does not lead to weight gain. Further study of the potential role of walnut intake in diabetes and CVD prevention is warranted.", "title": "Effects of Walnuts on Endothelial Function in Overweight Adults with Visceral Obesity: A Randomized, Controlled, Crossover Trial" }, { "docid": "MED-2674", "text": "The process of malignant transformation universally entails genetic damage and oncogenic signaling, two stresses that are signaled to p53 through different genetic pathways. Based on this, it is possible to distinguish two jobs for p53: \"guardian of the genome\" that consists in sensing and reacting to DNA damage through the ATM/ATR and Chk1/Chk2 kinases, and \"policeman of the oncogenes\" that, correspondingly, consists in responding to oncogenic signaling through the p53-stabilizing protein ARF. Contrary to expectation, recent genetic evidence in mice indicates that the response of p53 to DNA damage has little or no impact on cancer protection. In contrast, ARF-dependent activation of p53 is critical for p53-mediated tumor suppression. Here, we discuss the mechanistic implications of these observations and their relevance for cancer therapy.", "title": "p53: guardian of the genome and policeman of the oncogenes." }, { "docid": "MED-3024", "text": "This experiment aimed to study the molecular toxicity of methylmercury (MeHg) in liver, brain and white muscle of Atlantic salmon fed a diet based on fish oil (FO, high dietary n-3/n-6 ratio) compared to an alternative diet mainly based on vegetable oil (VO, low dietary n-3/n-6 ratio). Juvenile salmon were fed decontaminated diets or the FO and VO diets enriched with 5 mg Hg/kg (added as MeHg) for three months. The dietary lipid composition affected the fatty acid composition in the tissues, especially in liver and white muscle. After 84 days of exposure, the liver accumulated three times as much MeHg as the brain and white muscle. Vitamin C content and heme oxygenase, tubulin alpha (TUBA) and Cpt1 transcriptional levels all showed significant effects of MeHg exposure in the liver. TBARS, α-tocopherol, γ-tocopherol, and the transcriptional levels of thioredoxin, heme oxygenase, TUBA, PPARB1, D5D and D6D showed an effect of dietary lipid composition in liver tissue. Effects of dietary lipids were observed in brain tissue for MT-A, HIF1, Bcl-X and TUBA. Interaction effects between MeHg exposure and dietary lipid composition were observed in all tissues. Our data suggest that dietary fats have modulating effects on MeHg toxicity in Atlantic salmon. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Dietary lipids modulate methylmercury toxicity in Atlantic salmon." }, { "docid": "MED-2262", "text": "The role of cadmium (Cd) bioaccessibility in risk assessment is less well studied. The aim of this study was to assess human health risk to Cd through inhalation and seafood consumption by incorporating bioaccessibility. The relationships between trophically available Cd and bioaccessibility were constructed based on available experimental data. We estimated Cd concentrations in human urine and blood via daily intake from seafood consumption and inhalation based on a physiologically-based pharmacokinetic (PBPK) model. A Hill-based dose-response model was used to assess human renal dysfunction and peripheral arterial disease risks for long-term Cd exposure. Here we showed that fish had higher bioaccessibility (~83.7%) than that of shellfish (~73.2%) for human ingestion. Our results indicated that glomerular and tubular damage among different genders and smokers ranged from 18.03 to 18.18%. Our analysis showed that nonsmokers had 50% probability of peripheral arterial disease level exceeding from 3.28 to 8.80%. Smoking populations had 2-3 folds higher morbidity risk of peripheral arterial disease than those of nonsmokers. Our study concluded that the adverse effects of Cd exposure are exacerbated when high seafood consumption coincides with cigarette smoking. Our work provides a framework that could more accurately address risk dose dependency of Cd hazard. Copyright © 2012 Elsevier B.V. All rights reserved.", "title": "Assessing human exposure risk to cadmium through inhalation and seafood consumption." }, { "docid": "MED-3958", "text": "Flanders is densely populated with much industry and intensive farming. Sexual maturation of adolescents (aged 14-15 years) was studied in relation to internal exposure to pollutants. Serum levels of pollutants and sex hormones were measured in 1679 participants selected as a random sample of the adolescents residing in the study areas. Data on sexual development were obtained from the medical school examination files. Self-assessment questionnaires provided information on health, use of medication and lifestyle factors. In boys, serum levels of hexachlorobenzene (HCB), p,p'-DDE and polychlorinated biphenyls (sum of marker PCB138, 153 and 180) were significantly and positively associated with pubertal staging (pubic hair and genital development). Higher levels of serum HCB and blood lead were associated with, respectively, a lower and a higher risk of gynecomastia. In girls, significant and negative associations were detected between blood lead and pubic hair development; higher exposure to PCBs was significantly associated with a delay in timing of menarche. Environmental exposures to pollutants at levels actually present in the Flemish population are associated with measurable effects on pubertal development. However, further understanding of toxic mode of action and sensitive windows of exposure is needed to explain the current findings.", "title": "Internal exposure to pollutants and sexual maturation in Flemish adolescents." }, { "docid": "MED-3436", "text": "Erectile dysfunction (ED) is an early marker for systemic atherosclerosis and is a predictor for coronary artery disease and cardiac events. The aim of this paper is to convey the importance of addressing cardiovascular risk factors in patients with ED and to inform urologists as well as other physicians who are not specialized in cardiology how to carry out a basic cardiovascular evaluation, including history, physical examination and objective data. We review the evidence and pathophysiology linking ED to cardiovascular disease, and then describe how to carry out a basic cardiovascular evaluation. We present data from the literature showing that appropriate use of lifestyle modifications and medical therapy has a positive effect on mortality, on numerous cardiovascular end points and on ED. Suggestions of when to refer the ED patient to an internist or cardiologist are provided. Identifying and treating cardiovascular risk factors may not only benefit the patient's ED, but it might also save the patient's life.", "title": "How to save a life during a clinic visit for erectile dysfunction by modifying cardiovascular risk factors." }, { "docid": "MED-2249", "text": "High-level cadmium (Cd) exposure has long been known to induce nephropathy, severe osteoporosis, and fractures in humans. More recent epidemiology, however, reveals that, in populations not known to have important industrial exposure to this heavy metal, high-normal blood or urine Cd levels correlate with increased risk for vascular disorders, cancers, diabetes, and total mortality, as well as osteoporosis and nephropathy. Since these disorders appear unlikely to expedite Cd absorption, and since Cd has promoted these pathologies in rodent studies, it seems reasonable to conclude that Cd is an important mediating risk factor for these disorders in humans. Avoiding tobacco smoke or frequent ingestion of shellfish or organ meats can lessen humans exposure to Cd, but the chief dietary sources of Cd are plant-derived foods - green leafy vegetables, whole grains, tubers, and root vegetables - typically recommended for their health-supportive properties; indeed, among non-smokers, vegans tend to have the highest Cd body burden. Fortunately, iron sufficiency and ample dietary intakes of calcium, magnesium, and zinc can impede absorption of dietary Cd, both by down-regulating intestinal expression of mineral transporters, and by directly competing with Cd for access to these transporters. Correction of iron deficiency appears to be of particular importance for controlling Cd absorption. Moreover, zinc supplementation can counteract the toxicity of Cd already in the body via induction of metallothionein, which binds Cd avidly via its sulfhydryl groups; so long as it remains sequestered in this form, Cd is innocuous. Zinc supplementation may in any case be recommendable, as optimal zinc status exerts protective anti-inflammatory, antioxidant, and immunosupportive effects. Inasmuch as the toxicity of Cd appears to be mediated in large part by oxidative stress, ingestion of spirulina, lipoic acid, melatonin, and N-acetylcysteine may also have potential for mitigating the risk associated with Cd exposure, as suggested by rodent studies. Hence, although Cd may prove to be a major risk factor for morbidity and mortality in humans, practical strategies for limiting its absorption and pathogenic impact are at hand. Copyright © 2012 Elsevier Ltd. All rights reserved.", "title": "Zinc and multi-mineral supplementation should mitigate the pathogenic impact of cadmium exposure." }, { "docid": "MED-2573", "text": "A significant anticancer activity of the naturally occurring carbohydrate inositol hexaphosphate (IP(6)) has been reported against numerous cancer models. Since tumors require angiogenesis for growth and metastasis, we hypothesize that IP(6) reduces tumor growth by inhibiting angiogenesis. Because angiogenesis depends on the interaction between endothelial and tumor cells, we investigated the effect of IP(6) on both. IP(6) inhibited the proliferation and induced the differentiation of endothelial cells in vitro; the growth of bovine aortic endothelial cells (BAECs) evaluated by MTT proliferation assay was inhibited in a dose-dependent manner (IC(50) = 0.74 mM). The combination of IP(6) and vasostatin, a calreticulin fragment with anti-angiogenic activity, was synergistically superior in growth inhibition than either compound. IP(6) inhibited human umbilical vein endothelial cell (HUVEC) tube formation (in vitro capillary differentiation) on a reconstituted extracellular matrix, Matrigel, and disrupted pre-formed tubes. IP(6) significantly reduced basic fibroblast growth factor (bFGF)-induced vessel formation (P < 0.01) in vivo in Matrigel plug assay. Exposure of HepG2, a human hepatoma cell line, to IP(6) for 8 h, resulted in a dose-dependent decrease in the mRNA levels of vascular endothelial growth factor (VEGF), as assessed by RT-PCR. IP(6) treatment of HepG2 cells for 24 h also significantly reduced the VEGF protein levels in conditioned medium, in a concentration-dependent manner (P = 0.012). Thus, IP(6) has an inhibitory effect on induced angiogenesis.", "title": "Anti-angiogenic activity of inositol hexaphosphate (IP6)." }, { "docid": "MED-1324", "text": "Six noninsulin-dependent diabetic subjects received meals containing 25 g carbohydrate either as potato or as spaghetti. The meals were repeated with the addition of 25 g protein and with 25 g protein and 25 g fat. Blood glucose and insulin responses were measured for 4 h after the test meal. When carbohydrate was given alone, the blood glucose and serum insulin increments were higher for the potato meal. The addition of protein increased the insulin responses to both carbohydrates and slightly reduced the glycemic response to mashed potato (F = 2.04, p less than 0.05). The further addition of fat reduced the glycemic response to mashed potato (F = 14.63, p less than 0.001) without any change in the blood glucose response to spaghetti (F = 0.94, NS). The different responses to coingestion of protein and fat reduced the difference between the glycemic responses to the two carbohydrates.", "title": "Differential effect of protein and fat ingestion on blood glucose responses to high- and low-glycemic-index carbohydrates in noninsulin-dependent d..." }, { "docid": "MED-3891", "text": "Escherichia coli isolates were recovered from the National Antimicrobial Resistance Monitoring System retail meat program and examined for antimicrobial susceptibility. Retail meat samples (n = 11,921) from four U.S. states collected during 2002 to 2008, consisting of 2,988 chicken breast, 2,942 ground turkey, 2,991 ground beef, and 3,000 pork chop samples, were analyzed. A total of 8,286 E. coli isolates were recovered. The greatest numbers of samples contaminated with the organism were chicken (83.5%) and turkey (82.0%), followed by beef (68.9%) and pork (44.0%). Resistance was most common to tetracycline (50.3%), followed by streptomycin (34.6%), sulfamethoxazole-sulfisoxazole (31.6%), ampicillin (22.5%), gentamicin (18.6%), kanamycin (8.4%), amoxicillin-clavulanic acid (6.4%), and cefoxitin (5.2%). Less than 5% of the isolates had resistance to trimethoprim, ceftriaxone, ceftiofur, nalidixic acid, chloramphenicol, and ciprofloxacin. All isolates were susceptible to amikacin. Compared to beef and pork isolates, the poultry meat isolates had a greater percentage of resistance to all tested drugs, with the exception of chloramphenicol, to which pork isolates had the most resistance. More than half of the turkey isolates (56%) were resistant to multidrugs (≥3 classes) compared to 38.9% of chicken, 17.3% of pork, and 9.3% of beef isolates. The blaCMY gene was present in all ceftriaxone- and ceftiofur-resistant isolates. The cmlA, flo, and catI genes were present in 45%, 43%, and 40% of chloramphenicol-resistant isolates, respectively. Most nalidixic acid-resistant isolates (98.5%) had a gyrA mutation in S83 or D87 or both, whereas only 6.7% had a parC mutation in either S80 or E84. The results showed that E. coli was commonly present in the retail meats, and antimicrobial resistance profiles differed according to the animal origin of the isolates.", "title": "Comparison of the Prevalences and Antimicrobial Resistances of Escherichia coli Isolates from Different Retail Meats in the United States, 2002 to 2008" }, { "docid": "MED-2122", "text": "OBJECTIVE: To clarify the hormonal context of breast cancer etiology we used data from a large, population-based case-control study to investigate the relationship between breast cancer risk and a history of diabetes mellitus, disorders associated with estrogen stimulation (uterine fibroids, endometriosis, gallstones), and disorders associated with androgen stimulation (acne, hirsutism, and polycystic ovaries). METHODS: Breast cancer patients between 50 and 75 years old were identified from state-wide tumor registries in Wisconsin, Massachusetts, and New Hampshire; controls were randomly selected from drivers' license lists (age less than 65) or Medicare enrollment files (age 65-74). Information on reproductive history, medical history, and personal habits was obtained by telephone interview. A total of 5659 cases and 5928 controls were interviewed and provided suitable data. RESULTS: There was no overall association between breast cancer risk and reported history of diabetes mellitus, endometriosis, uterine fibroids, gallstones, or cholecystectomy. However, the disorders with androgenic associations all conferred an increased risk: the overall odds ratio (OR) for a history of acne was 1.4 (95% CI 1.0-1.9), that for hirsutism was 1.2 (95% CI 0.81-1.8), and that for polycystic ovaries 1.6 (95% CI 0.8-3.2). Diabetes mellitus diagnosed before age 35 conferred an odds ratio of 0.52 (95% 0.25-1.1), while diabetes diagnosed at a later age was associated with an increased risk (OR = 1.2, 95% CI 1.0-1.4). CONCLUSIONS: Androgen-related phenomena are likely to be important in the etiology of breast cancer.", "title": "Metabolic disorders and breast cancer risk (United States)." }, { "docid": "MED-2852", "text": "AIMS/HYPOTHESIS: The aim of this study was to prospectively examine whether dietary patterns are related to risk of gestational diabetes mellitus (GDM). METHODS: This prospective cohort study included 13,110 women who were free of cardiovascular disease, cancer, type 2 diabetes and history of GDM. Subjects completed a validated semi-quantitative food frequency questionnaire in 1991, and reported at least one singleton pregnancy between 1992 and 1998 in the Nurses' Health Study II. Two major dietary patterns (i.e. 'prudent' and 'Western') were identified through factor analysis. The prudent pattern was characterised by a high intake of fruit, green leafy vegetables, poultry and fish, whereas the Western pattern was characterised by high intake of red meat, processed meat, refined grain products, sweets, French fries and pizza. RESULTS: We documented 758 incident cases of GDM. After adjustment for age, parity, pre-pregnancy BMI and other covariates, the relative risk (RR) of GDM, comparing the highest with the lowest quintile of the Western pattern scores, was 1.63 (95% CI 1.20-2.21; p (trend)=0.001), whereas the RR comparing the lowest with the highest quintile of the prudent pattern scores was 1.39 (95% CI 1.08-1.80; p (trend)=0.018). The RR for each increment of one serving/day was 1.61 (95% CI 1.25-2.07) for red meat and 1.64 (95% CI 1.13-2.38) for processed meat. CONCLUSIONS/INTERPRETATION: These findings suggest that pre-pregnancy dietary patterns may affect women's risk of developing GDM. A diet high in red and processed meat was associated with a significantly elevated risk.", "title": "A prospective study of dietary patterns, meat intake and the risk of gestational diabetes mellitus." }, { "docid": "MED-3858", "text": "BACKGROUND: Observational and preclinical studies suggest that dietary fiber intake may reduce the risk of breast cancer, but the results are inconclusive. OBJECTIVE: We aimed to examine the association between dietary fiber intake and risk of breast cancer by conducting a meta-analysis of prospective cohort studies. DESIGN: Relevant studies were identified by a PubMed database search through January 2011. Reference lists from retrieved articles were also reviewed. We included prospective cohort studies that reported RRs with 95% CIs for the association between dietary fiber intake and breast cancer risk. Both fixed- and random-effects models were used to calculate the summary risk estimates. RESULTS: We identified 10 prospective cohort studies of dietary fiber intake and risk of breast cancer involving 16,848 cases and 712,195 participants. The combined RR of breast cancer for the highest compared with the lowest dietary fiber intake was 0.89 (95% CI: 0.83, 0.96), and little evidence of heterogeneity was observed. The association between dietary fiber intake and risk of breast cancer did not significantly differ by geographic region, length of follow-up, or menopausal status of the participants. Omission of any single study had little effect on the combined risk estimate. Dose-response analysis showed that every 10-g/d increment in dietary fiber intake was associated with a significant 7% reduction in breast cancer risk. Little evidence of publication bias was found. CONCLUSION: This meta-analysis provides evidence of a significant inverse dose-response association between dietary fiber intake and breast cancer risk.", "title": "Dietary fiber intake and risk of breast cancer: a meta-analysis of prospective cohort studies." }, { "docid": "MED-3954", "text": "BACKGROUND: A male epidemic of ischaemic heart disease (IHD) emerges with economic development. It has previously been hypothesised that this epidemic is due to nutritionally driven levels of pubertal sex steroids, which lead to a more atherogenic body shape and lipid profile in boys but not girls, without any sex-specific effects on glucose metabolism. This study tests this hypothesis by examining the association of childhood meat eating with IHD risk in a developing Chinese population. METHODS: Multivariable linear and censored regression was used in a cross-sectional study of 19,418 Chinese older (≥ 50 years) men and women from the Guangzhou Biobank Cohort Study (phases 2 and 3) to assess the adjusted associations of childhood meat eating with waist to hip ratio (WHR), high-density lipoprotein cholesterol and fasting plasma glucose. RESULTS: Adjusted for age, childhood hunger, life-course socioeconomic position and current lifestyle childhood almost daily meat eating compared with less than weekly meat eating was associated with higher WHR (0.007, 95% CI 0.0003 to 0.01) in men but not women. No association with fasting glucose was observed. CONCLUSIONS: Given the potential limitations of this study, especially the crude nature of the exposure and modest findings, the results should be considered as preliminary. However, they do lend support to the hypothesis that the male epidemic of premature IHD and sexual divergence in IHD rates that occur with economic development may be nutritionally driven in childhood. In elucidating the developmental origins of non-communicable chronic diseases, more attention should be focused on the sociohistorical context and the role of puberty.", "title": "Does childhood meat eating contribute to sex differences in risk factors for ischaemic heart disease in a developing population?" }, { "docid": "MED-3723", "text": "Epidemiological studies investigating the association between dietary intake and oesophageal cancer have mostly focused on nutrients and food groups instead of dietary patterns. We conducted a population-based case-control study, which included 365 oesophageal adenocarcinoma (OAC), 426 oesophagogastric junction adenocarcinoma (OGJAC) and 303 oesophageal squamous cell carcinoma (OSCC) cases, with frequency matched on age, sex and geographical location to 1580 controls. Data on demographic, lifestyle and dietary factors were collected using self-administered questionnaires. We used principal component analysis to derive three dietary patterns: 'meat and fat', 'pasta and pizza' and 'fruit and vegetable', and unconditional logistic regression models to estimate risks of OAC, OGJAC and OSCC associated with quartiles (Q) of dietary pattern scores. A high score on the meat-and-fat pattern was associated with increased risk of all three cancers: multivariable-adjusted OR 2·12 (95 % CI 1·30, 3·46) for OAC; 1·88 (95% CI 1·21, 2·94) for OGJAC; 2·84 (95% CI 1·67, 4·83) for OSCC (P-trend <0·01 for all three cancers). A high score on the pasta-and-pizza pattern was inversely associated with OSCC risk (OR 0·58, 95 % CI 0·36, 0·96, P for trend=0·009); and a high score on the fruit-and-vegetable pattern was associated with a borderline significant decreased risk of OGJAC (OR for Q4 v. Q1 0·66, 95% CI 0·42, 1·04, P=0·07) and significantly decreased risk of OSCC (OR 0·41, 95% CI 0·24, 0·70, P for trend=0·002). High-fat dairy foods appeared to play a dominant role in the association between the meat-and-fat pattern and risk of OAC and OGJAC. Further investigation in prospective studies is needed to confirm these findings.", "title": "Dietary patterns and risk of oesophageal cancers: a population-based case-control study." }, { "docid": "MED-2988", "text": "This review describes the present state of knowledge about phytic acid (phytate), which is often present in legume seeds. The antinutritional effects of phytic acid primarily relate to the strong chelating associated with its six reactive phosphate groups. Its ability to complex with proteins and particularly with minerals has been a subject of investigation from chemical and nutritional viewpoints. The hydrolysis of phytate into inositol and phosphates or phosphoric acid occurs as a result of phytase or nonenzymatic cleavage. Enzymes capable of hydrolysing phytates are widely distributed in micro-organisms, plants and animals. Phytases act in a stepwise manner to catalyse the hydrolysis of phytic acid. To reduce or eliminate the chelating ability of phytate, dephosphorylation of hexa- and penta-phosphate forms is essential since a high degree of phosphorylation is necessary to bind minerals. There are several methods of decreasing the inhibitory effect of phytic acid on mineral absorption (cooking, germination, fermentation, soaking, autolysis). Nevertheless, inositol hexaphosphate is receiving increased attention owing to its role in cancer prevention and/or therapy and its hypocholesterolaemic effect.", "title": "The role of phytic acid in legumes: antinutrient or beneficial function?" }, { "docid": "MED-2361", "text": "The most common clinical manifestation of Lyme disease is the characteristic rash, erythema migrans (EM). In the 1980s EM-like eruptions were reported in Missouri and other southeastern states. The EM-like eruptions, which were of unknown etiology, often followed the bite of the Lone Star tick (Amblyomma americanum) and the rash is called STARI (southern tick-associated rash illness). Although the Lone Star tick is found in the Lyme disease-endemic areas of New England and Mid-Atlantic regions of the United States, STARI has been reported only once from the Northeast and Mid-Atlantic regions. We report a child from Connecticut who visited Long Island, New York, and developed a rash that was thought to be EM. Because the patient failed to respond to antibiotics used to treat Lyme disease, an investigation ensued, and the diagnosis of STARI was established.", "title": "Southern Tick-Associated Rash Illness (STARI) in the North: STARI following a tick bite in Long Island, New York." }, { "docid": "MED-5004", "text": "BACKGROUND: Cross-sectional studies have shown that vegetarians and vegans are leaner than omnivores. Longitudinal data on weight gain in these groups are sparse. OBJECTIVE: We investigated changes in weight and body mass index (BMI) over a 5-year period in meat-eating, fish-eating, vegetarian, and vegan men and women in the UK. DESIGN: Self-reported anthropometric, dietary and lifestyle data were collected at baseline in 1994-1999 and at follow-up in 2000-2003; the median duration of follow-up was 5.3 years. SUBJECTS: A total of 21,966 men and women participating in Oxford arm of the European Prospective Investigation into Cancer and Nutrition aged 20-69 years at baseline. RESULTS: The mean annual weight gain was 389 (SD 884) g in men and 398 (SD 892) g in women. The differences between meat-eaters, fish-eaters, vegetarians and vegans in age-adjusted mean BMI at follow-up were similar to those seen at baseline. Multivariable-adjusted mean weight gain was somewhat smaller in vegans (284 g in men and 303 g in women, P<0.05 for both sexes) and fish-eaters (338 g, women only, P<0.001) compared with meat-eaters. Men and women who changed their diet in one or several steps in the direction meat-eater --> fish-eater --> vegetarian --> vegan showed the smallest mean annual weight gain of 242 (95% CI 133-351) and 301 (95% CI 238-365) g, respectively. CONCLUSION: During 5 years follow-up, the mean annual weight gain in a health-conscious cohort in the UK was approximately 400 g. Small differences in weight gain were observed between meat-eaters, fish-eaters, vegetarians and vegans. Lowest weight gain was seen among those who, during follow-up, had changed to a diet containing fewer animal food.", "title": "Weight gain over 5 years in 21,966 meat-eating, fish-eating, vegetarian, and vegan men and women in EPIC-Oxford." }, { "docid": "MED-4853", "text": "OBJECTIVE: To demonstrate the effects of a very low-fat, vegan diet on patients with rheumatoid arthritis (RA). DESIGN: Single-blind dietary intervention study. SUBJECTS AND STUDY INTERVENTIONS: This study evaluated the influence of a 4-week, very low-fat (approximately 10%), vegan diet on 24 free-living subjects with RA, average age, 56 +/- 11 years old. OUTCOME MEASUREMENTS: Prestudy and poststudy assessment of RA symptomatology was performed by a rheumatologist blind to the study design. Biochemical measures and 4-day diet data were also collected. Subjects met weekly for diet instruction, compliance monitoring, and progress assessments. RESULTS: There were significant (p < 0.001) decreases in fat (69%), protein (24%), and energy (22%), and a significant increase in carbohydrate (55%) intake. All measures of RA symptomatology decreased significantly (p < 0.05), except for duration of morning stiffness (p > 0.05). Weight also decreased significantly (p < 0.001). At 4 weeks, C-reactive protein decreased 16% (ns, p > 0.05), RA factor decreased 10% (ns, p > 0.05), while erythrocyte sedimentation rate was unchanged (p > 0.05). CONCLUSION: This study showed that patients with moderate-to-severe RA, who switch to a very low-fat, vegan diet can experience significant reductions in RA symptoms.", "title": "Effects of a very low-fat, vegan diet in subjects with rheumatoid arthritis." }, { "docid": "MED-1158", "text": "The efficiencies of acidic solutions (radish, citric acid, ascorbic acid, acetic acid and hydrogen peroxide), neutral solutions (sodium chloride) and alkaline solution (sodium carbonate) as well as tap water in the elimination of organochlorine and organophosphorus pesticides from naturally contaminated potatoes were examined. The results indicated that acidic solutions were more effective than neutral and alkaline solutions in the elimination of the organochlorine compounds under investigation, Radish solutions eliminated pesticides completely, except o,p'-DDE (73.1% loss), followed by citric and ascorbic acid solutions. On the other hand, organophosphorus pesticides (pirimphos methyl, malathion and profenofos) were eliminated more by acidic, neutral and alkaline solutions than by organochlorines. The percentage of removal ranged from 98.5 to 100% for pirimphos methyl, 87.9 to 100% for malathion and 100% for profenofos.", "title": "Behaviour of some organophosphorus and organochlorine pesticides in potatoes during soaking in different solutions." }, { "docid": "MED-1322", "text": "Several studies have suggested a protective effect of intake of whole grains, but not refined grains on type 2 diabetes risk, but the dose-response relationship between different types of grains and type 2 diabetes has not been established. We conducted a systematic review and meta-analysis of prospective studies of grain intake and type 2 diabetes. We searched the PubMed database for studies of grain intake and risk of type 2 diabetes, up to June 5th, 2013. Summary relative risks were calculated using a random effects model. Sixteen cohort studies were included in the analyses. The summary relative risk per 3 servings per day was 0.68 (95% CI 0.58-0.81, I(2) = 82%, n = 10) for whole grains and 0.95 (95% CI 0.88-1.04, I(2) = 53%, n = 6) for refined grains. A nonlinear association was observed for whole grains, p nonlinearity < 0.0001, but not for refined grains, p nonlinearity = 0.10. Inverse associations were observed for subtypes of whole grains including whole grain bread, whole grain cereals, wheat bran and brown rice, but these results were based on few studies, while white rice was associated with increased risk. Our meta-analysis suggests that a high whole grain intake, but not refined grains, is associated with reduced type 2 diabetes risk. However, a positive association with intake of white rice and inverse associations between several specific types of whole grains and type 2 diabetes warrant further investigations. Our results support public health recommendations to replace refined grains with whole grains and suggest that at least two servings of whole grains per day should be consumed to reduce type 2 diabetes risk.", "title": "Whole grain and refined grain consumption and the risk of type 2 diabetes: a systematic review and dose-response meta-analysis of cohort studies." }, { "docid": "MED-4450", "text": "Little is known about the effects of diet after breast cancer diagnosis on survival. We prospectively examined the relation between post-diagnosis dietary factors and breast cancer and all-cause survival in women with a history of invasive breast cancer diagnosed between 1987 and 1999 (at ages 20–79 years). Diet after breast cancer diagnosis was measured using a 126-item food frequency questionnaire. Among 4,441 women without a history of breast cancer recurrence prior to completing the questionnaire, 137 subsequently died from breast cancer within 7 years of enrollment. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for intake of macronutrients as well as selected micronutrients and food groups from Cox proportional hazards regression models. After adjustment for factors at diagnosis (age, state of residence, menopausal status, smoking, breast cancer stage, alcohol, history of hormone replacement therapy), interval between diagnosis and diet assessment, and at follow-up (energy intake, breast cancer treatment, body mass index, and physical activity), women in the highest compared to lowest quintile of intake of saturated fat and trans fat had a significantly higher risk of dying from any cause (HR = 1.41, 95% CI = 1.06 to 1.87, P-trend = 0.03) for saturated fat; (HR = 1.78, 95% CI = 1.35 to 2.32, P-trend = 0.01) for trans fat intake. Associations were similar, though did not achieve statistical significance, for breast cancer survival. This study suggests that lower intake of saturated and trans fat in the post-diagnosis diet is associated with improved survival after breast cancer diagnosis.", "title": "Post-diagnosis dietary factors and survival after invasive breast cancer" }, { "docid": "MED-1377", "text": "Increased attention in dietary research and guidance has been focused on dietary patterns, rather than on single nutrients or food groups, because dietary components are consumed in combination and correlated with one another. However, the collective body of research on the topic has been hampered by the lack of consistency in methods used. We examined the relationships between 4 indices—the Healthy Eating Index–2010 (HEI-2010), the Alternative Healthy Eating Index–2010 (AHEI-2010), the alternate Mediterranean Diet (aMED), and Dietary Approaches to Stop Hypertension (DASH)—and all-cause, cardiovascular disease (CVD), and cancer mortality in the NIH-AARP Diet and Health Study (n = 492,823). Data from a 124-item food-frequency questionnaire were used to calculate scores; adjusted HRs and 95% CIs were estimated. We documented 86,419 deaths, including 23,502 CVD- and 29,415 cancer-specific deaths, during 15 y of follow-up. Higher index scores were associated with a 12–28% decreased risk of all-cause, CVD, and cancer mortality. Specifically, comparing the highest with the lowest quintile scores, adjusted HRs for all-cause mortality for men were as follows: HEI-2010 HR: 0.78 (95% CI: 0.76, 0.80), AHEI-2010 HR: 0.76 (95% CI: 0.74, 0.78), aMED HR: 0.77 (95% CI: 0.75, 0.79), and DASH HR: 0.83 (95% CI: 0.80, 0.85); for women, these were HEI-2010 HR: 0.77 (95% CI: 0.74, 0.80), AHEI-2010 HR: 0.76 (95% CI: 0.74, 0.79), aMED HR: 0.76 (95% CI: 0.73, 0.79), and DASH HR: 0.78 (95% CI: 0.75, 0.81). Similarly, high adherence on each index was protective for CVD and cancer mortality examined separately. These findings indicate that multiple scores reflect core tenets of a healthy diet that may lower the risk of mortality outcomes, including federal guidance as operationalized in the HEI-2010, Harvard’s Healthy Eating Plate as captured in the AHEI-2010, a Mediterranean diet as adapted in an Americanized aMED, and the DASH Eating Plan as included in the DASH score.", "title": "Higher Diet Quality Is Associated with Decreased Risk of All-Cause, Cardiovascular Disease, and Cancer Mortality among Older Adults" }, { "docid": "MED-1802", "text": "Hypotheses regarding the role of meat consumption in body weight modulation are contradictory. Prospective studies on an association between meat consumption and BMI change are limited. We assessed the association between meat consumption and change in BMI over time in 3902 men and women aged 55-69 y from the Netherlands Cohort Study. Dietary intake was estimated at baseline using a FFQ. BMI was ascertained through baseline self-reported height (1986) and weight (1986, 1992, and 2000). Analyses were based on sex-specific categories of daily total fresh meat, red meat, beef, pork, minced meat, chicken, processed meat, and fish consumption at baseline. Linear mixed effect modeling adjusted for confounders was used to assess longitudinal associations. Significant cross-sectional differences in BMI between quintiles of total meat intake were observed (P-trend < 0.01; both sexes). No association between total fresh meat consumption and prospective BMI change was observed in men (BMI change highest vs. lowest quintile after 14 y: -0.06 kg/m²; P = 0.75) and women (BMI change: 0.26 kg/m²; P = 0.20). Men with the highest intake of beef experienced a significantly lower increase in BMI after 6 and 14 y than those with the lowest intake (BMI change after 14 y 0.60 kg/m²). After 14 y, a significantly higher increase in BMI was associated with higher intakes of pork in women (BMI change highest vs. lowest quintile: 0.47 kg/m²) and chicken in both sexes (BMI change highest vs. lowest category in both men and women: 0.36 kg/m²). The results remained similar when stratifying on median baseline BMI, and age-stratified analyses yielded mixed results. Differential BMI change effects were observed for several subtypes of meat. However, total meat consumption, or factors directly related to total meat intake, was not strongly associated with weight change during the 14-y prospective follow-up in this elderly population.", "title": "Longitudinal changes in BMI in older adults are associated with meat consumption differentially, by type of meat consumed." }, { "docid": "MED-2655", "text": "Background Broad dietary patterns have been linked to asthma but the relative contribution of specific nutrients is unclear. Soy genistein has important anti-inflammatory and other biological effects that might be beneficial in asthma. A positive association was previously reported between soy genistein intake and lung function but not with asthma exacerbations. Aims To conduct a post-hoc analysis of patients with inadequately controlled asthma enrolled in a prospective multicentre clinical trial to replicate this association. Methods A total of 300 study participants were included in the analysis. Dietary soy genistein intake was measured using the Block Soy Foods Screener. The level of soy genistein intake (little or no intake, moderate intake, or high intake) was compared with baseline lung function (pre-bronchodilator forced expiratory volume in 1 second (FEV1)) and asthma control (proportion of participants with an episode of poor asthma control (EPAC) and annualised rates of EPACs over a 6-month follow-up period. Results Participants with little or no genistein intake had a lower baseline FEV1 than those with a moderate or high intake (2.26L vs. 2.53L and 2.47L, respectively; p=0.01). EPACs were more common among those with no genistein intake than in those with a moderate or high intake (54% vs. 35% vs. 40%, respectively; p<0.001). These findings remained significant after adjustment for patient demographics and body mass index. Conclusions In patients with asthma, consumption of a diet with moderate to high amounts of soy genistein is associated with better lung function and better asthma control.", "title": "Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial" }, { "docid": "MED-1762", "text": "Background In the United States, anabolic sex steroids are administered to cattle for growth promotion. There is concern regarding the reproductive consequences of this practice for men who eat beef. We investigated whether meat consumption was associated with semen quality parameters and reproductive hormone levels in young men. Methods Semen samples were obtained from 189 men aged 18-22 years. Diet was assessed with a previously validated food frequency questionnaire. We used linear regression to analyze the cross-sectional associations of meat intake with semen quality parameters and reproductive hormones, while adjusting for potential confounders. Results There was an inverse relation between processed red meat intake and total sperm count. The adjusted relative differences in total sperm counts for men in increasing quartiles of processed meat intake were 0 (ref), −3 (95% confidence interval = −67 to 37), −14 (−82 to 28), and −78 (−202 to −5) million (test for trend, P = 0.01). This association was strongest among men with abstinence time less than 2 days and was driven by a strong inverse relation between processed red meat intake and ejaculate volume (test for trend, P =0.003). Conclusions In our population of young men, processed meat intake was associated with lower total sperm count. We cannot distinguish whether this association is due to residual confounding by abstinence time or represents a true biological effect.", "title": "Meat intake and reproductive parameters among young men" }, { "docid": "MED-1593", "text": "OBJECTIVE: Based on the hypothesis that high-meat diets may increase breast cancer risk through hormonal pathways, the present analysis compared oestrogens in serum and urine by meat-eating status. DESIGN: Intervention with repeated measures. SETTING: Two randomized soya trials (BEAN1 and BEAN2) among premenopausal healthy women. SUBJECTS: BEAN1 participants completed seven unannounced 24 h dietary recalls and donated five blood and urine samples over 2 years. BEAN2 women provided seven recalls and three samples over 13 months. Serum samples were analysed for oestrone (E₁) and oestradiol (E₂) using RIA. Nine oestrogen metabolites were measured in urine by LC-MS. Semi-vegetarians included women who reported consuming <30 g of red meat, poultry and fish daily, and pescatarians those who reported consuming <20 g of meat/poultry but >10 g of fish daily. All other women were classified as non-vegetarians. We applied mixed models to compute least-square means by vegetarian status adjusted for potential confounders. RESULTS: The mean age of the 272 participants was 41·9 (SD 4·5) years. Serum E₁ (85 v. 100 pg/ml, P = 0·04) and E₂ (140 v. 154 pg/ml, P = 0·04) levels were lower in the thirty-seven semi-vegetarians than in the 235 non-vegetarians. The sum of the nine urinary oestrogen metabolites (183 v. 200 pmol/mg creatinine, P = 0·27) and the proportions of individual oestrogens and pathways did not differ by meat-eating status. Restricting the models to the samples collected during the luteal phase strengthened the associations. CONCLUSIONS: Given the limitations of the study, the lower levels of serum oestrogens in semi-vegetarians than non-vegetarians need confirmation in larger populations.", "title": "Oestrogen levels in serum and urine of premenopausal women eating low and high amounts of meat." }, { "docid": "MED-4058", "text": "A facile method was established to measure heterocyclic aromatic amines (HAAs) accumulated in human hair and rodent fur. The samples were digested by base hydrolysis, and the liberated HAAs were isolated by tandem solvent/solid-phase extraction. Quantification was done by liquid chromatography/tandem mass spectrometry, using a triple stage quadrupole mass spectrometer in the selected reaction monitoring mode. In a pilot study of 12 human volunteers, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was detected in hair of six meat-eaters at levels ranging from 290 to 890 pg/g hair. 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-9H-pyrido[2,3-b]indole (AαC) were below the limit of quantification (LOQ) (50 pg/g hair) in hair from meat-eaters and six vegetarians. PhIP was detected in the hair from one vegetarian, and at level just above the LOQ (65 pg/g hair), indicating PhIP exposure occurs primarily through meat consumption. The levels of PhIP in hair samples from two meat-eaters varied by less than 24% over a 6-month interval, signifying that the exposure to PhIP and its accumulation in hair are relatively constant over time. In a controlled feeding study, female C57BL/6 mice were given these HAAs in their drinking water for 1 month, at six daily dose concentrations ranging from 0, 0.080 to 800 µg/kg body weight. PhIP was detected in fur of mice at all doses, whereas AαC and MeIQx were detected in fur at dosages ≥0.8 µg AαC/kg body weight and ≥8 µg MeIQx/kg body weight. There was a strong positive relationship between dosage and each of the HAAs accumulated in fur and their DNA adducts formed in liver and colon (p-values <0.0001); however, the levels of HAA in fur did not correlate to the levels of DNA adducts after adjustment of dose. Thus, hair appears to be a promising long-lived biomarker with by which we can assess the exposure to PhIP, a potential human carcinogen.", "title": "Biomonitoring of Carcinogenic Heterocyclic Aromatic Amines in Hair: A Validation Study" }, { "docid": "MED-3790", "text": "Background: Processed meat and fish have been shown to be associated with the risk of advanced prostate cancer, but few studies have examined diet after prostate cancer diagnosis and risk of its progression. Objective: We examined the association between postdiagnostic consumption of processed and unprocessed red meat, fish, poultry, and eggs and the risk of prostate cancer recurrence or progression. Design: We conducted a prospective study in 1294 men with prostate cancer, without recurrence or progression as of 2004–2005, who were participating in the Cancer of the Prostate Strategic Urologic Research Endeavor and who were followed for an average of 2 y. Results: We observed 127 events (prostate cancer death or metastases, elevated prostate-specific antigen concentration, or secondary treatment) during 2610 person-years. Intakes of processed and unprocessed red meat, fish, total poultry, and skinless poultry were not associated with prostate cancer recurrence or progression. Greater consumption of eggs and poultry with skin was associated with 2-fold increases in risk in a comparison of extreme quantiles: eggs [hazard ratio (HR): 2.02; 95% CI: 1.10, 3.72; P for trend = 0.05] and poultry with skin (HR: 2.26; 95% CI: 1.36, 3.76; P for trend = 0.003). An interaction was observed between prognostic risk at diagnosis and poultry. Men with high prognostic risk and a high poultry intake had a 4-fold increased risk of recurrence or progression compared with men with low/intermediate prognostic risk and a low poultry intake (P for interaction = 0.003). Conclusions: Our results suggest that the postdiagnostic consumption of processed or unprocessed red meat, fish, or skinless poultry is not associated with prostate cancer recurrence or progression, whereas consumption of eggs and poultry with skin may increase the risk.", "title": "Intakes of meat, fish, poultry, and eggs and risk of prostate cancer progression" }, { "docid": "MED-3959", "text": "Context: Earlier age at menarche is associated with rapid infancy weight gain and childhood obesity. The role of hormone levels in mediating these associations is unclear. Objective: The aim of this study was to identify childhood hormone levels at age 8 yr that are associated with early menarche, independent of body size. Design, Settings, and Subjects: A total of 329 girls from a prospective United Kingdom birth cohort study provided blood samples at mean age 8.1 yr (range, 8.0–8.5) for hormone measurements and were followed longitudinally to establish age at menarche. Main Outcome Measures: Fasting plasma levels of IGF-I, androstenedione, dehydroepiandrosterone sulfate (DHEAS), leptin, insulin, IGF binding protein-1, and SHBG were measured. Age at menarche was reported by questionnaire and categorized as before 12.0, 12.0–13.0, or later than 13 yr. Results: Earlier menarche was associated with greater body weight, height, and body mass index at age 8 yr (all P-trend <0.001). Before adjustment for body size, earlier menarche was associated with higher levels of IGF-I, androstenedione, DHEAS, leptin, and fasting insulin, and with lower levels of IGF binding protein-1 and SHBG at age 8 yr (all P < 0.01). After adjustment for body mass index and height at age 8 yr, only IGF-I (P = 0.004), androstenedione (P = 0.01), and DHEAS (P = 0.01) remained associated with earlier menarche. Conclusions: Associations between higher levels of IGF-I and adrenal androgens at age 8 yr with earlier menarche, independent of body size, support functional roles of these hormones in regulating puberty timing in girls. Higher levels of these hormones reported in children who exhibited rapid weight gain during infancy may indicate their role in developmental pathways leading to earlier sexual maturation.", "title": "Higher Levels of IGF-I and Adrenal Androgens at Age 8 Years Are Associated with Earlier Age at Menarche in Girls" }, { "docid": "MED-4854", "text": "In a controlled clinical trial we have recently shown that patients with rheumatoid arthritis (RA) improved after fasting for 7-10 d and that the improvement could be sustained through 3.5 months with a vegan diet and 9 months with a lactovegetarian diet. Other studies have indicated that the inflammatory process in RA can be reduced through manipulation of dietary fatty acids. A switch to a vegetarian diet significantly alters the intake of fatty acids. Therefore, we have analysed the changes in fatty acid profiles of the plasma phospholipid fraction and related these changes to disease activity. The concentrations of the fatty acids 20:3n-6 and 20:4n-6 were significantly reduced after 3.5 months with a vegan diet (P < 0.0001 and P < 0.01 respectively), but the concentration increased to baseline values with a lactovegetarian diet. The concentration of 20:5n-3 was significantly reduced after the vegan diet (P < 0.0001) and the lactovegetarian diet periods (P < 0.01). There was no significant difference in fatty acid concentrations between diet responders and diet non-responders after the vegan or lactovegetarian diet periods. Our results indicate that the changes in the fatty acid profiles cannot explain the clinical improvement.", "title": "Changes in plasma phospholipid fatty acids and their relationship to disease activity in rheumatoid arthritis patients treated with a vegetarian diet." }, { "docid": "MED-2211", "text": "BACKGROUND: China is increasingly facing the challenge of control of the growing burden of non-communicable diseases. We assessed the epidemiology of Alzheimer's disease and other forms of dementia in China between 1990, and 2010, to improve estimates of the burden of disease, analyse time trends, and inform health policy decisions relevant to China's rapidly ageing population. METHODS: In our systematic review we searched for reports of Alzheimer's disease or dementia in China, published in Chinese and English between 1990 and 2010. We searched China National Knowledge Infrastructure, Wanfang, and PubMed databases. Two investigators independently assessed case definitions of Alzheimer's disease and dementia: we excluded studies that did not use internationally accepted case definitions. We also excluded reviews and viewpoints, studies with no numerical estimates, and studies not done in mainland China. We used Poisson regression and UN demographic data to estimate the prevalence (in nine age groups), incidence, and standardised mortality ratio of dementia and its subtypes in China in 1990, 2000, and 2010. FINDINGS: Our search returned 12,642 reports, of which 89 met the inclusion criteria (75 assessed prevalence, 13 incidence, and nine mortality). In total, the included studies had 340,247 participants, in which 6357 cases of Alzheimer's disease were recorded. 254,367 people were assessed for other forms of dementia, of whom 3543 had vascular dementia, frontotemporal dementia, or Lewy body dementia. In 1990 the prevalence of all forms of dementia was 1·8% (95% CI 0·0-44·4) at 65-69 years, and 42·1% (0·0-88·9) at age 95-99 years. In 2010 prevalence was 2·6% (0·0-28·2) at age 65-69 years and 60·5% (39·7-81·3) at age 95-99 years. The number of people with dementia in China was 3·68 million (95% CI 2·22-5·14) in 1990, 5·62 million (4·42-6·82) in 2000, and 9·19 million (5·92-12·48) in 2010. In the same period, the number of people with Alzheimer's disease was 1·93 million (1·15-2·71) in 1990, 3·71 million (2·84-4·58) people in 2000, and 5·69 million (3·85-7·53) in 2010. The incidence of dementia was 9·87 cases per 1000 person-years, that of Alzheimer's disease was 6·25 cases per 1000 person-years, that of vascular dementia was 2·42 cases per 1000 person-years, and that of other rare forms of dementia was 0·46 cases per 1000 person-years. We retrieved mortality data for 1032 people with dementia and 20,157 healthy controls, who were followed up for 3-7 years. The median standardised mortality ratio was 1·94:1 (IQR 1·74-2·45). INTERPRETATION: Our analysis suggests that previous estimates of dementia burden, based on smaller datasets, might have underestimated the burden of dementia in China. The burden of dementia seems to be increasing faster than is generally assumed by the international health community. Rapid and effective government responses are needed to tackle dementia in low-income and middle-income countries. FUNDING: Nossal Institute of Global Health (University of Melbourne, Australia), the National 12th Five-Year Major Projects of China, National Health and Medical Research Council Australia-China Exchange Fellowship, Importation and Development of High-Calibre Talents Project of Beijing Municipal Institutions, and the Bill & Melinda Gates Foundation. Copyright © 2013 Elsevier Ltd. All rights reserved.", "title": "Epidemiology of Alzheimer's disease and other forms of dementia in China, 1990-2010: a systematic review and analysis." }, { "docid": "MED-2273", "text": "Objective To examine and quantify the relation between purine intake and the risk of recurrent gout attacks among gout patients. Methods The authors conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for 1 year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, clinical symptoms and signs, medications (including antigout medications), and presence of potential risk factors (including daily intake of various purine-containing food items) during the 2-day period prior to the gout attack. The same exposure information was also assessed over 2-day control periods. Results This study included 633 participants with gout. Compared with the lowest quintile of total purine intake over a 2-day period, OR of recurrent gout attacks were 1.17, 1.38, 2.21 and 4.76, respectively, with each increasing quintile (p for trend <0.001). The corresponding OR were 1.42, 1.34, 1.77 and 2.41 for increasing quintiles of purine intake from animal sources (p for trend <0.001), and 1.12, 0.99, 1.32 and 1.39 from plant sources (p=0.04), respectively. The effect of purine intake persisted across subgroups by sex, use of alcohol, diuretics, allopurinol, NSAIDs and colchicine. Conclusions The study findings suggest that acute purine intake increases the risk of recurrent gout attacks by almost fivefold among gout patients. Avoiding or reducing amount of purine-rich foods intake, especially of animal origin, may help reduce the risk of gout attacks.", "title": "Purine-rich foods intake and recurrent gout attacks" }, { "docid": "MED-3781", "text": "In this study, a panel of normal human prostate cells (HPCs) and tumor cells derived from metastases were studied by (1)H NMR spectroscopy to determine whether the malignant transformation of HPCs results in the elevation of choline compounds. Although an elevated choline signal has been observed previously in clinical studies, the contribution of the different Cho compounds to this elevation, as well as their quantification, has not been established until now. Here we have shown that HPCs derived from metastases exhibit significantly higher phosphocholine as well as glycerophosphocholine levels compared with normal prostate epithelial and stromal cells. Thus the elevation of the choline peak observed clinically in prostate cancer is attributable to an alteration of phospholipid metabolism and not simply to increased cell density, doubling time, or other nonspecific effects. Androgen deprivation of the androgen receptor-positive cell lines resulted in a significant increase of choline compounds after chronic androgen deprivation of the LNCaP cell line and in a decrease of choline compounds after a more acute androgen deprivation of the LAPC-4 cell line. These data strongly support the use of proton magnetic resonance spectroscopic imaging to detect the presence of prostate cancer for diagnosis, to detect response subsequent to androgen ablation therapy, and to detect recurrence.", "title": "Detection of increased choline compounds with proton nuclear magnetic resonance spectroscopy subsequent to malignant transformation of human prosta..." }, { "docid": "MED-4746", "text": "Americans consume about 5 billion hamburgers a year. It is presumed that most hamburgers are composed primarily of meat. The purpose of this study is to assess the content of 8 fast food hamburger brands using histologic methods. Eight different brands of hamburgers were evaluated for water content by weight and microscopically for recognizable tissue types. Glial fibrillary acidic protein (GFAP) staining was used to evaluate for brain tissue. Water content by weight ranged from 37.7% to 62.4% (mean, 49%). Meat content in the hamburgers ranged from 2.1% to 14.8% (median, 12.1%). The cost per gram of hamburger ranged from $0.02 to $0.16 (median, $0.03) and did not correlate with meat content. Electron microscopy showed relatively preserved skeletal muscle. A variety of tissue types besides skeletal muscle were observed including connective tissue (n = 8), blood vessels (n = 8), peripheral nerve (n = 8), adipose tissue (n = 7), plant material (n = 4), cartilage (n = 3), and bone (n = 2). In 2 hamburgers, intracellular parasites (Sarcocystis) were identified. The GFAP immunostaining was not observed in any of the hamburgers. Lipid content on oil-red-O staining was graded as 1+ (moderate) in 6 burgers and 2+ (marked) in 2 burgers. Fast food hamburgers are comprised of little meat (median, 12.1%). Approximately half of their weight is made up of water. Unexpected tissue types found in some hamburgers included bone, cartilage, and plant material; no brain tissue was present. Sarcocystis parasites were discovered in 2 hamburgers.", "title": "Fast food hamburgers: what are we really eating?" }, { "docid": "MED-4820", "text": "Background: Few prospective studies have examined cancer incidence among vegetarians. Methods: We studied 61 566 British men and women, comprising 32 403 meat eaters, 8562 non-meat eaters who did eat fish (‘fish eaters') and 20 601 vegetarians. After an average follow-up of 12.2 years, there were 3350 incident cancers of which 2204 were among meat eaters, 317 among fish eaters and 829 among vegetarians. Relative risks (RRs) were estimated by Cox regression, stratified by sex and recruitment protocol and adjusted for age, smoking, alcohol, body mass index, physical activity level and, for women only, parity and oral contraceptive use. Results: There was significant heterogeneity in cancer risk between groups for the following four cancer sites: stomach cancer, RRs (compared with meat eaters) of 0.29 (95% CI: 0.07–1.20) in fish eaters and 0.36 (0.16–0.78) in vegetarians, P for heterogeneity=0.007; ovarian cancer, RRs of 0.37 (0.18–0.77) in fish eaters and 0.69 (0.45–1.07) in vegetarians, P for heterogeneity=0.007; bladder cancer, RRs of 0.81 (0.36–1.81) in fish eaters and 0.47 (0.25–0.89) in vegetarians, P for heterogeneity=0.05; and cancers of the lymphatic and haematopoietic tissues, RRs of 0.85 (0.56–1.29) in fish eaters and 0.55 (0.39–0.78) in vegetarians, P for heterogeneity=0.002. The RRs for all malignant neoplasms were 0.82 (0.73–0.93) in fish eaters and 0.88 (0.81–0.96) in vegetarians (P for heterogeneity=0.001). Conclusion: The incidence of some cancers may be lower in fish eaters and vegetarians than in meat eaters.", "title": "Cancer incidence in British vegetarians" }, { "docid": "MED-2363", "text": "We have previously shown that an antibody pool present in normal human serum binds cytokine receptors in vitro and may therefore interfere with assays that capture cytokines using their receptors. Here we show that this antibody pool is the same as the natural antibody termed anti-gal, that binds to the alpha-galactosyl carbohydrate epitope (alpha-gal) and which is the predominant obstacle to xenotransplantation. We report that there are high levels of IgD anti alpha-gal in most volunteers, in addition to the IgG2, IgA and IgM immunoglobulin isotypes against alpha-gal previously described. To determine if anti-gal may interfere with assays that depend on capture of cytokine with its receptor, we measured levels of several anti-carbohydrate antibodies in a cohort of patients with advanced atherosclerosis that had previously been used to measure levels of active TGF-beta using such an assay. For many isotype / carbohydrate combinations, there is a large and significant difference between the levels of anti-carbohydrate antibodies in patients with atherosclerosis and controls, after adjustment for age, sex and blood group. These results are similar to the previous data obtained for active TGF-beta, and therefore we cannot discount the possibility that anti-gal contributed to the previous data. Following further adjustment for several risk factors associated with cardiovascular disease, several anti-carbohydrate antibodies were still significantly different between patients and controls. Therefore, anti-carbohydrate antibodies may represent a new class of risk factors that may be associated with presence of advanced atherosclerosis, although larger studies will be required to confirm this hypothesis.", "title": "A pattern of anti-carbohydrate antibody responses present in patients with advanced atherosclerosis." }, { "docid": "MED-4951", "text": "OBJECTIVE: To evaluate the role of the environmental estrogens polychlorinated biphenyls (PCBs) and phthalate esters (PEs) as potential environmental hazards in the deterioration of semen parameters in infertile men without an obvious etiology. DESIGN: Randomized controlled study. SETTING: Tertiary care referral infertility clinic and academic research center. PATIENT(S): Twenty-one infertile men with sperm counts <20 million/mL and/or rapid progressive motility <25% and/or <30% normal forms without evidence of an obvious etiology and 32 control men with normal semen analyses and evidence of conception. Semen and blood samples were obtained as part of the treatment protocol. MAIN OUTCOME MEASURE(S): Evaluation of semen parameters such as ejaculate volume, sperm count, motility, morphology, vitality, osmoregulatory capacity, sperm chromatin stability, and sperm nuclear DNA integrity. RESULT(S): PCBs were detected in the seminal plasma of infertile men but not in controls, and the concentration of PEs was significantly higher in infertile men compared with controls. Ejaculate volume, sperm count, progressive motility, normal morphology, and fertilizing capacity were significantly lower in infertile men compared with controls. The highest average PCB and PE concentrations were found in urban fish eaters, followed by rural fish eaters, urban vegetarians, and rural vegetarians. The total motile sperm counts in infertile men were inversely proportional to their xenoestrogen concentrations and were significantly lower than those in the respective controls. CONCLUSION(S): PCBs and PEs may be instrumental in the deterioration of semen quality in infertile men without an obvious etiology.", "title": "Role of environmental estrogens in the deterioration of male factor fertility." }, { "docid": "MED-4841", "text": "OBJECTIVES: The goal of this study was to determine the incidence of serum antibodies to gliadin and to cow's milk proteins (CMP) using ELISA test, within patients who have recurrent aphthous ulcers (RAU). SUBJECTS AND METHODS: Fifty patients with recurrent aphthous ulcers and fifty healthy people were included in this research. Levels of serum IgA and IgG antibodies to gliadin and IgA, IgG and IgE to CMP were determined using ELISA. RESULTS: The levels of serum antigliadin IgA and IgG antibodies were not significantly higher in patients with RAU in comparison with the controls (P = 0.937 and P = 0.1854 respectively). The levels of serum anti-CMP IgA, IgG and IgE antibodies were significantly higher in patients with RAU in comparison with the controls (P < 0.005, P < 0.002 and P < 0.001 respectively). In general, the increased humoral (IgA or IgG) immunoreactivity to CMP was found in 32 of 50 patients, while 17 of them showed the increased levels of both IgA and IgG immunoreactivity to CMP. At the same time, 16 out of 50 patients had IgA, IgG and IgE immunoreactivity to CMP. CONCLUSION: These results indicate the strong association between high levels of serum anti-CMP IgA, IgG and IgE antibodies and clinical manifestations of recurrent aphthous ulcers.", "title": "Humoral immunity to cow's milk proteins and gliadin within the etiology of recurrent aphthous ulcers?" }, { "docid": "MED-2906", "text": "BACKGROUND: Different chemical forms of mercury occur naturally in human milk. The most controversial aspect of early post-natal exposure to organic mercury is ethylmercury (EtHg) in thimerosal-containing vaccines (TCV) still being used in many countries. Thus exclusively breastfed infants can be exposed to both, fish derived methylmercury (MeHg) in maternal diets and to EtHg from TCV. The aim of the study is to evaluate a new analytical method for ethyl and methyl mercury in hair samples of breastfed infants who had received the recommended schedule of TCV. METHODS: The hair of infants (<12 months) that had been exposed to TCV (Hepatitis B and DTaP) was analysed. A method coupling isothermal gas chromatography with cold-vapor atomic fluorescence spectrometry was used for MeHg which can also speciate EtHg in biological matrices. RESULTS: In 20 samples of infants' hair, all but two samples showed variable amounts of MeHg (10.3 to 668 ng/g), while precise and reliable concentrations of EtHg (3.7 to 65.0 ng/g) were found in 15 of the 20 samples. A statistically significant inverse association (r=-05572; p=0.0384) was found between hair-EtHg concentrations and the time elapsed after the last TCV shot. CONCLUSIONS: The analytical method proved sensitive enough to quantify EtHg in babies' hair after acute exposure to thimerosal in vaccine shots. Provided that the mass of hair was above 10mg, organic-mercury exposure during early life can be speciated, and quantified in babies' first hair, thus opening opportunities for clinical and forensic studies. Copyright © 2011 Elsevier B.V. All rights reserved.", "title": "Speciation of methyl- and ethyl-mercury in hair of breastfed infants acutely exposed to thimerosal-containing vaccines." }, { "docid": "MED-1609", "text": "To examine extra-alimentary effects of high-carbohydrate, high-fiber (HCF) diets, insulin-mediated glucose disposal employing the euglycemic clamp and hepatic glucose output (HGO) employing [6,6-2H2]glucose were measured in 12 healthy young and old individuals before and after 21-28 d of an HCF diet. Diet lowered fasting concentrations of glucose from 5.3 +/- 0.2 to 5.1 +/- 0.1 mmol/L (p less than 0.01) and insulin from 66.0 +/- 7.9 to 49.5 +/- 5.7 pmol/L (p less than 0.01). Fasting serum cholesterol decreased from 5.17 +/- 0.18 to 3.80 +/- 0.20 mmol/L (p less than 0.01) in young individuals and from 6.15 +/- 0.52 to 4.99 +/- 0.49 mmol/L (p less than 0.01) in elderly individuals. Fasting serum triglyceride concentrations, basal HGO, and insulin suppression of HGO were unchanged by the diet. Glucose disposal rates increased from 18.87 +/- 1.66 before 23.87 +/- 2.78 mumol.kg-1.min-1 after the diet (p less than 0.02). Therefore, HCF diets may improve carbohydrate economy by enhanced peripheral sensitivity to insulin.", "title": "High-carbohydrate, high-fiber diets increase peripheral insulin sensitivity in healthy young and old adults." }, { "docid": "MED-3927", "text": "Objective: Epidemiologic studies consistently link caffeine, a nonselective adenosine antagonist, to lower risk of Parkinson disease (PD). However, the symptomatic effects of caffeine in PD have not been adequately evaluated. Methods: We conducted a 6-week randomized controlled trial of caffeine in PD to assess effects upon daytime somnolence, motor severity, and other nonmotor features. Patients with PD with daytime somnolence (Epworth >10) were given caffeine 100 mg twice daily ×3 weeks, then 200 mg twice daily ×3 weeks, or matching placebo. The primary outcome was the Epworth Sleepiness Scale score. Secondary outcomes included motor severity, sleep markers, fatigue, depression, and quality of life. Effects of caffeine were analyzed with Bayesian hierarchical models, adjusting for study site, baseline scores, age, and sex. Results: Of 61 patients, 31 were randomized to placebo and 30 to caffeine. On the primary intention-to-treat analysis, caffeine resulted in a nonsignificant reduction in Epworth Sleepiness Scale score (−1.71 points; 95% confidence interval [CI] −3.57, 0.13). However, somnolence improved on the Clinical Global Impression of Change (+0.64; 0.16, 1.13, intention-to-treat), with significant reduction in Epworth Sleepiness Scale score on per-protocol analysis (−1.97; −3.87, −0.05). Caffeine reduced the total Unified Parkinson's Disease Rating Scale score (−4.69 points; −7.7, −1.6) and the objective motor component (−3.15 points; −5.50, −0.83). Other than modest improvement in global health measures, there were no changes in quality of life, depression, or sleep quality. Adverse events were comparable in caffeine and placebo groups. Conclusions: Caffeine provided only equivocal borderline improvement in excessive somnolence in PD, but improved objective motor measures. These potential motor benefits suggest that a larger long-term trial of caffeine is warranted. Classification of evidence: This study provides Class I evidence that caffeine, up to 200 mg BID for 6 weeks, had no significant benefit on excessive daytime sleepiness in patients with PD.", "title": "Caffeine for treatment of Parkinson disease" }, { "docid": "MED-4308", "text": "We examined the occurrence and coincidence of depressed mood and excessive carbohydrate intake in 19 patients who claimed to suffer from severe premenstrual syndrome and in nine control subjects, all as inpatients, during the early follicular and late luteal phases of their menstrual cycles. Mood was assessed with the Hamilton Depression Scale and an addendum that evaluated fatigue, sociability, appetite, and carbohydrate craving. Calorie and nutrient intakes were measured directly. The subjects with premenstrual syndrome significantly increased calorie intake during the late luteal phase (from 1892 +/- 104 to 2395 +/- 93 kcal, mean +/- SEM); carbohydrate intake increased by 24% from meals and by 43% from snacks. Protein intake failed to change, whereas intake of fat, a fixed constituent of all of the test foods, rose in proportion to calorie intake. The Hamilton Depression Scale and addendum scores rose from 2.0 +/- 0.5 to 21.2 +/- 0.8 (Hamilton Scale) and from 0.5 +/- 0.5 to 10.2 +/- 0.6 (addendum) among subjects with premenstrual syndrome during the luteal phase but failed to change among the controls (2.1 +/- 0.8 to 2.4 +/- 0.8, and 0.4 +/- 0.3 to 0.6 +/- 0.3). Consumption of a carbohydrate-rich, protein-poor evening test meal during the late luteal phase of the menstrual cycle improved depression, tension, anger, confusion, sadness, fatigue, alertness, and calmness scores (p less than 0.01) among patients with premenstrual syndrome. No effect of the meal was observed during the follicular phase or among the control subjects during either phase. Because synthesis of brain serotonin, which is known to be involved in mood and appetite, increases after carbohydrate intake, premenstrual syndrome subjects may overconsume carbohydrates in an attempt to improve their dysphoric mood state.", "title": "Effect of nutrient intake on premenstrual depression." }, { "docid": "MED-2510", "text": "Dietary restriction (DR) extends the lifespan of a wide range of species, although the universality of this effect has never been quantitatively examined. Here, we report the first comprehensive comparative meta-analysis of DR across studies and species. Overall, DR significantly increased lifespan, but this effect is modulated by several factors. In general, DR has less effect in extending lifespan in males and also in non-model organisms. Surprisingly, the proportion of protein intake was more important for life extension via DR than the degree of caloric restriction. Furthermore, we show that reduction in both age-dependent and age-independent mortality rates drives life extension by DR among the well-studied laboratory model species (yeast, nematode worms, fruit flies and rodents). Our results suggest that convergent adaptation to laboratory conditions better explains the observed DR-longevity relationship than evolutionary conservation although alternative explanations are possible. © 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.", "title": "Comparative and meta-analytic insights into life extension via dietary restriction." }, { "docid": "MED-2121", "text": "The purpose of this paper is to highlight the endocrine signaling of Western diet, a fundamental environmental factor involved in the pathogenesis of epidemic acne. Western nutrition is characterized by high calorie uptake, high glycemic load, high fat and meat intake, as well as increased consumption of insulin- and IGF-1-level elevating dairy proteins. Metabolic signals of Western diet are sensed by the nutrient-sensitive kinase, mammalian target of rapamycin complex 1 (mTORC1), which integrates signals of cellular energy, growth factors (insulin, IGF-1) and protein-derived signals, predominantly leucine, provided in high amounts by milk proteins and meat. mTORC1 activates SREBP, the master transcription factor of lipogenesis. Leucine stimulates mTORC1-SREBP signaling and leucine is directly converted by sebocytes into fatty acids and sterols for sebaceous lipid synthesis. Over-activated mTORC1 increases androgen hormone secretion and most likely amplifies androgen-driven mTORC1 signaling of sebaceous follicles. Testosterone directly activates mTORC1. Future research should investigate the effects of isotretinoin on sebocyte mTORC1 activity. It is conceivable that isotretinoin may downregulate mTORC1 in sebocytes by upregulation of nuclear levels of FoxO1. The role of Western diet in acne can only be fully appreciated when all stimulatory inputs for maximal mTORC1 activation, i.e., glucose, insulin, IGF-1 and leucine, are adequately considered. Epidemic acne has to be recognized as an mTORC1-driven disease of civilization like obesity, type 2 diabetes, cancer and neurodegenerative diseases. These new insights into Western diet-mediated mTORC1-hyperactivity provide a rational basis for dietary intervention in acne by attenuating mTORC1 signaling by reducing (1) total energy intake, (2) hyperglycemic carbohydrates, (3) insulinotropic dairy proteins and (4) leucine-rich meat and dairy proteins. The necessary dietary changes are opposed to the evolution of industrialized food and fast food distribution of Westernized countries. An attenuation of mTORC1 signaling is only possible by increasing the consumption of vegetables and fruit, the major components of vegan or Paleolithic diets. The dermatologist bears a tremendous responsibility for his young acne patients who should be advised to modify their dietary habits in order to reduce activating stimuli of mTORC1, not only to improve acne but to prevent the harmful and expensive march to other mTORC1-related chronic diseases later in life.", "title": "Dietary intervention in acne" }, { "docid": "MED-1601", "text": "Natural and organic food regulations preclude the use of sodium nitrite/nitrate and other antimicrobials for processed meat products. Consequently, processors have begun to use natural nitrate/nitrite sources, such as celery juice/powder, sea salt, and turbinado sugar, to manufacture natural and organic products with cured meat characteristics but without sodium nitrite. The objective of this study was to compare physio-chemical characteristics that affect Clostridium perfringens and Listeria monocytogenes growth in naturally cured and traditionally cured commercial frankfurters, hams, and bacon. Correlations of specific product characteristics to pathogen growth varied between products and pathogens, though water activity, salt concentration, and product composition (moisture, protein and fat) were common intrinsic factors correlated to pathogen growth across products. Other frequently correlated traits were related to curing reactions such as % cured pigment. Residual nitrite and nitrate were significantly correlated to C. perfringens growth but only for the ham products. Copyright © 2012 Elsevier Ltd. All rights reserved.", "title": "Survey of naturally and conventionally cured commercial frankfurters, ham, and bacon for physio-chemical characteristics that affect bacterial growth." }, { "docid": "MED-4306", "text": "When plasma tryptophan is elevated by the injection of tryptophan or insulin, or by the consumption of carbohydrates, brain tryptophan and serotonin also rise; however, when even larger elevations of plasma tryptophan are produced by the ingestion of protein-containing diets, brain tryptophan and serotonin do not change. The main determinant of brain tryptophan and serotonin concentrations does not appear to be plasma tryptophan alone, but the ratio of this amino acid to other plasma neutral amino acids (that is, tyrosine, phenylalanine, leucine, isoleucine, and valine) that compete with it for uptake into the brain.", "title": "Brain serotonin content: physiological regulation by plasma neutral amino acids." }, { "docid": "MED-3930", "text": "Studies that have addressed the association between the intake of coffee or caffeine and Parkinson's disease (PD) were conducted mainly in Western countries. Little is known about this relationship in an Asian population. Therefore, we performed an assessment of the association of the intake of coffee, other caffeine-containing beverages, and caffeine with the risk of PD in Japan. The study involved 249 PD cases and 368 control subjects. Information on dietary factors was obtained through a self-administered diet history questionnaire. Adjustment was made for sex, age, region of residence, educational level, pack-years of smoking, body mass index, the dietary glycemic index, and intake of cholesterol, vitamin E, β-carotene, vitamin B(6,) alcohol, and iron. Intake of coffee, black tea, and Japanese and Chinese teas was significantly inversely associated with the risk of PD: the adjusted odds ratios in comparison of the highest with the lowest quartile were 0.52, 0.58, and 0.59, respectively (95% confidence intervals = 0.30-0.90, 0.35-0.97, and 0.35-0.995, respectively). A clear inverse dose-response relationship between total caffeine intake and PD risk was observed. We confirmed that the intake of coffee and caffeine reduced the risk of PD. Furthermore, this is the first study to show a significant inverse relationship between the intake of Japanese and Chinese teas and the risk of PD. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Intake of Japanese and Chinese teas reduces risk of Parkinson's disease." }, { "docid": "MED-4255", "text": "The world's advanced countries have easy access to plentiful high-fat food; ironically, it is this rich diet that produces atherosclerosis. In the world's poorer nations, many people subsist on a primarily plant-based diet, which is far healthier, especially in terms of heart disease. To treat coronary heart disease, a century of scientific investigation has produced a device-driven, risk factor-oriented strategy. Nevertheless, many patients treated with this approach experience progressive disability and death. This strategy is a rear-guard defensive one. In contrast, compelling data from nutritional studies, population surveys, and interventional studies support the effectiveness of a plant-based diet and aggressive lipid lowering to arrest, prevent, and selectively reverse heart disease. In essence, this is an offensive strategy. The single biggest step toward adopting this strategy would be to have United States dietary guidelines support a plant-based diet. An expert committee purged of industrial and political influence is required to assure that science is the basis for dietary recommendations. (c)2001 CHF, Inc.", "title": "Resolving the Coronary Artery Disease Epidemic Through Plant-Based Nutrition." }, { "docid": "MED-4036", "text": "Oral health is related to diet in many ways, for example, nutritional influences on craniofacial development, oral cancer and oral infectious diseases. Dental diseases impact considerably on self-esteem and quality of life and are expensive to treat. The objective of this paper is to review the evidence for an association between nutrition, diet and dental diseases and to present dietary recommendations for their prevention. Nutrition affects the teeth during development and malnutrition may exacerbate periodontal and oral infectious diseases. However, the most significant effect of nutrition on teeth is the local action of diet in the mouth on the development of dental caries and enamel erosion. Dental erosion is increasing and is associated with dietary acids, a major source of which is soft drinks. Despite improved trends in levels of dental caries in developed countries, dental caries remains prevalent and is increasing in some developing countries undergoing nutrition transition. There is convincing evidence, collectively from human intervention studies, epidemiological studies, animal studies and experimental studies, for an association between the amount and frequency of free sugars intake and dental caries. Although other fermentable carbohydrates may not be totally blameless, epidemiological studies show that consumption of starchy staple foods and fresh fruit are associated with low levels of dental caries. Fluoride reduces caries risk but has not eliminated dental caries and many countries do not have adequate exposure to fluoride. It is important that countries with a low intake of free sugars do not increase intake, as the available evidence shows that when free sugars consumption is <15-20 kg/yr ( approximately 6-10% energy intake), dental caries is low. For countries with high consumption levels it is recommended that national health authorities and decision-makers formulate country-specific and community-specific goals for reducing the amount of free sugars aiming towards the recommended maximum of no more than 10% of energy intake. In addition, the frequency of consumption of foods containing free sugars should be limited to a maximum of 4 times per day. It is the responsibility of national authorities to ensure implementation of feasible fluoride programmes for their country.", "title": "Diet, nutrition and the prevention of dental diseases." }, { "docid": "MED-4726", "text": "The aim of these studies was to evaluate the potential of some nutritional approaches to prevent or reduce the body load of organochlorines (OC) in humans. Study 1 compared plasma OC concentrations between vegans and omnivores while study 2 verified if the dietary fat substitute olestra could prevent the increase in OC concentrations that is generally observed in response to a weight-reducing programme. In study 1, nine vegans and fifteen omnivores were recruited and the concentrations of twenty-six OC (beta-hexachlorocyclohexane (beta-HCH), p, p'-dichlorodiphenyldichloroethane (p, p'-DDE), p, p'-dichlorodiphenyltrichloroethane (p, p'-DDT), hexachlorobenzene, mirex, aldrin, alpha-chlordane, gamma-chlordane, oxychlordane, cis-nonachlor, trans-nonachlor, polychlorinated biphenyl (PCB) nos. 28, 52, 99, 101, 105, 118, 128, 138, 153, 156, 170, 180, 183 and 187, and aroclor 1260) were determined. In study 2, the concentrations of these twenty-six OC were measured before and after weight loss over 3 months in thirty-seven obese men assigned to one of the following treatments: standard group (33 % fat diet; n 13), fat-reduced group (25 % fat diet; n 14) or fat-substituted group (1/3 of dietary lipids substituted by olestra; n 10). In study 1, plasma concentrations of five OC compounds (aroclor 1260 and PCB 99, PCB 138, PCB 153 and PCB 180) were significantly lower in vegans compared with omnivores. In study 2, beta-HCH was the only OC which decreased in the fat-substituted group while increasing in the other two groups (P = 0.045). In conclusion, there was a trend toward lesser contamination in vegans than in omnivores, and olestra had a favourable influence on beta-HCH but did not prevent plasma hyperconcentration of the other OC during ongoing weight loss.", "title": "Impact of adopting a vegan diet or an olestra supplementation on plasma organochlorine concentrations: results from two pilot studies." }, { "docid": "MED-4797", "text": "The objectives of this study were to compare the prevalence of Clostridium difficile (Cd) among different age and production groups of swine in a vertically integrated swine operation in Texas in 2006 and to compare our isolates to other animal and human isolates. Results are based on 131 Cd isolates from 1008 swine fecal samples and pork trim samples (overall prevalence of 13%). The prevalence (number positive/number tested in production type) of Cd was different between the groups (P<or=0.001), and was highest among suckling piglets at 50.0% (61/122), followed by 23.8% (34/143) for lactating sows and effluent from the farrowing barn, 8.4% (10/119) for nursery, 6.5% (4/62) for pork products, 3.9% (15/382) for grower-finisher, and 3.9% (7/180) for breeding boars and sows. Of the 131 isolates, 122 were positive by PCR for both toxins A (tcdA) and B (tcdB) genes, 129 isolates harbored a 39 base pair deletion in the tcdC gene, 120 isolates were toxinotype V, and all 131 of the isolates were positive for the binary toxin gene cdtB. All isolates were resistant to cefoxitin, ciprofloxacin, and imipenem, whereas all were sensitive to metronidazole, piperacillin/tazobactam, amoxicillin/clavulanic acid, and vancomycin. The majority of isolates were resistant to clindamycin; resistant or intermediate to ampicillin; and sensitive to tetracycline and chloramphenicol. There was an increased (P</=0.001) number of isolates for the timeframe of September to February compared to March to August.", "title": "Varied prevalence of Clostridium difficile in an integrated swine operation." }, { "docid": "MED-5190", "text": "To investigate the association between dietary exposure to food mutagens and risk of pancreatic cancer, we conducted a hospital-based case-control study at the University of Texas M. D. Anderson Cancer Center during June 2002 to May 2006. Atotal of 626 cases and 530 noncancer controls were frequency matched for race, sex and age (±5 years). Dietary exposure information was collected via personal interview using a meat preparation questionnaire. A significantly greater portion of the cases than controls showed a preference to well-done pork, bacon, grilled chicken, and pan-fried chicken, but not to hamburger and steak. Cases had a higher daily intake of food mutagens and mutagenicity activity (revertants per gram of daily meat intake) than controls did. The daily intakes of 2-amino-3,4,8-trimethylimidazo[4,5—f]quinoxaline (DiMeIQx) and benzo(a)pyrene (BaP), as well as the mutagenic activity, were significant predictors for pancreatic cancer (P = 0.008, 0.031, and 0.029, respectively) with adjustment of other confounders. A significant trend of elevated cancer risk with increasing DiMeIQx intake was observed in quintile analysis (Ptrend= 0.024). Ahigher intake of dietary mutagens (those in the two top quintiles) was associated with a 2-fold increased risk of pancreatic cancer among those without a family history of cancer but not among those with a family history of cancer. Apossible synergistic effect of dietary mutagen exposure and smoking was observed among individuals with the highest level of exposure (top 10%) to PhIP and BaP, Pinteraction= 0.09 and 0.099, respectively. These data support the hypothesis that dietary mutagen exposure alone and in interaction with other factors contribute to the development of pancreatic cancer.", "title": "Dietary Mutagen Exposure and Risk of Pancreatic Cancer" }, { "docid": "MED-3420", "text": "Introduction Erectile dysfunction (ED) and cardiovascular disease (CVD) share pathophysiological mechanisms and often co-occur. Yet it is not known whether ED provides an early warning for increased CVD or other causes of mortality. Aim We sought to examine the association of ED with all-cause and cause-specific mortality. Methods Prospective, population-based study of 1,709 men (of 3,258 eligible) aged 40–70 years. ED was measured by self-report. Subjects were followed for a mean of 15 years. Hazard ratios (HR) were calculated using the Cox proportional hazards regression model. Main outcome measures Mortality due to all causes, CVD, malignant neoplasms, and other causes. Results Of 1,709 men, 1,284 survived to the end of 2004 and had complete ED and age data. Of 403 men who died, 371 had complete data. After adjustment for age, body mass index, alcohol consumption, physical activity, cigarette smoking, self-assessed health, and self-reported heart disease, hypertension, and diabetes, ED was associated with HRs of 1.26 [95% confidence interval (CI), 1.01–1.57] for all-cause mortality and 1.43 (95% CI, 1.00–2.05) for CVD mortality. The HR for CVD mortality associated with ED is of comparable magnitude to HRs of some conventional CVD risk factors. Conclusions These findings demonstrate that ED is significantly associated with increased all-cause mortality, primarily through its association with CVD mortality.", "title": "Erectile Dysfunction and Mortality" }, { "docid": "MED-4794", "text": "Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has become a matter of concern worldwide, in particular in the USA. For the analysis of emergence and spread, clear definitions based on epidemiological origin are needed for discrimination between CA-MRSA, healthcare-associated community MRSA, and healthcare-associated MRSA (HA-MRSA). Although its role in pathogenesis is currently under debate, the capability for Panton-Valentine leukocidin formation is associated with the majority of CA-MRSA isolates from North America and from Europe. Most CA-MRSA isolates are attributed to clonal lineages different from HA-MRSA; there are, however, clonal lineages from which both HA-MRSA and CA-MRSA have been reported (e.g. ST1, ST5, ST8, and ST22); CA-MRSA ST8 (USA300), which is most frequent in the USA, has meanwhile been reported from Europe. CA-MRSA ST80 is widely disseminated in Europe; because of its pronounced oxacillin heteroresistance phenotype, cefoxitin-based assays are advisable for reliable detection. So far, CA-MRSA infections seem to be much less frequent in Europe than in the USA, where patients with particular predispositions and low social status are at especial risk.", "title": "Community-acquired methicillin-resistant Staphylococcus aureus: what do we need to know?" }, { "docid": "MED-1540", "text": "A number of studies have evaluated the health of vegetarians. Others have studied the health effects of foods that are preferred or avoided by vegetarians. The purpose of this review is to look critically at the evidence on the health effects of vegetarian diets and to seek possible explanations where results appear to conflict. There is convincing evidence that vegetarians have lower rates of coronary heart disease, largely explained by low LDL cholesterol, probable lower rates of hypertension and diabetes mellitus, and lower prevalence of obesity. Overall, their cancer rates appear to be moderately lower than others living in the same communities, and life expectancy appears to be greater. However, results for specific cancers are much less convincing and require more study. There is evidence that risk of colorectal cancer is lower in vegetarians and in those who eat less meat; however, results from British vegetarians presently disagree, and this needs explanation. It is probable that using the label “vegetarian” as a dietary category is too broad and that our understanding will be served well by dividing vegetarians into more descriptive subtypes. Although vegetarian diets are healthful and are associated with lower risk of several chronic diseases, different types of vegetarians may not experience the same effects on health.", "title": "Vegetarian diets: what do we know of their effects on common chronic diseases?" }, { "docid": "MED-2413", "text": "Results from observational studies on the association of fish and n-3 fatty acid consumption with type 2 diabetes mellitus (T2DM) risk are conflicting. Hence, a meta-analysis was performed to investigate this association from cohort studies. A comprehensive search was then conducted to identify cohort studies on the association of fish and/or n-3 fatty acid intake with T2DM risk. In the highest v. lowest categorical analyses, the fixed or random-effect model was selected based on the homogeneity test among studies. Linear and non-linear dose-response relationships were also assessed by univariate and bivariate random-effect meta-regression with restricted maximum likelihood estimation. In the highest v. lowest categorical analyses, the pooled relative risk (RR) of T2DM for intake of fish and n-3 fatty acid was 1·146 (95 % CI 0·975, 1·346) and 1·076 (95 % CI 0·955, 1·213), respectively. In the linear dose-response relationship, the pooled RR for an increment of one time (about 105 g)/week of fish intake (four times/month) and of 0·1 g/d of n-3 fatty acid intake was 1·042 (95 % CI 1·026, 1·058) and 1·057 (95 % CI 1·042, 1·073), respectively. The significant non-linear dose-response associations of fish and n-3 fatty acid intake with T2DM risk were not observed. The present evidence from observational studies suggests that the intake of both fish and n-3 fatty acids might be weakly positively associated with the T2DM risk. Further studies are needed to confirm these results.", "title": "Association of fish and n-3 fatty acid intake with the risk of type 2 diabetes: a meta-analysis of prospective studies." }, { "docid": "MED-3547", "text": "Monoamine theories associate depression with reduced brain monoamine levels. These theories achieved broad popularity in the mid-1960s. The present article reviews the historical development of monoamine theories and their subsequent impact on biomedical research. Alleged divisions between West European and US researchers over competing versions of the theories are investigated using bibliometrics. Subsequently, the application of monoamine theories in the NIMH Collaborative Program on the Psychobiology of Depression is covered. The article argues that the impact of monoamine theories is best explained by the ability of researchers, governmental agencies, and pharmaceutical companies to invoke theories that advance various projects and agendas.", "title": "Monoamine theories of depression: historical impact on biomedical research." }, { "docid": "MED-3596", "text": "OBJECTIVE: To determine if eating habits, physical activity and BMI can influence assisted reproduction outcomes. MATERIAL AND METHODS: This study analyzed 436 patients undergoing intracytoplasmic sperm injection cycles. Patients answered a questionnaire and regression analysis examined the relationship between lifestyle and BMI with the intracytoplasmic sperm injection cycles outcomes. RESULTS: No influence of lifestyle and obesity was observed on the number of oocytes recovered. Obesity reduced the normal fertilization rate (coefficient [Coef.]: -16.0; p = 0.01) and increased the risk of miscarriage (OR: 14.3; p = 0.03). Physical activity positively affected implantation (Coef.: 9.4; p = 0.009), increased the chance of pregnancy (OR: 1.83; p = 0.013) and tended to decrease the risk of miscarriage (OR: 0.30; p = 0.068). In addition, an inverse correlation was found between physical activity and BMI, and a direct correlation was found between soft-drink consumption and BMI. CONCLUSIONS: Eating habits, physical activity and obesity could affect clinical outcomes of assisted reproduction.", "title": "Physical activity, obesity and eating habits can influence assisted reproduction outcomes." }, { "docid": "MED-4059", "text": "2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic amine formed in meat and fish during cooking and can be used as a model compound for this class of chemicals possibly involved in human carcinogenesis. Knowing the exposure to heterocyclic amines is important for establishing their role in human diseases. Serum albumin (SA) and globin (Gb) adducts were first tested as biomarkers of exposure to PhIP in male Fischer 344 rats given oral doses of 0.1, 0.5, 1 and 10 mg/kg. Blood samples were collected 24 hr after treatment and PhIP released from SA and Gb after acidic hydrolysis was analyzed by gas chromatography-mass spectrometry or liquid chromatography-tandem mass spectrometry. PhIP-SA and Gb adducts increased linearly with the dose. Studies on 35 volunteers with different dietary habits exhibited that diet was a major determinant in the formation of both adducts. PhIP-SA adducts were significantly higher in meat consumers than in vegetarians (6.7 +/- 1.6 and 0.7 +/- 0.3 fmol/mg SA; respectively, mean +/- SE; p = 0.04, Mann-Whitney U test). The Gb adduct pattern was quantitatively lower but paralleled SA (3 +/- 0.8 in meat consumers and 0.3 +/- 0.1 in vegetarians). PhIP-SA adducts were no different in smokers and in non-smokers. The results show for the first time that PhIP-blood protein adducts are present in humans not given the synthetic compound. Both biomarkers appear to be suitable for assessing dietary exposure and internal PhIP dose and may be promising tools for studying the role of heterocyclic amines in the etiology of colon cancer and other diseases. Copyright 2000 Wiley-Liss, Inc.", "title": "Effect of diet on serum albumin and hemoglobin adducts of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in humans." }, { "docid": "MED-1580", "text": "Background Crohn's disease is common in developed nations where the typical diet is low in fibre and high in processed food. Primary lesions overlie Peyer's patches and colonic lymphoid follicles where bacterial invasion through M-cells occurs. We have assessed the effect of soluble non-starch polysaccharide (NSP) and food emulsifiers on translocation of Escherichia coli across M-cells. Methods To assess effects of soluble plant fibres and food emulsifiers on translocation of mucosa-associated E coli isolates from Crohn's disease patients and from non-Crohn's controls, we used M-cell monolayers, generated by co-culture of Caco2-cl1 and Raji B cells, and human Peyer's patches mounted in Ussing chambers. Results E coli translocation increased across M-cells compared to parent Caco2-cl1 monocultures; 15.8-fold (IQR 6.2–32.0) for Crohn's disease E coli (N=8) and 6.7-fold (IQR 3.7–21.0) for control isolates (N=5). Electron microscopy confirmed E coli within M-cells. Plantain and broccoli NSP markedly reduced E coli translocation across M-cells at 5 mg/ml (range 45.3–82.6% inhibition, p<0.01); apple and leek NSP had no significant effect. Polysorbate-80, 0.01% vol/vol, increased E coli translocation through Caco2-cl1 monolayers 59-fold (p<0.05) and, at higher concentrations, increased translocation across M-cells. Similarly, E coli translocation across human Peyer's patches was reduced 45±7% by soluble plantain NSP (5 mg/ml) and increased 2-fold by polysorbate-80 (0.1% vol/vol). Conclusions Translocation of E coli across M-cells is reduced by soluble plant fibres, particularly plantain and broccoli, but increased by the emulsifier Polysorbate-80. These effects occur at relevant concentrations and may contribute to the impact of dietary factors on Crohn's disease pathogenesis.", "title": "Translocation of Crohn's disease Escherichia coli across M-cells: contrasting effects of soluble plant fibres and emulsifiers" }, { "docid": "MED-1611", "text": "A growing body of evidence from observational studies and meta-analyses of the data suggest that diabetes mellitus is associated with an increased risk of cancer. Meta-analyses have shown that diabetes increases the risks of total cancer, and of site-specific cancers of the breast, endometrium, bladder, liver, colorectum and pancreas, and that it decreases the risk of prostate cancer. Insulin resistance and secondary hyperinsulinemia is the most frequently proposed hypothesis, and hyperglycemia itself might promote carcinogenesis. In addition to several facets of lifestyle including obesity, smoking and lack of exercise, treatment for diabetes might affect the risk of cancer. For instance, metformin, an insulin sensitizer, reportedly has a potential anticancer effect. In light of the exploding global epidemic of diabetes, even a modest increase in the cancer risk will translate into a substantial socioeconomic burden. The current insights underscore the need for clinical attention and better-designed studies of the complex interactions between diabetes and cancer.", "title": "Latest insights into the risk of cancer in diabetes" }, { "docid": "MED-2700", "text": "Blood components, especially hemoglobin, are powerful promoters of lipid oxidation and may decrease the shelf life of meat products. Therefore, this study examined different slaughter techniques to determine their effects on pH (24 h), color (L*a*b* values at 24 h), lipid oxidation, residual hemoglobin concentration (24 h), and sensory evaluation (d 1 and 4 postmortem; PM) in broiler breast fillets. The treatments included 1) CO(2) slaughter and not bled, 2) no stunning and bled, 3) electrical stunning (ES) and bled, 4) CO(2) stunning and bled, and 5) ES and decapitation. The birds were conventionally processed, and analyses were performed at 24 h PM except residual hemoglobin for which the samples were frozen (-80 degrees C) until analyses ( < 2 mo). There were no significant differences in pH or b* values at 24 h PM among any of the treatments. L* values were significantly higher, indicating lighter fillets in the ES and decapitated birds compared with the darker fillets from the CO(2) stunned and bled birds. The CO(2) slaughter and not bled birds had significantly higher a* values, indicating more red color, when compared with the ES and bled and decapitated birds. There were no significant differences in the residual hemoglobin contents in the broiler breast muscle when comparing all of the treatments except CO(2) slaughter and not bled, which was significantly (around 15%) greater. Overall TBA-reactive substances (TBARS; raw, cooked at 24 h, and cooked at 72 h PM) indicated that ES and bled birds had the lowest TBARS when compared with the remaining treatments. Consumer panels detected increased aroma (chicken meaty and warmed-over aromas) and flavor (chicken meaty and warmed-over flavors) in not bled samples at 24 h PM. By 72 h PM, however, there were no significant differences in aroma or flavor. Therefore, different slaughter and bleeding method may affect color and sensory properties of the broiler breast fillets, and the ES and decapitation method had the most favorable results for sensory quality.", "title": "The effect of blood removal on oxidation and shelf life of broiler breast meat." }, { "docid": "MED-1582", "text": "Background & Aims Increased intake of dietary fiber has been proposed to reduce risk of inflammatory bowel diseases (Crohn’s disease [CD], ulcerative colitis [UC]). However, few prospective studies have examined associations between long-term intake of dietary fiber and risk of incident CD or UC. Methods We collected and analyzed data from 170,776 women, followed over 26 y, who participated in the Nurses’ Health Study, followed for 3,317,425 person-y. Dietary information was prospectively ascertained via administration of a validated semi-quantitative food frequency questionnaire every 4 y. Self-reported CD and UC were confirmed through review of medical records. Cox proportional hazards models, adjusting for potential confounders, were used to calculate hazard ratios (HRs). Results We confirmed 269 incident cases of CD (incidence 8/100,000 person-y) and 338 cases of UC (incidence 10/100,000 person-y). Compared to the lowest quintile of energy-adjusted cumulative average intake of dietary fiber, intake of the highest quintile (median of 24.3 g/day) was associated with a 40% reduction in risk of CD (multivariate HR for CD, 0.59; 95% confidence interval [CI], 0.39–0.90). This apparent reduction appeared to be greatest for fiber derived from fruits; fiber from cereals, whole grains, or legumes did not modify risk. In contrast, neither total intake of dietary fiber (multivariate HR, 0.82; 95% CI 0.58–1.17) nor intake of fiber from specific sources appeared to be significantly associated with risk of UC. Conclusion Based on data from the Nurses’ Health Study, long-term intake of dietary fiber, particularly from fruit, is associated with lower risk of CD but not UC. Further studies are needed to determine the mechanisms that mediate this association.", "title": "A Prospective Study of Long-term Intake of Dietary Fiber and Risk of Crohn’s Disease and Ulcerative Colitis" }, { "docid": "MED-1935", "text": "Recent evidences have highlighted an influence of micronutrients in the maintenance of telomere length (TL). In order to explore whether diet-related telomere shortening had any physiological relevance and was accompanied by significant damage in the genome, in the present study, TL was assessed by terminal restriction fragment (TRF) analysis in peripheral blood lymphocytes of 56 healthy subjects for which detailed information on dietary habits was available and data were compared \\with the incidence of nucleoplasmic bridges (NPBs), a marker of chromosomal instability related to telomere dysfunction visualised with the cytokinesis-blocked micronucleus assay. To increase the capability to detect even slight impairment of telomere function, the incidence of NPBs was also evaluated on cells exposed in vitro to ionising radiation. Care was taken to control for potential confounding factors that might influence TL, viz. age, hTERT genotype and smoking status. Data showed that higher consumption of vegetables was related with significantly higher mean TL (P = 0.013); in particular, the analysis of the association between micronutrients and mean TL highlighted a significant role of antioxidant intake, especially beta-carotene, on telomere maintenance (P = 0.004). However, the diet-related telomere shortening did not result in associated increased spontaneous or radiation-induced NPBs. The distribution of TRFs was also analysed and a slight prevalence of radiation-induced NPBs (P = 0.03) was observed in subjects with higher amount of very short TRFs (<2 kb). The relative incidence of very short TRFs was positively associate with ageing (P = 0.008) but unrelated to vegetables consumption and daily intake of micronutrients, suggesting that the degree of telomere erosion related with low dietary intake of antioxidants observed in this study was not so extensive to lead to chromosome instability.", "title": "Diet-related telomere shortening and chromosome stability" }, { "docid": "MED-2703", "text": "Extensive experimental data have revealed a central role for oxidative stress in atherogenesis and suggested a potential role for 'antioxidant' treatment in cardiovascular disease (CVD) [1-11]. Experimental data, however, have not translated into clinical benefit: most antioxidant vitamin trials have failed to reduce cardiovascular morbidity and mortality [12]. Moreover, recent clinical trials have suggested that mono-therapy with certain antioxidant vitamins like vitamin E may, in fact, be detrimental [13]. As a result of the disappointing outcome of 'antioxidant' vitamin trials, some authors have questioned both the utility of 'antioxidant' treatment in CVD and the supposedly central role of oxidative stress in atherogenesis [14-19]. Other investigators, however, sustain that the beneficial effects of lipid lowering and anti-hypertensive treatment are at least, in part, due to their 'antioxidant' properties, in addition to their specific pharmacological properties [20, 21]. Oxidant stress plays a pivotal role in atherogenesis, however, the clinical promise of antioxidant vitamins has failed to translate into clinical benefit. Increasing evidence suggests that more rigorous clinical trial designs are necessary to effectively divulge antioxidant utility and that a multifaceted antioxidant approach to atherosclerosis may yield the most clinical reward. This article reviews currently available evidence on the role of oxidant stress in atherosclerosis, analyzes the results of large anti-oxidant trials, and suggests ways to investigate the true role of antioxidant treatment in the clinical setting.", "title": "Atherosclerosis and oxidant stress: the end of the road for antioxidant vitamin treatment?" }, { "docid": "MED-1604", "text": "Previous cohort and case-control studies on the association between cruciferous vegetables consumption and risk of renal cell carcinoma have illustrated conflicting results so far. To demonstrate the potential association between them, a meta-analysis was performed. Eligible studies were retrieved via both computerized searches and review of references. The summary relative risks (RRs) with 95% confidence interval (CI) for the highest vs. the lowest consumption of cruciferous vegetables were calculated. Heterogeneity and publication bias were also evaluated. Stratified analyses were performed as well. Three cohort and 7 case-control studies were included. A significantly decreased risk with renal cell carcinoma was observed in overall cruciferous vegetables consumption group (RR = 0.73; 95% CI, 0.63-0.83) and subgroup of case-control studies (RR = 0.69; 95% CI, 0.60-0.78), but not in cohort studies (RR = 0.96; 95% CI, 0.71-1.21). No heterogeneity and publication bias were detected across studies. Our findings supported that cruciferous vegetables consumption was related to the decreased risk of renal cell carcinoma. Because of the limited number of studies, further well-designed prospective studies and researches need to be conducted to better clarify the protective effect of cruciferous vegetables on renal cell carcinoma and potential mechanism.", "title": "Cruciferous vegetables consumption and risk of renal cell carcinoma: a meta-analysis." }, { "docid": "MED-2662", "text": "A human breast cancer cell line (MCF-7) was used to develop an in vitro screening assay for the detection of xenoestrogenic environmental pollutants. MCF-7 cells were cultured in DMEM containing 5% fetal bovine serum (FBS). An estrogenic response was defined as an increase in the frequency of proliferating MCF-7 cells, and was measured using a thymidine analog, bromodeoxyuridine, and flow cytometry. Di-2-ethylhexyl phthalate (DEHP) and 4-n-nonylphenol (4-n-NP) were used as model chemicals. The proliferation rate of S-phase cells after 24 h of exposure to various concentrations of 17beta-estradiol and to model compounds was compared with a positive and a negative control, containing 1 nM 17beta-estradiol and 0.1% ethanol, respectively. DEHP and 4-n-NP increased the frequency of proliferating MCF-7 cells in a dose-dependent manner. The lowest concentration that significantly increased the proliferation of MCF-7 cells was 10 microM for DEHP and 1 microM for 4-n-NP. The results showed that the assay is accurate and quick to perform. It may prove a valuable tool for screening potential estrogen-mimicking environmental pollutants.", "title": "Effects of xenoestrogenic environmental pollutants on the proliferation of a human breast cancer cell line (MCF-7)." }, { "docid": "MED-2585", "text": "Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plant and mammalian cells. It was recently recognized to possess multiple biological functions. A striking anticancer effect of IP6 was demonstrated in different experimental models. Inositol is also a natural constituent possessing moderate anticancer activity. The most consistent and best anticancer results were obtained from the combination of IP6 plus inositol. In addition to reducing cell proliferation, IP6 increases differentiation of malignant cells, often resulting in a reversion to normal phenotype. Exogenously administered IP6 is rapidly taken into the cells and dephosphorylated to lower-phosphate inositol phosphates, which further interfere with signal transduction pathways and cell cycle arrest. Enhanced immunity and antioxidant properties can also contribute to tumor cell destruction. However, the molecular mechanisms underlying this anticancer action are not fully understood. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP6 holds great promise in our strategies for the prevention and treatment of cancer. IP6 plus inositol enhances the anticancer effect of conventional chemotherapy, controls cancer metastases, and improves the quality of life, as shown in a pilot clinical trial. The data strongly argue for the use of IP6 plus inositol in our strategies for cancer prevention and treatment. However, the effectiveness and safety of IP6 plus inositol at therapeutic doses needs to be determined in phase I and phase II clinical trials in humans.", "title": "Cancer inhibition by inositol hexaphosphate (IP6) and inositol: from laboratory to clinic." }, { "docid": "MED-1993", "text": "Type 2 diabetes mellitus is emerging as a new clinical problem within pediatric practice. Recent reports indicate an increasing prevalence of type 2 diabetes mellitus in children and adolescents around the world in all ethnicities, even if the prevalence of obesity is not increasing any more. The majority of young people diagnosed with type 2 diabetes mellitus was found in specific ethnic subgroups such as African-American, Hispanic, Asian/Pacific Islanders and American Indians. Clinicians should be aware of the frequent mild or asymptomatic manifestation of type 2 diabetes mellitus in childhood. Therefore, a screening seems meaningful especially in high risk groups such as children and adolescents with obesity, relatives with type 2 diabetes mellitus, and clinical features of insulin resistance (hypertension, dyslipidemia, polycystic ovarian syndrome, or acanthosis nigricans). Treatment of choice is lifestyle intervention followed by pharmacological treatment (e.g., metformin). New drugs such as dipeptidyl peptidase inhibitors or glucagon like peptide 1 mimetics are in the pipeline for treatment of youth with type 2 diabetes mellitus. However, recent reports indicate a high dropout of the medical care system of adolescents with type 2 diabetes mellitus suggesting that management of children and adolescents with type 2 diabetes mellitus requires some remodeling of current healthcare practices.", "title": "Type 2 diabetes mellitus in children and adolescents" }, { "docid": "MED-1959", "text": "Since 1991 the US Department of Agriculture (USDA) has conducted annual surveys of pesticide residues in foods under the Agricultural Marketing Service's Pesticide Data Program (PDP). To assess chemical residues in domestically marketed catfish products, 1479 catfish samples were collected during the 2008-2010 PDPs. A subset of 202 samples was analysed for 17 toxic polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs). The average pattern of the individual PCDD/F congener concentrations in the catfish was rather unique in that it had almost no measurable amounts of polychlorinated dibenzofurans (PCDFs), but all PCDDs were present. This pattern was more dominant in the domestically produced catfish products than in the imported products (China/Taiwan). Comparison of the pattern to known sources of PCDD/Fs showed strong similarities to the pattern of PCDD/Fs found in kaolin clays which have often been used as anti-caking agents in animal feeds. To investigate whether catfish feeds may be the source of the PCDD/Fs found in the catfish, archived catfish feed data from a US Food and Drug Administration (USFDA) database were examined. In 61 out of 112 feed samples, the PCDD concentrations were 50 times higher than the PCDF concentrations and resembled the pattern found in the catfish products and in clays mined in the south-eastern United States. Although the source of PCDD/Fs in domestically marketed catfish products cannot be definitively established, mined clay products used in feeds should be considered a likely source and, given the wide concentration range of PCDD/Fs that has been found in clays, a critical control point for PCDD/Fs entrance to the food supply.", "title": "Dioxin congener patterns in commercial catfish from the United States and the indication of mineral clays as the potential source." }, { "docid": "MED-1181", "text": "Demand for organic foods is partially driven by consumers' perceptions that they are more nutritious. However, scientific opinion is divided on whether there are significant nutritional differences between organic and non-organic foods, and two recent reviews have concluded that there are no differences. In the present study, we carried out meta-analyses based on 343 peer-reviewed publications that indicate statistically significant and meaningful differences in composition between organic and non-organic crops/crop-based foods. Most importantly, the concentrations of a range of antioxidants such as polyphenolics were found to be substantially higher in organic crops/crop-based foods, with those of phenolic acids, flavanones, stilbenes, flavones, flavonols and anthocyanins being an estimated 19 (95 % CI 5, 33) %, 69 (95 % CI 13, 125) %, 28 (95 % CI 12, 44) %, 26 (95 % CI 3, 48) %, 50 (95 % CI 28, 72) % and 51 (95 % CI 17, 86) % higher, respectively. Many of these compounds have previously been linked to a reduced risk of chronic diseases, including CVD and neurodegenerative diseases and certain cancers, in dietary intervention and epidemiological studies. Additionally, the frequency of occurrence of pesticide residues was found to be four times higher in conventional crops, which also contained significantly higher concentrations of the toxic metal Cd. Significant differences were also detected for some other (e.g. minerals and vitamins) compounds. There is evidence that higher antioxidant concentrations and lower Cd concentrations are linked to specific agronomic practices (e.g. non-use of mineral N and P fertilisers, respectively) prescribed in organic farming systems. In conclusion, organic crops, on average, have higher concentrations of antioxidants, lower concentrations of Cd and a lower incidence of pesticide residues than the non-organic comparators across regions and production seasons.", "title": "Higher antioxidant and lower cadmium concentrations and lower incidence of pesticide residues in organically grown crops: a systematic literature review and meta-analyses" }, { "docid": "MED-1376", "text": "Background. There are places around the world where people live longer and they are active past the age of 100 years, sharing common behavioral characteristics; these places (i.e., Sardinia in Italy, Okinawa in Japan, Loma Linda in California and Nicoya Peninsula in Costa Rica) have been named the “Blue Zones”. Recently it was reported that people in Ikaria Island, Greece, have also one of the highest life expectancies in the world, and joined the “Blue Zones”. The aim of this work work was to evaluate various demographic, lifestyle and psychological characteristics of very old (>80 years) people participated in Ikaria Study. Methods. During 2009, 1420 people (aged 30+) men and women from Ikaria Island, Greece, were voluntarily enrolled in the study. For this work, 89 males and 98 females over the age of 80 yrs were studied (13% of the sample). Socio-demographic, clinical, psychological and lifestyle characteristics were assessed using standard questionnaires and procedures. Results. A large proportion of the Ikaria Study's sample was over the age of 80; moreover, the percent of people over 90 were much higher than the European population average. The majority of the oldest old participants reported daily physical activities, healthy eating habits, avoidance of smoking, frequent socializing, mid-day naps and extremely low rates of depression. Conclusion. Modifiable risk factors, such as physical activity, diet, smoking cessation and mid-day naps, might depict the “secrets” of the long-livers; these findings suggest that the interaction of environmental, behavioral together with clinical characteristics may determine longevity. This concept must be further explored in order to understand how these factors relate and which are the most important in shaping prolonged life.", "title": "Sociodemographic and Lifestyle Statistics of Oldest Old People (>80 Years) Living in Ikaria Island: The Ikaria Study" }, { "docid": "MED-3028", "text": "OBJECTIVE The evidence on the association between fish consumption, dietary long-chain n-3 fatty acids, and risk of type 2 diabetes is inconsistent. We therefore performed a systematic review and meta-analysis of the available prospective evidence. RESEARCH DESIGN AND METHODS Studies were identified by searching the PubMed and EMBASE databases through 15 December 2011 and by reviewing the reference lists of retrieved articles. Prospective studies were included if they reported relative risk (RR) estimates with 95% CIs for the association between fish consumption and/or dietary long-chain n-3 fatty acids and incidence of type 2 diabetes. A dose-response random-effects model was used to combine study-specific RRs. Potential sources of heterogeneity were explored by prespecified stratifications. RESULTS Sixteen studies involving 527,441 participants and 24,082 diabetes cases were included. Considerable statistical heterogeneity in the overall summary estimates was partly explained by geographical differences. For each serving per week increment in fish consumption, the RRs (95% CIs) of type 2 diabetes were 1.05 (1.02–1.09), 1.03 (0.96–1.11), and 0.98 (0.97–1.00) combining U.S., European, and Asian/Australian studies, respectively. For each 0.30 g per day increment in long-chain n-3 fatty acids, the corresponding summary estimates were 1.17 (1.09–1.26), 0.98 (0.70–1.37), and 0.90 (0.82–0.98). CONCLUSIONS Results from this meta-analysis indicate differences between geographical regions in observed associations of fish consumption and dietary intake of long-chain n-3 fatty acids with risk of type 2 diabetes. In consideration of the heterogeneous results, the relationship warrants further investigation. Meanwhile, current public health recommendations on fish consumption should be upheld unchanged.", "title": "Fish Consumption, Dietary Long-Chain n-3 Fatty Acids, and Risk of Type 2 Diabetes" }, { "docid": "MED-2397", "text": "Background Studies have demonstrated ubiquitous human exposure to persistent organic pollutants (POPs) such as p,p′-diphenyldichloroethene (DDE) and polychlorinated biphenyls (PCBs). Although there is considerable evidence that POP exposures are associated with prevalent diabetes, these studies do not establish causality because the cross-sectional study design does not allow for assessment of temporality of the exposure–disease association. Prospective studies, however, have been lacking. Objectives This study was designed to determine whether POP body burdens are related to incidence of diabetes in a cohort of Great Lakes sport fish consumers. Methods The cohort was established in the early 1990s and followed through 2005. We tested serum for DDE and PCB congeners and assessed diabetes diagnosis, demographics, and fish consumption. Associations of diabetes with exposures were examined prospectively in participants without diabetes in 1994–1995, followed through 2005. Annual percent changes in DDE and PCB-132/153 from 1994 to 2005 were examined by diabetes status. Results DDE exposure was associated with incident diabetes. Incident diabetes was not associated with mono-ortho PCB-118, total PCBs, or years of sport fish consumption. Annual percent change in DDE and PCB-132/153 did not differ significantly by diabetes status. Conclusions This study demonstrates an association between DDE exposure and incident diabetes. The findings of an association of DDE with incident diabetes and the lack of effect of diabetes on annual percent change in POPs do not support the hypothesis that associations of POPs with diabetes are attributable to reverse causality. Additional studies should address the biological pathways by which DDE could affect glucose homeostasis.", "title": "Organochlorine Exposure and Incidence of Diabetes in a Cohort of Great Lakes Sport Fish Consumers" }, { "docid": "MED-3023", "text": "Exposure to methylmercury at any stage of central nervous system development could induce alterations and result in severe congenital abnormalities. Total mercury level in maternal hair during pregnancy correlates well with blood levels of methylmercury and with total mercury levels in fetal brain. A prospective study has been conducted and a total of 137 childbearing women living at the coastal region with term, normal pregnancies were included and their newborns evaluated by ultrasonography. Mothers and their newborns are divided in two groups according to their hair mercury levels; examined group with high body levels of mercury (≥ 1 μg/g) and control group with low body levels of mercury (<1 μg/g). Neurosonographic examination was conducted to all newborns. Two dimensions of cerebellum in the sagital-medial plane have been measured: maximum height and width starting from the roof of the fourth chamber. Majority of mothers had hair mercury levels lower than 1 μg/g (N = 107). Mean value was 0.88 μg/g (SD 1.24), ranging from 0.02 to 8.71 μg/g. There was no significant difference between the two groups when it comes to the width of cerebellum (Mann-Whitney test: Z = 1471; p = 0.141). However, comparison related to the length of cerebellum shows statistically significant smaller cerebellum in newborns whose mother had hair mercury levels higher than 1 μg/g (Mann-Whitney test: Z = 2329; p = 0.019). Our results lead to a conclusion that prenatal exposure to, what we consider to be, low-levels of methylmercury does influence fetal brain development detected as decreased size of newborn's cerebellum. From a clinical point of view, a question related to the influence of prenatal low-level methylmercury exposure on fetal neurodevelopment remains open. Our further objectives are to direct the research towards performing detailed neuropshychological tests on children at the age of 18 months. Such tests could indicate the presence of subtle neurological or neuropsychological deficits. Copyright © 2010 Elsevier Ltd. All rights reserved.", "title": "Relationship between the prenatal exposure to low-level of mercury and the size of a newborn's cerebellum." }, { "docid": "MED-3587", "text": "In 1992 Carlsen et al. reported a significant global decline in sperm density between 1938 and 1990 [Evidence for Decreasing Quality of Semen during Last 50 Years. Br Med J 305:609-613 (1992)]. We subsequently published a reanalysis of the studies included by Carlsen et al. [Swan et al. Have Sperm Densities Declined? A Reanalysis of Global Trend Data. Environ Health Perspect 105:1228-1232 (1997)]. In that analysis we found significant declines in sperm density in the United States and Europe/Australia after controlling for abstinence time, age, percent of men with proven fertility, and specimen collection method. The declines in sperm density in the United States (approximately 1.5%/year) and Europe/Australia (approximately 3%/year) were somewhat greater than the average decline reported by Carlsen et al. (approximately 1%/year). However, we found no decline in sperm density in non-Western countries, for which data were very limited. In the current study, we used similar methods to analyze an expanded set of studies. We added 47 English language studies published in 1934-1996 to those we had analyzed previously. The average decline in sperm count was virtually unchanged from that reported previously by Carlsen et al. (slope = -0.94 vs. -0.93). The slopes in the three geographic groupings were also similar to those we reported earlier. In North America, the slope was somewhat less than the slope we had found for the United States (slope = -0.80; 95% confidence interval (CI), -1.37--0.24). Similarly, the decline in Europe (slope = -2.35; CI, -3.66--1.05) was somewhat less than reported previously. As before, studies from other countries showed no trend (slope = -0.21; CI, -2.30-1.88). These results are consistent with those of Carlsen et al. and our previous results, suggesting that the reported trends are not dependent on the particular studies included by Carlsen et al. and that the observed trends previously reported for 1938-1990 are also seen in data from 1934-1996.", "title": "The question of declining sperm density revisited: an analysis of 101 studies published 1934-1996." }, { "docid": "MED-3226", "text": "Context and Objective: Dietary intake of animal proteins is associated with an increase in urinary calcium and nephrolithiasis risk. We tested the hypothesis that the acid load imposed by dietary proteins causes this hypercalciuria. Design and Setting: In a short-term crossover metabolic study, an alkali salt was provided with a high-protein diet (HPD) to neutralize the acid load imparted by dietary proteins. Participants and Interventions: Eleven healthy volunteers were evaluated at the end of each of four phases while consuming metabolic diets with fixed calcium and sodium content. Phases 1 and 3 consisted of a control diet (CD). Phases 2 and 4 consisted of a eucaloric HPD (60 g/d animal proteins added to CD). Along with HPD in phases 2 and 4, subjects ingested 30 mEq twice daily of either potassium citrate (KCitrate, alkaline salt) or potassium chloride (KCl, control neutral salt). Results: KCitrate completely neutralized the acid load imparted by HPD (based on changes in urine pH and net acid excretion) and increased urinary citrate. Urinary calcium increased during both HPD phases compared with CD but was not significantly different between the HPD + KCl and HPD + KCitrate phases (182 ± 85 vs. 170 ± 85 mg/d; P = 0.28). Increased urinary saturation with respect to calcium oxalate and uric acid with HPD was abrogated by KCitrate. Conclusions: This study suggests that, at least in the short-term, mechanism(s) other than acid load account for hypercalciuria induced by HPD. The beneficial effect of KCitrate on nephrolithiasis risk with HPD is through correction of declines in urine pH and citrate.", "title": "Hypercalciuria Associated with High Dietary Protein Intake Is Not Due to Acid Load" }, { "docid": "MED-3726", "text": "Cancer is the second leading cause of death worldwide. Therefore, the fight against cancer is one of the most important areas of research in medicine, and one that possibly contributes to the increased interest in chemoprevention as an alternative approach to the control of cancer. Cancer prevention by nutraceuticals present in fruits and vegetables has received considerable attention because of their low cost and wide safety margin. A substantial amount of evidence from human, animal, and cell culture studies has shown cancer chemopreventive effects from these natural products. However, single-agent intervention has failed to produce the expected outcome in clinical trials; therefore, combinations of nutraceuticals are gaining increasing popularity. Thus, combinations of nutraceuticals that mimic real-life situations and are competent in targeting multiple targets with very little or virtually no toxicity are needed. In this review, we summarize the results of those studies that report combinatorial cancer chemopreventive action of various nutraceuticals and their combinations with anticancer drugs. © 2011 New York Academy of Sciences.", "title": "Combinatorial strategies employing nutraceuticals for cancer development." }, { "docid": "MED-1134", "text": "BACKGROUND: The purpose of this article is to evaluate the impact of low protein and high fiber intakes on risk factors of stone recurrence in idiopathic calcium stone formers (ICSFs). METHODS: Ninety-six ICSFs were randomly assigned a low animal protein diet (< 10% of total energy), a high-fiber diet (> 25 g/day), or a usual diet (control group); all patients were recommended to increase their fluid intake. Their daily urine compositions were analyzed at baseline and at four months. Compliance with dietary recommendations was checked by validated food frequency questionnaires. Compliance with total and animal protein intakes was assessed by 24-hour urea and sulfate outputs, respectively. The nutritional intervention (oral instructions, written leaflet, phoning) and food assessment were carried out by a research dietitian. RESULTS: At baseline, diets and the daily urine composition did not differ between the three groups. At four months, while diets differed significantly, the 24-hour output of calcium and oxalate did not differ significantly within and between groups after adjustment for potential confounders (age, sex, and personal and family history of calcium stones) and baseline values. However, as many as 12 out of 31 ICSFs (95% CI, 22 to 58%) assigned to a low animal protein diet achieved a reduction in the urine urea excretion rate of more than 50 mmol/day and also exhibited a significant decrease in urinary calcium excretion that averaged 1.8 mmol/day. A significant correlation between urea and calcium outputs was observed only among patients with hypercalciuria. CONCLUSIONS: These results show that only ICSFs who markedly decrease their animal protein intake, especially those with hypercalciuria, can expect to benefit from dietary recommendations.", "title": "Effects of low animal protein or high-fiber diets on urine composition in calcium nephrolithiasis." }, { "docid": "MED-2506", "text": "Long-term caloric restriction (CR) is a robust means of reducing age-related diseases and extending life span in multiple species, but the effects in humans are unknown. The low caloric intake, long life expectancy, and the high prevalence of centenarians in Okinawa have been used as an argument to support the CR hypothesis in humans. However, no long-term, epidemiologic analysis has been conducted on traditional dietary patterns, energy balance, and potential CR phenotypes for the specific cohort of Okinawans who are purported to have had a calorically restricted diet. Nor has this cohort's subsequent mortality experience been rigorously studied. Therefore, we investigated six decades of archived population data on the elderly cohort of Okinawans (aged 65-plus) for evidence of CR. Analyses included traditional diet composition, energy intake, energy expenditure, anthropometry, plasma DHEA, mortality from age-related diseases, and current survival patterns. Findings include low caloric intake and negative energy balance at younger ages, little weight gain with age, life-long low BMI, relatively high plasma DHEA levels at older ages, low risk for mortality from age-related diseases, and survival patterns consistent with extended mean and maximum life span. This study lends epidemiologic support for phenotypic benefits of CR in humans and is consistent with the well-known literature on animals with regard to CR phenotypes and healthy aging.", "title": "Caloric restriction, the traditional Okinawan diet, and healthy aging: the diet of the world's longest-lived people and its potential impact on mor..." }, { "docid": "MED-1254", "text": "OBJECTIVE: To investigate the effect of replacing lean meat with a soy product, tofu, on coronary heart disease risk factors including serum lipoproteins, lipoprotein (a), factor VII, fibrinogen and in vitro susceptibility of LDL to oxidation. DESIGN: A randomized cross over dietary intervention study. SETTING: Free-living individuals studied at Deakin University. SUBJECTS: Forty-five free-living healthy males aged 35 to 62 years completed the dietary intervention. Three subjects were non-compliant and excluded prior to analysis. INTERVENTIONS: A diet containing 150 grams of lean meat per day was compared to a diet containing 290 grams of tofu per day in an isocaloric and isoprotein substitution. Each dietary period was one month duration. RESULTS: Analysis of the seven-day diet record showed that diets were similar in energy, protein, carbohydrate, total fat, saturated and unsaturated fat, polyunsaturated to saturated fat ratio, alcohol and fiber. Total cholesterol and triglycerides were significantly lower, and in vitro LDL oxidation lag phase was significantly longer on the tofu diet compared to the meat diet. The hemostatic factors, factor VII and fibrinogen, and lipoprotein(a) were not significantly affected by the tofu diet. CONCLUSIONS: The increase in LDL oxidation lag phase would be expected to be associated with a decrease in coronary heart disease risk.", "title": "Effect of meat replacement by tofu on CHD risk factors including copper induced LDL oxidation." }, { "docid": "MED-3729", "text": "Oxidative stress is a key component in linking environmental toxicity to the multistage carcinogenic process. Reactive oxygen species (ROS) are generated in response to both endogenous and exogenous stimuli. To counterbalance ROS-mediated injury, an endogenous antioxidants defense system exists; however, when oxidation exceeds the control mechanisms, oxidative stress arises. Chronic and cumulative oxidative stress induces deleterious modifications to a variety of macromolecular components, such as DNA, lipids, and proteins. A primary mechanism of many chemotherapy drugs against cancer cells is the formation of ROS, or free radicals. Radiotherapy is based on the fact that ionizing radiation destroys tumor cells. Radiotherapy induces direct lesions in the DNA or biological molecules, which eventually affect DNA. Free radicals produced by oncology therapy are often a source of serious side effects as well. The objective of this review is to provide information about the effects of antioxidants during oncology treatments and to discuss the possible events and efficacy. Much debate has arisen about whether antioxidant supplementation alters the efficacy of cancer chemotherapy. There is still limited evidence in both quality and sample size, suggesting that certain antioxidant supplements may reduce adverse reactions and toxicities. Significant reductions in toxicity may alleviate dose-limiting toxicities so that more patients are able to complete prescribed chemotherapy regimens and thus, in turn, improve the potential for success in terms of tumor response and survival. Copyright © 2013 Elsevier Inc. All rights reserved.", "title": "Role of antioxidants in cancer therapy." }, { "docid": "MED-2272", "text": "To assess the physiologic effects of cherry consumption, we measured plasma urate, antioxidant and inflammatory markers in 10 healthy women who consumed Bing sweet cherries. The women, age 22-40 y, consumed two servings (280 g) of cherries after an overnight fast. Blood and urine samples were taken before the cherry dose, and at 1.5, 3 and 5 h postdose. Plasma urate decreased 5 h postdose, mean +/- SEM = 183 +/- 15 micro mol/L compared with predose baseline of 214 +/- 13 micro mol/L (P < 0.05). Urinary urate increased postdose, with peak excretion of 350 +/- 33 micro mol/mmol creatinine 3 h postdose compared with 202 +/- 13 at baseline (P < 0.01). Plasma C-reactive protein (CRP) and nitric oxide (NO) concentrations had decreased marginally 3 h postdose (P < 0.1), whereas plasma albumin and tumor necrosis factor-alpha were unchanged. The vitamin C content of the cherries was solely as dehydroascorbic acid, but postdose increases in plasma ascorbic acid indicated that dehydroascorbic acid in fruits is bioavailable as vitamin C. The decrease in plasma urate after cherry consumption supports the reputed anti-gout efficacy of cherries. The trend toward decreased inflammatory indices (CRP and NO) adds to the in vitro evidence that compounds in cherries may inhibit inflammatory pathways.", "title": "Consumption of cherries lowers plasma urate in healthy women." }, { "docid": "MED-2504", "text": "It is well established that the target of rapamycin (TOR) protein kinase has pivotal roles in controlling cell functions (including protein synthesis, cell growth and cell proliferation) and is implicated in numerous human diseases. Mammalian TOR complex 1 (mTORC1) signalling is activated by hormones and growth factors, and is also stimulated by intracellular amino acids. Recent research has provided important new insight into the poorly understood mechanism by which amino acids activate mTORC1 signalling, showing that the protein kinase MAP4K3 and Rag GTPases have important roles in this. mTORC1 is known to control the G1/S transition of the cell cycle: new data show that (m)TORC1 also controls G2/M progression in yeast and mammals, albeit in contrasting ways.", "title": "Nutrient control of TORC1, a cell-cycle regulator." }, { "docid": "MED-3424", "text": "The purpose of this study is to investigate the possible underlying pathogenesis of erectile dysfunction(ED) in young men with low risk of coronary heart disease and no well-known aetiology. To conduct this study, 122 patients with ED under the age of 40 were enrolled, along with 33 age-matched normal control subjects. The patients with ED had significantly higher levels of systolic blood pressure (SBP), total cholesterol and triglyceride, high sensitivity C-reactive protein (hs-CRP), greater carotid intima-media thickness (CIMT) and Framingham risk score (FRS) than the control group, though all of these values were within the respective normal range. Further, the brachial artery flow- mediated vasodilation (FMD) values were significantly lower in ED patients and correlated positively with the severity of ED (r = 0.714, p < 0.001). When these significant factors were studied in the multivariate logistic regression model, FMD, SBP, hs-CRP and FRS remained the statistical significance. The receiver-operating characteristic (ROC) analysis demonstrated that FMD had a high ability to predict ED in young male with low FRS [area under the curve (AUC) 0.921, p < 0.001]. The cutoff value of FMD <10.25% had sensitivity of 82.8% and specificity of 100% for diagnosis of ED. FRS and hs- CRP were also proven to be predictors of ED (AUC 0.812, p < 0.001; AUC 0.645, p = 0.011, respectively). The results of this study validated that subclinical endothelial dysfunction and low-grade inflammation may be the underlying pathogenesis of ED with no well-known aetiology. Young patients complaining of ED should be screened for cardiovascular risk factors and possible subclinical atherosclerosis. Measurement of FMD, hs-CRP and FRS can improve our ability to predict and treat ED, as well as subclinical cardiovascular disease early for young male. © 2012 The Authors. International Journal of Andrology © 2012 European Academy of Andrology.", "title": "Subclinical endothelial dysfunction and low-grade inflammation play roles in the development of erectile dysfunction in young men with low risk of ..." }, { "docid": "MED-3724", "text": "Drug resistance remains an on-going challenge in ovarian cancer chemotherapy. The objective of this study was to determine the effect on synergism in activity from the sequenced combinations of cisplatin (Cis) with curcumin (Cur) and epigallocatechin-3-gallate (EGCG) in the human ovarian cancer cell lines. The drugs were added in binary combinations: Cis combined with Cur, and Cis combined with EGCG to the human ovarian A2780 and A2780(cisR) cancer cell lines, using five different sequences of administration: 0/0 h, 4/0 h, 0/4 h, 24/0 h and 0/24 h. The combination index (CI) was used to assess the combined action of the drugs. CIs <1, =1 and >1 indicated synergism, additiveness and antagonism respectively. Cellular accumulation of platinum and platinum-DNA binding levels from Cis and its combination with the phytochemicals were determined using graphite furnace atomic absorption spectrometry. Addition of Cis 4 h before Cur and EGCG (0/4 h combination) produced the most synergistic outcomes in both the A2780 and A2780(cisR) cell lines. The cellular accumulations of platinum and platinum-DNA binding resulting from the 0/4 h combinations were greater as compared to the values using Cis alone, thus providing an explanation for the synergistic action. When sequenced combinations of Cis with Cur and with EGCG are applied to human ovarian A2780 and A2780(cisR) cancer cell lines, lower concentrations and shorter time gap between the two additions seem to produce a higher cytotoxic effect.", "title": "Synergism from sequenced combinations of curcumin and epigallocatechin-3-gallate with cisplatin in the killing of human ovarian cancer cells." }, { "docid": "MED-4644", "text": "We studied 10 vegetarian and 10 nonvegetarian premenopausal women on four occasions approximately four months apart. During each study period, the participants kept three-day dietary records, and estrogens were measured in plasma, urinary, and fecal samples. Vegetarians consumed less total fat than omnivores did (30 per cent of total calories, as compared with 40 per cent) and more dietary fiber (28 g per day, as compared with 12 g). There was a positive correlation between fecal weight and fecal excretion of estrogens in both groups (P less than 0.001), with vegetarians having higher fecal weight and increased fecal excretion of estrogens. Urinary excretion of estriol was lower in vegetarians (P less than 0.05), and their plasma levels of estrone and estradiol were negatively correlated with fecal excretion of estrogen (P = 0.005). Among the vegetarians the beta-glucuronidase activity of fecal bacteria was significantly reduced (P = 0.05). We conclude that vegetarian women have an increased fecal output, which leads to increased fecal excretion of estrogen and a decreased plasma concentration of estrogen.", "title": "Estrogen excretion patterns and plasma levels in vegetarian and omnivorous women." }, { "docid": "MED-3700", "text": "Background An increased risk of breast cancer is associated with alcohol consumption; however, it is controversial whether red wine increases this risk. Aromatase inhibitors (AIs) prevent the conversion of androgens to estrogen and occur naturally in grapes, grape juice, and red, but not white wine. We tested whether red wine is a nutritional AI in premenopausal women. Methods In a cross-over design, 36 women (mean age [SD], 36 [8] years) were assigned to 8 ounces (237 mL) of red wine daily then white wine for 1 month each, or the reverse. Blood was collected twice during the menstrual cycle for measurement of estradiol (E2), estrone (E1), androstenedione (A), total and free testosterone (T), sex hormone binding globulin (SHBG), luteinizing hormone (LH), and follicle stimulating hormone (FSH). Results Red wine demonstrated higher free T vs. white wine (mean difference 0.64 pg/mL [0.2 SE], p=0.009) and lower SHBG (mean difference −5.0 nmol/L [1.9 SE], p=0.007). E2 levels were lower in red vs. white wine but not statistically significant. LH was significantly higher in red vs. white wine (mean difference 2.3 mIU/mL [1.3 SE], p=0.027); however, FSH was not. Conclusion Red wine is associated with significantly higher free T and lower SHBG levels, as well as a significant higher LH level vs. white wine in healthy premenopausal women. These data suggest that red wine is a nutritional AI and may explain the observation that red wine does not appear to increase breast cancer risk.", "title": "Red Versus White Wine as a Nutritional Aromatase Inhibitor in Premenopausal Women: A Pilot Study" }, { "docid": "MED-3235", "text": "Background Maintaining muscle mass while aging is important to prevent falls and fractures. Metabolic acidosis promotes muscle wasting, and the net acid load from diets that are rich in net acid–producing protein and cereal grains relative to their content of net alkali–producing fruit and vegetables may therefore contribute to a reduction in lean tissue mass in older adults. Objective We aimed to determine whether there was an association of 24-h urinary potassium and an index of fruit and vegetable content of the diet with the percentage lean body mass (%LBM) or change in %LBM in older subjects. Design Subjects were 384 men and women ≥65 y old who participated in a 3-y trial comparing calcium and vitamin D with placebo. Potassium was measured in 24-h urine collections at baseline. The %LBM, defined as total body nonfat, nonbone tissue weight ÷ weight × 100, was measured by using dual-energy X-ray absorptiometry at baseline and at 3 y. Physical activity, height, and weight were assessed at baseline and at 3 y. Results At baseline, the mean urinary potassium excretion was 67.0 ± 21.1 mmol/d. Urinary potassium (mmol/d) was significantly positively associated with %LBM at baseline (β = 0.033, P = 0.006; adjusted for sex, weight, and nitrogen excretion) but not with 3-y change in %LBM. Over the 3-y study, %LBM increased by 2.6 ± 3.6%. Conclusion Higher intake of foods rich in potassium, such as fruit and vegetables, may favor the preservation of muscle mass in older men and women.", "title": "Alkaline diets favor lean tissue mass in older adults" }, { "docid": "MED-1618", "text": "To study the effect of a moderate increase in insulin secretion produced by an increased daily protein intake on dehydroepiandrosterone sulfate (DHEAS), a balanced randomized crossover trial consisting of three strictly controlled dietary regimens was performed in six healthy male volunteers. The basic diet (B) contained 50 g protein/d; diets P and M (also basic diets) were enriched with either 32 g protein/d (P) or 10 mmol L-methionine/d (M). Methionine was given (as a specific nonprotein source of endogenously derived sulfate) to control for possible confounding effects on DHEAS due to an increased sulfate supply. At the end of each 4-day diet period, blood and 24-hour urine samples were collected. Fasting plasma levels of testosterone, cortisol, insulin-like growth factor-I (IGF-I), and insulin, as well as urinary output of total (hot acid-cleaved) testosterone conjugates and 3alpha-androstanediol glucuronide, did not show significant changes in response to dietary manipulations. Endogenous sulfate availability (as reflected by renal sulfate output per 24 hours) approximately doubled with diets P and M. However, plasma levels (6.3 +/- 1.5, 6.8 +/- 1.8, and 6.9 +/- 2.1 micromol/L for B, P, and M, respectively) and urinary excretion (8.8 +/- 9.8, 9.4 +/- 11.2, 8.0 +/- 8.3 micromol/d) of DHEAS remained unaffected. Considering the clear increments (P < .01) in urinary C-peptide excretion with diet P (20.4 +/- 10.3 nmol/d) versus diets B and M (12.6 +/- 5.1 and 13.2 +/- 3.6 nmol/d), respectively, our results suggest that a moderately strong diet-induced increase in daily insulin secretion does not alter urinary and plasma levels of DHEAS.", "title": "A moderate increase in daily protein intake causing an enhanced endogenous insulin secretion does not alter circulating levels or urinary excretion..." }, { "docid": "MED-4320", "text": "Bioavailability of micronutrients iron and zinc is particularly low from plant foods. Hence there is a need to evolve a food-based strategy to improve the same to combat widespread deficiencies of these minerals in a population dependent on plant foods. Dietary sulfur-containing amino acids have been reported to improve the mineral status of experimental animals. Our objective was to examine whether sulfur compound-rich Allium spices have a similar potential of beneficially modulating the mineral bioavailability. In this context, we examined the influence of exogenously added garlic and onion on the bioaccessibility of iron and zinc from food grains. Two representative cereals and pulses each were studied in both raw and cooked condition employing two levels of garlic (0.25 and 0.5 g/10 g of grain) and onion (1.5 and 3 g/10 g of grain). The enhancing effect of these two spices on iron bioaccessibility was generally evidenced in the case of both the cereals (9.4-65.9% increase) and pulses (9.9-73.3% increase) in both raw and cooked conditions. The two spices similarly enhanced the bioaccessibility of zinc from the food grains, the extent of increase in cereals ranging from 10.4% to 159.4% and in pulses from 9.8% to 49.8%. Thus, both garlic and onion were evidenced here to have a promoting influence on the bioaccessibility of iron and zinc from food grains. This novel information has the potential application in evolving a food-based strategy to improve the bioavailability of trace minerals and hence contributes to the human health benefit.", "title": "Higher bioaccessibility of iron and zinc from food grains in the presence of garlic and onion." }, { "docid": "MED-2649", "text": "Background Dietary fat exerts numerous complex effects on proinflammatory and immunologic pathways. Several epidemiological studies have examined the relationships between intake of fatty acids and/or foods high in fat and allergic rhinitis, but have provided conflicting findings. The current cross-sectional study investigated such relationships in Japan. Methods Study subjects were 1745 pregnant women. The definition of rhinoconjunctivitis was based on criteria from the International Study of Asthma and Allergies in Childhood. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for age; gestation; region of residence; number of older siblings; number of children; smoking; secondhand smoke exposure at home and at work; family history of asthma, atopic eczema, and allergic rhinitis; household income; education; and body mass index. Results The prevalence of rhinoconjunctivitis in the past 12 months was 25.9%. Higher meat intake was significantly associated with an increased prevalence of rhinoconjunctivitis: the adjusted odds ratio between extreme quartiles was 1.71 (95% confidence interval: 1.25-2.35, P for trend = 0.002). No measurable association was found between fish intake and rhinoconjunctivitis. Intake of total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid, and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid intake were not evidently related to the prevalence of rhinoconjunctivitis. Conclusions The current results suggest that meat intake may be positively associated with the prevalence of rhinoconjunctivitis in young adult Japanese women.", "title": "Dietary meat and fat intake and prevalence of rhinoconjunctivitis in pregnant Japanese women: baseline data from the Kyushu Okinawa Maternal and Child Health Study" }, { "docid": "MED-4075", "text": "Liquid chromatography electrospray ionization mass spectrometry (MS) with a triple quadrupole MS was used to identify known and novel heterocyclic aromatic amines (HAAs) in human urine. The identities of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were confirmed by their product ion spectra. The constant neutral loss scan mode was employed to probe for other analytes in urine that display the transition [M+H]+-->[M+H-CH3*]+*, which is common to HAAs containing an N-methylimidazo moiety, and led to the detection of a previously unreported isomer of 8-MeIQx [Holland, R., et al. (2004) Chem. Res. Toxicol. 17, 1121-1136]. We now report the identification of another novel HAA, 2-amino-1-methylimidazo[4,5-b]quinoline (IQ[4,5-b]), an isomer of the powerful animal carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). The amounts of IQ[4,5-b] measured in the urine of human volunteers who consumed grilled beef ranged from 15 to 135% of the ingested dose, while the amounts of 8-MeIQx and PhIP excreted in urine were on average <2% of the ingested dose. Base treatment of urine at 70 degrees C increased the concentrations of 8-MeIQx and PhIP by as much as 6-fold, indicating the presence of phase II conjugates; however, the amount of IQ[4,5-b] increased by more than 100-fold. IQ[4,5-b] was also detected in the urine of vegetarians following base hydrolysis. The formation of IQ[4,5-b], but not IQ, 8-MeIQx, or PhIP, also occurred in urine incubated at 37 degrees C. Creatinine and 2-aminobenzaldehyde are likely precursors of IQ[4,5-b]. The detection of IQ[4,5-b] in the urine of both meat eaters and vegetarians suggests that this HAA may be present in nonmeat staples or that IQ[4,5-b] formation may occur endogenously within the urinary bladder or other biological fluids.", "title": "Formation of a mutagenic heterocyclic aromatic amine from creatinine in urine of meat eaters and vegetarians." }, { "docid": "MED-2646", "text": "BACKGROUND: Certain foods may increase or decrease the risk of developing asthma, rhinoconjunctivitis and eczema. We explored the impact of the intake of types of food on these diseases in Phase Three of the International Study of Asthma and Allergies in Childhood. METHODS: Written questionnaires on the symptom prevalence of asthma, rhinoconjunctivitis and eczema and types and frequency of food intake over the past 12 months were completed by 13-14-year-old adolescents and by the parents/guardians of 6-7-year-old children. Prevalence ORs were estimated using logistic regression, adjusting for confounders, and using a random (mixed) effects model. RESULTS: For adolescents and children, a potential protective effect on severe asthma was associated with consumption of fruit ≥3 times per week (OR 0.89, 95% CI 0.82 to 0.97; OR 0.86, 95% CI 0.76 to 0.97, respectively). An increased risk of severe asthma in adolescents and children was associated with the consumption of fast food ≥3 times per week (OR 1.39, 95% CI 1.30 to 1.49; OR 1.27, 95% CI 1.13 to 1.42, respectively), as well as an increased risk of severe rhinoconjunctivitis and severe eczema. Similar patterns for both ages were observed for regional analyses, and were consistent with gender and affluence categories and with current symptoms of all three conditions. CONCLUSIONS: If the association between fast foods and the symptom prevalence of asthma, rhinoconjunctivitis and eczema is causal, then the findings have major public health significance owing to the rising consumption of fast foods globally.", "title": "Do fast foods cause asthma, rhinoconjunctivitis and eczema? Global findings from the International Study of Asthma and Allergies in Childhood (ISAA..." }, { "docid": "MED-1599", "text": "In addition to passive inhalation, non-smokers, and especially children, are exposed to residual tobacco smoke gases and particles that are deposited to surfaces and dust, known as thirdhand smoke (THS). However, until now the potential cancer risks of this pathway of exposure have been highly uncertain and not considered in public health policy. In this study, we estimate for the first time the potential cancer risk by age group through non-dietary ingestion and dermal exposure to carcinogen N-nitrosamines and tobacco-specific nitrosamines (TSNAs) measured in house dust samples. Using a highly sensitive and selective analytical approach we have determined the presence of nicotine, eight N-nitrosamines and five tobacco-specific nitrosamines in forty-six settled dust samples from homes occupied by both smokers and non-smokers. Using observations of house dust composition, we have estimated the cancer risk by applying the most recent official toxicological information. Calculated cancer risks through exposure to the observed levels of TSNAs at an early life stage (1 to 6years old) exceeded the upper-bound risk recommended by the USEPA in 77% of smokers' and 64% of non-smokers' homes. The maximum risk from exposure to all nitrosamines measured in a smoker occupied home was one excess cancer case per one thousand population exposed. The results presented here highlight the potentially severe long-term consequences of THS exposure, particularly to children, and give strong evidence of its potential health risk and, therefore, they should be considered when developing future environmental and health policies. Copyright © 2014 Elsevier Ltd. All rights reserved.", "title": "Exposure to nitrosamines in thirdhand tobacco smoke increases cancer risk in non-smokers." }, { "docid": "MED-2489", "text": "A historical view on how our agricultural systems evolved and how they are contributing to obesity and disease.", "title": "Agricultural policies, food and public health" }, { "docid": "MED-4278", "text": "OBJECTIVE: To describe the lifestyle characteristics and nutrient intakes of the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN: Cohort of men and women recruited through general practices or by post to include a high proportion of non meat-eaters. Dietary, anthropometric and lifestyle data were collected at baseline and four diet groups were defined. SETTING: United Kingdom. PARTICIPANTS: In total, 65 429 men and women aged 20 to 97 years, comprising 33 883 meat-eaters, 10 110 fish-eaters, 18 840 lacto-ovo vegetarians and 2596 vegans. RESULTS: Nutrient intakes and lifestyle factors differed across the diet groups, with striking differences between meat-eaters and vegans, and fish-eaters and vegetarians usually having intermediate values. Mean fat intake in each diet group was below the UK dietary reference value of 33% of total energy intake. The mean intake of saturated fatty acids in vegans was approximately 5% of energy, less than half the mean intake among meat-eaters (10-11%). Vegans had the highest intakes of fibre, vitamin B1, folate, vitamin C, vitamin E, magnesium and iron, and the lowest intakes of retinol, vitamin B12, vitamin D, calcium and zinc. CONCLUSIONS: The EPIC-Oxford cohort includes 31 546 non meat-eaters and is one of the largest studies of vegetarians in the world. The average nutrient intakes in the whole cohort are close to those currently recommended for good health. Comparisons of the diet groups show wide ranges in the intakes of major nutrients such as saturated fat and dietary fibre. Such variation should increase the ability of the study to detect associations of diet with major cancers and causes of death.", "title": "EPIC-Oxford: lifestyle characteristics and nutrient intakes in a cohort of 33 883 meat-eaters and 31 546 non meat-eaters in the UK." }, { "docid": "MED-4790", "text": "It is a pleasure and an honor to contribute a paper to a special issue of the Journal of the American College of Nutrition honoring Stanley Wallach and Pearl Small. In this brief review I advance the hypothesis that copper toxicity is the major cause of the epidemic of mild cognitive impairment and Alzheimer's disease engulfing our aging population. This epidemic is recent, exploding in the last 50-60 years. The disease was virtually unknown 100 years ago. And it involves only developed countries that use copper plumbing. Something in our environment associated with development is poisoning the minds of our aged. The epidemic is associated with the use of copper plumbing, and the taking of copper in multi-mineral supplements. Food copper (organic copper) is processed by the liver and is transported and sequestered in a safe manner. Inorganic copper, such as that in drinking water and copper supplements, largely bypasses the liver and enters the free copper pool of the blood directly. This copper is potentially toxic because it may penetrate the blood/brain barrier. I review a web of animal and human data that tightens the noose around the hypothesis that copper toxicity is causing the epidemic of Alzeimer's disease and loss of cognition in our aging population.", "title": "The risks of copper toxicity contributing to cognitive decline in the aging population and to Alzheimer's disease." }, { "docid": "MED-3435", "text": "INTRODUCTION: Previous cross-sectional studies have suggested that erectile dysfunction (ED) represents an independent risk factor for future cardiovascular events. However, very few studies have attempted to examine the association between ED and subsequent stroke. AIM: The aim of this study is to estimate the risk of stroke during a 5-year follow-up period after the first ambulatory care visit for the treatment of ED using nationwide, population-based data and a retrospective case-control cohort design in Taiwan. METHODS: This study used data sourced from the \"Longitudinal Health Insurance Database.\" The study cohort comprised 1,501 patients who received a principal diagnosis of ED between 1997 and 2001 and 7,505 randomly selected subjects as the comparison cohort. Each patient (N = 9,006) was then individually tracked for 5 years from their index ambulatory care visit to identify those who had diagnosed episodes of stroke. MAIN OUTCOME MEASURE: Stratified Cox proportional hazard regressions were performed as a means of comparing the 5-year stroke-free survival rate for the two cohorts. RESULTS: Of the sampled patients, 918 (10.2%) developed stroke within the 5-year follow-up period, that is, 188 individuals (12.5% of the patients with ED) from the study cohort and 730 individuals (9.7% of patients in the comparison cohort) from the comparison cohort. The log-rank test indicated that patients with ED had significantly lower 5-year stroke-free survival rates than those in the comparison cohort (P < 0.001). After adjusting for the patient's monthly income, geographical location, hypertension, diabetes, coronary heart disease, peripheral vascular disease, atrial fibrillation, and hyperlipidemia, patients with ED were more likely to have a stroke during the 5-year follow-up period than patients in the comparison cohort (hazard ratio = 1.29, 95% confidence interval = 1.08 - 1.54, P < 0.01). CONCLUSIONS: These results suggest that ED is a surrogate marker for future stroke in men. © 2010 International Society for Sexual Medicine.", "title": "Increased risk of stroke among men with erectile dysfunction: a nationwide population-based study." }, { "docid": "MED-1610", "text": "The effects of three different meat-containing breakfast meals (pork, beef or chicken) on acute satiety and appetite regulatory hormones were compared using a within-subjects study design. Thirty fasting non-smoking pre-menopausal women attended a research centre on three test days to consume, a meat-containing meal matched in energy (kJ) and protein content, palatability, and appearance. No difference was found between meat groups for either energy intake or macronutrient profile of food consumed at a subsequent ad libitum buffet lunch, or over the rest of the day. Visual Analogue Scale (VAS) ratings for hunger and satiety over an 180 min period did not differ between test meals. After consumption of the test meals, a significant difference was found in PYY response between pork and chicken meals (P=0.027) but not for levels of CCK, ghrelin, insulin or glucose. This study positions pork, beef, and chicken as equal in their effect on satiety and release of appetite-related intestinal hormones and of insulin. Copyright © 2010 Elsevier Ltd. All rights reserved.", "title": "Pork, beef and chicken have similar effects on acute satiety and hormonal markers of appetite." }, { "docid": "MED-2582", "text": "Nonstarch polysaccharide (NSP) intake was measured in representative samples of 30 men aged 50-59 in 2 urban and 2 rural Scandinavian populations that exhibited a 3-4 fold difference in incidence of large bowel cancer. Intake was measured by chemical analysis of complete duplicate portions of all food eaten over one day by each individual. NSP intakes showed a rural-urban gradient, with 18.4 +/- 7.8 g/day in rural Finland and 18.0 +/- 6.4 g/day in rural Denmark versus 14.5 +/- 5.4 g/day in urban Finland and 13.2 +/- 4.8 g/day in urban Denmark. NSP intakes were also calculated (using food tables) from weighed food records kept over 4 days, one of which was the day on which the duplicate collection was made. Intakes were 2-2.5 g/day higher with this method than with direct chemical analysis, mainly because published tables of values have become outdated and inaccurate as a result of improved methods for measuring NSP in food. Individual variation from day to day in NSP intake was considerable. Average NSP intake and intake of some of its component sugars were inversely related to colon cancer incidence in this geographical comparison. To show a relationship at the individual level between diet and cancer risk in a prospective study would require detailed and accurate methods for the assessment of NSP consumption.", "title": "Nonstarch polysaccharide consumption in four Scandinavian populations." }, { "docid": "MED-4034", "text": "OBJECTIVES: To determine whether foods that are good to excellent sources of fiber reduce periodontal disease progression in men. DESIGN: Prospective, observational study. SETTING: Greater Boston, Massachusetts, metropolitan area. PARTICIPANTS: Six hundred twenty-five community-dwelling men participating in the Department of Veterans Affairs Dental Longitudinal Study. MEASUREMENTS: Dental and physical examinations were conducted every 3 to 5 years. Diet was assessed using food frequency questionnaires (FFQs). Mean follow-up was 15 years (range: 2-24 years). Periodontal disease progression on each tooth was defined as alveolar bone loss (ABL) advancement of 40% or more, probing pocket depth (PPD) of 2 mm or more, or tooth loss. Good and excellent fiber sources provided 2.5 g or more of fiber per serving. Multivariate proportional hazards regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs) of periodontal disease progression and tooth loss in relation to fiber sources, stratified according to age younger than 65 versus 65 and older, and controlled for smoking, body mass index, calculus, baseline periodontal disease level, caries, education, exercise, carotene, thiamin and caffeine intake, and tooth brushing. RESULTS: In men aged 65 and older, each serving of good to excellent sources of total fiber was associated with lower risk of ABL progression (HR = 0.76, 95% CI = 0.60-0.95) and tooth loss (HR = 0.72, 95% CI = 0.53-0.97). Of the different food groups, only fruits that were good to excellent sources of fiber were associated with lower risk of progression of ABL (HR = 0.86 per serving, 95% CI = 0.78-0.95), PPD (HR = 0.95, 95% CI = 0.91-0.99), and tooth loss (HR = 0.88, 95% CI = 0.78-0.99). No significant associations were seen in men younger than 65. CONCLUSION: Benefits of higher intake of high-fiber foods, especially fruits, on slowing periodontal disease progression are most evident in men aged 65 and older. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.", "title": "High-fiber foods reduce periodontal disease progression in men aged 65 and older: the Veterans Affairs normative aging study/Dental Longitudinal St..." }, { "docid": "MED-2216", "text": "BACKGROUND: Alzheimer's disease (AD) rates in Japan and developing countries have risen rapidly in recent years. Researchers have associated factors such as the Western diet, obesity, alcohol consumption, and smoking with risk of AD. OBJECTIVE: This paper evaluates whether the dietary transition might explain the rising trend of AD prevalence in Japan and in developing countries, evaluating other factors when possible. METHODS: This study used two approaches to see whether dietary or other changes could explain AD trends in Japan and developing countries. One approach involved comparing trends of AD in Japan with changes in national dietary supply factors, alcohol consumption, and lung cancer mortality rates from zero to 25 years before the prevalence data. The second compared AD prevalence values for eight developing countries with dietary supply factors from zero to 25 years before the prevalence data. RESULTS: For Japan, alcohol consumption, animal product, meat and rice supply, and lung cancer rates correlated highly with AD prevalence data, with the strongest correlation for a lag of 15-25 years. In the eight-country study, total energy and animal fat correlated highly with AD prevalence data, with a lag of 15-20 years. Mechanisms to explain the findings include increased obesity for the eight countries, and increases in cholesterol, saturated fat, and iron from increases in animal products and meat supply for Japan. CONCLUSION: Evidently AD rates will continue rising in non-Western countries for some time unless we address major risk factors involving diet, obesity, and smoking.", "title": "Trends in diet and Alzheimer's disease during the nutrition transition in Japan and developing countries." }, { "docid": "MED-3464", "text": "The purpose of this study was to determine the effects of consuming sweet cherries on plasma lipids and markers of inflammation in healthy humans. Healthy men and women (n = 18) supplemented their diets with Bing sweet cherries (280 g/d) for 28 d. After a 12-h fast, blood samples were taken before the start of cherry consumption (study d 0 and 7), 14 and 28 d after the start of cherry supplementation (study d 21 and 35), and 28 d after the discontinuation (study d 64) of cherry consumption. After cherries were consumed for 28 d, circulating concentrations of C-reactive protein (CRP), regulated upon activation, normal T-cell expressed, and secreted (RANTES), and NO decreased by 25 (P < 0.05), 21 (P < 0.05), and 18% (P = 0.07) respectively. After the discontinuation of cherry consumption for 28 d (d 64), concentrations of RANTES continued to decrease (P = 0.001), whereas those of CRP and NO did not differ from either d 7 (pre-cherries) or d 35 (post-cherries). Plasma concentrations of IL-6 and its soluble receptor, intercellular adhesion molecule-1, and tissue inhibitor of metalloproteinases-2 did not change during the study. Cherry consumption did not affect the plasma concentrations of total-, HDL-, LDL-, and VLDL- cholesterol, triglycerides, subfractions of HDL, LDL, VLDL, and their particle sizes and numbers. It also did not affect fasting blood glucose or insulin concentrations or a number of other chemical and hematological variables. Results of the present study suggest a selective modulatory effect of sweet cherries on CRP, NO, and RANTES. Such anti-inflammatory effects may be beneficial for the management and prevention of inflammatory diseases.", "title": "Consumption of Bing sweet cherries lowers circulating concentrations of inflammation markers in healthy men and women." }, { "docid": "MED-1162", "text": "Consumers are frequently urged to avoid imported foods as well as specific fruits and vegetables due to health concerns from pesticide residues and are often encouraged to choose organic fruits and vegetables rather than conventional forms. Studies have demonstrated that while organic fruits and vegetables have lower levels of pesticide residues than do conventional fruits and vegetables, pesticide residues are still frequently detected on organic fruits and vegetables; typical dietary consumer exposure to pesticide residues from conventional fruits and vegetables does not appear to be of health significance. Similarly, research does not demonstrate that imported fruits and vegetables pose greater risks from pesticide residues than do domestic fruits and vegetables or that specific fruits and vegetables singled out as being the most highly contaminated by pesticides should be avoided in their conventional forms.", "title": "Pesticide residues in imported, organic, and \"suspect\" fruits and vegetables." }, { "docid": "MED-2362", "text": "The study of the expression of Gal alpha 1----3Gal beta 1----4GlcNAc residues on mammalian glycoconjugates is of particular interest since as many as 1% of circulating IgG antibodies in man (the natural anti-Gal antibody) interact specifically with this carbohydrate residue. In recent studies, we have found that Gal alpha 1----3Gal beta 1----4GlcNAc residues are abundant on red cells and nucleated cells of nonprimate mammals, prosimians, and New World monkeys, but their expression is diminished in Old World monkeys, apes, and humans. In the present work, we have analyzed the expression of these residues on secreted mammalian glycoproteins. For this purpose, we have developed a radioimmunoassay (RIA) which enables the quantification of Gal alpha 1----3Gal beta 1----4GlcNAc residues on the secreted glycoproteins. Purified biotinylated anti-Gal was used as the antibody in the RIA, and bovine thyroglobulin enriched for Gal alpha 1----3Gal beta 1----4GlcNAc residues served as a solid-phase antigen. In this study, it is reported for the first time that the evolutionary pattern of Gal alpha 1----3Gal beta 1----4GlcNAc residue distribution in in vivo secreted glycoproteins is similar to that observed in membranes of cell lines and of red cells. Thyroglobulin, fibrinogen, or IgG molecules from nonprimate mammals and from New World monkeys express varying amounts of Gal alpha 1----3Gal beta 1----4GlcNAc residues ranging between 0.01 and 11 residues per molecule, whereas no such residues are present on any of these glycoproteins of human or Old World monkey origin.(ABSTRACT TRUNCATED AT 250 WORDS)", "title": "Distribution of Gal alpha 1----3Gal beta 1----4GlcNAc residues on secreted mammalian glycoproteins (thyroglobulin, fibrinogen, and immunoglobulin G..." }, { "docid": "MED-4692", "text": "Recent studies of shift-working women have reported that excessive exposure to light at night (LAN) may be a risk factor for breast cancer. However, no studies have yet attempted to examine the co-distribution of LAN and breast cancer incidence on a population level with the goal to assess the coherence of these earlier findings with population trends. Coherence is one of Hill's \"criteria\" (actually, viewpoints) for an inference of causality. Nighttime satellite images were used to estimate LAN levels in 147 communities in Israel. Multiple regression analysis was performed to investigate the association between LAN and breast cancer incidence rates and, as a test of the specificity of our method, lung cancer incidence rates in women across localities under the prediction of a link with breast cancer but not lung cancer. After adjusting for several variables available on a population level, such as ethnic makeup, birth rate, population density, and local income level, a strong positive association between LAN intensity and breast cancer rate was revealed (p<0.05), and this association strengthened (p<0.01) when only statistically significant factors were filtered out by stepwise regression analysis. Concurrently, no association was found between LAN intensity and lung cancer rate. These results provide coherence of the previously reported case-control and cohort studies with the co-distribution of LAN and breast cancer on a population basis. The analysis yielded an estimated 73% higher breast cancer incidence in the highest LAN exposed communities compared to the lowest LAN exposed communities.", "title": "Light at night co-distributes with incident breast but not lung cancer in the female population of Israel." }, { "docid": "MED-1766", "text": "We studied 19 male patients with primary hyperlipoproteinaemia, a control group of 28 healthy men and 44 infertile males before any treatment was undertaken. Spermiogram, seminal biochemical studies, measurements of plasma hormone levels and lipid determinations were carried out. Most hyperlipoproteinaemic patients showed abnormalities in the spermiograms and the mean values were lower than in the controls except for semen volume. Seminal biochemical determinations were normal in the majority and the hormone profile showed some abnormal values, mainly for E2. Lipid abnormalities were more common in azoospermic infertile men and mean lipid levels were higher. Correlation studies suggest that high levels of C and/or Tg are associated with poor semen quality and higher FSH levels. The results of our studies suggest that high lipid levels exert adverse direct effects at the testicular level.", "title": "Lipids and testicular function." }, { "docid": "MED-3149", "text": "Many health conditions are treated, at least in part, by therapeutic diets. Although the success of any intervention depends on its acceptability to the patient, the acceptability of therapeutic diets and factors that influence it have been largely neglected in nutrition research. A working definition of acceptability is proposed and an examination and summary are provided of available data on the acceptability of common diet regimens used for medical conditions. The goal is to suggest ways to improve the success of therapeutic diets. The proposed working definition of \"acceptability\" refers to the user's judgment of the advantages and disadvantages of a therapeutic diet-in relation to palatability, costs, and effects on eating behaviour and health-that influence the likelihood of adherence. Very low-calorie, reduced-fat omnivorous, vegetarian and vegan, and low-carbohydrate diets all achieve acceptability among the majority of users in studies of up to one year, in terms of attrition and adherence rates and results of questionnaires assessing eating behaviours. Longer studies are fewer, but they suggest that vegetarian, vegan, and reduced-fat diets are acceptable, as indicated by sustained changes in nutrient intake. Few studies of this length have been published for very low-calorie or low-carbohydrate diets. Long-term studies of adherence and acceptability of these and other therapeutic diets are warranted.", "title": "Four therapeutic diets: adherence and acceptability." }, { "docid": "MED-4633", "text": "Background The physical health status of vegetarians has been extensively reported, but there is limited research regarding the mental health status of vegetarians, particularly with regard to mood. Vegetarian diets exclude fish, the major dietary source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), critical regulators of brain cell structure and function. Omnivorous diets low in EPA and DHA are linked to impaired mood states in observational and experimental studies. Methods We examined associations between mood state and polyunsaturated fatty acid intake as a result of adherence to a vegetarian or omnivorous diet in a cross-sectional study of 138 healthy Seventh Day Adventist men and women residing in the Southwest. Participants completed a quantitative food frequency questionnaire, Depression Anxiety Stress Scale (DASS), and Profile of Mood States (POMS) questionnaires. Results Vegetarians (VEG:n = 60) reported significantly less negative emotion than omnivores (OMN:n = 78) as measured by both mean total DASS and POMS scores (8.32 ± 0.88 vs 17.51 ± 1.88, p = .000 and 0.10 ± 1.99 vs 15.33 ± 3.10, p = .007, respectively). VEG reported significantly lower mean intakes of EPA (p < .001), DHA (p < .001), as well as the omega-6 fatty acid, arachidonic acid (AA; p < .001), and reported higher mean intakes of shorter-chain α-linolenic acid (p < .001) and linoleic acid (p < .001) than OMN. Mean total DASS and POMS scores were positively related to mean intakes of EPA (p < 0.05), DHA (p < 0.05), and AA (p < 0.05), and inversely related to intakes of ALA (p < 0.05), and LA (p < 0.05), indicating that participants with low intakes of EPA, DHA, and AA and high intakes of ALA and LA had better mood. Conclusions The vegetarian diet profile does not appear to adversely affect mood despite low intake of long-chain omega-3 fatty acids.", "title": "Vegetarian diets are associated with healthy mood states: a cross-sectional study in Seventh Day Adventist adults" }, { "docid": "MED-2253", "text": "Twenty three adults ingested 203Pb as lead acetate on the 12th hour of a 19 h fast. Retention measured 7 days later in a whole-body counter was 61% and whole-body turnover rates suggested that initial uptake had been considerably greater. Balanced meals eaten with 203Pb reduced lead uptake to 4% and the influence of the food lasted for up to 3 h. The effects of phytate, ethylene-diaminetetra acetate (EDTA), caffeine, alcohol, glucose, a liquid meal and a light snack were tested separately with intermediate results. The effect of a meal was probably largely due to its content of calcium and phosphate salts but lead uptake was probably further reduced by phytate which is plentiful in whole cereals and it was probably increased by a factor in milk. Uptake with skimmed milk was the same as with whole milk and we suggested that the factor was not fat. Comestibles with low mineral and phytate contents reduced lead uptake by intermediate amounts, possibly by stimulation of digestive secretions. The avid uptake of lead during a fast, the large reduction of lead uptake with meals and the likelihood of variations in gastric-emptying rates and dietary habits may be major causes of variation in body burdens of lead in the population.", "title": "Effects of meals and meal times on uptake of lead from the gastrointestinal tract in humans." }, { "docid": "MED-2568", "text": "Inositol hexaphosphate (InsP6 or IP6) is ubiquitous. At 10 microM to 1 mM concentrations, IP6 and its lower phosphorylated forms (IP(1-5)) as well as inositol (Ins) are contained in most mammalian cells, wherein they are important in regulating vital cellular functions such as signal transduction, cell proliferation and differentiation. A striking anti-cancer action of IP6 has been demonstrated both in vivo and in vitro, which is based on the hypotheses that exogenously administered IP6 may be internalized, dephosphorylated to IP(1-5), and inhibit cell growth. There is additional evidence that Ins alone may further enhance the anti-cancer effect of IP6. Besides decreasing cellular proliferation, IP6 also causes differentiation of malignant cells often resulting in a reversion to normal phenotype. These data strongly point towards the involvement of signal transduction pathways, cell cycle regulatory genes, differentiation genes, oncogenes and perhaps, tumor suppressor genes in bringing about the observed anti-neoplastic action of IP6.", "title": "IP6: a novel anti-cancer agent." }, { "docid": "MED-4132", "text": "Understanding the relative public health impact of major microbiological hazards across the food supply is critical for a risk-based national food safety system. This study was conducted to estimate the U.S. health burden of 14 major pathogens in 12 broad categories of food and to then rank the resulting 168 pathogen-food combinations. These pathogens examined were Campylobacter, Clostridium perfringens, Escherichia coli O157:H7, Listeria monocytogenes, norovirus, Salmonella enterica, Toxoplasma gondii, and all other FoodNet pathogens. The health burden associated with each pathogen was measured using new estimates of the cost of illness and loss of quality-adjusted life years (QALYs) from acute and chronic illness and mortality. A new method for attributing illness to foods was developed that relies on both outbreak data and expert elicitation. This method assumes that empirical data are generally preferable to expert judgment; thus, outbreak data were used for attribution except where evidence suggests that these data are considered not representative of food attribution. Based on evaluation of outbreak data, expert elicitation, and published scientific literature, outbreak-based attribution estimates for Campylobacter, Toxoplasma, Cryptosporidium, and Yersinia were determined not representative; therefore, expert-based attribution were included for these four pathogens. Sensitivity analyses were conducted to assess the effect of attribution data assumptions on rankings. Disease burden was concentrated among a relatively small number of pathogen-food combinations. The top 10 pairs were responsible for losses of over $8 billion and 36,000 QALYs, or more than 50 % of the total across all pairs. Across all 14 pathogens, poultry, pork, produce, and complex foods were responsible for nearly 60 % of the total cost of illness and loss of QALYs.", "title": "Ranking the disease burden of 14 pathogens in food sources in the United States using attribution data from outbreak investigations and expert elic..." }, { "docid": "MED-4337", "text": "The ingestion of fatty meals is associated with a transient, low-grade systemic inflammatory response in human subjects, involving the activation of circulating monocytes and the secretion of pro-inflammatory cytokines. However, it is not yet clear how different foodstuffs may promote inflammatory signalling. In a screen of forty filter-sterilised soluble extracts from common foodstuffs, seven were found to induce the secretion of TNF-α and IL-6 from human monocytes in vitro. To investigate what may differentiate inflammatory from non-inflammatory food extracts, stimulants of Toll-like receptor (TLR) 2 and TLR4 were quantified using human embryonic kidney-293 cells transfected with each TLR, and calibrated with defined bacterial lipopeptide (BLP) and lipopolysaccharide (LPS) standards. These assays revealed that while most foods contained undetectable levels of TLR2 or TLR4 stimulants, all TNF-α-inducing foods contained stimulants of either TLR2 (up to 1100 ng BLP-equivalent/g) or TLR4 (up to 2700 ng LPS-equivalent/g) in both the soluble and insoluble fractions. TLR stimulants were present mainly in meat products and processed foods, but were minimal or undetectable in fresh fruit and vegetables. The capacity of food extracts to induce TNF-α secretion in monocytes correlated with the content of both TLR2 (r 0·837) and TLR4 stimulants (r 0·748), and was completely abolished by specific inhibition of TLR2 and TLR4. LPS and BLP were found to be highly resistant to typical cooking times and temperatures, low pH and protease treatment. In conclusion, apparently unspoiled foodstuffs can contain large quantities of stimulants of TLR2 and TLR4, both of which may regulate their capacity to stimulate inflammatory signalling.", "title": "The capacity of foodstuffs to induce innate immune activation of human monocytes in vitro is dependent on food content of stimulants of Toll-like r..." }, { "docid": "MED-2398", "text": "The worldwide increasing prevalence of type 2 diabetes mellitus (T2DM) poses an immense public health hazard leading to a variety of complications such as cardiovascular diseases, nephropathy and neuropathy. Diet, as a key component of a healthy human lifestyle, plays an important role in the prevention and management of T2DM and its complications. The dietary n-3 polyunsaturated fatty acids (PUFAs) have been associated with various favourable functions such as anti-inflammatory effects, improving endothelial function, controlling the blood pressure, and reducing hypertriglyceridemia and insulin insensitivity. According to some epidemiological studies, a lower prevalence of T2DM was found in populations consuming large amounts of seafood products, which are rich in n-3 PUFAs. However, the evidence on the relation between fish intake, dietary n-3 PUFAs, and risk of T2DM is controversial. Therefore, this paper aimed to review the epidemiological and clinical studies on the role of dietary n-3 PUFAs in T2DM. Also, the limitations of these studies and the need for potential further research on the subject are discussed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.", "title": "Role of dietary n-3 polyunsaturated fatty acids in type 2 diabetes: a review of epidemiological and clinical studies." }, { "docid": "MED-4290", "text": "BACKGROUND AND AIMS: Nut intake has been inversely related to body mass index (BMI) in prospective studies. We examined dietary determinants of adiposity in an elderly Mediterranean population with customarily high nut consumption. METHODS AND RESULTS: A cross-sectional study was conducted in 847 subjects (56% women, mean age 67 years, BMI 29.7kg/m(2)) at high cardiovascular risk recruited into the PREDIMED study. Food consumption was evaluated by a validated semi-quantitative questionnaire, energy expenditure in physical activity by the Minnesota Leisure Time Activity questionnaire, and anthropometric variables by standard measurements. Nut intake decreased across quintiles of both BMI and waist circumference (P-trend <0.005; both). Alcohol ingestion was inversely related to BMI (P-trend=0.020) and directly to waist (P-trend=0.011), while meat intake was directly associated with waist circumference (P-trend=0.018). In fully adjusted multivariable models, independent dietary associations of BMI were the intake of nuts inversely (P=0.002) and that of meat and meat products directly (P=0.042). For waist circumference, independent dietary associations were intake of nuts (P=0.002) and vegetables (P=0.040), both inversely, and intake of meat and meat products directly (P=0.009). From the regression coefficients, it was predicted that BMI and waist circumference decreased by 0.78kg/m(2) and 2.1cm, respectively, for each serving of 30g of nuts. Results were similar in men and women. CONCLUSION: Nut consumption was inversely associated with adiposity independently of other lifestyle variables. It remains to be explored whether residual confounding related to a healthier lifestyle of nut eaters might in part explain these results. Copyright © 2009 Elsevier B.V. All rights reserved.", "title": "Cross-sectional association of nut intake with adiposity in a Mediterranean population." }, { "docid": "MED-1557", "text": "AIM: To systematically review data from different countries on population intakes of total fat, saturated fatty acids (SFA) and polyunsaturated fatty acids (PUFA), and to compare these to recommendations from the Food and Agriculture Organization of the United Nations/the World Health Organization (FAO/WHO). METHODS: Data from national dietary surveys or population studies published from 1995 were searched via MEDLINE, Web of Science and websites of national public health institutes. RESULTS: Fatty acid intake data from 40 countries were included. Total fat intake ranged from 11.1 to 46.2 percent of energy intake (% E), SFA from 2.9 to 20.9% E and PUFA from 2.8 to 11.3% E. The mean intakes met the recommendation for total fat (20-35% E), SFA (<10% E) and PUFA (6-11% E) in 25, 11 and 20 countries, respectively. SFA intake correlated with total fat intake (r = 0.76, p < 0.01) but not with PUFA intake (r = 0.03, p = 0.84). Twenty-seven countries provided data on the distribution of fatty acids intake. In 18 of 27 countries, more than 50% of the population had SFA intakes >10% E and in 13 of 27 countries, the majority of the population had PUFA intakes <6% E. CONCLUSIONS: In many countries, the fatty acids intake of adults does not meet the levels that are recommended to prevent chronic diseases. The relation between SFA and PUFA intakes shows that lower intakes of SFA in the populations are not accompanied by higher intakes of PUFA, as is recommended for preventing coronary heart disease.", "title": "Intake of fatty acids in general populations worldwide does not meet dietary recommendations to prevent coronary heart disease: a systematic review..." }, { "docid": "MED-2455", "text": "BACKGROUND: It has been postulated that dietary antioxidants may influence the expression of allergic diseases and asthma. To test this hypothesis a case-control study was performed, nested in a cross sectional study of a random sample of adults, to investigate the relationship between allergic disease and dietary antioxidants. METHODS: The study was performed in rural general practices in Grampian, Scotland. A validated dietary questionnaire was used to measure food intake of cases, defined, firstly, as people with seasonal allergic-type symptoms and, secondly, those with bronchial hyperreactivity confirmed by methacholine challenge, and of controls without allergic symptoms or bronchial reactivity. RESULTS: Cases with seasonal symptoms did not differ from controls except with respect to the presence of atopy and an increased risk of symptoms associated with the lowest intake of zinc. The lowest intakes of vitamin C and manganese were associated with more than fivefold increased risks of bronchial reactivity. Decreasing intakes of magnesium were also significantly associated with an increased risk of hyperreactivity. CONCLUSIONS: This study provides evidence that diet may have a modulatory effect on bronchial reactivity, and is consistent with the hypothesis that the observed reduction in antioxidant intake in the British diet over the last 25 years has been a factor in the increase in the prevalence of asthma over this period.", "title": "Bronchial reactivity and dietary antioxidants" }, { "docid": "MED-1408", "text": "OBJECTIVE: This meta-analysis aims to quantitatively synthesize all studies that examine the association between adherence to a Mediterranean diet and risk of stroke, depression, cognitive impairment, and Parkinson disease. METHODS: Potentially eligible publications were those providing effect estimates of relative risk (RR) for the association between Mediterranean diet and the aforementioned outcomes. Studies were sought in PubMed up to October 31, 2012. Maximally adjusted effect estimates were extracted; separate analyses were performed for high and moderate adherence. RESULTS: Twenty-two eligible studies were included (11 covered stroke, 9 covered depression, and 8 covered cognitive impairment; only 1 pertained to Parkinson's disease). High adherence to Mediterranean diet was consistently associated with reduced risk for stroke (RR = 0.71, 95% confidence interval [CI] = 0.57-0.89), depression (RR = 0.68, 95% CI = 0.54-0.86), and cognitive impairment (RR = 0.60, 95% CI = 0.43-0.83). Moderate adherence was similarly associated with reduced risk for depression and cognitive impairment, whereas the protective trend concerning stroke was only marginal. Subgroup analyses highlighted the protective actions of high adherence in terms of reduced risk for ischemic stroke, mild cognitive impairment, dementia, and particularly Alzheimer disease. Meta-regression analysis indicated that the protective effects of Mediterranean diet in stroke prevention seemed more sizeable among males. Concerning depression, the protective effects of high adherence seemed independent of age, whereas the favorable actions of moderate adherence seemed to fade away with more advanced age. INTERPRETATION: Adherence to a Mediterranean diet may contribute to the prevention of a series of brain diseases; this may be of special value given the aging of Western societies. © 2013 American Neurological Association.", "title": "Mediterranean diet, stroke, cognitive impairment, and depression: A meta-analysis." }, { "docid": "MED-3314", "text": "OBJECTIVES: Evidence suggests that certain occupations and related exposures may increase the risk of malignant lymphoma. Farming, printing and paper industry, wood processing, meat handling and processing, welding, shoe and leather manufacturing and teaching profession are among the categories that have been implicated in previous studies. The relationship between occupation and malignant lymphoma has been investigated in a large European prospective study. METHODS: We investigated occupational risks for lymphomas in the European Prospective Investigation into Cancer and Nutrition (EPIC). The mean follow-up time for 348,555 subjects was 9 years (SD: 2 years). The analysis was based on 866 and 48 newly diagnosed cases of non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). These were identified in the EPIC subcohorts with occupational data. Data on 52 occupations were collected through standardised questionnaires. Cox proportional hazard models were used to explore the association between occupation and risk of malignant lymphoma. RESULTS: The following occupations were positively associated with malignant NHL after adjustment for study centre, age, sex, socioeconomic status (SES), smoking and alcohol: butchers (HR=1.53, 95% CI 1.05 to 2.48, including multiple myeloma/plasmacytoma; HR=1.30, 95% CI 1.00 to 2.66, excluding multiple myeloma/plasmacytoma) and car repair workers (HR=1.50, 95% CI 1.01 to 2.00, including multiple myeloma/plasmacytoma; HR=1.51, 95% CI 1.01 to 2.31, excluding multiple myeloma/plasmacytoma). HL was associated with gasoline station occupation (HR=4.59, 95% CI 1.08 to 19.6). CONCLUSION: The findings in this current study of a higher risk of NHL among car repair workers and butchers and a higher risk of HL among gasoline station workers suggest a possible role from occupationally related exposures, such as solvents and zoonotic viruses, as risk factors for malignant lymphoma.", "title": "Occupation and risk of lymphoma: a multicentre prospective cohort study (EPIC)." }, { "docid": "MED-5193", "text": "BACKGROUND: The relation between dairy product intake and the risk of ischemic heart disease (IHD) remains controversial. OBJECTIVE: We aimed to explore biomarkers of dairy fat intake in plasma and erythrocytes and to assess the hypothesis that higher concentrations of these biomarkers are associated with a greater risk of IHD in US women. DESIGN: Among 32,826 participants in the Nurses' Health Study who provided blood samples in 1989-1990, 166 incident cases of IHD were ascertained between baseline and 1996. These cases were matched with 327 controls for age, smoking, fasting status, and date of blood drawing. RESULTS: Among controls, correlation coefficients between average dairy fat intake in 1986-1990 and 15:0 and trans 16:1n-7 content were 0.36 and 0.30 for plasma and 0.30 and 0.32 for erythrocytes, respectively. In multivariate analyses, with control for age, smoking, and other risk factors of IHD, women with higher plasma concentrations of 15:0 had a significantly higher risk of IHD. The multivariate-adjusted relative risks (95% CI) from the lowest to highest tertile of 15:0 concentrations in plasma were 1.0 (reference), 2.18 (1.20, 3.98), and 2.36 (1.16, 4.78) (P for trend = 0.03). Associations for other biomarkers were not significant. CONCLUSIONS: Plasma and erythrocyte contents of 15:0 and trans 16:1n-7 can be used as biomarkers of dairy fat intake. These data suggest that a high intake of dairy fat is associated with a greater risk of IHD.", "title": "Plasma and erythrocyte biomarkers of dairy fat intake and risk of ischemic heart disease." }, { "docid": "MED-4071", "text": "An increased risk of breast cancer has been observed in women who consume \"very well-done\" meats. Heterocyclic amines are mutagenic and carcinogenic pyrolysis products formed during high temperature cooking of meats. In the present study, human milk samples were analyzed for PhIP, one of the most abundant dietary heterocyclic amine. A protocol was developed with a mixed-mode cation exchange sorbent for the extraction of heterocyclic amines from milk. Milk samples were acquired from healthy Canadian women. With LC/MS analysis and the method of isotope dilution for quantification, levels of PhIP were determined in human milk samples. PhIP was detected in 9 of the 11 milk samples, at levels as high as 59 pg/mL (ppt). No PhIP was detected in the milk of the vegetarian donor. Detection of PhIP in milk indicates that ductal mammary epithelial cells are directly exposed to this carcinogen, suggesting that heterocyclic amines are possible human mammary carcinogens.", "title": "Detection of PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) in the milk of healthy women." }, { "docid": "MED-3439", "text": "Erectile dysfunction (ED) is common, affecting 40% of men over 40 years of age (so-called 40 over 40) and 1 in 3 men over 70 years of age. It is predominantly a vascular condition, often preceding a cardiovascular event by 3-5 years. ED is associated as a consequence with acute coronary syndromes and increased cardiovascular and all-cause mortality. Its early identification therefore offers a window of opportunity for cardiovascular risk reduction. ED has for many a devastating impact on a couple's relationship. Its treatment is often successful, maintaining quality of life in the middle aged and elderly. ED should always be queried as part of the ongoing health care worker and patient relationship - its early detection may prevent early death. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.", "title": "Erectile dysfunction and coronary disease: evaluating the link." }, { "docid": "MED-4116", "text": "The growths of many and perhaps all tumors may be stimulated rather than inhibited by a quantitatively low level of immunity. The reason tumors have antigens may be that tumors do not develop in vivo in the absence of at least a minimal immune reaction; in this sense, cancer may be considered an autoimmune disease. This review, based largely on the work of our own laboratory, outlines the data showing that the titration of anti-tumor immunity exhibits the phenomenon of hormesis, i.e. the dose-response curve is non-linear such that low levels of immunity are generally stimulatory but larger quantities of the same immune reactants may inhibit tumor growth. Evidence is also reviewed that suggests that the immune response may vary qualitatively and quantitatively during progression, such that there seems to be, during oncogenesis, a very low level of immune reaction that aids initial tumor growth, followed by a larger reaction that may cause remission of early neoplasms, followed, if the neoplasm survives, by a relative immunologic tolerance to the tumor that may be dependent, at least in part, on suppressor cells. This knowledge may help to explain some clinical observations concerning the relationships among tumor types and the organ distribution of metastases.", "title": "The flip side of immune surveillance: immune dependency." }, { "docid": "MED-2380", "text": "BACKGROUND AND AIMS: High blood pressure (BP) is considered a major risk factor for cardiovascular disease. Among lifestyle factors, diet plays a key role in the prevention and control of high BP. Therefore, it is important to elucidate which dietary components can exert beneficial effects on BP through modulation of endothelial function (EF) or by other mechanisms. In this paper we review the role of nutrients, foods, particularly nuts, and dietary patterns on BP control. DATA SYNTHESIS: Because nuts are low in sodium and contain significant amounts of mono- and polyunsaturated fatty acids, fiber, minerals such as magnesium, potassium and calcium, and antioxidants, they have been suggested as potentially protective foods against hypertension. Limited evidence from prospective studies and clinical trials suggests that nut consumption has a beneficial effect on both BP and EF. However, BP changes were a secondary outcome in nut feeding trials and no study used ambulatory BP monitoring as the standard for BP measurements. CONCLUSIONS: Further clinical trials, ideally using ambulatory BP monitoring, are needed to establish the potential protective effect of nut consumption on hypertension and vascular reactivity. Copyright © 2011 Elsevier B.V. All rights reserved.", "title": "Nuts, hypertension and endothelial function." }, { "docid": "MED-3731", "text": "Esophageal cancer is highly aggressive and is a common cancer both worldwide and in the US. In the past two decades, the incidence and mortality of esophageal cancer in the US have both increased, where as the incidence and mortality of other cancers have decreased. Although esophageal squamous cell carcinoma and esophageal adenocarcinoma differ in their histology and epidemiologic distribution, some of their risk factors (e.g. dietary deficiencies and tobacco) and underlying mechanisms of carcinogenesis are the same. Intensive research into risk factors combined with the ability to identify precursor lesions (e.g.squamous dysplasia in esophageal squamous cell carcinoma and Barrett's esophagus in esophageal adenocarcinoma) has paved the way for studies of chemoprevention for esophageal cancer, some of which have shown promising results.", "title": "Esophageal cancer: epidemiology, pathogenesis and prevention." }, { "docid": "MED-4336", "text": "Dark chocolate contains high concentrations of flavonoids and may have antiinflammatory properties. We evaluated the association of dark chocolate intake with serum C-reactive protein (CRP). The Moli-sani Project is an ongoing cohort study of men and women aged >/=35 y randomly recruited from the general population. By July 2007, 10,994 subjects had been enrolled. Of 4849 subjects apparently free of any chronic disease, 1317 subjects who declared having eaten any chocolate during the past year (mean age 53 +/- 12 y; 51% men) and 824 subjects who ate chocolate regularly in the form of dark chocolate only (50 +/- 10 y; 55% men) were selected. High sensitivity-CRP was measured by an immunoturbidimetric method. The European Prospective Investigation into Cancer and Nutrition FFQ was used to evaluate nutritional intake. After adjustment for age, sex, social status, physical activity, systolic blood pressure, BMI, waist:hip ratio, food groups, and total energy intake, dark chocolate consumption was inversely associated with CRP (P = 0.038). When adjusted for nutrient intake, analyses showed similar results (P = 0.016). Serum CRP concentrations [geometric mean (95% CI)] univariate concentrations were 1.32 (1.26-1.39 mg/L) in nonconsumers and 1.10 (1.03-1.17 mg/L) in consumers (P < 0.0001). A J-shaped relationship between dark chocolate consumption and serum CRP was observed; consumers of up to 1 serving (20 g) of dark chocolate every 3 d had serum CRP concentrations that were significantly lower than nonconsumers or higher consumers. Our findings suggest that regular consumption of small doses of dark chocolate may reduce inflammation.", "title": "Regular consumption of dark chocolate is associated with low serum concentrations of C-reactive protein in a healthy Italian population." }, { "docid": "MED-1962", "text": "The concentrations of the 2,3,7,8-Cl substituted dibenzo-p-dioxins/-furans (PCDDs/PCDFs) were determined in the edible tissues of whole chicken fryers and compared with the values found in their abdominal fat. The values are presented both on a whole weight basis and on a lipid adjusted basis for each tissue. While there is a marked difference in the concentration of the 2,3,7,8-dibenzo-p-dioxins in the edible tissues expressed on a whole weight basis, the lipid-adjusted concentrations of the individual dioxins were not statistically different in the various tissues. This validates the use of lipid adjusted concentrations of 2,3,7,8-PCDDs/PCDFs in abdominal fat for the determination of the presence of these compounds in different tissues.", "title": "The concentration and distribution of 2,3,7,8-dibenzo-p-dioxins/-furans in chickens." }, { "docid": "MED-2651", "text": "The aims of this study were to determine the concentrations of 4-nonylphenol (NP) and 4-octylphenol (OP) in 59 human milk samples and to examine related factors including mothers' demographics and dietary habits. Women who consumed over the median amount of cooking oil had significantly higher OP concentrations (0.98 ng/g) than those who consumed less (0.39 ng/g) (P < 0.05). OP concentration was significantly associated with the consumption of cooking oil (beta = 0.62, P < 0.01) and fish oil capsules (beta = 0.39, P < 0.01) after adjustment for age and body mass index (BMI). NP concentration was also significantly associated with the consumption of fish oil capsules (beta = 0.38, P < 0.01) and processed fish products (beta = 0.59, P < 0.01). The food pattern of cooking oil and processed meat products from factor analysis was strongly associated with OP concentration in human milk (P < 0.05). These determinations should aid in suggesting foods for consumption by nursing mothers in order to protect their infants from NP/OP exposure. 2010 Elsevier Ltd. All rights reserved.", "title": "Alkylphenols in human milk and their relations to dietary habits in central Taiwan." }, { "docid": "MED-4559", "text": "The cardiovascular risk reduction associated with different statins for the prevention of cardiovascular disease and the cardiovascular risk increase associated with excess dietary intake of fat have been quantified. However, these relative risks have never been directly juxtaposed to determine whether an increase in relative risk by 1 activity could be neutralized by an opposing change in relative risk from a second activity. The investigators compared the increase in relative risk for cardiovascular disease associated with the total fat and trans fat content of fast foods against the relative risk decrease provided by daily statin consumption from a meta-analysis of statins in primary prevention of coronary artery disease (7 randomized controlled trials including 42,848 patients). The risk reduction associated with the daily consumption of most statins, with the exception of pravastatin, is more powerful than the risk increase caused by the daily extra fat intake associated with a 7-oz hamburger (Quarter Pounder) with cheese and a small milkshake. In conclusion, statin therapy can neutralize the cardiovascular risk caused by harmful diet choices. In other spheres of human activity, individuals choosing risky pursuits (motorcycling, smoking, driving) are advised or compelled to use measures to minimize the risk (safety equipment, filters, seatbelts). Likewise, some individuals eat unhealthily. Routine accessibility of statins in establishments providing unhealthy food might be a rational modern means to offset the cardiovascular risk. Fast food outlets already offer free condiments to supplement meals. A free statin-containing accompaniment would offer cardiovascular benefits, opposite to the effects of equally available salt, sugar, and high-fat condiments. Although no substitute for systematic lifestyle improvements, including healthy diet, regular exercise, weight loss, and smoking cessation, complimentary statin packets would add, at little cost, 1 positive choice to a panoply of negative ones.", "title": "Can a statin neutralize the cardiovascular risk of unhealthy dietary choices?" }, { "docid": "MED-3348", "text": "Fruit and vegetable consumption is inadequate among adults in the United States; this contributes to preventable morbidity and mortality. More effective dietary intervention strategies are needed. Recently, interventions that advertise the consequences of behavior for appearance have been successful in modifying sun-exposure habits and tobacco use. Such an approach might also facilitate dietary improvement. Consumption of carotenoid-rich fruit and vegetables positively affects skin color, which influences perceptions of health and attractiveness, and promoting such an effect may motivate target audiences to increase consumption of this important food group. This approach represents a novel direction for the field and is potentially suitable for cost-effective, population-level dissemination through the visual media.", "title": "Appealing to Vanity: Could Potential Appearance Improvement Motivate Fruit and Vegetable Consumption?" }, { "docid": "MED-2904", "text": "Background Prenatal exposure to mercury has been associated with adverse childhood neurologic outcomes in epidemiologic studies. Dose–response information for this relationship is useful for estimating benefits of reduced mercury exposure. Objectives We estimated a dose–response relationship between maternal mercury body burden and subsequent childhood decrements in intelligence quotient (IQ), using a Bayesian hierarchical model to integrate data from three epidemiologic studies. Methods Inputs to the model consist of dose–response coefficients from studies conducted in the Faroe Islands, New Zealand, and the Seychelles Islands. IQ coefficients were available from previous work for the latter two studies, and a coefficient for the Faroe Islands study was estimated from three IQ subtests. Other tests of cognition/achievement were included in the hierarchical model to obtain more accurate estimates of study-to-study and end point–to–end point variability. Results We find a central estimate of −0.18 IQ points (95% confidence interval, −0.378 to −0.009) for each parts per million increase of maternal hair mercury, similar to the estimates for both the Faroe Islands and Seychelles studies, and lower in magnitude than the estimate for the New Zealand study. Sensitivity analyses produce similar results, with the IQ coefficient central estimate ranging from −0.13 to −0.25. Conclusions IQ is a useful end point for estimating neurodevelopmental effects, but may not fully represent cognitive deficits associated with mercury exposure, and does not represent deficits related to attention and motor skills. Nevertheless, the integrated IQ coefficient provides a more robust description of the dose–response relationship for prenatal mercury exposure and cognitive functioning than results of any single study.", "title": "Dose–Response Relationship of Prenatal Mercury Exposure and IQ: An Integrative Analysis of Epidemiologic Data" }, { "docid": "MED-1407", "text": "The Mediterranean tradition offers a cousine rich in colors, aromas and memories, which support the taste and the spirit of those who live in harmony with nature. Everyone is talking about the Mediterranean diet, but few are those who do it properly, thus generating a lot of confusion in the reader. And so for some it coincides with the pizza, others identified it with the noodles with meat sauce, in a mixture of pseudo historical traditions and folklore that do not help to solve the question that is at the basis of any diet: combine and balance the food so as to satisfy the qualitative and quantitative needs of an individual and in a sense, preserves his health through the use of substances that help the body to perform normal vital functions. The purpose of our work is to demonstrate that the combination of taste and health is a goal that can be absolutely carried out by everybody, despite those who believe that only a generous caloric intake can guarantee the goodness of a dish and the satisfaction of the consumers. That should not be an absolute novelty, since the sound traditions of the Mediterranean cuisine we have used for some time in a wide variety of tasty gastronomic choices, from inviting colors and strong scents and absolutely in line with health.", "title": "The Mediterranean Diet: A History of Health" }, { "docid": "MED-3698", "text": "Purpose Single-variable analyses have associated physical activity, diet, and obesity with survival after breast cancer. This report investigates interactions among these variables. Patients and Methods A prospective study was performed of 1,490 women diagnosed and treated for early-stage breast cancer between 1991 and 2000. Enrollment was an average of 2 years postdiagnosis. Only seven women were lost to follow-up through December 2005. Results In univariate analysis, reduced mortality was weakly associated with higher vegetable-fruit consumption, increased physical activity, and a body mass index that was neither low weight nor obese. In a multivariate Cox model, only the combination of consuming five or more daily servings of vegetables-fruits, and accumulating 540+ metabolic equivalent tasks-min/wk (equivalent to walking 30 minutes 6 d/wk), was associated with a significant survival advantage (hazard ratio, 0.56; 95% CI, 0.31 to 0.98). The approximate 50% reduction in risk associated with these healthy lifestyle behaviors was observed in both obese and nonobese women, although fewer obese women were physically active with a healthy dietary pattern (16% v 30%). Among those who adhered to this healthy lifestyle, there was no apparent effect of obesity on survival. The effect was stronger in women who had hormone receptor–positive cancers. Conclusion A minority of breast cancer survivors follow a healthy lifestyle that includes both recommended intakes of vegetables-fruits and moderate levels of physical activity. The strong protective effect observed suggests a need for additional investigation of the effect of the combined influence of diet and physical activity on breast cancer survival.", "title": "Greater Survival After Breast Cancer in Physically Active Women With High Vegetable-Fruit Intake Regardless of Obesity" }, { "docid": "MED-2459", "text": "BACKGROUND: Free radical-mediated oxidative damage to lipids is thought to be an important process in the pathogenesis of atherosclerosis. Although previous studies have demonstrated a beneficial impact of antioxidant vitamin supplements on lipid peroxidation, the effect of dietary patterns on lipid peroxidation is unknown. METHODS AND RESULTS: During the 3-week run-in period of a randomized trial, 123 healthy individuals were fed a control diet, low in fruits, vegetables, and dairy products, with 37% of calories from fat. Participants were then randomized to consume for 8 weeks: (1) the control diet, (2) a diet rich in fruits and vegetables but otherwise similar to the control diet, and (3) a combination diet rich in fruits, vegetables, and low-fat dairy products and reduced in fat. Serum oxygen radical-absorbing capacity, malondialdehyde (an in vitro measure of lipid peroxidation), and breath ethane (an in vivo measure of lipid peroxidation) were measured at the end of run-in and intervention periods. Between run-in and intervention, mean (95% CI) change in oxygen radical-absorbing capacity (U/mL) was -35 (-93, 13) in the control diet, 26 (-15, 67) in the fruits and vegetables diet (P=0.06 compared with control), and 19 (-22, 54) in the combination diet (P=0.10 compared with control). Median (interquartile range) change in ethane was 0.84 (0.10, 1.59) in the control diet, 0.02 (-0.61, 0.83) in the fruits and vegetables diet (P=0.04 compared with control), and -1.00 (-1.97, 0.25) in the combination diet (P=0.005 compared with control). Change in malondialdehyde did not differ between diets. CONCLUSIONS: This study demonstrates that modification of diet can favorably affect serum antioxidant capacity and protect against lipid peroxidation.", "title": "Effect of dietary patterns on measures of lipid peroxidation: results from a randomized clinical trial." }, { "docid": "MED-3442", "text": "Gim (Porphyra sp.) and miyeok (Undaria pinnatifida) are the seaweeds most consumed by Koreans. We investigated the association between the intake of gim and miyeok and the risk of breast cancer in a case-control study. Cases were 362 women aged 30-65 years old, who were histologically confirmed to have breast cancer. Controls visiting the same hospital were matched to cases according to their age (sd 2 years) and menopausal status. Food intake was estimated by the quantitative FFQ with 121 items, including gim and miyeok. Conditional logistic regression analysis was used to obtain the OR and corresponding 95 % CI. The average intake and consumption frequency of gim in cases were lower than in controls. The daily intake of gim was inversely associated with the risk of breast cancer (5th v. 1st quintile, OR, 0.48; 95 % CI, 0.27, 0.86; P for trend, 0.026) after adjustment for potential confounders. After stratification analysis was performed according to menopausal status, premenopausal women (5th v. 1st quintile, OR, 0.44; 95 % CI, 0.24, 0.80; P for trend, 0.007) and postmenopausal women (5th v. 1st quintile, OR, 0.32; 95 % CI, 0.13, 0.80; P for trend, 0.06) showed similar inverse associations between gim intake and the risk of breast cancer after an adjustment for potential confounders except dietary factors. Miyeok consumption did not have any significant associations with breast cancer. These results suggest that high intake of gim may decrease the risk of breast cancer.", "title": "A case-control study on seaweed consumption and the risk of breast cancer." }, { "docid": "MED-2412", "text": "OBJECTIVE: To determine the effects of fish oil supplementation on lipid levels and glycemic control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A comprehensive search of Medline, Embase, Lilacs, the Cochrane Clinical Trials Registry bibliographies of relevant papers, and expert input updated through September 1998 was undertaken. All randomized placebo-controlled trials were included in which fish oil supplementation was the only intervention in subjects with type 2 diabetes. Three investigators performed data extraction and quality scoring independently with discrepancies resolved by consensus. Eighteen trials including 823 subjects followed for a mean of 12 weeks were included. Doses of fish oil used ranged from 3 to 18 g/day The outcomes studied were glycemic control and lipid levels. RESULTS: Meta-analysis of pooled data demonstrated a statistically significant effect of fish oil on lowering triglycerides (-0.56 mmol/l [95% CI -0.71 to -0.41]) and raising LDL cholesterol (0.21 mmol/l [0.02 to 0.41]). No statistically significant effect was observed for fasting glucose. HbA1c total cholesterol, or HDL cholesterol. The triglyceride-lowering effect and the elevation in LDL cholesterol were most marked in those trials that recruited hypertriglyceridemic subjects and used higher doses of fish oil. Heterogeneity was observed and explained by the recruitment of subjects with baseline hypertriglyceridemia in some studies. CONCLUSIONS: Fish oil supplementation in type 2 diabetes lowers triglycerides, raises LDL cholesterol, and has no statistically significant effect on glycemic control. Trials with hard clinical end points are needed.", "title": "Fish oil supplementation in type 2 diabetes: a quantitative systematic review." }, { "docid": "MED-1596", "text": "Recent observed feminization of aquatic animals has raised concerns about estrogenic compounds in water supplies and the potential for these chemicals to reach drinking water. Public perception frequently attributes this feminization to oral contraceptives (OCs) in wastewater and raises concerns that exposure to OCs in drinking water may contribute to the recent rise in human reproductive problems. This paper reviews the literature regarding various sources of estrogens, in surface, source and drinking water, with an emphasis on the active molecule that comes from OCs. It includes discussion of the various agricultural, industrial, and municipal sources and outlines the contributions of estrogenic chemicals to the estrogenicity of waterways and estimates that the risk of exposure to synthetic estrogens in drinking water on human health is negligible. This paper also provides recommendations for strategies to better understand all the potential sources of estrogenic compounds in the environment and possibilities to reduce the levels of estrogenic chemicals in the water supply.", "title": "Are oral contraceptives a significant contributor to the estrogenicity of drinking water?" }, { "docid": "MED-3085", "text": "Objective To determine the prevalence of phosphorus-containing food additives in best selling processed grocery products and to compare the phosphorus content of a subset of top selling foods with and without phosphorus additives. Design The labels of 2394 best selling branded grocery products in northeast Ohio were reviewed for phosphorus additives. The top 5 best selling products containing phosphorus additives from each food category were matched with similar products without phosphorus additives and analyzed for phosphorus content. Four days of sample meals consisting of foods with and without phosphorus additives were created and daily phosphorus and pricing differentials were computed. Setting Northeast Ohio Main outcome measures Presence of phosphorus-containing food additives, phosphorus content Results 44% of the best selling grocery items contained phosphorus additives. The additives were particularly common in prepared frozen foods (72%), dry food mixes (70%), packaged meat (65%), bread & baked goods (57%), soup (54%), and yogurt (51%) categories. Phosphorus additive containing foods averaged 67 mg phosphorus/100 gm more than matched non-additive containing foods (p=.03). Sample meals comprised mostly of phosphorus additive-containing foods had 736 mg more phosphorus per day compared to meals consisting of only additive-free foods. Phosphorus additive-free meals cost an average of $2.00 more per day. Conclusion Phosphorus additives are common in best selling processed groceries and contribute significantly to their phosphorus content. Moreover, phosphorus additive foods are less costly than phosphorus additive-free foods. As a result, persons with chronic kidney disease may purchase these popular low-cost groceries and unknowingly increase their intake of highly bioavailable phosphorus.", "title": "The Prevalence of Phosphorus Containing Food Additives in Top Selling Foods in Grocery Stores" }, { "docid": "MED-4628", "text": "BACKGROUND & AIMS: Dietary arachidonic acid, an n-6 polyunsaturated fatty acid (n-6 PUFA), might be involved in the etiology of ulcerative colitis (UC). We performed a prospective cohort study to determine whether high levels of arachidonic acid in adipose tissue samples (which reflects dietary intake) are associated with UC. METHODS: We analyzed data collected from 57,053 men and women in the EPIC-Denmark Prospective Cohort Study from 1993 to 1997. Adipose tissue biopsy samples were collected from gluteal regions at the beginning of the study, the cohort was monitored over subsequent years, and participants who developed UC were identified. A subcohort of 2510 randomly selected participants were used as controls. Concentrations of arachidonic acid were measured in adipose tissue samples. In the analysis, arachidonic acid levels were divided into quartiles; relative risks (RR) were calculated and adjusted for smoking, use of aspirin and nonsteroidal anti-inflammatory drugs, and levels of n-3 PUFAs. RESULTS: A total of 34 subjects (56% men) developed incident UC at a median age of 58.8 years (range, 50.0-69.0 years). Those in the highest quartile for arachidonic acid concentrations in adipose tissue had an RR for UC of 4.16 (95% confidence interval [CI]: 1.56-11.04); a trend per 0.1% increase in arachidonic acid of 1.77 in RR was observed (95% CI: 1.38-2.27). The fraction attributed the highest levels of arachidonic acid was 40.3%. CONCLUSIONS: Individuals with the highest relative concentrations of arachidonic acid in adipose tissue have a significantly greater risk of developing UC. Dietary modifications might therefore prevent UC or reduce disease symptoms. Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.", "title": "An association between dietary arachidonic acid, measured in adipose tissue, and ulcerative colitis." }, { "docid": "MED-3426", "text": "OBJECTIVES: The purpose of our study was to assess the prevalence and extent of coronary artery atherosclerosis in asymptomatic patients with vascular erectile dysfunction (ED). BACKGROUND: An association between ED and ischemic heart disease has been suggested, but it is unknown if it represents a marker of subclinical coronary atherosclerosis. METHODS: We studied 70 consecutive patients with vascular ED, evaluated by penile Doppler, and 73 control subjects with no history of coronary artery disease. We measured traditional coronary risk factors, circulating levels of C-reactive protein (CRP), endothelial function by ultrasound of brachial artery, and coronary artery calcification by multi-slice computed tomography. RESULTS: The patients and the control group were similar for age, race, and coronary risk score. Patients with ED had significantly higher high-sensitivity C-reactive protein levels (2.62 vs. 1.03 mg/l, p < 0.001). Flow-mediated dilation of the brachial artery was more impaired in patients with ED than in controls (2.36 vs. 3.92, p < 0.001). Coronary artery calcification was more frequent in individuals with ED than in control subjects (p = 0.01). Multiple logistic regression analysis showed that patients with ED had an overall odds ratio of 3.68 for having calcium score above the 75th percentile, compared to the controls. CONCLUSIONS: Coronary atherosclerosis is more severe in patients with vascular ED; ED predicts the presence and extent of subclinical atherosclerosis independent of traditional risk factors for cardiovascular disease. Thus, ED may be considered an additional, early warning sign of coronary atherosclerosis.", "title": "Subclinical coronary artery atherosclerosis in patients with erectile dysfunction." }, { "docid": "MED-4823", "text": "Background Previous research relating dietary fat, a modifiable risk factor, to pancreatic cancer has been inconclusive. Methods We prospectively analyzed the association between intakes of fat, fat subtypes, and fat food sources and exocrine pancreatic cancer in the National Institutes of Health–AARP Diet and Health Study, a US cohort of 308 736 men and 216 737 women who completed a 124-item food frequency questionnaire in 1995–1996. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models, with adjustment for energy intake, smoking history, body mass index, and diabetes. Statistical tests were two-sided. Results Over an average follow-up of 6.3 years, 865 men and 472 women were diagnosed with exocrine pancreatic cancer (45.0 and 34.5 cases per 100 000 person-years, respectively). After multivariable adjustment and combination of data for men and women, pancreatic cancer risk was directly related to the intakes of total fat (highest vs lowest quintile, 46.8 vs 33.2 cases per 100 000 person-years, HR = 1.23, 95% CI = 1.03 to 1.46; Ptrend  = .03), saturated fat (51.5 vs 33.1 cases per 100 000 person-years, HR = 1.36, 95% CI = 1.14 to 1.62; Ptrend < .001), and monounsaturated fat (46.2 vs 32.9 cases per 100 000 person-years, HR = 1.22, 95% CI = 1.02 to 1.46; Ptrend = .05) but not polyunsaturated fat. The associations were strongest for saturated fat from animal food sources (52.0 vs 32.2 cases per 100 000 person-years, HR = 1.43, 95% CI = 1.20 to 1.70; Ptrend < .001); specifically, intakes from red meat and dairy products were both statistically significantly associated with increased pancreatic cancer risk (HR = 1.27 and 1.19, respectively). Conclusion In this large prospective cohort with a wide range of intakes, dietary fat of animal origin was associated with increased pancreatic cancer risk.", "title": "Dietary Fatty Acids and Pancreatic Cancer in the NIH-AARP Diet and Health Study" }, { "docid": "MED-1366", "text": "My concern about diet as a public health problem began in the early 1950s in Naples, where we observed very low incidences of coronary heart disease associated with what we later came to call the \"good Mediterranean diet.\" The heart of this diet is mainly vegetarian, and differs from American and northern European diets in that it is much lower in meat and dairy products and uses fruit for dessert. These observations led to our subsequent research in the Seven Countries Study, in which we demonstrated that saturated fat is the major dietary villain. Today, the healthy Mediterranean diet is changing and coronary heart disease is no longer confined to medical textbooks. Our challenge is to persuade children to tell their parents to eat as Mediterraneans do.", "title": "Mediterranean diet and public health: personal reflections." }, { "docid": "MED-4113", "text": "Clonal deletion is arguably the most important mechanism of eliminating self-reactive thymocytes from the T-cell repertoire. Recent work has identified new players in this process. On the thymocyte side, several molecules have been newly implicated in the pathway from initial T-cell receptor signaling through to the final result: gene transcription and thymocyte apoptosis. In addition, several proapoptotic molecules have been found to be necessary for the death of self-reactive thymocytes. On the antigen-presenting cell side, the expression of peripheral self-antigens, regulated at least in part by the autoimmune regulator (AIRE) protein, is crucial for complete elimination of autoreactive thymocytes. The importance of thymic peripheral antigen expression and clonal deletion to self-tolerance is demonstrated in the autoimmune diseases autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy and type-1 diabetes mellitus.", "title": "Good riddance: Thymocyte clonal deletion prevents autoimmunity." }, { "docid": "MED-1768", "text": "The role of environmental compounds with estrogenic activity in the development of male reproductive disorders has been a source of great concern. Among the routes of human exposure to estrogens, we are particularly concerned about cows' milk, which contains considerable amounts of estrogens. The major sources of animal-derived estrogens in the human diet are milk and dairy products, which account for 60-70% of the estrogens consumed. Humans consume milk obtained from heifers in the latter half of pregnancy, when the estrogen levels in cows are markedly elevated. The milk that we now consume may be quite unlike that consumed 100 years ago. Modern genetically-improved dairy cows, such as the Holstein, are usually fed a combination of grass and concentrates (grain/protein mixes and various by-products), allowing them to lactate during the latter half of pregnancy, even at 220 days of gestation. We hypothesize that milk is responsible, at least in part, for some male reproductive disorders. Copyright 2001 Harcourt Publishers Ltd.", "title": "Is milk responsible for male reproductive disorders?" }, { "docid": "MED-4851", "text": "The notion that dietary factors may influence rheumatoid arthritis (RA) has been a part of the folklore of the disease, but scientific support for this has been sparse. In a controlled, single-blind trial we tested the effect of fasting for 7-10 d, then consuming an individually adjusted, gluten-free, vegan diet for 3.5 mo, and then consuming an individually adjusted lactovegetarian diet for 9 mo on patients with RA. For all clinical variables and most laboratory variables measured, the 27 patients in the fasting and vegetarian diet groups improved significantly compared with the 26 patients in the control group who followed their usual omnivorous diet throughout the study period. One year after the patients completed the trial, they were reexamined. Compared with baseline, the improvements measured were significantly greater in the vegetarians who previously benefited from the diet (diet responders) than in diet nonresponders and omnivores. The beneficial effect could not be explained by patients' psychologic characteristics, antibody activity against food antigens, or changes in concentrations of prostaglandin and leukotriene precursors. However, the fecal flora differed significantly between samples collected at time points at which there was substantial clinical improvement and time points at which there were no or only minor improvements. In summary, the results show that some patients with RA can benefit from a fasting period followed by a vegetarian diet. Thus, dietary treatment may be a valuable adjunct to the ordinary therapeutic armamentarium for RA.", "title": "Rheumatoid arthritis treated with vegetarian diets." }, { "docid": "MED-1613", "text": "The present study was designed to examine the effects of habitual consumption of Taiwanese vegetarian diets on hormonal secretion, and on lipid and glycaemic control. Of the ninety-eight healthy female adults recruited from Hualien, Taiwan (aged 31-45 years), forty-nine were Buddhist lactovegetarians and forty-nine were omnivores. Dietary intakes were measured, and blood levels of nutrients and hormones were analysed. Vegetarians consumed less energy, fat and protein, but more fibre than the omnivores. Compared with the omnivores, the vegetarians had, on average, lower BMI and smaller waist circumference. Except for slightly lower levels of thyroxine (T4) in vegetarians, vegetarians and omnivores both showed similar levels of triiodothyronine (T3), free T4, thyroid-stimulating hormone, T3:T4 ratio and cortisol. Compared with the omnivores, the vegetarians had significantly lower levels of fasting insulin (median: 35.3 v. 50.6 pmol/l) and plasma glucose (mean: 4.7 (se 0.05) v. 4.9 (se 0.05) mmol/l). Insulin resistance, as calculated by the homeostasis model assessment method, was significantly lower in the vegetarians than in the omnivores (median: 1.10 v. 1.56), while beta-cell function was not different between the two groups. BMI and diet were both independent predictors for insulin resistance, and contributed 18 and 15 % of the variation in insulin resistance, respectively. In conclusion, Taiwanese vegetarians had lower glucose and insulin levels and higher insulin sensitivity than did the omnivores. Diet and lower BMI were partially responsible for the high insulin sensitivity observed in young Taiwanese vegetarians.", "title": "Taiwanese vegetarians have higher insulin sensitivity than omnivores." }, { "docid": "MED-4030", "text": "BACKGROUND: Oral health care professionals can play an important role in preventing oral cancer by performing oral mucosal examinations to detect pre-cancerous changes and by educating patients about oral cancer prevention strategies, including dietary approaches. CONCLUSIONS: Current evidence supports a diet high in fruits, vegetables and plant-based foods for prevention of oral cancer. Dietary supplements-including vitamins and minerals-have not been shown to be effective as substitutes for a diet high in fruits and vegetables. CLINICAL IMPLICATIONS: In addition to discussing tobacco and alcohol use with patients (and, if relevant, betel nut and gutka consumption), as well as the risk of sexual transmission of human papillo-mavirus, clinicians should provide dietary advice for the prevention of oral cancer as part of routine patient education practices.", "title": "Diet and prevention of oral cancer: strategies for clinical practice." }, { "docid": "MED-1375", "text": "BACKGROUND: Vegetarian diets have been associated with reduced mortality. Because a pure vegetarian diet might not easily be embraced by many individuals, consuming preferentially plant-derived foods would be a more easily understood message. A provegetarian food pattern (FP) emphasizing preference for plant-derived foods might reduce all-cause mortality. OBJECTIVE: The objective was to identify the association between an a priori-defined provegetarian FP and all-cause mortality. DESIGN: We followed 7216 participants (57% women; mean age: 67 y) at high cardiovascular risk for a median of 4.8 y. A validated 137-item semiquantitative food-frequency questionnaire was administered at baseline and yearly thereafter. Fruit, vegetables, nuts, cereals, legumes, olive oil, and potatoes were positively weighted. Added animal fats, eggs, fish, dairy products, and meats or meat products were negatively weighted. Energy-adjusted quintiles were used to assign points to build the provegetarian FP (range: 12-60 points). Deaths were confirmed by review of medical records and the National Death Index. RESULTS: There were 323 deaths during the follow-up period (76 from cardiovascular causes, 130 from cancer, 117 for noncancer, noncardiovascular causes). Higher baseline conformity with the provegetarian FP was associated with lower mortality (multivariable-adjusted HR for ≥ 40 compared with <30 points: 0.59; 95% CI: 0.40, 0.88). Similar results were found with the use of updated information on diet (RR: 0.59; 95% CI: 0.39, 0.89). CONCLUSIONS: Among omnivorous subjects at high cardiovascular risk, better conformity with an FP that emphasized plant-derived foods was associated with a reduced risk of all-cause mortality. This trial was registered at www.controlled-trials.com as ISRCTN35739639. © 2014 American Society for Nutrition.", "title": "A provegetarian food pattern and reduction in total mortality in the Prevención con Dieta Mediterránea (PREDIMED) study." }, { "docid": "MED-2264", "text": "Cadmium is a toxic element ubiquitous in the environment, which damages biological systems in various ways. The major source of cadmium exposure is food. High cadmium content in the soil leads to high cadmium concentrations in certain plants such as grains (above all surface layers and germs), oil or non-oil seeds, fruit and vegetables. These food commodities are the crucial components of a vegetarian nutrition. Blood cadmium concentrations were measured in two non-smoking population groups: the vegetarian group (n = 80) and the non-vegetarian (control) group of general population on traditional mixed diet (n = 84). The significantly higher blood cadmium content (1.78 +/- 0.22 vs. 0.45 +/- 0.04 microg/l) was measured in vegetarian group. Healthy risk values > 5 microg/l were found in 6 vegetarians vs. no non-vegetarian. The highest cadmium concentration (3.15 +/- 0.77 microg/l) was measured in vegan subgroup (plant food only, n = 10) and that value decreased with increasing animal food consumption (1.75 +/- 0.36 microg/l, lactovegetarian and lactoovovegetarian subgroup/added dairy products and eggs, n = 41/, 1.34 +/- 0.21 microg/I, semivegetarian subgroup /as a previous subgroup and added white meat, n = 291). Risk vegetarians vs. non-risk vegetarians consume significantly higher amounts of whole grain products, grain sprouts and oil seeds. Blood cadmium content is directly influenced by age (r = 0.32, p < 0.001), by whole grain product intake (r = 0.66, p < 0.001) and by duration of vegetarianism (r = 0.5, p < 0.001). Oxidative stress plays a major role in chronic cadmium induced hepatic and renal toxicity as well as in other consequences of cadmium injuries. Vegetarians have significantly higher plasma concentrations of natural antioxidants. The sufficient antioxidative protection against cadmium induced free radical formation in vegetarians may inhibit the harmful effects of greater cadmium intake from plant food.", "title": "Cadmium blood concentrations in relation to nutrition." }, { "docid": "MED-1614", "text": "AIM: To compare the insulin sensitivity indices between Chinese vegetarians and omnivores. METHODS: The study included 36 healthy volunteers (vegetarian, n=19; omnivore, n=17) who had normal fasting plasma glucose levels. Each participant completed an insulin suppression test. We compared steady-state plasma glucose (SSPG), fasting insulin, the homeostasis model assessment for insulin sensitivity (HOMA-IR and HOMA %S) and beta-cell function (HOMA %beta) between the groups. We also tested the correlation of SSPG with years on a vegetarian diet. RESULTS: The omnivore subjects were younger than the vegetarians (55.7+/-3.7 vs 58.6+/-3.6 year of age, P=0.022). There was no difference between the two groups in sex, blood pressure, renal function tests and lipid profiles. The omnivores had higher serum uric acid levels than vegetarians (5.25+/-0.84 vs 4.54+/-0.75 mg/dl, P=0.011). The results of the indices were different between omnivores and vegetarians (SSPG (mean+/-s.d.) 105.4+/-10.2 vs 80.3+/-11.3 mg/dl, P<0.001; fasting insulin, 4.06+/-0.77 vs 3.02+/-1.19 microU/ml, P=0.004; HOMA-IR, 6.75+/-1.31 vs 4.78+/-2.07, P=0.002; HOMA %S, 159.2+/-31.7 vs 264.3+/-171.7%, P=0.018) except insulin secretion index, HOMA %beta (65.6+/-18.0 vs 58.6+/-14.8%, P=0.208). We found a clear linear relation between years on a vegetarian diet and SSPG (r=-0.541, P=0.017). CONCLUSIONS: The vegetarians were more insulin sensitive than the omnivore counterparts. The degree of insulin sensitivity appeared to be correlated with years on a vegetarian diet.", "title": "Insulin sensitivity in Chinese ovo-lactovegetarians compared with omnivores." }, { "docid": "MED-3546", "text": "CONTEXT: The monoamine theory of depression proposes that monoamine levels are lowered, but there is no explanation for how monoamine loss occurs. Monoamine oxidase A (MAO-A) is an enzyme that metabolizes monoamines, such as serotonin, norepinephrine, and dopamine. OBJECTIVE: To determine whether MAO-A levels in the brain are elevated during untreated depression. SETTING: Tertiary care psychiatric hospital. PATIENTS: Seventeen healthy and 17 depressed individuals with major depressive disorder that met entry criteria were recruited from the care of general practitioners and psychiatrists. All study participants were otherwise healthy and nonsmoking. Depressed individuals had been medication free for at least 5 months. MAIN OUTCOME MEASURE: Harmine labeled with carbon 11, a radioligand selective for MAO-A and positron emission tomography, was used to measure MAO-A DVS (specific distribution volume), an index of MAO-A density, in different brain regions (prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex, caudate, putamen, thalamus, anterior temporal cortex, midbrain, hippocampus, and parahippocampus). RESULTS: The MAO-A DVS was highly significantly elevated in every brain region assessed (t test; P=.001 to 3x10(-7)). The MAO-A DVS was elevated on average by 34% (2 SDs) throughout the brain during major depression. CONCLUSIONS: The sizable magnitude of this finding and the absence of other compelling explanations for monoamine loss during major depressive episodes led to the conclusion that elevated MAO-A density is the primary monoamine-lowering process during major depression.", "title": "Elevated monoamine oxidase a levels in the brain: an explanation for the monoamine imbalance of major depression." }, { "docid": "MED-3433", "text": "OBJECTIVES: Our goal was to evaluate the association between erectile dysfunction (ED) and risk of cardiovascular disease (CVD) and all-cause mortality by conducting a meta-analysis of prospective cohort studies. BACKGROUND: Observational studies suggest an association between ED and the incidence of CVD. However, whether ED is an independent risk factor of CVD remains controversial. METHODS: The PubMed database was searched through January 2011 to identify studies that met pre-stated inclusion criteria. Reference lists of retrieved articles were also reviewed. Two authors independently extracted information on the designs of the studies, the characteristics of the study participants, exposure and outcome assessments, and control for potential confounding factors. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. RESULTS: Twelve prospective cohort studies involving 36,744 participants were included in the meta-analysis. The overall combined relative risks for men with ED compared with the reference group were 1.48 (95% confidence interval [CI]: 1.25 to 1.74) for CVD, 1.46 (95% CI: 1.31 to 1.63) for coronary heart disease, 1.35 (95% CI: 1.19 to 1.54) for stroke, and 1.19 (95% CI: 1.05 to 1.34) for all-cause mortality. Sensitivity analysis restricted to studies with control for conventional cardiovascular risk factors yielded similar results. No evidence of publication bias was observed. CONCLUSIONS: This meta-analysis of prospective cohort studies suggests that ED significantly increases the risk of CVD, coronary heart disease, stroke, and all-cause mortality, and the increase is probably independent of conventional cardiovascular risk factors. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.", "title": "Erectile dysfunction and risk of cardiovascular disease: meta-analysis of prospective cohort studies." }, { "docid": "MED-2276", "text": "A limited number of studies have demonstrated that some modulators of inflammation can be altered by the consumption of sweet cherries. We have taken a proteomics approach to determine the effects of dietary cherries on targeted gene expression. The purpose was then to determine changes caused by cherry consumption in the plasma concentrations of multiple biomarkers for several chronic inflammatory diseases in healthy humans with modestly elevated C-reactive protein (CRP; range, 1-14 mg/L; mean, 3.5 mg/L; normal, <1.0 mg/L). Eighteen men and women (45-61 y) supplemented their diets with Bing sweet cherries (280 g/d) for 28 d. Fasting blood samples were taken before the start of consuming the cherries (study d 7), 28 d after the initiation of cherry supplementation (d 35), and 28 d after the discontinuation (d 63). Of the 89 biomarkers assessed, cherry consumption for 28 d altered concentrations of 9, did not change those of 67, and the other 13 were below the detection limits. Cherry consumption decreased (P < 0.05) plasma concentrations of extracellular newly identified ligand for the receptor for advanced glycation end products (29.0%), CRP (20.1%), ferritin (20.3%), plasminogen activator inhibitor-1 (19.9%), endothelin-1 (13.7%), epidermal growth factor (13.2%), and IL-18 (8.1%) and increased that of IL-1 receptor antagonist (27.9%) compared with corresponding values on study d 7. The ferritin concentration continued to decrease between d 35 and 63 and it was significantly lower on d 63 than on d 7. Because the participants in this study were healthy, no clinical pathology end points were measured. However, results from the present study demonstrate that cherry consumption selectively reduced several biomarkers associated with inflammatory diseases.", "title": "Sweet bing cherries lower circulating concentrations of markers for chronic inflammatory diseases in healthy humans." }, { "docid": "MED-3888", "text": "BACKGROUND: Salmonella enterica causes an estimated 1 million cases of domestically acquired foodborne illness in humans annually in the United States; Enteritidis (SE) is the most common serotype. Public health authorities, regulatory agencies, food producers, and food processors need accurate information about rates and changes in SE infection to implement and evaluate evidence-based control policies and practices. METHODS: We analyzed the incidence of human SE infection during 1996-2009 in the Foodborne Diseases Active Surveillance Network (FoodNet), an active, population-based surveillance system for laboratory-confirmed infections. We compared FoodNet incidence with passively collected data from complementary surveillance systems and with rates of SE isolation from processed chickens and egg products; shell eggs are not routinely tested. We also compared molecular subtyping patterns of SE isolated from humans and chickens. RESULTS: Since the period 1996-1999, the incidence of human SE infection in FoodNet has increased by 44%. This change is mirrored in passive national surveillance data. The greatest relative increases were in young children, older adults, and FoodNet sites in the southern United States. The proportion of patients with SE infection who reported recent international travel has decreased in recent years, whereas the proportion of chickens from which SE was isolated has increased. Similar molecular subtypes of SE are commonly isolated from humans and chickens. CONCLUSIONS: Most SE infections in the United States are acquired from domestic sources, and the problem is growing. Chicken and eggs are likely major sources of SE. Continued close attention to surveillance data is needed to monitor the impact of recent regulatory control measures.", "title": "Salmonella enterica serotype Enteritidis: increasing incidence of domestically acquired infections." }, { "docid": "MED-2368", "text": "BACKGROUND: Microparticles (MPs) with procoagulant activity are present in human atherosclerosis, but no detailed information is available on their composition. METHODS AND RESULTS: To obtain insights into the role of MPs in atherogenesis, MP proteins were identified by tandem mass spectrometry, metabolite profiles were determined by high-resolution nuclear magnetic resonance spectroscopy, and antibody reactivity was assessed against combinatorial antigen libraries. Plaque MPs expressed surface antigens consistent with their leukocyte origin, including major histocompatibility complex classes I and II, and induced a dose-dependent stimulatory effect on T-cell proliferation. Notably, taurine, the most abundant free organic acid in human neutrophils, which scavenges myeloperoxidase-catalyzed free radicals, was highly enriched in plaque MPs. Moreover, fluorescent labeling of proteins on the MP surface suggested immunoglobulins to be trapped inside, which was confirmed by flow cytometry analysis on permeabilized and nonpermeabilized plaque MPs. Colabeling for CD14 and IgG established that more than 90% of the IgG containing MPs were CD14(+), indicating a macrophage origin. Screening against an antigen library revealed that the immunologic profiles of antibodies in MPs were similar to those found in plaques but differed profoundly from antibodies in plasma and unexpectedly, showed strong reactions with oligosaccharide antigens, in particular blood group antigen A. CONCLUSIONS: This study provides the first evidence that immunoglobulins are present within MPs derived from plaque macrophages, that the portfolio of plaque antibodies is different from circulating antibodies in plasma, and that anticarbohydrate antibodies are retained in human atherosclerotic lesions.", "title": "Proteomics, metabolomics, and immunomics on microparticles derived from human atherosclerotic plaques." }, { "docid": "MED-3092", "text": "BACKGROUND: Restriction of dietary phosphorus is a major aspect of patient care in those with renal disease. Restriction of dietary phosphorus is necessary to control for phosphate balance during both conservative therapy and dialysis treatment. The extra amount of phosphorus which is consumed as a result of phosphate-containing food additives is a real challenge for patients with renal disease and for dieticians because it represents a \"hidden\" phosphate load. The objective of this study was to measure phosphorus content in foods, common protein sources in particular, and comprised both those which included a listing of phosphate additives and those which did not. METHODS: Determinations of dry matter, nitrogen, total and soluble phosphate ions were carried out in 60 samples of foods, namely cooked ham, roast breast turkey, and roast breast chicken, of which, 30 were with declared phosphate additives and the other 30 similar items were without additives. RESULTS: Total phosphorus (290 ± 40 mg/100 g vs. 185 ± 23 mg/100 g, P < .001) and soluble phosphorus (164 ± 25 mg/100 g vs. 100 ± 19 mg/100 g, P < .001) content were higher in products containing additives than in foods without additives. No difference was detected between the 2 groups regarding dry matter (27.2 ± 2.0 g/100 g vs. 26.7 ± 1.9 g/100 g) or total nitrogen (3.15 ± 0.40 g/100 g vs. 3.19 ± 0.40 g/100 g). Consequently, phosphorus intake per gram of protein was much greater in the foods containing phosphorus additives (15.0 ± 3.1 mg/g vs. 9.3 ± 0.7 mg/g, P < .001). CONCLUSIONS: Our results show that those foods which contain phosphate additives have a phosphorus content nearly 70% higher than the samples which did not contain additives. This creates a special concern because this extra amount of phosphorus is almost completely absorbed by the intestinal tract. These hidden phosphates worsen phosphate balance control and increase the need for phosphate binders and related costs. Information and educational programs are essential to make patients with renal disease aware of the existence of foods with phosphate additives. Moreover, these facts highlight the need for national and international authorities to devote more attention to food labels which should clearly report the amount of natural or added phosphorus. Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.", "title": "Extra-phosphate load from food additives in commonly eaten foods: a real and insidious danger for renal patients." }, { "docid": "MED-4112", "text": "Co-stimulatory signals through the CD28 receptor enhance the survival of T cells that have their antigen receptor (TCR) engaged. Here we show that stimulation through the CD28 receptor in the absence of TCR engagement with either an anti-CD28 cross-linking antibody or the CD80 ligand transiently increases expression of the insulin-like growth factor-I receptor (IGF-IR) on T cells. Antibodies that block signaling through the IGF-IR decrease the survival of T cells activated through the TCR and CD28 in the presence of IL-2 by more than 50%, and also enhance susceptibility to Fas-induced apoptosis. CD28 stimulation increases IGF-IR expression on Jurkat cells, and exogenously added IGF-I can protect these cells from Fas-induced apoptosis. We conclude that CD28-mediated enhancement of IGF-IR expression provides activated T cells with essential survival signals that are independent of survival mediated by IL-2 and Bcl-xl.", "title": "The insulin-like growth factor-I receptor is regulated by CD28 and protects activated T cells from apoptosis." }, { "docid": "MED-3091", "text": "Phosphate toxicity is an important determinant of mortality in patients with chronic kidney disease (CKD), particularly those undergoing hemodialysis treatments. CKD patients are advised to take a low phosphate-containing diet, and are additionally prescribed with phosphate-lowering drugs. Since these patients usually seek guidance from their physicians and nurses for their dietary options, we conducted a survey to determine the levels of awareness regarding the high phosphate content in commercially processed food and drinks among medical and nursing students at the Hirosaki University School of Medicine in Japan. For this survey, 190 medical and nursing students (average age 21.7±3 years) were randomly selected, and provided with a list of questions aimed at evaluating their awareness of food and drinks containing artificially added phosphate ingredients. While 98.9% of these students were aware of the presence of sugar in commercially available soda drinks, only 6.9% were aware of the presence of phosphate (phosphoric acid). Similarly, only 11.6% of these students were aware of the presence of phosphate in commercially processed food, such as hamburgers and pizza. Moreover, around two thirds of the surveyed students (67.7%) were unaware of the harmful effects of unrestricted consumption of phosphate-containing food and drinks. About 28% of the surveyed students consume such “fast food” once a week, while 40% drink at least 1∼5 cans of soda drinks/week. After realizing the potential long-term risks of consuming excessive phosphate-containing food and drinks, 40.5% of the survey participants considered reducing their phosphate intake by minimizing the consumption of commercially processed “fast food” items and soda drinks. Moreover, another 48.4% of students showed interest in obtaining more information on the negative health effects of consuming excessive amounts of phosphate. This survey emphasizes the need for educational initiative to raise awareness of the health risks posed by excessive consumption of phosphate additives.", "title": "Lack of Awareness among Future Medical Professionals about the Risk of Consuming Hidden Phosphate-Containing Processed Food and Drinks" }, { "docid": "MED-3283", "text": "Available information indicates that long-lived mammals have low rates of reactive oxygen species (ROS) generation and oxidative damage at their mitochondria. On the other hand, many studies have consistently shown that dietary restriction (DR) in rodents also decreases mitochondrial ROS (mtROS) production and oxidative damage to mitochondrial DNA and proteins. It has been observed that protein restriction also decreases mtROS generation and oxidative stress in rat liver, whereas neither carbohydrate nor lipid restriction change these parameters. This is interesting because protein restriction also increases maximum longevity in rodents (although to a lower extent than DR) and is a much more practicable intervention for humans than DR, whereas neither carbohydrate nor lipid restriction seem to change rodent longevity. Moreover, it has been found that isocaloric methionine restriction also decreases mtROS generation and oxidative stress in rodent tissues, and this manipulation also increases maximum longevity in rats and mice. In addition, excessive dietary methionine also increases mtROS generation in rat liver. These studies suggest that the reduced intake of dietary methionine can be responsible for the decrease in mitochondrial ROS generation and the ensuing oxidative damage that occurs during DR, as well as for part of the increase in maximum longevity induced by this dietary manipulation. In addition, the mean intake of proteins (and thus methionine) of Western human populations is much higher than needed. Therefore, decreasing such levels to the recommended ones has a great potential to lower tissue oxidative stress and to increase healthy life span in humans while avoiding the possible undesirable effects of DR diets.", "title": "Lowered methionine ingestion as responsible for the decrease in rodent mitochondrial oxidative stress in protein and dietary restriction possible i..." }, { "docid": "MED-1250", "text": "The effect of plant and animal protein on blood lipid levels was investigated in eight healthy normolipidemic men aged 18 to 27 yr. All subjects were fed both plant and animal protein diets in a cross-over design. Each diet was consumed for a 21-day period. Proteins from commonly used plant sources made up the plant protein diet. Beef protein was substituted for 55% of the plant proteins in the animal protein diet. Fasting venous blood samples were collected at the beginning of the study and at 7-day intervals throughout the 42-day study. Serum was analyzed for total cholesterol and triglycerides. Plasma low-density and high-density lipoprotein cholesterol were determined. There were not any statistically significant differences in mean serum total cholesterol or mean plasma low-density lipoprotein cholesterol when subjects consumed the diets. Mean plasma high-density lipoprotein cholesterol levels were significantly (p less than 0.05) elevated at the end of the 21-day period when the animal protein diet was consumed (48 +/- 3 mg/dl) compared to the period when the plant protein diet was fed (42 +/- 2 mg/dl). Mean serum triglyceride values were significantly (p less than 0.05) increased at day 7 of the plant protein diet period (136 +/- 19 mg/dl) compared to the same time period when the animal protein diet was consumed (84 +/- 12 mg/dl). The results of the study indicated that the ingestion of a diet in which 55% of the protein was supplied by beef protein was not associated with a hypercholesterolemic effect in healthy normolipidemic young men.", "title": "A comparison of the effect of diets containing beef protein and plant proteins on blood lipids of healthy young men." }, { "docid": "MED-2581", "text": "A hospital-based case-control study of diet and colorectal cancer was conducted among Chinese in Singapore (who constitute 77% of the population). A total of 203 cases and 425 controls were included. A history of the usual dietary intake one year prior to interview was taken using a quantitative food frequency questionnaire. Daily intakes of nutrients and selected food items were computed and stratified by tertiles of the control range, to assess risk in low-, medium- and high-intake categories. Effects were adjusted in analysis for age, sex, Chinese dialect group and occupation. For cancers of colon and rectum combined, significant observations were a protective effect of high cruciferous vegetable intake (OR = 0.50, p less than 0.01) and a predisposing effect of a high meat/vegetable consumption ratio (OR = 1.77, p less than 0.05). Similar results were observed for colon cancer alone. For rectal cancer alone (only 71 cases), significant (p less than 0.05) protective effects were observed for high intakes of protein (OR = 0.61), fibre (OR = 0.46), beta-carotene (OR = 0.54), cruciferous vegetables (OR = 0.51) and total vegetables (OR = 0.51). When further assessed by multiple logistic regression, tests for trend and assessment of risk in the extreme highest and lowest quintiles of the control range, the factors consistently significant were cruciferous vegetable intake and the meat/vegetable ratio. A particularly high relative risk was also noted in association with low coffee consumption (OR = 1.59, with p less than 0.05 for trend). No consistent trends were noted for fat or fibre intakes. For non-dietary variables investigated, a history of cholecystectomy increased the risk of both cancers combined (OR = 3.43, p less than 0.05) and colon cancer alone (OR = 4.39, p less than 0.01). This study in an Asian population of countries of Southern and Eastern Asia newly undergoing industrialization and in which rapid economic change is reflected in changing cancer patterns, suggests that the protective effects of certain dietary constituents, notably the cruciferous vegetables, may be more important than the hitherto stressed carcinogenic potential of fat and protein.", "title": "Colorectal cancer and diet in an Asian population--a case-control study among Singapore Chinese." }, { "docid": "MED-3543", "text": "Inhibition of monoamine oxidase is one way to treat depression and anxiety. The information now available on the pharmacokinetics of flavonoids and of the components of tobacco prompted an exploration of whether a healthy diet (with or without smoking) provides active compounds in amounts sufficient to partially inhibit monoamine oxidase. A literature search was used to identify dietary monoamine oxidase inhibitors, the levels of these compounds in foods, the pharmacokinetics of the absorption and distribution, and tissue levels observed. An estimated daily intake and the expected tissue concentrations were compared with the measured efficacies of the compounds as inhibitors of monoamine oxidases. Norharman, harman and quercetin dietary presence, pharmacokinetics, and tissue levels were consistent with significant levels reaching neuronal monoamine oxidase from the diet or smoking; 1,2,3,4-tetrahydroisoquinoline, eugenol, 1-piperoylpiperidine, and coumarin were not. Quercetin was equipotent with norharman as a monoamine oxidase A inhibitor and its metabolite, isorhamnetin, also inhibits. Total quercetin was the highest of the compounds in the sample diet. Although bioavailability was variable depending on the source, a healthy diet contains amounts of quercetin that might give sufficient amounts in brain to induce, by monoamine oxidase A inhibition, a small decrease in neurotransmitter breakdown.", "title": "Dietary inhibitors of monoamine oxidase A." }, { "docid": "MED-1133", "text": "Background The last nationally representative assessment of kidney stone prevalence in the United States occurred in 1994. After a 13-yr hiatus, the National Health and Nutrition Examination Survey (NHANES) reinitiated data collection regarding kidney stone history. Objective Describe the current prevalence of stone disease in the United States, and identify factors associated with a history of kidney stones. Design, setting, and participants A cross-sectional analysis of responses to the 2007–2010 NHANES (n = 12 110). Outcome measurements and statistical analysis Self-reported history of kidney stones. Percent prevalence was calculated and multivariable models were used to identify factors associated with a history of kidney stones. Results and limitations The prevalence of kidney stones was 8.8% (95% confidence interval [CI], 8.1–9.5). Among men, the prevalence of stones was 10.6% (95% CI, 9.4–11.9), compared with 7.1% (95% CI, 6.4–7.8) among women. Kidney stones were more common among obese than normal-weight individuals (11.2% [95% CI, 10.0–12.3] compared with 6.1% [95% CI, 4.8–7.4], respectively; p < 0.001). Black, non-Hispanic and Hispanic individuals were less likely to report a history of stone disease than were white, non-Hispanic individuals (black, non-Hispanic: odds ratio [OR]: 0.37 [95% CI, 0.28–0.49], p < 0.001; Hispanic: OR: 0.60 [95% CI, 0.49–0.73], p < 0.001). Obesity and diabetes were strongly associated with a history of kidney stones in multivariable models. The cross-sectional survey design limits causal inference regarding potential risk factors for kidney stones. Conclusions Kidney stones affect approximately 1 in 11 people in the United States. These data represent a marked increase in stone disease compared with the NHANES III cohort, particularly in black, non-Hispanic and Hispanic individuals. Diet and lifestyle factors likely play an important role in the changing epidemiology of kidney stones.", "title": "Prevalence of Kidney Stones in the United States" }, { "docid": "MED-1335", "text": "AIMS: Diabetes rates are especially high in China. Risk of Type 2 diabetes increases with high intakes of white rice, a staple food of Chinese people. Ethnic differences in postprandial glycaemia have been reported. We compared glycaemic responses to glucose and five rice varieties in people of European and Chinese ethnicity and examined possible determinants of ethnic differences in postprandial glycaemia. METHODS: Self-identified Chinese (n = 32) and European (n = 31) healthy volunteers attended on eight occasions for studies following ingestion of glucose and jasmine, basmati, brown, Doongara(®) and parboiled rice. In addition to measuring glycaemic response, we investigated physical activity levels, extent of chewing of rice and salivary α-amylase activity to determine whether these measures explained any differences in postprandial glycaemia. RESULTS: Glycaemic response, measured by incremental area under the glucose curve, was over 60% greater for the five rice varieties (P < 0.001) and 39% greater for glucose (P < 0.004) amongst Chinese compared with Europeans. The calculated glycaemic index was approximately 20% greater for rice varieties other than basmati (P = 0.01 to 0.05). Ethnicity [adjusted risk ratio 1.4 (1.2-1.8) P < 0.001] and rice variety were the only important determinants of incremental area under the glucose curve. CONCLUSIONS: Glycaemic responses following ingestion of glucose and several rice varieties are appreciably greater in Chinese compared with Europeans, suggesting the need to review recommendations regarding dietary carbohydrate amongst rice-eating populations at high risk of diabetes. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.", "title": "Glycaemic responses to glucose and rice in people of Chinese and European ethnicity." }, { "docid": "MED-4318", "text": "Preliminary data in the literature indicate that iron absorption from a meal may be increased when consumed with low-pH beverages such as cola, and it is also possible that sugar iron complexes may alter iron availability. A randomized, crossover trial was conducted to compare the bioavailability of nonheme iron from a vegetarian pizza meal when consumed with 3 different beverages (cola, diet cola, and mineral water). Sixteen women with serum ferritin concentrations of 11-54 µg/L were recruited and completed the study. The pizza meal contained native iron and added ferric chloride solution as a stable isotope extrinsic label; the total iron content of the meal was ~5.3 mg. Incorporation of iron from the meal into RBC was not affected by the type of drink (9.9% with cola, 9.4% with diet cola, and 9.6% with water). Serum ferritin and plasma hepcidin were correlated (r = 0.66; P<0.001) and both were significant predictors of iron bioavailability, but their combined effect explained only 30% of the inter-individual variation (P<0.001) and illustrates the current lack of understanding of mechanisms responsible for the fine-tuning of iron absorption. Although there was no effect of low-pH drinks on iron bioavailability in healthy women, their effect on absorption of fortification iron that requires solubilization in dilute acid, such as reduced iron, and in individuals with low gastric acid production, such as older people and individuals with Helicobacter pylori infection, warrants further investigation.", "title": "Low-pH cola beverages do not affect women's iron absorption from a vegetarian meal." }, { "docid": "MED-4806", "text": "Escherichia coli is probably the best-known bacterial species and one of the most frequently isolated organisms from clinical specimens. Despite this, underappreciation and misunderstandings exist among medical professionals and the lay public alike regarding E. coli as an extraintestinal pathogen. Underappreciated features include (i) the wide variety of extraintestinal infections E. coli can cause, (ii) the high incidence and associated morbidity, mortality, and costs of these diverse clinical syndromes, (iii) the pathogenic potential of different groups of E. coli strains for causing intestinal versus extraintestinal disease, and (iv) increasing antimicrobial resistance. In this era in which health news often sensationalizes uncommon infection syndromes or pathogens, the strains of E. coli that cause extraintestinal infection are an increasingly important endemic problem and underappreciated \"killers\". Billions of health care dollars, millions of work days, and hundreds of thousands of lives are lost each year to extraintestinal infections due to E. coli. New treatments and prevention measures will be needed for improved outcomes and a diminished disease burden.", "title": "Medical and economic impact of extraintestinal infections due to Escherichia coli: focus on an increasingly important endemic problem." }, { "docid": "MED-3311", "text": "OBJECTIVES: We studied mortality in two separate cohorts of workers in abattoirs (N=4996) and meat processing plants (N=3642) belonging to a meatcutters' union, because they were exposed to viruses that cause cancer in food animals, and also to chemical carcinogens at work. METHODS: Standardized mortality ratios (SMRs) and proportional mortality ratios (PMRs) were estimated for each cohort as a whole and in subgroups defined by race and sex, using the US general population mortality rates for comparison. Study subjects were followed up from January 1950 to December 2006, during which time over 60% of them died. RESULTS: An excess of deaths from cancers of the base of the tongue, esophagus, lung, skin, bone and bladder, lymphoid leukemia, and benign tumors of the thyroid and other endocrine glands, and possibly Hodgkin's disease, was observed in abattoir and meat processing workers. Significantly lower SMRs were recorded for cancer of the thymus, mediastinum, pleura, etc., breast cancer, and non-Hodgkin's lymphoma. CONCLUSION: This study confirms the excess occurrence of cancer in workers in abattoirs and meat processing plants, butchers, and meatcutters, previously reported in this cohort and other similar cohorts worldwide. Large nested case-control studies are now needed to examine which specific occupational and non-occupational exposures are responsible for the excess. There is now sufficient evidence for steps to be taken to protect workers from carcinogenic exposures at the workplace. There are also serious implications for the general population which may also be exposed to some of these viruses. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Cancer mortality in workers employed in cattle, pigs, and sheep slaughtering and processing plants." }, { "docid": "MED-2357", "text": "Patients with cancer have circulating heterophile antibodies that agglutinate animal red cells via recognition of the mammalian cell surface sialic acid N-glycolylneuraminic acid (Neu5Gc), which was long considered an oncofetal antigen in humans. However, humans are genetically deficient in Neu5Gc production and instead metabolically accumulate Neu5Gc from dietary sources, particularly red meats and milk products. Moreover, mice with a human-like defect showed no alternate pathway for Neu5Gc synthesis and even normal humans express anti-Neu5Gc antibodies. We show here that human tumors accumulate Neu5Gc that is covalently attached to multiple classes of glycans. The paradox of human tumor Neu5Gc accumulation in the face of circulating anti-Neu5Gc antibodies was hypothesized to be due to facilitation of tumor progression by the resulting low-grade chronic inflammation. Indeed, murine tumors expressing human-like levels of Neu5Gc show accelerated growth in syngeneic mice with a human-like Neu5Gc deficiency, coincident with the induction of anti-Neu5Gc antibodies and increased infiltration of inflammatory cells. Transfer of polyclonal monospecific syngeneic mouse anti-Neu5Gc serum also enhanced growth of transplanted syngeneic tumors bearing human-like levels of Neu5Gc, with tumors showing evidence for antibody deposition, enhanced angiogenesis and chronic inflammation. These effects were suppressed by a cyclooxygenase-2 inhibitor, a drug type known to reduce human carcinoma risk. Finally, affinity-purified human anti-Neu5Gc antibodies also accelerate growth of Neu5Gc-containing tumors in Neu5Gc-deficient mice. Taken together, the data suggest that the human propensity to develop diet-related carcinomas is contributed to by local chronic inflammation, resulting from interaction of metabolically-accumulated dietary Neu5Gc with circulating anti-Neu5Gc antibodies.", "title": "Evidence for a human-specific mechanism for diet and antibody-mediated inflammation in carcinoma progression" }, { "docid": "MED-4847", "text": "Clinical experience suggests that fasting followed by vegetarian diet may help patients with rheumatoid arthritis (RA). We reviewed the available scientific evidence, because patients frequently ask for dietary advice, and exclusive pharmacological treatment of RA is often not satisfying. Fasting studies in RA were searched in MEDLINE and by checking references in relevant reports. The results of the controlled studies which reported follow-up data for at least three months after fasting were quantitatively pooled. Thirty-one reports of fasting studies in patients with RA were found. Only four controlled studies investigated the effects of fasting and subsequent diets for at least three months. The pooling of these studies showed a statistically and clinically significant beneficial long-term effect. Thus, available evidence suggests that fasting followed by vegetarian diets might be useful in the treatment of RA. More randomised long-term studies are needed to confirm this view by methodologically convincing data.", "title": "Fasting followed by vegetarian diet in patients with rheumatoid arthritis: a systematic review." }, { "docid": "MED-1165", "text": "The cooking-induced changes in the levels of polybrominated diphenyl ethers (PBDEs), hexachlorobenzene (HCB), and 16 polycyclic aromatic hydrocarbons (PAHs) in various foodstuffs were investigated. Foods included fish (sardine, hake and tuna), meat (veal steak, loin of pork, breast and thigh of chicken, and steak and rib of lamb), string bean, potato, rice, and olive oil. For each food item, raw and cooked (fried, grilled, roasted, boiled) samples were analyzed. There were some variations in the concentrations of PBDEs before and after cooking. However, they depended not only on the cooking process, but mainly on the specific food item. The highest HCB concentrations were found in sardine, being lower in cooked samples. All cooking processes enhanced HCB levels in hake, while very scarce differences could be noted in tuna (raw and cooked). In general terms, the highest PAH concentrations were found after frying by being the values especially notable in fish, excepting hake, where the highest total PAH levels corresponded to roasted samples. The results of this study show that, in general, cooking processes are only of a limited value as a means of reducing PBDE, HCB and PAH concentrations in food.", "title": "Concentrations of polybrominated diphenyl ethers, hexachlorobenzene and polycyclic aromatic hydrocarbons in various foodstuffs before and after coo..." }, { "docid": "MED-2512", "text": "Ageing is a challenge for any living organism and human longevity is a complex phenotype. With increasing life expectancy, maintaining long-term health, functionality and well-being during ageing has become an essential goal. To increase our understanding of how ageing works, it may be advantageous to analyze the phenotype of centenarians, perhaps one of the best examples of successful ageing. Healthy ageing involves the interaction between genes, the environment, and lifestyle factors, particularly diet. Besides evaluating specific gene-environment interactions in relation to exceptional longevity, it is important to focus attention on modifiable lifestyle factors such as diet and nutrition to achieve extension of health span. Furthermore, a better understanding of human longevity may assist in the design of strategies to extend the duration of optimal human health. In this article we briefly discuss relevant topics on ageing and longevity with particular focus on dietary patterns of centenarians and nutrient-sensing pathways that have a pivotal role in the regulation of life span. Finally, we also discuss the potential role of Nrf2 system in the pro-ageing signaling emphasizing its phytohormetic activation.", "title": "Extending healthy ageing: nutrient sensitive pathway and centenarian population" }, { "docid": "MED-1138", "text": "PURPOSE: We compared the effect of 3 animal protein sources on urinary stone risk. MATERIALS AND METHODS: A total of 15 healthy subjects completed a 3-phase randomized, crossover metabolic study. During each 1-week phase subjects consumed a standard metabolic diet containing beef, chicken or fish. Serum chemistry and 24-hour urine samples collected at the end of each phase were compared using mixed model repeated measures analysis. RESULTS: Serum and urinary uric acid were increased for each phase. Beef was associated with lower serum uric acid than chicken or fish (6.5 vs 7.0 and 7.3 mg/dl, respectively, each p <0.05). Fish was associated with higher urinary uric acid than beef or chicken (741 vs 638 and 641 mg per day, p = 0.003 and 0.04, respectively). No significant difference among phases was noted in urinary pH, sulfate, calcium, citrate, oxalate or sodium. Mean saturation index for calcium oxalate was highest for beef (2.48), although the difference attained significance only compared to chicken (1.67, p = 0.02) but not to fish (1.79, p = 0.08). CONCLUSIONS: Consuming animal protein is associated with increased serum and urine uric acid in healthy individuals. The higher purine content of fish compared to beef or chicken is reflected in higher 24-hour urinary uric acid. However, as reflected in the saturation index, the stone forming propensity is marginally higher for beef compared to fish or chicken. Stone formers should be advised to limit the intake of all animal proteins, including fish. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.", "title": "Animal protein and the risk of kidney stones: a comparative metabolic study of animal protein sources." }, { "docid": "MED-3356", "text": "OBJECTIVE: This study examined changes in desires to eat high-fat and low-fat foods across an obesity treatment program. The hypotheses under examination were (1) preferences for low-fat foods would increase across time and (2) preferences for high-fat foods would decrease across time. DESIGN: Single-group, prospective examination of desires to eat 48 foods, categorized according to fat content, before and after the 16-week treatment program. SETTING: University clinic, Memphis, Tennessee. PARTICIPANTS: 118 obese (mean weight = 194.4 lbs) women (mean age = 45.24 years) participating in an obesity treatment program. INTERVENTION: A 16-week cognitive-behavioral program for obesity. VARIABLES MEASURED: Desires to eat 48 foods varying in fat content and whether or not participants actually ate these foods. ANALYSIS: Analysis of variance, multiple regression, and paired t tests. RESULTS: The results indicate that during the program, preferences for low-fat foods increased, whereas preferences for high-fat foods decreased. These changes mirrored the changes in consumption of both low-fat and high-fat foods. CONCLUSIONS AND IMPLICATIONS: Within a behavioral economic perspective, the reinforcement value of low-fat foods may increase following a low-fat dietary intervention, whereas the reinforcing properties of high-fat foods may decline. This is desirable as low-fat foods hold many advantages over high-fat foods in terms of weight maintenance.", "title": "Desire to eat high- and low-fat foods following a low-fat dietary intervention." }, { "docid": "MED-3931", "text": "Although a plant-based diet can provide some benefits in Parkinson's disease (PD), no study to date has evaluated the effectiveness of a plant-food diet in the management of the disease. In this pilot study, we compared the effect of a plant-food menu (PFD) and of a omnivorous menu on motor performance of 25 PD patients, 12 in the intervention group (PDi) and 13 in the control group (PDc). After 4 weeks, the PDi group showed a significant reduction (Mann-Whitney test) in the Unified Parkinson's Disease Rating Scale, total score (47.67 vs. 74.46, P = 0.008) and sub-score III motor performances (25.42 vs. 46.46, P = 0.001), and the modified Hoehn and Yahr Staging Scale (1.96 vs. 3.15, P = 0.005). These data suggest that PFD may be useful in the management of PD patients by improving their motor performances. Additional studies are needed in order to confirm these preliminary results.", "title": "Pilot dietary study with normoproteic protein-redistributed plant-food diet and motor performance in patients with Parkinson's disease." }, { "docid": "MED-1447", "text": "Background/objectives: To assess the effects on macro- and micronutrient intake of a nutrition intervention program in corporate settings across the United States. Subjects/methods: Two hundred and ninety-two individuals who were overweight or had type 2 diabetes were recruited from 10 sites of a US insurance company. Two hundred and seventy-one participants completed baseline diet recalls, and 183 participants completed dietary recalls at 18 weeks. Sites were randomly assigned to an intervention group (five sites) or to a control group (five sites) for 18 weeks. At intervention sites, participants were asked to follow a low-fat vegan diet and attend weekly group meetings. At control sites, participants continued their usual diets. At baseline and 18 weeks, participants completed 2-day diet recalls. Between-group differences in changes in nutrient intake were assessed using an analysis of covariance. Results: Compared with those in the control group, intervention-group participants significantly reduced the reported intake of total fat (P=0.02), saturated (P=0.006) and monounsaturated fats (P=0.01), cholesterol (P=0.009), protein (P=0.03) and calcium (P=0.02), and increased the intake of carbohydrate (P=0.006), fiber (P=0.002), β-carotene (P=0.01), vitamin C (P=0.003), magnesium (P=0.04) and potassium (P=0.002). Conclusions: An 18-week intervention program in a corporate setting reduces intake of total fat, saturated fat and cholesterol and increases the intake of protective nutrients, particularly fiber, β-carotene, vitamin C, magnesium and potassium. The reduction in calcium intake indicates the need for planning for this nutrient.", "title": "Nutrient intake in the GEICO multicenter trial: the effects of a multicomponent worksite intervention" }, { "docid": "MED-2252", "text": "Studies suggested the intake of Cd from diet can be approximately equivalent to that from smoking. Moreover, a mutual metabolic influence between Cd and nutrients has been reported. The purpose of this study was to evaluate the relationship between blood cadmium concentration (BCdC) and food consumption, nutrients intake (Ca, Fe, Zn, vitamin C, and vitamin D), tobacco smoking, and some other variables (age, body mass index, and residence) in 243 adults living in the Italian island of Sardinia (Sassari Province). Specifically, we hypothesized that offal consumption contributes to Cd intakes and blood levels. The BCdC was quantified by graphite furnace atomic absorption spectrometry, and information on personal data was collected through questionnaires. Smoke significantly contributed to the BCdC (P < .001). Nonsmoker subjects who eat offal showed significantly higher BCdC (P = .04). Moreover, slightly higher BCdCs were also observed in nonsmoker subjects who eat rice, fish, and bread. The BCdC positively correlated with age of subjects (r = 0.144; P = .025) and offal daily intake in nonsmokers (r = 0.393; P < .001). The intake of Ca was negatively correlated (r = -0.281; P = .001) with the BCdC in females. The multiple linear regression analysis showed smoking > consumption of offal > body mass index ≈ age as the most important risk factors for the BCdC in the selected population. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Diet and nutrients are contributing factors that influence blood cadmium levels." }, { "docid": "MED-4433", "text": "BACKGROUND: The role of zoonotic biological agents in human cancer occurrence has been little studied. Humans are commonly exposed to viruses that naturally infect and cause cancer in food animals such as poultry that constitute part of the biological environment. It is not known if these viruses cause cancer in humans. OBJECTIVE: To study cancer mortality in the largest cohort to date, of 20,132 workers in poultry slaughtering and processing plants, a group with the highest human exposures to these viruses. METHODS: Mortality in poultry workers was compared with that in the US general population through the estimation of standardized mortality ratios. RESULTS: Significantly increased risks were observed in the cohort as a whole or in subgroups, for several cancer sites, viz: cancers of the buccal cavity and pharynx; pancreas; trachea/bronchus/lung; brain; cervix; lymphoid leukemia; monocytic leukemia; and tumors of the hemopoietic and lymphatic systems. Elevated SMRs that were not statistically significant were observed for cancers of the liver, nasopharynx, myelofibrosis, and myeloma. New sites observed to be significantly in excess in this study were cancers of the cervix and penis. CONCLUSION: This large study provides evidence that a human group with high exposure to poultry oncogenic viruses has increased risk of dying from several cancers. Other occupational carcinogenic exposures could be of importance in explaining some of the findings, such as fumes from wrapping machines. These findings may have implications for public health amongst persons in the general population who may also be exposed to these viruses. What is needed now are epidemiologic studies that can demonstrate whether the excess of specific cancers can be attributed to specific occupational exposures while adequately controlling for other potential occupational and non-occupational carcinogenic exposures. Copyright 2010 Elsevier Inc. All rights reserved.", "title": "Cancer mortality in poultry slaughtering/processing plant workers belonging to a union pension fund." }, { "docid": "MED-3542", "text": "The behavior of inhibitors of monoamine oxidase-A (MAO-A) is considered in terms of the possibility of having an effective antidepressant that does not give rise to hypertensive interactions with dietary tyramine. Studies with punch-biopsy samples of human intestine and rat intestinal samples show MAO-A to be the predominant form of the enzyme in both species. Transport studies with everted rat intestinal preparations indicate that tyramine is extensively metabolized during transport through the intestine. Selective inhibition of MAO-A by clorgyline results in a large increase in the amount of unchanged tyramine transported, whereas selective inhibition of MAO-B with L-deprenyl (selegiline) has no significant effect. The behavior of reversible MAO-A inhibitors can significantly reduce, but not entirely eliminate, these effects on the intestinal metabolism of tyramine, but only if the inhibition is competitive in nature.", "title": "Monoamine oxidase inhibitors and the cheese effect." }, { "docid": "MED-4878", "text": "Background Telomere length reflects biological aging and may be influenced by environmental factors, including those that affect inflammatory processes. Objective With data from 840 white, black, and Hispanic adults from the Multi-Ethnic Study of Atherosclerosis, we studied cross-sectional associations between telomere length and dietary patterns and foods and beverages that were associated with markers of inflammation. Design Leukocyte telomere length was measured by quantitative polymerase chain reaction. Length was calculated as the amount of telomeric DNA (T) divided by the amount of a single-copy control DNA (S) (T/S ratio). Intake of whole grains, fruit and vegetables, low-fat dairy, nuts or seeds, nonfried fish, coffee, refined grains, fried foods, red meat, processed meat, and sugar-sweetened soda were computed with responses to a 120-item food-frequency questionnaire completed at baseline. Scores on 2 previously defined empirical dietary patterns were also computed for each participant. Results After adjustment for age, other demographics, lifestyle factors, and intakes of other foods or beverages, only processed meat intake was associated with telomere length. For every 1 serving/d greater intake of processed meat, the T/S ratio was 0.07 smaller (β ± SE: −0.07 ± 0.03, P = 0.006). Categorical analysis showed that participants consuming ≥1 serving of processed meat each week had 0.017 smaller T/S ratios than did nonconsumers. Other foods or beverages and the 2 dietary patterns were not associated with telomere length. Conclusions Processed meat intake showed an expected inverse association with telomere length, but other diet features did not show their expected associations.", "title": "Dietary patterns, food groups, and telomere length in the Multi-Ethnic Study of Atherosclerosis (MESA)" }, { "docid": "MED-3787", "text": "Background Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8). Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.", "title": "11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma" }, { "docid": "MED-3801", "text": "21 patients with severe persistent cyclical mastopathy of at least 5 years' duration were randomised to a control group who received general dietary advice or to an intervention group who were taught how to reduce the fat content of their diet to 15% of calories while increasing complex carbohydrate consumption to maintain caloric intake. Both groups were followed for 6 months with food records and measurement of plasma hormone and lipid levels. Severity of symptoms was recorded with daily diaries and patients were assessed at the beginning and end of the study by a physician who was unaware of their dietary regimen. After 6 months there was a significant reduction in the intervention group in the severity of premenstrual breast tenderness and swelling. Physical examination showed reduced breast swelling, tenderness, and nodularity in 6 of 10 patients in the intervention group and 2 of 9 patients in the control group.", "title": "Effect of a low-fat high-carbohydrate diet on symptoms of cyclical mastopathy." }, { "docid": "MED-1781", "text": "BACKGROUND: Saturated fat intake has been associated with both cardiovascular disease and cancer risk, and a newly published study found an association between saturated fat intake and a lower sperm concentration in infertile men. OBJECTIVE: The objective was to examine the association between dietary fat intake and semen quality among 701 young Danish men from the general population. DESIGN: In this cross-sectional study, men were recruited when they were examined to determine their fitness for military service from 2008 to 2010. They delivered a semen sample, underwent a physical examination, and answered a questionnaire comprising a quantitative food-frequency questionnaire to assess food and nutrient intakes. Multiple linear regression analyses were performed with semen variables as outcomes and dietary fat intakes as exposure variables, adjusted for confounders. RESULTS: A lower sperm concentration and total sperm count in men with a high intake of saturated fat was found. A significant dose-response association was found, and men in the highest quartile of saturated fat intake had a 38% (95% CI: 0.1%, 61%) lower sperm concentration and a 41% (95% CI: 4%, 64%) lower total sperm count than did men in the lowest quartile. No association between semen quality and intake of other types of fat was found. CONCLUSIONS: Our findings are of potentially great public interest, because changes in diet over the past decades may be part of the explanation for the recently reported high frequency of subnormal human sperm counts. A reduction in saturated fat intake may be beneficial for both general and reproductive health.", "title": "High dietary intake of saturated fat is associated with reduced semen quality among 701 young Danish men from the general population." }, { "docid": "MED-3295", "text": "Background Few studies have investigated mortality in seafood workers worldwide, and no such study has been conducted in the United States. The objective of this study was to investigate mortality in American seafood workers. Methods The study population was derived from 4 states and consisted of 4116 subjects who worked mainly in seafood processing plants. They were followed up from 1966 to 2003. Standardized mortality ratios (SMRs) and proportional mortality ratios (PMRs) were estimated, using the US general population for comparison. Results About 45% of the cohort was born after 1949. A total of 788 deaths were recorded; 53% of the decedents were female, and 88% were white. The SMRs for stomach cancer and disorders of the thyroid gland in the cohort as a whole were 2.1 (95% confidence interval [CI], 1.1–3.8) and 6.1 (95% CI 1.3–18.0), respectively. The SMRs for breast cancer, and occlusion/stenosis of the pre-cerebral/cerebral arteries in the cohort as a whole were 0.5 (95% CI, 0.3–0.9) and 0.5 (95% CI, 0.2–0.8), respectively. The SMR for ischemic heart disease in white females was 0.8 (95% CI, 0.6–0.9). Conclusions This cohort had excess deaths from stomach cancer and disorders of the thyroid gland, and deficit of deaths from breast cancer, stroke and ischemic heart disease. The significance of these findings is unknown, especially as less than 20% of the cohort were deceased. Nevertheless, the cohort is unique and important, and further follow-up may shed more light on mortality patterns in this occupational group.", "title": "Cancer and Noncancer Mortality Among American Seafood Workers" }, { "docid": "MED-3321", "text": "Avian leukosis/sarcoma viruses (ALSV) infect and cause cancers in chickens. Poultry workers are exposed to ALSV and other infectious agents in the workplace. This study examines if industrial hygiene assessment of antibody levels in poultry workers can identify risky job tasks at the higher exposure risk to an infectious agent, i.e., ALSV. We compared ALSV antibody levels in poultry workers and control subjects. Occupational and demographical factors were examined for an association with the exposure risk in poultry workers. We found that the antibody levels were significantly higher in poultry workers than in control subjects. Job category and age together were significantly associated with the antibody levels in workers. Certain job tasks were identified with significantly higher antibody levels as compared to others, implying that recommendations should be made to protect workers at these jobs. The findings of this study indicate that the measurement of antibody levels in workers can be useful for industrial hygiene assessment of exposure to infectious agents.", "title": "Occupational exposure assessment using antibody levels: exposure to avian leukosis/sarcoma viruses in the poultry industry." }, { "docid": "MED-4765", "text": "BACKGROUND: Previous studies on the association between macronutrient intake and the development of abdominal obesity, which carries an increased health risk, have not shown a consistent pattern, possibly due to mixed effects of other aspects of the food intake. OBJECTIVE: This study investigated the association between intake from 21 food and beverage groups and the subsequent 5-year difference in waist circumference. METHODS: The study population consisted of 22,570 women and 20,126 men, aged 50 to 64 years at baseline, with complete data on baseline and follow-up waist circumference, baseline diet (192 items food frequency questionnaire), body mass index, and selected potential confounders (eg, smoking status, sport activities, and intake of alcoholic beverages). Multiple linear regression analyses were performed. RESULTS: For women, 5-year difference in waist circumference was inversely related to intake from red meat, vegetables, fruit, butter, and high-fat dairy products, whereas intake from potatoes, processed meat, poultry, and snack foods was positively associated. For men, red meat and fruit intakes were inversely associated with 5-year difference in waist circumference, whereas snack foods intake was positively associated. Sex differences occurred for vegetables, high-fat dairy products, and processed meat. CONCLUSIONS: The results suggest that a diet low in fruits and red meat and high in snack foods was associated with larger waist circumference gains in both sexes. Furthermore, in women a diet low in vegetables, butter, and high-fat dairy products, and high in poultry, potatoes, and processed meat were likely determinants of subsequent gain at the waist.", "title": "Dietary predictors of 5-year changes in waist circumference." }, { "docid": "MED-3232", "text": "High dietary acid load (DAL) may be detrimental to bone mineral density (BMD). The objectives of the study were to: 1) evaluate the cross-sectional relation between DAL and BMD; 2) determine whether calcium intake modifies this association. Men (n=1218) and women (n=907) ≥60y were included from the National Health and Nutrition Examination Survey 2005–2008. Nutrient intake from 2–24h recalls was used to calculate net endogenous acid production (NEAP) and potential renal acid load (PRAL) (mEq/d). PRAL was calculated from dietary calcium (PRALdiet) and diet + supplemental calcium (PRALtotal). Tests for linear trend in adjusted mean BMD of the hip and lumbar spine were performed across energy adjusted NEAP and PRAL quartiles. Modification by calcium intake (dietary or total) above or below 800 mg/d was assessed by interaction terms. Overall, mean age was 69 ± 0.3y. Among women, there was no association between NEAP and BMD. PRALdiet was positively associated with proximal femur BMD (p trend=0.04). No associations were observed with PRALtotal at any BMD site (P-range: 0.38–0.82). Among men, no significant associations were observed of BMD with NEAP or PRAL. However, an interaction between PRALdiet and calcium intake was observed with proximal femur BMD (p=0.08). An inverse association between PRALdiet and proximal femur BMD was detected among men <800 mg/d dietary calcium (p=0.02); and no associations ≥800 mg/d (p=0.98). A significant interaction with PRALtotal was not observed. In conclusion, when supplemental calcium is considered, there is no association between DAL and BMD among adults. Men with low dietary calcium showed an inverse relation with PRAL at the proximal femur; in women no interaction was observed. This study highlights the importance of calcium intakes in counteracting the adverse effect of DAL on bone health. Further research should determine the relation between DAL and change in BMD with very low calcium intake.", "title": "Dietary acid load is associated with lower bone mineral density in men with low intake of dietary calcium" }, { "docid": "MED-4231", "text": "OBJECTIVE: To analyze the relationship between onion and garlic intake and benign prostatic hyperplasia (BPH), using data from a multicenter case-control study conducted in Italy. METHODS: A multicenter case-control study of 1369 patients with BPH and 1451 controls, admitted to the same hospitals for a wide spectrum of acute, non-neoplastic conditions, was conducted in Italy between 1991 and 2002. Information was collected by trained interviewers using a validated and reproducible food frequency questionnaire. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were obtained after allowance for recognized confounding factors and energy intake. RESULTS: Compared with nonusers, the multivariate ORs for the highest category of onion and garlic intake were 0.41 (95% CI 0.24 to 0.72) and 0.72 (95% CI 0.57 to 0.91), respectively. The combined OR for frequent users versus nonusers of both onion and garlic was 0.65 (95% CI 0.49 to 0.86). The inverse relationships were consistent across age strata. CONCLUSIONS: This uniquely large data set from European populations showed an inverse association between allium vegetable consumption and BPH.", "title": "Onion and garlic intake and the odds of benign prostatic hyperplasia." }, { "docid": "MED-3593", "text": "The aim of this study was to determine the accumulation of selected heavy metals (Pb, Cd, Hg, As) in meat and liver of cattle. The animals were divided into four age-groups which allowed the analysis of statistical-mathematical correlations between the age of the animals and contamination of meat. The research material for determination of heavy metal levels was taken from the longissimus back muscle (m. longissimus dorsi) and samples from the tail lobe of the liver. Analysis showed that contamination by Cd and Pb is clearly dependent on the age of the animal.", "title": "Correlation of lead, cadmium and mercury levels in tissue and liver samples with age in cattle." }, { "docid": "MED-2112", "text": "Medical students in the United States are taught little about nutrition and dietetics. Worse yet, their training biases them against the studies that show the power of dietary approaches to managing disease. The current approach to evidence-based medicine encourages physicians to ignore any information that does not come from a double-blind, randomized controlled trial. Yet human beings cannot be blinded to a dietary intervention. As a result, physicians are biased toward drug treatments and against dietary interventions for the management of chronic disease. Copyright © 2013 Elsevier Ltd. All rights reserved.", "title": "How evidence-based medicine biases physicians against nutrition." }, { "docid": "MED-3306", "text": "OBJECTIVES: Occupation as a farmer has been associated with increased risks of haematological cancers in adults. This study aimed to examine whether farm exposures in childhood contribute to these risks, by using parental occupation in farming as a proxy for growing up on a farm. METHODS: New Zealand death records (1998-2003) of persons aged 35-85 were extracted (n=114 289). For 82.3% usual occupation and the occupation of at least one of the parents could be coded (n=94 054). Unconditional logistic regression analyses included 3119 haematological cancer deaths (cases) and 90 935 deaths from other causes (controls). ORs for farming and growing up on a farm were adjusted for each other, year of birth, age at death, socio-economic status, Māori ethnicity, immigration status and sex. RESULTS: Growing up on a livestock farm was positively associated with haematological cancer (OR 1.22, 95% CI 1.05 to 1.41), particularly for poultry farms (OR 2.99, 95% CI 1.44 to 6.21), while growing up on a crop farm was not (OR 0.81, 95% CI 0.64 to 1.03). Crop farming in adulthood was associated with an increased haematological cancer risk (OR 1.49, 95% CI 1.13 to 1.96), while livestock farming was not (OR 0.80, 95% CI 0.63 to 1.00), except for beef cattle farming (OR 2.99, 95% CI 1.28 to 7.00). These results did not change appreciably when different control groups with different causes of death were used. CONCLUSIONS: These results could suggest a role for early life biological exposures in the development of haematological cancers.", "title": "Farming, growing up on a farm, and haematological cancer mortality." }, { "docid": "MED-4678", "text": "The aim of this study was to obtain a better understanding of the role of hormonal factors in breast cancer risk and to determine whether the effect of reproductive events differs according to age at diagnosis. It analysed the effect of age at menarche, age at first full-term pregnancy, number of full-term pregnancies and number of spontaneous abortions both on the overall risk of breast cancer and on its pre- or postmenopausal onset, using the data on 1718 breast cancer cases, obtained from a large sample of around 100 000 French women participating in the E3N cohort study. The results provide further evidence that the overall risk of breast cancer increases with decreasing age at menarche, increasing age at first pregnancy and low parity. No overall effect of spontaneous abortions was observed. The effect of these reproductive factors differed according to menopausal status. Age at menarche had an effect on premenopausal breast cancer risk, with a decrease in risk with increasing age of 7% per year (P<0.05). Compared to those who had their first menstrual periods at 11 or before, women experiencing menarche at 15 or after had an RR of 0.66 (95% CI 0.45–0.97) in the premenopausal group. Age at first full-term pregnancy had an effect on both pre- and postmenopausal breast cancer risk, with significant tests showing increasing risk per year of increasing age (P=0.001 and P<0.05 respectively). A first full-term pregnancy above age 30 conveyed a risk of 1.63 (95% CI 1.12–2.38) and 1.35 (95% CI 1.02–1.78) in the pre- and postmenopausal groups respectively. A protective effect of high parity was observed only for postmenopausal breast cancer risk (P for trend test =0.001), with point estimates of 0.79 (95% CI 0.60–1.04), 0.69 (95% CI 0.54–0.88), 0.66 (95% CI 0.51–0.85) and 0.64 (95% CI 0.48–0.86) associated to a one, two, three and four or more full-term pregnancies. A history of spontaneous abortion had no significant effect on the risk of breast cancer diagnosed before or after menopause. Our results suggest that reproductive events have complex effects on the risk of breast cancer. British Journal of Cancer (2002) 86, 723–727. DOI: 10.1038/sj/bjc/6600124 www.bjcancer.com © 2002 Cancer Research UK", "title": "Differential effects of reproductive factors on the risk of pre- and postmenopausal breast cancer. Results from a large cohort of French women" }, { "docid": "MED-1999", "text": "Diabetes is a major and growing public health challenge which threatens to overwhelm medical services in the future. Type 2 diabetes confers significant morbidity and mortality, most notably with target organ damage to the eyes, kidneys, nerves and heart. The magnitude of cardiovascular risk associated with diabetes is best illustrated by its position as a coronary heart disease risk equivalent. Complications related to neuropathy are also vast, often working in concert with vascular abnormalities and resulting in serious clinical consequences such as foot ulceration. Increased understanding of the natural history of this disorder has generated the potential to intervene and halt pathological progression before overt disease ensues, after which point management becomes increasingly challenging. The concept of prediabetes as a formal diagnosis has begun to be translated from the research setting to clinical practice, but with continually updated guidelines, varied nomenclature, emerging pharmacotherapies and an ever-changing evidence base, clinicians may be left uncertain of best practice in identifying and managing patients at the prediabetic stage. This review aims to summarize the epidemiological data, new concepts in disease pathogenesis and guideline recommendations in addition to lifestyle, pharmacological and surgical therapies targeted at stopping progression of prediabetes to diabetes. While antidiabetic medications, with newer anti-obesity medications and interventional bariatric procedures have shown some promising benefits, diet and therapeutic lifestyle change remains the mainstay of management to improve the metabolic profile of individuals with glucose dysregulation. New risk stratification tools to identify at-risk individuals, coupled with unselected population level intervention hold promise in future practice.", "title": "Strategies for preventing type 2 diabetes: an update for clinicians" }, { "docid": "MED-3452", "text": "Vitamins have traditionally been considered as food components that are required in the normal diet to prevent deficiencies. However, a newer concept of the function of vitamins in nutrition has taken them beyond simply prevention of deficiency symptoms. This concept considers that many vitamins, when taken in relatively large doses, have important functions beyond preventing deficiencies. Linus Pauling was instrumental in putting forward this concept, particularly for vitamin C. Thus, relatively high intakes of vitamins, and in particular vitamins C and E which are antioxidants, are considered to be healthy for the human population. This may be true in some special situations such as, for instance, the prevention of Alzheimer's disease progression. However, recent epidemiological evidence has not supported the claim that antioxidant vitamins increase well-being and prolong life span. In fact, vitamin supplementation may be even detrimental and reduce life span. A new concept that we would like to put forward is that nutrients up-regulate the endogenous antioxidant defences. This is particularly true in the case of phytoestrogens for example, which bind to oestrogen receptors and eventually up-regulate the expression of antioxidant genes. In this review we discuss the pros and cons of antioxidant vitamin supplementation and also the possibility that the ingestion of some nutrients may be very effective in increasing antioxidant defences by up-regulating the activity of antioxidant enzymes which are normally present in the cell.", "title": "Fostering antioxidant defences: up-regulation of antioxidant genes or antioxidant supplementation?" }, { "docid": "MED-1985", "text": "The relationship between diet and attained height was studied in children and adolescents in Southern California. Diet pattern was determined from an extensive food frequency questionnaire in 1765 Caucasian children of 7-18 years, attending state schools (452 m and 443 f) and Seventh-day Adventist schools (427 m and 443 f). The major difference in diet pattern between state and Adventist school children was in meat consumption. The Adventist children were split evenly between three categories of frequency in meat consumption (less than 1/week, 1/week-less than 1/d, and greater than or equal to 1/d), while 92 percent of state school children consumed meat daily. Vegetarians (those consuming meat less than 1/week) differed significantly in the consumption of other major food groups, such as fruit and vegetables. All school and diet subgroups were at or above the 50th percentile of the National Center for Health Statistics. Age-adjusted regression analysis showed that on average Adventist vegetarian children were taller than their meat-consuming classmates (2.5 and 2.0 cm for boys and girls, respectively). These results did not change materially when adjusting for other food groups. Nor did adjustment for parental height and socioeconomic factors in a sub-sample of 518 children. The results indicate that vegetarian children and adolescents on a balanced diet grow at least as tall as children who consume meat.", "title": "Attained height of lacto-ovo vegetarian children and adolescents." }, { "docid": "MED-4588", "text": "Flavanols are the main flavonoids found in cocoa and chocolate, and can be especially abundant in certain cocoas. Research over the past decade has identified flavanols as showing diverse beneficial physiologic and antioxidant effects, particularly in context of vascular function. The present study employed functional magnetic resonance imaging based on blood oxygenation level-dependent (BOLD) contrast to explore the effect of flavanols on the human brain. Magnetic resonance imaging was used to measure BOLD responses to a cognitive task in 16 healthy young subjects. The data presented show an increase in the BOLD signal intensity in response to a cognitive task following ingestion of flavanol-rich cocoa (5 days of 150 mg of cocoa flavanols). This may arise either as a result of altered neuronal activity, or a change in vascular responsiveness, or both--the net effect then being dependent on which of the two effects is dominant. No significant effects were evident in behavioral reaction times, switch cost, and heart rate after consumption of this moderate dose of cocoa flavanols. A pilot study evaluated the relationship between cerebral blood flow and a single acute dose (450 mg flavanols) of flavanol-rich cocoa and showed that flavanol-rich cocoa can increase the cerebral blood flow to gray matter, suggesting the potential of cocoa flavanols for treatment of vascular impairment, including dementia and strokes, and thus for maintaining cardiovascular health.", "title": "The effect of flavanol-rich cocoa on the fMRI response to a cognitive task in healthy young people." }, { "docid": "MED-2494", "text": "Background In the absence of current cumulative dietary exposure assessments, this analysis was conducted to estimate exposure to multiple dietary contaminants for children, who are more vulnerable to toxic exposure than adults. Methods We estimated exposure to multiple food contaminants based on dietary data from preschool-age children (2–4 years, n=207), school-age children (5–7 years, n=157), parents of young children (n=446), and older adults (n=149). We compared exposure estimates for eleven toxic compounds (acrylamide, arsenic, lead, mercury, chlorpyrifos, permethrin, endosulfan, dieldrin, chlordane, DDE, and dioxin) based on self-reported food frequency data by age group. To determine if cancer and non-cancer benchmark levels were exceeded, chemical levels in food were derived from publicly available databases including the Total Diet Study. Results Cancer benchmark levels were exceeded by all children (100%) for arsenic, dieldrin, DDE, and dioxins. Non-cancer benchmarks were exceeded by >95% of preschool-age children for acrylamide and by 10% of preschool-age children for mercury. Preschool-age children had significantly higher estimated intakes of 6 of 11 compounds compared to school-age children (p<0.0001 to p=0.02). Based on self-reported dietary data, the greatest exposure to pesticides from foods included in this analysis were tomatoes, peaches, apples, peppers, grapes, lettuce, broccoli, strawberries, spinach, dairy, pears, green beans, and celery. Conclusions Dietary strategies to reduce exposure to toxic compounds for which cancer and non-cancer benchmarks are exceeded by children vary by compound. These strategies include consuming organically produced dairy and selected fruits and vegetables to reduce pesticide intake, consuming less animal foods (meat, dairy, and fish) to reduce intake of persistent organic pollutants and metals, and consuming lower quantities of chips, cereal, crackers, and other processed carbohydrate foods to reduce acrylamide intake.", "title": "Cancer and non-cancer health effects from food contaminant exposures for children and adults in California: a risk assessment" }, { "docid": "MED-1402", "text": "OBJECTIVE: To update previous meta-analyses of cohort studies that investigated the association between the Mediterranean diet and health status and to utilize data coming from all of the cohort studies for proposing a literature-based adherence score to the Mediterranean diet. DESIGN: We conducted a comprehensive literature search through all electronic databases up to June 2013. SETTING: Cohort prospective studies investigating adherence to the Mediterranean diet and health outcomes. Cut-off values of food groups used to compute the adherence score were obtained. SUBJECTS: The updated search was performed in an overall population of 4 172 412 subjects, with eighteen recent studies that were not present in the previous meta-analyses. RESULTS: A 2-point increase in adherence score to the Mediterranean diet was reported to determine an 8 % reduction of overall mortality (relative risk = 0·92; 95 % CI 0·91, 0·93), a 10 % reduced risk of CVD (relative risk = 0·90; 95 % CI 0·87, 0·92) and a 4 % reduction of neoplastic disease (relative risk = 0·96; 95 % CI 0·95, 0·97). We utilized data coming from all cohort studies available in the literature for proposing a literature-based adherence score. Such a score ranges from 0 (minimal adherence) to 18 (maximal adherence) points and includes three different categories of consumption for each food group composing the Mediterranean diet. CONCLUSIONS: The Mediterranean diet was found to be a healthy dietary pattern in terms of morbidity and mortality. By using data from the cohort studies we proposed a literature-based adherence score that can represent an easy tool for the estimation of adherence to the Mediterranean diet also at the individual level.", "title": "Mediterranean diet and health status: an updated meta-analysis and a proposal for a literature-based adherence score." }, { "docid": "MED-2501", "text": "Amino acids play fundamental roles in the cell both as the building blocks of new proteins and as metabolic precursors. To adapt to their limitation during periods of protein starvation, multiple adaptive mechanisms have evolved, including a rapid cessation of new protein synthesis, an increase in amino acid biosynthesis and transport, and autophagy. Here, we discuss what we currently know about how amino acid limitation is sensed, and how this sensing might be transmitted to mTORC1 to regulate protein synthesis and autophagy. Copyright © 2012 Elsevier Ltd. All rights reserved.", "title": "Amino acid sensing and regulation of mTORC1." }, { "docid": "MED-4849", "text": "We tested the effects of an uncooked vegan diet, rich in lactobacilli, in rheumatoid patients randomized into diet and control groups. The intervention group experienced subjective relief of rheumatic symptoms during intervention. A return to an omnivorous diet aggravated symptoms. Half of the patients experienced adverse effects (nausea, diarrhoea) during the diet and stopped the experiment prematurely. Indicators of rheumatic disease activity did not differ statistically between groups. The positive subjective effect experienced by the patients was not discernible in the more objective measures of disease activity (Health Assessment Questionnaire, duration of morning stiffness, pain at rest and pain on movement). However, a composite index showed a higher number of patients with 3-5 improved disease activity measures in the intervention group. Stepwise regression analysis associated a decrease in the disease activity (measured as change in the Disease Activity Score, DAS) with lactobacilli-rich and chlorophyll-rich drinks, increase in fibre intake, and no need for gold, methotrexate or steroid medication (R2=0.48, P=0.02). The results showed that an uncooked vegan diet, rich in lactobacilli, decreased subjective symptoms of rheumatoid arthritis. Large amounts of living lactobacilli consumed daily may also have positive effects on objective measures of rheumatoid arthritis.", "title": "Uncooked, lactobacilli-rich, vegan food and rheumatoid arthritis." }, { "docid": "MED-2213", "text": "CONTEXT: Alzheimer disease (AD) represents a major and increasing public health problem. If populations were identified with significantly lower or higher incidence rates of AD, the search for risk factors in the genesis of AD could be greatly enhanced. OBJECTIVE: To compare incidence rates of dementia and AD in 2 diverse, elderly community-dwelling populations. DESIGN: The Indianapolis-Ibadan Dementia Project, a longitudinal, prospective population-based study consisting of a baseline survey (1992-1993) and 2 subsequent follow-up waves after 2 years (1994-1995) and 5 years (1997-1998). Each wave followed a 2-stage design, with an in-home screening interview followed by a full diagnostic workup of a subsample of participants based on screening performance. SETTING AND PARTICIPANTS: A total of 2459 community-dwelling Yoruba residents of Ibadan, Nigeria, without dementia, and 2147 community-dwelling African American residents of Indianapolis, Ind, without dementia (all aged 65 years or older). The cohorts were followed up for a mean of 5.1 years and 4.7 years, respectively. MAIN OUTCOME MEASURES: Incident cases of dementia and AD in each of the 2 populations. RESULTS: The age-standardized annual incidence rates were significantly lower among Yoruba than among African Americans for dementia (Yoruba, 1.35% [95% confidence interval [CI], 1.13%-1.56%]; African Americans, 3.24% [95% CI, 2.11%-4.38%]) and for AD (Yoruba, 1.15% [95% CI, 0.96%-1.35%]; African Americans, 2.52% [95% CI, 1.40%-3.64%]). CONCLUSION: This is the first report of incidence rate differences for dementia and AD in studies of 2 populations from nonindustrialized and industrialized countries using identical methods and the same group of investigators in both sites. Further explorations of these population differences may identify potentially modifiable environmental or genetic factors to account for site differences in dementia and AD.", "title": "Incidence of dementia and Alzheimer disease in 2 communities: Yoruba residing in Ibadan, Nigeria, and African Americans residing in Indianapolis, I..." }, { "docid": "MED-1592", "text": "The presence of natural estrogen hormones as trace concentrations in the environment has been reported by many researchers and is of growing concern due to its possible adverse effects on the ecosystem. In this study, municipal biosolids, poultry manure (PM) and cow manure (CM), and spent mushroom compost (SMC) were analyzed for the presence of seven estrogen hormones. 17α-estradiol, 17β-estradiol, 17α-dihydroequilin, and estrone were detected in the sampled biosolids and manures at concentrations ranging from 6 to 462 ng/g of dry solids. 17α-estradiol, 17β-estradiol, and estrone were also detected in SMC at concentrations ranging from 4 to 28 ng/g of dry solids. Desorption experiments were simulated in the laboratory using deionized water (milli-Q), and the aqueous phase was examined for the presence of estrogen hormones to determine their desorption potential. Very low desorption of 0.4% and 0.2% estrogen hormones was observed from municipal biosolids and SMC, respectively. An estimate of total estrogen contribution from different solid waste sources is reported. Animal manures (PM and CM) contribute to a significant load of estrogen hormones in the natural environment.", "title": "Occurrence of estrogen hormones in biosolids, animal manure and mushroom compost." }, { "docid": "MED-3428", "text": "OBJECTIVES: The aim of this study was to assess erectile dysfunction prevalence, time of onset and association with risk factors in patients with acute chest pain and angiographically documented coronary artery disease. METHODS: 300 consecutive patients with acute chest pain and angiographically documented coronary artery disease were assessed using a semi-structured interview investigating their medical and sexual histories, the International Index of Erectile Function and other instruments. RESULTS: Patient mean age was 62.5+/-8 years (range 33-86 years). Mean duration of symptoms or signs of myocardial ischaemia prior to enrollment in the study was 49 months (range 1-200). Coronary angiography showed 1-, 2- and 3-vessel disease in 98 (32.6%), 88 (29.3%) and 114 (38%) patients, respectively. The prevalence of ED among all patients was 49% (147/300). Erectile dysfunction was scored as mild, mild to moderate, moderate and severe in 21 (14%), 31 (21%), 20 (14%), and 75 (51%) of patients, respectively. There was no significant difference between patients with ED (n=147) or without ED (n=153) as far as clinical and angiographic characteristics were concerned. In the 147 patients with co-existing ED and CAD, ED symptoms were reported as having become clinically evident prior to CAD symptoms by 99/147 (67%) patients. The mean time interval between the onset of ED and CAD was 38.8 months (range 1-168). There was no significant difference in terms of risk factor distribution and clinical and angiographic characteristics between patients with the onset of ED before vs. after CAD diagnosis. Interestingly, all patients with type I diabetes and ED actually developed sexual dysfunction before CAD onset (p<0.001). CONCLUSIONS: Our study suggests that a significant proportion of patients with angiographically documented coronary artery disease have erectile dysfunction and that this latter condition may become evident prior to angina symptoms in almost 70% of cases. Future studies including a control group of patients with coronary artery disease and normal erectile function are required in order to verify whether erectile dysfunction may be considered a real predictor of ischemic heart disease.", "title": "Erectile dysfunction prevalence, time of onset and association with risk factors in 300 consecutive patients with acute chest pain and angiographic..." }, { "docid": "MED-4722", "text": "BACKGROUND: There has been a resurgence of interest in the controversial relation between dietary protein and bone health. OBJECTIVE: This article reports on the first systematic review and meta-analysis of the relation between protein and bone health in healthy human adults. DESIGN: The MEDLINE (January 1966 to September 2007) and EMBASE (1974 to July 2008) databases were electronically searched for all relevant studies of healthy adults; studies of calcium excretion or calcium balance were excluded. RESULTS: In cross-sectional surveys, all pooled r values for the relation between protein intake and bone mineral density (BMD) or bone mineral content at the main clinically relevant sites were significant and positive; protein intake explained 1-2% of BMD. A meta-analysis of randomized placebo-controlled trials indicated a significant positive influence of all protein supplementation on lumbar spine BMD but showed no association with relative risk of hip fractures. No significant effects were identified for soy protein or milk basic protein on lumbar spine BMD. CONCLUSIONS: A small positive effect of protein supplementation on lumbar spine BMD in randomized placebo-controlled trials supports the positive association between protein intake and bone health found in cross-sectional surveys. However, these results were not supported by cohort study findings for hip fracture risk. Any effects found were small and had 95% CIs that were close to zero. Therefore, there is a small benefit of protein on bone health, but the benefit may not necessarily translate into reduced fracture risk in the long term.", "title": "Dietary protein and bone health: a systematic review and meta-analysis." }, { "docid": "MED-3796", "text": "Lignans are a group of phytochemicals shown to have weakly estrogenic and antiestrogenic properties. Two specific lignans, enterodiol and enterolactone, are absorbed after formation in the intestinal tract from plant precursors particularly abundant in fiber-rich food and are excreted in the urine. We evaluated the effect of the ingestion of flax seed powder, known to produce high concentrations of urinary lignans, on the menstrual cycle in 18 normally cycling women, using a balanced randomized cross-over design. Each subject consumed her usual omnivorous, low fiber (control) diet for 3 cycles and her usual diet supplemented with flax seed for another 3 cycles. The second and third flax cycles were compared to the second and third control cycles. Three anovulatory cycles occurred during the 36 control cycles, compared to none during the 36 flax seed cycles. Compared to the ovulatory control cycles, the ovulatory flax cycles were consistently associated with longer luteal phase (LP) lengths (mean +/- SEM, 12.6 +/- 0.4 vs. 11.4 +/- 0.4 days; P = 0.002). There were no significant differences between flax and control cycles for concentrations of either estradiol or estrone during the early follicular phase, midfollicular phase, or LP. Although flax seed ingestion had no significant effect on LP progesterone concentrations, the LP progesterone/estradiol ratios were significantly higher during the flax cycles. Midfollicular phase testosterone concentrations were slightly higher during flax cycles. Flax seed ingestion had no effect on early follicular phase concentrations of DHEA-S, PRL, or sex hormone-binding globulin. Our data suggest a significant specific role for lignans in the relationship between diet and sex steroid action, and possibly between diet and the risk of breast and other hormonally dependent cancers.", "title": "Effect of flax seed ingestion on the menstrual cycle." }, { "docid": "MED-3057", "text": "The ongoing epidemics of obesity is one main health concern of the present time. Overeating in some obese individuals shares similarities with the loss of control and compulsive behavior observed in drug-addicted subjects, suggesting that obesity may involve food addiction. Here, we review the contributions provided by the use of positron emission tomography to the current understanding of the cerebral control of obesity and food intake in humans. The available studies have shown that multiple areas in the brain are involved with the reward properties of food, such as prefrontal, orbitofrontal, somatosensory cortices, insula, thalamus, hypothalamus, amygdala, and others. This review summarizes the current evidence, supporting the concepts that i) regions involved in the somatosensory response to food sight, taste, and smell are activated by palatable foods and may be hyperresponsive in obese individuals, ii) areas controlling executive drive seem to overreact to the anticipation of pleasure during cue exposure, and iii) those involved in cognitive control and inhibitory behavior may be resistant to the perception of reward after food exposure in obese subjects. All of these features may stimulate, for different reasons, ingestion of highly palatable and energy-rich foods. Though these same regions are similarly involved in drug abusers and game-addicted individuals, any direct resemblance may be an oversimplification, especially as the heterogeneities between studies and the prevalent exclusion of sensitive groups still limit a coherent interpretation of the findings. Further work is required to comprehensively tackle the multifaceted phenotype of obesity and identify the role of food dependency in its pathophysiology. Copyright © 2012 S. Karger GmbH, Freiburg.", "title": "Brain PET imaging in obesity and food addiction: current evidence and hypothesis." }, { "docid": "MED-4038", "text": "We previously reported an association between prenatal exposure to airborne PAH and lower birth weight, birth length and head circumference. The main goal of the present analysis was to assess the possible impact of co-exposure to PAH-containing of barbecued meat consumed during pregnancy on birth outcomes. The birth cohort consisted of 432 pregnant women who gave birth at term (>36 weeks of gestation). Only non-smoking women with singleton pregnancies, 18-35 years of age, and who were free from chronic diseases such as diabetes and hypertension were included in the study. Detailed information on diet over pregnancy was collected through interviews and the measurement of exposure to airborne PAHs was carried out by personal air monitoring during the second trimester of pregnancy. The effect of barbecued meat consumption on birth outcomes (birthweight, length and head circumference at birth) was adjusted in multiple linear regression models for potential confounding factors such as prenatal exposure to airborne PAHs, child’s sex, gestational age, parity, size of mother (maternal prepregnancy weight, weight gain in pregnancy) and prenatal environmental tobacco smoke (ETS). The multivariable regression model showed a significant deficit in birthweight associated with barbecued meat consumption in pregnancy (coeff = −106.0 g; 95%CI: −293.3, −35.8); The effect of exposure to airborne PAHs was about the same magnitude order (coeff. = −164.6 g; 95%CI: −172.3, − 34.7). Combined effect of both sources of exposure amounted to birth weight deficit of 214.3 g (95%CI: −419.0, − 9.6). Regression models performed for birth length and head circumference showed similar trends but the estimated effects were of borderline significance level. As the intake of barbecued meat did not affect the duration of pregnancy, the reduced birthweight could not have been mediated by shortened gestation period. In conclusion, the study results provided epidemiologic evidence that prenatal PAH exposure from diet including grilled meat might be hazardous for fetal development.", "title": "IMPACT OF BARBECUED MEAT CONSUMED IN PREGNANCY ON BIRTH OUTCOMES ACCOUNTING FOR PERSONAL PRENATAL EXPOSURE TO AIRBORNE POLYCYCLIC AROMATIC HYDROCARBONS. BIRTH COHORT STUDY IN POLAND" }, { "docid": "MED-3440", "text": "INTRODUCTION: It is unclear whether men with erectile dysfunction (ED) ultimately die of cardiovascular (CV) causes. AIM: This study examined the causes of death in men with ED and their risk of CV death. METHODS: Based on statutory death registrations and hospital morbidity data, the risk of CV death in men with ED in a linked-data study was assessed against the CV mortality risk in a reference male population. MAIN OUTCOME MEASURES: Deaths from CV causes as proportions of all deaths. Age-specific rate, mortality rate ratio (MRR), standardized mortality rate ratio (SMRR), and adjusted hazard ratio (HR). RESULTS: CV mortality was 4.0%. Compared with the reference population, the risk of CV death was higher in men with ED (SMRR 2.2; 95% confidence interval [CI] 1.6, 3.0). Risk of CV mortality was higher in men with CV disease prior to ED (adjusted HR 1.7; 95% CI 1.1, 2.6) or with history of hospital admissions for CV events (adjusted HR 2.2; 95% CI 1.3, 3.8), compared with those without the respective history. MRR was significantly increased in the 40-69 years age group (MRR 4.1; 95% CI 3.2, 5.2). The median time interval between manifestation of ED and CV death was 10.0 years. A greater proportion of deaths from oncological than from CV causes (25.0% vs. 10.8%) occurred within the first 5 years of the manifestation of ED. CONCLUSIONS: Although the risk of CV mortality is greater in men with ED, almost as many men die of oncological as of CV causes, with a higher proportion of oncological deaths occurring sooner subsequent to the first manifestation of ED. © 2011 International Society for Sexual Medicine.", "title": "Cardiovascular mortality in men with erectile dysfunction: increased risk but not inevitable." }, { "docid": "MED-2114", "text": "Acne in adolescents of developed countries is an epidemic skin disease and has currently been linked to the Western diet (WD). It is the intention of this viewpoint to discuss the possible impact of WD-mediated nutrient signalling in the pathogenesis of acne. High glycaemic load and dairy protein consumption both increase insulin/insulin-like growth factor-1 (IGF-1) signalling (IIS) that is superimposed on elevated IGF-1 signalling of puberty. The cell's nutritional status is primarily sensed by the forkhead box transcription factor O1 (FoxO1) and the serine/threonine kinase mammalian target of rapamycin complex 1 (mTORC1). Increased IIS extrudes FoxO1 into the cytoplasm, whereas nuclear FoxO1 suppresses hepatic IGF-1 synthesis and thus impairs somatic growth. FoxO1 attenuates androgen signalling, interacts with regulatory proteins important for sebaceous lipogenesis, regulates the activity of innate and adaptive immunity, antagonizes oxidative stress and most importantly functions as a rheostat of mTORC1, the master regulator of cell growth, proliferation and metabolic homoeostasis. Thus, FoxO1 links nutrient availability to mTORC1-driven processes: increased protein and lipid synthesis, cell proliferation, cell differentiation including hyperproliferation of acroinfundibular keratinocytes, sebaceous gland hyperplasia, increased sebaceous lipogenesis, insulin resistance and increased body mass index. Enhanced androgen, TNF-α and IGF-1 signalling due to genetic polymorphisms promoting the risk of acne all converge in mTORC1 activation, which is further enhanced by nutrient signalling of WD. Deeper insights into the molecular interplay of FoxO1/mTORC1-mediated nutrient signalling are thus of critical importance to understand the impact of WD on the promotion of epidemic acne and more serious mTORC1-driven diseases of civilization.", "title": "Potential role of FoxO1 and mTORC1 in the pathogenesis of Western diet-induced acne" }, { "docid": "MED-2116", "text": "Over the past 10 years, the increase in comprehension of the mechanisms behind acne has been truly exponential. Starting with the ethnological work of Cordain, accelerated by the epidemiological work of Adebamowo, supported by the clinical trials of Smith and Mann, Kwon, DiLandro and others, the interface of diet and acne is coming into focus. Melnik now presents an exceptional pair of papers that illustrate for dermatologists what translational research is all about. The Western diet, the role of dairy, FoxO1 and mTORC1, the interplay of agonists and antagonists, therapeutics present and future – the jigsaw puzzle is coming together.", "title": "Turning acne on/off via mTORC1" }, { "docid": "MED-3316", "text": "BACKGROUND: Between November, 2006, and May, 2008, a subacute neurological syndrome affected workers from two swine abattoirs in Minnesota and Indiana who had occupational exposure to aerosolised porcine brain. We aimed to describe the pathogenic and immunological characteristics of this illness. METHODS: All patients from two abattoirs who presented or were referred to the Mayo Clinic (Rochester, MN, USA) with neurological symptoms were included. We recorded details of exposure to aerosolised brain tissue and did comprehensive neurological, laboratory, neuroimaging, electrophysiological, pathological, and autoimmune serological assessments. Healthy controls were recruited from the community and from workers at the plant in Minnesota. FINDINGS: 24 patients were identified (21 from Minnesota, three from Indiana). The shortest duration from first exposure to symptom onset was 4 weeks. No infectious agent that could trigger disease was identified. All patients developed polyradiculoneuropathy, which was usually sensory predominant and painful. Two patients had initial CNS manifestations: transverse myelitis and meningoencephalitis. Nerve conduction studies localised abnormalities to the most proximal and distal nerve segments. Quantitative sensory and autonomic testing revealed involvement of large and small sensory fibres and sweat fibres. MRI showed prominent abnormalities of roots and ganglia. Nerve biopsies identified mild demyelination, axonal degeneration, and perivascular inflammation. Protein concentrations were high in the CSF of 18 (86%) of 21 patients. Sera from all patients and 29 (34%) of 85 unaffected workplace controls (but none of 178 community controls) had a distinctive neural-reactive IgG; 75% of patients' sera contained an IgG specific to myelin basic protein. Seropositivity correlated directly with exposure risk in patients and controls. 17 patients required immunomodulatory therapies, six improved spontaneously, and one was lost to follow-up after exposure stopped. INTERPRETATION: The neurological disorder described is autoimmune in origin and is related to occupational exposure to multiple aerosolised porcine brain tissue antigens. The pattern of nerve involvement suggests vulnerability of nerve roots and terminals where the blood-nerve barrier is most permeable. FUNDING: Mayo Clinic Foundation; Minnesota Department of Health; Centers for Disease Control and Prevention. Copyright 2010 Elsevier Ltd. All rights reserved.", "title": "An outbreak of neurological autoimmunity with polyradiculoneuropathy in workers exposed to aerosolised porcine neural tissue: a descriptive study." }, { "docid": "MED-3033", "text": "Rates of lung cancer in American men have greatly exceeded those in Japanese men for several decades despite the higher smoking prevalence in Japanese men. It is not known whether the relative risk of lung cancer associated with cigarette smoking is lower in Japanese men than American men and whether these risks vary by the amount and duration of smoking. To estimate smoking-specific relative risks for lung cancer in men, a multicentric case-control study was carried out in New York City, Washington, DC, and Nagoya, Japan from 1992 to 1998. A total of 371 cases and 373 age-matched controls were interviewed in United States hospitals and 410 cases and 252 hospital controls in Japanese hospitals; 411 Japanese age-matched healthy controls were also randomly selected from electoral rolls. The odds ratio (OR) for lung cancer in current United States smokers relative to nonsmokers was 40.4 [95% confidence interval (CI) = 21.8-79.6], which was >10 times higher than the OR of 3.5 for current smokers in Japanese relative to hospital controls (95% CI = 1.6-7.5) and six times higher than in Japanese relative to community controls (OR = 6.3; 95% CI = 3.7-10.9). There were no substantial differences in the mean number of years of smoking or average daily number of cigarettes smoked between United States and Japanese cases or between United States and Japanese controls, but American cases began smoking on average 2.5 years earlier than Japanese cases. The risk of lung cancer associated with cigarette smoking was substantially higher in United States than in Japanese males, consistent with population-based statistics on smoking prevalence and lung cancer incidence. Possible explanations for this difference in risk include a more toxic cigarette formulation of American manufactured cigarettes as evidenced by higher concentrations of tobacco-specific nitrosamines in both tobacco and mainstream smoke, the much wider use of activated charcoal in the filters of Japanese than in American cigarettes, as well as documented differences in genetic susceptibility and lifestyle factors other than smoking.", "title": "Smoking and lung cancer risk in American and Japanese men: an international case-control study." }, { "docid": "MED-3882", "text": "Salmonella enterica is one of the most common causes of foodborne illness in the United States. Although salmonellosis is usually self-limiting, severe infections typically require antimicrobial treatment, and ceftriaxone, an extended-spectrum cephalosporin (ESC), is commonly used in both adults and children. Surveillance conducted by the National Antimicrobial Resistance Monitoring System (NARMS) has shown a recent increase in ESC resistance among Salmonella Heidelberg isolated from food animals at slaughter, retail meat, and humans. ESC resistance among Salmonella in the United States is usually mediated by a plasmid-encoded bla(CMY) β-lactamase. In 2009, we identified 47 ESC-resistant bla(CMY)-positive Heidelberg isolates from humans (n=18), food animals at slaughter (n=16), and retail meats (n=13) associated with a spike in the prevalence of this serovar. Almost 90% (26/29) of the animal and meat isolates were isolated from chicken carcasses or retail chicken meat. We screened NARMS isolates for the presence of bla(CMY), determined whether the gene was plasmid-encoded, examined pulsed-field gel electrophoresis patterns to assess the genetic diversities of the isolates, and categorized the bla(CMY) plasmids by plasmid incompatibility groups and plasmid multi-locus sequence typing (pMLST). All 47 bla(CMY) genes were found to be plasmid encoded. Incompatibility/replicon typing demonstrated that 41 were IncI1 plasmids, 40 of which only conferred bla(CMY)-associated resistance. Six were IncA/C plasmids that carried additional resistance genes. pMLST of the IncI1-bla(CMY) plasmids showed that 27 (65.8%) were sequence type (ST) 12, the most common ST among bla(CMY)-IncI1 plasmids from Heidelberg isolated from humans. Ten plasmids had a new ST profile, ST66, a type very similar to ST12. This work showed that the 2009 increase in ESC resistance among Salmonella Heidelberg was caused mainly by the dissemination of bla(CMY) on IncI1 and IncA/C plasmids in a variety of genetic backgrounds, and is likely not the result of clonal expansion.", "title": "Characterization of extended-spectrum cephalosporin-resistant Salmonella enterica serovar Heidelberg isolated from food animals, retail meat, and h..." }, { "docid": "MED-3699", "text": "BACKGROUND: In 2007 the World Cancer Research Fund (WCRF) and the American Institute of Cancer Research (AICR) issued 8 recommendations (plus 2 special recommendations) on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence. OBJECTIVE: We aimed to investigate whether concordance with the WCRF/AICR recommendations was related to cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. DESIGN: The present study included 386,355 EPIC participants from 9 European countries. At recruitment, dietary, anthropometric, and lifestyle information was collected. A score was constructed based on the WCRF/AICR recommendations on weight management, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, alcoholic drinks, and breastfeeding for women; the score range was 0-6 for men and 0-7 for women. Higher scores indicated greater concordance with WCRF/AICR recommendations. The association between the score and cancer risk was estimated by using multivariable Cox regression models. RESULTS: Concordance with the score was significantly associated with decreased risk of cancer. A 1-point increment in the score was associated with a risk reduction of 5% (95% CI: 3%, 7%) for total cancer, 12% (95% CI: 9%, 16%) for colorectal cancer, and 16% (95% CI: 9%, 22%) for stomach cancer. Significant associations were also observed for cancers of the breast, endometrium, lung, kidney, upper aerodigestive tract, liver, and esophagus but not for prostate, ovarian, pancreatic, and bladder cancers. CONCLUSION: Adherence to the WCRF/AICR recommendations for cancer prevention may lower the risk of developing most types of cancer.", "title": "Is concordance with World Cancer Research Fund/American Institute for Cancer Research guidelines for cancer prevention related to subsequent risk o..." }, { "docid": "MED-2258", "text": "Breast cancer is the most prevalent women's cancer, with an age-adjusted incidence of 122.9 per 100,000 US women. Cadmium, a ubiquitous carcinogenic pollutant with multiple biological effects, has been reported to be associated with breast cancer in one US regional case-control study. We examined the association of breast cancer with urinary cadmium (UCd), in a case-control sample of women living on Long Island (LI), NY (100 with breast cancer and 98 without), a region with an especially high rate of breast cancer (142.7 per 100,000 in Suffolk County) and in a representative sample of US women (NHANES 1999-2008, 92 with breast cancer and 2,884 without). In a multivariable logistic model, both samples showed a significant trend for increased odds of breast cancer across increasing UCd quartiles (NHANES, p=0.039 and LI, p=0.023). Compared to those in the lowest quartile, LI women in the highest quartile had increased risk for breast cancer (OR=2.69; 95% CI=1.07, 6.78) and US women in the two highest quartiles had increased risk (OR=2.50; 95% CI=1.11, 5.63 and OR=2.22; 95% CI=.89, 5.52, respectively). Further research is warranted on the impact of environmental cadmium on breast cancer risk in specific populations and on identifying the underlying molecular mechanisms.", "title": "Environmental cadmium and breast cancer risk" }, { "docid": "MED-2507", "text": "Increased plasma levels of adiponectin, metformin therapy of diabetes, rapamycin administration in transplant patients, and lifelong consumption of low-protein plant-based diets have all been linked to decreased risk for various cancers. These benefits may be mediated, at least in part, by down-regulated activity of the mTORC1 complex, a key regulator of protein translation. By boosting the effective availability of the translation initiator eIF4E, mTORC1 activity promotes the translation of a number of \"weak\" mRNAs that code for proteins, often up-regulated in cancer, that promote cellular proliferation, invasiveness, and angiogenesis, and that abet cancer promotion and chemoresistance by opposing apoptosis. Measures which inhibit eIF4E activity, either directly or indirectly, may have utility not only for cancer prevention, but also for the treatment of many cancers in which eIF4E drives malignancy. Since eIF4E is overexpressed in many cancers, strategies which target eIF4E directly--some of which are now being assessed clinically--may have the broadest efficacy in this regard. Many of the \"weak\" mRNAs coding for proteins that promote malignant behavior or chemoresistance are regulated transcriptionally by NF-kappaB and/or Stat3, which are active in a high proportion of cancers; thus, regimens concurrently targeting eIF4E, NF-kappaB, and Stat3 may suppress these proteins at both the transcriptional and translational levels, potentially achieving a very marked reduction in their expression. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "mTORC1 activity as a determinant of cancer risk--rationalizing the cancer-preventive effects of adiponectin, metformin, rapamycin, and low-protein ..." }, { "docid": "MED-2509", "text": "DR (dietary restriction), or reduced food intake without malnutrition, is associated with extended longevity, improved metabolic fitness and increased stress resistance in a wide range of organisms. DR is often referred to as calorie restriction, implying that reduced energy intake is responsible for its widespread and evolutionarily conserved benefits. However, recent data indicate dietary amino acid restriction as a key mediator of DR benefits. In fruitflies, an imbalance in essential amino acid intake is thought to underlie longevity benefits of DR. In mammals, reduced dietary protein or essential amino acid intake can extend longevity, improve metabolic fitness and increase stress resistance. In the present paper we review two evolutionarily conserved signal transduction pathways responsible for sensing amino acid levels. The eIF2α (eukaryotic initiation factor 2α) kinase GCN2 (general amino acid control non-derepressible 2) senses the absence of one or more amino acids by virtue of direct binding to uncharged cognate tRNAs. The presence of certain amino acids, such as leucine, permits activation of the master growth regulating kinase TOR (target of rapamycin). These two signal transduction pathways react to amino acid deprivation by inhibiting general protein translation while at the same time increasing translation of specific mRNAs involved in restoring homoeostasis. Together, these pathways may contribute to the regulation of longevity, metabolic fitness and stress resistance.", "title": "Amino acid sensing in dietary-restriction-mediated longevity: roles of signal-transducing kinases GCN2 and TOR" }, { "docid": "MED-1914", "text": "How can adverse experiences in early life, such as maltreatment, exert such powerful negative effects on health decades later? The answer may lie in changes to DNA. New research suggests that exposure to stress can accelerate the erosion of DNA segments called telomeres. Shorter telomere length correlates with chronological age and also disease morbidity and mortality. Thus, telomere erosion is a potential mechanism linking childhood stress to health problems later in life. However, an array of mechanistic, methodological, and basic biological questions must be addressed in order to translate telomere discoveries into clinical applications for monitoring health and predicting disease risk. This paper covers the current state of the science and lays out new research directions.", "title": "Early life stress and telomere length: Investigating the connection and possible mechanisms" }, { "docid": "MED-2645", "text": "The development of the male reproductive ducts and external genitalia in vertebrates is dependent on elevated androgen concentrations during embryonic development and the period of postnatal growth. We have observed that a population of juvenile alligators living on Lake Apopka exhibit significantly smaller penis size (24% average decrease) and lower plasma concentrations of testosterone (70% lower concentrations) when compared to animals of similar size on Lake Woodruff. In addition to smaller phalli, no relationship exists between plasma testosterone concentrations and penile size in males from Lake Apopka, whereas a positive relationship exists for males from Lake Woodruff. The alligators on Lake Apopka are known to have elevated concentrations of the antiandrogenic DDT breakdown product p.p'-DDE stored in their fat. We suggest a number of hypotheses that could explain the modification in the phenotype of the juvenile male living in Lake Apopka. These modifications in phenotype include a smaller penis size, lower plasma androgen concentrations, and lack of responsiveness of the penis to the plasma androgens present.", "title": "Reduction in penis size and plasma testosterone concentrations in juvenile alligators living in a contaminated environment." }, { "docid": "MED-3247", "text": "Objective: The chemotherapeutic agent mitoxantrone was approved for use in multiple sclerosis (MS) in 2000. After a review of all the available evidence, the original report of the Therapeutics and Technology Assessment Subcommittee in 2003 concluded that mitoxantrone probably reduced clinical attack rates, MRI activity, and disease progression. Subsequent reports of decreased systolic function, heart failure, and leukemia prompted the US Food and Drug Administration to institute a “black box” warning in 2005. This review was undertaken to examine the available literature on the efficacy and safety of mitoxantrone use in patients with MS since the initial report. Methods: Relevant articles were obtained through a review of the medical literature and the strength of the available evidence was graded according to the American Academy of Neurology evidence classification scheme. Results: The accumulated Class III and IV evidence suggests an increased incidence of systolic dysfunction and therapy-related acute leukemia (TRAL) with mitoxantrone therapy. Systolic dysfunction occurs in ∼12% of patients with MS treated with mitoxantrone, congestive heart failure occurs in ∼0.4%, and leukemia occurs in ∼0.8%. The number needed to harm is 8 for systolic dysfunction and 123 for TRAL. There is no new efficacy evidence that would change the recommendation from the previous report. Conclusions: The risk of systolic dysfunction and leukemia in patients treated with mitoxantrone is higher than suggested at the time of the previous report, although comprehensive postmarketing surveillance data are lacking. GLOSSARY", "title": "Evidence Report: The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis" }, { "docid": "MED-3430", "text": "BACKGROUND: Erectile dysfunction (ED) shares similar modifiable risks factors with coronary artery disease (CAD). Lifestyle modification that targets CAD risk factors may also lead to improvement in ED. We conducted a systematic review and meta-analysis of randomized controlled trials evaluating the effect of lifestyle interventions and pharmacotherapy for cardiovascular (CV) risk factors on the severity of ED. METHODS: A comprehensive search of multiple electronic databases through August 2010 was conducted using predefined criteria. We included randomized controlled clinical trials with follow-up of at least 6 weeks of lifestyle modification intervention or pharmacotherapy for CV risk factor reduction. Studies were selected by 2 independent reviewers. The main outcome measure of the study is the weighted mean differences in the International Index of Erectile Dysfunction (IIEF-5) score with 95% confidence intervals (CIs) using a random effects model. RESULTS: A total of 740 participants from 6 clinical trials in 4 countries were identified. Lifestyle modifications and pharmacotherapy for CV risk factors were associated with statistically significant improvement in sexual function (IIEF-5 score): weighted mean difference, 2.66 (95% CI, 1.86-3.47). If the trials with statin intervention (n = 143) are excluded, the remaining 4 trials of lifestyle modification interventions (n = 597) demonstrate statistically significant improvement in sexual function: weighted mean difference, 2.40 (95% CI, 1.19-3.61). CONCLUSION: The results of our study further strengthen the evidence that lifestyle modification and pharmacotherapy for CV risk factors are effective in improving sexual function in men with ED.", "title": "The effect of lifestyle modification and cardiovascular risk factor reduction on erectile dysfunction: a systematic review and meta-analysis." }, { "docid": "MED-3060", "text": "Context Research has implicated an addictive process in the development and maintenance of obesity. Although parallels in neural functioning between obesity and substance dependence have been found, no studies have examined the neural correlates of addictive-like eating behavior. Objective To test the hypothesis that elevated “food addiction” scores are associated with similar patterns of neural activation as substance dependence. Design Between-Subjects fMRI study. Participants Forty-eight healthy adolescent females ranging from lean to obese recruited for a healthy weight maintenance trial. Main Outcome Measure The relation between elevated “food addiction” scores and blood oxygen level-dependent fMRI activation in response to receipt and anticipated receipt of palatable food (chocolate milkshake). Results Food addiction scores (N = 39) correlated with greater activation in the anterior cingulate cortex (ACC), medial orbitofrontal cortex (OFC), and amygdala in response to anticipated receipt of food (P <0.05, false-discovery rate (FDR) corrected for multiple comparisons in small volumes). Participants with higher (n=15) versus lower (n=11) food addiction scores showed greater activation in the dorsolateral prefrontal cortex (DLPFC) and the caudate in response to anticipated receipt of food, but less activation in the lateral OFC in response to receipt of food (pFDR <0.05). Conclusions Similar patterns of neural activation are implicated in addictive-like eating behavior and substance dependence; elevated activation in reward circuitry in response to food cues and reduced activation of inhibitory regions in response to food intake.", "title": "The Neural Correlates of “Food Addiction”" }, { "docid": "MED-3956", "text": "Early onset of puberty may confer adverse health consequences. Thus, modifiable factors influencing the timing of puberty are of public health interest. Childhood overweight as a factor in the earlier onset of menarche has been supported by prospective evidence; nonetheless, its overall contribution may have been overemphasized, since secular trends toward a younger age at menarche have not been a universal finding during the recent obesity epidemic. Current observational studies suggest notable associations between dietary intakes and pubertal timing beyond contributions to an energy imbalance: children with the highest intakes of vegetable protein or animal protein experience pubertal onset up to 7 months later or 7 months earlier, respectively. Furthermore, girls with high isoflavone intakes may experience the onset of breast development and peak height velocity approximately 7-8 months later. These effect sizes are on the order of those observed for potentially neuroactive steroid hormones. Thus, dietary patterns characterized by higher intakes of vegetable protein and isoflavones and lower intakes of animal protein may contribute to a lower risk of breast cancer or a lower total mortality. © 2012 International Life Sciences Institute.", "title": "Beyond overweight: nutrition as an important lifestyle factor influencing timing of puberty." }, { "docid": "MED-1588", "text": "Multiple pregnancy rates remain high after assisted conception because of a misconceived assumption that transferring three or more embryos will maximize pregnancy rates. Maternal morbidity is sevenfold greater in multiple pregnancies than in singletons, perinatal mortality rates are fourfold higher for twins and sixfold higher for triplets, while cerebral palsy rates are 1-1.5% in twin and 7-8% in triplet pregnancies. Therefore, multiple pregnancies must be considered a serious adverse outcome of assisted reproductive techniques. Primary prevention of multiple pregnancies is the solution. The overwhelming evidence presented in this chapter demonstrates that limiting the embryo transfer in in vitro fertilization to two embryos would significantly reduce adverse maternal and perinatal outcomes by reducing the incidence of high order multiple pregnancies without reducing take-home-baby rates. Secondary prevention by multifetal pregnancy reduction is effective, but not acceptable to all patients. New developments in blastocyst culture, single embryo transfer, embryo cryopreservation and pre-implantation aneuploidy exclusion, should allow improvements in pregnancy rates without increasing multiple pregnancies.", "title": "Reducing the incidence of twins and triplets." }, { "docid": "MED-2123", "text": "Milk has been recognized to represent a functionally active nutrient system promoting neonatal growth of mammals. Cell growth is regulated by the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1). There is still a lack of information on the mechanisms of mTORC1 up-regulation by milk consumption. This review presents milk as a materno-neonatal relay system functioning by transfer of preferential amino acids, which increase plasma levels of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), insulin, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) for mTORC1 activation. Importantly, milk exosomes, which regularly contain microRNA-21, most likely represent a genetic transfection system enhancing mTORC1-driven metabolic processes. Whereas human breast milk is the ideal food for infants allowing appropriate postnatal growth and species-specific metabolic programming, persistent high milk signaling during adolescence and adulthood by continued cow´s milk consumption may promote mTORC1-driven diseases of civilization.", "title": "Milk is not just food but most likely a genetic transfection system activating mTORC1 signaling for postnatal growth" }, { "docid": "MED-3148", "text": "We examined the resting metabolic rate (RMR) and sympathetic nervous system activity of young male vegetarians (n = 17) and nonvegetarians (n = 40). Subjects were characterized for RMR by indirect calorimetry, norepinephrine kinetics from infusions of tritiated norepinephrine, energy and macronutrient intake from a 3-day food diary, and body composition by underwater weighing. Vegetarians reported a greater relative intake of carbohydrates (62% +/- 5% v 51% +/- 6%, P < .01) and a lower relative intake of fat (25% +/- 5% v 33% +/- 6%, P < .01) than nonvegetarians, whereas no differences were observed in daily energy intake, body composition, or maximal aerobic capacity (VO2max) between groups. Vegetarians exhibited an 11% higher absolute RMR (1.29 +/- 0.15 v 1.16 +/- 0.13 kcal/min, P < .01), a higher plasma concentration of norepinephrine (216 +/- 33 v 165 +/- 18 pg/mL, P < .01), and a greater norepinephrine appearance rate (0.50 +/- 0.08 v 0.36 +/- 0.09 micrograms/min, P < .01) than nonvegetarians. After statistically controlling for differences in relative amounts of carbohydrate and fat in the diet and for norepinephrine concentrations, no significant differences in adjusted RMR between vegetarians and nonvegetarians were noted. These results suggest that the higher RMR observed in young male vegetarians is partially mediated by differences in dietary macronutrient composition and increased sympathetic nervous system activity.", "title": "Sympathetic nervous system activity and resting metabolic rate in vegetarians." }, { "docid": "MED-4681", "text": "BACKGROUND: It has been suggested that phytoestrogens and dietary fiber can affect puberty timing. OBJECTIVE: We examined whether intake of isoflavone and fiber in healthy white children before their pubertal growth spurt [age at take-off (ATO)] was associated with puberty timing. DESIGN: Multivariate regression analyses were performed in 227 DONALD (DOrtmund Nutritional and Anthropometric Longitudinally Designed) Study participants with 3-d weighed dietary records and information on potential confounders at baseline (1 and 2 y before ATO). In a subsample (n = 111), urinary isoflavones were determined in 24-h urine samples by gas chromatography-mass spectrometry analysis. Puberty timing was examined by using ATO and chronologic ages at pubertal stage 2 for breast development (B2) or gonadal development, peak height velocity (PHV), and menarche or voice break. RESULTS: Girls whose diet was in the highest dietary isoflavone tertile experienced Tanner stage 2 for breast development ap 0.7 y later and reached PHV ap 0.6 y later than did girls whose diet was in the lowest isoflavone tertile [age (95% CI) at B2: 10.7 y (10.4, 10.9 y) compared with 10.0 y ( 9.7, 10.3 y), respectively; P for trend = 0.04; age at PHV: 11.9 y (11.6, 12.2 y) compared with 11.3 y (11.0, 11.6 y), respectively; P for trend = 0.04; adjusted for body mass index z score and fiber intake]. In boys, dietary isoflavones were not associated with pubertal markers. Urinary isoflavone and dietary fiber intakes were not associated with pubertal markers. CONCLUSIONS: Girls, but not boys, with higher prepubertal isoflavone intakes appear to enter puberty at a later age. Fiber intake in this sample of healthy white girls and boys was not relevant for puberty timing.", "title": "Relation of isoflavones and fiber intake in childhood to the timing of puberty." }, { "docid": "MED-4695", "text": "Night is no longer dark in the modern world, and the Milky Way has disappeared. Electric light has benefits but there are also a few detriments. These are (1) loss of the night sky, (2) wasted energy, (3) harm to animal and plant life, (4) and perhaps increases in some severe human maladies such as cancers of breast and prostate. The science on phototransduction for the circadian system and on clock gene function is evolving rapidly, and it provides a rationale for the idea that circadian disruption from light at night could cause disease. Direct evidence from humans and rodent models has also accumulated to the point where the idea is no longer fanciful. Although it may seem logical now, the journey on the path from electric light to breast cancer has been a tortuous one, at least for me.", "title": "Electric light causes cancer? Surely you're joking, Mr. Stevens." }, { "docid": "MED-2120", "text": "In a recent study, prostatectomy specimens from which Propionibacterium acnes was cultured were more likely to have inflammation than culture-negative specimens or specimens positive for other bacteria, leading the authors to hypothesize that P. acnes-mediated inflammation may contribute to prostate carcinogenesis. To indirectly explore associations between P. acnes and prostate cancer, we investigated severe acne, as measured by tetracycline use for four or more years, in relation to incident prostate cancer in the Health Professionals Follow-up Study. On the 1992 follow-up questionnaire, participants were asked whether they had ever used “tetracycline for at least two months at a time (e.g., for acne or other reason)” and their duration of use. Prostate cancer diagnoses were ascertained on each subsequent biennial questionnaire and confirmed by medical record review. Between 1992 and 2002, 2,147 cases of prostate cancer were reported among 34,629 eligible participants. Men who used tetracycline for four or more years had a significantly higher risk of prostate cancer (16 cases, 1,569 person-years) than men who did not use tetracycline (2,071 cases, 304,822 person-years, multivariable-adjusted RR=1.70, 95% CI:1.03–2.80). Although intriguing, this finding should be viewed cautiously because of the small number of exposed cases, indirect assessment of severe acne, and complex etiology of acne, which is not limited to P. acnes infection. Therefore, additional biologic and epidemiologic studies are necessary to determine and elucidate the possible role of P. acnes infection in prostate carcinogenesis.", "title": "ACNE AND RISK OF PROSTATE CANCER" }, { "docid": "MED-5072", "text": "Antioxidant-rich diets are associated with reduced asthma prevalence. However, direct evidence that altering intake of antioxidant-rich foods affects asthma is lacking. The objective was to investigate changes in asthma and airway inflammation resulting from a low antioxidant diet and subsequent use of lycopene-rich treatments. Asthmatic adults (n=32) consumed a low antioxidant diet for 10 days, then commenced a randomized, cross-over trial involving 3 x 7 day treatment arms (placebo, tomato extract (45 mg lycopene/day) and tomato juice (45 mg lycopene/day)). With consumption of a low antioxidant diet, plasma carotenoid concentrations decreased, Asthma Control Score worsened, %FEV(1) and %FVC decreased and %sputum neutrophils increased. Treatment with both tomato juice and extract reduced airway neutrophil influx. Treatment with tomato extract also reduced sputum neutrophil elastase activity. In conclusion, dietary antioxidant consumption modifies clinical asthma outcomes. Changing dietary antioxidant intake may be contributing to rising asthma prevalence. Lycopene-rich supplements should be further investigated as a therapeutic intervention.", "title": "Lycopene-rich treatments modify noneosinophilic airway inflammation in asthma: proof of concept." }, { "docid": "MED-4029", "text": "We compared the effect on enamel demineralisation in situ of both whole and juiced fruits and vegetables. Volunteers wore removable mandibular appliances carrying pre-demineralised human enamel slabs and consumed one of the test foods 7 times a day for 10 days. The test foods were apples, oranges, grapes, carrots, and tomatoes, consumed either whole (sugars located intrinsically) or as a juice (extrinsic or free sugars). Raisins containing 64% sugars, but intrinsic by definition, were also studied. The mineral profile of the enamel slabs was studied before and after the test period using transverse microradiography and showed further demineralisation for all test foods, irrespective of the form of consumption. Significant demineralisation was also observed with raisins. No significant differences were found between the solid and juiced foods. In conclusion, sugars present intrinsically on consumption had a similar demineralising potential as free sugars and could not be considered less cariogenic. Copyright © 2011 S. Karger AG, Basel.", "title": "Comparison of the effects of whole and juiced fruits and vegetables on enamel demineralisation in situ." }, { "docid": "MED-1615", "text": "Hyperinsulinemia, hypertension, hypertriglyceridemia and obesity are independent risk factors for coronary artery disease and are often found in the same person. This study investigated the effects of an intensive, 3-week, dietary and exercise program on these risk factors. The group was divided into diabetic patients (non-insulin-dependent diabetes mellitus [NIDDM], n = 13), insulin-resistant persons (n = 29) and those with normal insulin, less than or equal to 10 microU/ml (n = 30). The normal groups had very small but statistically significant decreases in all of the risk factors. The patients with NIDDM had the greatest decreases. Insulin was reduced from 40 +/- 15 to 27 +/- 11 microU/ml, blood pressure from 142 +/- 9/83 +/- 3 to 132 +/- 6/71 +/- 3 mm Hg, triglycerides from 353 +/- 76 to 196 +/- 31 mg/dl and body mass index from 31.1 +/- 4.0 to 29.7 +/- 3.7 kg/m2. Although there was a significant weight loss for the group with NIDDM, resulting in the decrease in body mass index, 8 of 9 patients who were initially overweight were still overweight at the end of the program, and 5 of the 8 were still obese (body mass index greater than 30 kg/m2), indicating that normalization of body weight is not a requisite for a reduction or normalization of other risk factors. Insulin was reduced from 18.2 +/- 1.8 to 11.6 +/- 1.2 microU/ml in the insulin-resistant group, with 17 of the 29 subjects achieving normal fasting insulin (less than 10 microU/ml).(ABSTRACT TRUNCATED AT 250 WORDS)", "title": "Role of diet and exercise in the management of hyperinsulinemia and associated atherosclerotic risk factors." }, { "docid": "MED-3308", "text": "An occupational health survey conducted in a workshop in which asbestos cement was used showed initial atmospheric asbestos levels ranging from 1.9 to 27.5 fibres per millilitre of air. Radiological changes suggestive of asbestos-related pleural disease were found in 2 workers (2.5%), while 3 (3.8%) had borderline features of asbestosis. The survey confirmed that uncontrolled and hazardous use of asbestos continues in industry despite public awareness of its dangers and the Asbestos Regulations of 1987.", "title": "Third wave of asbestos-related disease from secondary use of asbestos. A case report from industry." }, { "docid": "MED-4022", "text": "BACKGROUND: Erectile dysfunction (ED) and chronic periodontitis (CP) share common risk factors. There is only one report on the association between ED and CP. Thus, the aim of this study is to find the association between vasculogenic ED and CP. METHODS: A total of 70 patients (mean age: 35.3 ± 3.64 years) clinically diagnosed with ED were included in the study. They were given the Sexual Health Inventory for Men Questionnaire and subjected to colored penile Doppler ultrasound. Periodontal parameters of probing depth and periodontal attachment level were recorded. Five patients with ED and CP were selected randomly for cardiac color Doppler to assess the integrity. RESULTS: Among the selected vasculogenic patients with ED, mild-to-moderate vasculogenic ED showed the highest prevalence, whereas prevalence for CP among all vasculogenic patients with ED was highest among severe ED (81.8%). Association of CP and vasculogenic ED was found to be correlated positively, but it showed no statistical significance. Two of five patients were found to have vascular insufficiency. CONCLUSIONS: It can be hypothesized that an association exists between vasculogenic ED and CP in young males. However, a large-scale study with confounder analysis and a longitudinal follow-up is warranted.", "title": "Association between chronic periodontitis and vasculogenic erectile dysfunction." }, { "docid": "MED-3288", "text": "In the fall of 2007, the Minnesota Department of Health was notified of 11 cases of an unexplained neurological illness, all linked to a pork processing plant, Quality Pork Processors, Inc., in Austin, MN. The cluster of workers had been experiencing similar symptoms, including fatigue, pain, numbness, and tingling in their extremities as well as weakness. The symptoms were described as more sensory than motor, and all patients had evidence of polyradiculoneuropathy with signs of nerve root irritation. An epidemiological investigation revealed that the only commonality between cases was their exposure to a pork brain extraction procedure involving compressed air. As relatives of the cases remained asymptomatic and all cultures for known pathogens were negative, the etiology of the syndrome seemed not to be infectious. Clinically, the syndrome was most akin to chronic inflammatory demyelinating polyneuropathy. Laboratory tests corroborated the clinical findings, revealing inflammation of peripheral nerves and nerve roots; however, these cases also had features clinically distinct from chronic inflammatory demyelinating polyneuropathy as well as laboratory testing revealing a novel immunoglobulin G immunostaining pattern. This suggested that the observed inflammation was the result of 1 or more unidentified antigens. This syndrome was ultimately dubbed progressive inflammatory neuropathy and was theorized to be an autoimmune reaction to aerosolized porcine neural tissue. Since the investigation's outset, 18 cases of progressive inflammatory neuropathy have been identified at the Minnesota pork processing plant, with 5 similar cases at an Indiana plant and 1 case at a Nebraskan plant. The plants in which cases have been identified have since stopped the use of compressed air in removing pork brains. All cases have stabilized or improved, with some requiring immunosuppressive and analgesic treatment. The study of progressive inflammatory neuropathy is ongoing, and the details of this investigation highlight the value of epidemiological principles in the identification and containment of outbreaks while researchers attempt to uncover the unique pathophysiology and potential etiology of the illness. Mt Sinai J Med 76:442-447, 2009. (c) 2009 Mount Sinai School of Medicine.", "title": "Outbreak of progressive inflammatory neuropathy following exposure to aerosolized porcine neural tissue." }, { "docid": "MED-4047", "text": "The total phenolic contents and antioxidant activities of garlics from California, Oregon, Washington, and New York were determined by Fourier transform infrared (FT-IR) spectroscopy (400-4000 cm(-1)). The total phenolic content was quantified [Folin-Ciocalteu assay (FC)] and three antioxidant activity assays, 2,2-diphenyl-picrylhydrazyl (DPPH) assay, Trolox equivalent antioxidant capacity (TEAC) assay, and ferric reducing antioxidant power (FRAP), were employed for reference measurements. Four independent partial least-squares regression (PLSR) models were constructed with spectra from 25 extracts and their corresponding FC, DPPH, TEAC, and FRAP with values for 20 additional extracts predicted (R > 0.95). The standard errors of calibration and standard error of cross-validation were <1.45 (TEAC), 0.36 (FRAP), and 0.33 μmol Trolox/g FW (DPPH) and 0.55 mg gallic acid/g FW (FC). Cluster and dendrogram analyses could segregate garlic grown at different locations. Hydroxyl and phenolic functional groups most closely correlated with garlic antioxidant activity.", "title": "Determination of total phenolic content and antioxidant activity of garlic (Allium sativum) and elephant garlic (Allium ampeloprasum) by attenuated..." }, { "docid": "MED-4068", "text": "The cooked meat derived genotoxic carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induces cancer of the colon, prostate and mammary gland when fed to rats. Epidemiology studies link these tumours to a Western diet and exposure to heterocyclic amines such as PhIP. We have shown that PhIP is also potently estrogenic and have proposed that this hormonal activity contributes to its target site carcinogenicity. We now postulate that the estrogenic properties of PhIP influence metastatic potential. We have used an in vitro assay for cell invasion based upon digestion and migration through a reconstituted basement membrane model. Zymography and immunoblotting were used to confirm PhIP-mediated changes associated with induction of the invasive phenotype. Treatment of the mammary cancer cell lines MCF-7 and T47D with PhIP induces cells to digest and migrate through a reconstituted basement membrane. The response was dose dependent, observed at sub-nanomolar concentrations of PhIP and was inhibited by the antiestrogen ICI 182,780. The PhIP-induced invasive phenotype was associated with expression of cathepsin D, cyclooxygenase-2 and matrix metalloproteinase activity. These findings emphasise the range and potency of the biological activities associated with this cooked meat product and mechanistically support the tissue-specific carcinogenicity of the chemical. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.", "title": "The cooked meat-derived mammary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine promotes invasive behaviour of breast cancer cells." }, { "docid": "MED-2383", "text": "During the last decades, nuts have attracted the attention of researchers for their potential benefits in cardiovascular prevention. We discuss here some aspects of the assumed beneficial effects of nuts, weighing them against potential harm. Epidemiological observations and controlled intervention trials consistently suggest that nuts consumption is associated with improved serum lipid profile, thus helping decrease cardiovascular risk. Being nuts an energy dense food, their impact on energy balance and body weight should be considered. In particular, the claim that adding nuts to the habitual diet, thus increasing calorie intake, does not cause body fat accumulation still needs evidence and biological plausibility. The potential risk associated with the relatively frequent occurrence of allergic reactions following the consumption of nuts is also discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.", "title": "The role of nuts in the optimal diet: time for a critical appraisal?" }, { "docid": "MED-4025", "text": "Excessive consumption of acidic drinks and foods contributes to tooth erosion. The aims of the present in vitro study were twofold: (1) to assess the erosive potential of different dietary substances and medications; (2) to determine the chemical properties with an impact on the erosive potential. We selected sixty agents: soft drinks, an energy drink, sports drinks, alcoholic drinks, juice, fruit, mineral water, yogurt, tea, coffee, salad dressing and medications. The erosive potential of the tested agents was quantified as the changes in surface hardness (ΔSH) of enamel specimens within the first 2 min (ΔSH2-0 = SH2 min - SHbaseline) and the second 2 min exposure (ΔSH4-2 = SH4 min - SH2 min). To characterise these agents, various chemical properties, e.g. pH, concentrations of Ca, Pi and F, titratable acidity to pH 7·0 and buffering capacity at the original pH value (β), as well as degree of saturation (pK - pI) with respect to hydroxyapatite (HAP) and fluorapatite (FAP), were determined. Erosive challenge caused a statistically significant reduction in SH for all agents except for coffee, some medications and alcoholic drinks, and non-flavoured mineral waters, teas and yogurts (P < 0·01). By multiple linear regression analysis, 52 % of the variation in ΔSH after 2 min and 61 % after 4 min immersion were explained by pH, β and concentrations of F and Ca (P < 0·05). pH was the variable with the highest impact in multiple regression and bivariate correlation analyses. Furthermore, a high bivariate correlation was also obtained between (pK - pI)HAP, (pK - pI)FAP and ΔSH.", "title": "Analysis of the erosive effect of different dietary substances and medications." }, { "docid": "MED-4073", "text": "The cooked meat carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induces tumours of the breast, colon and prostate in rats. Here we show that in addition to its well-established genotoxicity, which can be detected at concentrations >10(-6) M, PhIP is also oestrogenic. In COS-1 cells transiently transfected with an oestrogen-responsive reporter gene, PhIP (10(-10)-10(-6) M) mediated transcription through oestrogen receptor (ER) alpha, but not ER-beta, and inhibition by the pure ER antagonist ICI 182 780 demonstrated a requirement for a functional ER. In contrast, the structurally related food-derived carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) failed to induce reporter gene transcription. Additionally, we show that in a hormonally responsive breast cancer cell line (MCF-7 cells), PhIP induced transcriptional activation using endogenously expressed ER. Examination of the genotoxic potential of PhIP using a model mammalian cell mutation assay (hprt(-) locus) demonstrated that the genetic toxicology of PhIP was readily detectable, but separate, in terms of effective concentration, from its oestrogenic activity. To determine whether the oestrogenicity of PhIP could mediate oestrogen-dependent responses such as cell growth, we examined the growth of hormonally responsive cells (MCF-7 cells). We show that PhIP can stimulate cell proliferation and, again, this was dependent upon a functional ER. Using ligand blotting, we further show that PhIP can stimulate the expression of progesterone receptor (PR-A and PR-B) and c-MYC and activate the MAPK signal transduction pathway. These responses were similar to that produced by oestradiol, in terms of temporal aspects, potency and a requirement for a functional ER. Each of these dose-dependent mitogenic responses occurred at concentrations of PhIP ( approximately 10(-9)-10(-11)M) that are likely to be equivalent to systemic human exposure via consumption of cooked meat. Thus PhIP can induce cellular responses that encompass altered gene expression and mitogenesis. We suggest that the combination of genetic toxicology and oestrogen-like promotion of genomic and cellular events provide a mechanism for the tissue-specific tumorigenicity of this compound.", "title": "The cooked food derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine is a potent oestrogen: a mechanistic basis for its tissue-speci..." }, { "docid": "MED-1578", "text": "Crohn's disease is a complex inherited disorder of unknown pathogenesis with environmental, genetic and microbial factors involved in the development of the disease. A remarkable feature of this disease in childhood is the effective response to exclusive enteral nutrition (EEN) therapy and the need for complete exclusion of normal diet required for success (principle of exclusivity). EEN or dietary interventions might act through removal of dietary components, which affect microbial composition, decrease a proinflammatory response and promote restitution of the epithelial barrier, likewise allowing termination of this vicious disease-forming cycle before a critical threshold is reached. Multiple traditional and nontraditional dietary components may affect the microbiome, mucous layer, intestinal permeability, or adherence and translocation of pathobionts. We review the epidemiological data, as well as data from animal models and cell lines, and propose a model for pathogenesis we have termed the 'bacterial penetration cycle', whereby dietary components such as animal fat, high sugar intake and gliadin, and consumption of emulsifiers, maltodextrin as well as low-fiber diets may be able to cause a localized acquired bacterial clearance defect, leading to bacterial adhesion and penetration, and subsequently inflammation in the gut. © 2014 S. Karger AG, Basel.", "title": "Dietary clues to the pathogenesis of Crohn's disease." }, { "docid": "MED-3889", "text": "Contamination of retail chicken meat by Extended Spectrum Beta-Lactamase (ESBL) producing bacteria likely contributes to the increasing incidence of infections with these bacteria in humans. This study aimed to compare the prevalence and load of ESBL positive isolates between organic and conventional retail chicken meat samples, and to compare the distribution of ESBL genes, strain genotypes and co-resistance. In 2010, 98 raw chicken breasts (n=60 conventional; n=38 organic) were collected from 12 local stores in the Netherlands. Prevalence of ESBL producing micro-organisms was 100% on conventional and 84% on organic samples (p<0.001). Median loads of ESBL producing micro-organisms were 80 (range <20-1360) in conventional, and <20 (range 0-260) CFU/25 g in organic samples (p=0.001). The distribution of ESBL genes in conventional samples and organic samples was 42% versus 56%, respectively (N.S.), for CTX-M-1, 20% versus 42% (N.S.) for TEM-52, and 23% versus 3% (p<0.001) for SHV-12. CTX-M-2 (7%), SHV-2 (5%) and TEM-20 (3%) were exclusively found in conventional samples. Co-resistance rates of ESBL positive isolates were not different between conventional and organic samples (co-trimoxazole 56%, ciprofloxacin 14%, and tobramycin 2%), except for tetracycline, 73% and 46%, respectively, p<0.001). Six of 14 conventional meat samples harbored 4 MLST types also reported in humans and 5 of 10 organic samples harbored 3 MLST types also reported in humans (2 ST10, 2 ST23, ST354). In conclusion, the majority of organic chicken meat samples were also contaminated with ESBL producing E. coli, and the ESBL genes and strain types were largely the same as in conventional meat samples. Copyright © 2011 Elsevier B.V. All rights reserved.", "title": "Comparison of ESBL contamination in organic and conventional retail chicken meat." }, { "docid": "MED-2657", "text": "BACKGROUND: Japanese cedar pollinosis, caused by the pollen of the Japanese cedar tree (Cryptomeria japonica), is the commonest seasonal allergic disease in Japan. A number of epidemiological surveys have been reported on Japanese cedar pollinosis, but it has never been assessed systematically or quantitatively. To confirm the increasing prevalence of Japanese cedar pollinosis and related factors, we conducted a meta-regression analysis on population-based surveys in Japan. METHODS: We searched for data from population-based surveys in which serological methods were used to test all participants. Weighted regression of logit-transformed prevalence and sensitization rates were used to evaluate the effects of the year of survey, age, and degree of urbanization. We also analyzed the relationship between prevalence and sensitization rate. RESULTS: Thirty-eight reports with 27 subgroups for prevalence and 134 subgroups for sensitization rate were selected from the literature published in the years between 1986 and 2000. The Japanese cedar pollen sensitization rate was found to be significantly correlated with the year of survey, age, and degree of urbanization (adjusted R(2) = 0.55). The coefficient for the correlation between the prevalence and the sensitization rate revealed a statistically significant correlation (Pearson's r = 0.70, p < 0.001). CONCLUSIONS: The prevalence of Japanese cedar pollinosis among adolescents was predicted to be 28.7% in metropolitan areas and 24.5% in the general population in urban areas in the year 2004, derived from the estimated sensitization rate and the relationship between sensitization rate and prevalence. The prevalence of Japanese cedar pollinosis increased 2.6-fold between 1980 and 2000, and the prevalence differed considerably according to age and degree of urbanization. Copyright (c) 2005 S. Karger AG, Basel", "title": "Increasing prevalence of Japanese cedar pollinosis: a meta-regression analysis." }, { "docid": "MED-3877", "text": "OBJECTIVES: Dietary factors may influence the prostate and have an impact on prostatic growth and disease. A small number of studies have suggested that flaxseed-supplemented, fat-restricted diets may thwart prostate cancer growth in both animals and humans. Unknown, however, is the potential effect of such a diet on benign prostatic epithelium. METHODS: We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet affects the proliferation rates in benign epithelium. We also explored the effects on circulating levels of prostate-specific antigen (PSA), total testosterone, and cholesterol. Fifteen men who were scheduled to undergo repeat prostate biopsy were instructed to follow a low-fat (less than 20% kcal), flaxseed-supplemented (30 g/day) diet and were provided with a supply of flaxseed to last throughout the 6-month intervention period. The PSA, total testosterone, and cholesterol levels were determined at baseline and at 6 months of follow-up. Reports from the original and repeat biopsies were compared, and proliferation (MIB-1) rates were quantified in the benign prostatic epithelium. RESULTS: Statistically significant decreases in PSA (8.47 +/- 3.82 to 5.72 +/- 3.16 ng/mL; P = 0.0002) and cholesterol (241.1 +/- 30.8 to 213.3 +/- 51.2 mg/dL; P = 0.012) were observed. No statistically significant change was seen in total testosterone (434.5 +/- 143.6 to 428.3 +/- 92.5 ng/dL). Although 6-month repeat biopsies were not performed in 2 cases because of PSA normalization, of the 13 men who underwent repeat biopsy, the proliferation rates in the benign epithelium decreased significantly from 0.022 +/- 0.027 at baseline to 0.007 +/- 0.014 at 6 months of follow-up (P = 0.0168). CONCLUSIONS: These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect the biology of the prostate and associated biomarkers. A randomized controlled trial is needed to determine whether flaxseed supplementation, a low-fat diet, or a combination of the two regimens may be of use in controlling overall prostatic growth.", "title": "Pilot study to explore effects of low-fat, flaxseed-supplemented diet on proliferation of benign prostatic epithelium and prostate-specific antigen." }, { "docid": "MED-5194", "text": "BACKGROUND: Dairy consumption affects biological pathways associated with carcinogenesis. Evidence for a link between cancer risk and dairy consumption in adulthood is increasing, but associations with childhood dairy consumption have not been studied adequately. OBJECTIVE: We investigated whether dairy consumption in childhood is associated with cancer incidence and mortality in adulthood. DESIGN: From 1937 through 1939, some 4,999 children living in England and Scotland participated in a study of family food consumption, assessed from 7-d household food inventories. The National Health Service central register was used to ascertain cancer registrations and deaths between 1948 and 2005 in the 4,383 traced cohort members. Per capita household intake estimates for dairy products and calcium were used as proxy for individual intake. RESULTS: During the follow-up period, 770 cancer registrations or cancer deaths occurred. High childhood total dairy intake was associated with a near-tripling in the odds of colorectal cancer [multivariate odds ratio: 2.90 (95% CI: 1.26, 6.65); 2-sided P for trend = 0.005] compared with low intake, independent of meat, fruit, and vegetable intakes and socioeconomic indicators. Milk intake showed a similar association with colorectal cancer risk. High milk intake was weakly inversely associated with prostate cancer risk (P for trend = 0.11). Childhood dairy intake was not associated with breast and stomach cancer risk; a positive association with lung cancer risk was confounded by smoking behavior during adulthood. CONCLUSIONS: A family diet rich in dairy products during childhood is associated with a greater risk of colorectal cancer in adulthood. Confirmation of possible underlying biological mechanisms is needed.", "title": "Childhood dairy intake and adult cancer risk: 65-y follow-up of the Boyd Orr cohort." }, { "docid": "MED-3595", "text": "The effect of heavy metals at environmentally relevant concentrations on couple fecundity has received limited study despite ubiquitous exposure. In 2005–2009, couples (n=501) desiring pregnancy and discontinuing contraception were recruited and asked to complete interviews and to provide blood specimens for the quantification of cadmium (μg/L), lead (μg/dL) and mercury (μg/L) using inductively coupled plasma-mass spectrometry. Couples completed daily journals on lifestyle and intercourse along with menstruation and pregnancy testing for women. Couples were followed for 12 months or until pregnant. Fecundability odds ratios (FORs) and 95% confidence intervals (CIs) were estimated adjusting for age, body mass index, cotinine, and serum lipids in relation to female then male exposures. FORs <1 denote a longer time to pregnancy. In adjusted models, reduced FORs were observed for both female cadmium (0.78; 95% CI 0.63–0.97) and male lead (0.85; 95% CI 0.73–0.98) concentrations. When jointly modeling couples’ exposures, only male lead concentration significantly reduced the FOR (0.82; 95% CI 0.68, 0.97), though the FOR remained <1 for female cadmium (0.80; 95% CI 0.64, 1.00). This prospective couple based cohort with longitudinal capture of time to pregnancy is suggestive of cadmium and lead’s reproductive toxicity at environmentally relevant concentrations.", "title": "Heavy Metals and Couple Fecundity, the LIFE Study" }, { "docid": "MED-3570", "text": "A recent report that 93 per cent of invasive cervical cancers worldwide contain human papillomavirus (HPV) may be an underestimate, due to sample inadequacy or integration events affecting the HPV L1 gene, which is the target of the polymerase chain reaction (PCR)-based test which was used. The formerly HPV-negative cases from this study have therefore been reanalyzed for HPV serum antibodies and HPV DNA. Serology for HPV 16 VLPs, E6, and E7 antibodies was performed on 49 of the 66 cases which were HPV-negative and a sample of 48 of the 866 cases which were HPV-positive in the original study. Moreover, 55 of the 66 formerly HPV-negative biopsies were also reanalyzed by a sandwich procedure in which the outer sections in a series of sections are used for histological review, while the inner sections are assayed by three different HPV PCR assays targeting different open reading frames (ORFs). No significant difference was found in serology for HPV 16 proteins between the cases that were originally HPV PCR-negative and -positive. Type-specific E7 PCR for 14 high-risk HPV types detected HPV DNA in 38 (69 per cent) of the 55 originally HPV-negative and amplifiable specimens. The HPV types detected were 16, 18, 31, 33, 39, 45, 52, and 58. Two (4 per cent) additional cases were only HPV DNA-positive by E1 and/or L1 consensus PCR. Histological analysis of the 55 specimens revealed that 21 were qualitatively inadequate. Only two of the 34 adequate samples were HPV-negative on all PCR tests, as against 13 of the 21 that were inadequate ( p< 0.001). Combining the data from this and the previous study and excluding inadequate specimens, the worldwide HPV prevalence in cervical carcinomas is 99.7 per cent. The presence of HPV in virtually all cervical cancers implies the highest worldwide attributable fraction so far reported for a specific cause of any major human cancer. The extreme rarity of HPV-negative cancers reinforces the rationale for HPV testing in addition to, or even instead of, cervical cytology in routine cervical screening. Copyright 1999 John Wiley & Sons, Ltd.", "title": "Human papillomavirus is a necessary cause of invasive cervical cancer worldwide." }, { "docid": "MED-1924", "text": "Cellular senescence is an in vivo and in vitro phenomenon, accompanied by physiological changes including cessation of division and disturbances of organelle structure and function. Review of the literature was undertaken to determine whether there is evidence that whole organism aging and cell senescence share a common initiation pathway. In vivo aged cells of different lineages, including aged T lymphocytes, show high expression of the INK4A-p16 gene. In cell culture when telomeres are shortened past a key length or state, the Arf/Ink gene system (p16/p14 humans, p16/p19 mice) switches on and activates p53, which suppresses further cell division. The p53 gene is a key tumor suppressor and its deletion or mutation allows cancerous growth. The switching on of p53 also causes changes in fatty acid metabolism, especially down-regulation of both fatty acid synthase and stearoyl-CoA (delta-9) desaturase. The co-suppression of these genes together with enhanced uptake of extracellular fatty acids, leads to raised levels of cellular palmitate and induction of either apoptosis or senescence. In senescent cells, the fatty acid composition of the cellular membranes alters and leads to changes in both structure and function of organelles, especially mitochondria. Animal models of accelerated aging exhibit repression of stearoyl-CoA desaturase activity while anti-aging calorie restriction stimulates the same enzyme system. It is concluded that aging in cells and whole organisms share a common initiation pathway and that cellular senescence is protective against cancer. Healthy longevity is likely to be most enhanced by factors that actively suppress excessive cell division.", "title": "Saturated fatty acid metabolism is key link between cell division, cancer, and senescence in cellular and whole organism aging" }, { "docid": "MED-2997", "text": "If disease patterns emerge which show that certain diseases can be related, this is a valuable pointer to a common cause. This article traces the principle of interpreting disease relationships, illustrated by several common conditions of western civilization, for which the common cause is postulated as being removal of fiber from the diet.", "title": "The Etiological Significance of Related Diseases" }, { "docid": "MED-3448", "text": "Iodine is a suspected risk factor for thyroid cancer. Seaweed accounts for about 80% of Japanese people's iodine intake. We examined the association between seaweed consumption and the risk of thyroid cancer in Japanese women. Women participating in the Japan Public Health Center-based Prospective Study (n=52 679; age: 40-69 years) were followed up for a mean of 14.5 years; 134 new thyroid cancer cases, including 113 papillary carcinoma cases, were identified. Seaweed consumption was assessed using a food-frequency questionnaire and divided into three categories: 2 days/week or less (reference); 3-4 days/week; and almost daily. The Cox proportional hazards model was applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Seaweed consumption was clearly associated with an increased risk of papillary carcinoma (HR for almost daily consumption compared with 2 days/week or less=1.71; 95% CI: 1.01-2.90; trend P=0.04). After stratification for menopausal status, an increased risk was observed in postmenopausal women (papillary carcinoma HR for almost daily consumption compared with 2 days/week or less=3.81, 95% CI: 1.67-8.68; trend P<0.01), but not in premenopausal women (HR=0.91, 95% CI: 0.44-1.91; trend P=0.76). This study identified a positive association between seaweed consumption and the risk of thyroid cancer (especially for papillary carcinoma) in postmenopausal women.", "title": "Seaweed consumption and the risk of thyroid cancer in women: the Japan Public Health Center-based Prospective Study." }, { "docid": "MED-3577", "text": "PROBLEM/CONDITION: During the twenty first century, growth in the number of older adults (persons aged > or =65 years) in the United States will produce an unprecedented increase in the number of persons at risk for costly age-associated chronic diseases and other health conditions and injuries. REPORTING PERIOD: 1995-1996. DESCRIPTION OF SYSTEMS: This report uses data from CDC's National Center for Health Statistics (NCHS) to report on leading causes of death in 1996 (from the National Vital Statistics System), major causes of hospitalization (1996 National Hospital Discharge Survey [NHDSI), and major chronic conditions (1995 National Health Interview Survey [NHIS]). The National Vital Statistics System compiles information regarding all death certificates filed in the United States. NHDS is an annual probability sample of discharges from nonfederal, short-stay hospitals. NHIS is an ongoing annual cross-sectional household survey of the U.S. civilian, noninstitutionalized population. In addition, health-care expenditures for older adults are examined by using information obtained from published reports from the U.S. Health Care Financing Administration (HCFA) and health-services literature. RESULTS: The leading causes of death among adults aged > or =65 years were heart disease (1,808 deaths/100,000 population), malignant neoplasms (1,131/100,000), and cerebrovascular disease (415/100,000). Several leading causes of mortality among older adults differed by race, with deaths caused by Alzheimer's disease more frequent among whites and deaths caused by diabetes, kidney diseases, septicemia, and hypertension more frequent among blacks. Rates of hospitalization and length of hospital stays increased with age. Hospitalizations for heart disease represented the highest proportion of all discharges among older adults (23%). Discharge rates for malignant neoplasms, stroke, and pneumonia were similar for adults aged > or =65 years and, as with heart disease, were higher for men than for women. However, the rate of hospitalization for fractures among women exceeded the rate among men. Arthritis was the most prevalent chronic condition among adults aged > or =65 years (48.9/100 adults), followed by hypertension (40.3/100) and heart disease (28.6/100). In 1995, adults aged > or =65 years comprised 13% of the population but accounted for 35% of total personal health care dollars spent ($310 billion), and real per capita personal health-care expenditure for this age group increased at an average annual rate of 5.8% during 1985-1995. Projections for future medical expenditures for older adults vary; however, all project substantial increases after the year 2000. Hip fracture, dementia, and urinary incontinence are discussed as examples of prevalent and costly health conditions among older adults that differ in potential for prevention. These conditions were selected because they result in substantial medical and social costs and they differ in potential for prevention. INTERPRETATION: The higher prevalence of serious and costly health conditions among adults aged > or =65 years highlights the importance of implementing preventive health measures in this population. PUBLIC HEALTH ACTIONS: Data regarding causes of morbidity, mortality, and health-care expenditures among older adults provide information for measuring the effectiveness of public health efforts to reduce modifiable risk factors for morbidity and mortality in this population.", "title": "Surveillance for morbidity and mortality among older adults--United States, 1995-1996." }, { "docid": "MED-1585", "text": "As the incidence of twin gestation increases, it is important to consider the maternal risks associated with carrying multiples. Compared with singleton gestation, there are increased risks to the mother during the antepartum, intrapartum, and postpartum periods. Certain pregnancy complications are more likely to occur during a twin gestation, including preeclampsia and other hypertensive disorders, antepartum hospitalization for preterm labor or abnormal bleeding, nutritional deficiencies, cesarean delivery, and postpartum hemorrhage. Women carrying twins may benefit from early education regarding these issues, close maternal monitoring as well as physical therapy sessions, and nutrition counseling during their pregnancies. Copyright © 2012 Elsevier Inc. All rights reserved.", "title": "Effects of twin gestation on maternal morbidity." }, { "docid": "MED-4837", "text": "BACKGROUND: Gallstone disease known as cholelithiasis is the most common digestive surgical disorder and account for an important part of health care expenditure. Attempt was made to analyse the gallstone for typing depending upon the composition. AIMS & OBJECTIVES: The main objective of this study was to see the prevalence of different types of gallstone in Nepal and to correlate them with the clinical findings. MATERIALS & METHODS: Gallstones of 80 different patients who underwent cholecystectomy for cholelithiasis were collected from 20th January 2005 to 16th May 2006 in Department of Pathology, Kathmandu Medical College Teaching Hospital. Detailed history was taken. Stones were analyzed with chemical and enzymatic methods using clinical spectrophotometer. RESULTS & CONCLUSION: The most commonly involved age group for cholelithiasis (32.5%) is found to be 30-39 years with a female predominance (M: F=1:3.2). Cholelithiasis was found more commonly among non-vegetarian with the vegetarian: non-vegetarian ratio 1:9. Mixed type stone was found to be the most common type of stone comprising 78.75%, followed by cholesterol stone 12.5%, Brown pigment stone 7.5% and Black pigment stone 1.25%.", "title": "Prevalence of different types of gallstone in the patients with cholelithiasis at Kathmandu Medical College, Nepal." }, { "docid": "MED-4739", "text": "Contemporary reproductive aged women and their offspring are facing an unprecedented onslaught of toxicant exposures from myriad sources in their day-to-day life. Public health recommendations regarding optimal diet and nutrition in pregnancy must incorporate several considerations including safety of available foodstuffs, cultural practices and lifestyle issues. Gestational consumption of contaminated seafood remains a potential source of toxicant exposure, including mercury, for the developing child. Health care professionals responsible for the care of women and their developing children need to become apprised of: a) risks associated with toxicant bioaccumulation in pregnancy; b) ongoing information emerging in the important field of reproductive toxicology; and c) strategies within the clinical setting to facilitate nutritional sufficiency and precautionary avoidance of adverse exposure among young women.", "title": "Nowhere to hide: Chemical toxicants and the unborn child." }, { "docid": "MED-1771", "text": "Semen analysis of 66 unmarried medical students in the age group of 17-21 years was carried out. A higher liquefaction time pH, motility, lower sperm count and abnormal forms were observed compared to reported values. Liquefaction time, pH and sperm count was found significantly different in non-vegetarians and vegetarians, perhaps due to difference in their dietary proteins.", "title": "Some observations on human semen analysis." }, { "docid": "MED-4749", "text": "For the first time in the field of steroid residues in humans, demonstration of 19-norandrosterone (19-NA: 3alpha-hydroxy-5alpha-estran-17-one) and 19-noretiocholanolone (19-NE: 3alpha-hydroxy-5beta-estran-17-one) excretion in urine subsequent to boar consumption is reported. Three male volunteers agreed to consume 310 g of tissues from the edible parts (meat, liver, heart and kidney) of a boar. The three individuals delivered urine samples before and during 24 h after meal intake. After deconjugation of phase II metabolites, purification and specific derivatisation of target metabolites, the urinary extracts were analysed by mass spectrometry. Identification was carried out using measurements obtained by gas chromatography/high resolution mass spectrometry (GC/HRMS) (R = 7000) and liquid chromatography/tandem mass spectrometry (LC/MS/MS) (positive electrospray ionisation (ESI+)). Quantification was realised using a quadrupole mass filter. 19-NA and 19-NE concentrations in urine reached 3.1 to 7.5 microg/L nearby 10 hours after boar tissue consumption. Levels returned to endogenous values 24 hours after. These two steroids are usually exploited to confirm the exogenous administration of 19-nortestosterone (19-NT: 17beta-hydroxyestr-4-en-3-one), especially in the antidoping field. We have thus proved that eating tissues of non-castrated male pork (in which 17beta-nandrolone is present) might induce some false accusations of the abuse of nandrolone in antidoping. Copyright 2000 John Wiley & Sons, Ltd.", "title": "Consequence of boar edible tissue consumption on urinary profiles of nandrolone metabolites. I. Mass spectrometric detection and quantification of ..." }, { "docid": "MED-2848", "text": "Type 1 diabetes is increasing rapidly in many parts of the Western world, most evidently in Scandinavia. A low concordance rate of insulin-dependent diabetes mellitus among monozygotic twins clearly indicates that genetic risk factors may be necessary, but are not sufficient for the disease to occur. The strongest genetic risk markers are located in the HLA region of chromosome 6, but these DNA specificities differ in different populations. Risk genes are indicated in other chromosomes of the human genome, suggesting a complex interaction between genes and environment as the cause of the disease. The pathogenesis of the disease is proposed to be autoimmune in nature and environmental risk factors may either initiate autoimmunity or accelerate an already ongoing beta-cell destruction. Risk factors disclosed by epidemiological studies that may accelerate the pathogenetic process are: a cold environment, a high growth rate, infections and stressful life events. Risk factors that may initiate the autoimmune process include early exposure to cow's milk proteins, nitrosamines or early foetal events such as blood group incompatibility or foetal viral infections. In conclusion, population-based epidemiological studies have helped to confirm proposed aetiological models that have arisen from experimental research. These epidemiological studies have also introduced important new findings that may reveal the complex aetiology of the disease and advance understanding closer to the ultimate goal of primary prevention.", "title": "The aetiology of type 1 diabetes: an epidemiological perspective." }, { "docid": "MED-3437", "text": "INTRODUCTION: The use of the penile peak systolic velocity (PSV) measured in the flaccid state during penile color Doppler ultrasound (PCDU) examination has been questioned without substantial evidence. AIM: To assess the validity of PSV measured in the flaccid state during PCDU, in patients consulting for erectile dysfunction (ED). METHODS: A consecutive series of 1,346 (mean age 55.0 +/- 12.0 years) male patients was studied. MAIN OUTCOMES MEASURES: All patients underwent PCDU performed both in the flaccid state and dynamic (after prostaglandin E1 stimulation) conditions. A subset of 20 subjects with uncomplicated type 2 diabetes underwent diagnostic testing for silent coronary heart disease by means of adenosine stress myocardial perfusion scintigraphy (SPECT). In these subjects penile arterial flow was simultaneously assessed by PCDU before and after systemic adenosine administration. RESULTS: Flaccid PSV showed a significant (r = 0.513, P < 0.0001) correlation with dynamic PSV. Receiver operating characteristic (ROC) curve analysis demonstrated that when a threshold of 13 cm/seconds was chosen, flaccid PSV was predictive for dynamic PSV < 25 and <35 cm/seconds with an accuracy of 89% and 82%, respectively. Among the subset of patients who underwent SPECT, an impaired coronary flow reserve (ICFR) occurred in nine cases (45%). When the same threshold of <13 cm/seconds was chosen, PSV before SPECT was predictive of ICFR with an accuracy of 80% (area under the ROC curve = 0.798 +/- 0.10; P < 0.05). After adjustment for confounders, anxiety symptoms were related to dynamic PSV (Adj. r = -0.154, P < 0.05) but not to flaccid PSV. CONCLUSIONS: Our results show that flow in the cavernosal arteries can be routinely evaluated by PCDU in the flaccid state. Performing PCDU only in the flaccid state allows identifying subjects with pathological dynamic PSV with accuracy higher than 80%. Furthermore, our preliminary data suggest that the same examination could identify diabetic subjects with ICFR with an accuracy of 80%.", "title": "Penile doppler ultrasound in patients with erectile dysfunction (ED): role of peak systolic velocity measured in the flaccid state in predicting ar..." }, { "docid": "MED-1404", "text": "OBJECTIVE: The purpose of this work was to meta-analyze prospective studies that have evaluated the effect of a Mediterranean diet on the development of type 2 diabetes. MATERIALS/METHODS: PubMed, Embase and the Cochrane Central Register of Controlled Trials databases were searched up to 20 November 2013. English language publications were allocated; 17 original research studies (1 clinical trial, 9 prospective and 7 cross-sectional) were identified. Primary analyses were limited to prospective studies and clinical trials, yielding to a sample of 136,846 participants. A systematic review and a random effects meta-analysis were conducted. RESULTS: Higher adherence to the Mediterranean diet was associated with 23% reduced risk of developing type 2 diabetes (combined relative risk for upper versus lowest available centile: 0.77; 95% CI: 0.66, 0.89). Subgroup analyses based on region, health status of participants and number of confounders controlling for, showed similar results. Limitations include variations in Mediterranean diet adherence assessment tools, confounders' adjustment, duration of follow up and number of events with diabetes. CONCLUSIONS: The presented results are of major public health importance, since no consensus exists concerning the best anti-diabetic diet. Mediterranean diet could, if appropriately adjusted to reflect local food availability and individual's needs, constitute a beneficial nutritional choice for the primary prevention of diabetes. Copyright © 2014 Elsevier Inc. All rights reserved.", "title": "The effect of Mediterranean diet on the development of type 2 diabetes mellitus: a meta-analysis of 10 prospective studies and 136,846 participants." }, { "docid": "MED-4844", "text": "Rheumatoid arthritis (RA) is characterized by inflammation of the synovial tissues in the joints. A number of papers related to dietary components that are associated with this inflammation are reviewed. In addition, the ecological approach is used to study the links between diet and RA. Multi-country data for prevalence of RA for females from eight and fifteen countries were compared statistically with components of national dietary supply. Fat from meat and offal for the period 2 years before the prevalence data was found to have the highest statistical association with the prevalence of RA (r(2) 0.877, P<0.001 for eight countries). The statistical correlations for meat and offal were almost as high as those for their fat. Similar correlations were found for temporal changes in indices of effects of RA in several European countries between 1968 and 1978 as more meat was added to the national diets, although the correlations were higher for meat than for fat. It is hypothesized that meat and offal may be a major factor contributing to the inflammation in RA. In the present short review, the author examines some of the data that associate meat consumption with RA and the possible factors, e.g. fat, Fe and nitrite, which may contribute to the inflammation.", "title": "The role of meat in the expression of rheumatoid arthritis." }, { "docid": "MED-4896", "text": "BACKGROUND: In westernized societies, acne vulgaris is a nearly universal skin disease afflicting 79% to 95% of the adolescent population. In men and women older than 25 years, 40% to 54% have some degree of facial acne, and clinical facial acne persists into middle age in 12% of women and 3% of men. Epidemiological evidence suggests that acne incidence rates are considerably lower in nonwesternized societies. Herein we report the prevalence of acne in 2 nonwesternized populations: the Kitavan Islanders of Papua New Guinea and the Aché hunter-gatherers of Paraguay. Additionally, we analyze how elements in nonwesternized environments may influence the development of acne. OBSERVATIONS: Of 1200 Kitavan subjects examined (including 300 aged 15-25 years), no case of acne (grade 1 with multiple comedones or grades 2-4) was observed. Of 115 Aché subjects examined (including 15 aged 15-25 years) over 843 days, no case of active acne (grades 1-4) was observed. CONCLUSIONS: The astonishing difference in acne incidence rates between nonwesternized and fully modernized societies cannot be solely attributed to genetic differences among populations but likely results from differing environmental factors. Identification of these factors may be useful in the treatment of acne in Western populations.", "title": "Acne vulgaris: a disease of Western civilization." }, { "docid": "MED-2124", "text": "Acne appears to represent a visible indicator disease of over-activated mTORC1 signalling, an unfavour-able metabolic deviation on the road to serious common Western diseases of civilisation associated with increased body mass index and insulin resistance. Exaggerated mTORC1 signalling by Western diet explains the association of acne with increased body mass index, insulin resistance, and early onset of menarche. Both, a high glycaemic load and increased consumption of milk and milk products, staples of Western diet, aggravate mammalian target of rapamycin complex 1 signalling. This review of the literature summarises present evidence for an association between acne, increased body mass index, insulin resistance and Western diet. By dietary intervention with a Palaeolithic-type diet, the dermatologist has the chance to attenuate patients' increased mTORC1 signalling by reducing glycaemic load and milk consumption, which may not only improve acne but may delay the march to more serious mTORC1-driven diseases of civilisation.", "title": "Acne: risk indicator for increased body mass index and insulin resistance." }, { "docid": "MED-4585", "text": "The total phenolic content of 13 commercially available fruit juices and juice drinks, selected to represent the most popular juice flavors in the United Kingdom, were analyzed using the Folin-Ciocalteu assay. Individual phenolic compounds were identified and quantified using HPLC-PDA-MS2. The catechin content and degree of polymerization of proanthocyanidins were also analyzed. Purple grape juice contained the largest number of individual phenolic compounds and also the highest concentration of total phenolics. The main components were flavan-3-ols, anthocyanins, and hydroxycinnamates, which accounted for 93% of the total phenolic content. In contrast, white grape juice, which contained principally hydroxycinnamates, had the lowest total phenolic content. Antioxidant activity was measured using the ORAC and FRAP assays, and the data obtained were in broad agreement with total phenol content. In view of the recent findings of the Kame project indicating that long-term fruit juice consumption can provide protection against Alzheimer's disease (Dai et al. Am. J. Med. 2006, 379, 464-475), it is suggested that the protective effects may be enhanced by consumption of a combination of juices rich in phenolics and containing a diverse variety of individual phenolic compounds, namely, juices derived from purple grapes, grapefruit, cranberries, and apples.", "title": "Evaluation of phenolic compounds in commercial fruit juices and fruit drinks." }, { "docid": "MED-2672", "text": "To quantify objectionable levels of connective tissues, restructured beef products were made with 2·5 and 5% added tendon; 5 and 10% added epimysium, gristle, or peri/endomysium; and a control. Initial tenderness (IT), residual connective tissue (CT), and overall texture (OT) were evaluated by a sensory panel. Panelists adversely scored IT, CT, and OT for 2·5 and 5% tendon and CT and OT for 10% epimysium and gristle. CT and OT scores correlated with hydroxyproline content and Lee-Kramer peak shear force for uncooked steaks with added tendon, gristle and epimysium but not peri/endomysium. Acceptable products can be made when raw materials are free of tendons and contain only limited amounts of epimysium. Copyright © 1990. Published by Elsevier Ltd.", "title": "Effects of added connective tissues on the sensory and mechanical properties of restructured beef steaks." }, { "docid": "MED-4852", "text": "OBJECTIVES: A dietary link to rheumatoid arthritis (RA) has been suspected and an influence on arthritic symptoms by different diets has been reported. Our primary aim was to record the self-experienced adverse food reactions in patients with RA. A secondary aim was to relate self-experienced adverse reactions to dairy produce and wheat to the local mucosal reactivity observed after rectal challenge with cow's milk protein (CM) and wheat gluten. METHODS: A questionnaire about self-experienced adverse reaction to food was sent to 347 RA patients. Rectal challenge with CM and gluten was performed in 27 of these patients and in healthy controls (n = 18). After a 15-h challenge the mucosal production of nitric oxide (NO) and the mucosal release of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were measured by using the mucosal patch technique. RESULTS: Twenty-seven per cent of the RA patients reported food intolerance (FI) to various foods, and in particular to CM, meat, and wheat gluten. Strong mucosal reactivity to CM was observed in 11% of the patients. Moderately increased mucosal reactivity to CM and gluten was found in 22% and 33%, respectively, of the patients. No relationship was found between self-experienced adverse reactions to CM or gluten and mucosal reactivity to these proteins. CONCLUSIONS: Perceived FI is reported frequently by RA patients, with a prevalence similar to that reported previously in the general population. Mucosal reactivity to CM and gluten is seen in a minor fraction of RA patients and is not related to the frequently perceived intolerance to these proteins.", "title": "Self-reported food intolerance and mucosal reactivity after rectal food protein challenge in patients with rheumatoid arthritis." }, { "docid": "MED-2849", "text": "Higher egg and cholesterol intakes are associated with increased risk of type 2 diabetes mellitus. However, their association with gestational diabetes mellitus (GDM) has not been evaluated. The authors assessed such associations in both a prospective cohort study (1996–2008; 3,158 participants) and a case-control study (1998–2002; 185 cases, 411 controls). A food frequency questionnaire was used to assess maternal diet. Multivariable models were used to derive relative risks and 95% confidence intervals. Compared with no egg consumption, adjusted relative risks for GDM were 0.94, 1.01, 1.12, 1.54, and 2.52 for consumption of ≤1, 2–3, 4–6, 7–9, and ≥10 eggs/week, respectively (P for trend = 0.008). Women with high egg consumption (≥7/week) had a 1.77-fold increased risk compared with women with lower consumption (95% confidence interval (CI): 1.19, 2.63). The relative risk for the highest quartile of cholesterol intake (≥294 mg/day) versus the lowest (<151 mg/day) was 2.35 (95% CI: 1.35, 4.09). In the case-control study, the adjusted odds ratio for consuming ≥7 eggs/week versus <7 eggs/week was 2.65 (95% CI: 1.48, 4.72), and the odds of GDM increased with increasing cholesterol intake (P for trend = 0.021). In conclusion, high egg and cholesterol intakes before and during pregnancy are associated with increased risk of GDM.", "title": "Risk of Gestational Diabetes Mellitus in Relation to Maternal Egg and Cholesterol Intake" }, { "docid": "MED-2495", "text": "We investigated whether prenatal exposure from the maternal diet to the toxicants polychlorinated biphenyls (PCBs) and dioxins is associated with the development of immune-related diseases in childhood. Children participating in BraMat, a sub-cohort of the Norwegian Mother and Child Cohort Study (MoBa), were followed in the three first years of life using annual questionnaires (0-3years; n=162, 2-3years; n=180), and blood parameters were examined at three years of age (n=114). The maternal intake of the toxicants was calculated using a validated food frequency questionnaire from MoBa. Maternal exposure to PCBs and dioxins was found to be associated with an increased risk of wheeze and more frequent upper respiratory tract infections. Furthermore, maternal exposure to PCBs and dioxins was found to be associated with reduced antibody response to a measles vaccine. No associations were found between prenatal exposure and immunophenotype data, allergic sensitization and vaccine-induced antibody responses other than measles. Our results suggest that prenatal dietary exposure to PCBs and dioxins may increase the risk of wheeze and the susceptibility to infectious diseases in early childhood. Copyright © 2012 Elsevier Ltd. All rights reserved.", "title": "Prenatal exposure to polychlorinated biphenyls and dioxins from the maternal diet may be associated with immunosuppressive effects that persist int..." }, { "docid": "MED-2678", "text": "Smoked foods including turkey, pork, chicken, beef and fish products were screened for the presence of carcinogenic and non-carcinogenic polycyclic aromatic hydrocarbons (PAHs). Eighteen commercial liquid smoke flavourings and seasonings were also analysed. Total PAH concentrations in smoked meat products ranged from 2.6 micrograms/kg in a cooked ham sample to 29.8 micrograms/kg in grilled pork chops, while those in fish products ranged from 9.3 micrograms/kg in smoked shrimp to 86.6 micrograms/kg in smoked salmon. Total concentrations of the carcinogenic PAHs (benzo[a]anthracene, benzo[b]fluoranthene, benzo[a]pyrene, dibenzo[a,h]anthracene, and indeno[1,2,3-c,d]pyrene) ranged from non-detectable in several meat products to 7.4 micrograms/kg in grilled pork chops, and from 0.2 micrograms/kg in trout to 16.0 micrograms/kg in salmon. In liquid smoke flavourings and seasonings, total PAH concentrations ranged from 6.3 to 43.7 micrograms/kg, with the carcinogenic PAHs ranging from 0.3 to 10.2 micrograms/kg.", "title": "Polycyclic aromatic hydrocarbons in smoked food products and commercial liquid smoke flavourings." }, { "docid": "MED-3786", "text": "This article describes the development of a series of choline- and betaine-controlled diets that were served to research subjects as part of an ongoing study of diet requirements in humans. These diets were developed based on the analysis of choline and betaine in individual foods. The calculated diets were compared with analyses of all foods combined into a single sample for each day. The laboratory analyses of choline and betaine in the whole-diet aliquots matched the estimated amounts in the diets that were calculated from the analyses of individual foods. These diets were adjusted for several levels of choline and betaine and were well accepted by research subjects who consumed them for a time period of up to 2 months. This article describes applications of this diet for use in clinical research on methyl-group requirements in humans and for use in clinical practice for counseling the client who requires a choline-controlled diet.", "title": "Choline- and betaine-defined diets for use in clinical research and for the management of trimethylaminuria." }, { "docid": "MED-3434", "text": "INTRODUCTION: Although epidemiological evidence seems to support a role for lifestyle factors in the pathogenesis of erectile dysfunction (ED), limited data are available suggesting that dietary changes may improve ED. AIM: To provide an update on clinical evidence regarding the role of dietary factors in ED. METHODS: A systematic literature search was performed using MEDLINE and other database (EMBASE, SCOPUS) with MeSH terms and keywords for \"erectile dysfunction\", \"diet\", \"dietary patterns\", \"Mediterranean diet\", and \"lifestyle\". MAIN OUTCOME MEASURES: To examine the data relating to erectile dysfunction with dietary factors, its relationship and the impact of dietary treatment. RESULTS: Only few studies assessed the role or the effect of diet on ED. A dietary pattern which is high in fruit, vegetables, nuts, whole grains, and fish but low in red and processed meat and refined grains is more represented in subjects without ED. Mediterranean diet has been proposed as a healthy dietary pattern based on evidence that greater adherence to this diet is associated with lower all-cause and disease-specific survival. In type 2 diabetic men, those with the highest adherence to the Mediterranean diet had the lowest prevalence of ED and were more likely to be sexually active. In clinical trials, Mediterranean diet was more effective than a control diet in ameliorating ED or restoring absent ED in people with obesity or metabolic syndrome. CONCLUSION: The adoption of a Mediterranean diet may be associated with an improvement of erectile dysfunction.", "title": "Dietary factors, Mediterranean diet and erectile dysfunction." }, { "docid": "MED-3198", "text": "BACKGROUND: Despite its high content of saturated fatty acids, cheese does not seem to increase plasma total and LDL-cholesterol concentrations when compared with an equivalent intake of fat from butter. This effect may be due to the high calcium content of cheese, which results in a higher excretion of fecal fat. OBJECTIVES: The objective was to compare the effects of diets of equal fat content rich in either hard cheese or butter or a habitual diet on blood pressure and fasting serum blood lipids, C-reactive protein, glucose, and insulin. We also examined whether fecal fat excretion differs with the consumption of cheese or butter. DESIGN: The study was a randomized dietary intervention consisting of two 6-wk crossover periods and a 14-d run-in period during which the subjects consumed their habitual diet. The study included 49 men and women who replaced part of their habitual dietary fat intake with 13% of energy from cheese or butter. RESULTS: After 6 wk, the cheese intervention resulted in lower serum total, LDL-, and HDL-cholesterol concentrations and higher glucose concentrations than did the butter intervention. Cheese intake did not increase serum total or LDL-cholesterol concentrations compared with the run-in period, during which total fat and saturated fat intakes were lower. Fecal fat excretion did not differ between the cheese and butter periods. CONCLUSION: Cheese lowers LDL cholesterol when compared with butter intake of equal fat content and does not increase LDL cholesterol compared with a habitual diet. This trial is registered at clinicaltrials.gov as NCT01140165.", "title": "Cheese intake in large amounts lowers LDL-cholesterol concentrations compared with butter intake of equal fat content." }, { "docid": "MED-4735", "text": "BACKGROUND/OBJECTIVES: To assess biomarkers and frequency questions as measures of fish consumption. SUBJECTS/METHODS: Participants in the Fishermen substudy numbered 125 men and 139 women (aged 22-74), and in the Health 2000 substudy, 577 men and 712 women (aged 45-74) participated. The aim of the Fishermen study was to examine the overall health effect of fish consumption in a high-consumption population, whereas the aim of the Health 2000 substudy was to obtain in-depth information on cardiovascular diseases and diabetes. Fish consumption was measured by the same validated food frequency questionnaire (FFQ) in both the studies, with a further two separate frequency questions used in the Fishermen substudy. Dioxins, polychlorinated biphenyls (PCBs) and methyl mercury (MeHg) (in the Fishermen substudy alone), and omega-3 polyunsaturated fatty acids (omega-3 PUFAs) (in both studies) were analyzed from fasting serum/blood samples. RESULTS: The Spearman's correlation coefficients between FFQ fish consumption and dioxins, PCBs, MeHg and omega-3 PUFAs were respectively 0.46, 0.48, 0.43 and 0.38 among the Fishermen substudy men, and 0.28, 0.36, 0.45 and 0.31 among women. Similar correlation coefficients were observed between FFQ fish consumption and serum omega-3 PUFAs in the Health 2000 substudy, and also between FFQ fish consumption and the frequency questions on fish consumption in the Fishermen substudy. According to multiple regression modeling and LMG metrics, the most important fish consumption biomarkers were dioxins and PCBs among the men and MeHg among the women. CONCLUSIONS: Environmental contaminants seemed to be slightly better fish consumption biomarkers than omega-3 PUFAs in the Baltic Sea area. The separate frequency questions measured fish consumption equally well when compared with the FFQ.", "title": "Dioxins, polychlorinated biphenyls, methyl mercury and omega-3 polyunsaturated fatty acids as biomarkers of fish consumption." }, { "docid": "MED-2488", "text": "Cardiovascular diseases (CVD) cost Americans billions of dollars per year. High cholesterol levels, which are closely related to dietary habits, are a major contributor to CVD. In this article, we study whether changes in food prices are related to cholesterol levels and whether taxes or subsidies on particular foods would be effective in lowering cholesterol levels and, consequently, CVD costs. We find that prices of vegetables, processed foods, whole milk and whole grains are significantly associated with blood cholesterol levels. Having analyzed the costs and benefits of government interventions, we find that a subsidy of vegetables and whole grains would be an efficient way to reduce CVD expenditures. Published by Elsevier B.V.", "title": "Food prices and blood cholesterol." }, { "docid": "MED-3369", "text": "Background: Strategies are needed to increase children's intake of a variety of vegetables, including vegetables that are not well liked. Objective: We investigated whether incorporating puréed vegetables into entrées to reduce the energy density (ED; in kcal/g) affected vegetable and energy intake over 1 d in preschool children. Design: In this crossover study, 3- to 5-y-old children (n = 40) were served all meals and snacks 1 d/wk for 3 wk. Across conditions, entrées at breakfast, lunch, dinner, and evening snack were reduced in ED by increasing the proportion of puréed vegetables. The conditions were 100% ED (standard), 85% ED (tripled vegetable content), and 75% ED (quadrupled vegetable content). Entrées were served with unmanipulated side dishes and snacks, and children were instructed to eat as much as they liked. Results: The daily vegetable intake increased significantly by 52 g (50%) in the 85% ED condition and by 73 g (73%) in the 75% ED condition compared with that in the standard condition (both P < 0.0001). The consumption of more vegetables in entrées did not affect the consumption of the vegetable side dishes. Children ate similar weights of food across conditions; thus, the daily energy intake decreased by 142 kcal (12%) from the 100% to 75% ED conditions (P < 0.05). Children rated their liking of manipulated foods similarly across ED amounts. Conclusion: The incorporation of substantial amounts of puréed vegetables to reduce the ED of foods is an effective strategy to increase the daily vegetable intake and decrease the energy intake in young children. This trial was registered at clinicaltrials.gov as NCT01252433.", "title": "Hiding vegetables to reduce energy density: an effective strategy to increase children's vegetable intake and reduce energy intake" }, { "docid": "MED-1380", "text": "Objective To investigate the relative importance of the individual components of the Mediterranean diet in generating the inverse association of increased adherence to this diet and overall mortality. Design Prospective cohort study. Setting Greek segment of the European Prospective Investigation into Cancer and nutrition (EPIC). Participants 23 349 men and women, not previously diagnosed with cancer, coronary heart disease, or diabetes, with documented survival status until June 2008 and complete information on nutritional variables and important covariates at enrolment. Main outcome measure All cause mortality. Results After a mean follow-up of 8.5 years, 652 deaths from any cause had occurred among 12 694 participants with Mediterranean diet scores 0-4 and 423 among 10 655 participants with scores of 5 or more. Controlling for potential confounders, higher adherence to a Mediterranean diet was associated with a statistically significant reduction in total mortality (adjusted mortality ratio per two unit increase in score 0.864, 95% confidence interval 0.802 to 0.932). The contributions of the individual components of the Mediterranean diet to this association were moderate ethanol consumption 23.5%, low consumption of meat and meat products 16.6%, high vegetable consumption 16.2%, high fruit and nut consumption 11.2%, high monounsaturated to saturated lipid ratio 10.6%, and high legume consumption 9.7%. The contributions of high cereal consumption and low dairy consumption were minimal, whereas high fish and seafood consumption was associated with a non-significant increase in mortality ratio. Conclusion The dominant components of the Mediterranean diet score as a predictor of lower mortality are moderate consumption of ethanol, low consumption of meat and meat products, and high consumption of vegetables, fruits and nuts, olive oil, and legumes. Minimal contributions were found for cereals and dairy products, possibly because they are heterogeneous categories of foods with differential health effects, and for fish and seafood, the intake of which is low in this population.", "title": "Anatomy of health effects of Mediterranean diet: Greek EPIC prospective cohort study" }, { "docid": "MED-2251", "text": "The ubiquitous food contaminant cadmium has features of an estrogen mimetic that may promote the development of estrogen-dependent malignancies, such as breast cancer. However, no prospective studies of cadmium exposure and breast cancer risk have been reported. We examined the association between dietary cadmium exposure (at baseline, 1987) and the risk of overall and estrogen receptor (ER)-defined (ER(+) or ER(-)) breast cancer within a population-based prospective cohort of 55,987 postmenopausal women. During an average of 12.2 years of follow-up, 2,112 incident cases of invasive breast cancer were ascertained (1,626 ER(+) and 290 ER(-)). After adjusting for confounders, including consumption of whole grains and vegetables (which account for 40% of the dietary exposure, but also contain putative anticarcinogenic phytochemicals), dietary cadmium intake was positively associated with overall breast cancer tumors, comparing the highest tertile with the lowest [rate ratio (RR), 1.21; 95% confidence interval (CI), 1.07-1.36; P(trend) = 0.02]. Among lean and normal weight women, statistically significant associations were observed for all tumors (RR, 1.27; 95% CI, 1.07-1.50) and for ER(+) tumors (RR, 1.25; 95% CI, 1.03-1.52) and similar, but not statistically significant associations were found for ER(-) tumors (RR, 1.22; 95% CI, 0.76-1.93). The risk of breast cancer increased with increasing cadmium exposure similarly within each tertile of whole grain/vegetable consumption and decreased with increasing consumption of whole grain/vegetables within each tertile of cadmium exposure (P(interaction) = 0.73). Overall, these results suggest a role for dietary cadmium in postmenopausal breast cancer development.", "title": "Dietary cadmium exposure and risk of postmenopausal breast cancer: a population-based prospective cohort study." }, { "docid": "MED-2353", "text": "Summary Anti-Gal is the most abundant natural antibody in humans, constituting ∼ 1% of immunoglobulins. Anti-Gal is naturally produced also in apes and Old World monkeys. The ligand of anti-Gal is a carbohydrate antigen called the ‘α-gal epitope’ with the structure Galα1-3Galβ1-4GlcNAc-R. The α-gal epitope is present as a major carbohydrate antigen in non-primate mammals, prosimians and New World monkeys. Anti-Gal can contributes to several immunological pathogeneses. Anti-Gal IgE produced in some individuals causes allergies to meat and to the therapeutic monoclonal antibody cetuximab, all presenting α-gal epitopes. Aberrant expression of the α-gal epitope or of antigens mimicking it in humans may result in autoimmune processes, as in Graves' disease. α-Gal epitopes produced by Trypanosoma cruzi interact with anti-Gal and induce ‘autoimmune like’ inflammatory reactions in Chagas' disease. Anti-Gal IgM and IgG further mediate rejection of xenografts expressing α-gal epitopes. Because of its abundance, anti-Gal may be exploited for various clinical uses. It increases immunogenicity of microbial vaccines (e.g. influenza vaccine) presenting α-gal epitopes by targeting them for effective uptake by antigen-presenting cells. Tumour lesions are converted into vaccines against autologous tumour-associated antigens by intra-tumoral injection of α-gal glycolipids, which insert into tumour cell membranes. Anti-Gal binding to α-gal epitopes on tumour cells targets them for uptake by antigen-presenting cells. Accelerated wound healing is achieved by application of α-gal nanoparticles, which bind anti-Gal, activate complement, and recruit and activate macrophages that induce tissue regeneration. This therapy may be of further significance in regeneration of internally injured tissues such as ischaemic myocardium and injured nerves.", "title": "Anti-Gal: an abundant human natural antibody of multiple pathogeneses and clinical benefits" }, { "docid": "MED-3541", "text": "OBJECTIVE: The study evaluated the association between consumption frequencies of the major food categories and the risk of new depression four years later in older Taiwanese. DESIGN: A prospective cohort study with multistage random sampling. Logistic regression analysis evaluated the significance of the longitudinal associations of intake frequencies of the major food categories with future (4 years later) risk of new depression, controlled for possible confounding factors with or without adjustment for cognitive status. SETTING: Population-based free-living elderly. SUBJECTS: Men and women (n 1609) ≥65 years of age. RESULTS: In a regression model that controlled for demographic, socio-economic, lifestyle and disease/health-related variables but not cognitive status, both fruits (OR = 0·66, 95 % CI 0·45, 0·98, P = 0·038) and vegetables (OR = 0·38, 95 % CI 0·17, 0·86, P = 0·021) were protective against depressive symptoms 4 years later. However, when the same regression model was also adjusted for cognitive status, only vegetables (OR = 0·40, 95 % CI 0·17, 0·95, P = 0·039) were protective against depressive symptoms. Higher consumption of eggs was close to being significant in both regression models (P = 0·087 and 0·069, respectively). Other food categories including meat/poultry, fish, seafood, dairy, legumes, grains and tea showed no significant associations. CONCLUSIONS: Results suggest that although confounding factors cannot be totally ruled out, more frequent consumption of vegetables seems to be protective against depressive symptoms in the elderly. Further studies are needed to elucidate the causal role and the mechanism of the association.", "title": "Frequent consumption of vegetables predicts lower risk of depression in older Taiwanese - results of a prospective population-based study." }, { "docid": "MED-1920", "text": "Overweight and obesity are major contributors to both type 2 diabetes and cardiovascular disease (CVD). Moreover, individuals with type 2 diabetes who are overweight or obese are at particularly high risk for CVD morbidity and mortality. Although short-term weight loss has been shown to ameliorate obesity-related metabolic abnormalities and CVD risk factors, the long-term consequences of intentional weight loss in overweight or obese individuals with type 2 diabetes have not been adequately examined. The primary objective of the Look AHEAD clinical trial is to assess the long-term effects (up to 11.5 years) of an intensive weight loss program delivered over 4 years in overweight and obese individuals with type 2 diabetes. Approximately 5000 male and female participants who have type 2 diabetes, are 45-74 years of age, and have a body mass index >or=25 kg/m(2) will be randomized to one of the two groups. The intensive lifestyle intervention is designed to achieve and maintain weight loss through decreased caloric intake and increased physical activity. This program is compared to a control condition given diabetes support and education. The primary study outcome is time to incidence of a major CVD event. The study is designed to provide a 0.90 probability of detecting an 18% difference in major CVD event rates between the two groups. Other outcomes include components of CVD risk, cost and cost-effectiveness, diabetes control and complications, hospitalizations, intervention processes, and quality of life.", "title": "Look AHEAD (Action for Health in Diabetes): design and methods for a clinical trial of weight loss for the prevention of cardiovascular disease in ..." }, { "docid": "MED-3090", "text": "Background Hyperphosphatemia has been identified in the past decade as a strong predictor of mortality in advanced chronic kidney disease (CKD). For example, a study of patients in stage CKD 5 (with an annual mortality of about 20%) revealed that 12% of all deaths in this group were attributable to an elevated serum phosphate concentration. Recently, a high-normal serum phosphate concentration has also been found to be an independent predictor of cardiovascular events and mortality in the general population. Therefore, phosphate additives in food are a matter of concern, and their potential impact on health may well have been underappreciated. Methods We reviewed pertinent literature retrieved by a selective search of the PubMed and EU databases (www.zusatzstoffe-online.de, www.codexalimentarius.de), with the search terms “phosphate additives” and “hyperphosphatemia.” Results There is no need to lower the content of natural phosphate, i.e. organic esters, in food, because this type of phosphate is incompletely absorbed; restricting its intake might even lead to protein malnutrition. On the other hand, inorganic phosphate in food additives is effectively absorbed and can measurably elevate the serum phosphate concentration in patients with advanced CKD. Foods with added phosphate tend to be eaten by persons at the lower end of the socioeconomic scale, who consume more processed and “fast” food. The main pathophysiological effect of phosphate is vascular damage, e.g. endothelial dysfunction and vascular calcification. Aside from the quality of phosphate in the diet (which also requires attention), the quantity of phosphate consumed by patients with advanced renal failure should not exceed 1000 mg per day, according to the guidelines. Conclusion Prospective controlled trials are currently unavailable. In view of the high prevalence of CKD and the potential harm caused by phosphate additives to food, the public should be informed that added phosphate is damaging to health. Furthermore, calls for labeling the content of added phosphate in food are appropriate.", "title": "Phosphate Additives in Food—a Health Risk" }, { "docid": "MED-1801", "text": "OBJECTIVE: In 1976, the Royal College of Physicians and the British Cardiac Society recommended eating less fatty red meat and more poultry instead because it was lean. However, the situation has changed since that time, with a striking increase in fat content of the standard broiler chicken. The aim of the present study was to report a snapshot of data on fat in chickens now sold to the public. DESIGN: Samples were obtained randomly between 2004 and 2008 from UK supermarkets, farm shops and a football club. The amount of chicken fat was estimated by emulsification and chloroform/methanol extraction. SETTING: Food sold in supermarkets and farms in England. SUBJECTS: Chicken samples. RESULTS: The fat energy exceeded that of protein. There has been a loss of n-3 fatty acids. The n-6:n-3 ratio was found to be as high as 9:1, as opposed to the recommendation of about 2:1. Moreover, the TAG level in the meat and whole bird mostly exceeded the proportion of phospholipids, which should be the higher for muscle function. The n-3 fatty acid docosapentaenoic acid (DPA, 22 : 5n-3) was in excess of DHA (22 : 6n-3). Previous analyses had, as usual for birds, more DHA than DPA. CONCLUSIONS: Traditional poultry and eggs were one of the few land-based sources of long-chain n-3 fatty acids, especially DHA, which is synthesized from its parent precursor in the green food chain. In view of the obesity epidemic, chickens that provide several times the fat energy compared with protein seem illogical. This type of chicken husbandry needs to be reviewed with regard to its implications for animal welfare and human nutrition.", "title": "Modern organic and broiler chickens sold for human consumption provide more energy from fat than protein." }, { "docid": "MED-2402", "text": "Despite a proposed protective effect of fish intake on the risk of cardiovascular disease, epidemiologic evidence on fish intake and mortality is inconsistent. We investigated associations of fish intake, assessed through a validated food frequency questionnaire, with risks of total and cause-specific mortality in 2 prospective cohort studies of 134,296 Chinese men and women (1997–2009). Vital status and date and cause of death were ascertained through annual linkage to the Shanghai Vital Statistics Registry database and biennial home visits. Cox regression was used to calculate hazard ratios and corresponding 95% confidence intervals. After excluding the first year of observation, the analysis included 3,666 deaths among women and 2,170 deaths among men. Fish intake was inversely associated with risks of total, ischemic stroke, and diabetes mortality; the corresponding hazard ratios for the highest quintiles of intake compared with the lowest were 0.84 (95% confidence interval (CI): 0.76, 0.92), 0.63 (95% CI: 0.41, 0.94), and 0.61 (95% CI: 0.39, 0.95), respectively. No associations with cancer or ischemic heart disease mortality were observed. Further analyses suggested that the inverse associations with total, ischemic stroke, and diabetes mortality were primarily related to consumption of saltwater fish and intake of long-chain n-3 fatty acids. Overall, our findings support the postulated health benefits of fish consumption.", "title": "Fish Intake and Risks of Total and Cause-specific Mortality in 2 Population-based Cohort Studies of 134,296 Men and Women" }, { "docid": "MED-3928", "text": "Seven patients with Parkinson's disease who experienced severe motor fluctuations in response to levodopa were studied in detail with relation to the effect of dietary protein on their motor function. The levodopa dose for each patient was not changed during the period of study, and no other antiparkinsonian drugs were used. Regular and high-protein diets resulted in a marked elevation in the plasma concentrations of large neutral amino acids (LNAAs) that are known to compete with levodopa for transport across the blood-brain barrier. Despite elevated plasma levodopa levels, all patients with elevated LNAA levels experienced parkinsonian symptoms. When the amino acid level dropped while plasma levodopa levels were elevated, patients experienced relief of these symptoms. On a low-protein diet, LNAA levels remained low and all patients were consistently dyskinetic throughout the day, even though the mean plasma levodopa levels were somewhat lower than when the patients consumed a high-protein diet. A redistribution diet that is virtually protein free until supper and then unrestricted until bedtime is tolerated by patients because this simple manipulation permits near-normal daytime motor function.", "title": "Plasma levels of amino acids correlate with motor fluctuations in parkinsonism." }, { "docid": "MED-4845", "text": "Fasting is an effective treatment for rheumatoid arthritis, but most patients relapse on reintroduction of food. The effect of fasting followed by one year of a vegetarian diet was assessed in a randomised, single-blind controlled trial. 27 patients were allocated to a four-week stay at a health farm. After an initial 7-10 day subtotal fast, they were put on an individually adjusted gluten-free vegan diet for 3.5 months. The food was then gradually changed to a lactovegetarian diet for the remainder of the study. A control group of 26 patients stayed for four weeks at a convalescent home, but ate an ordinary diet throughout the whole study period. After four weeks at the health farm the diet group showed a significant improvement in number of tender joints, Ritchie's articular index, number of swollen joints, pain score, duration of morning stiffness, grip strength, erythrocyte sedimentation rate, C-reactive protein, white blood cell count, and a health assessment questionnaire score. In the control group, only pain score improved score. In the control group, only pain score improved significantly. The benefits in the diet group were still present after one year, and evaluation of the whole course showed significant advantages for the diet group in all measured indices. This dietary regimen seems to be a useful supplement to conventional medical treatment of rheumatoid arthritis.", "title": "Controlled trial of fasting and one-year vegetarian diet in rheumatoid arthritis." }, { "docid": "MED-3421", "text": "INTRODUCTION: Although penile blood flow (PBF) has been recommended as an additional diagnostic test in identifying erectile dysfunction (ED) patients at risk for latent cardiovascular disease, no study has ever assessed the possible association of PBF and the relational component of sexual function with incident major cardiovascular events (MACE). AIM: The aim of this study is to investigate whether severity of ED, PBF, and other factors related to a couple's relationship predict incident MACE. METHODS: A consecutive series of 1,687 patients was studied. Different clinical, biochemical, and instrumental (penile flow at color Doppler ultrasound) parameters were evaluated. MAIN OUTCOME MEASURES: Information on MACE was obtained through the City of Florence Registry Office. RESULTS: During a mean follow-up of 4.3 +/- 2.6 years, 139 MACE, 15 of which were fatal, were observed. Cox regression analysis, after adjustment for age and Chronic Disease Score, showed that severe ED predicted MACE (hazard ratio [HR] 1.75; 95% confidence interval 1.10-2.78; P < 0.05). In addition, lower PBF, evaluated both in flaccid (before) and dynamic (after prostaglandin-E1 stimulation) conditions, was associated with an increased risk of MACE (HR = 2.67 [1.42-5.04] and 1.57 [1.01-2.47], respectively, for flaccid [<13 cm/second] and dynamic [<25 cm/second] peak systolic velocity; both P < 0.05). Reported high sexual interest in the partner and low sexual interest in the patient proved to have a protective effect against MACE. CONCLUSIONS: The investigation of male sexuality, and in particular PBF, and sexual desire, could provide insights not only into present cardiovascular status but also into prospective risk.", "title": "Male sexuality and cardiovascular risk. A cohort study in patients with erectile dysfunction." }, { "docid": "MED-1619", "text": "BACKGROUND: Diets rich in carbohydrates with a low glycemic index and with high fiber content are associated with flat post-prandial rises of blood glucose, minimal post-prandial insulin secretion and maintenance of insulin sensitivity. Protective food commodities in the prevention of cardiovascular disease, insulin resistance syndrome or diabetes are crucial components of the vegetarian diet. AIM OF THE STUDY: Insulin resistance values were assessed in relation to different nutrition. Metabolic abnormality is a predictor of age-related diseases and can be more pronounced in obese subjects. Insulin resistance values in normal weight subjects of two different nutritional habits were correlated with age. METHODS: Fasting concentrations of glucose and insulin as well as calculated values of insulin resistance IR (HOMA) were assessed in two nutritional groups of apparently healthy adult subjects (age range 19 - 64 years) with normal weight (body mass index 18.6 - 25.0 kg/m(2)): a vegetarian group (95 long-term lacto-ovo-vegetarians; duration of vegetarianism 10.2 +/- 0.5 years) and a non-vegetarian control group (107 subjects of general population on traditional western diet). Intake of energy and main nutrients (fats, saccharides, proteins) was similar in both groups. RESULTS: Glucose and insulin concentrations and IR (HOMA) values were significantly lower in vegetarians (glucose 4.47 +/- 0.05 vs. 4.71 +/- 0.07 mmol/l; insulin 4.96 +/- 0.23 vs. 7.32 +/- 0.41 mU/l; IR (HOMA) 0.99 +/- 0.05 vs. 1.59 +/- 0.10). IR (HOMA) dependence on age was only significant in subjects on a western diet. A significant increase of IR was found already in the age range 31-40 years, compared to vegetarians and it continued in later age decades. Age independent and low insulin resistance values in vegetarians are a consequence of an effective diet prevention by long-term frequent consumption of protective food. Vegetarians had a significantly higher consumption of whole grain products, pulses, products from oat and barley. CONCLUSION: The results of age independent and low values of insulin resistance document a beneficial effect of long-term vegetarian nutrition in prevention of metabolic syndrome, diabetes and cardiovascular disease.", "title": "No evidence of insulin resistance in normal weight vegetarians. A case control study." }, { "docid": "MED-2360", "text": "Lyme-like illness (also known as southern tick-associated rash illness [STARI] or Masters disease) is vectored by the Lone Star tick (Amblyomma americanum). Lyme-like illness lesions, which are similar to the erythema migrans rash of Lyme disease, tend to have lymphocytic dermal infiltrates. With the exception of Borrelia lonestari, the possible causative agent or agents of Lyme-like illness have not been cultured. More research is needed to fully understand this newly recognized zoonosis. Clinicians are encouraged to increase their knowledge and awareness of this Lyme disease mimic.", "title": "STARI, or Masters disease: Lone Star tick-vectored Lyme-like illness." }, { "docid": "MED-3250", "text": "The purpose of this study was to determine whether a single LDL apheresis would improve impaired endothelium-dependent dilation of the coronary artery in patients with hypercholesterolemia. Hypercholesterolemia is associated with impaired endothelial function, and human studies using cholesterol-lowering drugs indicate that endothelial function in the coronary arteries improves with reduction of serum LDL cholesterol over 6 to 12 months. The internal diameter of the left coronary artery and the coronary blood flow were measured by intracoronary Doppler-wire measurement and quantitative angiography before and immediately after a single LDL apheresis in a population of 15 patients with familial hypercholesterolemia. Endothelium-dependent vasodilation was assessed by intracoronary infusion of acetylcholine (1, 10, and 50 microg/min), and endothelium-independent vasodilation was assessed by intracoronary bolus infusion of isosorbide dinitrate (2.5 mg) or papaverine (10 mg). A single 3-hour LDL apheresis reduced serum LDL cholesterol by an average of 86.6 +/- 1.7%. After the LDL apheresis, the changes in the coronary artery diameter and coronary blood flow in response to an infusion of 50 microg/min of acetylcholine increased significantly compared to the pre-apheresis values (from -19.7 +/- 4.8 to -2.9 +/- 3.0% [P < 0.01] and from 80.7 +/- 27.6 to 155.3 +/- 23.5% [P < 0.01], respectively). The LDL apheresis did not significantly change the response of either parameter to infusion with isosorbide dinitrate or papaverine. The endothelial function of the epicardial coronary artery and the coronary microvasculature improved in hypercholesterolemic patients after only a single LDL apheresis, a procedure that markedly reduces the serum level of LDL cholesterol. Copyright 2004 Wiley-Liss, Inc.", "title": "Improvement of endothelium-dependent coronary vasodilation after a single LDL apheresis in patients with hypercholesterolemia." }, { "docid": "MED-3788", "text": "Intestinal microbiota metabolism of choline/phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). Herein we demonstrate that intestinal microbiota metabolism of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis. Omnivorous subjects are shown to produce significantly more TMAO than vegans/vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. Specific bacterial taxa in human feces are shown to associate with both plasma TMAO and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predict increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (MI, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice significantly altered cecal microbial composition, markedly enhanced synthesis of TMA/TMAO, and increased atherosclerosis, but not following suppression of intestinal microbiota. Dietary supplementation of TMAO, or either carnitine or choline in mice with intact intestinal microbiota, significantly reduced reverse cholesterol transport in vivo. Intestinal microbiota may thus participate in the well-established link between increased red meat consumption and CVD risk.", "title": "Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis" }, { "docid": "MED-3793", "text": "OBJECTIVES: To determine cross-cultural and other effects on women's experiences of premenstrual symptoms and their impact on activities of daily life (ADL). STUDY DESIGN: Cross-sectional survey. Sample A total of 7226 women aged 15-49 recruited by random sampling with approximately 400 each from France, Germany, Hungary, Italy, Spain, UK, Brazil, Mexico, Hong Kong, Pakistan and Thailand. Approximately 1000 women in Japan and Korea and 500 Australian women were found using Internet panels. MAIN OUTCOME MEASURES: Questionnaire of 23 premenstrual symptoms, sociodemographic and lifestyle variables, ADL and women's knowledge of premenstrual terms. RESULTS: The most prevalent symptoms were abdominal bloating, cramps or abdominal pain, irritability, mastalgia and joint/muscle/back pains. Severity of symptoms was directly proportional to duration (number of affected cycles) (R = 0.78). A linear model found that symptom prevalence (duration × severity) was associated with age (linear and quadratic effects), parity, current smoking and country. Premenstrual physical and mental symptom domains had similar negative effects on ADL. Impact on ADL was affected by education and exercise participation. Women's knowledge of the terms premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) varied by symptom intensity, age, education and country. CONCLUSIONS: Four of the five most prevalent premenstrual symptoms were physical. There was a great deal of similarities of women's experiences of these symptoms across countries and regions. Women's knowledge of PMS terms is highly dependent on the country in which they live.", "title": "Global study of women's experiences of premenstrual symptoms and their effects on daily life." }, { "docid": "MED-4051", "text": "The food mutagens IQ (2-amino-3-methylimidazo[4,5-f]quinoline) and PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) are heterocyclic amines (HCA), generated when heating proteinaceous food. This study investigates the protective potential of the flavonoids quercetin (Q) and rutin (R) against oxidative stress induced in vitro by IQ and PhIP in lymphocytes from healthy individuals and untreated, newly diagnosed colon cancer patients using the Comet assay. In the presence of up to 500μM Q and R, the DNA damage resulting from a high dose of PhIP (75μM) or IQ (150μM) was significantly reduced (P<0.001) to levels comparable to six times lower IQ or 7.5 times lower PhIP doses. Lymphocytes from colon cancer patients had greater baseline DNA damage than those from healthy individuals (P<0.01) and this higher level of damage was also observed throughout in vitro treatment. Except for the >50years of age group and male gender, confounding factors such as smoking, drinking and/or dietary habits were not found to be significant. In conclusion, flavonoids reduced oxidative stress caused by food mutagens in vitro in lymphocytes of healthy individuals and colon cancer patients. Thus, dietary supplementation with flavonoid-rich vegetables and fruits may prove very effective in protecting against oxidative stress. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "The protective effect of the flavonoids on food-mutagen-induced DNA damage in peripheral blood lymphocytes from colon cancer patients." }, { "docid": "MED-3982", "text": "OBJECTIVE: To test the claim that pet ownership reduces cardiovascular risk. DESIGN: Community survey. PARTICIPANTS: 2528 adults aged 40-44 years and 2551 aged 60-64 years who lived in the Australian Capital Territory and Queanbeyan, New South Wales, and were drawn randomly from the Australian electoral roll in 2000 and 2001. MAIN OUTCOME MEASURES: Sociodemographic measures, including pet ownership, and measures of physical health (including body mass index [BMI], alcohol and cigarette consumption, and levels of physical activity). Two readings of diastolic and systolic blood pressure were also taken. RESULTS: While pet owners and non-pet owners had similar levels of systolic blood pressure, those with pets had significantly higher diastolic blood pressure. Pet owners also had higher BMI and were more likely to smoke. While those with pets undertook more mild physical activity, they continued to have significantly higher diastolic blood pressure after controlling for hypertensive risk factors. CONCLUSIONS: In this study, we found no evidence that pet ownership per se is associated with cardiovascular health benefits. Rather, pet owners had higher diastolic blood pressure than those without pets. It is likely that this increased health risk is linked to other hypertensive risk factors that are only indirectly associated with pet ownership.", "title": "Pet ownership and risk factors for cardiovascular disease: another look." }, { "docid": "MED-3058", "text": "Recent research indicates similarities between obesity and addictive disorders on both the phenomenological and neurobiological level. In particular, neuroendocrine and imaging studies suggest a close link between the homeostatic regulation of appetite on the on hand, and motivation and reward expectancy on the other. In addition, findings from neuropsychological studies additionally demonstrate alterations of cognitive function in both obesity and addictive disorders that possibly contribute to a lack of control in resisting consumption. In this review, recent findings on overlapping neurobiological and phenomenological pathways are summarized and the impact with regard to new treatment approaches for obesity is discussed. © 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.", "title": "Implications from addiction research towards the understanding and treatment of obesity." }, { "docid": "MED-2643", "text": "The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand.", "title": "Endocrine-Disrupting Chemicals: Associated Disorders and Mechanisms of Action" }, { "docid": "MED-2673", "text": "Transglutaminase is an enzyme that can be used to cross-link pieces of meat, fish or meat products. The resulting product gives the optical impression of an intact chunk of meat. The usage of transglutaminase as a food additive is permitted in some countries. However, its utilisation has to be declared to ensure transparency for consumers. This paper describes two orthogonal analytical methods suited for the detection of technological relevant transglutaminase concentrations (around 25 mg pure enzyme in 1 kg of product) in meat and meat products. The mass spectrometry-based approach relies on a previous digestion with Achromobacter lyticus protease and LC-MS/MS separation and detection. Sufficient selectivity was obtained by monitoring four different peptides. The orthogonal (complementary and independent), ELISA-based approach relies on two commercially available bacterial transglutaminase-specific antibodies, combined to a sandwich ELISA. The two methods were tested by analysing some 60 samples obtained from the market.", "title": "Determination of microbial transglutaminase in meat and meat products." }, { "docid": "MED-3035", "text": "Prenatal and early childhood exposure to methylmercury (MeHg) or polychlorinated biphenyls (PCBs) are associated with deficits in cognitive, sensory, motor and other functions measured by neurobehavioral tests. The main objective of this pilot study was to determine whether functional magnetic resonance imaging (fMRI) is effective for visualization of brain function alterations related to neurobehavior in subjects with high prenatal exposure to the two neurotoxicants, MeHg and PCBs. Twelve adolescents (all boys) from a Faroese birth cohort assembled in 1986–1987 were recruited based on their prenatal exposures to MeHg and PCB. All underwent fMRI scanning during behavioral tasks at age 15 years. Subjects with high mixed exposure to MeHg and PCBs were compared to those with low mixed exposure on fMRI photic stimulation and a motor task. Boys with low mixed exposures showed patterns of fMRI activation during visual and motor tasks that are typical of normal control subjects. However, those with high exposures showed activation in more areas of the brain and different and wider patterns of activation than the low mixed exposure group. The brain activation patterns observed in association with increased exposures to MeHg and PCBs are meaningful in regard to the known neurotoxicity of these substances. This methodology therefore has potential utility in visualizing structural neural system determinants of exposure-induced neurobehavioral dysfunction.", "title": "Functional MRI approach to developmental methylmercury and polychlorinated biphenyl neurotoxicity" }, { "docid": "MED-3815", "text": "Aims The aim of this study was to compare the effects of calorie-restricted vegetarian and conventional diabetic diets alone and in combination with exercise on insulin resistance, visceral fat and oxidative stress markers in subjects with Type 2 diabetes. Methods A 24-week, randomized, open, parallel design was used. Seventy-four patients with Type 2 diabetes were randomly assigned to either the experimental group (n = 37), which received a vegetarian diet, or the control group (n = 37), which received a conventional diabetic diet. Both diets were isocaloric, calorie restricted (-500 kcal/day). All meals during the study were provided. The second 12 weeks of the diet were combined with aerobic exercise. Participants were examined at baseline, 12 weeks and 24 weeks. Primary outcomes were: insulin sensitivity measured by hyperinsulinaemic isoglycaemic clamp; volume of visceral and subcutaneous fat measured by magnetic resonance imaging; and oxidative stress measured by thiobarbituric acid reactive substances. Analyses were by intention to treat. Results Forty-three per cent of participants in the experimental group and 5% of participants in the control group reduced diabetes medication (P < 0.001). Body weight decreased more in the experimental group than in the control group [–6.2 kg (95% CI –6.6 to –5.3) vs. –3.2 kg (95% CI –3.7 to –2.5); interaction group × time P = 0.001]. An increase in insulin sensitivity was significantly greater in the experimental group than in the control group [30% (95% CI 24.5–39) vs. 20% (95% CI 14–25), P = 0.04]. A reduction in both visceral and subcutaneous fat was greater in the experimental group than in the control group (P = 0.007 and P = 0.02, respectively). Plasma adiponectin increased (P = 0.02) and leptin decreased (P = 0.02) in the experimental group, with no change in the control group. Vitamin C, superoxide dismutase and reduced glutathione increased in the experimental group (P = 0.002, P < 0.001 and P = 0.02, respectively). Differences between groups were greater after the addition of exercise training. Changes in insulin sensitivity and enzymatic oxidative stress markers correlated with changes in visceral fat. Conclusions A calorie-restricted vegetarian diet had greater capacity to improve insulin sensitivity compared with a conventional diabetic diet over 24 weeks. The greater loss of visceral fat and improvements in plasma concentrations of adipokines and oxidative stress markers with this diet may be responsible for the reduction of insulin resistance. The addition of exercise training further augmented the improved outcomes with the vegetarian diet.", "title": "Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes" }, { "docid": "MED-4032", "text": "AIM: The aim of this study was to investigate oral changes in subjects who have assumed a vegan diet for a long time (at least 18 months), that is to say, a diet completely lacking in meat and animal derivatives. METHODS: A sample of 15 subjects was analyzed, all from northern Italy and aged 24 to 60 year, composed of 11 men and 4 women who had been following a vegan diet for a minimum of 18 months to a maximum of 20 years. In parallel with the study sample, a control group (15 subjects) with the same criteria of age, sex, and place of origin all following an omnivorous diet was chosen. The sample answered a questionnaire that investigated their eating habits, the frequency with which they eat meals, the main foodstuffs assumed, oral hygiene habits, and any painful symptomatology of the teeth or more general problems in the oral cavity. The sample was then subject to objective examination in which the saliva pH was measured and the teeth were checked for demineralization of the enamel, white spots, and caries (using KaVo DIAGNOdent) with particular attention being paid to the localization of these lesions, and lastly, sounding was carried out to detect any osseous defects and periodontal pockets. RESULTS: The study revealed greater incidence of demineralization and white spots in the vegan subjects compared to the omnivorous ones localized at the neck of the teeth and on the vestibular surfaces of dental elements (with the exception of the lower anterior group). The saliva pH, more acid in the omnivorous patients, ranged between four and six. Changes in oral conditions in both groups of subjects were observed. CONCLUSION: In order to research into the cause-effect relationship of the vegan diet on the oral cavity effectively, the sample needs to be studied for a longer period of time and the results re-evaluated.", "title": "Oral implications of the vegan diet: observational study." }, { "docid": "MED-4745", "text": "Early puberty onset is associated with hormone-related cancers, but whether diet in childhood influences pubertal timing is controversial. We examined the association of protein intake in early and mid-childhood with the ages at take-off of the pubertal growth spurt (ATO), peak height velocity (APHV), and menarche in girls and voice break in boys using data from the longitudinal Dortmund Nutritional and Anthropometric Longitudinally Designed Study. Among participants who provided 3-d weighed dietary records at 12 mo, 18-24 mo, 3-4 y, and 5-6 y, 112 had sufficient anthropometric measurements between 6 and 13 y to allow estimation of ATO. Life-course plots were used to identify critical periods of total, animal, and vegetable protein intake (percentage of total energy intake) for pubertal timing. At these ages, the association between tertiles of protein intake (T1-T3) and the outcomes was investigated using multiple linear regression analysis. A higher total and animal protein intake at 5-6 y was related to an earlier ATO. In the highest tertile of animal protein intake at 5-6 y, ATO occurred 0.6 y earlier than in the lowest [(mean, 95% CI) T1: 9.6, 9.4-9.9 vs. T2: 9.4, 9.1-9.7 vs. T3: 9.0, 8.7-9.3 y; P-trend = 0.003, adjusted for sex, total energy, breast-feeding, birth year, and paternal university degree]. Similar findings were seen for APHV (P-trend = 0.001) and the timing of menarche/voice break (P-trend = 0.02). Conversely, a higher vegetable protein intake at 3-4 and 5-6 y was related to later ATO, APHV, and menarche/voice break (P-trend = 0.02-0.04). These results suggest that animal and vegetable protein intake in mid-childhood might be differentially related to pubertal timing.", "title": "Dietary protein intake throughout childhood is associated with the timing of puberty." }, { "docid": "MED-3252", "text": "It is commonly accepted that nutrition is one of the possible environmental factors involved in the pathogenesis of multiple sclerosis (MS), but its role as complementary MS treatment is unclear and largely disregarded. At present, MS therapy is not associated to a particular diet, probably due to lack of information on the effects of nutrition on the disease. To overcome the distrust of the usefulness of dietary control in MS and to encourage nutritional interventions in the course of the disease, it is necessary to assess the nature and the role of bioactive dietary molecules and their targets, and establish how a dietary control can influence cell metabolism and improve the wellness of MS patients. The aim of this review is to provide a rationale for a nutritional intervention in MS by evaluating at the molecular level the effects of dietary molecules on the inflammatory and autoimmune processes involved in the disease. Present data reveal that healthy dietary molecules have a pleiotropic role and are able to change cell metabolism from anabolism to catabolism and down-regulate inflammation by interacting with enzymes, nuclear receptors and transcriptional factors. The control of gut dysbiosis and the combination of hypo-caloric, low-fat diets with specific vitamins, oligoelements and dietary integrators, including fish oil and polyphenols, may slow-down the progression of the disease and ameliorate the wellness of MS patients. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "The molecular basis of nutritional intervention in multiple sclerosis: a narrative review." }, { "docid": "MED-5191", "text": "We evaluated animal food intake and cooking methods in relation to endometrial cancer risk in a population-based case–control study in Shanghai, China. A validated food frequency questionnaire was used to collect the usual dietary habits of 1204 cases and 1212 controls aged 30–69 years between 1997 and 2003. Statistical analyses were based on an unconditional logistic regression model adjusting for potential confounders. High intake of meat and fish was associated with an increased risk of endometrial cancer, with adjusted odds ratios for the highest vs the lowest quartile groups being 1.7 (95% confidence interval: 1.3–2.2) and 2.4 (1.8–3.1), respectively. The elevated risk was observed for all types of meat and fish intake. Intake of eggs and milk was not related to risk. Cooking methods and doneness levels for meat and fish were not associated with risk, nor did they modify the association with meat and fish consumption. Our study suggests that animal food consumption may play an important role in the aetiology of endometrial cancer, but cooking methods have minimal influence on risk among Chinese women.", "title": "Animal food intake and cooking methods in relation to endometrial cancer risk in Shanghai" }, { "docid": "MED-3592", "text": "Levels of contaminants in fish are of particular interest because of the potential risk to humans who consume them. While attention has focused on self-caught fish, most of the fish eaten by the American public comes from commercial sources. We sampled 11 types of fish and shellfish obtained from supermarkets and specialty fish markets in New Jersey and analyzed them for arsenic, cadmium, chromium, lead, manganese, mercury, and selenium. We test the null hypothesis that metal levels do not vary among fish types, and we consider whether the levels of any metals could harm the fish themselves or their predators or pose a health risk for human consumers. There were significant interspecific differences for all metals, and no fish types had the highest levels of more than two metals. There were few significant correlations (Kendall tau) among metals for the three most numerous fish (yellowfin tuna, bluefish, and flounder), the correlations were generally low (below 0.40), and many correlations were negative. Only manganese and lead positively were correlated for tuna, bluefish, and flounder. The levels of most metals were below those known to cause adverse effects in the fish themselves. However, the levels of arsenic, lead, mercury, and selenium in some fish were in the range known to cause some sublethal effects in sensitive predatory birds and mammals and in some fish exceeded health-based standards. The greatest risk from different metals resided in different fish; the species of fish with the highest levels of a given metal sometimes exceeded the human health guidance or standards for that metal. Thus, the risk information given to the public (mainly about mercury) does not present a complete picture. The potential of harm from other metals suggests that people not only should eat smaller quantities of fish known to accumulate mercury but also should eat a diversity of fish to avoid consuming unhealthy quantities of other heavy metals. However, consumers should bear in mind that standards have a margin of safety.", "title": "Heavy metals in commercial fish in New Jersey." }, { "docid": "MED-4114", "text": "Induced apoptosis of autoreactive T-lymphocyte precursors in the thymus is crucial for the prevention of autoimmune disorders. IGF-I and prolactin, which are lymphocyte growth factors, may have the potential to suppress apoptosis in thymocytes and thus encourage autoimmunity; conversely, dietary fish oil rich in omega-3 fats appears to upregulate apoptosis in lymphocytes. Since whole-food vegan diets may downregulate systemic IGF-I activity, it is proposed that such a diet, in conjunction with fish oil supplementation and treatment with dopamine agonists capable of suppressing prolactin secretion, may have utility for treating and preventing autoimmune disorders. This prediction is consistent with the extreme rarity of autoimmune disorders among sub-Saharan black Africans as long as they followed their traditional quasi-vegan lifestyles, and with recent ecologic studies correlating risks for IDDM and for multiple sclerosis mortality with animal product and/or saturated fat consumption. Moreover, there is evidence that vegan or quasi-vegan diets are useful in the management of rheumatoid arthritis, multiple sclerosis, and possibly SLE. The dopamine agonist bromocryptine exerts anti-inflammatory effects in rodent models of autoimmunity, and there is preliminary evidence that this drug may be clinically useful in several human autoimmune diseases; better tolerated D2-specific agonists such as cabergoline may prove to be more practical for use in therapy. The moderate clinical utility of supplemental fish oil in rheumatoid arthritis and certain other autoimmune disorders is documented. It is not unlikely that extra-thymic anti-inflammatory effects contribute importantly to the clinical utility of vegan diets, bromocryptine, and fish oil in autoimmunity. The favorable impact of low latitude or high altitude on autoimmune risk may be mediated by superior vitamin D status, which is associated with decreased secretion of parathyroid hormone; there are theoretical grounds for suspecting that parathyroid hormone may inhibit apoptosis in thymocytes. Androgens appear to up-regulate thymocyte apoptosis, may be largely responsible for the relative protection from autoimmunity enjoyed by men, and merit further evaluation for the management of autoimmunity in women. It will probably prove more practical to prevent autoimmune disorders than to reverse them once established; a whole-food vegan diet, coupled with fish oil and vitamin D supplementation, may represent a practical strategy for achieving this prevention, while concurrently lowering risk for many other life-threatening 'Western' diseases. Copyright 2001 Harcourt Publishers Ltd.", "title": "Upregulation of lymphocyte apoptosis as a strategy for preventing and treating autoimmune disorders: a role for whole-food vegan diets, fish oil an..." }, { "docid": "MED-2661", "text": "This paper presents the results of an investigation on the occurrence of alkylphenols (APs) and their ethoxylates (APEs) in 8 edible marine species from the Adriatic Sea and tries to estimate the corresponding intake for the Italian population. Two crustaceans, Nephrops norvegicus (Norway lobster) and Squilla mantis (spottail mantis shrimp), plus six fish species, Engraulis enchrascicolus (anchovy), Scomber scombrus (Atlantic mackerel), Merluccius merluccius (European hake), Mullus barbatus (red mullet), Solea vulgaris (common sole) and Lophius piscatorius (angler) were analyzed for their content of nonylphenol (NP), octylphenol (OP) and octylphenol polyethoxylates (OPEs). These compounds were found in all analysed samples. NP was detected at the highest concentrations: 118-399 and 9.5-1431 ng g(-1) fresh weight (fw) respectively in crustaceans and fish. OP was found at respective levels of 2.7-4.7 and 0.3-3.8 ng g(-1) fw in crustaceans and fish, whereas OPE was determined at respective concentrations of 1.2-16.8 and 0.2-21.1 ng g(-1) fw in the same species. These results, together with those from a previous study on 4 edible mollusc, allow to estimate respective daily intakes for NP, OP, and OPE of about 12, 0.1, and 0.1 microg day(-1) for an Italian adult living along the Adriatic Coast. In relation to NP and OP, these intakes are much lower than the doses associated with toxic effects in laboratory animals (9 mg kg(-1) bw for rats). Nevertheless, data of exposure from other sources to these chemicals and others with similar biological characteristics are needed.", "title": "Alkylphenols and alkylphenol ethoxylates contamination of crustaceans and fishes from the Adriatic Sea (Italy)." }, { "docid": "MED-4181", "text": "Exposure of pregnant women to organochlorine (OC) pesticides largely derives from contaminated food, but environmental, occupational, and domestic factors have also been implicated. We investigated the presence of nine OC residues in the umbilical cord blood of newborns in Southern Spain and analyzed the relationship of this exposure with maternal and pregnancy variables, including maternal adherence to the Mediterranean Diet (MD). OCs were detected in 95% of umbilical cord blood samples from the 318 mothers, who had a mean degree of adherence to the MD of 56.77 (SD: 16.35) (range, 0-100). The MD prioritizes consumption of vegetable and fruit over meat and dairy products, and OCs are generally lipophilic molecules that accumulate in foods of animal origin. Consumption of meat, fish, and dairy products was associated with dichlorodiphenyldichloroethylene (DDE) in umbilical cord serum, and dairy product intake with lindane. Vegetable consumption was also associated with lindane and fruit intake with endosulfan I. We found no significant association between MD adherence and the presence of OC residues in serum. However, closer adherence to the MD may offer greater protection against OC exposure because of its reduced content in meat and dairy products. Copyright (c) 2010 Elsevier Ltd. All rights reserved.", "title": "Organochlorine pesticides in umbilical cord blood serum of women from Southern Spain and adherence to the Mediterranean diet." }, { "docid": "MED-4798", "text": "OBJECTIVE To review the evidence for the efficacy of products used for environmental or hand cleaning on the rates of Clostridium difficile–associated diarrhea (CDAD). QUALITY OF EVIDENCE MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews were searched for articles pertinent to the efficacy of cleaning products against C difficile or studies with outcomes related to rates of CDAD. Evidence was level II. MAIN MESSAGE Minimizing the incidence of CDAD in geriatric rehabilitation units is essential to achieving the goals of increasing patient function and independence for discharge into the community. Attention to environmental control of C difficile and its spores by health care workers and patient visitors is an important secondary prevention strategy. CONCLUSION Chlorine-releasing agents are more effective than detergents for killing spores produced by C difficile. No level I evidence is available to determine if the use of chlorine-releasing agents has an effect on rates of CDAD. Hand-washing is currently the recommended strategy for reducing transmission of C difficile. Alcohol gels do not inactivate C difficile spores; however, increased use of alcohol hand gel has not been associated with higher rates of CDAD. Résumé OBJECTIF Examiner les preuves indiquant que les produits utilisés pour nettoyer l’environnement et les mains sont efficaces pour réduire le taux de diarrhée due au Clostridium difficile (DDCD). QUALITÉ DES PREUVES On a consulté MEDLINE, EMBASE et la Cochrane Database of Systematic Reviews en retenant les articles portant sur l’efficacité des agents de nettoyage contre le C difficile ou les études traitant de questions liées aux taux de DDCD. Les preuves étaient de niveau II. PRINCIPAL MESSAGE La réduction de l’incidence de la DDCD dans les unités de réadaptation gériatrique est une condition essentielle pour accroître l’état fonctionnel et l’indépendance des patients qui retournent dans la communauté. Pour les intervenants et pour les visiteurs des patients, le contrôle du C difficile et de ses spores dans l’environnement est primordial comme stratégie de prévention secondaire. Les agents qui libèrent du chlore sont plus efficaces que les détergents pour tuer les spores du C difficile. Il n’existe pas de preuves de niveau I indiquant que l’utilisation d’agents libérant du chlore influence les taux de DDCD. Le lavage des mains est la stratégie présentement recommandée pour réduire la transmission du C difficile. Les gels d’alcool n’inactivent pas les spores du C difficile; toutefois, une utilisation accrue de gels d’alcool n’a pas entraîné d’augmentation du taux de DDCD.", "title": "Efficacy of cleaning products for C difficile" }, { "docid": "MED-2697", "text": "OBJECTIVES: The purpose of this study was to test the hypothesis that intake of used cooking fat is associated with impaired endothelial function. BACKGROUND: Diets containing high levels of lipid oxidation products may accelerate atherogenesis, but the effect on endothelial function is unknown. METHODS: Flow-mediated endothelium-dependent dilation and glyceryl trinitrate-induced endothelium-independent dilation of the brachial artery were investigated in 10 men. Subjects had arterial studies before and 4 h after three test meals: 1) a meal (fat 64.4 g) rich in cooking fat that had been used for deep frying in a fast food restaurant; 2) the same meal (fat 64.4 g) rich in unused cooking fat, and 3) a corresponding low fat meal (fat 18.4 g) without added fat. RESULTS: Endothelium-dependent dilation decreased between fasting and postprandial studies after the used fat meal (5.9 +/- 2.3% vs. 0.8 +/- 2.2%, p = 0.0003), but there was no significant change after the unused fat meal (5.3 +/- 2.1% vs. 6.0 +/- 2.5%) or low fat meal (5.3 +/- 2.3% vs. 5.4 +/- 3.3%). There was no significant difference in endothelium-independent dilation after any of the meals. Plasma free fatty acid concentration did not change significantly during any of the meals. The level of postprandial hypertriglyceridemia was not associated with change in endothelial function. CONCLUSIONS: Ingestion of a meal rich in fat previously used for deep frying in a commercial fast food restaurant resulted in impaired arterial endothelial function. These findings suggest that intake of degradation products of heated fat contribute to endothelial dysfunction.", "title": "Impaired endothelial function following a meal rich in used cooking fat." }, { "docid": "MED-4755", "text": "OBJECTIVE: To critically evaluate the clinical evidence, and when not available, the animal data, most relevant to concerns that isoflavone exposure in the form of supplements or soy foods has feminizing effects on men. DESIGN: Medline literature review and cross-reference of published data. RESULT(S): In contrast to the results of some rodent studies, findings from a recently published metaanalysis and subsequently published studies show that neither isoflavone supplements nor isoflavone-rich soy affect total or free testosterone (T) levels. Similarly, there is essentially no evidence from the nine identified clinical studies that isoflavone exposure affects circulating estrogen levels in men. Clinical evidence also indicates that isoflavones have no effect on sperm or semen parameters, although only three intervention studies were identified and none were longer than 3 months in duration. Finally, findings from animal studies suggesting that isoflavones increase the risk of erectile dysfunction are not applicable to men, because of differences in isoflavone metabolism between rodents and humans and the excessively high amount of isoflavones to which the animals were exposed. CONCLUSION(S): The intervention data indicate that isoflavones do not exert feminizing effects on men at intake levels equal to and even considerably higher than are typical for Asian males. Copyright 2010. Published by Elsevier Inc.", "title": "Soybean isoflavone exposure does not have feminizing effects on men: a critical examination of the clinical evidence." }, { "docid": "MED-3051", "text": "The hypothalamus is intimately involved in the regulation of food intake, integrating multiple neural and hormonal signals. Several hypothalamic nuclei contain glucose-sensitive neurons, which play a crucial role in energy homeostasis. Although a few functional magnetic resonance imaging (fMRI) studies have indicated that glucose consumption has some effect on the neuronal activity levels in the hypothalamus, this matter has not been investigated extensively yet. For instance, dose-dependency of the hypothalamic responses to glucose ingestion has not been addressed. We measured the effects of two different glucose loads on neuronal activity levels in the human hypothalamus using fMRI. After an overnight fast, the hypothalamus of 15 normal weight men was scanned continuously for 37 min. After 7 min, subjects ingested either water or a glucose solution containing 25 or 75 g of glucose. We observed a prolonged decrease of the fMRI signal in the hypothalamus, which started shortly after subjects began drinking the glucose solution and lasted for at least 30 min. Moreover, the observed response was dose-dependent: a larger glucose load resulted in a larger signal decrease. This effect was most pronounced in the upper anterior hypothalamus. In the upper posterior hypothalamus, the signal decrease was similar for both glucose loads. No effect was found in the lower hypothalamus. We suggest a possible relation between the observed hypothalamic response and changes in the blood insulin concentration.", "title": "Functional MRI of human hypothalamic responses following glucose ingestion." }, { "docid": "MED-3089", "text": "Objective Phosphorus containing additives are increasingly added to food products. We sought to determine the potential impact of these additives. We focused on chicken products as an example. Methods We purchased a variety of chicken products, prepared them according to package directions, and performed laboratory analyses to determine their actual phosphorus content. We used ESHA Food Processor SQL Software to determine the expected phosphorus content of each product. Results Of 38 chicken products, 35 (92%) had phosphorus containing additives listed among their ingredients. For every category of chicken products containing additives, the actual phosphorus content was greater than the content expected from nutrient database. For example, actual phosphorus content exceeded expected phosphorus content by an average of 84 mg/100g for breaded breast strips. There was also a great deal of variation within each category. For example, the difference between actual and expected phosphorus content ranged from 59 to 165 mg/100g for breast patties. Two 100 g servings of additive containing products contain an average of 440 mg of phosphorus, or about half the total daily recommended intake for dialysis patients. Conclusion Phosphorus containing additives significantly increase the amount of phosphorus in chicken products. Available nutrient databases do not reflect this higher phosphorus content, and the variation between similar products makes it impossible for patients and dietitians to accurately estimate phosphorus content. We recommend that dialysis patients limit their intake of additive containing products and that the phosphorus content of food products be included on nutrition facts labels.", "title": "PHOSPHORUS CONTAINING FOOD ADDITIVES AND THE ACCURACY OF NUTRIENT DATABASES: IMPLICATIONS FOR RENAL PATIENTS" }, { "docid": "MED-4313", "text": "BACKGROUND: Population-based studies have shown that vegetarians have lower body mass index than nonvegetarians, suggesting that vegetarian diet plans may be an approach for weight management. However, a perception exists that vegetarian diets are deficient in certain nutrients. OBJECTIVE: To compare dietary quality of vegetarians, nonvegetarians, and dieters, and to test the hypothesis that a vegetarian diet would not compromise nutrient intake when used to manage body weight. DESIGN: Cross-sectional analysis of National Health and Nutrition Examination Survey (1999-2004) dietary and anthropometric data. Diet quality was determined using United States Department of Agriculture's Healthy Eating Index 2005. Participants included adults aged 19 years and older, excluding pregnant and lactating women (N = 13,292). Lacto-ovo vegetarian diets were portrayed by intakes of participants who did not eat meat, poultry, or fish on the day of the survey (n = 851). Weight-loss diets were portrayed by intakes of participants who consumed 500 kcal less than their estimated energy requirements (n = 4,635). Mean nutrient intakes and body mass indexes were adjusted for energy, sex, and ethnicity. Using analysis of variance, all vegetarians were compared to all nonvegetarians, dieting vegetarians to dieting nonvegetarians, and nondieting vegetarians to nondieting nonvegetarians. RESULTS: Mean intakes of fiber, vitamins A, C, and E, thiamin, riboflavin, folate, calcium, magnesium, and iron were higher for all vegetarians than for all nonvegetarians. Although vegetarian intakes of vitamin E, vitamin A, and magnesium exceeded that of nonvegetarians (8.3 ± 0.3 vs 7.0 ± 0.1 mg; 718 ± 28 vs 603 ± 10 μg; 322 ± 5 vs 281 ± 2 mg), both groups had intakes that were less than desired. The Healthy Eating Index score did not differ for all vegetarians compared to all nonvegetarians (50.5 ± 0.88 vs 50.1 ± 0.33, P = 0.6). CONCLUSIONS: These findings suggest that vegetarian diets are nutrient dense, consistent with dietary guidelines, and could be recommended for weight management without compromising diet quality. Copyright © 2011 American Dietetic Association. Published by Elsevier Inc. All rights reserved.", "title": "A vegetarian dietary pattern as a nutrient-dense approach to weight management: an analysis of the national health and nutrition examination survey..." }, { "docid": "MED-3795", "text": "Mastalgia affects up to two-thirds of women at some time during their reproductive lives. It is usually benign, but thefear of underlying breast cancer is why many women present for evaluation. Mastalgia can be associated with premenstrual syndrome, fibrocystic breast disease, psychologic disturbance and, rarely, breast cancer. Occasionally, extramammary conditions, like Tietzie syndrome, present as mastalgia. A thorough clinical evaluation is required to assess the cause. The majority of women can be reassured after a clinical evaluation. Approximately 15% require pain-relieving therapy. Mechanical breast support; a low-fat, high-carbohydrate diet; and topical nonsteroidal antiinflammatory agents are reasonable first-line treatments. Hormonal agents, such as bromocriptine, tamoxifen and danazol, have all demonstrated efficacy in the treatment of mastalgia. Side effects, however, limit their extensive use. Danazol is the only FDA-approved hormonal treatment and is best used in cyclic form to limit the adverse effects. Lisuride maleate is a new agent recently studied for the treatment of mastalgia. Initial data on this medication are encouraging. Sixty percent of cyclic mastalgia recurs after treatment. Noncyclic mastalgia responds poorly to treatment but resolves spontaneously in up to 50% of cases.", "title": "Mastalgia: a review of management." }, { "docid": "MED-3038", "text": "The effects of 50 mg naltrexone on eating and subjective appetite were assessed in a double-blind placebo-controlled study with 20 male volunteers. Appetite was monitored using a disguised digital balance connected to a micro-computer, which constantly monitored the amount of food remaining, and which automatically interrupted feeding for 30 s after every 50 g consumed to allow appetite ratings to be made. Half the subjects ate pasta with a cheese sauce, and the remainder pasta with a tomato sauce. Subjects ate significantly less of both foods after 50 mg naltrexone than in either the placebo condition or on the initial (familiarisation) day. Naltrexone also reduced the rated pleasantness of both foods, and reduced overall eating rate. When best-fit quadratic functions were used to describe changes in rated hunger in relation to intake within the meal, naltrexone abolished the positive linear component reflecting the initial stimulation of appetite without altering either intercept or the negative quadratic function. Although mood ratings suggested that naltrexone had a mild sedative effect, mood changes alone could not explain the effects of naltrexone on appetite. Overall, these data suggest a specific role for opioids in the stimulation of appetite through palatability.", "title": "Effects of naltrexone on food intake and changes in subjective appetite during eating: evidence for opioid involvement in the appetizer effect." }, { "docid": "MED-4767", "text": "We previously reported that chickens infected with the avian adenovirus SMAM-1 developed a unique syndrome characterized by excessive intra-abdominal fat deposition accompanied by paradoxically low serum cholesterol and triglyceride levels. There have been no previous reports of avian adenoviruses infecting humans. We screened the serum of 52 humans with obesity in Bombay, India, for antibodies against SMAM-1 virus using the agar gel precipitation test (AGPT) method. Bodyweights and serum cholesterol and triglyceride levels were compared in SMAM-1-positive (P-AGPT) and SMAM-1-negative (N-AGPT) groups. Ten subjects were positive for antibodies to SMAM-1, and 42 subjects did not have antibodies. The P-AGPT group had a significantly higher bodyweight (p < 0.02) and body mass index (p < 0.001) (95.1 +/- 2.1 kg and 35.3 +/- 1.5 kg/m2, respectively) compared with the N-AGPT group (80.1 +/- 0.6 kg and 30.7 +/- 0.6 kg/m2, respectively). Also, the P-AGPT group had significantly lower serum cholesterol (p < 0.02) and triglyceride (p < 0.001) values (4.65 mmol/L and 1.45 mmol/L, respectively) compared with the N-AGPT group (5.51 mmol/L and 2.44 mmol/L, respectively). Two subjects positive for SMAM-1 antibodies had antibodies against each others' serum, suggesting the presence of antigens in one or both. When these two serum samples were inoculated into chicken embryos, macroscopic lesions compatible with SMAM-1 infection developed. The inoculation of serum from N-AGPT subjects did not produce such lesions. The presence of increased obesity, antibodies to SMAM-1, reduced levels of blood lipids, and viremia that produces a typical infection in chicken embryos suggests that SMAM-1, or a serologically similar human virus, may be involved in the cause of obesity in some humans.", "title": "Association of adenovirus infection with human obesity." }, { "docid": "MED-5188", "text": "BACKGROUND: Nitrosamines, which are known bladder carcinogens, or their precursors are found in certain meat items, and concentrations of these compounds are especially high in bacon. Only 3 cohort studies, all with <100 case subjects, have examined the relation between meat intake and bladder cancer, and few studies have examined the relation of different meat types with bladder cancer. OBJECTIVE: The aim was to examine the association between specific meat items and bladder cancer in 2 large prospective studies. DESIGN: We analyzed data from 2 cohorts with up to 22 y of follow-up and 808 incident bladder cancer cases. Detailed data on meat were obtained from multiple food-frequency questionnaires administered over time. Multivariate relative risks (RRs) and 95% CIs were estimated by using Cox proportional hazards models with control for potential confounders, including detailed smoking history. RESULTS: Men and women with a high intake of bacon (>/=5 servings/wk) had an elevated risk of bladder cancer compared with those who never ate bacon (multivariate RR = 1.59; 95% CI = 1.06, 2.37), although the overall association was not statistically significant (P for trend = 0.06). However, the association with bacon was stronger and became statistically significant after the removal of individuals who indicated having \"greatly\" changed their red meat (men) or bacon (women) intake during the 10 y before baseline (multivariate RR = 2.10; 95% CI = 1.24, 3.55; P for trend = 0.006). A positive association was also detected for intake of chicken without skin, but not for chicken with skin or for other meats, including processed meats, hot dogs, and hamburgers. CONCLUSIONS: In these 2 cohorts combined, frequent consumption of bacon was associated with an elevated risk of bladder cancer. Other studies with data on specific meat items are necessary to confirm our findings.", "title": "Meat intake and bladder cancer risk in 2 prospective cohort studies." }, { "docid": "MED-1445", "text": "PURPOSE: This study investigated the effect of a low-fat, plant-based diet on body weight, metabolism, and insulin sensitivity, while controlling for exercise in free-living individuals. SUBJECTS AND METHODS: In an outpatient setting, 64 overweight, postmenopausal women were randomly assigned to a low-fat, vegan diet or a control diet based on National Cholesterol Education Program guidelines, without energy intake limits, and were asked to maintain exercise unchanged. Dietary intake, body weight and composition, resting metabolic rate, thermic effect of food, and insulin sensitivity were measured at baseline and 14 weeks. RESULTS: Mean +/- standard deviation intervention-group body weight decreased 5.8 +/- 3.2 kg, compared with 3.8 +/- 2.8 kg in the control group (P = .012). In a regression model of predictors of weight change, including diet group and changes in energy intake, thermic effect of food, resting metabolic rate, and reported energy expenditure, significant effects were found for diet group (P < .05), thermic effect of food (P < .05), and resting metabolic rate (P < .001). An index of insulin sensitivity increased from 4.6 +/- 2.9 to 5.7 +/- 3.9 (P = .017) in the intervention group, but the difference between groups was not significant (P = .17). CONCLUSION: Adoption of a low-fat, vegan diet was associated with significant weight loss in overweight postmenopausal women, despite the absence of prescribed limits on portion size or energy intake.", "title": "The effects of a low-fat, plant-based dietary intervention on body weight, metabolism, and insulin sensitivity." }, { "docid": "MED-2575", "text": "Introduction Matrix metalloproteinases (MMPs) have repeatedly been shown to play a very active role in extracellular matrix degradation associated with tumor invasion and metastasis. Tissue inhibitors of MMPs (TIMPs) are well-known for their ability to inhibit MMP activity thereby inhibiting malignant progression. Inositol hexaphosphate (IP6 phytic acid) has been recognized to have both preventive and therapeutic effects against various cancers including that of colon. In in vitro studies, IP6 has been demonstrated to inhibit cancer cell adhesion and migration. In the present study, the effect of IP6 on the expression of MMP and TIMP genes was evaluated in unstimulated and IL-1β-stimulated colon cancer cell line Caco-2. Materials and methods Real-time QRT-PCR was used to validate the transcription level of selected MMP and TIMP genes in Caco-2 cells after treatment with 1 ng/ml of IL-1β, 2.5 mM of IP6, and both for 6, 12, and 24 h. Results Stimulation of cells with IL-1β only resulted in an overexpression of MMP and their TIMP mRNAs. A significant decrease in MMP-13, MMP-3, MMP-2, and TIMP-1 basal expression was achieved by IP6. IP6 was also an efficient downregulator of MMP-1, MMP-9, and TIMP-2 genes transcription stimulated by IL-1β in 6 h lasting culture. After 12 h, IL-1β-induced MMP-2 mRNA expression was significantly reduced by IP6. Conclusion Proinflammatory cytokine IL-1β upregulates MMP and TIMP mRNAs expression in colon cancer epithelial cells Caco-2. IP6 (2.5 mM) influences constitutive expression of both MMP and TIMP genes and downregulates IL-1β stimulated transcription of some of these genes. IP6 exerts its anti-metastatic activity through modulation of MMP and TIMP genes expression to prevent cancer cell migration and invasion.", "title": "The effect of inositol hexaphosphate on the expression of selected metalloproteinases and their tissue inhibitors in IL-1β-stimulated colon cancer cells" }, { "docid": "MED-4800", "text": "AIMS: This study was designed to evaluate the prevalence of Clostridium difficile contamination of retail chicken. METHODS AND RESULTS: Chicken legs, thighs and wings were purchased using a standardized method from retail outlets across Ontario, Canada. Selective culture was used for qualitative and quantitative detection of C. difficile. Clostridium difficile was isolated from 26/203 (12.8%) chicken samples; 10/111 (9.0%) thighs, 13/72 (18%) wings and 3/20 (15%) legs (P = 0.19). All isolates were ribotype 078, a strain that has been associated with food animals and potentially community-associated disease in humans. All positive samples were positive only on enrichment culture. CONCLUSIONS: Clostridium difficile could be found relatively commonly in retail chicken meat, albeit at low levels. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to report C. difficile in chicken meat. Contamination of meat with C. difficile strains implicated in human infections raises concerns about food as a source of C. difficile infection. The relevance of food contamination is completely unclear at this point but food should be investigated as a source of infection.", "title": "Detection and characterization of Clostridium difficile in retail chicken." }, { "docid": "MED-2405", "text": "The contribution of exposure to persistent organic pollutants (POPs) to the incidence of diabetes has received little attention until recently. A number of reports have emerged, however, concerning elevated diabetes in persons occupationally exposed to dioxin. United States (US) Air Force personnel in Vietnam who sprayed Agent Orange containing dioxin as a contaminant had elevated rates of diabetes, leading to US government compensation for diabetes in these veterans. Recent studies in populations exposed to polychlorinated biphenyls (PCBs) and chlorinated pesticides found a dose-dependent elevated risk of diabetes. An elevation in risk of diabetes in relation to levels of several POPs has been demonstrated by two different groups using the National Health and Nutrition Examination Survey (NHANES), a random sampling of US citizens. The strong associations seen in quite different studies suggest the possibility that exposure to POPs could cause diabetes. One striking observation is that obese persons that do not have elevated POPs are not at elevated risk of diabetes, suggesting that the POPs rather than the obesity per se is responsible for the association. Although a specific mechanism is not known, most POPs induce a great number and variety of genes, including several that alter insulin action. Because diabetes is a dangerous disease that is increasing in frequency throughout the world, further study of the possibility that exposure to POPs contributes to the etiology of diabetes is critical.", "title": "Environmental contaminants as risk factors for developing diabetes." }, { "docid": "MED-1931", "text": "Caregivers of Alzheimer’s disease patients endure chronic stress associated with a decline of immune function. To assess the psychological and immunological changes of caregivers, we compared depressive symptoms, PBMC composition, in vitro activation-induced proliferation and cytokine production, and telomere length and telomerase activity of 82 individuals (41 caregivers and 41 age- and gender-matched controls). We found depressive symptoms were significantly higher in caregivers than in controls (p < 0.001). Correspondingly, caregivers had significantly lower T cell proliferation but higher production of immune-regulatory cytokines (TNF-α and IL-10) than controls in response to stimulation in vitro. We examined the impact of these changes on cellular replicative lifespan and found that caregivers had significantly shorter telomere lengths in PBMC than controls (6.2 and 6.4 kb, respectively, p < 0.05) with similar shortening in isolated T cells and monocytes and that this telomere attrition in caregivers was not due to an increase of shorter telomere possessing T cell subsets in PBMC. Finally, we showed that basal telomerase activity in PBMC and T cells was significantly higher in caregivers than in controls (p < 0.0001), pointing to an unsuccessful attempt of cells to compensate the excessive loss of telomeres in caregivers. These findings demonstrate that chronic stress is associated with altered T cell function and accelerated immune cell aging as suggested by excessive telomere loss.", "title": "Accelerated Telomere Erosion Is Associated with a Declining Immune Function of Caregivers of Alzheimer’s Disease Patients" }, { "docid": "MED-1933", "text": "Numerous studies demonstrate links between chronic stress and indices of poor health, including risk factors for cardiovascular disease and poorer immune function. Nevertheless, the exact mechanisms of how stress gets “under the skin” remain elusive. We investigated the hypothesis that stress impacts health by modulating the rate of cellular aging. Here we provide evidence that psychological stress— both perceived stress and chronicity of stress—is significantly associated with higher oxidative stress, lower telomerase activity, and shorter telomere length, which are known determinants of cell senescence and longevity, in peripheral blood mononuclear cells from healthy premenopausal women. Women with the highest levels of perceived stress have telomeres shorter on average by the equivalent of at least one decade of additional aging compared to low stress women. These findings have implications for understanding how, at the cellular level, stress may promote earlier onset of age-related diseases.", "title": "From the Cover: Accelerated telomere shortening in response to life stress" }, { "docid": "MED-1321", "text": "Phospholipids (PLs) are a major class of lipid in rice grain. Although PLs are only a minor nutrient compared to starch and protein, they may have both nutritional and functional significance. We have systemically reviewed the literature on the class, distribution and variation of PLs in rice, their relation to rice end-use quality and human health, as well as available methods for analytical profiling. Phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and their lyso forms are the major PLs in rice. The deterioration of PC in rice bran during storage was considered as a trigger for the degradation of rice lipids with associated rancid flavour in paddy and brown rice. The lyso forms in rice endosperm represent the major starch lipid, and may form inclusion complexes with amylose, affecting the physicochemical properties and digestibility of starch, and hence its cooking and eating quality. Dietary PLs have a positive impact on several human diseases and reduce the side-effects of some drugs. As rice has long been consumed as a staple food in many Asian countries, rice PLs may have significant health benefits for those populations. Rice PLs may be influenced both by genetic (G) and environmental (E) factors, and resolving G×E interactions may allow future exploitation of PL composition and content, thus boosting rice eating quality and health benefits for consumers. We have identified and summarised the different methods used for rice PL analysis, and discussed the consequences of variation in reported PL values due to inconsistencies between methods. This review enhances the understanding of the nature and importance of PLs in rice and outlines potential approaches for manipulating PLs to improve the quality of rice grain and other cereals. Copyright © 2013 Elsevier Ltd. All rights reserved.", "title": "Phospholipids in rice: significance in grain quality and health benefits: a review." }, { "docid": "MED-3215", "text": "The average American diet, which is high in protein and low in fruits and vegetables, generates a large amount of acid, mainly as sulfates and phosphates. The kidneys respond to this dietary acid challenge with net acid excretion, as well as ammonium and titratable acid excretion. Concurrently, the skeleton supplies buffer by active resorption of bone. Indeed, calciuria is directly related to net acid excretion. Different food proteins differ greatly in their potential acid load, and therefore in their acidogenic effect. A diet high in acid-ash proteins causes excessive calcium loss because of its acidogenic content. The addition of exogenous buffers, as chemical salts or as fruits and vegetables, to a high protein diet results in a less acid urine, a reduction in net acid excretion, reduced ammonium and titratable acid excretion, and decreased calciuria. Bone resorption may be halted, and bone accretion may actually occur. Alkali buffers, whether chemical salts or dietary fruits and vegetables high in potassium, reverse acid-induced obligatory urinary calcium loss. We conclude that excessive dietary protein from foods with high potential renal acid load adversely affects bone, unless buffered by the consumption of alkali-rich foods or supplements.", "title": "Excess dietary protein can adversely affect bone." }, { "docid": "MED-3229", "text": "High-protein (HP) diets exert a hypercalciuric effect at constant levels of calcium intake, even though the effect may depend on the nature of the dietary protein. Lower urinary pH is also consistently observed for subjects consuming HP diets. The combination of these two effects was suspected to be associated with a dietary environment favorable for demineralization of the skeleton. However, increased calcium excretion due to HP diet does not seem to be linked to impaired calcium balance. In contrast, some data indicate that HP intakes induce an increase of intestinal calcium absorption. Moreover, no clinical data support the hypothesis of a detrimental effect of HP diet on bone health, except in a context of inadequate calcium supply. In addition, HP intake promotes bone growth and retards bone loss and low-protein diet is associated with higher risk of hip fractures. The increase of acid and calcium excretion due to HP diet is also accused of constituting a favorable environment for kidney stones and renal diseases. However, in healthy subjects, no damaging effect of HP diets on kidney has been found in either observational or interventional studies and it seems that HP diets might be deleterious only in patients with preexisting metabolic renal dysfunction. Thus, HP diet does not seem to lead to calcium bone loss, and the role of protein seems to be complex and probably dependent on other dietary factors and the presence of other nutrients in the diet.", "title": "Protein intake, calcium balance and health consequences." }, { "docid": "MED-3313", "text": "INTRODUCTION: Asbestos is banned in most Western countries but related malignancies are still of clinical concern because of their long latencies. This review identifies and addresses some controversial occupational and clinical aspects of asbestos-related malignancies. METHODS: Papers published in English from 1980 to 2009 were retrieved from PubMed. A total of 307 original articles were identified and 159 were included. ASSESSMENT OF EXPOSURE: The retrospective assessment of exposure is usually performed by using questionnaires and job exposure matrices and by careful collection of medical history. In this way crucial information about manufacturing processes and specific jobs can be obtained. In addition, fibers and asbestos bodies are counted in lung tissue, broncho-alveolar lavage, and sputum, but different techniques and interlaboratory variability hamper the interpretation of reported measurements. SCREENING FOR MALIGNANCIES: The effectiveness of low-dose chest CT screening in exposed workers is debatable. Several biomarkers have also been considered to screen individuals at risk for lung cancer and mesothelioma but reliable signatures are still missing. ATTRIBUTION OF LUNG CANCER: Exposures correlating with lung cancer are high and in the same range where asbestosis occurs. However, the unresolved question is whether the presence of fibrosis is a requirement for the attribution of lung cancer to asbestos. The etiology of lung cancer is difficult to define in cases of low-level asbestos exposure and concurrent smoking habits. MESOTHELIOMA: The diagnosis of malignant mesothelioma may also be difficult, because of procedures in sampling, fixation, and processing, and uses of immunohistochemical probes. CONCLUSIONS: Assessment of exposure is crucial and requires accurate medical and occupational histories. Quantitative analysis of asbestos body burden is better performed in digested lung tissues by counting asbestos bodies by light microscopy and/or uncoated fibers by transmission electron microscopy. The benefits of screenings for asbestos-related malignancies are equivocal. The attribution of lung cancer to asbestos exposure is difficult in a clinical setting because of the need to assess asbestos body burden and the fact that virtually all these patients are also tobacco smokers or former smokers. Given the premise that asbestosis is necessary to causally link lung cancer to asbestos, it follows that the assessment of both lung fibrosis and asbestos body burden is necessary.", "title": "Occupational toxicology of asbestos-related malignancies." }, { "docid": "MED-2366", "text": "Glycoconjugates and their antibodies are vital components of host-tumor interaction. This review concentrates on the oncological implications of research concerning the alpha gal triad; the alpha 1-->3 galactosyl epitope (alpha Gal), the enzyme responsible for its construction, alpha 1,3 galactosyl transferase (alpha 1-3GT), and its associated antibody: anti-gal. Alpha gal epitopes, previously assumed to be absent from human tissue, have been demonstrated on several human cancer cell lines, senescent red blood cells, and Graves' disease thyrocytes. Alpha-gal presence on neoplastic lines is correlated with increased metastatic formation in animal models. The mechanisms of human response to these neoantigens are complex, as natural anti-gal antibodies exist in high titers in normal sera, thus predicting immunological recognition of cells expressing alpha gal epitopes. Hypotheses vary regarding the pathogenic contributions of metastasis-associated phenomena such as de novo expression of alpha gal and its unmasking by desialylation. The means by which alpha gal is sporadically expressed in human tissue remain unknown, as the galactosyl transferase which produces this epitope in constitutively expressive animals has undergone significant mutation at the genomic level in humans. Pathological re-expression is presumed to require permissive changes at a cellular level. Detailing these alterations is a prerequisite to the comprehension of the metastatic phenotype. In this context, the possibility of therapeutic strategies affecting alpha gal expression are also discussed.", "title": "A possible role for the alpha 1-->3 galactosyl epitope and the natural anti-gal antibody in oncogenesis." }, { "docid": "MED-3728", "text": "On the basis of copious preclinical data supporting the preventive efficacy of small fruits such as berries and grapes, Chen and colleagues conducted a randomized (noncomparative) phase II trial evaluating two doses of strawberry powder (60 g/d or 30 g/d for six months) to prevent esophageal cancer in China (reported in this issue of the journal, beginning on page 41); 60 g/d reduced the histologic grade of dysplastic lesions and reduced localized biomarkers, whereas 30 g/d was not effective. Fundamental questions remain such as the best formulation of strawberry powder, the active components associated with powder, and the actual mechanism of action, and standardized preparations will be required to permit the widespread use of strawberry powder with a predicable outcome. Clearly, however, this work is a good example of proof-of-principle and highlights the important role of diet, nutrition, and natural products in cancer prevention. ©2012 AACR.", "title": "Strawberry fields forever?" }, { "docid": "MED-1764", "text": "The decline in sperm count rates over the last 50 years appears to parallel the rising prevalence of obesity. As lipids levels are strongly associated with obesity, high lipids levels or hyperlipidemia may thus play an important role in the decline in fertility in addition to other environmental or lifestyle factors. The objective of this population based cohort study was to evaluate the association between men’s serum lipid concentrations and semen quality parameters among 501 male partners of couples desiring pregnancy and discontinuing contraception. Each participant provided prospectively up to two semen samples (94% of men provided one or more semen samples, and 77% of men provided a second sample approximately one month later). Linear mixed effects models were used to estimate the associations between baseline lipid concentrations and semen quality parameters, adjusted for age, body mass index, and race. We found that higher levels of serum total cholesterol, free cholesterol and phospholipids were associated with a significantly lower percentage of sperm with intact acrosome and smaller sperm head area and perimeter. Our results suggest that lipid concentrations may affect semen parameters, specifically sperm head morphology, highlighting the importance of cholesterol and lipid homeostasis for male fecundity.", "title": "Lipid Concentrations and Semen Quality: The LIFE Study" }, { "docid": "MED-3292", "text": "The human APOBEC3G protein is an innate anti-viral factor that can dominantly inhibit the replication of some endogenous and exogenous retroviruses. The prospects of purposefully harnessing such an anti-viral defense are under investigation. Here, long-term co-culture experiments were used to show that porcine endogenous retrovirus (PERV) transmission from pig to human cells is reduced to nearly undetectable levels by expressing human APOBEC3G in virus-producing pig kidney cells. Inhibition occurred by a deamination-independent mechanism, likely after particle production but before the virus could immortalize by integration into human genomic DNA. PERV inhibition did not require the DNA cytosine deaminase activity of APOBEC3G and, correspondingly, APOBEC3G-attributable hypermutations were not detected. In contrast, over-expression of the sole endogenous APOBEC3 protein of pigs failed to interfere significantly with PERV transmission. Together, these data constitute the first proof-of-principle demonstration that APOBEC3 proteins can be used to fortify the innate anti-viral defenses of cells to prevent the zoonotic transmission of an endogenous retrovirus. These studies suggest that human APOBEC3G-transgenic pigs will provide safer, PERV-less xenotransplantation resources and that analogous cross-species APOBEC3-dependent restriction strategies may be useful for thwarting other endogenous as well as exogenous retrovirus infections.", "title": "The Restriction of Zoonotic PERV Transmission by Human APOBEC3G" }, { "docid": "MED-2406", "text": "Objective. To examine the association between fish and marine long-chain omega-3 polyunsaturated fatty acid (LC n-3 PUFA) consumption and incidence of type 2 diabetes (T2D) in prospective cohort studies. Methods. Meta-analytic procedures were used to estimate the relative risk (RR) using random effects or fixed effects generic inverse variance model. Publication bias and study heterogeneity were assessed using Egger's test and I2 statistic. Results. We found no significant association between the intake of fish/seafood (pooled RR: 1.04; P = 0.63, 95% CI: 0.9 to 1.2, 549, 955 participants) or marine LC n-3 PUFA (pooled RR: 1.08, P = 0.39, 95% CI: 0.90 to 1.30, 346, 710 participants) and T2D risk. Significant study heterogeneity was observed in fish/seafood and marine LC n-3 PUFA studies (P < 0.00001). Subgroup analysis revealed no obvious sources for high heterogeneity. We also found a significant protective effect of oily fish intake on T2D risk (pooled RR = 0.89, P = 0.005, 95% CI: 0.82 to 0.96). Dose-response analysis suggested that every 80 g per day intake of oily fish may reduce 20% risk of T2D. Conclusion. We found no significant effect of fish/seafood or marine LC n-3 PUFA intake on risk of T2D but a significant effect of oily fish intake on risk of T2D.", "title": "Fish and Marine Omega-3 Polyunsatured Fatty Acid Consumption and Incidence of Type 2 Diabetes: A Systematic Review and Meta-Analysis" }, { "docid": "MED-3310", "text": "We observed five consecutive cases of Hypersensitivity Pneumonitis in subjects working in a salami factory. The workers had to clean the white mould growing on salami surface using a manual wire brush. The five patients (four female) had a mean age of 39 +/- 15 years; two were smokers. Three patients had an acute clinical presentation with fever, dyspnoea, dry cough, oxygen desaturation, and presented at the emergency department with suspected diagnosis of community acquired pneumonia. The mean latency for developing respiratory symptoms was 11.6 days. Pulmonary function test demonstrated a reduction in diffusing capacity (DLCO) in all 5 patients (60 +/- 15% of predicted value). Skin prick test was positive for Penicillium spp in 3 cases and for Cladosporium and Aspergillus spp in 2 others. Specific IgG antibodies against Penicillium spp were positive in 3 subjects; 2 were positive for Aspergillus Fumigatus. The prevailing radiological pattern was a ground glass appearance in the three patients with acute clinical onset and a centrilobular one in patients with subacute onset. All patients were advised to avoid exposure to the antigens. Follow-up visits including pulmonary function testing, and DLCO measurement were conducted at one, three and six months. HRCT was performed at six month. Four subjects had a complete radiological and clinical resolution after changing work. Only one patient was treated with oral steroids for severe dyspnoea and progressive reduction of DLCO, gaining a complete radiological and clinical stability at six months.", "title": "A new type of Hypersensitivity Pneumonitis: salami brusher's disease." }, { "docid": "MED-5003", "text": "Genistein, a major soy isoflavone, has been reported to exhibit antiadipogenic and proapoptotic potential in vivo and in vitro. It is also a phytoestrogen which has high affinity to estrogen receptor beta. In this study, we determined the effect of genistein on adipogenesis and estrogen receptor (ER) alpha and beta expression during differentiation in primary human preadipocytes. Genistein inhibited lipid accumulation in a dose-dependent manner at concentrations of 6.25 microM and higher, with 50 microM genistein inhibiting lipid accumulation almost completely. Low concentrations of genistein (3.25 microM) increased cell viability and higher concentrations (25 and 50 microM) decreased it by 16.48+/-1.35% (P<.0001) and 50.68+/-1.34% (P<.0001). Oil Red O staining was used to confirm the effects on lipid accumulation. The inhibition of lipid accumulation was associated with inhibition of glycerol-3-phosphate dehydrogenase activity and down-regulation of expression of adipocyte-specific genes, including peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein alpha, glycerol-3-phosphate dehydrogenase, adipocyte fatty acid binding protein, fatty acid synthase, sterol regulatory element-binding protein 1, perilipin, leptin, lipoprotein lipase and hormone-sensitive lipase. These effects of genistein during the differentiation period were associated with down-regulation of ERalpha and ERbeta expression. This study adds to the elucidation of the molecular pathways involved in the inhibition of adipogenesis by phytoestrogens.", "title": "Genistein inhibits differentiation of primary human adipocytes." }, { "docid": "MED-1617", "text": "Background Dietary modification via caloric restriction is associated with multiple effects related to improved metabolic and cardiovascular health. However, a mandated reduction in kilocalories is not well-tolerated by many individuals, limiting the long-term application of such a plan. The Daniel Fast is a widely utilized fast based on the Biblical book of Daniel. It involves a 21 day ad libitum food intake period, devoid of animal products and preservatives, and inclusive of fruits, vegetables, whole grains, legumes, nuts, and seeds. The purpose of the present study was to determine the efficacy of the Daniel Fast to improve markers of metabolic and cardiovascular disease risk. Methods 43 subjects (13 men; 30 women; 35 ± 1 yrs; range: 20-62 yrs) completed a 21 day period of modified food intake in accordance with detailed guidelines provided by investigators. All subjects purchased and prepared their own food. Following initial screening, subjects were given one week to prepare for the fast, after which time they reported to the lab for their pre-intervention assessment (day 1). After the 21 day fast, subjects reported to the lab for their post-intervention assessment (day 22). For both visits, subjects reported in a 12 hr fasted state, performing no strenuous physical activity during the preceding 24-48 hrs. At each visit, mental and physical health (SF-12 form), resting heart rate and blood pressure, and anthropometric variables were measured. Blood was collected for determination of complete blood count, metabolic panel, lipid panel, insulin, HOMA-IR, and C-reactive protein (CRP). Subjects' self-reported compliance, mood, and satiety in relation to the fast were also recorded. Diet records were maintained by all subjects during the 7 day period immediately prior to the fast (usual intake) and during the final 7 days of the fast. Results Subjects' compliance to the fast was 98.7 ± 0.2% (mean ± SEM). Using a 10 point scale, subjects' mood and satiety were both 7.9 ± 0.2. The following variables were significantly (p < 0.05) lower following the fast as compared to before the fast: white blood cell count (5.68 ± 0.24 vs. 4.99 ± 0.19 103·μL-1), blood urea nitrogen (13.07 ± 0.58 vs. 10.14 ± 0.59 mg·dL-1), blood urea nitrogen/creatinine (14.74 ± 0.59 vs. 11.67 ± 0.68), protein (6.95 ± 0.07 vs. 6.77 ± 0.06 g·dL-1), total cholesterol (171.07 ± 4.57 vs. 138.69 ± 4.39 mg·dL-1), LDL-C (98.38 ± 3.89 vs. 76.07 ± 3.53 mg·dL-1), HDL-C (55.65 ± 2.50 vs. 47.58 ± 2.19 mg·dL-1), SBP (114.65 ± 2.34 vs. 105.93 ± 2.12 mmHg), and DBP (72.23 ± 1.59 vs. 67.00 ± 1.43 mmHg). Insulin (4.42 ± 0.52 vs. 3.37 ± 0.35 μU·mL-1; p = 0.10), HOMA-IR (0.97 ± 0.13 vs.0.72 ± 0.08; p = 0.10), and CRP (3.15 ± 0.91 vs. 1.60 ± 0.42 mg·L-1; p = 0.13), were lowered to a clinically meaningful, albeit statistically insignificant extent. No significant difference was noted for any anthropometric variable (p > 0.05). As expected, multiple differences in dietary intake were noted (p < 0.05), including a reduction in total kilocalorie intake (2185 ± 94 vs. 1722 ± 85). Conclusion A 21 day period of modified dietary intake in accordance with the Daniel Fast is 1) well-tolerated by men and women and 2) improves several risk factors for metabolic and cardiovascular disease. Larger scale, randomized studies, inclusive of a longer time period and possibly a slight modification in food choice in an attempt to maintain HDL cholesterol, are needed to extend these findings.", "title": "Effect of a 21 day Daniel Fast on metabolic and cardiovascular disease risk factors in men and women" }, { "docid": "MED-4317", "text": "Iron is an essential trace metal in human metabolism. However, imbalances in iron homeostasis are prevalent worldwide and have detrimental effects on human health. Humans do not have the ability to remove excess iron and therefore iron homeostasis is maintained by regulating the amount of iron entering the body from the diet. Iron is present in the human diet in number of different forms, including heme (from meat) and a variety of non-heme iron compounds. While heme is absorbed intact, the bioavailability of non-heme iron varies greatly depending on dietary composition. A number of dietary components are capable of interacting with iron to regulate its solubility and oxidation state. Interestingly, there is an emerging body of evidence suggesting that some nutrients also have direct effects on the expression and function of enterocyte iron transporters. In addition to dietary factors, body iron status is a major determinant of iron absorption. The roles of these important dietary and systemic factors in regulating iron absorption will be discussed in this review.", "title": "Intestinal iron absorption: regulation by dietary & systemic factors." }, { "docid": "MED-3932", "text": "Background Caffeine consumption has been associated with a reduced risk of Parkinson disease. The association is strong and consistent in men, but uncertain in women, possibly because of an interaction with hormone replacement therapy. We sought to confirm these findings using data on Parkinson disease incidence in the CPS II Nutrition Cohort, a large prospective study of men and women. Methods We conducted a prospective study of caffeine intake and risk of PD within the Cancer Prevention Study II Nutrition Cohort. Intakes of coffee and other sources of caffeine were assessed at baseline. Incident cases of PD (n = 317; 197 men and 120 women) were confirmed by treating physicians and medical record review. Relative risks (RR) were estimated using proportional hazards models, adjusting for age, smoking and alcohol consumption. Results After adjustment for age, smoking and alcohol intake, high caffeine consumption was associated with a reduced risk of PD. The relative risk comparing the 5th to the 1st quintile of caffeine intake was 0.43 (CI: 0.26, 0.71, p-trend = <0.002) in men, and 0.61 (95% CI: 0.34, 1.09; p for trend =0.05) in women. Among women, this association was stronger among never users of hormone replacement therapy (RR=0.32) than among ever users (RR=0.81, p-interaction = 0.15). Consumption of decaffeinated coffee was not associated with PD risk. Conclusion Findings from this large prospective study of men and women are consistent with a protective effect of caffeine intake on PD incidence, with an attenuating influence of hormone replacement therapy in women.", "title": "Caffeine and risk of Parkinson disease in a large cohort of men and women" }, { "docid": "MED-4768", "text": "The rapid increase in obesity and the associated health care costs have prompted a search for better approaches for its prevention and management. Such efforts may be facilitated by better understanding the etiology of obesity. Of the several etiological factors, infection, an unusual causative factor, has recently started receiving greater attention. In the last two decades, 10 adipogenic pathogens were reported, including human and nonhuman viruses, scrapie agents, bacteria, and gut microflora. Some of these pathogens are associated with human obesity, but their causative role in human obesity has not been established. This chapter presents information about the natural hosts, signs and symptoms, and pathogenesis of the adipogenic microorganisms. If relevant to humans, \"Infectobesity\" would be a relatively novel, yet extremely significant concept. A new perspective about the infectious etiology of obesity may stimulate additional research to assess the contribution of hitherto unknown pathogens to human obesity and possibly to prevent or treat obesity of infectious origins.", "title": "Infectobesity: obesity of infectious origin." }, { "docid": "MED-3862", "text": "We conducted a combined analysis of the original data to evaluate the consistency of 12 case-control studies of diet and breast cancer. Our analysis shows a consistent, statistically significant, positive association between breast cancer risk and saturated fat intake in postmenopausal women (relative risk for highest vs. lowest quintile, 1.46; P less than .0001). A consistent protective effect for a number of markers of fruit and vegetable intake was demonstrated; vitamin C intake had the most consistent and statistically significant inverse association with breast cancer risk (relative risk for highest vs. lowest quintile, 0.69; P less than .0001). If these dietary associations represent causality, the attributable risk (i.e., the percentage of breast cancers that might be prevented by dietary modification) in the North American population is estimated to be 24% for postmenopausal women and 16% for premenopausal women.", "title": "Dietary factors and risk of breast cancer: combined analysis of 12 case-control studies." }, { "docid": "MED-4743", "text": "Performance of SBR treatment for nitrogen removal from tannery is evaluated for a wide range of wastewater temperature between 7 and 30 degrees C. A pilot-scale SBR unit fed with plain-settled wastewater is operated on site for this purpose. Effective nitrogen removal is sustained by adjustment of the sludge age from 28 to 5 days. Concentration profiles of nitrogen compounds within a selected complete SBR cycle during the steady state operation at different wastewater temperatures and sludge ages are evaluated by model simulation. System performance is also interpreted in terms of modeling and stoichiometric calculation. Additional nitrate loss was observed during aerobic period when the aeration intensity was reduced by the factor of 50%.", "title": "Performance evaluation of SBR treatment for nitrogen removal from tannery wastewater." }, { "docid": "MED-2359", "text": "INTRODUCTION: ALPHA-GAL is a glycoconjugate present on cell membranes of mammals and bacteria but not humans who display anti-Gal antibodies (AB) in high titers provoked by the commensal gut flora. In the present study, we sought to determine the longitudinal course of alpha-Gal specific AB titers of all isotypes over 8 weeks among healthy adult subjects. Furthermore, we hypothesized that inflammatory bowel disease (IBD) patients display increased anti-Gal titers. MATERIALS AND METHODS: We drew serum from healthy probands (n=20) weekly for 8 weeks and obtained plasma samples of from patients suffering from Crohn's disease (n=20) and ulcerative colitis (n=20). We measured anti-Gal ABs of all isotypes and total immunoglobulin (Ig) content using an enzyme-linked immunosorbent assay technique. For statistical evaluation of the longitudinal titers, we calculated confidence intervals for the slopes of a random intercept model, comparing variances between and within the probands. For group comparisons, we performed paired student t-tests and Pearson correlations. RESULTS: Alpha-Gal specific IgG, IgM, IgD, and IgA titers remained unvaried within a narrow range upon longitudinal observation. Most probands did not display alpha-Gal specific IgE ABs. Crohn's disease patients showed highly increased alpha-Gal-specific IgA titers compared with control subjects (P<.01). CONCLUSION: Apart from IgE, alpha-Gal-specific ABs of all isotypes remained constant over longer time periods in healthy subjects. Thus, significant titer changes actually represent increased antigen exposure and a specific anti-alpha-Gal response. Crohn's disease patients display increased anti-Gal IgA titers compared with healthy controls, which reflects a chronically impaired mucosal gut barrier in this patient cohort. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Anti-Gal titers in healthy adults and inflammatory bowel disease patients." }, { "docid": "MED-3438", "text": "Erectile dysfunction (ED) is defined as the inability to achieve or maintain an erection satisfactory for sexual performance. Evidence is accumulating to consider ED as a vascular disorder. Common risk factors for atherosclerosis are frequently found in association with ED, and ED is frequently reported in vascular syndromes, such as coronary artery disease (CAD), hypertension, cerebrovascular disease, peripheral arterial disease, and diabetes mellitus. Finally, similar early impairment of endothelium-dependent vasodilatation and late obstructive vascular changes has been reported in both ED and other vascular syndromes. Recently, we proposed a pathophysiologic mechanism to explain the link between ED and CAD called the artery size hypothesis. Given the systemic nature of atherosclerosis, all major vascular beds should be affected to the same extent. However, symptoms rarely become evident at the same time. This difference in rate of occurrence of different symptoms is proposed to be caused by the different size of the arteries supplying different vascular beds that allow a larger vessel to better tolerate the same amount of plaque compared with a smaller one. According to this hypothesis, because penile arteries are smaller in diameter than coronary arteries, patients with ED will seldom have concomitant symptoms of CAD, whereas patients with CAD will frequently complain of ED. Available clinical evidence appears to support this hypothesis.", "title": "The artery size hypothesis: a macrovascular link between erectile dysfunction and coronary artery disease." }, { "docid": "MED-4747", "text": "In contrast to the use of hormonal doping agents in sports to enhance the performance of athletes, in the livestock industry hormonal growth promoters (\"anabolics\") are used to increase the production of muscle meat. This leads to international disputes about the safety of meat originating from animals treated with such anabolics.As a consequence of the total ban in the EU of all hormonal active growth promoters (\"hormones\") in livestock production, in contrast to their legal use [e.g. of five such hormones (17beta-estradiol, testosterone, progesterone, trenbolone and zeranol) as small solid ear implants and two hormones as feed additives for feedlot heifers (melengestrol acetate) and for swine (ractopamine) in the USA], the regulatory controls also differ sharply between the EU and the USA.In the EU the treatment of slaughter animals is the regulatory offence that has to be controlled in inspection programs. In the USA testing for compliance of a regulatory maximum residue level in the edible product (muscle, fat, liver or kidney) is the purpose of the inspection program (if any).The EU inspection programs focus on sample materials that are more suitable for testing for banned substances, especially if the animals are still on the farm, such as urine and feces or hair. In the case of slaughtered animals, the more favored sample materials are bile, blood, eyes and sometimes liver. Only in rare occasions is muscle meat sampled. This happens only in the case of import controls or in monitoring programs of meat sampled in butcher shops or supermarkets.As a result, data on hormone concentrations in muscle meat samples from the EU market are very rare and are obtained in most cases from small programs on an ad hoc basis. EU data for natural hormones in meat are even rarer because of the absence of \"legal natural levels\" for these hormones in compliance testing. With the exception of samples from the application sites - in the EU the site of injection of liquid hormone preparations or the site of application of \"pour on\" preparations - the hormone concentrations observed in meat samples of illegally treated animals are typically in the range of a few micrograms per kilogram (ppb) down to a few tenths of a microgram per kilogram. In the EU dozens of illegal hormones are used and the number of active compounds is still expanding. Besides estrogenic, androgenic and progestagenic compounds also thyreostatic, corticosteroidal and beta-adrenergic compounds are used alone or in \"smart\" combinations.An overview is given of the compounds identified on the EU black market. An estimate is also given of the probability of consumption in the EU of \"highly\" contaminated meat from the application sites in cattle. Finally some data are presented on the concentration of estradiol in bovine meat from animals treated and not treated with hormone implants. These data are compared with the recent findings for estradiol concentrations in hen's eggs. From this comparison, the preliminary conclusion is that hen's eggs are the major source of 17alpha- and 17beta-estradiol in the consumer's daily \"normal\" diet.", "title": "Hormonal growth promoting agents in food producing animals." }, { "docid": "MED-4627", "text": "The emerging role of chronic inflammation in the major degenerative diseases of modern society has stimulated research into the influence of nutrition and dietary patterns on inflammatory indices. Most human studies have correlated analyses of habitual dietary intake as determined by a food frequency questionnaire or 24-hour recall with systemic markers of inflammation like high-sensitivity C-reactive protein (HS-CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). An occasional study also includes nutrition analysis of blood components. There have been several controlled interventions which evaluated the effect of a change in dietary pattern or of single foods on inflammatory markers in defined populations. Most studies reveal a modest effect of dietary composition on some inflammatory markers in free-living adults, although different markers do not vary in unison. Significant dietary influences have been established for glycemic index (GI) and load (GL), fiber, fatty acid composition, magnesium, carotenoids, and flavonoids. A traditional Mediterranean dietary pattern, which typically has a high ratio of monounsaturated (MUFA) to saturated (SFA) fats and ω-3 to ω-6 polyunsaturated fatty acid (PUFAs) and supplies an abundance of fruits, vegetables, legumes, and grains, has shown anti-inflammatory effects when compared with typical North American and Northern European dietary patterns in most observational and interventional studies and may become the diet of choice for diminishing chronic inflammation in clinical practice.", "title": "Diet and inflammation." }, { "docid": "MED-3429", "text": "Sexual problems are diffuse in both genders. Although epidemiologic evidence seems to support a role for lifestyle factors in erectile dysfunction, limited data are available suggesting the treatment of underlying risk factors may improve erectile dysfunction. The results are sparse regarding associations between lifestyle factors and female sexual dysfunction, and conclusions regarding influence of healthy behaviors on female sexual dysfunction cannot be made before more studies have been performed. Beyond the specific effects on sexual dysfunctions in men and women, adoption of these measures promotes a healthier life and increased well-being, which may help reduce the burden of sexual dysfunction. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Lifestyle/dietary recommendations for erectile dysfunction and female sexual dysfunction." }, { "docid": "MED-1988", "text": "PURPOSE OF REVIEW: To review recent literature on important topics in pediatric office practice: bullying, screening for the prediabetic state, and pediatric oral health. RECENT FINDINGS: Recent literature shows that bullying behaviors are common in children as young as kindergarten age, that there is a strong association between being a bully or victim and a range of psychosomatic and depressive symptoms in children, and that interventions including family therapy and school-based programs are effective for bullies and victims. Recent studies have further delineated glucose and insulin metabolism. Recent work has provided new models to help practitioners screen for the prediabetic state in hope of providing earlier opportunities to intervene and avoid the morbidities associated with type 2 diabetes mellitus. Recent literature emphasizes continued gaps in dental healthcare for patients who are most at risk. Recent studies emphasize the important role that diet and sealants have in preventing dental caries. SUMMARY: Recent literature emphasizes the important role that office-based pediatricians have in identifying patients who are involved in bullying, at risk of developing type 2 diabetes mellitus, or have poor dental health. Future research will help delineate these problems and provide us with refined primary prevention and treatment guidelines.", "title": "Pediatrician's role in screening and treatment: bullying, prediabetes, oral health." }, { "docid": "MED-3890", "text": "The connection between farm-generated animal waste and the dissemination of antibiotic resistance in soil microbial communities, via mobile genetic elements, remains obscure. In this study, electromagnetic induction (EMI) surveying of a broiler chicken farm assisted soil sampling from a chicken-waste-impacted site and a marginally affected site. Consistent with the EMI survey, a disparity existed between the two sites with regard to soil pH, tetracycline resistance (Tcr) levels among culturable soil bacteria, and the incidence and prevalence of several tet and erm genes in the soils. No significant difference was observed in these aspects between the marginally affected site and several sites in a relatively pristine regional forest. When the farm was in operation, tet(L), tet(M), tet(O), erm(A), erm(B), and erm(C) genes were detected in the waste-affected soil. Two years after all waste was removed from the farm, tet(L), tet(M), tet(O), and erm(C) genes were still detected. The abundances of tet(L), tet(O), and erm(B) were measured using quantitative PCR, and the copy numbers of each were normalized to eubacterial 16S rRNA gene copy numbers. tet(L) was the most prevalent gene, whereas tet(O) was the most persistent, although all declined over the 2-year period. A mobilizable plasmid carrying tet(L) was identified in seven of 14 Tcr soil isolates. The plasmid's hosts were identified as species of Bhargavaea, Sporosarcina, and Bacillus. The plasmid's mobilization (mob) gene was quantified to estimate its prevalence in the soil, and the ratio of tet(L) to mob was shown to have changed from 34:1 to 1:1 over the 2-year sampling period.", "title": "Detection of a Common and Persistent tet(L)-Carrying Plasmid in Chicken-Waste-Impacted Farm Soil" }, { "docid": "MED-1249", "text": "The effect of dietary protein on the level of plasma cholesterol in young, healthy, normolipidemic women was investigated in two separate studies by feeding either a conventional diet containing mixed protein, or a plant protein diet in which the animal protein of the first diet was replaced by soy protein meat analogues and soy milk. The diets were similar with respect to carbohydrate, fat and sterol composition. The first study, lasting 73 days and involving six subjects, gave an indication that plasma cholesterol levels were lower on the plant protein diet. The second study, which incorporated a number of improvements based on experience, lasted 78 days and used a cross-over design involving two groups of five subjects each. In this study, the mean plasma cholesterol level was found to be significantly lower on the plant protein diet.", "title": "Hypocholesterolemic effect of substituting soybean protein for animal protein in the diet of healthy young women." }, { "docid": "MED-1410", "text": "In 15 cohorts of the Seven Countries Study, comprising 11,579 men aged 40-59 years and \"healthy\" at entry, 2,288 died in 15 years. Death rates differed among cohorts. Differences in mean age, blood pressure, serum cholesterol, and smoking habits \"explained\" 46% of variance in death rate from all causes, 80% from coronary heart disease, 35% from cancer, and 45% from stroke. Death rate differences were unrelated to cohort differences in mean relative body weight, fatness, and physical activity. The cohorts differed in average diets. Death rates were related positively to average percentage of dietary energy from saturated fatty acids, negatively to dietary energy percentage from monounsaturated fatty acids, and were unrelated to dietary energy percentage from polyunsaturated fatty acids, proteins, carbohydrates, and alcohol. All death rates were negatively related to the ratio of monounsaturated to saturated fatty acids. Inclusion of that ratio with age, blood pressure, serum cholesterol, and smoking habits as independent variables accounted for 85% of variance in rates of deaths from all causes, 96% coronary heart disease, 55% cancer, and 66% stroke. Oleic acid accounted for almost all differences in monounsaturates among cohorts. All-cause and coronary heart disease death rates were low in cohorts with olive oil as the main fat. Causal relationships are not claimed but consideration of characteristics of populations as well as of individuals within populations is urged in evaluating risks.", "title": "The diet and 15-year death rate in the seven countries study." }, { "docid": "MED-2218", "text": "OBJECTIVE: To determine prevalence of dementia and its subtypes in Japanese-American men and compare these findings with rates reported for populations in Japan and elsewhere. DESIGN AND SETTING: The Honolulu Heart Program is a prospective population-based study of cardiovascular disease established in 1965. Prevalence estimates were computed from cases identified at the 1991 to 1993 examination. Cognitive performance was assessed using standardized methods, instruments, and diagnostic criteria. PARTICIPANTS: Subjects were 3734 Japanese-American men (80% of surviving cohort) aged 71 through 93 years, living in the community or in institutions. MAIN OUTCOME MEASURES: Age-specific, age-standardized, and cohort prevalence estimates were computed for dementia (all cause) defined by 2 sets of diagnostic criteria and 4 levels of severity. Prevalence levels for Alzheimer disease and vascular dementia were also estimated. RESULTS: Dementia prevalence by Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised ranged from 2.1% in men aged 71 through 74 years to 33.4% in men aged 85 through 93 years. Age-standardized prevalence was 7.6%. Prevalence estimates for the cohort were 9.3% for dementia (all cause), 5.4% for Alzheimer disease (primary or contributing), and 4.2% for vascular dementia (primary or contributing). More than 1 possible cause was found in 26% of cases. The Alzheimer disease/vascular dementia ratio was 1.5 for cases attributed primarily to Alzheimer disease or vascular dementia. CONCLUSIONS: Prevalence of Alzheimer disease in older Japanese-American men in Hawaii appears to be higher than in Japan but similar to European-ancestry populations. Prevalence of vascular dementia appears to be slightly lower than in Japan, but higher than in European-ancestry populations. Further cross-national research with emphasis on standardized diagnostic methods is needed.", "title": "Prevalence of dementia in older Japanese-American men in Hawaii: The Honolulu-Asia Aging Study." }, { "docid": "MED-3030", "text": "Consumption of marine fish provides both benefits (lean protein, omega-3 fatty acids and essential nutrients) and risks (main source of mercury (Hg) exposure for humans). Mercury is a potent neurotoxin and the source of more fish advisories nationwide than any other toxicant. Despite the widespread nature of Hg, it is unknown whether local Hg contamination reflects national and regional levels often used as bases to inform consumers of potential fish consumption risk. Thus, the objectives of our study were to examine Hg levels of six commonly consumed marine species harvested locally off the North Carolina coast and to compare our results to published regional (Monterey Bay Aquarium's Seafood Watch List) and national (Environmental Protection Agency, EPA, and Food and Drug Administration, FDA) Hg averages, action levels, and guidelines. We found significant differences in Hg concentrations among collected species, and we identified correlations between Hg concentration and fish length and trophic levels. Collected mahi mahi and triggerfish were below the EPA fish tissue action level (0.3ppm). Wahoo and grouper exceeded the EPA action level but were below the FDA action level (1.0ppm). King mackerel had the highest Hg concentration among targeted species, exceeding both EPA and FDA action levels. Further, our local results were not always consistent with calculated averages from EPA and FDA databases for the same species, and although many of our findings were consistent with Monterey Bay Aquarium's Seafood Watch List (southeast region), recommendations based on Hg levels would conflict with recommendations they provide based on sustainability. We find regional and national averages are not always reflective of local Hg contamination and suggest local data may be needed to accurately assess consumer risk.", "title": "Do national advisories serve local consumers: an assessment of mercury in economically important North Carolina fish." }, { "docid": "MED-4629", "text": "In a controlled, single blind clinical trial we have demonstrated recently a beneficial effect of fasting and vegetarian diet in RA. In the present study we compared 53 patients who participated in this clinical trial with 71 other RA patients with regard to some psychological parameters. The patients who participated in the clinical trial differed significantly from other RA patients. Firstly, they had a higher internal score and a lower chance score on the Multi-dimensional Health Locus of Control Scale (MHLCS). Secondly, their belief in the effect of ordinary medical treatment, evaluated by a 10-cm visual analogue scale, was lower, and their belief in the effect of 'alternative', unconventional forms of treatment was higher. Of the patients who were randomized to a vegetarian diet, there was no significant difference between diet responders and diet non-responders with regard to the MHLCS scores. But, diet responders had a significantly lower belief in the effect of ordinary medical treatment compared with diet non-responders. The psychological distress imposed on the patients by changing from an omnivorous diet to a vegetarian diet was monitored during the clinical trial by means of the General Health Questionnaire. Throughout the clinical trial, this variable favoured the vegetarians compared with the omnivorous and the diet responders vs the diet non-responders. We conclude, firstly, that patients with certain psychological characteristics were selected to the clinical trial; secondly, that the MHLCS scores could not explain the clinical improvement, but it may have been influenced by the patients' beliefs in ordinary and 'alternative' forms of treatment; and thirdly, that dietary treatment decreased psychological distress.", "title": "Vegetarian diet for patients with rheumatoid arthritis: can the clinical effects be explained by the psychological characteristics of the patients?" }, { "docid": "MED-2355", "text": "Anaphylaxis is a severe allergic reaction that can be rapidly progressing and fatal. In instances where the triggering allergen is not known, establishing the etiology of anaphylaxis is pivotal to long-term risk management. Our recent work has identified a novel IgE antibody (Ab) response to a mammalian oligosaccharide epitope, galactose-alpha-1,3-galactose (alpha-gal), that has been associated with two distinct forms of anaphylaxis: (1) immediate onset anaphylaxis during first exposure to intravenous cetuximab, and (2) delayed onset anaphylaxis 3–6 h after ingestion of mammalian food products (e.g., beef and pork). The results of our studies strongly suggest that tick bites are a cause, if not the only significant cause, of IgE Ab responses to alpha-gal in the southern, eastern and central United States. Patients with IgE Ab to alpha-gal continue to emerge and, increasingly, these cases involve children. This IgE Ab response cross-reacts with cat and dog but does not appear to pose a risk for asthma; however, it may impair diagnostic testing in some situations.", "title": "Delayed Anaphylaxis to Red Meat in Patients with IgE Specific for Galactose alpha-1,3-Galactose (alpha-gal)" }, { "docid": "MED-2698", "text": "BACKGROUND AND PURPOSE: Consumption of antioxidant-rich foods may reduce the risk of stroke by inhibition of oxidative stress and inflammation. Total antioxidant capacity (TAC) takes into account all antioxidants and the synergistic effects between them. We examined the association between dietary TAC and stroke incidence in cardiovascular disease (CVD)-free women and in women with CVD history at baseline. METHODS: The study included women (31,035 CVD-free and 5680 with CVD history at baseline), aged 49 to 83 years, from the Swedish Mammography Cohort. Diet was assessed with a food frequency questionnaire. Dietary TAC was calculated using oxygen radical absorbance capacity values. Stroke cases were ascertained by linkage with the Swedish Hospital Discharge Registry. RESULTS: During follow-up (September 1997 to December 2009), we identified 1322 stroke cases (988 cerebral infarctions, 226 hemorrhagic strokes, and 108 unspecified strokes) among CVD-free women and 1007 stroke cases (796 cerebral infarctions, 100 hemorrhagic strokes, and 111 unspecified strokes) among women with a CVD history. The multivariable hazard ratio of total stroke comparing the highest with the lowest quintile of dietary TAC was 0.83 (95% CI, 0.70-0.99; P for trend=0.04) in CVD-free women. Among women with a CVD history, the hazard ratios for the highest versus lowest quartile of TAC were 0.90 (95% CI, 0.75-1.07; P for trend=0.30) for total stroke and 0.55 (95% CI, 0.32-0.95; P for trend=0.03) for hemorrhagic stroke. CONCLUSIONS: These findings suggest that dietary TAC is inversely associated with total stroke among CVD-free women and hemorrhagic stroke among women with CVD history.", "title": "Total antioxidant capacity of diet and risk of stroke: a population-based prospective cohort of women." }, { "docid": "MED-1451", "text": "OBJECTIVE: To test the hypothesis that comprehensive efforts to reduce a workforce's health and safety risks can be associated with a company's stock market performance. METHODS: Stock market performance of Corporate Health Achievement Award winners was tracked under four different scenarios using simulation and past market performance. RESULTS: A portfolio of companies recognized as award winning for their approach to the health and safety of their workforce outperformed the market. Evidence seems to support that building cultures of health and safety provides a competitive advantage in the marketplace. This research may have also identified an association between companies that focus on health and safety and companies that manage other aspects of their business equally well. CONCLUSIONS: Companies that build a culture of health by focusing on the well-being and safety of their workforce yield greater value for their investors.", "title": "The link between workforce health and safety and the health of the bottom line: tracking market performance of companies that nurture a \"culture of..." }, { "docid": "MED-3875", "text": "BACKGROUND: Mammalian lignans, enterolactone (EL) and enterodiol (ED), have been shown to inhibit breast and colon carcinoma. To date, there have been no reports of the effect of lignans on prostatic carcinoma. We investigated the effects of ED and EL on three human prostate cancer cell lines (PC-3, DU-145 and LNCaP). MATERIALS AND METHODS: Cells were treated with either 0.1% (v/v) DMSO (vehicle) or 10-100 microM of EL, ED or genistein (positive control) for 72 hours. Cell viability was measured by the propidium iodide nuclei staining fluorometric assay with each assay performed in triplicate. RESULTS: At 10-100 microM, EL significantly inhibited the growth of all cell lines, whereas ED only inhibited PC-3 and LNCaP cells. While EL was a more potent growth inhibitor than ED, both were less potent than genistein. The dose for 50% growth inhibition of LNCaP cells (IC50) by EL was 57 microM, whereas IC50 was 100 microM for ED, (the observed IC50 for genistein was 25 microM). CONCLUSION: ED and EL suppress the growth of prostate cancer cells, and may do so via hormonally-dependent and independent mechanisms.", "title": "Effect of mammalian lignans on the growth of prostate cancer cell lines." }, { "docid": "MED-3926", "text": "Sixteen parkinsonian patients with daily fluctuations in the clinical response to levodopa have been placed on a redistribution protein diet. The diet was virtually protein-free until the evening meal and then unrestricted until bedtime. While on the redistribution protein diet, a group of patients (5 out of 16) had a clear and significant benefit from dietary therapy showing a definite reduction of diurnal motor performance fluctuations. In addition, all patients tended to show an improvement and a more constant response to levodopa treatment. A trial of redistribution protein diet appears a simple, reasonable, worthwhile approach to PD patients who begin to experience oscillating clinical response to levodopa treatment.", "title": "Protein redistribution diet and antiparkinsonian response to levodopa." }, { "docid": "MED-4070", "text": "It has been suggested that mutagens in fried meat may be involved in the cancer process. Therefore the relationships between intake of fried meat and subsequent risk of cancers at different sites were studied among 9,990 Finnish men and women, 15-99 years of age and initially free of cancer. The baseline study was carried out in 1966-1972, and cases of cancer were identified through data linkage with the Finnish Cancer Registry. During a 24-year follow-up, 853 cancer cases were diagnosed. The intake of fried meat was estimated from a dietary history interview covering the total diet of the participants during the previous year. There was a positive association between fried meat intake and the risk of female-hormone-related cancers, i.e., cancer of the breast, endometrium and ovary combined. The relative risk of these cancers combined between persons in the highest and lowest tertiles of daily intake of fried meat adjusted for age, personal characteristics and intake of other main food groups was 1.77 (95% confidence interval = 1.11-2.84). Pancreatic and nervous system cancers also presented non-significant suggestive associations. No associations were observed with respect to other single cancer sites studied or to all sites of cancer combined. Further epidemiological efforts are needed to ascertain the potential link between fried-food mutagens and cancer risk.", "title": "Intake of fried meat and risk of cancer: a follow-up study in Finland." }, { "docid": "MED-1947", "text": "The present report, describes for the first time the clinical efficacy of curcumin, the active constituent of rhizomes of Curcuma longa, in the treatment of patients suffering from idiopathic inflammatory orbital pseudotumours. Curcumin was administered orally at a dose of 375 mg/3 times/day orally for a period of 6-22 months in eight patients. They were followed up for a period of 2 years at 3 monthly intervals. Five patients completed the study, out of which four recovered completely and in one patient the swelling regressed completely but some limitation of movement persisted. No side effect was noted in any patient and there was no recurrence. It is suggested that curcumin could be used as a safe and effective drug in the treatment of idiopathic inflammatory orbital pseudotumours. Copyright 2000 John Wiley & Sons, Ltd.", "title": "Role of curcumin in idiopathic inflammatory orbital pseudotumours." }, { "docid": "MED-1961", "text": "Dioxins and related compounds are undesirable and unintended contaminants in the food supply, and dietary intake is the major route of exposure. Reducing dietary exposure to dioxins among the most vulnerable segments of the population (i.e., pregnant women, infants, and young girls) is an effective strategy for reducing body burdens in future generations. Exposure to dioxins through foods can be minimized by selecting lower-fat versions of meats, poultry, and dairy products. Consuming all foods, including fatty fish, in recommended amounts is congruent with the goal of reducing dioxin intake exposure and maintaining good health.", "title": "Reducing exposure to dioxins and related compounds through foods in the next generation." }, { "docid": "MED-3792", "text": "Basal serum prolactin and serum oestradiol-17-beta concentrations were measured four times during one menstrual cycle in 20 women with severe cyclical mastalgia and normal to slightly fibroadenotic breasts. A group of 10 normal women who had never experienced mastalgia served as controls. Basal serum prolactin was significantly elevated in patients compared to normals, although within the normal range. Serum oestradiol concentrations did not differ in the two groups and were also within the normal range. A significant positive correlation between oestradiol and prolactin was found in patients and normals, but with larger prolactin levels in patients. The results point towards a prolactin secretory hypersensitivity for oestradiol in patients with cyclical mastalgia. Prolactin is considered a central factor in the eliciting of cyclical mastalgia.", "title": "Serum prolactin and oestradiol levels in women with cyclical mastalgia." }, { "docid": "MED-3955", "text": "BACKGROUND Polybrominated Diphenyl Ethers (PBDEs), widely used as flame retardants since the 1970s, have exhibited endocrine disruption in experimental studies. Tetra- to hexa-BDE congeners are estrogenic, while hepta-BDE and 6-OH-BDE-47 are antiestrogenic. Most PBDEs also have antiandrogenic activity. It is not clear, however, whether PBDEs affect human reproduction. OBJECTIVES The analysis was designed to investigate the potential endocrine disruption of PBDEs on the age at menarche in adolescent girls. METHODS We analyzed the data from a sample of 271 adolescent girls (age 12–19 years) in the National Health and Nutrition Examination Survey (NHANES), 2003–2004. We estimated the associations between individual and total serum BDEs (BDE-28, -47, -99, -100, -153, and -154, lipid adjusted) and mean age at menarche. We also calculated the risk ratios (RRs) and 95% confidence intervals (CI) for menarche prior to age 12 years in relation to PBDE exposure. RESULTS The median total serum BDE concentration was 44.7 ng/g lipid. Higher serum PBDE concentrations were associated with slightly earlier ages at menarche. Each natural log unit of total BDEs was related to a change of −0.10 (95% CI: −0.33, 0.13) years of age at menarche and a RR of 1.60 (95% CI: 1.12, 2.28) for experiencing menarche before 12 years of age, after adjustment for potential confounders. CONCLUSION These data suggest high concentrations of serum PBDEs during adolescence are associated with a younger age of menarche.", "title": "Serum PBDEs and Age at Menarche in Adolescent Girls: Analysis of the National Health and Nutrition Examination Survey 2003–2004" }, { "docid": "MED-2699", "text": "Significance: The free radical theory of aging has provided a theoretical framework for an enormous amount of work leading to significant advances in our understanding of aging. Up to the turn of the century, the theory received abundant support from observations coming from fields as far apart as comparative physiology or molecular biology. Recent Advances: Work from many laboratories supports the theory, for instance showing that overexpression of antioxidant enzymes results in increases in life-span. But other labs have shown that in some cases, there is an increased oxidative stress and increased longevity. The discovery that free radicals can not only cause molecular damage to cells, but also serve as signals; led to the proposal that they act as modulators of physiological processes. For instance, reactive oxygen species (ROS) stimulate physiological adaptations to physical exercise. Critical Issues: A critical blow to the free radical theory of aging came from epidemiological studies showing that antioxidant supplementation did not lower the incidence of many age-associated diseases but, in some cases, increased the risk of death. Moreover, recent molecular evidence has shown that increasing generation of ROS, in some cases, increases longevity. Future Directions: Gerontologists interested in free radical biology are at a crossroads and clearly new insights are required to clarify the role of ROS in the process of aging. The hurdles are, no doubt, very high, but the intellectual and practical promise of these studies is of such magnitude that we feel that all efforts will be generously rewarding. Antioxid. Redox Signal. 19, 779–787.", "title": "The Free Radical Theory of Aging Revisited: The Cell Signaling Disruption Theory of Aging" }, { "docid": "MED-3270", "text": "Aging affects all organisms and its basic mechanisms are expected to be conserved across species. Oxidation of proteins has been proposed to be one of the basic mechanisms linking oxygen radicals with the basic aging process. If oxidative damage to proteins is involved in aging, long-lived animals (which age slowly) should show lower levels of markers of this kind of damage than short-lived ones. However, this possibility has not been investigated yet. In this study, steady-state levels of markers of different kinds of protein damage--oxidation (glutamic and aminoadipic semialdehydes), mixed glyco- and lipoxidation (carboxymethyl- and carboxyethyllysine), lipoxidation (malondialdehydelysine) and amino acid composition--were measured in the heart of eight mammalian species ranging in maximum life span (MLSP) from 3.5 to 46 years. Oxidation markers were directly correlated with MLSP across species. Mixed glyco- and lipoxidation markers did not correlate with MLSP. However, the lipoxidation marker malondialdehydelysine was inversely correlated with MLSP (r2=0.85; P<0.001). The amino acid compositional analysis revealed that methionine is the only amino acid strongly correlated MLSP and that such correlation is negative (r2=0.93; P<0.001). This trait may contribute to lower steady-state levels of oxidized methionine residues in cellular proteins. These results reinforce the notion that high longevity in homeothermic vertebrates is achieved in part by constitutively decreasing the sensitivity of both tissue proteins and lipids to oxidative damage. This is obtained by modifying the constituent structural components of proteins and lipids, selecting those less sensitive to oxidative modifications.", "title": "Protein methionine content and MDA-lysine adducts are inversely related to maximum life span in the heart of mammals." }, { "docid": "MED-3819", "text": "Adiponectin is discussed to regulate energy balance and insulin sensitivity. Several studies indicated an association of fasting adiponectin with parameters of the metabolic syndrome. We investigated postprandial adiponectin release and its relation to traits of the metabolic syndrome. Serum adiponectin concentration after an oral glucose tolerance test and after ingestion of a standardised mixed, fat-containing meal in 110 male non-diabetic subjects was assessed. Fasting and postprandial adiponectin and the decrease of adiponectin were correlated with anthropometric and metabolic parameters. Subjects were genotyped for adiponectin - 11 388 G/A promoter single nucleotide polymorphism. Adiponectin slightly decreased after both test meals. A significant decrease was attained 5 and 6 h after the lipid load and 2 h after the glucose load. Particularly, the mixed meal postprandial adiponectin showed stronger correlations with most traits of the metabolic syndrome than fasting adiponectin: postprandial adiponectin with HDL (r 0.30) v. fasting adiponectin with HDL (r 0.23); with postprandial insulin (area under the curve): r - 0.20 v. r - 0.16; with fasting insulin: r 0.10 v. r 0.14; with BMI: r - 0.23 v. r - 0.20; with waist: r - 0.18 v. - 0.16; with systolic blood pressure: r - 0.14 v. r - 0.12; with diastolic blood pressure: r - 0.18 v. r - 0.15. In multivariate analysis, postprandial TAG were the only independent predictor of adiponectin. There was no significant association of adiponectin, NEFA and TAG with - 11 388 G/A adiponectin promoter polymorphism. Our findings favour the interpretation that postprandial adiponectin has the strongest and independent associations to postprandial TAG metabolism.", "title": "Postprandial plasma adiponectin decreases after glucose and high fat meal and is independently associated with postprandial triacylglycerols but no..." }, { "docid": "MED-4026", "text": "AIM: The aim of this study was to investigate possible risk factors for dental caries in primary school children. METHODS: Children aged 10-12 years (n = 257) residing in Lithgow, a non-fluoridated community in New South Wales, Australia, were examined for caries experience in the permanent dentition. Information on dental practices, diet, residential movements, and socioeconomic status were obtained from self-completed questionnaires. RESULTS: Caries risk in the permanent teeth was associated with social disadvantage and diet. Among the dietary factors, the frequency of fruit consumption was associated with higher odds of caries experience (odds ratio: 1.52, 95% confidence intervals: 1.05, 2.21). CONCLUSIONS: Exposure to a high level of fruit consumption was suggestive of increased caries risk. Longitudinal studies are required to investigate the relationship between fruit consumption and dental caries. © 2011 Blackwell Publishing Asia Pty Ltd.", "title": "Is the consumption of fruit cariogenic?" }, { "docid": "MED-2999", "text": "Many of the commonest diseases in the economically more developed communities are characteristic of modern Western culture. Evidence is presented suggesting that they represent a failure of adaptation to the dramatic changes in diet that have been associated with the emergence of modern Western culture. Dietary changes aimed at the alleviation and prevention of these diseases are discussed and recommended.", "title": "Western diseases and their emergence related to diet." }, { "docid": "MED-3697", "text": "BACKGROUND: Many studies have analyzed the effect of behavioral risk factors such as common lifestyle patterns on the risk of disease. The aim of this study was to assess the effect of a healthy lifestyle index on the risk of breast cancer. METHODS: A population-based case-control study was conducted in Mexico from 2004 to 2007. One thousand incident cases and 1,074 controls, matched to cases by 5-year age category, region, and health institution, participated in the study. A healthy lifestyle index was developed by means of principal components by using dietary pattern, physical activity, alcohol consumption, and tobacco smoking. A conditional logistic regression model was used to assess this association. RESULTS: The healthy lifestyle index was defined as the combined effect of moderate and/or vigorous-intensity physical activity, low consumption of fat, processed foods, refined cereals, complex sugars, and the avoidance of tobacco smoking and alcohol consumption. Results showed a protective effect on both pre- (OR = 0.50, 95% CI: 0.29-0.84) and postmenopausal women (OR = O.20, 95% CI: 0.11-0.37) when highest versus lowest index quintiles were compared. CONCLUSIONS: Healthy lifestyle was associated with a reduction in the odds of having breast cancer. Primary prevention of this disease should be promoted in an integrated manner. Effective strategies need to be identified to engage women in healthy lifestyles. IMPACT: This study is the first to assess a healthy lifestyle index in relation to the risk of breast cancer. ©2011 AACR.", "title": "Healthy lifestyle on the risk of breast cancer." }, { "docid": "MED-4796", "text": "Clostridium difficile is a critically important cause of disease in humans, particularly in hospitalized individuals. Three major factors have raised concern about the potential for this pathogen to be a cause of foodborne disease: the increasing recognition of community-associated C. difficile infection, recent studies identifying C. difficile in food animals and food, and similarities in C. difficile isolates from animals, food and humans. It is clear that C. difficile can be commonly found in food animals and food in many regions, and that strains important in human infections, such as ribotype 027/NAP1/toxinotype III and ribotype 078/toxinotype V, are often present. However, it is currently unclear whether ingestion of contaminated food can result in colonization or infection. Many questions remain unanswered regarding the role of C. difficile in community-associated diarrhoea: its source when it is a food contaminant, the infective dose, and the association between ingestion of contaminated food and disease. The significant role of this pathogen in human disease and its potential emergence as an important community-associated pathogen indicate that careful evaluation of different sources of exposure, including food, is required, but determination of the potential role of food in C. difficile infection may be difficult.", "title": "Clostridium difficile in food--innocent bystander or serious threat?" }, { "docid": "MED-3984", "text": "In recent years, the number of human rabies cases in the People’s Republic of China has increased during severe epidemics in 3 southern provinces (Guizhou, Guangxi, and Hunan). To analyze the causes of the high incidence of human rabies in this region, during 2005–2007, we collected 2,887 brain specimens from apparently healthy domestic dogs used for meat consumption in restaurants, 4 specimens from suspected rabid dogs, and 3 from humans with rabies in the 3 provinces. Partial nucleoprotein gene sequences were obtained from rabies-positive specimens. Phylogenetic relationships and distribution of viruses were determined. We infer that the spread of rabies viruses from high-incidence regions, particularly by long-distance movement or transprovincial translocation of dogs caused by human-related activities, may be 1 cause of the recent massive human rabies epidemics in southern China.", "title": "Molecular Epidemiology of Rabies in Southern People’s Republic of China" }, { "docid": "MED-1928", "text": "Purpose of review There has been growing evidence that lifestyle factors may affect the health and lifespan of an individual by affecting telomere length. The purpose of this review was to highlight the importance of telomeres in human health and aging and to summarize possible lifestyle factors that may affect health and longevity by altering the rate of telomere shortening. Recent findings Recent studies indicate that telomere length, which can be affected by various lifestyle factors, can affect the pace of aging and onset of age-associated diseases. Summary Telomere length shortens with age. Progressive shortening of telomeres leads to senescence, apoptosis, or oncogenic transformation of somatic cells, affecting the health and lifespan of an individual. Shorter telomeres have been associated with increased incidence of diseases and poor survival. The rate of telomere shortening can be either increased or decreased by specific lifestyle factors. Better choice of diet and activities has great potential to reduce the rate of telomere shortening or at least prevent excessive telomere attrition, leading to delayed onset of age-associated diseases and increased lifespan. This review highlights the role of telomeres in aging and describes the lifestyle factors which may affect telomeres, human health, and aging.", "title": "Telomeres, lifestyle, cancer, and aging" }, { "docid": "MED-4431", "text": "BACKGROUND: Workers in poultry plants have high exposure to a variety of transmissible agents present in poultry and their products. Subjects in the general population are also exposed. It is not known whether many of these agents cause disease in humans. If they do, we reason this would be readily evident in a highly exposed group such as poultry workers. We report here on mortality from non-malignant diseases in a cohort of poultry workers. METHODS: Mortality was compared with that of the US general population, and with that of a comparison group from the same union. Risk was estimated by standardized mortality ratio, proportional mortality ratio, and directly standardized risk ratio. RESULTS: Poultry workers as a group had an overall excess of deaths from diabetes, anterior horn disease, and hypertensive disease, and a deficit of deaths from intracerebral hemorrhage. Deaths from zoonotic bacterial diseases, helminthiasis, myasthenia gravis, schizophrenia, other diseases of the spinal cord, diseases of the esophagus and peritonitis were non-significantly elevated overall by all analyses, and significantly so in particular race/sex subgroups. CONCLUSIONS: Poultry workers may have excess occurrence of disease affecting several organs and systems, probably originating from widespread infection with a variety of microorganisms. The results for neurologic diseases could well represent important clues to the etiology of these diseases in humans. The small numbers of deaths involved in some cases limit interpretation.", "title": "Mortality in the Baltimore union poultry cohort: non-malignant diseases." }, { "docid": "MED-2410", "text": "Background and aims Previous research on the association between fish consumption and incident type 2 diabetes has been inconclusive. In addition, few studies have investigated how fish consumption may be related to the metabolic abnormalities underlying diabetes. Therefore, we examined the association of fish consumption with measures of insulin sensitivity and beta-cell function in a multi-ethnic population. Methods and results We examined the cross-sectional association between fish consumption and measures of insulin sensitivity and secretion in 951 non-diabetic participants in the Insulin Resistance Atherosclerosis Study (IRAS). Fish consumption, categorized as <2 vs. ≥2 portions/week, was measured using a validated food frequency questionnaire. Insulin sensitivity (SI) and acute insulin response (AIR) were determined from frequently sampled intravenous glucose tolerance tests. Higher fish consumption was independently associated with lower SI-adjusted AIR (β=−0.13 [−0.25, −0.016], p=0.03, comparing ≥ 2 vs. <2 portions/week). Fish consumption was positively associated with intact and split proinsulin/C-peptide ratios, however, these associations were confounded by ethnicity (multivariable-adjusted β=0.073 [−0.014, 0.16] for intact proinsulin/C-peptide ratio, β=0.031 [−0.065, 0.13] for split proinsulin/C-peptide ratio). We also observed a significant positive association between fish consumption and fasting blood glucose (multivariable-adjusted β=2.27 [0.68, 3.86], p=0.005). We found no association between fish consumption and SI (multivariable-adjusted β= −0.015 [−0.083, 0.053]) or fasting insulin (multivariable-adjusted β=0.016 [−0.066, 0.10]). Conclusions Fish consumption was not associated with measures of insulin sensitivity in the multi-ethnic IRAS cohort. However, higher fish consumption may be associated with pancreatic beta-cell dysfunction.", "title": "Fish consumption, insulin sensitivity and beta-cell function in the Insulin Resistance Atherosclerosis Study (IRAS)" }, { "docid": "MED-1161", "text": "Pesticides are one of the major inputs used for increasing agricultural productivity of crops. The pesticide residues, left to variable extent in the food materials after harvesting, are beyond the control of consumer and have deleterious effect on human health. The presence of pesticide residues is a major bottleneck in the international trade of food commodities. The localization of pesticides in foods varies with the nature of pesticide molecule, type and portion of food material and environmental factors. The food crops treated with pesticides invariably contain unpredictable amount of these chemicals, therefore, it becomes imperative to find out some alternatives for decontamination of foods. The washing with water or soaking in solutions of salt and some chemicals e.g. chlorine, chlorine dioxide, hydrogen peroxide, ozone, acetic acid, hydroxy peracetic acid, iprodione and detergents are reported to be highly effective in reducing the level of pesticides. Preparatory steps like peeling, trimming etc. remove the residues from outer portions. Various thermal processing treatments like pasteurization, blanching, boiling, cooking, steaming, canning, scrambling etc. have been found valuable in degradation of various pesticides depending upon the type of pesticide and length of treatment. Preservation techniques like drying or dehydration and concentration increase the pesticide content many folds due to concentration effect. Many other techniques like refining, fermentation and curing have been reported to affect the pesticide level in foods to varied extent. Milling, baking, wine making, malting and brewing resulted in lowering of pesticide residue level in the end products. Post harvest treatments and cold storage have also been found effective. Many of the decontamination techniques bring down the concentration of pesticides below MRL. However, the diminution effect depends upon the initial concentration at the time of harvest, substrate/food and type of pesticide. There is diversified information available in literature on the effect of preparation, processing and subsequent handling and storage of foods on pesticide residues which has been compiled in this article.", "title": "Effect of handling and processing on pesticide residues in food- a review" }, { "docid": "MED-4319", "text": "The article gives an overview of phytic acid in food and of its significance for human nutrition. It summarises phytate sources in foods and discusses problems of phytic acid/phytate contents of food tables. Data on phytic acid intake are evaluated and daily phytic acid intake depending on food habits is assessed. Degradation of phytate during gastro-intestinal passage is summarised, the mechanism of phytate interacting with minerals and trace elements in the gastro-intestinal chyme described and the pathway of inositol phosphate hydrolysis in the gut presented. The present knowledge of phytate absorption is summarised and discussed. Effects of phytate on mineral and trace element bioavailability are reported and phytate degradation during processing and storage is described. Beneficial activities of dietary phytate such as its effects on calcification and kidney stone formation and on lowering blood glucose and lipids are reported. The antioxidative property of phytic acid and its potentional anticancerogenic activities are briefly surveyed. Development of the analysis of phytic acid and other inositol phosphates is described, problems of inositol phosphate determination and detection discussed and the need for standardisation of phytic acid analysis in foods argued.", "title": "Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis." }, { "docid": "MED-2369", "text": "Background Carbohydrate moieties are frequently encountered in food and can elicit IgE responses, the clinical significance of which has been unclear. Recent work, however, has shown that IgE antibodies to galactose-α-1,3-galactose (α-gal), a carbohydrate commonly expressed on nonprimate mammalian proteins, are capable of eliciting serious, even fatal, reactions. Objective We sought to determine whether IgE antibodies to α-gal are present in sera from patients who report anaphylaxis or urticaria after eating beef, pork, or lamb. Methods Detailed histories were taken from patients presenting to the University of Virginia Allergy Clinic. Skin prick tests (SPTs), intradermal skin tests, and serum IgE antibody analysis were performed for common indoor, outdoor, and food allergens. Results Twenty-four patients with IgE antibodies to α-gal were identified. These patients described a similar history of anaphylaxis or urticaria 3 to 6 hours after the ingestion of meat and reported fewer or no episodes when following an avoidance diet. SPTs to mammalian meat produced wheals of usually less than 4 mm, whereas intradermal or fresh-food SPTs provided larger and more consistent wheal responses. CAP-RAST testing revealed specific IgE antibodies to beef, pork, lamb, cow’s milk, cat, and dog but not turkey, chicken, or fish. Absorption experiments indicated that this pattern of sensitivity was explained by an IgE antibody specific for α-gal. Conclusion We report a novel and severe food allergy related to IgE antibodies to the carbohydrate epitope α-gal. These patients experience delayed symptoms of anaphylaxis, angioedema, or urticaria associated with eating beef, pork, or lamb.", "title": "Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-α-1,3-galactose" }, { "docid": "MED-2409", "text": "Background Prospective cohort studies in relation to the associations between n-3 polyunsaturated fatty acids (PUFA) and risk of type 2 diabetes (T2D) were inconsistent. Differences in tissue n-3 PUFA compositions in subjects with and without T2D were also inconsistent in both cohort and case-control studies. We conducted a systematic review and meta-analysis of prospective cohort studies to examine the associations of fish and n-3 PUFA intake with T2D risk. The differences in tissue n-3 PUFA compositions in subjects with and without T2D were investigated based on cohort and case-control studies. Methods and Findings PubMed, Embase, Cochrane library, China National Knowledge Infrastructure (CNKI) and Chinese VIP database up to January 2012 was used to identify relevant studies, and reference lists from retrieved studies were reviewed. Two authors independently extracted the data. Random-effects models were used to pool the summary relative risk (RR). Twenty-four studies including 24,509 T2D patients and 545,275 participants were identified. For cohort studies, the summary RR of T2D for the highest vs lowest categories of total fish, marine n-3 PUFA and alpha-linolenic acid intake was 1.07 (95% CI: 0.91, 1.25), 1.07 (95% CI: 0.95, 1.20) and 0.93 (95% CI: 0.81, 1.07), respectively. Subgroup analyses indicated that summary RR (highest vs lowest category) of T2D for fish and marine n-3 PUFA intake was 0.89 (95% CI: 0.81, 0.98) and 0.87 (95% CI: 0.79, 0.96) for Asian populations, and 1.20 (95% CI: 1.01, 1.44) and 1.16 (95% CI: 1.04, 1.28) for Western populations. Asian subjects with T2D had significantly lower tissue compositions of C22∶6n-3 (SMD: −1.43; 95% CI: −1.75, −1.12) and total n-3 PUFA (SMD: −1.41; 95% CI: −2.23, −0.59) compared with those without T2D. Conclusion This systematic review and meta-analysis provides evidence that marine n-3 PUFA have beneficial effects on the prevention of T2D in Asian populations.", "title": "Marine N-3 Polyunsaturated Fatty Acids Are Inversely Associated with Risk of Type 2 Diabetes in Asians: A Systematic Review and Meta-Analysis" }, { "docid": "MED-2695", "text": "BACKGROUND: There are no previous studies investigating the effect of all dietary antioxidants in relation to myocardial infarction. The total antioxidant capacity of diet takes into account all antioxidants and synergistic effects between them. The aim of this study was to examine how total antioxidant capacity of diet and antioxidant-containing foods were associated with incident myocardial infarction among middle-aged and elderly women. METHODS: In the population-based prospective Swedish Mammography Cohort of 49-83-year-old women, 32,561 were cardiovascular disease-free at baseline. Women completed a food-frequency questionnaire, and dietary total antioxidant capacity was calculated using oxygen radical absorbance capacity values. Information on myocardial infarction was identified from the Swedish Hospital Discharge and the Cause of Death registries. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazard models. RESULTS: During the follow-up (September 1997-December 2007), we identified 1114 incident cases of myocardial infarction (321,434 person-years). In multivariable-adjusted analysis, the HR for women comparing the highest quintile of dietary total antioxidant capacity to the lowest was 0.80 (95% CI, 0.67-0.97; P for trend=0.02). Servings of fruit and vegetables and whole grains were nonsignificantly inversely associated with myocardial infarction. CONCLUSIONS: These data suggest that dietary total antioxidant capacity, based on fruits, vegetables, coffee, and whole grains, is of importance in the prevention of myocardial infarction. Copyright © 2012 Elsevier Inc. All rights reserved.", "title": "Total antioxidant capacity from diet and risk of myocardial infarction: a prospective cohort of women." }, { "docid": "MED-2696", "text": "A high intake of dietary antioxidant compounds has been hypothesized to be an appropriate strategy to reduce gastric cancer (GC) development. We investigated the effect of dietary total antioxidant capacity (TAC) in relation to GC in the European Prospective Investigation into Cancer (EPIC) study including 23 centers in 10 European countries. A total of 521,457 subjects (153,447 men) aged mostly 35-70 years old, were recruited largely between 1992 and 1998. Ferric reducing antioxidant potential (FRAP) and total radical-trapping antioxidant parameter (TRAP), measuring reducing and chain-breaking antioxidant capacity were used to measure dietary TAC from plant foods. Dietary antioxidant intake is associated with a reduction in the risk of GC for both FRAP (adjusted HR 0.66; 95%CI (0.46-0.95) and TRAP (adjusted HR 0.61; 95%CI (0.43-0.87) (highest vs. lowest quintile). The association was observed for both cardia and noncardia cancers. A clear effect was observed in smokers with a significant reduction in GC risk for the fifth quintile of intake for both assays (highest vs. lowest quintile: adjusted HR 0.41; 95%CI (0.22-0.76) p for trend <0.001 for FRAP; adjusted HR 0.52; 95%CI (0.28-0.97) p for trend <0.001 for TRAP) but not in nonsmokers. In former smokers, the association with FRAP intake was statistically significant (highest vs. lowest quintile: adjusted HR 0.4; 95%CI (0.21-0.75) p < 0.05); no association was observed for TRAP. Dietary antioxidant capacity intake from different sources of plant foods is associated with a reduction in the risk of GC. Copyright © 2011 UICC.", "title": "Dietary total antioxidant capacity and gastric cancer risk in the European prospective investigation into cancer and nutrition study." }, { "docid": "MED-4037", "text": "In the present study, 21 polycyclic aromatic hydrocarbon (PAH) congeners were measured in the exhaust stack of 3 types of restaurants: 9 Chinese, 7 Western, and 4 barbeque (BBQ). The total PAH concentration of BBQ restaurants (58.81 ± 23.89 μg m(-3)) was significantly higher than that of Chinese (20.99 ± 13.67 μg m(-3)) and Western (21.47 ± 11.44 μg m(-3)) restaurants. The total benzo[a]pyrene potency equivalent (B[a]P(eq)) concentrations, however, were highest in Chinese restaurants (1.82 ± 2.24 μg m(-3)), followed by Western (0.86 ± 1.43 μg m(-3), p<0.01) and BBQ-type restaurants (0.59 ± 0.55 μg m(-3), p<0.01). We further developed a probabilistic risk model to assess the incremental lifetime cancer risk (ILCR) for people exposed to carcinogenic PAHs. Because the exhaust stack directly affected the back-door neighbors of these restaurants, we were concerned with the real exposure of groups near the exhaust stack outlets of these restaurants. The ILCRs for total exposure of the neighbors (inhalation+dermal contact+ingestion) were 2.6-31.3, 1.5-14.8, and 1.3-12.2 × 10(-6) in Chinese, Western, and BBQ restaurants, respectively. We suggest that the maximum acceptable exposure time to the exhaust stack outlet area for Chinese, Western, and BBQ restaurants ranges between 5-19, 17-42, and 18-56 h month(-1), respectively, based on an ILCR of less than 10(-6). Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.", "title": "Carcinogenic potencies of polycyclic aromatic hydrocarbons for back-door neighbors of restaurants with cooking emissions." }, { "docid": "MED-1620", "text": "Background The Daniel Fast is a vegan diet that prohibits the consumption of animal products, refined foods, white flour, preservatives, additives, sweeteners, flavorings, caffeine, and alcohol. Following this dietary plan for 21 days has been demonstrated to improve blood pressure, LDL-C, and certain markers of oxidative stress, but it has also been shown to lower HDL-C. Krill oil supplementation has been shown to increase HDL-C. Methods We investigated the effects of following a Daniel Fast dietary plan with either krill oil supplementation (2 g/day) or placebo supplementation (coconut oil; 2 g/day) for 21 days. The subjects in this study (12 men and 27 women) were heterogeneous with respect to body mass index (BMI) (normal weight, overweight, and obese), blood lipids (normolipidemic and hyperlipidemic), blood glucose (normal fasting glucose, impaired fasting glucose, and type 2 diabetic), and blood pressure (normotensive and hypertensive). Results Krill oil supplementation had no effect on any outcome measure (all p > 0.05), and so the data from the krill oil group and the placebo group were collapsed and analyzed to examine the effects of following a 21-day Daniel Fast. Significant reductions were observed in LDL-C (100.6 ± 4.3 mg/dL vs. 80.0 ± 3.7 mg/dL), the LDL:HDL ratio (2.0 ± 0.1 vs. 1.7 ± 0.1), fasting blood glucose (101.4 ± 7.5 mg/dL vs. 91.7 ± 3.4 mg/dL), fasting blood insulin (7.92 ± 0.80 μU/mL vs. 5.76 ± 0.59 μU/mL), homeostasis model assessment of insulin resistance (HOMA-IR) (2.06 ± 0.30 vs. 1.40 ± 0.21), systolic BP (110.7 ± 2.2 mm Hg vs. 105.5 ± 1.7 mm Hg), and body weight (74.1 ± 2.4 kg vs. 71.5 ± 2.3 kg) (all p < 0.05). Conclusion Following a Daniel Fast dietary plan improves a variety of cardiometabolic parameters in a wide range of individuals in as little as 21 days, and these improvements are unaffected by krill oil supplementation. Trial registration Clinicaltrial.govNCT01378767", "title": "A 21-day Daniel fast with or without krill oil supplementation improves anthropometric parameters and the cardiometabolic profile in men and women" }, { "docid": "MED-2693", "text": "Antioxidants, primarily from fruits and vegetables, have been hypothesized to protect against non-Hodgkin lymphoma (NHL). The Oxygen Radical Absorbance Capacity (ORAC) assay, which measures total antioxidant capacity of individual foods and accounts for synergism, can be estimated using a food-frequency questionnaire (FFQ). We tested the hypothesis that higher intake of antioxidant nutrients from foods, supplements, and FFQ-based ORAC values are associated with a lower risk of NHL in a clinic-based study of 603 incident cases and 1007 frequency-matched controls. Diet was assessed with a 128-item FFQ. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals adjusted for age, sex, residence and total energy. Dietary intake of α-tocopherol (OR=0.50; p-trend=0.0002), β-carotene (OR=0.58; p-trend=0.0005), lutein/zeaxanthin (OR=0.62; p-trend=0.005), zinc (OR=0.54; p-trend=0.003) and chromium (OR=0.68; p-trend=0.032) were inversely associated with NHL risk. Inclusion of supplement use had little impact on these associations. Total vegetables (OR=0.52; p-trend<0.0001), particularly green leafy (OR=0.52; p-trend<0.0001) and cruciferous (OR=0.68; p-trend=0.045) vegetables, were inversely associated with NHL risk. NHL risk was inversely associated with both hydrophilic ORAC (OR=0.61, p-trend=0.003) and lipophilic ORAC (OR=0.48, p-trend=0.0002), although after simultaneous adjustment for other antioxidants or total vegetables only the association for lipophilic ORAC remained significant. There was no striking heterogeneity in results across the common NHL subtypes. Higher antioxidant intake as estimated by the FFQ-ORAC, particularly the lipophilic component, was associated with a lower NHL risk after accounting for other antioxidant nutrients and vegetable intake, supporting this as potentially useful summary measure of total antioxidant intake.", "title": "Food-Frequency Questionnaire Based Estimates of Total Antioxidant Capacity and Risk of Non-Hodgkin Lymphoma" }, { "docid": "MED-2850", "text": "Background: Fatty acids play a vital role in glucose homeostasis; however, studies on habitual dietary fat intakes and gestational diabetes mellitus (GDM) risk are limited and provide conflicting findings. Objective: We determined whether the total amount and the type and source of prepregnancy dietary fats are related to risk of GDM. Design: A prospective study was conducted in 13,475 women who reported a singleton pregnancy between 1991 and 2001 in the Nurses’ Health Study II. In these women, 860 incident GDM cases were reported. The adjusted RR of GDM was estimated for quintiles of total fat, specific fat, and the source of fat intakes by pooled logistic regression. Results: Higher animal fat and cholesterol intakes were significantly associated with increased GDM risk. Across increasing quintiles of animal fat, RRs (95% CIs) for GDM were 1.00 (reference), 1.55 (1.20, 1.98), 1.43 (1.09, 1.88), 1.40 (1.04, 1.89), and 1.88 (1.36, 2.60) (P-trend = 0.05). Corresponding RRs (95% CIs) for dietary cholesterol were 1.00 (reference), 1.08 (0.84, 1.32), 1.02 (0.78, 1.29), 1.20 (0.93, 1.55), and 1.45 (1.11, 1.89) (P-trend = 0.04). The substitution of 5% of energy from animal fat for an equal percentage of energy from carbohydrates was associated with significantly increased risk of GDM [RR (95% CI): 1.13 (1.08, 1.18); P < 0.0001]. No significant associations were observed between dietary polyunsaturated fat, monounsaturated fat, or trans fat intakes and GDM risk. Conclusion: Higher prepregnancy intakes of animal fat and cholesterol were associated with elevated GDM risk.", "title": "A prospective study of prepregnancy dietary fat intake and risk of gestational diabetes" }, { "docid": "MED-2704", "text": "Lipid peroxidation is, in most instances, a free radical chain reaction that can be described in terms of initiation, propagation, branching and termination processes. With regard to lipid peroxidation, one of the most important questions concerns the source of the primary catalysts that initiate peroxidation in situ in muscle foods. When cells are injured, such as in muscle foods after slaughtering, lipid peroxidation is favored, and traces of O(2) and H(2)O(2), indicating lipid peroxides, are formed. The stability of a muscle food product will depend on the 'tone' of these peroxides and especially from the involvement of metal ions in the process. The cytosol contains not only prooxidants but also antioxidants and the tone of both affects the overall oxidation. Lipid peroxidation is one of the primary mechanisms of quality deterioration in foods and especially in meat products. The changes in quality can be manifested by deterioration in flavor, color, texture, nutritive value and the production of toxic compounds. Copyright © 1993. Published by Elsevier Ltd.", "title": "Oxidative processes in meat and meat products: Quality implications." }, { "docid": "MED-4687", "text": "Vegetarian diets are rich in antioxidant phytochemicals. However, they may not act as antioxidants in vivo, and yet still have important signaling and regulatory functions. Some may act as pro-oxidants, modulating cellular redox tone and oxidizing redox sensitive sites. In this review, evidence for health benefits of vegetarian diets is presented from different perspectives: epidemiological, biomarker, evolutionary, and public health, as well as antioxidant. From the perspective of molecular connections between diet and health, evidence of a role for plasma ascorbic acid as a biomarker for future disease risk is presented. Basic concepts of redox-based cell signaling are presented, and effects of antioxidant phytochemicals on signaling, especially via redox tone, sulfur switches and the Antioxidant Response Element (ARE), are explored. Sufficient scientific evidence exists for public health policy to promote a plant-rich diet for health promotion. This does not need to wait for science to provide all the answers as to why and how. However, action and interplay of dietary antioxidants in the nonequilibrium systems that control redox balance, cell signaling, and cell function provide rich ground for research to advance understanding of orthomolecular nutrition and provide science-based evidence to advance public health in our aging population.", "title": "Vegetarian diets and public health: biomarker and redox connections." }, { "docid": "MED-4912", "text": "Rice is more elevated in arsenic than all other grain crops tested to date, with whole grain (brown) rice having higher arsenic levels than polished (white). It is reported here that rice bran, both commercially purchased and specifically milled for this study, have levels of inorganic arsenic, a nonthreshold, class 1 carcinogen, reaching concentrations of approximately 1 mg/kg dry weight, around 10-20 fold higher than concentrations found in bulk grain. Although pure rice bran is used as a health food supplement, perhaps of more concern is rice bran solubles, which are marketed as a superfood and as a supplement to malnourished children in international aid programs. Five rice bran solubles products were tested, sourced from the United States and Japan, and were found to have 0.61-1.9 mg/kg inorganic arsenic. Manufactures recommend approximately 20 g servings of the rice bran solubles per day, which equates to a 0.012-0.038 mg intake of inorganic arsenic. There are no maximum concentration levels (MCLs) set for arsenic or its species in food stuffs. EU and U.S. water regulations, set at 0.01 mg/L total or inorganic arsenic, respectively, are based on the assumption that 1 L of water per day is consumed, i.e., 0.01 mg of arsenic/ day. At the manufacturers recommended rice bran solubles consumption rate, inorganic arsenic intake exceeds 0.01 mg/ day, remembering that rice bran solubles are targeted at malnourished children and that actual risk is based on mg kg(-1) day(-1) intake.", "title": "Inorganic arsenic in rice bran and its products are an order of magnitude higher than in bulk grain." }, { "docid": "MED-1994", "text": "PURPOSE OF REVIEW: The prevalence of obesity in youth is increasing alarmingly among children and adolescents in the United States. The problem falls disproportionately on African-American and Hispanic children. Many of the metabolic and cardiovascular complications associated with obesity are already present during childhood and are closely linked to the concomitant insulin resistance/hyperinsulinemia and degree of obesity. Moreover, these co-morbidities persist into adulthood. RECENT FINDINGS: The progression from normal glucose tolerance to type 2 diabetes mellitus involves an intermediate stage known as prediabetes or impaired glucose regulation. Prediabetes is characterized by peripheral insulin-resistance and impaired glucose sensitivity of first-phase insulin secretion. On the other hand, in overt type 2 diabetes mellitus beta-cell failure becomes fully manifested. Progression from prediabetes to type 2 diabetes mellitus in youth is characterized by marked weight gain and further reduction in insulin secretion and insulin resistance. SUMMARY: Reverting obesity through lifestyle modification, that involves nutrition education, behavior modification and exercise, is an important step to prevent the progression to diabetes.", "title": "Prediabetes and type 2 diabetes in youth: an emerging epidemic disease?" }, { "docid": "MED-4809", "text": "Closely related strains of Escherichia coli have been shown to cause extraintestinal infections in unrelated persons. This study tests whether a food reservoir may exist for these E. coli. Isolates from 3 sources over the same time period (2005–2007) and geographic area were compared. The sources comprised prospectively collected E. coli isolates from women with urinary tract infection (UTI) (n = 353); retail meat (n = 417); and restaurant/ready-to-eat foods (n = 74). E. coli were evaluated for antimicrobial drug susceptibility and O:H serotype and compared by using 4 different genotyping methods. We identified 17 clonal groups that contained E. coli isolates (n = 72) from >1 source. E. coli from retail chicken (O25:H4-ST131 and O114:H4-ST117) and honeydew melon (O2:H7-ST95) were indistinguishable from or closely related to E. coli from human UTIs. This study provides strong support for the role of food reservoirs or foodborne transmission in the dissemination of E. coli causing common community-acquired UTIs.", "title": "Food Reservoir for Escherichia coli Causing Urinary Tract Infections" }, { "docid": "MED-2580", "text": "Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial–based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18–0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial–based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence.", "title": "High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial" }, { "docid": "MED-2111", "text": "Coronary artery disease is essentially nonexistent in cultures whose nutrition assures cholesterol levels <150 mg/dl. Patients with advanced coronary artery disease may abolish disease progression through a plant-based diet and cholesterol-lowering medication to achieve and maintain a total cholesterol <150 mg/dl.", "title": "Updating a 12-year experience with arrest and reversal therapy for coronary heart disease (an overdue requiem for palliative cardiology)." }, { "docid": "MED-3427", "text": "Lifestyle and nutrition have been increasingly recognized as central factors influencing vascular nitric oxide (NO) production and erectile function. This review underscores the importance of NO as the principal mediator influencing cardiovascular health and erectile function. Erectile dysfunction (ED) is associated with smoking, excessive alcohol intake, physical inactivity, abdominal obesity, diabetes, hypertension, and decreased antioxidant defenses, all of which reduce NO production. Better lifestyle choices; physical exercise; improved nutrition and weight control; adequate intake of or supplementation with omega-3 fatty acids, antioxidants, calcium, and folic acid; and replacement of any testosterone deficiency will all improve vascular and erectile function and the response to phosphodiesterase-5 inhibitors, which also increase vascular NO production. More frequent penile-specific exercise improves local endothelial NO production. Excessive intake of vitamin E, calcium, l-arginine, or l-citrulline may impart significant cardiovascular risks. Interventions discussed also lower blood pressure or prevent hypertension. Certain angiotensin II receptor blockers improve erectile function and reduce oxidative stress. In men aged <60 years and in men with diabetes or hypertension, erectile dysfunction can be a critical warning sign for existing or impending cardiovascular disease and risk for death. The antiarrhythmic effect of omega-3 fatty acids may be particularly crucial for these men at greatest risk for sudden death. In conclusion, by better understanding the complex factors influencing erectile and overall vascular health, physicians can help their patients prevent vascular disease and improve erectile function, which provides more immediate motivation for men to improve their lifestyle habits and cardiovascular health. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "The link between erectile and cardiovascular health: the canary in the coal mine." }, { "docid": "MED-3050", "text": "Background: Weight gain leads to reduced reward-region responsivity to energy-dense food receipt, and consumption of an energy-dense diet compared with an isocaloric, low-energy-density diet leads to reduced dopamine receptors. Furthermore, phasic dopamine signaling to palatable food receipt decreases after repeated intake of that food, which collectively suggests that frequent intake of an energy-dense food may reduce striatal response to receipt of that food. Objective: We tested the hypothesis that frequent ice cream consumption would be associated with reduced activation in reward-related brain regions (eg, striatum) in response to receipt of an ice cream–based milkshake and examined the influence of adipose tissue and the specificity of this relation. Design: Healthy-weight adolescents (n = 151) underwent fMRI during receipt of a milkshake and during receipt of a tasteless solution. Percentage body fat, reported food intake, and food craving and liking were assessed. Results: Milkshake receipt robustly activated the striatal regions, yet frequent ice cream consumption was associated with a reduced response to milkshake receipt in these reward-related brain regions. Percentage body fat, total energy intake, percentage of energy from fat and sugar, and intake of other energy-dense foods were not related to the neural response to milkshake receipt. Conclusions: Our results provide novel evidence that frequent consumption of ice cream, independent of body fat, is related to a reduction in reward-region responsivity in humans, paralleling the tolerance observed in drug addiction. Data also imply that intake of a particular energy-dense food results in attenuated reward-region responsivity specifically to that food, which suggests that sensory aspects of eating and reward learning may drive the specificity.", "title": "Frequent ice cream consumption is associated with reduced striatal response to receipt of an ice cream–based milkshake" }, { "docid": "MED-2117", "text": "Recent evidence underlines the role of Western diet in the pathogenesis of acne. Acne is absent in populations consuming Palaeolithic diets with low glycaemic load and no consumption of milk or dairy products. Two randomized controlled studies, one of which is presented in this issue of Acta Dermato-Venereologica, have provided evidence for the beneficial therapeutic effects of low glycaemic load diets in acne. Epidemiological evidence confirms that milk consumption has an acne-promoting or acne-aggravating effect. Recent progress in understanding the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1) allows a new view of nutrient signalling in acne by both high glycaemic load and increased insulin-, IGF-1-, and leucine signalling due to milk protein consumption. Acne should be regarded as an mTORC1-driven disease of civilization, like obesity, type 2 diabetes and cancer induced by Western diet. Early dietary counselling of teenage acne patients is thus a great opportunity for dermatology, which will not only help to improve acne but may reduce the long-term adverse effects of Western diet on more serious mTORC1-driven diseases of civilization.", "title": "Diet in acne: further evidence for the role of nutrient signalling in acne pathogenesis." }, { "docid": "MED-1327", "text": "Whole-grain and high fiber intakes are routinely recommended for prevention of vascular diseases; however, there are no comprehensive and quantitative assessments of available data in humans. The aim of this study was to systematically examine longitudinal studies investigating whole-grain and fiber intake in relation to risk of type 2 diabetes (T2D), cardiovascular disease (CVD), weight gain, and metabolic risk factors. We identified 45 prospective cohort studies and 21 randomized-controlled trials (RCT) between 1966 and February 2012 by searching the Cumulative Index to Nursing and Allied Health Literature, Cochrane, Elsevier Medical Database, and PubMed. Study characteristics, whole-grain and dietary fiber intakes, and risk estimates were extracted using a standardized protocol. Using random effects models, we found that compared with never/rare consumers of whole grains, those consuming 48-80 g whole grain/d (3-5 serving/d) had an ~26% lower risk of T2D [RR = 0.74 (95% CI: 0.69, 0.80)], ~21% lower risk of CVD [RR = 0.79 (95% CI: 0.74, 0.85)], and consistently less weight gain during 8-13 y (1.27 vs 1.64 kg; P = 0.001). Among RCT, weighted mean differences in post-intervention circulating concentrations of fasting glucose and total and LDL-cholesterol comparing whole-grain intervention groups with controls indicated significantly lower concentrations after whole-grain interventions [differences in fasting glucose: -0.93 mmol/L (95% CI: -1.65, -0.21), total cholesterol: -0.83 mmol/L (-1.23, -0.42); and LDL-cholesterol: -0.82 mmol/L (-1.31, -0.33)]. [corrected] Findings from this meta-analysis provide evidence to support beneficial effects of whole-grain intake on vascular disease prevention. Potential mechanisms responsible for whole grains' effects on metabolic intermediates require further investigation in large intervention trials.", "title": "Greater whole-grain intake is associated with lower risk of type 2 diabetes, cardiovascular disease, and weight gain." }, { "docid": "MED-1916", "text": "BACKGROUND: Physical inactivity is an important risk factor for many aging-related diseases. Leukocyte telomere dynamics (telomere length and age-dependent attrition rate) are ostensibly a biological indicator of human aging. We therefore tested the hypothesis that physical activity level in leisure time (over the past 12 months) is associated with leukocyte telomere length (LTL) in normal healthy volunteers. METHODS: We studied 2401 white twin volunteers, comprising 2152 women and 249 men, with questionnaires on physical activity level, smoking status, and socioeconomic status. Leukocyte telomere length was derived from the mean terminal restriction fragment length and adjusted for age and other potential confounders. RESULTS: Leukocyte telomere length was positively associated with increasing physical activity level in leisure time (P< .001); this association remained significant after adjustment for age, sex, body mass index, smoking, socioeconomic status, and physical activity at work. The LTLs of the most active subjects were 200 nucleotides longer than those of the least active subjects (7.1 and 6.9 kilobases, respectively; P= .006). This finding was confirmed in a small group of twin pairs discordant for physical activity level (on average, the LTL of more active twins was 88 nucleotides longer than that of less active twins; P= .03). CONCLUSIONS: A sedentary lifestyle (in addition to smoking, high body mass index, and low socioeconomic status) has an effect on LTL and may accelerate the aging process. This provides a powerful message that could be used by clinicians to promote the potentially antiaging effect of regular exercise.", "title": "The association between physical activity in leisure time and leukocyte telomere length." }, { "docid": "MED-1997", "text": "The increased prevalence of childhood overweight and obesity is not unique to industrialized societies; dramatic increases are occurring in urbanized areas of developing countries. In light of the consensus that obesity is a significant public health concern and that many weight-loss interventions have been unsuccessful in the long term, an exploration of food patterns that are beneficial in the primary prevention of obesity is warranted. The focus of this article is to review the relation between vegetarian diets and obesity, particularly as they relate to childhood obesity. Epidemiologic studies indicate that vegetarian diets are associated with a lower body mass index (BMI) and a lower prevalence of obesity in adults and children. A meta-analysis of adult vegetarian diet studies estimated a reduced weight difference of 7.6 kg for men and 3.3 kg for women, which resulted in a 2-point lower BMI (in kg/m(2)). Similarly, compared with nonvegetarians, vegetarian children are leaner, and their BMI difference becomes greater during adolescence. Studies exploring the risk of overweight and food groups and dietary patterns indicate that a plant-based diet seems to be a sensible approach for the prevention of obesity in children. Plant-based diets are low in energy density and high in complex carbohydrate, fiber, and water, which may increase satiety and resting energy expenditure. Plant-based dietary patterns should be encouraged for optimal health and environmental benefits. Food policies are warranted to support social marketing messages and to reduce the cultural and economic forces that make it difficult to promote plant-based dietary patterns.", "title": "Vegetarian diets and childhood obesity prevention." }, { "docid": "MED-4335", "text": "Chronic and acute inflammation underlies the molecular basis of atherosclerosis. Cocoa-based products are among the richest functional foods based upon flavanols and their influence on the inflammatory pathway, as demonstrated by several in vitro or ex vivo studies. Indeed, flavanols modify the production of pro-inflammatory cytokines, the synthesis of eicosanoids, the activation of platelets, and nitric oxide-mediated mechanisms. A relative paucity of data still characterizes the in vivo implications of these findings albeit there have been studies suggesting that the regular or occasional consumption of cocoa-rich compounds exerts beneficial effects on blood pressure, insulin resistance, vascular damage, and oxidative stress. Accordingly, rigorous controlled human studies with adequate follow-up and with the use of critical dietary questionnaires are needed to determine the effects of flavanols on the major endpoints of cardiovascular health.", "title": "Chocolate at heart: the anti-inflammatory impact of cocoa flavanols." }, { "docid": "MED-4514", "text": "Background Data on the long-term association between low-carbohydrate diets and mortality are sparse. Objective To examine the association of low-carbohydrate diets with mortality during 26 years of follow-up in women and 20 years in men. Design A prospective cohort study of women and men, followed from 1980 (women) or 1986 (men) until 2006. Low-carbohydrate diets, either animal-based (emphasizing animal sources of fat and protein), or vegetable-based (emphasizing vegetable sources of fat and protein) were computed from multiple validated food frequency questionnaire assessed during follow-up. Setting Nurses' Health Study and Health Professionals' Follow-up Study Participants 85,168 women (aged 34-59 years at baseline) and 44,548 men (aged 40-75 years at baseline) without heart disease, cancer, or diabetes. Measurement Investigator documented 12,555 deaths (2,458 cardiovascular, 5,780 cancer) in women and 8,678 deaths (2,746 cardiovascular, 2,960 cancer) in men. Results The overall low-carbohydrate score was associated with a modest increase in overall mortality in pooled analysis (Hazard Ratio, HR, comparing extreme deciles=1.12 (95% CI=1.01-1.24, p-trend=0.14). The animal low-carbohydrate score was associated with a higher all-cause mortality (pooled HR comparing extreme deciles=1.23, 95% CI=1.11-1.37, p-trend=0.05), cardiovascular mortality (corresponding HR=1.14, 95% CI=1.01-1.29, p-trend=0.029), and cancer mortality (corresponding HR=1.28, 95% CI 1.02-1.60, p for trend = 0.09). In contrast, a higher vegetable low-carbohydrate score was associated with lower all-cause (HR=0.80, 95% CI=0.75-0.85, p-trend<0.001) and cardiovascular mortality (HR=0.77, 95% CI=0.68-0.87, p-trend<0.001). Limitations Diet and lifestyle characteristics were assessed with some degree of error, however, sensitivity analyses indicated that results were not unlikely to be substantially affected by residual or confounding or an unmeasured confounder. In addition, participants were not a representative sample of the U.S. population. Conclusion A low-carbohydrate diet based on animal sources was associated with higher all-cause mortality in both men and women, whereas a vegetable-based low-carbohydrate diet was associated with lower all-cause and cardiovascular disease mortality rates. Primary funding source NIH grants CA87969, HL60712, and CA95589", "title": "Low-carbohydrate diets and all-cause and cause-specific mortality: Two cohort Studies" }, { "docid": "MED-4333", "text": "OBJECTIVE To evaluate the changes in circulating endotoxin after a high–saturated fat meal to determine whether these effects depend on metabolic disease state. RESEARCH DESIGN AND METHODS Subjects (n = 54) were given a high-fat meal (75 g fat, 5 g carbohydrate, 6 g protein) after an overnight fast (nonobese control [NOC]: age 39.9 ± 11.8 years [mean ± SD], BMI 24.9 ± 3.2 kg/m2, n = 9; obese: age 43.8 ± 9.5 years, BMI 33.3 ± 2.5 kg/m2, n = 15; impaired glucose tolerance [IGT]: age 41.7 ± 11.3 years, BMI 32.0 ± 4.5 kg/m2, n = 12; type 2 diabetic: age 45.4 ± 10.1 years, BMI 30.3 ± 4.5 kg/m2, n = 18). Blood was collected before (0 h) and after the meal (1–4 h) for analysis. RESULTS Baseline endotoxin was significantly higher in the type 2 diabetic and IGT subjects than in NOC subjects, with baseline circulating endotoxin levels 60.6% higher in type 2 diabetic subjects than in NOC subjects (P < 0.05). Ingestion of a high-fat meal led to a significant rise in endotoxin levels in type 2 diabetic, IGT, and obese subjects over the 4-h time period (P < 0.05). These findings also showed that, at 4 h after a meal, type 2 diabetic subjects had higher circulating endotoxin levels (125.4%↑) than NOC subjects (P < 0.05). CONCLUSIONS These studies have highlighted that exposure to a high-fat meal elevates circulating endotoxin irrespective of metabolic state, as early as 1 h after a meal. However, this increase is substantial in IGT and type 2 diabetic subjects, suggesting that metabolic endotoxinemia is exacerbated after high fat intake. In conclusion, our data suggest that, in a compromised metabolic state such as type 2 diabetes, a continual snacking routine will cumulatively promote their condition more rapidly than in other individuals because of the greater exposure to endotoxin.", "title": "High Fat Intake Leads to Acute Postprandial Exposure to Circulating Endotoxin in Type 2 Diabetic Subjects" }, { "docid": "MED-1446", "text": "Literature on the association of protein intake with body weight is inconsistent. Little is known about the relation of long-term protein intake to obesity. This study aimed to determine the association between protein intake and obesity. A cohort of 1,730 employed white men ages 40–55 years from the Chicago Western Electric Study was followed from 1958 to 1966. Diet was assessed twice with Burke’s comprehensive diet history method, at two baseline examinations; height, weight, and other covariates were measured annually by trained interviewers. Generalized estimating equation (GEE) was used to examine the relation of baseline total, animal, and vegetable protein intake to likelihood of being overweight or obese at sequential annual examinations. Dietary animal protein was positively related to overweight and obesity over seven years of follow up. With adjustment for potential confounders (age, education, cigarette smoking, alcohol intake, energy, carbohydrate and saturated fat intake, and history of diabetes or other chronic disease), the odds ratios (95% confidence intervals) for obesity were 4.62 (2.68–7.98, p for trend<0.01) for participants in the highest compared to the lowest quartile of animal protein and 0.58 (0.36, 0.95, p for trend=0.053) for those in the highest quartile of vegetable protein intake. A statistically significant, positive association was seen between animal protein intake and obesity; those in higher quartiles of vegetable protein intake had lower odds of being obese. These results indicate that animal and vegetable protein may relate differently to occurrence of obesity in the long run.", "title": "Longitudinal association between animal and vegetable protein intake and obesity among adult males in the United States: the Chicago Western Electric Study" }, { "docid": "MED-4911", "text": "Arsenic exposures contribute significantly to the burden of preventable disease worldwide, specifically related to increased risks of cancer, diabetes, and cardiovascular disease. Most exposures are associated with natural contamination of groundwater, which is difficult to mitigate when these sources are used for drinking water. An anthropogenic source of arsenic exposure stems from the widespread use of arsenical drugs in food-animal production in the United States and China, among many countries. This use results in residual contamination of food products from animals raised with the drugs, as well as environmental contamination associated with disposal of wastes from these animals. Land disposal of these wastes can contaminate surface and ground water, and the conversion of animal wastes into fertilizer pellets for home use as well as the introduction of animal waste incinerators may increase opportunities for exposure. As an intentional additive to animal feed, use of arsenical drugs is a preventable source of human exposure. The domestic practice of using these drugs in poultry production has been the subject of media attention and limited research, though the use of these drugs in domestic swine production and in the rapidly growing foreign animal production industry remains largely uncharacterized. This continued expansion of arsenical drug use may likely increase the burden of global human arsenic exposure and risk.", "title": "The environmental and public health risks associated with arsenical use in animal feeds." }, { "docid": "MED-1778", "text": "Objective To examine the relationship between dairy food intake and semen parameters Design Longitudinal study Setting Men attending academic medical center fertility clinic in Boston, MA Patients 155 men Interventions None Main Outcome Measures total sperm count, sperm concentration, progressive motility, and morphology Results Low-fat dairy intake was positively related to sperm concentration and progressive motility. On average, men in the highest quartile of intake (1.22–3.54 servings/day) had 33% (95% confidence interval (CI) 1, 55) higher sperm concentration and 9.3 (95%CI 1.4, 17.2) percentage units higher sperm motility than men in the lowest quartile of intake (≤0.28 servings/day). These associations were primarily explained by intake of low-fat milk. The corresponding results for low-fat milk were 30% (95%CI 1,51) higher sperm concentration and 8.7 (95%CI 3.0, 14.4) percentage units higher sperm motility. Cheese intake was associated with lower sperm concentration among ever smokers. In this group, men in the highest tertile of intake (0.82–2.43 servings/day) had 53.2% (95%CI 9.7, 75.7) lower sperm concentration than men in the lowest tertile of cheese intake (<0.43 servings/day). Conclusions Our findings suggest that low-fat dairy intake, particularly low-fat milk, is related to higher sperm concentration and progressive motility, while cheese intake to lower sperm concentration among past or current smokers.", "title": "Dairy intake and semen quality among men attending a fertility clinic" }, { "docid": "MED-3447", "text": "To investigate the chemopreventive effects of seaweed on breast cancer, we have been studying the relationship between iodine and breast cancer. We found earlier that the seaweed, wakame, showed a suppressive effect on the proliferation of DMBA (dimethylbenz(a)anthracene)-induced rat mammary tumors, possibly via apoptosis induction. In the present study, powdered mekabu was placed in distilled water, and left to stand for 24 h at 4 degrees C. The filtered supernatant was used as mekabu solution. It showed an extremely strong suppressive effect on rat mammary carcinogenesis when used in daily drinking water, without toxicity. In vitro, mekabu solution strongly induced apoptosis in 3 kinds of human breast cancer cells. These effects were stronger than those of a chemotherapeutic agent widely used to treat human breast cancer. Furthermore, no apoptosis induction was observed in normal human mammary cells. In Japan, mekabu is widely consumed as a safe, inexpensive food. Our results suggest that mekabu has potential for chemoprevention of human breast cancer.", "title": "Seaweed prevents breast cancer?" }, { "docid": "MED-2913", "text": "The elimination kinetics of polychlorinated biphenyls (PCBs) in humans is difficult to assess in observational studies, because PCB exposure is never completely abolished. In a community with high dietary PCB exposures from whale blubber, we examined two groups of children with increased body burdens from breast-feeding. Follow-up was from ages 4.5 years to 7.5 years (99 subjects) and 7 to 14 years (101 subjects). The calculations were performed by the use of structural equation models, with adjustment for body weight and dietary blubber intake as the main source of postnatal exposure. As a likely result of background exposures, apparent elimination half-lives were unexpectedly long when based on results from all cohort members. Subjects with exposures above the median and in the highest quartile showed half-lives of about 3-4 years for CB-138, and 4.5-5.5 years for CB-105 and CB-118; 6.5-7.5 years for CB-156, CB-170, and CB-187; and 7-9 years for CB-153 and CB-180. The longest half-lives correspond to elimination of the parent PCB solely with a daily fat excretion rate of 1-2 g, while shorter half-lives assume metabolic break-down.", "title": "Elimination Half-lives of Polychlorinated Biphenyl Congeners in Children" }, { "docid": "MED-2214", "text": "Summary Background 100 years after the first description, Alzheimer's disease is one of the most disabling and burdensome health conditions worldwide. We used the Delphi consensus method to determine dementia prevalence for each world region. Methods 12 international experts were provided with a systematic review of published studies on dementia and were asked to provide prevalence estimates for every WHO world region, for men and women combined, in 5-year age bands from 60 to 84 years, and for those aged 85 years and older. UN population estimates and projections were used to estimate numbers of people with dementia in 2001, 2020, and 2040. We estimated incidence rates from prevalence, remission, and mortality. Findings Evidence from well-planned, representative epidemiological surveys is scarce in many regions. We estimate that 24·3 million people have dementia today, with 4·6 million new cases of dementia every year (one new case every 7 seconds). The number of people affected will double every 20 years to 81·1 million by 2040. Most people with dementia live in developing countries (60% in 2001, rising to 71% by 2040). Rates of increase are not uniform; numbers in developed countries are forecast to increase by 100% between 2001 and 2040, but by more than 300% in India, China, and their south Asian and western Pacific neighbours. Interpretation We believe that the detailed estimates in this paper constitute the best currently available basis for policymaking, planning, and allocation of health and welfare resources.", "title": "Global prevalence of dementia: a Delphi consensus study" }, { "docid": "MED-2351", "text": "Anti-Gal is a natural Ab abundantly produced in humans. It interacts specifically with the carbohydrate epitope Gal alpha 1-3Gal beta 1-4GlcNAc-R (termed the alpha-galactosyl epitope). This epitope is expressed in large amounts on thyrocytes of nonprimate mammals, but not of humans. We have previously found that binding of anti-Gal to alpha-galactosyl epitopes on porcine thyrocytes results in stimulatory effects similar to those exerted by thyroid-stimulating hormone (thyrotropin). In the present study, we tested the hypothesis that anti-Gal may contribute to Graves' disease (GD) pathogenesis by stimulation of the thyrocytes of patients with this autoimmune disorder. Anti-Gal binding and stimulatory effects were assessed in primary thyrocyte cultures. Anti-Gal specifically bound to GD thyrocytes and induced an increase in cAMP synthesis, 125I uptake, and DNA synthesis in these cells. Furthermore, the stimulatory effects of autologous sera on GD thyrocytes were greatly reduced after specific depletion of anti-Gal from these sera. No binding and no stimulatory effects of anti-Gal were observed, however, with normal human thyrocytes and with thyrocytes from thyrotoxic patients who lack thyroid-stimulating Igs or thyrotropin binding inhibiting Igs. These in vitro stimulatory effects of anti-Gal on GD thyrocytes suggest that this natural Ab may contribute to the in vivo continuous stimulation of thyrocytes in GD patients. The possibility that anti-Gal may stimulate GD thyrocytes via interaction with aberrantly expressed alpha-galactosyl epitopes on the thyroid-stimulating hormone receptor is discussed.", "title": "Specific stimulation of Graves' disease thyrocytes by the natural anti-Gal antibody from normal and autologous serum." }, { "docid": "MED-2404", "text": "Background Epidemiologic studies suggest that there may be an association between environmental exposure to persistent organic pollutants (POPs) and diabetes. Objective The aim of this study was to test the hypothesis that residential proximity to POP-contaminated waste sites result in increased rates of hospitalization for diabetes. Methods We determined the number of hospitalized patients 25–74 years of age diagnosed with diabetes in New York State exclusive of New York City for the years 1993–2000. Descriptive statistics and negative binomial regression were used to compare diabetes hospitalization rates in individuals who resided in ZIP codes containing or abutting hazardous waste sites containing POPs (“POP” sites); ZIP codes containing hazardous waste sites but with wastes other than POPs (“other” sites); and ZIP codes without any identified hazardous waste sites (“clean” sites). Results Compared with the hospitalization rates for diabetes in clean sites, the rate ratios for diabetes discharges for people residing in POP sites and “other” sites, after adjustment for potential confounders were 1.23 [95% confidence interval (CI), 1.15–1.32] and 1.25 (95% CI, 1.16–1.34), respectively. In a subset of POP sites along the Hudson River, where there is higher income, less smoking, better diet, and more exercise, the rate ratio was 1.36 (95% CI, 1.26–1.47) compared to clean sites. Conclusions After controlling for major confounders, we found a statistically significant increase in the rate of hospitalization for diabetes among the population residing in the ZIP codes containing toxic waste sites.", "title": "Increased Rate of Hospitalization for Diabetes and Residential Proximity of Hazardous Waste Sites" }, { "docid": "MED-1164", "text": "We assessed organophosphorus (OP) pesticide exposure from diet by biological monitoring among Seattle, Washington, preschool children. Parents kept food diaries for 3 days before urine collection, and they distinguished organic and conventional foods based on label information. Children were then classified as having consumed either organic or conventional diets based on analysis of the diary data. Residential pesticide use was also recorded for each home. We collected 24-hr urine samples from 18 children with organic diets and 21 children with conventional diets and analyzed them for five OP pesticide metabolites. We found significantly higher median concentrations of total dimethyl alkylphosphate metabolites than total diethyl alkylphosphate metabolites (0.06 and 0.02 micro mol/L, respectively; p = 0.0001). The median total dimethyl metabolite concentration was approximately six times higher for children with conventional diets than for children with organic diets (0.17 and 0.03 micro mol/L; p = 0.0003); mean concentrations differed by a factor of nine (0.34 and 0.04 micro mol/L). We calculated dose estimates from urinary dimethyl metabolites and from agricultural pesticide use data, assuming that all exposure came from a single pesticide. The dose estimates suggest that consumption of organic fruits, vegetables, and juice can reduce children's exposure levels from above to below the U.S. Environmental Protection Agency's current guidelines, thereby shifting exposures from a range of uncertain risk to a range of negligible risk. Consumption of organic produce appears to provide a relatively simple way for parents to reduce their children's exposure to OP pesticides.", "title": "Organophosphorus pesticide exposure of urban and suburban preschool children with organic and conventional diets." }, { "docid": "MED-3818", "text": "BACKGROUND: Cellulite, which appears as orange peel-type or cottage cheese-like dimpling of the skin on the thighs and buttocks, is a complex, multifactorial, cosmetic disorder of the subcutaneous fat layer and the overlying superficial skin. Adiponectin is an adipocyte-derived hormone mainly produced by subcutaneous fat that shows important protective anti-inflammatory and vasodilatory effects. We hypothesized that adiponectin expressed in the subcutaneous adipose tissue (SAT) might play a role in the pathogenesis of cellulite. We reasoned that a reduction in the expression of adiponectin - a humoral vasodilator - in the SAT of cellulite areas might contribute to the altered microcirculation frequently found in these regions. METHODS: A total of 15 lean (body mass index [BMI] < 25 kg/m(2) ) women with cellulite and 15 age- and BMI-matched women without cellulite participated in this study. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to assess adiponectin gene expression. Plasma adiponectin levels were measured using a commercial enzyme immunoassay kit. RESULTS: Adiponectin mRNA expression in the SAT of the gluteal region was significantly lower in areas with cellulite compared with those without (12.6 ± 3.1 AU versus 16.6 ± 4.1 AU; P=0.006). However, plasma adiponectin levels did not differ between women with (20.3 ± 7.3 μg/ml) and without (19.3 ± 6.1 μg/ml) cellulite (P=0.69). CONCLUSIONS: Adiponectin expression is significantly reduced in the SAT in areas affected by cellulite. Our findings provide novel insights into the nature of cellulite and may give clues to the treatment of this cosmetic issue. © 2011 The International Society of Dermatology.", "title": "Adiponectin expression in subcutaneous adipose tissue is reduced in women with cellulite." }, { "docid": "MED-3025", "text": "Detailed clinical and neuropathological studies have been made in two fullterm newborn human infants who were exposed to methylmercury in utero as a result of maternal ingestion of methylmercury-contaminated bread in early phases of pregnancy. High levels of mercury were detected in various regions of the brain at autopsy. Study of the brains revealed a disturbance in the development in both cases, consisting essentially of an incomplete or abnormal migration of neurons to the cerebellar and cerebral cortices, and deranged cortical organization of the cerebrum. There were numerous heterotopic neurons, both isolated and in groups, in the white matter of cerebrum and cerebellum and the laminar cortical pattern of the laminar cortical pattern of the cerebrum was disturbed in many regions as was shown by the irregular groupings and the deranged alignment of cortical. Prominent in the white matter of the cerebrum and the cerebellum was diffuse gemistocytic astrocytosis accompanied by an accumulation of mercury grains in their cytoplasm. These findings indicate a high degree of vulnerability of human fetal brain to maternal intoxication by methylmercury. A major effect appears to be related to faulty development and not to destructive focal neuronal damage as has been observed in mercury intoxicaiton in adults and children exposed postnatally.", "title": "Abnormal neuronal migration, deranged cerebral cortical organization, and diffuse white matter astrocytosis of human fetal brain: a major effect of..." }, { "docid": "MED-4232", "text": "OBJECTIVES: To evaluate the role of a wide range of foods on the risk of benign prostatic hyperplasia (BPH), we conducted a case-control study in Italy between 1991 and 2002. Although BPH is an extremely common condition, particularly among older men, its risk factors, including dietary ones, remain largely undefined. METHODS: Included in the study were 1369 patients younger than 75 years old surgically treated for BPH and 1451 controls younger than 75 years of age who had been admitted to the same hospitals as cases for a wide spectrum of acute, non-neoplastic conditions. A validated and reproducible food frequency questionnaire, including 78 foods and beverages, plus a separate section on alcoholic beverages, was used to assess patients' dietary habits 2 years before diagnosis or hospital admission. Multivariate odds ratios (OR) were obtained after allowance for energy intake and other major potential confounding factors. RESULTS: A significant trend of increasing risk with more frequent consumption was found for cereals (OR 1.55 for the greatest versus lowest quintile), bread (OR 1.69), eggs (OR 1.43), and poultry (OR 1.39). Inverse associations were observed for soups (OR 0.74), pulses (OR 0.74), cooked vegetables (OR 0.66), and citrus fruit (OR 0.82). No association was observed for milk and yogurt products, coffee and tea, pasta and rice, fish, cheese, row vegetables, potatoes, fruit, or desserts. CONCLUSIONS: The results of this study suggest a role for dietary habits on the risk of BPH. In particular, a diet rich in cereals and some types of meat and poor in vegetables and pulses may have an unfavorable effect in this Italian population.", "title": "Food groups and risk of benign prostatic hyperplasia." }, { "docid": "MED-2248", "text": "The consequences of a change from a mixed to a lactovegetarian diet for 12 mo on trace element concentrations in plasma, hair, urine, and feces were studied in 16 women and 4 men. After the diet shift, intakes of zinc and magnesium did not change but that of selenium decreased by 40%. Three months after the diet shift, plasma and hair concentrations of zinc, copper, and selenium had decreased but those of magnesium had increased and the concentrations of mercury, lead, and cadmium in hair were lower. Also, the excretion of zinc, copper, and magnesium in urine, and that of selenium in urine and feces had decreased. Only small changes occurred during the remaining lactovegetarian-diet period. Three years later trace element concentrations had reverted towards baseline concentrations; copper values were similar to baseline concentrations but data for magnesium were slightly higher, and more complex patterns were observed for zinc and selenium. It is concluded that a shift to a lactovegetarian diet changes trace element status.", "title": "Trace element status in healthy subjects switching from a mixed to a lactovegetarian diet for 12 mo." }, { "docid": "MED-3355", "text": "OBJECTIVE: To evaluate the effects of a high-fat and low-fat diet on taste sensitivity to oleic acid (C18:1) in lean and overweight/obese (OW/OB) subjects. DESIGN: Randomized cross-over dietary intervention involving the consumption of a high-fat (>45% fat) and low-fat (<20% fat) diet, both consumed over a 4-week period. SUBJECTS: A total of 19 lean, mean age 33±13 years, mean body mass index (BMI) 23.2±2.2 kg m(-2) and 12 OW/OB, mean age 39.5±3 years, mean BMI 28±2.6 kg m(-2), subjects participated in the study, which measured taste thresholds for C18:1, fat perception and hedonic ratings for regular (RF) and lowered-fat (LF) foods before, and following consumption of a high- and low-fat diet. RESULTS: Consumption of the low-fat diet increased taste sensitivity to C18:1 among lean and OW/OB subjects (P<0.05) and increased the subjects ability to perceive small differences in the fat content of custard (P=0.05). Consumption of the high-fat diet significantly decreased taste sensitivity to C18:1 among lean subjects (P<0.05), with no change in sensitivity among OW/OB persons (P=0.609). The hedonic ratings for several RF and LF foods differed following the diets. CONCLUSION: Alterations in the fat content of the diet modulated taste sensitivity to C18:1 among lean subjects, which was increased following a 4-week period of fat restriction and attenuated following the high-fat diet. The failure of the high-fat diet to alter fatty acid taste thresholds among OW/OB subjects suggests that these individuals were 'adapted' to high-fat exposure, perhaps because of differences in habitual fat consumption. Taken together, these data suggest that excessive dietary fat attenuates nutrient sensing epithelia response in the oral cavity, which could be associated with changes in diet and weight status.", "title": "Recent fat intake modulates fat taste sensitivity in lean and overweight subjects." }, { "docid": "MED-4316", "text": "The intestinal absorption of the essential trace element iron and its mobilization from storage sites in the body are controlled by systemic signals that reflect tissue iron requirements. Recent advances have indicated that the liver-derived peptide hepcidin plays a central role in this process by repressing iron release from intestinal enterocytes, macrophages and other body cells. When iron requirements are increased, hepcidin levels decline and more iron enters the plasma. It has been proposed that the level of circulating diferric transferrin, which reflects tissue iron levels, acts as a signal to alter hepcidin expression. In the liver, the proteins HFE, transferrin receptor 2 and hemojuvelin may be involved in mediating this signal as disruption of each of these molecules decreases hepcidin expression. Patients carrying mutations in these molecules or in hepcidin itself develop systemic iron loading (or hemochromatosis) due to their inability to down regulate iron absorption. Hepcidin is also responsible for the decreased plasma iron or hypoferremia that accompanies inflammation and various chronic diseases as its expression is stimulated by pro-inflammatory cytokines such as interleukin 6. The mechanisms underlying the regulation of hepcidin expression and how it acts on cells to control iron release are key areas of ongoing research. IUBMB Life, 57: 499-503, 2005.", "title": "Systemic regulation of intestinal iron absorption." }, { "docid": "MED-3816", "text": "Most of adult women exhibit cellulite on the hips, buttock and thighs. Although extracellular matrix and lymphatic system disorders can increase its appearance, cellulite basically results from an excessive fat storage in the adipose tissue which exerts considerable pressure on the surrounding skin tissue and creates a dimpled irregular appearance. Caffeine, the most widely used anti-cellulite ingredient, favours fat break-down by inhibiting the phosphodiesterase enzyme and encouraging a high intracellular level of cAMP. A series of studies has shown that spermine and spermidine, two ubiquitous polyamines, encouraged fat storage and slowed fat break-down in the adipose tissue. Besides, it was shown that heparan sulfate glycosaminoglycans had a strong affinity for polyamines. To design a new cosmetic ingredient with anti-cellulite properties, we used molecular modelling to screen several ingredients with a structure similar to that of heparan sulfate glycosaminoglycans. This way, we identified sulfo-carrabiose as a potent molecule for trapping spermine and spermidine. These virtual results were first confirmed in tubo where sulfo-carrabiose was shown to dose-dependently inactivate spermine and spermidine. In vitro, adipocytes cultured with sulfo-carrabiose exhibited a significant reduction of lipogenesis and a significant increase of lipolysis. When sulfo-carrabiose was incorporated in a cosmetic formula, significant improvements were observed in thigh circumference, with better results than those obtained with caffeine after 28 days of use. Furthermore, a combination of caffeine and sulfo-carrabiose led to results significantly better than those obtained with caffeine alone. As measured by fringe projection, thigh volume was also significantly reduced after sulfo-carrabiose treatment. Finally, the appearance of cellulite assessed by clinical evaluation was also significantly reduced within 28 days. © 2010 BASF Beauty Care Solutions. ICS © 2010 Society of Cosmetic Scientists and the Société Française de Cosmétologie.", "title": "In vitro and in vivo efficacy of sulfo-carrabiose, a sugar-based cosmetic ingredient with anti-cellulite properties." }, { "docid": "MED-4728", "text": "Over the last two decades, the incidence of obesity and associated metabolic syndrome diseases has risen dramatically, becoming a global health crisis. Increased caloric intake and decreased physical activity are believed to represent the root causes of this dramatic rise. However, recent findings highlight the possible involvement of environmental obesogens, xenobiotic chemicals that can disrupt the normal developmental and homeostatic controls over adipogenesis and energy balance. Environmental estrogens, i.e. chemicals with estrogenic potential, have been reported to perturb adipogenic mechanisms using in vitro model systems, but other classes of endocrine-disrupting chemicals are now coming under scrutiny as well. Organotins represent one class of widespread persistent organic pollutants with potent endocrine-disrupting properties in both invertebrates and vertebrates. New data identify tributyltin chloride and triphenyltin chloride as nanomolar agonist ligands for retinoid X receptor (RXR alpha, RXR beta, and RXR gamma) and peroxisome proliferator-activated receptor gamma, nuclear receptors that play pivotal roles in lipid homeostasis and adipogenesis. The environmental obesogen hypothesis predicts that inappropriate receptor activation by organotins will lead directly to adipocyte differentiation and a predisposition to obesity and/or will sensitize exposed individuals to obesity and related metabolic disorders under the influence of the typical high-calorie, high-fat Western diet. The linking of organotin exposure to adipocyte differentiation and obesity opens an important new area of research into potential environmental influences on human health and disease.", "title": "Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling." }, { "docid": "MED-2747", "text": "Each year, >9 million foodborne illnesses are estimated to be caused by major pathogens acquired in the United States. Preventing these illnesses is challenging because resources are limited and linking individual illnesses to a particular food is rarely possible except during an outbreak. We developed a method of attributing illnesses to food commodities that uses data from outbreaks associated with both simple and complex foods. Using data from outbreak-associated illnesses for 1998–2008, we estimated annual US foodborne illnesses, hospitalizations, and deaths attributable to each of 17 food commodities. We attributed 46% of illnesses to produce and found that more deaths were attributed to poultry than to any other commodity. To the extent that these estimates reflect the commodities causing all foodborne illness, they indicate that efforts are particularly needed to prevent contamination of produce and poultry. Methods to incorporate data from other sources are needed to improve attribution estimates for some commodities and agents.", "title": "Attribution of Foodborne Illnesses, Hospitalizations, and Deaths to Food Commodities by using Outbreak Data, United States, 1998–2008" }, { "docid": "MED-4276", "text": "Propionate is produced along with acetate and butyrate as a result of fermentative activity of gut microflora on dietary fiber. It has long been known to exhibit hypophagic effects in ruminants, however, its potential physiological roles in non-ruminants as well as humans remained unnoticed over the years. In view of various studies pointing towards the hypophagic as well as hypocholesterolemic effects of propionate in humans, it may act as an important factor in amelioration of obesity, a lifestyle disease arising due to energy imbalance and growing at a startling rate globally. Short chain fatty acids have recently been ascribed as ligands to G-protein coupled receptors (GPRs) 41 and 43. Thus, propionate along with acetate may also be involved in the regulation of adipogenesis and adipokine release mediated via GPRs. The present review summarizes the evidence which collectively raise the possibility of propionate as a dietary factor to depress appetite and combat the obesity epidemic. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Propionate. Anti-obesity and satiety enhancing factor?" }, { "docid": "MED-3251", "text": "CONTEXT: Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established. OBJECTIVE: To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n = 868) were compared with untreated contemporary (n = 829) and historical (n = 959) cohorts. MAIN OUTCOME MEASURES: The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication. RESULTS: The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta-treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P = .14) or the historical control cohort (hazard ratio, 0.77; 95% CI, 0.58-1.02; P = .07) were considered. Further adjustment for comorbidities and socioeconomic status, where possible, did not change interpretations, and propensity score adjustment did not substantially change the results. CONCLUSION: Among patients with relapsing-remitting MS, administration of interferon beta was not associated with a reduction in progression of disability.", "title": "Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis." }, { "docid": "MED-1135", "text": "The hypothesis that the incidence of calcium stone disease is related to the consumption of animal protein has been examined. Within the male population, recurrent idiopathic stone formers consumed more animal protein than did normal subjects. Single stone formers had animal protein intakes intermediate between those of normal men and those of recurrent stone formers. A high animal protein intake caused a significant increase in the urinary excretion of calcium, oxalate and uric acid, 3 of the 6 main urinary risk factors for calcium stone formation. The overall relative probability of forming stones, calculated from the combination of the 6 main urinary risk factors, was markedly increased by a high animal protein diet. Conversely, a low animal protein intake, such as taken by vegetarians, was associated with a low excretion of calcium, oxalate and uric acid and a low relative probability of forming stones.", "title": "Should recurrent calcium oxalate stone formers become vegetarians?" }, { "docid": "MED-1323", "text": "Background: Fat and protein sources may influence whether low-carbohydrate diets are associated with type 2 diabetes (T2D). Objective: The objective was to compare the associations of 3 low-carbohydrate diet scores with incident T2D. Design: A prospective cohort study was conducted in participants from the Health Professionals Follow-Up Study who were free of T2D, cardiovascular disease, or cancer at baseline (n = 40,475) for up to 20 y. Cumulative averages of 3 low-carbohydrate diet scores (high total protein and fat, high animal protein and fat, and high vegetable protein and fat) were calculated every 4 y from food-frequency questionnaires and were associated with incident T2D by using Cox models. Results: We documented 2689 cases of T2D during follow-up. After adjustments for age, smoking, physical activity, coffee intake, alcohol intake, family history of T2D, total energy intake, and body mass index, the score for high animal protein and fat was associated with an increased risk of T2D [top compared with bottom quintile; hazard ratio (HR): 1.37; 95% CI: 1.20, 1.58; P for trend < 0.01]. Adjustment for red and processed meat attenuated this association (HR: 1.11; 95% CI: 0.95, 1.30; P for trend = 0.20). A high score for vegetable protein and fat was not significantly associated with the risk of T2D overall but was inversely associated with T2D in men aged <65 y (HR: 0.78; 95% CI: 0.66, 0.92; P for trend = 0.01, P for interaction = 0.01). Conclusions: A score representing a low-carbohydrate diet high in animal protein and fat was positively associated with the risk of T2D in men. Low-carbohydrate diets should obtain protein and fat from foods other than red and processed meat.", "title": "Low-carbohydrate diet scores and risk of type 2 diabetes in men" }, { "docid": "MED-2274", "text": "Objective To study the relation between cherry intake and the risk of recurrent gout attacks among individuals with gout. Methods We conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for one year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, symptoms and signs, medications (including anti-gout medications), and potential risk factors (including daily intake of cherries and cherry extract) during the 2-day period prior to the gout attack. We assessed the same exposure information over 2-day control periods. We estimated the risk of recurrent gout attacks related to cherry intake using conditional logistic regression. Results Our study included 633 individuals with gout. Cherry intake over a 2-day period was associated with a 35% lower risk of gout attacks compared with no intake (multivariate odds ratio [OR] = 0.65, 95% CI: 0.50-0.85). Cherry extract intake showed a similar inverse association (multivariate OR=0.55, 95% CI: 0.30-0.98). The effect of cherry intake persisted across subgroups by sex, obesity status, purine intake, alcohol use, diuretic use, and use of anti-gout medications. When cherry intake was combined with allopurinol use, the risk of gout attacks was 75% lower than periods without either exposure (OR=0.25, 95% CI: 0.15-0.42). Conclusions These findings suggest that cherry intake is associated with a lower risk of gout attacks.", "title": "Cherry Consumption and the Risk of Recurrent Gout Attacks" }, { "docid": "MED-3056", "text": "Opioids are important in reward processes leading to addictive behavior such as self-administration of opioids and other drugs of abuse including nicotine and alcohol. Opioids are also involved in a broadly distributed neural network that regulates eating behavior, affecting both homeostatic and hedonic mechanisms. In this sense, opioids are particularly implicated in the modulation of highly palatable foods, and opioid antagonists attenuate both addictive drug taking and appetite for palatable food. Thus, craving for palatable food could be considered as a form of opioid-related addiction. There are three main families of opioid receptors (µ, ĸ, and δ) of which µ-receptors are most strongly implicated in reward. Administration of selective µ-agonists into the NAcc of rodents induces feeding even in satiated animals, while administration of µ-antagonists reduces food intake. Pharmacological studies also suggest a role for ĸ- and δ-opioid receptors. Preliminary data from transgenic knockout models suggest that mice lacking some of these receptors are resistant to high-fat diet-induced obesity. Copyright © 2012 S. Karger GmbH, Freiburg.", "title": "The opioid system and food intake: homeostatic and hedonic mechanisms." }, { "docid": "MED-3312", "text": "BACKGROUND: Heavy alcohol consumption, viral hepatitis, and diabetes are risk factors for hepatocellular carcinoma (HCC). However, to the authors' knowledge, the information concerning their interaction effect in patients with risk of HCC is sparse. METHODS: A population-based, case-control study of HCC was conducted during 1984-2002. The study involved 295 HCC cases and 435 age-, gender-, and race-matched control subjects among Hispanic and non-Hispanic whites and blacks in Los Angeles County, California. Lifestyle risk factors were ascertained through in-person interviews. Infections with the hepatitis B and C (HCV) viruses were determined using their serologic markers. RESULTS: Fourteen HCC cases but no control subjects tested positive for the hepatitis B surface antigen. Seropositivity for antibodies to HCV was associated with an odds ratio (OR) of 125 (95% confidence interval [95% CI], 17-909) for HCC, whereas seropositivity for antibodies to the hepatitis B core antigen was related to an OR of 2.9 (95% CI, 1.7-5.0). Heavy alcohol consumption and cigarette smoking were found to be independently associated with a statistically significant two to threefold increase in risk of HCC after adjustment for hepatitis B and C serology. Subjects with a history of diabetes had an OR of 2.7 (95% CI, 1.6-4.3) for HCC compared with nondiabetic subjects. A synergistic interaction on HCC risk was observed between heavy alcohol consumption and diabetes (OR = 4.2; 95% CI, 2.6-5.8), heavy alcohol consumption and viral hepatitis (OR = 5.5; 95% CI, 3.9-7.0), or between diabetes and viral hepatitis (OR = 4.8; 95% CI, 2.7-6.9). CONCLUSIONS: Heavy alcohol consumption, diabetes, and viral hepatitis were found to exert independent and synergistic effects on risk of HCC in U.S. blacks and whites. Copyright 2004 American Cancer Society.", "title": "Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the U.S." }, { "docid": "MED-1411", "text": "OBJECTIVES: The aim of this study was to meta-analyze epidemiological studies and clinical trials that have assessed the effect of a Mediterranean diet on metabolic syndrome (MS) as well as its components. BACKGROUND: The Mediterranean diet has long been associated with low cardiovascular disease risk in adult population. METHODS: The authors conducted a systematic review and random effects meta-analysis of epidemiological studies and randomized controlled trials, including English-language publications in PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials until April 30, 2010; 50 original research studies (35 clinical trials, 2 prospective and 13 cross-sectional), with 534,906 participants, were included in the analysis. RESULTS: The combined effect of prospective studies and clinical trials showed that adherence to the Mediterranean diet was associated with reduced risk of MS (log hazard ratio: -0.69, 95% confidence interval [CI]: -1.24 to -1.16). Additionally, results from clinical studies (mean difference, 95% CI) revealed the protective role of the Mediterranean diet on components of MS, like waist circumference (-0.42 cm, 95% CI: -0.82 to -0.02), high-density lipoprotein cholesterol (1.17 mg/dl, 95% CI: 0.38 to 1.96), triglycerides (-6.14 mg/dl, 95% CI: -10.35 to -1.93), systolic (-2.35 mm Hg, 95% CI: -3.51 to -1.18) and diastolic blood pressure (-1.58 mm Hg, 95% CI: -2.02 to -1.13), and glucose (-3.89 mg/dl, 95% CI:-5.84 to -1.95), whereas results from epidemiological studies also confirmed those of clinical trials. CONCLUSIONS: These results are of considerable public health importance, because this dietary pattern can be easily adopted by all population groups and various cultures and cost-effectively serve for primary and secondary prevention of the MS and its individual components. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.", "title": "The effect of Mediterranean diet on metabolic syndrome and its components: a meta-analysis of 50 studies and 534,906 individuals." }, { "docid": "MED-5195", "text": "We performed a survival analysis to assess the effect of meat consumption and meat type on the risk of breast cancer in the UK Women's Cohort Study. Between 1995 and 1998 a cohort of 35 372 women was recruited, aged between 35 and 69 years with a wide range of dietary intakes, assessed by a 217-item food frequency questionnaire. Hazard ratios (HRs) were estimated using Cox regression adjusted for known confounders. High consumption of total meat compared with none was associated with premenopausal breast cancer, HR=1.20 (95% CI: 0.86–1.68), and high non-processed meat intake compared with none, HR=1.20 (95% CI: 0.86–1.68). Larger effect sizes were found in postmenopausal women for all meat types, with significant associations with total, processed and red meat consumption. Processed meat showed the strongest HR=1.64 (95% CI: 1.14–2.37) for high consumption compared with none. Women, both pre- and postmenopausal, who consumed the most meat had the highest risk of breast cancer.", "title": "Meat consumption and risk of breast cancer in the UK Women's Cohort Study" }, { "docid": "MED-2456", "text": "Several studies have suggested that the increasing prevalence of symptoms of asthma, rhinitis and eczema, could be associated with dietary factors. In the present paper, a global analysis of prevalence rates of wheeze, allergic rhinoconjunctivitis and atopic eczema was performed in relation to diet, as defined by national food intake data. Analyses were based on the International Study of Asthma and Allergies in Childhood (ISAAC) data for 6-7 and 13-14 yr old children. Symptoms of wheeze, allergic rhinoconjunctivitis and atopic eczema symptom prevalence were regressed against per capita food intake, and adjusted for gross national product to account for economic development. Dietary data were based on 1995 Food and Agriculture Organisation of the United Nations data for 53 of the 56 countries that took part in ISAAC phase I (1994/1995). The 13-14 year age group showed a consistent pattern of decreases in symptoms of wheeze (current and severe), allergic rhinoconjunctivitis and atopic eczema, associated with increased per capita consumption of calories from cereal and rice, protein from cereals and nuts, starch, as well as vegetables and vegetable nutrients. The video questionnaire data for 13-14 yr olds and the ISAAC data for 6-7 yr olds showed similar patterns for these foods. A consistent inverse relationship was seen between prevalence rates of the three conditions and the intake of starch, cereals, and vegetables. If these findings could be generalised, and if the average daily consumption of these foods increased, it is speculated that an important decrease in symptom prevalence may be achieved.", "title": "Diet and asthma, allergic rhinoconjunctivitis and atopic eczema symptom prevalence: an ecological analysis of the International Study of Asthma and..." }, { "docid": "MED-2702", "text": "BACKGROUND: Oxidative stress can cause cancer. Our aim was to establish whether antioxidant supplements reduce the incidence of gastrointestinal cancer and mortality. METHODS: With the Cochrane Collaboration methodology, we reviewed all randomised trials comparing antioxidant supplements with placebo for prevention of gastrointestinal cancers. We searched electronic databases and reference lists (February, 2003). Outcome measures were incidence of gastrointestinal cancers, overall mortality, and adverse effects. Outcomes were analysed with fixed-effect and random-effects model meta-analyses and were reported as relative risk with 95% CIs. FINDINGS: We identified 14 randomised trials (n=170,525). Trial quality was generally high. Heterogeneity of results was low to moderate. Neither the fixed-effect (relative risk 0.96, 95% CI 0.88-1.04) nor random-effects meta-analyses (0.90, 0.77-1.05) showed significant effects of supplementation with beta-carotene, vitamins A, C, E, and selenium (alone or in combination) versus placebo on oesophageal, gastric, colorectal, pancreatic, and liver cancer incidences. In seven high-quality trials (n=131727), the fixed-effect model showed that antioxidant significantly increased mortality (1.06, 1.02-1.10), unlike the random-effects meta-analysis (1.06, 0.98-1.15). Low-quality trials showed no significant effect of antioxidant supplementation on mortality. The difference between the mortality estimates in high-quality and low-quality trials was significant (Z=2.10, p=0.04 by test of interaction). beta-carotene and vitamin A (1.29, 1.14-1.45) and beta-carotene and vitamin E (1.10, 1.01-1.20) significantly increased mortality, whereas beta-carotene alone only tended to increase mortality (1.05, 0.99-1.11). In four trials (three with unclear or inadequate methodology), selenium showed significant beneficial effect on the incidence of gastrointestinal cancer. INTERPRETATION: We could not find evidence that antioxidant supplements can prevent gastrointestinal cancers; on the contrary, they seem to increase overall mortality. The potential preventive effect of selenium should be studied in adequate randomised trials.", "title": "Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis." }, { "docid": "MED-2458", "text": "BACKGROUND: Antioxidant-rich diets are associated with reduced asthma prevalence in epidemiologic studies. We previously showed that short-term manipulation of antioxidant defenses leads to changes in asthma outcomes. OBJECTIVE: The objective was to investigate the effects of a high-antioxidant diet compared with those of a low-antioxidant diet, with or without lycopene supplementation, in asthma. DESIGN: Asthmatic adults (n = 137) were randomly assigned to a high-antioxidant diet (5 servings of vegetables and 2 servings of fruit daily; n = 46) or a low-antioxidant diet (≤2 servings of vegetables and 1 serving of fruit daily; n = 91) for 14 d and then commenced a parallel, randomized, controlled supplementation trial. Subjects who consumed the high-antioxidant diet received placebo. Subjects who consumed the low-antioxidant diet received placebo or tomato extract (45 mg lycopene/d). The intervention continued until week 14 or until an exacerbation occurred. RESULTS: After 14 d, subjects consuming the low-antioxidant diet had a lower percentage predicted forced expiratory volume in 1 s and percentage predicted forced vital capacity than did those consuming the high-antioxidant diet. Subjects in the low-antioxidant diet group had increased plasma C-reactive protein at week 14. At the end of the trial, time to exacerbation was greater in the high-antioxidant than in the low-antioxidant diet group, and the low-antioxidant diet group was 2.26 (95% CI: 1.04, 4.91; P = 0.039) times as likely to exacerbate. Of the subjects in the low-antioxidant diet group, no difference in airway or systemic inflammation or clinical outcomes was observed between the groups that consumed the tomato extract and those who consumed placebo. CONCLUSIONS: Modifying the dietary intake of carotenoids alters clinical asthma outcomes. Improvements were evident only after increased fruit and vegetable intake, which suggests that whole-food interventions are most effective. This trial was registered at http://www.actr.org.au as ACTRN012606000286549.", "title": "Manipulating antioxidant intake in asthma: a randomized controlled trial." }, { "docid": "MED-1587", "text": "OBJECTIVE: To evaluate the possible biochemical effect of diet and heredity on the rates of monozygotic and dizygotic twinning. STUDY DESIGN: In that insulin-like growth factor (IGF) has been found to be elevated in cows selected for their demonstrated increased twinning rate, the effect of agents that influence the level of IGF in women was examined. This was correlated with their prior history of singleton versus twin birthing. In particular, the effect of diets consisting of or excluding animal products that have elevated IGF content (e.g., milk) was considered. RESULTS: Vegan women, who exclude dairy products from their diets, have a twinning rate which is one-fifth that of vegetarians and omnivores. CONCLUSION: The results reported here support the proposed IGF model of dizygotic twinning. Genotypes favoring elevated IGF and diets including dairy products, especially in areas where growth hormone is given to cattle, appear to enhance the chances of multiple pregnancies due to ovarian stimulation.", "title": "Mechanisms of twinning: VII. Effect of diet and heredity on the human twinning rate." }, { "docid": "MED-4551", "text": "Interest has increased in the possibility that maternal dietary intake during pregnancy might influence the development of allergic disorders in children. The present prospective study examined the association of maternal intake of selected foods high in fatty acids and specific types of fatty acids during pregnancy with the risk of suspected atopic eczema among Japanese infants aged 3-4 months. Subjects were 771 mother-child pairs. Information on maternal dietary intake during pregnancy was assessed with a validated self-administered diet history questionnaire. The term 'suspected atopic eczema' was used to define an outcome based on results of our questionnaire completed by mothers 3-4 months postpartum. The risk of suspected atopic eczema was 8.4% (n = 65). Higher maternal intake of meat during pregnancy was significantly associated with an increased risk of suspected atopic eczema in the offspring: the multivariate odds ratio (OR) for the highest vs. lowest quartile was 2.59 [95% confidence interval (CI): 1.15-6.17, p for trend = 0.01]. The positive association was strengthened when the definition of the outcome was confined to a definite physician's diagnosis of atopic eczema (n = 35): the multivariate OR between extreme quartiles was 3.53 (95% CI: 1.19-12.23, p for trend = 0.02). No material exposure-response relationships were observed between maternal intake of eggs, dairy products, fish, total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid consumption and the risk of suspected atopic eczema. Higher maternal meat intake may increase the risk of infantile atopic eczema, whereas we found no evidence that maternal intake of fish and n-3 polyunsaturated fatty acids are preventive against infantile atopic eczema. (c) 2009 John Wiley & Sons A/S", "title": "Maternal meat and fat consumption during pregnancy and suspected atopic eczema in Japanese infants aged 3-4 months: the Osaka Maternal and Child He..." } ]
[ { "docid": "MED-5208", "text": "OBJECTIVE: To investigate whether the rarity of colon cancer in black Africans (prevalence, < 1:100,000) can be accounted for by dietary factors considered to reduce risk, and by differences in colonic bacterial fermentation. METHODS: Samples of the adult black South African population were drawn from several rural and urban regions. Food consumption was assessed by home visits, food frequency questionnaires, computerized analysis of 72-h dietary recall, and blood sampling. Colonic fermentation was measured by breath H2 and CH4 response to a traditional meal, and to 10-g of lactulose. Cancer risk was estimated by measurement of epithelial proliferation indices (Ki-67 and BrdU) in rectal mucosal biopsies. Results were evaluated by comparison to measurements in high-risk white South Africans (prevalence, 17:100,000). RESULTS: Epithelial proliferation was significantly lower in rural and urban blacks than whites. The diets of all the black subgroups were characterized by a low animal product and high boiled maize-meal content, whereas whites consumed more fresh animal products, cheese, and wheat products. Blacks consumed below RDA quantities of fiber (43% of RDA), vitamin A (78%), C (62%), folic acid (80%) and calcium (67%), whereas whites consumed more animal protein (177% of RDA) and fat (153%). Fasting and food-induced breath methane production was two to three times higher in blacks. CONCLUSIONS: The low prevalence of colon cancer in black Africans cannot be explained by dietary \"protective\" factors, such as, fiber, calcium, vitamins A, C and folic acid, but may be influenced by the absence of \"aggressive\" factors, such as excess animal protein and fat, and by differences in colonic bacterial fermentation.", "title": "Rarity of colon cancer in Africans is associated with low animal product consumption, not fiber." }, { "docid": "MED-4095", "text": "Statistics compiled by the National Cancer Institute indicate that, between 1935 and 1974, age-adjusted mortality from most 'Western' cancers (those of the breast, colon, prostate, pancreas, ovary, and kidney) rose dramatically in African-Americans. This phenomenon is paralleled by marked increases in the incidence of these cancers in Asia and Southern Europe during the latter 20th century, in conjunction with increased intakes of dietary animal products. A credible case can be made that diets rich in animal products work in various complementary ways to up-regulate serum levels of insulin, free IGF-I, and free sex hormones: hormones that appear to have important promotional activity for Western cancers. It seems likely that dietary animal product intake by black Americans increased substantially during the 20th century, and that this fact is primarily responsible for their concurrent marked increase in mortality from Western cancers. A whole-food vegan diet rich in fruits and vegetables, especially if coupled with regular exercise and smoking avoidance, could be expected to have a remarkably positive impact on African-American cancer risk, reversing the increases in cancer risk incurred during the 20th century. Copyright 2001 Harcourt Publishers Ltd.", "title": "Mortality from Western cancers rose dramatically among African-Americans during the 20th century: are dietary animal products to blame?" }, { "docid": "MED-4358", "text": "Summary Since their discovery almost a century ago, bacterial viruses (bacteriophages or ‘phages’) have been used to prevent and treat a multitude of bacterial infections (phage therapy: PT). In addition, they have been the basis for many advances in genetics and biochemistry. Phage therapy was performed on human subjects in the United States, Europe and Asia in the few decades following their discovery. However, Western countries largely abandoned PT in favour of antibiotics in the 1940s. The relatively recent renaissance of PT in the West can be attributed partly to the increasing prevalence of antibiotic resistance in human and animal pathogens. However, the stringent controls on human trials now required in the United States and Europe have led to a greater number of domestic animal and agricultural applications as an alternative to PT in man. This trend is set to continue, at least in the short term, with recent approval from the Food and Drug Administration allowing commercial phage treatments to be used in human food in the USA. Nevertheless, despite these significant milestones and the growing number of successful PT trials, significant obstacles remain to their widespread use in animals, food and ultimately medicine in many parts of the world. This review will provide a brief overview of the history of PT in the West and will summarize some of the key findings of phage biocontrol studies in animals and meat products.", "title": "Bacteriophage biocontrol in animals and meat products" }, { "docid": "MED-2088", "text": "Organoarsenical drugs are widely used in the production of broiler chickens in the United States. Feathers from these chickens are processed into a meal product that is used as an animal feed additive and as an organic fertilizer. Research conducted to date suggests that arsenical drugs, specifically roxarsone, used in poultry production result in the accumulation of arsenic in the keratinous material of poultry feathers. The use of feather meal product in the human food system and in other settings may result in human exposures to arsenic. Consequently, the presence and nature of arsenic in twelve samples of feather meal product from six US states and China were examined. Since arsenic toxicity is highly species-dependent, speciation analysis using HPLC/ICPMS was performed to determine the biological relevance of detected arsenic. Arsenic was detected in all samples (44-4100 μg kg(-1)) and speciation analyses revealed that inorganic forms of arsenic dominated, representing 37 - 83% of total arsenic. Roxarsone was not detected in the samples (<20 μg As kg(-1)). Feather meal products represent a previously unrecognized source of arsenic in the food system, and may pose additional risks to humans as a result of its use as an organic fertilizer and when animal waste is managed. Copyright © 2011 Elsevier B.V. All rights reserved.", "title": "Arsenic species in poultry feather meal." }, { "docid": "MED-2335", "text": "Xenohormesis is a biological principle that explains how environmentally stressed plants produce bioactive compounds that can confer stress resistance and survival benefits to animals that consume them. Animals can piggyback off products of plants' sophisticated stress response which has evolved as a result of their stationary lifestyle. Factors eliciting the plant stress response can judiciously be employed to maximize yield of health-promoting plant compounds. The xenohormetic plant compounds can, when ingested, improve longevity and fitness by activating the animal's cellular stress response and can be applied in drug discovery, drug production, and nutritional enhancement of diet.", "title": "Xenohormesis: health benefits from an eon of plant stress response evolution" }, { "docid": "MED-1818", "text": "PURPOSE: Few data are available on the role of combinations of foods and/or nutrients on pancreatic cancer risk. To add further information on dietary patterns potentially associated to pancreatic cancer, we applied an exploratory principal component factor analysis on 28 major nutrients derived from an Italian case-control study. METHODS: Cases were 326 incident pancreatic cancer cases and controls 652 frequency-matched controls admitted to hospital for non-neoplastic diseases. Dietary information was collected through a validated and reproducible food frequency questionnaire. Multiple logistic regression models adjusted for sociodemographic variables and major recognized risk factors for pancreatic cancer were used to estimate the odds ratios (OR) of pancreatic cancer for each dietary pattern. RESULTS: We identified four dietary patterns-named \"animal products,\" \"unsaturated fats,\" \"vitamins and fiber,\" and \"starch rich,\" that explain 75% of the total variance in nutrient intake in this population. After allowing for all the four patterns, positive associations were found for the animal products and the starch rich patterns, the OR for the highest versus the lowest quartiles being 2.03 (95% confidence interval [CI], 1.29-3.19) and 1.69 (95% CI, 1.02-2.79), respectively; an inverse association emerged for the vitamins and fiber pattern (OR, 0.55; 95% CI, 0.35-0.86), whereas no association was observed for the unsaturated fats pattern (OR, 1.13; 95% CI, 0.71-1.78). CONCLUSIONS: A diet characterized by a high consumption of meat and other animal products, as well as of (refined) cereals and sugars, is positively associated with pancreatic cancer risk, whereas a diet rich in fruit and vegetables is inversely associated. Copyright © 2013 Elsevier Inc. All rights reserved.", "title": "Nutrient-based dietary patterns and pancreatic cancer risk." }, { "docid": "MED-5129", "text": "BACKGROUND: Vitamin B(12) deficiency can occur in individuals with dietary patterns that exclude animal foods and patients who are unable to absorb vitamin B(12 )in food. MATERIAL AND METHOD: Our clinic serves a high-income population living in Southern Israel. We hypothesize that a tendency to decrease of level of vitamin B(12) in our population is caused by a premeditated decrease in consumption of animal products. We analyzed 512 medical histories of patients undergoing blood tests for vitamin B(12) level for various reasons. RESULT: The level of vitamin B(12) in 192 patients (37.5%) was less than 250 pg/ml. CONCLUSION: As a result of media information disseminating the relationship between meat, cholesterol and cardiovascular diseases, consumption of meat, particularly beef, has decreased. Changes in life style among segments of the population with high socioeconomic level, on one hand, and the existence of poverty, on the other, are two main factors in the decreasing consumption of animal products. This causes a decrease in the level of vitamin B(12) in the general population, and as a consequence, this will increase pathology due to vitamin B(12) deficiency. In lieu of these possible developments and in order to prevent serious health problems, vitamin B(12) fortification should be seriously considered and discussed. (c) 2007 S. Karger AG, Basel.", "title": "Modern society and prospects of low vitamin B12 intake." }, { "docid": "MED-1221", "text": "Many articles have summarized the changing epidemiology of Clostridium difficile infections (CDI) in humans, but the emerging presence of C. difficile in foods and animals and possible measures to reduce human exposure to this important pathogen have been infrequently addressed. CDIs have traditionally been assumed to be restricted to health-care settings. However, recent molecular studies indicate that this is no longer the case; animals and foods might be involved in the changing epidemiology of CDIs in humans; and genome sequencing is disproving person-to-person transmission in hospitals. Although zoonotic and foodborne transmission have not been confirmed, it is evident that susceptible people can be inadvertently exposed to C. difficile from foods, animals, or their environment. Strains of epidemic clones present in humans are common in companion and food animals, raw meats, poultry products, vegetables, and ready-to-eat foods, including salads. In order to develop science-based prevention strategies, it is critical to understand how C. difficile reaches foods and humans. This review contextualizes the current understanding of CDIs in humans, animals, and foods. Based on available information, we propose a list of educational measures that could reduce the exposure of susceptible people to C. difficile. Enhanced educational efforts and behavior change targeting medical and non-medical personnel are needed.", "title": "Clostridium difficile in foods and animals: history and measures to reduce exposure." }, { "docid": "MED-4612", "text": "Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.", "title": "Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity." }, { "docid": "MED-1220", "text": "Clostridium difficile causes infectious diarrhoea in humans and animals. It has been found in both diarrhoeal and non-diarrhoeal pigs, horses and cattle, suggesting a potential reservoir for human insection, and in 20-40 % of meat products in Canada and the USA, suggesting the possibility, albeit not proven, of food-borne transmission. Although it is not yet completely clear, it is likely that excessive antimicrobial exposure is driving the establishment of C. difficile in animals, in a manner analogous to human infection, rather than the organism just being normal flora of the animal gastrointestinal tract. PCR ribotype 078 is the most common ribotype of C. difficile found in pigs (83 % in one study in the USA) and cattle (up to 100 %) and this ribotype is now the third most common ribotype of C. difficile found in human infection in Europe. Human and pig strains of C. difficile are genetically identical in Europe confirming that a zoonosis exists. Rates of community-acquired C. difficile infection (CDI) are increasing world wide, a fact that sits well with the notion that animals are a reservoir for human infection. Thus, there are three problems that require resolution: a human health issue, an animal health issue and the factor common to both these problems, environmental contamination. To successfully deal with these recent changes in the epidemiology of CDI will require a 'one health' approach involving human health physicians, veterinarians and environmental scientists.", "title": "Clostridium difficile infection in humans and piglets: a 'One Health' opportunity." }, { "docid": "MED-1433", "text": "Advanced glycation end products (AGEs) are a heterogeneous, complex group of compounds that are formed when reducing sugar reacts in a non-enzymatic way with amino acids in proteins and other macromolecules. This occurs both exogenously (in food) and endogenously (in humans) with greater concentrations found in older adults. While higher AGEs occur in both healthy older adults and those with chronic diseases, research is progressing to both quantify AGEs in food and in people, and to identify mechanisms that would explain why some human tissues are damaged, and others are not. In the last twenty years, there has been increased evidence that AGEs could be implicated in the development of chronic degenerative diseases of aging, such as cardiovascular disease, Alzheimer’s disease and with complications of diabetes mellitus. Results of several studies in animal models and humans show that the restriction of dietary AGEs has positive effects on wound healing, insulin resistance and cardiovascular diseases. Recently, the effect of restriction in AGEs intake has been reported to increase the lifespan in animal models. This paper will summarize the work that has been published for both food AGEs and in vivo AGEs and their relation with aging, as well as provide suggestions for future research.", "title": "Dietary Advanced Glycation End Products and Aging" }, { "docid": "MED-4898", "text": "We examined consumption of animal foods, protein and calcium in relation to risk of prostate cancer among 142 251 men in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by recruitment centre and adjusted for height, weight, education, marital status and energy intake. After an average of 8.7 years of follow-up, there were 2727 incident cases of prostate cancer, of which 1131 were known to be localised and 541 advanced-stage disease. A high intake of dairy protein was associated with an increased risk, with a hazard ratio for the top versus the bottom fifth of intake of 1.22 (95% confidence interval (CI): 1.07–1.41, Ptrend=0.02). After calibration to allow for measurement error, we estimated that a 35-g day−1 increase in consumption of dairy protein was associated with an increase in the risk of prostate cancer of 32% (95% CI: 1–72%, Ptrend=0.04). Calcium from dairy products was also positively associated with risk, but not calcium from other foods. The results support the hypothesis that a high intake of protein or calcium from dairy products may increase the risk for prostate cancer.", "title": "Animal foods, protein, calcium and prostate cancer risk: the European Prospective Investigation into Cancer and Nutrition" }, { "docid": "MED-5335", "text": "Three recent case-control studies conclude that diets high in animal fat or cholesterol are associated with a substantial increase in risk for Parkinson's disease (PD); in contrast, fat of plant origin does not appear to increase risk. Whereas reported age-adjusted prevalence rates of PD tend to be relatively uniform throughout Europe and the Americas, sub-Saharan black Africans, rural Chinese, and Japanese, groups whose diets tend to be vegan or quasi-vegan, appear to enjoy substantially lower rates. Since current PD prevalence in African-Americans is little different from that in whites, environmental factors are likely to be responsible for the low PD risk in black Africans. In aggregate, these findings suggest that vegan diets may be notably protective with respect to PD. However, they offer no insight into whether saturated fat, compounds associated with animal fat, animal protein, or the integrated impact of the components of animal products mediates the risk associated with animal fat consumption. Caloric restriction has recently been shown to protect the central dopaminergic neurons of mice from neurotoxins, at least in part by induction of heat-shock proteins; conceivably, the protection afforded by vegan diets reflects a similar mechanism. The possibility that vegan diets could be therapeutically beneficial in PD, by slowing the loss of surviving dopaminergic neurons, thus retarding progression of the syndrome, may merit examination. Vegan diets could also be helpful to PD patients by promoting vascular health and aiding blood-brain barrier transport of L-dopa. Copyright 2001 Harcourt Publishers Ltd.", "title": "Does a vegan diet reduce risk for Parkinson's disease?" }, { "docid": "MED-2206", "text": "Sweet potato is one of the crops selected for NASA's Advanced Life Support Program for potential long-duration lunar/Mars missions. This article presents recipes of products made from sweet potato and determines the consumer acceptability of products containing from 6% to 20% sweet potato on a dry weight basis. These products were developed for use in nutritious and palatable meals for future space explorers. Sensory evaluation (appearance/color, aroma, texture, flavor/taste, and overall acceptability) studies were conducted to determine the consumer acceptability of vegetarian products made with sweet potato using panelists at NASA/Johnson Space Center in Houston, TX. None of these products including the controls, contained any ingredient of animal origin with the exception of sweet potato pie. A 9-point hedonic scale (9 being like extremely and 1 being dislike extremely) was used to evaluate 10 products and compare them to similar commercially available products used as controls. The products tested were pancakes, waffles, tortillas, bread, pie, pound cake, pasta, vegetable patties, doughnuts, and pretzels. All of the products were either liked moderately or liked slightly with the exception of the sweet potato vegetable patties, which were neither liked nor disliked. Mean comparisons of sensory scores of sweet potato recipes and their controls were accomplished by using the Student t-test. Because of their nutritional adequacy and consumer acceptability, these products are being recommended to NASA's Advanced Life Support Program for inclusion in a vegetarian menu plan designed for lunar/Mars space missions.", "title": "Consumer acceptance of vegetarian sweet potato products intended for space missions." }, { "docid": "MED-3502", "text": "In this article I review the association between exposure to carrageenan and the occurrence of colonic ulcerations and gastrointestinal neoplasms in animal models. Although the International Agency for Research on Cancer in 1982 identified sufficient evidence for the carcinogenicity of degraded carrageenan in animals to regard it as posing a carcinogenic risk to humans, carrageenan is still used widely as a thickener, stabilizer, and texturizer in a variety of processed foods prevalent in the Western diet. I reviewed experimental data pertaining to carrageenan's effects with particular attention to the occurrence of ulcerations and neoplasms in association with exposure to carrageenan. In addition, I reviewed from established sources mechanisms for production of degraded carrageenan from undegraded or native carrageenan and data with regard to carrageenan intake. Review of these data demonstrated that exposure to undegraded as well as to degraded carrageenan was associated with the occurrence of intestinal ulcerations and neoplasms. This association may be attributed to contamination of undegraded carrageenan by components of low molecular weight, spontaneous metabolism of undegraded carrageenan by acid hydrolysis under conditions of normal digestion, or the interactions with intestinal bacteria. Although in 1972, the U.S. Food and Drug Administration considered restricting dietary carrageenan to an average molecular weight > 100,000, this resolution did not prevail, and no subsequent regulation has restricted use. Because of the acknowledged carcinogenic properties of degraded carrageenan in animal models and the cancer-promoting effects of undegraded carrageenan in experimental models, the widespread use of carrageenan in the Western diet should be reconsidered.", "title": "Review of harmful gastrointestinal effects of carrageenan in animal experiments." }, { "docid": "MED-5131", "text": "The usual dietary sources of vitamin B(12) are animal foods, meat, milk, egg, fish, and shellfish. As the intrinsic factor-mediated intestinal absorption system is estimated to be saturated at about 1.5-2.0 microg per meal under physiologic conditions, vitamin B(12) bioavailability significantly decreases with increasing intake of vitamin B(12) per meal. The bioavailability of vitamin B(12) in healthy humans from fish meat, sheep meat, and chicken meat averaged 42%, 56%-89%, and 61%-66%, respectively. Vitamin B(12) in eggs seems to be poorly absorbed (< 9%) relative to other animal food products. In the Dietary Reference Intakes in the United States and Japan, it is assumed that 50% of dietary vitamin B(12) is absorbed by healthy adults with normal gastro-intestinal function. Some plant foods, dried green and purple lavers (nori) contain substantial amounts of vitamin B(12), although other edible algae contained none or only traces of vitamin B(12). Most of the edible blue-green algae (cyanobacteria) used for human supplements predominantly contain pseudovitamin B(12), which is inactive in humans. The edible cyanobacteria are not suitable for use as vitamin B(12) sources, especially in vegans. Fortified breakfast cereals are a particularly valuable source of vitamin B(12) for vegans and elderly people. Production of some vitamin B(12)-enriched vegetables is also being devised.", "title": "Vitamin B12 sources and bioavailability." }, { "docid": "MED-4540", "text": "BACKGROUND: Red yeast rice (RYR) is a widely available dietary supplement used by millions of patients as an alternative therapy for hyperlipidemia. It contains 14 active compounds called monacolins that inhibit hepatic cholesterol synthesis. Although studies have suggested that some formulations of RYR may be effective and safe for lipid lowering, monacolin levels are not standardized among marketed products and are generally not published on labels. We evaluated monacolin levels in 12 commercial RYR formulations and tested for citrinin, a mycotoxin that is nephrotoxic in animals. METHODS: Each formulation of RYR was labeled \"600 mg/capsule\" of active product. Analyses for monacolins and citrinin were performed between August 2006 and June 2008 using high-performance liquid chromatography with mass spectroscopy-mass spectroscopy detection. Laboratory analyses of RYR products were conducted by ConsumerLab.com, White Plains, New York. RESULTS: There was marked variability in the 12 RYR products in total monacolins (0.31-11.15 mg/capsule), monacolin K (lovastatin) (0.10-10.09 mg/capsule), and monacolin KA (0.00-2.30 mg/capsule). Four products had elevated levels of citrinin. CONCLUSIONS: We found striking variability in monacolin content in 12 proprietary RYR products and the presence of citrinin in one-third of the formulations tested. Although RYR may have potential as an alternative lipid-lowering agent, our findings suggest the need for improved standardization of RYR products and product labeling. Until this occurs, physicians should be cautious in recommending RYR to their patients for the treatment of hyperlipidemia and primary and secondary prevention of cardiovascular disease.", "title": "Marked variability of monacolin levels in commercial red yeast rice products: buyer beware!" }, { "docid": "MED-913", "text": "In recent years, there has been a notable concern on the safety of genetically modified (GM) foods/plants, an important and complex area of research, which demands rigorous standards. Diverse groups including consumers and environmental Non Governmental Organizations (NGO) have suggested that all GM foods/plants should be subjected to long-term animal feeding studies before approval for human consumption. In 2000 and 2006, we reviewed the information published in international scientific journals, noting that the number of references concerning human and animal toxicological/health risks studies on GM foods/plants was very limited. The main goal of the present review was to assess the current state-of-the-art regarding the potential adverse effects/safety assessment of GM plants for human consumption. The number of citations found in databases (PubMed and Scopus) has dramatically increased since 2006. However, new information on products such as potatoes, cucumber, peas or tomatoes, among others was not available. Corn/maize, rice, and soybeans were included in the present review. An equilibrium in the number research groups suggesting, on the basis of their studies, that a number of varieties of GM products (mainly maize and soybeans) are as safe and nutritious as the respective conventional non-GM plant, and those raising still serious concerns, was currently observed. Nevertheless, it should be noted that most of these studies have been conducted by biotechnology companies responsible of commercializing these GM plants. These findings suggest a notable advance in comparison with the lack of studies published in recent years in scientific journals by those companies. All this recent information is herein critically reviewed. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "A literature review on the safety assessment of genetically modified plants." }, { "docid": "MED-5201", "text": "It is estimated that most colon cancers can be attributed to dietary causes. We have hypothesized that diet influences the health of the colonic mucosa through interaction with the microbiota and that it is the milieu interior that regulates mucosal proliferation and therefore cancer risk. To validate this further, we compared colonic contents from healthy 50- to 65-y-old people from populations with high and low risk, specifically low risk Native Africans (cancer incidence <1:100,000; n = 17), high risk African Americans (risk 65:100,000; n = 17), and Caucasian Americans (risk 50:100,000; n = 18). Americans typically consume a high-animal protein and -fat diet, whereas Africans consume a staple diet of maize meal, rich in resistant starch and low in animal products. Following overnight fasting, rapid colonic evacuation was performed with 2 L polyethylene glycol. Total colonic evacuants were analyzed for SCFA, vitamins, nitrogen, and minerals. Total SCFA and butyrate were significantly higher in Native Africans than in both American groups. Colonic folate and biotin content, measured by Lactobacillus rhamnoses and Lactobacillus plantarum ATCC 8014 bioassay, respectively, exceeded normal daily dietary intakes. Compared with Africans, calcium and iron contents were significantly higher in Caucasian Americans and zinc content was significantly higher in African Americans, but nitrogen content did not differ among the 3 groups. In conclusion, the results support our hypothesis that the microbiota mediates the effect diet has on colon cancer risk by their generation of butyrate, folate, and biotin, molecules known to play a key role in the regulation of epithelial proliferation.", "title": "Products of the colonic microbiota mediate the effects of diet on colon cancer risk." }, { "docid": "MED-5339", "text": "Recently, it has been suggested that the Escherichia coli causing urinary tract infection (UTI) may come from meat and animals. The purpose was to investigate if a clonal link existed between E. coli from animals, meat and UTI patients. Twenty-two geographically and temporally matched B2 E. coli from UTI patients, community-dwelling humans, broiler chicken meat, pork, and broiler chicken, previously identified to exhibit eight virulence genotypes by microarray-detection of approximately 300 genes, were investigated for clonal relatedness by PFGE. Nine isolates were selected and tested for in vivo virulence in the mouse model of ascending UTI. UTI and community-dwelling human strains were closely clonally related to meat strains. Several human derived strains were also clonally interrelated. All nine isolates regardless of origin were virulent in the UTI model with positive urine, bladder and kidney cultures. Further, isolates with the same gene profile also yielded similar bacterial counts in urine, bladder and kidneys. This study showed a clonal link between E. coli from meat and humans, providing solid evidence that UTI is zoonosis. The close relationship between community-dwelling human and UTI isolates may indicate a point source spread, e.g. through contaminated meat.", "title": "Is Escherichia coli urinary tract infection a zoonosis? Proof of direct link with production animals and meat." }, { "docid": "MED-1812", "text": "Epidemiologic studies of diet and pancreas cancer are few, and include ecologic comparisons and a limited number of prospective and case-control studies. Foods and/or nutrients that have been suggested to be associated with increased risk of this cancer include total fat intake, eggs, animal protein, sugar, meat, coffee and butter. Consumption of raw fruits and vegetables has been consistently associated with decreased risk. Dietary habits and medical history variables were evaluated in a prospective study of fatal pancreas cancer among 34,000 California Seventh-day Adventists between 1976 and 1983. Forty deaths from pancreas cancer occurred during the follow-up period. Compared to all US whites, Adventists experienced decreased risk from pancreas cancer death (standardized mortality ratio [SMR] = 72 for men; 90 for women), which was not statistically significant. Although there was a suggestive relationship between increasing meat, egg, and coffee consumption and increased pancreatic cancer risk, these variables were not significantly related to risk after controlling for cigarette smoking. However, increasing consumption of vegetarian protein products, beans, lentils, and peas as well as dried fruit was associated with highly significant protective relationships to pancreas cancer risk. A prior history of diabetes was associated with increased risk of subsequent fatal pancreas cancer, as was a history of surgery for peptic or duodenal ulcer. A history of tonsillectomy was associated with a slight, nonsignificant protective relationship as was history of various allergic reactions. These findings suggest that the protective relationships associated with frequent consumption of vegetables and fruits high in protease-inhibitor content are more important than any increase in pancreas cancer risk attendant on frequent consumption of meat or other animal products. Furthermore, the previously reported positive associations between diabetes and abdominal surgery and pancreas cancer risk are supported in these data.", "title": "Dietary habits and past medical history as related to fatal pancreas cancer risk among Adventists." }, { "docid": "MED-335", "text": "OBJECTIVE: Meat and milk products are important sources of dietary phosphorus (P) and protein. The use of P additives is common both in processed cheese and meat products. Measurement of in vitro digestible phosphorus (DP) content of foods may reflect absorbability of P. The objective of this study was to measure both total phosphorus (TP) and DP contents of selected meat and milk products and to compare amounts of TP and DP and the proportion of DP to TP among different foods. METHODS: TP and DP contents of 21 meat and milk products were measured by inductively coupled plasma optical emission spectrometry (ICP-OES). In DP analysis, samples were digested enzymatically, in principle, in the same way as in the alimentary canal before the analyses. The most popular national brands of meat and milk products were chosen for analysis. RESULTS: The highest TP and DP contents were found in processed and hard cheeses; the lowest, in milk and cottage cheese. TP and DP contents in sausages and cold cuts were lower than those in cheeses. Chicken, pork, beef, and rainbow trout contained similar amounts of TP, but slightly more variation was found in their DP contents. CONCLUSIONS: Foods containing P additives have a high content of DP. Our study confirms that cottage cheese and unenhanced meats are better choices than processed or hard cheeses, sausages, and cold cuts for chronic kidney disease patients, based on their lower P-to-protein ratios and sodium contents. The results support previous findings of better P absorbability in foods of animal origin than in, for example, legumes. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.", "title": "Differences among total and in vitro digestible phosphorus content of meat and milk products." }, { "docid": "MED-731", "text": "Anthrax is an acute bacterial infection caused by Bacillus anthracis. Humans become infected under natural conditions by contact with infected animals or contaminated animal products. About 95% of human anthrax is cutaneous and 5% respiratory. Gastrointestinal anthrax is very rare, and has been reported in less than 1% of all cases. Anthrax meningitis is a rare complication of any of the other three forms of disease. We report three rare cases of anthrax (gastrointestinal, oropharyngeal and meningitis) arising from the same source. The three patients were from a single family and were admitted with different clinical pictures after the ingestion of half-cooked meat from a sick sheep. These cases emphasize the need for awareness of anthrax in the differential diagnosis in areas where the disease remains endemic.", "title": "Three rare cases of anthrax arising from the same source." }, { "docid": "MED-2751", "text": "Recent data on fishmeal and fish-oil supply are presented identifying key producer countries and raw material sources and distinguishing between whole fish and by-products. The conversion of these raw materials into marine ingredients is discussed and global volumes presented. This is followed by a summary of the main countries using these marine ingredients over recent years. Uses of fishmeal and fish-oil by market segment are then presented. From this, a global mass balance of inputs and outputs is derived which allows the calculation of the input-to-output ratios (fish in:fish out; FIFO) for the main aquaculture production types to be made. Current areas of focus by the industry include the need to demonstrate sustainable practice, more strategic use of marine ingredients, greater use of fishery and land-animal by-products as well as vegetable substitutes, and novel sources of essential omega-3 fats, notably the long-chain polyunsaturated fatty acids, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Implications are drawn for future supply prospects of fishmeal and fish-oil and their future role in aquaculture, agriculture and human health. © 2013 The Fisheries Society of the British Isles.", "title": "Global fishmeal and fish-oil supply: inputs, outputs and markets." }, { "docid": "MED-4145", "text": "A number of technologies that increase feed efficiency and lean tissue deposition while decreasing fat deposition have been developed in an effort to improve profitability of animal production. In general, the mode of action of these metabolic modifiers is to increase muscle deposition while often simultaneously reducing fat deposition. However, there have been some concerns that the focus on increasing production efficiency and lean meat yield has been to the detriment of meat quality. The aim of this review is to collate data on the effects of these metabolic modifiers on meat quality, and then discuss these overall effects. When data from the literature are collated and subject to meta-analyses it appears that conservative use of each of these technologies will result in a 5-10% (0.3-0.5kg) increase in shear force with a similar reduction in perception of tenderness. However, it should be borne in mind that the magnitude of these increases are similar to those observed with similar increases in carcass leanness obtained through other means (e.g. nutritional, genetic selection) and may be an inherent consequence of the production of leaner meat. To counter this, there are some other metabolic factors and dietary additives that offer some potential to improve meat quality (for example immuncastration) and it is possible that these can be used on their own or in conjunction with somatotropin, approved β-agonists, anabolic implants and CLA to maintain or improve meat quality.", "title": "Effects of dietary factors and other metabolic modifiers on quality and nutritional value of meat." }, { "docid": "MED-4554", "text": "Modern diets are largely heat-processed and as a result contain high levels of advanced glycation end products (AGEs). Dietary advanced glycation end products (dAGEs) are known to contribute to increased oxidant stress and inflammation, which are linked to the recent epidemics of diabetes and cardiovascular disease. This report significantly expands the available dAGE database, validates the dAGE testing methodology, compares cooking procedures and inhibitory agents on new dAGE formation, and introduces practical approaches for reducing dAGE consumption in daily life. Based on the findings, dry heat promotes new dAGE formation by >10- to 100-fold above the uncooked state across food categories. Animal-derived foods that are high in fat and protein are generally AGE-rich and prone to new AGE formation during cooking. In contrast, carbohydrate-rich foods such as vegetables, fruits, whole grains, and milk contain relatively few AGEs, even after cooking. The formation of new dAGEs during cooking was prevented by the AGE inhibitory compound aminoguanidine and significantly reduced by cooking with moist heat, using shorter cooking times, cooking at lower temperatures, and by use of acidic ingredients such as lemon juice or vinegar. The new dAGE database provides a valuable instrument for estimating dAGE intake and for guiding food choices to reduce dAGE intake.", "title": "Advanced Glycation End Products in Foods and a Practical Guide to Their Reduction in the Diet" }, { "docid": "MED-4686", "text": "There is ample reason to believe that diets rich in phytochemicals provide protection from vascular diseases and many cancers; direct antioxidant activity as well as modulation of enzyme expression or hormone activity contribute to this effect. Phytochemicals derived from diverse foods presumably can interact additively and (possibly) synergistically; thus, the total dietary load of phytochemicals may have important implications for health. As a means of very roughly quantifying this load, a \"phytochemical index\" (PI) is proposed, defined as the percent of dietary calories derived from foods rich in phytochemicals. Calories derived from fruits, vegetables (excluding potatoes), legumes, whole grains, nuts, seeds, fruit/vegetable juices, soy products, wine, beer, and cider - and foods compounded therefrom - would be counted in this index. Partial credit could be given for antioxidant-rich extra virgin olive oil. Other added oils, refined sugars, refined grains, potato products, hard liquors, and animal products - regrettably, the chief sources of calories in typical Western diets - would be excluded. Although the PI would provide only a very rough approximation of the quantity or quality of phytochemical nutrition, it nonetheless could aid epidemiologists in exploring the health consequences of diets high in phytochemical-rich plant foods, and could also help clinical nutritionists in their efforts to improve the phytochemical nutrition of their clients.", "title": "Proposal for a dietary \"phytochemical index\"." }, { "docid": "MED-5019", "text": "Apples ( MALUS sp., Rosaceae) are a rich source of nutrient as well as non-nutrient components and contain high levels of polyphenols and other phytochemicals. Main structural classes of apple constituents include hydroxycinnamic acids, dihydrochalcones, flavonols (quercetin glycosides), catechins and oligomeric procyanidins, as well as triterpenoids in apple peel and anthocyanins in red apples. Several lines of evidence suggest that apples and apple products possess a wide range of biological activities which may contribute to health beneficial effects against cardiovascular disease, asthma and pulmonary dysfunction, diabetes, obesity, and cancer (reviewed by Boyer and Liu, Nutr J 2004). The present review will summarize the current knowledge on potential cancer preventive effects of apples, apple juice and apple extracts (jointly designated as apple products). In brief, apple extracts and components, especially oligomeric procyanidins, have been shown to influence multiple mechanisms relevant for cancer prevention in IN VITRO studies. These include antimutagenic activity, modulation of carcinogen metabolism, antioxidant activity, anti-inflammatory mechanisms, modulation of signal transduction pathways, antiproliferative and apoptosis-inducing activity, as well as novel mechanisms on epigenetic events and innate immunity. Apple products have been shown to prevent skin, mammary and colon carcinogenesis in animal models. Epidemiological observations indicate that regular consumption of one or more apples a day may reduce the risk for lung and colon cancer.", "title": "Cancer chemopreventive potential of apples, apple juice, and apple components." }, { "docid": "MED-1843", "text": "In the early 1970s, aluminium toxicity was first implicated in the pathogenesis of clinical disorders in patients with chronic renal failure involving bone (renal osteomalacia) or brain tissue (dialysis encephalopathy). Before that time the toxic effects of aluminium ingestion were not considered to be a major concern because absorption seemed unlikely to occur. Meanwhile, aluminium toxicity has been investigated in countless epidemiological and clinical studies as well as in animal experiments and many papers have been published on the subject. It is now commonly acknowledged that aluminium toxicity can be induced by infusion of aluminium-contaminated dialysis fluids, by parenteral nutrition solutions, and by oral exposure as a result of aluminium-containing pharmaceutical products such as aluminium-based phosphate binders or antacid intake. Over-the-counter antacids are the most important source for human aluminium exposure from a quantitative point of view. However, aluminium can act as a powerful neurological toxicant and provoke embryonic and fetal toxic effects in animals and humans after gestational exposure. Despite these facts, the patient information leaflets from European antacids that are available OTC show substantial differences regarding warnings from aluminium toxicity. It seems advisable that all patients should receive the same information on aluminium toxicity from patient information leaflets, in particular with regard to the increased absorption through concomitant administration with citrate-containing beverages and the use of such antacids during pregnancy.", "title": "Aluminium in over-the-counter drugs: risks outweigh benefits?" }, { "docid": "MED-957", "text": "Capsicum-derived ingredients function as skin-conditioning agents--miscellaneous, external analgesics, flavoring agents, or fragrance components in cosmetics. These ingredients are used in 19 cosmetic products at concentrations as high as 5%. Cosmetic-grade material may be extracted using hexane, ethanol, or vegetable oil and contain the full range of phytocompounds that are found in the Capsicum annuum or Capsicum frutescens plant (aka red chiles), including Capsaicin. Aflatoxin and N-nitroso compounds (N-nitrosodimethylamine and N-nitrosopyrrolidine) have been detected as contaminants. The ultraviolet (UV) absorption spectrum for Capsicum Annuum Fruit Extract indicates a small peak at approximately 275 nm, and a gradual increase in absorbance, beginning at approximately 400 nm. Capsicum and paprika are generally recognized as safe by the U.S. Food and Drug Administration for use in food. Hexane, chloroform, and ethyl acetate extracts of Capsicum Frutescens Fruit at 200 mg/kg resulted in death of all mice. In a short-term inhalation toxicity study using rats, no difference was found between vehicle control and a 7% Capsicum Oleoresin solution. In a 4-week feeding study, red chilli (Capsicum annuum) in the diet at concentrations up to 10% was relatively nontoxic in groups of male mice. In an 8-week feeding study using rats, intestinal exfoliation, cytoplasmic fatty vacuolation and centrilobular necrosis of hepatocytes, and aggregation of lymphocytes in the portal areas were seen at 10% Capsicum Frutescens Fruit, but not 2%. Rats fed 0.5 g/kg day-1 crude Capsicum Fruit Extract for 60 days exhibited no significant gross pathology at necropsy, but slight hyperemia of the liver and reddening of the gastric mucosa were observed. Weanling rats fed basal diets supplemented with whole red pepper at concentrations up to 5.0% for up to 8 weeks had no pathology of the large intestines, livers, and kidneys, but destruction of the taste buds and keratinization and erosion of the gastrointestinal (GI) tract were noted in groups fed 0.5% to 5.0% red pepper. The results of 9-and 12-month extension of this study showed normal large intestines and kidneys. In rabbits fed Capsicum Annuum Powder at 5 mg/kg day-1 in the diet daily for 12 months damage to the liver and spleen was noted. A rabbit skin irritation test of Capsicum Annuum Fruit Extract at concentrations ranging from 0.1% to 1.0% produced no irritation, but Capsicum Frutescens Fruit Extract induced concentration-dependent (at 25 to 500 microg/ml) cytotoxicity in a human buccal mucosa fibroblast cell line. An ethanol extract of red chili was mutagenic in Salmonella typhimurium TA98, but not in TA100, or in Escherichia coli. Other genotoxicity assays gave a similar pattern of mixed results. Adenocarcinoma of the abdomen was observed in 7/20 mice fed 100 mg red chilies per day for 12 months; no tumors were seen in control animals. Neoplastic changes in the liver and intestinal tumors were observed in rats fed red chili powder at 80 mg/kg day-1 for 30 days, intestinal and colon tumors were seen in rats fed red chili powder and 1,2-dimethyl hydrazine, but no tumors were observed in controls. In another study in rats, however, red chile pepper in the diet at the same dose decreased the number of tumors seen with 1,2-dimethylhydrazine. Other feeding studies evaluated the effect of red chili peppers on the incidence of stomach tumors produced by N-methyl-N'-nitro-N-nitrosoguanidine, finding that red pepper had a promoting effect. Capsicum Frutescens Fruit Extract promoted the carcinogenic effect of methyl(acetoxymethyl)nitrosamine (carcinogen) or benzene hexachloride (hepatocarcinogen) in inbred male and female Balb/c mice dosed orally (tongue application). Clinical findings include symptoms of cough, sneezing, and runny nose in chili factory workers. Human respiratory responses to Capsicum Oleoresin spray include burning of the throat, wheezing, dry cough, shortness of breath, gagging, gasping, inability to breathe or speak, and, rarely, cyanosis, apnea, and respiratory arrest. A trade name mixture containing 1% to 5% Capsicum Frutescens Fruit Extract induced very slight erythema in 1 of 10 volunteers patch tested for 48 h. Capsicum Frutescens Fruit Extract at 0.025% in a repeated-insult patch test using 103 subjects resulted in no clinically meaningful irritation or allergic contact dermatitis. One epidemiological study indicated that chili pepper consumption may be a strong risk factor for gastric cancer in populations with high intakes of chili pepper; however, other studies did not find this association. Capsaicin functions as an external analgesic, a fragrance ingredient, and as a skin-conditioning agent--miscellaneous in cosmetic products, but is not in current use. Capsaicin is not generally recognized as safe and effective by the U.S. Food and Drug Administration for fever blister and cold sore treatment, but is considered to be safe and effective as an external analgesic counterirritant. Ingested Capsaicin is rapidly absorbed from the stomach and small intestine in animal studies. Subcutaneous injection of Capsaicin in rats resulted in a rise in the blood concentration, reaching a maximum at 5 h; the highest tissue concentrations were in the kidney and lowest in the liver. In vitro percutaneous absorption of Capsaicin has been demonstrated in human, rat, mouse, rabbit, and pig skin. Enhancement of the skin permeation of naproxen (nonsteroidal anti-inflammatory agent) in the presence of Capsaicin has also been demonstrated. Pharmacological and physiological studies demonstrated that Capsaicin, which contains a vanillyl moiety, produces its sensory effects by activating a Ca2 +-permeable ion channel on sensory neurons. Capsaicin is a known activator of vanilloid receptor 1. Capsaicin-induced stimulation of prostaglandin biosynthesis has been shown using bull seminal vesicles and rheumatoid arthritis synoviocytes. Capsaicin inhibits protein synthesis in Vero kidney cells and human neuroblastoma SHSY-5Y cells in vitro, and inhibits growth of E. coli, Pseudomonas solanacearum, and Bacillus subtilis bacterial cultures, but not Saccharomyces cerevisiae. Oral LD50 values as low as 161.2 mg/kg (rats) and 118.8 mg/kg (mice) have been reported for Capsaicin in acute oral toxicity studies, with hemorrhage of the gastric fundus observed in some of the animals that died. Intravenous, intraperitoneal, and subcutaneous LD50 values were lower. In subchronic oral toxicity studies using mice, Capsaicin produced statistically significant differences in the growth rate and liver/body weight increases. Capsaicin is an ocular irritant in mice, rats, and rabbits. Dose-related edema was observed in animals receiving Capsaicin injections into the hindpaw (rats) or application to the ear (mice). In guinea pigs, dinitrochlorobenzene contact dermatitis was enhanced in the presence of Capsaicin, injected subcutaneously, whereas dermal application inhibited sensitization in mice. Immune system effects have been observed in neonatal rats injected subcutaneously with Capsaicin. Capsaicin produced mixed results in S. typhimurium micronucleus and sister-chromatid exchange genotoxicity assays. Positive results for Capsaicin were reported in DNA damage assays. Carcinogenic, cocarcinogenic, anticarcinogenic, antitumorigenic, tumor promotion, and anti-tumor promotion effects of Capsaicin have been reported in animal studies. Except for a significant reduction in crown-rump length in day 18 rats injected subcutaneously with Capsaicin (50 mg/kg) on gestation days 14, 16, 18, or 20, no reproductive or developmental toxicity was noted. In pregnant mice dosed subcutaneously with Capsaicin, depletion of substance P in the spinal cord and peripheral nerves of pregnant females and fetuses was noted. In clinical tests, nerve degeneration of intracutaneous nerve fibers and a decrease in pain sensation induced by heat and mechanical stimuli were evident in subjects injected intradermally with Capsaicin. An increase in mean inspiratory flow was reported for eight normal subjects who inhaled nebulized 10(-7) M Capsaicin. The results of provocative and predictive tests involving human subjects indicated that Capsaicin is a skin irritant. Overall, studies suggested that these ingredients can be irritating at low concentrations. Although the genotoxicity, carcinogenicity, and tumor promotion potential of Capsaicin have been demonstrated, so have opposite effects. Skin irritation and other tumor-promoting effects of Capsaicin appear to be mediated through interaction with the same vanilloid receptor. Given this mechanism of action and the observation that many tumor promoters are irritating to the skin, the Panel considered it likely that a potent tumor promoter may also be a moderate to severe skin irritant. Thus, a limitation on Capsaicin content that would significantly reduce its skin irritation potential is expected to, in effect, lessen any concerns relating to tumor promotion potential. Because Capsaicin enhanced the penetration of an anti-inflammatory agent through human skin, the Panel recommends that care should be exercised in using ingredients that contain Capsaicin in cosmetic products. The Panel advised industry that the total polychlorinated biphenyl (PCB)/pesticide contamination should be limited to not more than 40 ppm, with not more than 10 ppm for any specific residue, and agreed on the following limitations for other impurities: arsenic (3 mg/kg max), heavy metals (0.002% max), and lead (5 mg/kg max). Industry was also advised that aflatoxin should not be present in these ingredients (the Panel adopted < or =15 ppb as corresponding to \"negative\" aflatoxin content), and that ingredients derived from Capsicum annuum and Capsicum Frutescens Plant species should not be used in products where N-nitroso compounds may be formed. (ABSTRACT TRUNCATED)", "title": "Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powde..." } ]
42782
Peter Davison starred in a situational comedy.
[ { "docid": "Holding_the_Fort", "text": "Holding the Fort is an ITV situation comedy starring Peter Davison , Patricia Hodge and Matthew Kelly . It was an early product of the writing team of Laurence Marks and Maurice Gran . Three series were recorded , a total of twenty episodes , first aired between 1980 and 1982 , concurrent with Davison also starring in Doctor Who . It was made for the ITV network by LWT The situation was a role-reversal comedy , in which the premise was that Russell Milburn ( Davison ) becomes a `` house-husband '' to raise his baby daughter while his wife , Penny ( Hodge ) a captain in the Women 's Royal Army Corps , goes out to work . Russell 's friend Fitzroy , or `` Fitz '' ( Kelly ) , adds to the comic tension by encouraging Russell 's enthusiasm for football , pacifism and beer .", "title": "" }, { "docid": "Peter_Davison", "text": "Peter Davison ( born Peter Malcolm Gordon Moffett on 13 April 1951 ) is an English actor with many credits in television dramas and sitcoms . He became famous as Tristan Farnon in the BBC 's television adaptation of James Herriot 's All Creatures Great and Small stories . His subsequent starring roles included the sitcoms Holding the Fort and Sink or Swim , the fifth incarnation of the Doctor in Doctor Who , Dr. Stephen Daker in A Very Peculiar Practice and Albert Campion in Campion . He later played David Braithwaite in At Home with the Braithwaites , `` Dangerous '' Davies in The Last Detective and Henry Sharpe in Law & Order : UK .", "title": "" } ]
[ { "docid": "Peter_Davison_(disambiguation)", "text": "Peter Davison ( born 1951 ) is a British actor . Peter Davison may also refer to : Peter Davison ( footballer ) ( born 1944 ) , Australian rules footballer Peter Davison ( investor ) , Australian investor and entrepreneur Peter Davison ( poet ) ( 1928 -- 2004 ) , American poet Peter Davison ( professor ) ( born 1926 ) , professor of English and biographer", "title": "" }, { "docid": "The_Five(ish)_Doctors_Reboot", "text": "The Five ( ish ) Doctors Reboot is a 2013 comedy spoof and homage to the British science fiction television programme Doctor Who . It debuted on the BBC Red Button service after the broadcast of `` The Day of the Doctor '' , the official 50th anniversary special . The programme was written and directed by Peter Davison , who stars alongside fellow former Doctor actors Sylvester McCoy , Colin Baker , and Paul McGann . It features appearances from more recent stars of the show David Tennant , Matt Smith , Jenna Coleman , and John Barrowman , as well as Doctor Who executive producer Steven Moffat , his predecessor Russell T Davies , and numerous others connected to the programme , all playing themselves in a more or less parodic manner . The plot focuses on the fictionalised , disgruntled Davison , Baker and McCoy , who become embroiled in misadventures as they attempt to sneak onto the set of the official Doctor Who 50th anniversary special . The Five ( ish ) Doctors Reboot was nominated for the 2014 Hugo Award for Best Dramatic Presentation ( Short Form ) , along with `` The Day of the Doctor '' .", "title": "" }, { "docid": "Peter_Tilbury", "text": "Peter Tilbury ( born 20 October 1945 , in Redruth , Cornwall , England ) , is a British actor and writer . As an actor Tilbury 's television appearances include The Shadow of the Tower ( 1972 ) , Dixon of Dock Green ( 1974 ) , It Takes a Worried Man ( 1981 ) , a series he created and where he wrote most of the episodes , Miss Marple ( 1987 ) , Fortunes of War ( 1987 ) Casualty ( 1989 ) , The Bill ( 1990 ) , Birds of a Feather ( 1990 ) , and Chef ! ( 1993 ) . He appeared in the film Breaking Glass ( 1980 ) . As a television writer Tilbury 's credits include Sorry , I 'm A Stranger Here Myself , the first three series of Shelley , starring Hywel Bennett , nine episodes of Chef ! from 1993 to 1994 , starring Lenny Henry , ten episodes of Birds of a Feather from 1990 to 1996 , and two episodes of Not Going Out in 2007 . His play Under the Doctor starring Peter Davison and Anton Rodgers opened at the Comedy Theatre in London in 2001 . In 1994 he was nominated for a BAFTA for his series Chef ! .", "title": "" }, { "docid": "Jon_Harmon_Feldman", "text": "Jon Harmon Feldman ( born 1967 ) is an American screenwriter and director . He has created and worked on TV series such as The Wonder Years , Tru Calling , Reunion , Dawson 's Creek , Doctor , Doctor , American Dreams , Roswell , American Town , Dirty Sexy Money and Big Shots . He wrote and directed the 1997 romantic comedy Lovelife , starring Matt Letscher , Sherilyn Fenn , Saffron Burrows , Carla Gugino , Jon Tenney , Bruce Davison and Peter Krause . Feldman won an Audience Award at the 1997 Los Angeles Independent Film Festival for writing Lovelife '' .", "title": "" }, { "docid": "Paul_Smith_(television_writer)", "text": "Paul Smith is a British television writer who was born and lives in London . Paul 's four-part BBC1 drama One Night ( executive producer Hilary Salmon ) won the Reflet D'Or for Best Drama Series at the 2012 Festival Tous Ecrans as well as making the official selection for FIPA Biarritz . Lead writer on Jam Media/CBBC 's pioneering live action/animation series ROY ( RTS Award for Best Children 's Drama 2010 , two 2011 BAFTA nominations , including Writers ' Award ) , Paul also wrote ten-part CBBC teen drama series Desperados ( Prix Jeunesse 2008 ) , about a junior wheelchair basketball team . He has also written two BBC1 Afternoon Plays - Tea with Betty starring Rosemary Leach as Queen Elizabeth II and Death Becomes Him . His other recent work includes ITV1 comedy drama The Complete Guide to Parenting starring Peter Davison ( British Comedy Guide Editors ' Award ) , the Sunday serial dramatisation of Bootleg ( BAFTA Children 's Drama Award ) and BBC1 children 's thriller series Oscar Charlie . Further credits include Murder Most Horrid ( British Comedy Award and starring Dawn French ) , Grange Hill , Brittas Empire , Spitting Image , Alas Smith and Jones ; and , with Terry Kyan , Colin 's Sandwich ( two series starring Mel Smith ) and About Face , starring Maureen Lipman Paul is married to Eve Murray who works for the British Museum and GlobeScan - they have two children Daniel and Emma Smith .", "title": "" }, { "docid": "Peter_Davison_(investor)", "text": "Peter Davison is an Australian investor and entrepreneur . In the 1990s , Davison started a small VC firm in Silicon Valley with a friend . Davison 's VC firm had considerable success at the seed stage in PayPal and early stage in Anonymizer.com , which both led to substantial financial exits . He also founded Fishburners , Australia 's largest co-working space and business incubator .", "title": "" }, { "docid": "Peter_Davison_(professor)", "text": "Peter Hobley Davison ( born 1926 ) , OBE , Ph.D. , D.Litt , Hon. D. Arts , is Research Professor of English at De Montfort University , Leicester , and Emeritus Professor of English at Glyndŵr University . Davison is considered an authority on the life and works of George Orwell .", "title": "" }, { "docid": "100_Tears", "text": "100 Tears is an American independent slasher black comedy horror film directed by Marcus Koch and produced by Joe Davison . It follows the story of a circus clown going on a murderous rampage after being wrongfully accused of rape . The film stars Georgia Chris , Joe Davison ( who also produced the film ) , Jack Amos , and Raine Brown , and was distributed by Anthum Pictures in 2007 . The film was generally well received by independent horror film critics and has since garnered a cult following .", "title": "" }, { "docid": "The_Complete_Guide_to_Parenting", "text": "The Complete Guide to Parenting is a British television comedy drama series broadcast on ITV in 2006 . Created and written by Paul Smith , the series stars Peter Davison as George Huntley , Professor of Child Psychology at London University , best-selling author of Hey Mum & Dad , Get Your Act Together and LBC resident parenting guru . He finds this purported parenting expertise put to the test , when his wife Phoebe ( Josie Lawrence ) takes a job based in Paris . George has to hold the fort and look after his 7-year-old son Jamie ( Noah Hedges ) , for the very first time , whilst juggling the rest of his busy life . Whilst scenes are filmed at UCL , which is one of the universities that make up the University of London , it is unclear whether this show 's ` London University ' is meant to be the University of London .", "title": "" }, { "docid": "Peter_Davison_(footballer)", "text": "Peter Davison ( born 15 November 1944 ) is a former Australian rules footballer who played with North Melbourne in the Victorian Football League ( VFL ) .", "title": "" }, { "docid": "Peter_Davison_(poet)", "text": "Peter Davison ( June 27 , 1928 , New York , New York -- December 29 , 2004 , Boston , Massachusetts ) was an American poet , essayist , teacher , lecturer , editor , and publisher .", "title": "" }, { "docid": "Fear,_Stress_&_Anger", "text": "Fear , Stress & Anger is a British sitcom that aired on BBC Two in 2007 . Starring Peter Davison and Pippa Haywood , it was written by Michael Aitkens . There is no studio audience or laugh track .", "title": "" }, { "docid": "Gordon_Peters", "text": "Gordon Peter Wilkinson , known professionally as Gordon Peters ( born 29 November 1926 in Durham ) , is a British television actor . Peters starred in a BBC TV comedy series in 1973 called The Gordon Peters Show . It was a situation comedy in which he played a character with his own name . It was not a success and only lasted one season . As a child , he sang in the choir of Durham Cathedral . He later enrolled at Durham Commercial College to learn bookkeeping . He worked as a junior clerk before volunteering for the Royal Navy . Peters has had many roles in other television shows , including Oh Brother ! , two episodes of Hi-de-Hi ! , four episodes of Dad 's Army , two episodes of Are You Being Served ? , one episode of Grace & Favour ( also called Are You Being Served ? Again ! in the United States ) , three episodes of One Foot in the Grave , five episodes of Never the Twain , one episode of Little Britain , one episode of Keeping Up Appearances and one episode of HBO 's Tales from the Crypt .", "title": "" }, { "docid": "King_Street_Junior", "text": "King Street Junior is a radio comedy about a junior school broadcast on BBC Radio 4 between March 1985 and November 1998 . For most of its run , it was broadcast in Radio 4 's lunchtime comedy slot at 12.27 , later series moving to a morning broadcast . A continuation of the series renamed King Street Junior Revisited started in 2002 and continued until 2005 . The series is written by Jim Eldridge . The cast has included Peter Davison , James Grout and Karl Howman . Research for the show was done at Newtown Road School in Carlisle . All series have been repeated on BBC 7 .", "title": "" }, { "docid": "Time_Crash", "text": "`` Time Crash '' is a mini-episode of the British science fiction television series Doctor Who . It was broadcast on 16 November 2007 , as part of the BBC One telethon for the children 's charity Children in Need . Written by Steven Moffat , it starred David Tennant and Peter Davison as the Doctor . The episode , set during the last scene of the previous episode `` Last of the Time Lords '' , depicts a humorous encounter between the Doctor 's fifth and tenth incarnations , played by Davison and Tennant respectively . `` Time Crash '' was praised by critics who reviewed the episode , and was a ratings success ; it was the most-viewed show of the night , and briefly the most-viewed episode of Doctor Who since 2005 , with 11 million viewers .", "title": "" }, { "docid": "The_Tim_Conway_Show", "text": "The Tim Conway Show may refer to : The Tim Conway Show ( 1970 TV series ) , a spring 1970 American situation comedy starring Tim Conway The Tim Conway Comedy Hour , a fall 1970 American comedy-variety show starring Tim Conway The Tim Conway Show ( 1980 TV series ) , a 1980-1981 American comedy-variety show starring Tim Conway Tim Conway 's Funny America , a 1990 American comedic hidden-camera-prank show starring Tim Conway The Tim Conway Jr. . Show , a weeknight talk radio program in Los Angeles , California , hosted by Tim Conway Jr. . See also Rango ( TV series ) , a 1967 American situation comedy starring Tim Conway Ace Crawford , Private Eye , a 1983 American situation comedy starring Tim Conway", "title": "" }, { "docid": "Rosolino_Paternò,_soldato...", "text": "Rosolino Paternò , soldato ... ( also known as Operation Snafu and Situation Normal : A.F.U ) is a 1970 Italian comedy film . The film stars Martin Landau , Jason Robards , and Peter Falk . In the title role is Nino Manfredi .", "title": "" }, { "docid": "Cloud_of_Ash", "text": "Cloud of Ash is an English-language comedy webseries , produced and set in Reykjavík , Iceland . It stars Atli Bollason and Brogan Davison as disinterested employees in Iceland 's booming tourism sector . Noted as the first-ever scripted Icelandic comedy webseries , Cloud of Ash debuted on 30 March 2015 and has run 12 episodes . Upon release , the series garnered interest in domestic and international media for its subject matter , particularly its portrayal of a German hipster tourist .", "title": "" }, { "docid": "The_Sirens_of_Time", "text": "The Sirens of Time is the first Big Finish Productions audio drama based on the long-running British science fiction television series Doctor Who . The story was written by Nicholas Briggs and stars Peter Davison , Colin Baker and Sylvester McCoy . It was recorded between 6 -- 7 March 1999 . To coincide with the release of this new Doctor Who range , a CD was given away free with Doctor Who Magazine # 279 . Titled Talking ` Bout My Regeneration , this documentary considered the history of the show in audio and featured behind the scenes interviews with the cast and production crew . Davison 's and Baker 's interpretation of their respective regeneration of The Doctor was well received , with each having a distinct voice and considerable character development .", "title": "" }, { "docid": "Lovelife", "text": "Lovelife is a 1997 romantic comedy film written and directed by Jon Harmon Feldman . The ensemble cast includes Matt Letscher , Sherilyn Fenn , Saffron Burrows , Carla Gugino , Bruce Davison , Jon Tenney and Peter Krause . Lovelife was nominated for a Feature Film Award at the 1997 Austin Film Festival , and won an Audience Award at the Los Angeles Independent Film Festival . The film was winner of the screenplay award at the L.A. Indie fest .", "title": "" }, { "docid": "Ain't_Misbehavin'_(TV_series)", "text": "Ai n't Misbehavin ' is a British sitcom that aired on BBC1 from 20 March 1994 to 14 February 1995 . It stars Peter Davison and Nicola Pagett and was written by Roy Clarke , the writer of Last of the Summer Wine and Keeping Up Appearances .", "title": "" }, { "docid": "Fiddlers_Three_(TV_series)", "text": "Fiddlers Three is a short-lived British sitcom series produced by Yorkshire Television for ITV , and it ran for 14 episodes from 19 February to 21 May 1991 . Written by Eric Chappell and directed by Graham Wetherell , it stars Peter Davison as Ralph West , Paula Wilcox as Ros West , Charles Kay as J.J. Morley , Peter Blake as Harvey , Tyler Butterworth as Osborne and Cindy Marshall-Day as Norma . The sitcom show is of the home of office politics in an accounts department in Wakefield , West Yorkshire .", "title": "" }, { "docid": "Airplane!", "text": "Airplane ! ( titled Flying High ! in Australia , New Zealand , South Africa , Japan and the Philippines ) is a 1980 American satirical parody film directed and written by David and Jerry Zucker as well as Jim Abrahams , and produced by Jon Davison . It stars Robert Hays and Julie Hagerty and features Leslie Nielsen , Robert Stack , Lloyd Bridges , Peter Graves , Kareem Abdul-Jabbar , and Lorna Patterson . The film is a parody of the disaster film genre , particularly the 1957 Paramount film Zero Hour ! , from which it borrows the plot and the central characters , as well as many elements from Airport 1975 . The film is known for its use of surreal humor and its fast-paced slapstick comedy , including visual and verbal puns and gags . Airplane ! was a critical and financial success , grossing over $ 83 million in North America against a budget of $ 3.5 million , being released by Paramount Pictures . The film 's creators received the Writers Guild of America Award for Best Adapted Comedy , and nominations for the Golden Globe Award for Best Motion Picture -- Musical or Comedy and for the BAFTA Award for Best Screenplay . In the years since its release , the film 's reputation has grown substantially . The film was ranked sixth on Bravo 's 100 Funniest Movies . In a 2007 survey by Channel 4 in the United Kingdom , it was judged the second greatest comedy film of all time , after Monty Python 's Life of Brian . In 2008 , Airplane ! was selected by Empire magazine as one of The 500 Greatest Movies of All Time and in 2012 was voted number one in The 50 Funniest Comedies Ever poll . In 2010 , the film was selected for preservation in the United States National Film Registry by the Library of Congress as being `` culturally , historically , or aesthetically significant '' .", "title": "" }, { "docid": "Chef!", "text": "Chef ! is a British situation comedy starring Lenny Henry that aired as twenty episodes over three series from 1993 to 1996 on the BBC . The show was created and primarily written by Peter Tilbury based on an idea from Lenny Henry and produced for the BBC by Henry 's production company , Crucial Films .", "title": "" }, { "docid": "Campion_(TV_series)", "text": "Campion is a British television mystery drama first broadcast on the BBC on January 22 , 1989 . Each of the eight stories featured across the two series , broadcast in 1989 and 1990 respectively , are adapted from the Albert Campion mystery novels written by Margery Allingham . The series starred Peter Davison as Albert Campion , Brian Glover as his manservant Magersfontein Lugg and Andrew Burt as his policeman friend Stanislaus Oates . Four novels were adapted for each series , each of which was originally broadcast as two separate hour-long episodes . Davison himself sang the title music for the first series ; in the second series , it was replaced with an instrumental version . A Lagonda 16/80 featured extensively in the series . The car used in the series is now kept in Germany . The complete series was released on DVD on May 12 , 2008 , distributed by Acorn Media UK .", "title": "" }, { "docid": "The_Foretelling", "text": "`` The Foretelling '' is the first episode of the BBC sitcom The Black Adder , the first series of the long-running comedy programme Blackadder . It marks Rowan Atkinson 's début as the character Edmund Blackadder , and is the first appearance of the recurring characters Baldrick ( Tony Robinson ) and Percy ( Tim McInnerny ) . The comedy actor Peter Cook guest stars as King Richard III . The Black Adder is a historical comedy set in late Medieval England on the cusp of the Tudor Period , and centres on the eponymous `` Black Adder '' , the pseudonym adopted from this episode onwards by Edmund Plantagenet , Duke of Edinburgh . The premise is that Henry Tudor did not become king in 1485 , but instead rewrote history to portray himself as the man who killed Richard III . The show sets out to rectify the situation by telling the `` real story '' and presents the alternative history of King Richard IV . The script of this episode contains many lines and situations which borrow from or parody William Shakespeare 's plays Richard III and Macbeth .", "title": "" }, { "docid": "Rose_Marie", "text": "Rose Marie Mazetta ( born August 15 , 1923 ) , known professionally as Rose Marie , is an American actress . As a child performer she had a successful singing career as Baby Rose Marie . A veteran of vaudeville and one of its last surviving stars , her career includes film , radio , records , theater , night clubs and television . Her most famous role was television comedy writer Sally Rogers on the CBS situation comedy The Dick Van Dyke Show . She later portrayed Myrna Gibbons on The Doris Day Show and was also a frequent panelist on the game show Hollywood Squares . She was the first major star to be known simply by her first name and is the subject of an upcoming documentary film currently in production ( as of June 2016 ) which will feature interviews from numerous co-stars , including Carl Reiner , Dick Van Dyke , Peter Marshall and Tim Conway .", "title": "" }, { "docid": "Surgical_Spirit_(TV_series)", "text": "Surgical Spirit is a British situation-comedy television series starring Nichola McAuliffe and Duncan Preston that was broadcast from 14 April 1989 through to 7 July 1995 . It was written by Annie Bruce , Raymond Dixon , Graeme Garden , Peter Learmouth , Paul McKenzie and Annie Wood . It was made for the ITV network by Humphrey Barclay Productions for Granada Television .", "title": "" }, { "docid": "Edward_Davison_(poet)", "text": "Edward Lewis Davison ( 1898 -- 1970 ) was a Scottish poet and critic , born in Glasgow . He emigrated to the United States in 1925 , and became an academic , teaching at Vassar College , the University of Miami , and the University of Colorado at Boulder , where he was involved in the Colorado Writers 1937 conference . He was a friend of Robert Frost . The poet Peter Davison is his son . He was widely published as a poet in the 1920s , featured in the J. C. Squire anthologies , and became known as a writer of sonnets . His Be Thou At Peace has been set to music by John Raynor .", "title": "" }, { "docid": "Peter_Moffett", "text": "Peter Mof ( f ) at ( t ) or Moffett may refer to : Peter Moffat , English playwright and screenwriter Peter Moffatt ( 1922 -- 2007 ) , English television director Peter Davison , real name Peter Moffett , ( born 1951 ) , British actor Peter Moffett ( drummer ) , for the bands Government Issue and Wool", "title": "" } ]
PLAIN-1955
psychosis
[ { "docid": "MED-5128", "text": "BACKGROUND: Elevated total homocysteine (tHcy) concentrations have been associated with cognitive impairment, but it is unclear whether low vitamin B-12 or folate status is responsible for cognitive decline. OBJECTIVE: We examined the associations of cognitive decline with vitamin B-12 and folate status in a longitudinal cohort study performed from 1993 to 2003 in Oxford, United Kingdom. DESIGN: Cognitive function was assessed with the Mini-Mental State Examination on >/=3 occasions during 10 y and related to serum concentrations of vitamin B-12, holotranscobalamin (holoTC), tHcy, methylmalonic acid (MMA), and folate with the use of linear mixed models in 1648 participants who provided blood in 1995. RESULTS: Cognitive function declined abruptly at younger ages in some participants but remained intact in others until very old age. In multivariate regression analyses after adjustment for established risk factors, concentrations of holoTC (a marker of reduced vitamin B-12 status), tHcy, and MMA predicted cognitive decline, but folate did not. A doubling in holoTC concentrations (from 50 to 100 pmol/L) was associated with a 30% slower rate of cognitive decline (-0.137 to -0.083), whereas a doubling in tHcy (from 10 to 20 micromol/L) or MMA (from 0.25 to 0.50 micromol/L) was associated with >50% more rapid cognitive decline (-0.090 to -0.169) and (-0.104 to -0.169), respectively. After adjustment for all vitamin markers simultaneously, the associations of cognitive decline with holoTC and MMA remained significant. CONCLUSIONS: Low vitamin B-12 status was associated with more rapid cognitive decline. Randomized trials are required to determine the relevance of vitamin B-12 supplementation for prevention of dementia.", "title": "Low vitamin B-12 status and risk of cognitive decline in older adults." }, { "docid": "MED-2042", "text": "An ever-growing volume of peer-reviewed publications speaks to the recent and rapid growth in both scope and understanding of exercise immunology. Indeed, more than 95% of all peer-reviewed publications in exercise immunology (currently >2, 200 publications using search terms \"exercise\" and \"immune\") have been published since the formation of the International Society of Exercise and Immunology (ISEI) in 1989 (ISI Web of Knowledge). We recognise the epidemiological distinction between the generic term \"physical activity\" and the specific category of \"exercise\", which implies activity for a specific purpose such as improvement of physical condition or competition. Extreme physical activity of any type may have implications for the immune system. However, because of its emotive component, exercise is likely to have a larger effect, and to date the great majority of our knowledge on this subject comes from exercise studies.", "title": "Position statement. Part one: Immune function and exercise." }, { "docid": "MED-2051", "text": "In 2011, the protease inhibitors boceprevir and telaprevir were approved in the United States and European Union for the treatment of hepatitis C infection. While remarkably effective, the newly approved therapies are also accompanied by additional side effects and considerable costs. Understanding the balance between costs and effectiveness is critical to making decisions about the optimal use of these new agents, especially for health care systems constrained by rising costs. Our goal for this review is to facilitate an understanding of the importance of cost-effectiveness analyses in guiding policy decisions about the use of newly approved drugs as well as future therapies for hepatitis C.", "title": "Economic evaluation of direct-acting antiviral therapy in chronic hepatitis C." }, { "docid": "MED-2046", "text": "AIM: To evaluate the safety and efficacy of Chlorella in 18 patients chronically infected with hepatitis C virus (HCV) genotype 1. METHODS: Eighteen adults with chronic infection by HCV genotype 1 received daily oral supplementation of Chlorella for 12 wk. Changes in the RNA levels of HCV, as well as those of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were evaluated following this treatment period. Paired t tests were conducted to compare the means of the different variables at the beginning and end of the study. Side effects and quality of life aspects were also compared between weeks 0 and 12 of the study period. RESULTS: A majority 84.61% of the patients had a significant decrease in their ALT levels from week 0 to week 12. Evaluation of side effects showed that Chlorella was well tolerated. Quality of life assessment showed that 76.9 of the participants reported an improvement in their energy levels and 46.1% reported an improvement in their perception of general health. Although 69.23% also showed a decrease in their AST levels, this was not statistically significant. Most patients that exhibited an improvement in their ALT and AST levels also showed a tendency toward a decreased HCV viral load. The HCV RNA levels showed a decrease in 69.23% of the patients, which along with changes in AST/ALT ratios from week 0 to week 12, these results were not statistically significant. CONCLUSION: Chlorella supplementation was well tolerated in patients with chronic HCV and associated with a significant decrease in ALT liver enzyme levels.", "title": "Efficacy and safety of Chlorella supplementation in adults with chronic hepatitis C virus infection" }, { "docid": "MED-5131", "text": "The usual dietary sources of vitamin B(12) are animal foods, meat, milk, egg, fish, and shellfish. As the intrinsic factor-mediated intestinal absorption system is estimated to be saturated at about 1.5-2.0 microg per meal under physiologic conditions, vitamin B(12) bioavailability significantly decreases with increasing intake of vitamin B(12) per meal. The bioavailability of vitamin B(12) in healthy humans from fish meat, sheep meat, and chicken meat averaged 42%, 56%-89%, and 61%-66%, respectively. Vitamin B(12) in eggs seems to be poorly absorbed (< 9%) relative to other animal food products. In the Dietary Reference Intakes in the United States and Japan, it is assumed that 50% of dietary vitamin B(12) is absorbed by healthy adults with normal gastro-intestinal function. Some plant foods, dried green and purple lavers (nori) contain substantial amounts of vitamin B(12), although other edible algae contained none or only traces of vitamin B(12). Most of the edible blue-green algae (cyanobacteria) used for human supplements predominantly contain pseudovitamin B(12), which is inactive in humans. The edible cyanobacteria are not suitable for use as vitamin B(12) sources, especially in vegans. Fortified breakfast cereals are a particularly valuable source of vitamin B(12) for vegans and elderly people. Production of some vitamin B(12)-enriched vegetables is also being devised.", "title": "Vitamin B12 sources and bioavailability." }, { "docid": "MED-4400", "text": "Milk is one of the main source of biologically-active peptides that may function as regulatory substances called food hormones. After passing the gut-blood barrier, the μ-opioid receptor agonist and antagonist peptides may become the new factors influencing various functions of the human organism. The aim of the conducted research was to determine the influence of μ-opioid receptor agonist peptides: human and bovine β-casomorphin-7 (h/bBCM-7) and antagonistic peptides: casoxin-6 and- D (CXN-6/D) on proliferation and cytokine secretion of human peripheral blood mononuclear cells (PBMCs). The PBMCs proliferation was measured by the use of the BrdU test, which assesses the DNA synthesis activity and the WST-1 test which assesses the activity of mitochondrial dehydrogenase enzymes. The influence of all the investigated peptides on secretion of IL-4, IL-8, IL-13 and IFN-γ was determined by the use of the ELISA tests. Incubating the cells with the peptides has not caused any changes to their enzymatic activity, which has been proved by a WST-1 test. When using a BrdU test, however, it has been observed that there appear changes to proliferation of PBMCs correlated to amounts of bromodeoxyuridine incorporated into the cellular DNA. Moreover, changes to secretion of IL-4 and IL-13 by the cells under the influence of agonists were detected, as well as changes to secretion of IFN-gamma under the influence of all the examined substances. The obtained results provide information on immunomodulatory effects of food-derived opioid peptides, which may be of clinical significance especially in the case of allergic diseases in newborns. Copyright © 2010 Elsevier Inc. All rights reserved.", "title": "The influence of μ-opioid receptor agonist and antagonist peptides on peripheral blood mononuclear cells (PBMCs)." }, { "docid": "MED-2049", "text": "Background In vitro and animal studies have demonstrated that Chlorella is a potent biological response modifier on immunity. However, there were no direct evidences for the effect of Chlorella supplementation on immune/inflammation response in healthy humans. Methods This study was designed for an 8-week randomized, double-blinded, placebo-controlled trial: 5g of Chlorella (n=23) or Placebo (n=28) as form of tablets. Mainly, cytotoxic activities of Natural killer (NK) cells and serum concentrations of interferon-γ, interleukin-1β and interleukin-12 were measured. Results After the 8-week, serum concentrations of interferon-γ (p<0.05) and interleukin-1β (p<0.001) significantly increased and that of interleukin-12 (p<0.1) tended to increase in the Chlorella group. The increments of these cytokines after the intervention were significantly bigger in the Chlorella group than those in the placebo group. In addition, NK cell activities (%) were significantly increased in Chlorella group, but not in Placebo group. The increments of NK cell activities (%) were also significantly bigger in the Chlorella group than the placebo group. Additionally, changed levels of NK cell activity were positively correlated with those of serum interleukin-1β (r=0.280, p=0.047) and interferon-γ (r=0.271, p<0.005). Signficantly positive correlations were also observed among the changed levels of serum cytokines; between interferon-γ and interleukin-1β (r=0.448, p<0.001), between interleukin-12 and interleukin-1β (r=0.416, p=0.003) and between interleukin-12 and interferon-γ (r=0.570, p<001). Conclusion These results may suggest a beneficial immunostimulatory effect of short-term Chlorella supplementation which enhances the NK cell activity and produces interferon-γ and interleukin-12 as well as interleukin-1β, the Th-1 cell-induced cytokines in healthy people.", "title": "Beneficial immunostimulatory effect of short-term Chlorella supplementation: enhancement of Natural Killer cell activity and early inflammatory response (Randomized, double-blinded, placebo-controlled trial)" }, { "docid": "MED-5132", "text": "Vitamin B12 deficiency anemia may have psychiatric manifestations preceding the hematological symptoms. Although a variety of symptoms are described, there are only sparse data on the role of vitamin B12 in depression. We report a case of vitamin B12 deficiency presenting with recurrent episodes of depression.", "title": "Role of vitamin B12 in depressive disorder--a case report." }, { "docid": "MED-2043", "text": "Natural killer (NK) cell activity and concentration of CD16+ cells (NK cells) and CD20+ cells (monocytes) in peripheral blood were measured in highly trained racing cyclists and in age- and sex-matched untrained controls. Median NK cell activity was 38.1% (range 20.0%-57.1%) in trained vs 30.3% (range 19.7%-43.1%) in untrained (P = 0.008). Median %CD16+ cells was 17% (range 7%-33%) in trained vs 11% (3%-29%) in untrained (P = 0.007). Indomethacin in vitro enhanced the NK cell activity in both groups. There was, however, no significant difference between the NK cell activity in trained and untrained after exposure to indomethacin in vitro. Indomethacin-enhanced NK cell activity was 45.9% (range 24.4%-67.5%) in trained and 40.0% (range 23.9%-68.5%) in untrained (P = 0.138). Mean %CD14+ cells was 8.3% (range 2%-15%) in trained vs 3.8% (2%-8%) in untrained (P less than 0.0001). The increased NK cell function thus demonstrated in highly trained persons might result in better resistance against infectious disease.", "title": "Natural killer cell activity in peripheral blood of highly trained and untrained persons." }, { "docid": "MED-4724", "text": "We report on the case of an infant who was hospitalized because of failure to thrive, megaloblastic anemia, and delayed psychomotor development. He was 10 months old and had been exclusively breast-fed by his vegan mother. Investigations showed vitamin B(12) deficiency with hematocytopenia and pervasive developmental disorders as well as vitamin K and vitamin D deficiencies. The infant's mother presented the same deficiencies. Introduction of vitamin supplementation normalized the biological disorders, and the infant showed weight gain and neurological improvement. This case highlights that a vegan diet during pregnancy followed by exclusive breast-feeding can induce nutritional deficiencies in the newborn, with clinical consequences. Detecting mother and child vitamin deficiencies and preventing them is essential.", "title": "[Consequences of exclusive breast-feeding in vegan mother newborn--case report]." }, { "docid": "MED-4399", "text": "Casomorphins are the most important during the first year of life, when postnatal formation is most active and milk is the main source of both nutritive and biologically active material for infants. This study was conducted on a total of 90 infants, of which 37 were fed with breast milk and 53 were fed with formula containing cow milk. The study has firstly indicated substances with immunoreactivity of human (irHCM) and bovine (irBCM) beta-casomorphins-7 in blood plasma of naturally and artificially fed infants, respectively. irHCM and irBCM were detected both in the morning before feeding (basal level), and 3h after feeding. Elevation of irHCM and irBCM levels after feeding was detected mainly in infants in the first 3 months of life. Chromatographic characterization of the material with irBCM has demonstrated that it has the same molecular mass and polarity as synthetic bovine beta-casomorphin-7. The highest basal irHCM was observed in breast-fed infants with normal psychomotor development and muscle tone. In contrast, elevated basal irBCM was found in formula-fed infants showing delay in psychomotor development and heightened muscle tone. Among formula-fed infants with normal development, the rate of this parameter directly correlated to basal irBCM. The data indicate that breast feeding has an advantage over artificial feeding for infants' development during the first year of life and support the hypothesis for deterioration of bovine casomorphin elimination as a risk factor for delay in psychomotor development and other diseases such as autism.", "title": "Beta-casomorphins-7 in infants on different type of feeding and different levels of psychomotor development." }, { "docid": "MED-5129", "text": "BACKGROUND: Vitamin B(12) deficiency can occur in individuals with dietary patterns that exclude animal foods and patients who are unable to absorb vitamin B(12 )in food. MATERIAL AND METHOD: Our clinic serves a high-income population living in Southern Israel. We hypothesize that a tendency to decrease of level of vitamin B(12) in our population is caused by a premeditated decrease in consumption of animal products. We analyzed 512 medical histories of patients undergoing blood tests for vitamin B(12) level for various reasons. RESULT: The level of vitamin B(12) in 192 patients (37.5%) was less than 250 pg/ml. CONCLUSION: As a result of media information disseminating the relationship between meat, cholesterol and cardiovascular diseases, consumption of meat, particularly beef, has decreased. Changes in life style among segments of the population with high socioeconomic level, on one hand, and the existence of poverty, on the other, are two main factors in the decreasing consumption of animal products. This causes a decrease in the level of vitamin B(12) in the general population, and as a consequence, this will increase pathology due to vitamin B(12) deficiency. In lieu of these possible developments and in order to prevent serious health problems, vitamin B(12) fortification should be seriously considered and discussed. (c) 2007 S. Karger AG, Basel.", "title": "Modern society and prospects of low vitamin B12 intake." }, { "docid": "MED-2048", "text": "Background Chlorella, a unicellular green alga that grows in fresh water, contains high levels of proteins, vitamins, minerals, and dietary fibers. Some studies have reported favorable immune function-related effects on biological secretions such as blood and breast milk in humans who have ingested a chlorella-derived multicomponent supplement. However, the effects of chlorella-derived supplement on mucosal immune functions remain unclear. The purpose of this study was to investigate whether chlorella ingestion increases the salivary secretory immunoglobulin A (SIgA) secretion in humans using a blind, randomized, crossover study design. Methods Fifteen men took 30 placebo and 30 chlorella tablets per day for 4 weeks separated by a 12-week washout period. Before and after each trial, saliva samples were collected from a sterile cotton ball that was chewed after overnight fasting. Salivary SIgA concentrations were measured using ELISA. Results Compliance rates for placebo and chlorella ingestions were 97.0 ± 1.0% and 95.3 ± 1.6%, respectively. No difference was observed in salivary SIgA concentrations before and after placebo ingestion (P = 0.38). However, salivary SIgA concentrations were significantly elevated after chlorella ingestion compared to baseline (P < 0.01). No trial × period interaction was identified for the saliva flow rates. Although the SIgA secretion rate was not affected by placebo ingestion (P = 0.36), it significantly increased after 4-week chlorella ingestion than before intake (P < 0.01). Conclusions These results suggest 4-week ingestion of a chlorella-derived multicomponent supplement increases salivary SIgA secretion and possibly improves mucosal immune function in humans.", "title": "Salivary Secretory Immunoglobulin a secretion increases after 4-weeks ingestion of chlorella-derived multicomponent supplement in humans: a randomized cross over study" }, { "docid": "MED-2050", "text": "A randomly controlled 15-wk exercise training (ET) study (five 45-min sessions/wk, brisk walking at 60% heart rate reserve) with a group of 36 mildly obese, sedentary women was conducted to investigate the relationship between improvement in cardiorespiratory fitness, changes in natural killer (NK) cell number and activity, and acute upper respiratory tract infection (URI) symptomatology. The study was conducted using a 2 (exercise and nonexercise groups) x 3 (baseline, 6-, and 15-wk testing sessions) factorial design, with data analyzed using repeated measures ANOVA. No significant change in NK cell number occurred as a result of ET as measured by the CD16 and Leu-19 monoclonal antibodies. ET did have a significant effect on NK cell activity (E:T 50:1) especially during the initial 6-wk period [F(2.68) = 12.34, p less than 0.001]. Using data from daily logs kept by each subject, the exercise group was found to have significantly fewer URI symptom days/incident than the nonexercise group (3.6 +/- 0.7 vs 7.0 +/- 1.4 days, respectively, p = 0.049). Improvement in cardiorespiratory fitness was correlated significantly with a reduction in URI symptom days/incident (r = 0.37, p = 0.025) and a change in NK cell activity from baseline to six but not 15 wks (r = 0.35, p = 0.036). In summary, moderate ET is associated with elevated NK cell activity after six but not 15 weeks, and reduced URI symptomatology in comparison to a randomized, sedentary control group.", "title": "The effects of moderate exercise training on natural killer cells and acute upper respiratory tract infections." }, { "docid": "MED-4946", "text": "In order to assess early neurotoxic effects associated with relatively low levels of mercury absorbed through fish eating, two groups of 22 adult male subjects, habitual consumers of tuna fish, and 22 controls were examined using a cross-sectional field study. The assessment included neurobehavioral tests of vigilance and psychomotor function, hand tremor measurements and serum prolactin assessment. Mercury in urine (U-Hg) and serum prolactin (sPRL) were measured in all exposed subjects and controls, whereas measurements of the organic component of mercury in blood (O-Hg) were available for only 10 exposed and six controls. U-Hg was significant higher among exposed subjects (median 6.5 microg/g of creatinine, range 1.8-21.5) than controls (median 1.5 microg/g of creatinine, range 0.5-5.3). The median values of O-Hg were 41.5 microg/l among the tuna fish eaters and 2.6 microg/l in the control group. Both U-Hg and O-Hg were significantly correlated with the quantity of fish consumed per week. Significant differences in sPRL were found between exposed (12.6 ng/ml) and controls (9.1 ng/ml). Individual sPRL were significantly correlated with both U-Hg and O-Hg levels. The neurobehavioral performance of subjects who consumed tuna fish regularly was significantly worse on color word reaction time, digit symbol reaction time and finger tapping speed (FT). After considering the education level and other covariates, the multiple stepwise regression analysis indicated that O-Hg concentration was most significantly associated with individual performance on these tests, accounting for about 65% of the variance in test scores.", "title": "Sub-clinical neurobehavioral abnormalities associated with low level of mercury exposure through fish consumption." }, { "docid": "MED-2044", "text": "Cancer incidence increases with advancing age. Over 60% of new cancers and 70% of cancer deaths occur in individuals aged 65 years or older. One factor that may contribute to this is immunosenescence - a canopy term that is used to describe age-related declines in the normal functioning of the immune system. There are multiple age-related deficits in both the innate and adaptive systems that may play a role in the increased incidence of cancer. These include decreased NK-cell function, impaired antigen uptake and presentation by monocytes and dendritic cells, an increase in 'inflammaging', a decline in the number of naïve T-cells able to respond to evolving tumor cells, and an increase in functionally exhausted senescent cells. There is consensus that habitual physical exercise can offer protection against certain types of cancer; however the evidence linking immunological mechanisms, exercise, and reduced cancer risk remain tentative. Multiple studies published over the last two decades suggest that exercise can mitigate the deleterious effects of age on immune function, thus increasing anti-cancer immunity. The potential ameliorative effect of exercise on these mechanisms include evidence that physical activity is able to stimulate greater NK-cell activity, enhance antigen-presentation, reduce inflammation, and prevent senescent cell accumulation in the elderly. Here we discuss the role played by the immune system in preventing and controlling cancer and how aging may retard these anti-cancer mechanisms. We also propose a pathway by which exercise-induced alterations in immunosenescence may decrease the incidence of cancer and help improve prognosis in cancer patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.", "title": "Can exercise-related improvements in immunity influence cancer prevention and prognosis in the elderly?" }, { "docid": "MED-5130", "text": "Although cobalamin deficiency is widely known and usually presents with hematologic and neuropsychiatric manifestations, the psychiatric symptoms are not usually the predominant manifestation. We describe a young single male vegetarian who developed a cobalamin-induced psychotic episode without preceding neurologic manifestations and without any hematologic symptoms. He recovered after a short course of antipsychotics and oral cobalamin supplementation and remained asymptomatic and functionally independent at 1 year of follow-up.", "title": "Schizophrenia-like psychotic episode precipitated by cobalamin deficiency." }, { "docid": "MED-2047", "text": "The relationship between cardiorespiratory exercise, immune function, and upper respiratory tract infection (URTI) was studied in elderly women utilizing a randomized controlled experimental design with a follow-up of 12 wk. Thirty-two sedentary, elderly Caucasian women, 67-85 yr of age, who met specific selection criteria, were randomized to either a walking or calisthenic group; 30 completed the study. Twelve highly conditioned elderly women, 65-84 yr of age, who were active in endurance competitions, were recruited at baseline for cross-sectional comparisons. Intervention groups exercised 30-40 min, 5 d.wk-1, for 12 wk, with the walking group training at 60% heart rate reserve and the calisthenic group engaging in mild range-of-motion and flexibility movements that kept their heart rates close to resting levels. At baseline, the highly conditioned subjects exhibited superior NK (119 +/- 13 vs 77 +/- 8 lytic units, P < 0.01) and T (33.3 +/- 4.9 vs 21.4 +/- 2.1 cpm x 10(-3) using PHA, P < 0.05) cell function, despite no differences in circulating levels of lymphocyte subpopulations. Twelve weeks of moderate cardiorespiratory exercise improved the VO2max of the sedentary subjects 12.6%, but did not result in any improvement in NK cell activity or T cell function. Incidence of URTI was lowest in the highly conditioned group and highest in the calisthenic control group during the 12-wk study, with the walkers in an intermediate position (chi-square = 6.36, P = 0.042). In conclusion, the highly conditioned elderly women in this study had superior NK and T cell function when compared with their sedentary counterparts.(ABSTRACT TRUNCATED AT 250 WORDS)", "title": "Physical activity and immune function in elderly women." }, { "docid": "MED-5135", "text": "Vitamin B(12) deficiency in infants often produces haematological and neurological deficits, including macrocytic anaemia, neurodevelopmental delay or regression, irritability, weakness, hypotonia, ataxia, apathy, tremor, and seizures. The diagnosis of vitamin B(12) deficiency can be difficult when the typical macrocytic anaemia is absent. We report the case of a 10-month-old female diagnosed with West syndrome associated with vitamin B(12) deficiency but without macrocytic anaemia caused by nutritional inadequacy in the mother. The patient's motor skills and cognitive development were normal until she was 9 months old, when she began to exhibit a series of sudden flexions of the head, trunk, arms, and legs. She was exclusively breast-fed and had received no vitamin supplementation. Results of electroencephalography (EEG) indicated modified hypsarrhythmia and the patient was diagnosed as having West syndrome. Synthetic adrenocorticotropic hormone was administered and although her spasms had resolved, the patient remained apathic and could not sit without assistance. EEG results indicated generalized slow activity. After she was diagnosed as having vitamin B(12) deficiency, parenteral treatment with vitamin B(12) was initiated. Her symptoms resolved and EEG was completely normal. When she was 20 months old she exhibited an age-appropriate developmental and neurological profile. To our knowledge, this is the first report of West syndrome as a presenting symptom of vitamin B(12) deficiency.", "title": "West syndrome in an infant with vitamin B12 deficiency in the absence of macrocytic anaemia." }, { "docid": "MED-2052", "text": "The addition of direct-acting antivirals (DAAs) to hepatitis C virus (HCV) treatment regimens has made treatment more effective and patient management more complex. Shepherding patients through a full course of HCV therapy requires motivation and involvement on the part of the patient and the physician. Indeed, physician inexperience and lack of confidence in guiding patients through the challenges of treatment appears to be a primary reason for early discontinuation of therapy. Among the many complications of HCV treatment that must be managed efficiently and effectively are depression and other psychiatric disorders; hematologic abnormalities including DAA- and ribavirin-associated anemia and peginterferon alfa-associated neutropenia and thrombocytopenia; rash and drug eruptions, including telaprevir-associated rash; and weight loss. Practical considerations in management of these common complications are offered. This article summarizes a presentation by Kenneth E. Sherman, MD, PhD, at the IAS-USA live continuing medical education course held in New York in June 2012.", "title": "Managing adverse effects and complications in completing treatment for hepatitis C virus infection." }, { "docid": "MED-4356", "text": "OBJECTIVE: Delusional parasitosis has been described in a wide range of patients with general medical conditions, but there are few reports about its frequency and possible pathogenic mechanisms in neurological patients. This paper describes this delusional syndrome in a sample of neurological patients. METHODS: We reviewed all clinical charts of hospitalized patients at the neuropsychiatry ward of a neurological center, from January 2005 to June 2009. Cases with delusional parasitosis were described in terms of demographic, clinical and brain imaging features. RESULTS: From a total sample of 1598 patients, we identified 636 patients with neurological disease (39.80%); of these, four patients showed delusional parasitosis (0.62% of the neurological sample). Their diagnoses were brain cysticercosis (n=1), cerebrovascular disease (n=2), and dementia due to vitamin B12 deficit (n=1). They were women in late life, with depressive features. Three of them had significant cognitive decline. Two of them had paraesthesia and pruritus related to peripheral neuropathy. One of them had pruritus of unknown origin (possibly hallucinatory). CONCLUSIONS: Delusional parasitosis was infrequent in this sample of hospitalized neurological patients. Female sex, advanced age, depressive features, cognitive decline, pruritus and paraesthesia of peripheral or central origin may contribute to delusional parasitosis in this population. Copyright 2010 Elsevier Inc. All rights reserved.", "title": "Delusional parasitosis in neurological patients." }, { "docid": "MED-4431", "text": "BACKGROUND: Workers in poultry plants have high exposure to a variety of transmissible agents present in poultry and their products. Subjects in the general population are also exposed. It is not known whether many of these agents cause disease in humans. If they do, we reason this would be readily evident in a highly exposed group such as poultry workers. We report here on mortality from non-malignant diseases in a cohort of poultry workers. METHODS: Mortality was compared with that of the US general population, and with that of a comparison group from the same union. Risk was estimated by standardized mortality ratio, proportional mortality ratio, and directly standardized risk ratio. RESULTS: Poultry workers as a group had an overall excess of deaths from diabetes, anterior horn disease, and hypertensive disease, and a deficit of deaths from intracerebral hemorrhage. Deaths from zoonotic bacterial diseases, helminthiasis, myasthenia gravis, schizophrenia, other diseases of the spinal cord, diseases of the esophagus and peritonitis were non-significantly elevated overall by all analyses, and significantly so in particular race/sex subgroups. CONCLUSIONS: Poultry workers may have excess occurrence of disease affecting several organs and systems, probably originating from widespread infection with a variety of microorganisms. The results for neurologic diseases could well represent important clues to the etiology of these diseases in humans. The small numbers of deaths involved in some cases limit interpretation.", "title": "Mortality in the Baltimore union poultry cohort: non-malignant diseases." }, { "docid": "MED-4402", "text": "Sudden infant death syndrome (SIDS) is the most common cause of death in infants and its pathogenesis is complex and multifactorial. The aim of this review is to summarize recent novel findings regarding the possible association of beta-casomorphin (beta-CM) to apnea in SIDS, which has not been widely appreciated by pediatricians and scientists. beta-CM is an exogenous bioactive peptide derived from casein, a major protein in milk and milk products, which has opioid activity. Mechanistically, circulation of this peptide into the infant's immature central nervous system might inhibit the respiratory center in the brainstem leading to apnea and death. This paper will review the possible relationship between beta-CM and SIDS in the context of passage of beta-CM through the gastrointestinal tract and the blood-brain barrier (BBB), permeability of the BBB to peptides in infants, and characterization of the casomorphin system in the brain.", "title": "Relation of beta-casomorphin to apnea in sudden infant death syndrome." }, { "docid": "MED-2045", "text": "BACKGROUND & AIMS: The prevalence of chronic hepatitis C (CH-C) remains high and the complications of infection are common. Our goal was to project the future prevalence of CH-C and its complications. METHODS: We developed a multicohort natural history model to overcome limitations of previous models for predicting disease outcomes and benefits of therapy. RESULTS: Prevalence of CH-C peaked in 2001 at 3.6 million. Fibrosis progression was inversely related to age at infection, so cirrhosis and its complications were most common after the age of 60 years, regardless of when infection occurred. The proportion of CH-C with cirrhosis is projected to reach 25% in 2010 and 45% in 2030, although the total number with cirrhosis will peak at 1.0 million (30.5% higher than the current level) in 2020 and then decline. Hepatic decompensation and liver cancer will continue to increase for another 10 to 13 years. Treatment of all infected patients in 2010 could reduce risk of cirrhosis, decompensation, cancer, and liver-related deaths by 16%, 42%, 31%, and 36% by 2020, given current response rates to antiviral therapy. CONCLUSIONS: Prevalence of hepatitis C cirrhosis and its complications will continue to increase through the next decade and will mostly affect those older than 60 years of age. Current treatment patterns will have little effect on these complications, but wider application of antiviral treatment and better responses with new agents could significantly reduce the impact of this disease in coming years.", "title": "Aging of hepatitis C virus (HCV)-infected persons in the United States: a multiple cohort model of HCV prevalence and disease progression." }, { "docid": "MED-5134", "text": "This position paper on complementary feeding summarizes evidence for health effects of complementary foods. It focuses on healthy infants in Europe. After reviewing current knowledge and practices, we have formulated these conclusions: Exclusive or full breast-feeding for about 6 months is a desirable goal. Complementary feeding (ie, solid foods and liquids other than breast milk or infant formula and follow-on formula) should not be introduced before 17 weeks and not later than 26 weeks. There is no convincing scientific evidence that avoidance or delayed introduction of potentially allergenic foods, such as fish and eggs, reduces allergies, either in infants considered at increased risk for the development of allergy or in those not considered to be at increased risk. During the complementary feeding period, >90% of the iron requirements of a breast-fed infant must be met by complementary foods, which should provide sufficient bioavailable iron. Cow's milk is a poor source of iron and should not be used as the main drink before 12 months, although small volumes may be added to complementary foods. It is prudent to avoid both early (<4 months) and late (>or=7 months) introduction of gluten, and to introduce gluten gradually while the infant is still breast-fed, inasmuch as this may reduce the risk of celiac disease, type 1 diabetes mellitus, and wheat allergy. Infants and young children receiving a vegetarian diet should receive a sufficient amount ( approximately 500 mL) of breast milk or formula and dairy products. Infants and young children should not be fed a vegan diet.", "title": "Complementary feeding: a commentary by the ESPGHAN Committee on Nutrition." }, { "docid": "MED-5133", "text": "We report the case of a 7 month-old girl that presented with acute anemia, generalized muscular hypotonia and failure to thrive. Laboratory evaluation revealed cobalamin deficiency, due to a vegan diet of the mother. The clinical triad of an acquired floppy baby syndrome with megaloblastic anemia and failure to thrive is pathognomic for infantile cobalamin deficiency. Neurological abnormalities are often irreversible and may be associated with delayed myelinization in the MRI. A normal cobalamin level in maternal serum and absence of anemia do not exclude subclinical deficiency. If cobalamin deficiency is suspected, e.g. in pregnant women on vegan diet, urinary methylmalonic acid excretion and plasma homocysteine levels should be determined and cobalamin substitution should be started at an early stage to avoid potentially irreversible damage of the fetus.", "title": "[Floppy baby with macrocytic anemia and vegan mother]." } ]
[ { "docid": "MED-991", "text": "Background Cognitive impairment without dementia is associated with increased risk for disability, increased health care costs, and progression to dementia. There are no population-based prevalence estimates of this condition in the United States. Objective To estimate the prevalence of cognitive impairment without dementia in the United States and determine longitudinal cognitive and mortality outcomes. Design Longitudinal study from July 2001 to March 2005. Setting In-home assessment for cognitive impairment. Participants Participants in ADAMS (Aging, Demographics, and Memory Study) who were age 71 years or older drawn from the nationally representative HRS (Health and Retirement Study). Of 1770 selected individuals, 856 completed initial assessment, and of 241 selected individuals, 180 completed 16- to 18-month follow-up assessment. Measurements Assessments, including neuropsychological testing, neurologic examination, and clinical and medical history, were used to assign a diagnosis of normal cognition, cognitive impairment without dementia, or dementia. National prevalence rates were estimated by using a population-weighted sample. Results In 2002, an estimated 5.4 million people (22.2%) in the United States age 71 years or older had cognitive impairment without dementia. Prominent subtypes included prodromal Alzheimer disease (8.2%) and cerebrovascular disease (5.7%). Among participants who completed follow-up assessments, 11.7% with cognitive impairment without dementia progressed to dementia annually, whereas those with subtypes of prodromal Alzheimer disease and stroke progressed at annual rates of 17% to 20%. The annual death rate was 8% among those with cognitive impairment without dementia and almost 15% among those with cognitive impairment due to medical conditions. Limitations Only 56% of the nondeceased target sample completed the initial assessment. Population sampling weights were derived to adjust for at least some of the potential bias due to nonresponse and attrition. Conclusion Cognitive impairment without dementia is more prevalent in the United States than dementia, and its subtypes vary in prevalence and outcomes.", "title": "Prevalence of Cognitive Impairment without Dementia in the United States" }, { "docid": "MED-1814", "text": "Pancreatic cancer is highly lethal, and identifying modifiable risk factors could have substantial public health impact. In this population-based case-control study (532 cases, 1701 controls), we used principal component analysis and multivariable unconditional logistic regression models to examine whether a particular dietary pattern was associated with risk of pancreatic cancer, adjusting for other known risk factors. A Prudent dietary pattern, characterized by greater intake of vegetables, fruit, fish, poultry, whole grains, and low-fat dairy, was associated with an approximate 50% reduction in pancreatic cancer risk among men (OR=0.51, 95% CI 0.31-0.84, p-trend=0.001) and women (OR=0.51, 95% CI 0.29-0.90, p-trend=0.04). A Western dietary pattern, characterized by higher intake of red and processed meats, potato chips, sugary beverages, sweets, high fat dairy, eggs, and refined grains, was associated with a 2.4-fold increased risk of pancreatic cancer among men (95% CI 1.3-4.2, p-trend=0.008); but was not associated with risk among women. Among men, those in the upper quintiles of the Western diet and lower quintiles of the Prudent diet had a 3-fold increased risk. Consistent with what has been recommended for several other chronic diseases, consuming a diet rich in plant-based foods, whole grains, and white meat, might reduce risk of pancreatic cancer.", "title": "Dietary patterns and risk of pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area" }, { "docid": "MED-2116", "text": "Over the past 10 years, the increase in comprehension of the mechanisms behind acne has been truly exponential. Starting with the ethnological work of Cordain, accelerated by the epidemiological work of Adebamowo, supported by the clinical trials of Smith and Mann, Kwon, DiLandro and others, the interface of diet and acne is coming into focus. Melnik now presents an exceptional pair of papers that illustrate for dermatologists what translational research is all about. The Western diet, the role of dairy, FoxO1 and mTORC1, the interplay of agonists and antagonists, therapeutics present and future – the jigsaw puzzle is coming together.", "title": "Turning acne on/off via mTORC1" }, { "docid": "MED-5050", "text": "Tea is the most widely consumed beverage in the world after water. Tea is known to be a rich source of flavonoid antioxidants. However tea also contains a unique amino acid, L-theanine that may modulate aspects of brain function in humans. Evidence from human electroencephalograph (EEG) studies show that it has a direct effect on the brain (Juneja et al. Trends in Food Science & Tech 1999;10;199-204). L-theanine significantly increases activity in the alpha frequency band which indicates that it relaxes the mind without inducing drowsiness. However, this effect has only been established at higher doses than that typically found in a cup of black tea (approximately 20mg). The aim of the current research was to establish this effect at more realistic dietary levels. EEG was measured in healthy, young participants at baseline and 45, 60, 75, 90 and 105 minutes after ingestion of 50mg L-theanine (n=16) or placebo (n=19). Participants were resting with their eyes closed during EEG recording. There was a greater increase in alpha activity across time in the L-theanine condition (relative to placebo (p+0.05). A second study replicated this effect in participants engaged in passive activity. These data indicate that L-theanine, at realistic dietary levels, has a significant effect on the general state of mental alertness or arousal. Furthermore, alpha activity is known to play an important role in critical aspects of attention, and further research is therefore focussed on understanding the effect of L-theanine on attentional processes.", "title": "L-theanine, a natural constituent in tea, and its effect on mental state." }, { "docid": "MED-4222", "text": "Life span extending mutations in growth signaling pathways protect against age-dependent DNA damage in yeast and decrease insulin resistance and cancer in mice. To test their effect in humans, we monitored for 22 years Ecuadorian subjects with mutations in the growth hormone receptor gene leading to severe growth hormone receptor (GHR) and IGF-I deficiencies and combined this information with surveys to identify the cause and age of death for subjects who died before this period. The individuals with GHR deficiency (GHRD) exhibited only one non-lethal malignancy and no cases of diabetes, in contrast to 17% cancer and 5% diabetes prevalence in the controls. A possible explanation for the very low incidence of cancer may be revealed by in vitro studies: serum from GHRD subjects reduced DNA breaks but increased apoptosis in human mammary epithelial cells (HMECs) treated with hydrogen peroxide. We also observed reduced insulin concentrations (1.4 μU/ml vs. 4.4μU/ml in unaffected relatives) and a very low homoeostasis model assessment of insulin resistance (HOMA-IR) index (0.34 vs. 0.96 in unaffected relatives) in GHRD individuals, indicating increased insulin sensitivity, which could explain the absence of diabetes in these subjects. Incubation of HMECs with GHRD serum also resulted in reduced expression of RAS, PKA and TOR, and up-regulation of SOD2, changes that promote cellular protection and life span extension in model organisms. These results provide evidence for a role of evolutionarily conserved pathways in promoting aging and diseases in humans and identify a candidate drug target for healthy life span extension.", "title": "Growth Hormone Receptor Deficiency is Associated With a Major Reduction in Pro-aging Signaling, Cancer and Diabetes in Humans" }, { "docid": "MED-869", "text": "Yerba Mate (Ilex paraguariensis) tea consumption is higher in Argentina and other South American countries than those of coffee or tea (Camellia sinensis). The effects of Yerba Mate on bone health have not previously been explored. From a program for osteoporosis prevention and treatment, postmenopausal women who drank at least 1 L of Yerba Mate tea daily during 4 or more years (n=146) were identified, and matched by age and time since menopause with an equal number of women who did not drink Yerba Mate tea. Their bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and femoral neck. Yerba Mate drinkers had a 9.7% higher lumbar spine BMD (0.952 g/cm(2) versus 0.858 g/cm(2): p<0.0001) and a 6.2% higher femoral neck BMD (0.817 g/cm(2) versus 0.776 g/cm(2); p=0.0002). In multiple regression analysis, Yerba Mate drinking was the only factor, other than body mass index, which showed a positive correlation with BMD at both the lumbar spine (p<0.0001) and the femoral neck (p=0.0028). Results suggest a protective effect of chronic Yerba Mate consumption on bone. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Yerba Mate (Ilex paraguariensis) consumption is associated with higher bone mineral density in postmenopausal women." }, { "docid": "MED-2517", "text": "Many experts in the biology of ageing believe that pharmacological interventions to slow ageing are a matter of ‘when’ rather than ‘if’. A leading target for such interventions is the nutrient response pathway defined by the mechanistic target of rapamycin (mTOR). Inhibition of this pathway extends lifespan in model organisms and confers protection against a growing list of age-related pathologies. Characterized inhibitors of this pathway are already clinically approved, and others are under development. Although adverse side effects currently preclude use in otherwise healthy individuals, drugs that target the mTOR pathway could one day become widely used to slow ageing and reduce age-related pathologies in humans.", "title": "mTOR is a key modulator of ageing and age-related disease" }, { "docid": "MED-1665", "text": "Insufficient blood supply to the intervertebral disc (IVD) has been proposed to play a role as causative factor in IVD degeneration. There is an association between IVD diseases and increased risk of dying of ischaemic heart disease. Obesity and tobacco are potential risk factors for degenerative IVD disease. High blood cholesterol and triglycerides serum levels are risk factors for atherosclerosis, and could be responsible for a decreased in the blood supply to the already poor vascularized IVD. We performed a frequency-matched case–control study to determine the serum levels of patients with symptomatic herniated lumbar disc. We examined the fasting serum lipid levels in 384 subjects who were operated at our institution. Group 1 included 169 consecutive patients (115 men and 54 women; mean age: 59.1 years, range 29–85) who underwent surgery for symptomatic disc herniation. Group 2 (control group) included 169 patients (115 men and 54 women; mean age: 61 years, range 26–86) who underwent arthroscopic meniscectomy for a meniscal tear in the same period. These patients were frequency-matched by age (within 3 years) and gender with patients of Group 1. Sera were extracted from blood samples and the concentrations of total cholesterol (TC) and triglycerides (TG) were determined. When comparing the two groups, patients with symptomatic herniated lumbar disc showed statistically significant higher triglyceride concentration (P = 0.02) and total cholesterol concentration (P = 0.01). Serum lipid levels may be a risk factor for IVD pathology. An enhanced understanding of these factors holds the promise of new approaches to the prevention and management of IVD pathology.", "title": "Symptomatic disc herniation and serum lipid levels" }, { "docid": "MED-2379", "text": "Objectives Metabolic syndrome is a precursor of diabetes and cardiovascular disease (CVD). Walnut ingestion has been shown to reduce CVD risk indices in diabetes. This randomized controlled crossover trial was performed to investigate the effects of daily walnut consumption on endothelial function and other biomarkers of cardiac risk in a population of overweight individuals with visceral adiposity. Methods Forty-six overweight adults (average age, 57.4 years; 28 women, 18 men) with elevated waist circumference and 1 or more additional signs of metabolic syndrome were randomly assigned to two 8-week sequences of walnut-enriched ad libitum diet and ad libitum diet without walnuts, which were separated by a 4-week washout period. The primary outcome measure was the change in flow-mediated vasodilation (FMD) of the brachial artery. Secondary measures included serum lipid panel, fasting glucose and insulin, Homeostasis Model Assessment–Insulin Resistance values, blood pressure, and anthropometric measures. Results FMD improved significantly from baseline when subjects consumed a walnut-enriched diet as compared with the control diet (1.4% ± 2.4% versus 0.3% ± 1.5%; p = 0.019). Beneficial trends in systolic blood pressure reduction were seen, and maintenance of the baseline anthropometric values was also observed. Other measures were unaltered. Conclusion Daily ingestion of 56 g of walnuts improves endothelial function in overweight adults with visceral adiposity. The addition of walnuts to the diet does not lead to weight gain. Further study of the potential role of walnut intake in diabetes and CVD prevention is warranted.", "title": "Effects of Walnuts on Endothelial Function in Overweight Adults with Visceral Obesity: A Randomized, Controlled, Crossover Trial" }, { "docid": "MED-1242", "text": "BACKGROUND: Recently, two centers have independently developed a risk score for predicting postoperative nausea and vomiting (PONV). This study investigated (1) whether risk scores are valid across centers and (2) whether risk scores based on logistic regression coefficients can be simplified without loss of discriminating power. METHODS: Adult patients from two centers (Oulu, Finland: n = 520, and Wuerzburg, Germany: n = 2202) received inhalational anesthesia (without antiemetic prophylaxis) for various types of surgery. PONV was defined as nausea or vomiting within 24 h of surgery. Risk scores to estimate the probability of PONV were obtained by fitting logistic regression models. Simplified risk scores were constructed based on the number of risk factors that were found significant in the logistic regression analyses. Original and simplified scores were cross-validated. A combined data set was created to estimate a potential center effect and to construct a final risk score. The discriminating power of each score was assessed using the area under the receiver operating characteristic curves. RESULTS: Risk scores derived from one center were able to predict PONV from the other center (area under the curve = 0.65-0.75). Simplification did not essentially weaken the discriminating power (area under the curve = 0.63-0.73). No center effect could be detected in a combined data set (odds ratio = 1.06, 95% confidence interval = 0.71-1.59). The final score consisted of four predictors: female gender, history of motion sickness (MS) or PONV, nonsmoking, and the use of postoperative opioids. If none, one, two, three, or four of these risk factors were present, the incidences of PONV were 10%, 21%, 39%, 61% and 79%. CONCLUSIONS: The risk scores derived from one center proved valid in the other and could be simplified without significant loss of discriminating power. Therefore, it appears that this risk score has broad applicability in predicting PONV in adult patients undergoing inhalational anesthesia for various types of surgery. For patients with at least two out of these four identified predictors a prophylactic antiemetic strategy should be considered.", "title": "A simplified risk score for predicting postoperative nausea and vomiting: conclusions from cross-validations between two centers." }, { "docid": "MED-3681", "text": "OBJECTIVE: To determine the effects of the probiotic lactic acid bacterium, Lactobacillus rhamnosus HN001, on natural cellular immunity when delivered orally in normal low-fat milk (LFM) or lactose-hydrolyzed low-fat milk (LFM-LH). DESIGN: A three stage, pre-post intervention trial, spanning nine weeks. SETTING: Taipei Medical College Hospital, Taipei, Taiwan. SUBJECTS: Fifty-two healthy middle-aged and elderly volunteers (17 males, 35 females; median age 63.5, range 44-80). INTERVENTIONS: Stage 1 (run-in diet): 25 g/200 mL reconstituted LFM powder, twice daily for 3 weeks. Stage 2 (probiotic intervention): LFM or LFM-LH, supplemented with 10(9) CFUs/g L. rhamnosus HN001 in each case, for 3 weeks. Stage 3 (wash-out): LFM for 3 weeks. MEASURES OF OUTCOME: In vitro phagocytic capacity of peripheral blood polymorphonuclear (PMN) leukocytes; in vitro tumoricidal activity of natural killer (NK) leukocytes. RESULTS: Immunological responses were unaffected by the run-in diet of LFM alone. In contrast, the relative proportion of PMN cells showing phagocytic activity increased by 19% and 15%, respectively, following consumption of HN001 in either LFM or LFM-LH; the relative level of NK cell tumor killing activity increased by 71% and 147%. In most cases these levels declined following cessation, but remained above baseline. CONCLUSIONS: Dietary consumption of L. rhamnosus HN001, in a base of low-fat milk or lactose-hydrolyzed low-fat milk, appears to enhance systemic cellular immune responses and may be useful as a dietary supplement to boost natural immunity.", "title": "Systemic immunity-enhancing effects in healthy subjects following dietary consumption of the lactic acid bacterium Lactobacillus rhamnosus HN001." }, { "docid": "MED-1381", "text": "Perhaps one of the most unexpected and novel findings in nutritional epidemiology in the past 5 y has been that nut consumption seems to protect against ischemic heart disease (IHD). Frequency and quantity of nut consumption have been documented to be higher in vegetarian than in nonvegetarian populations. Nuts also constitute an important part of other plant-based diets, such as Mediterranean and Asian diets. In a large, prospective epidemiologic study of Seventh-day Adventists in California, we found that frequency of nut consumption had a substantial and highly significant inverse association with risk of myocardial infarction and death from IHD. The Iowa Women's Health Study also documented an association between nut consumption and decreased risk of IHD. The protective effect of nuts on IHD has been found in men and women and in the elderly. Importantly, nuts have similar associations in both vegetarians and nonvegetarians. The protective effect of nut consumption on IHD is not offset by increased mortality from other causes. Moreover, frequency of nut consumption has been found to be inversely related to all-cause mortality in several population groups such as whites, blacks, and the elderly. Thus, nut consumption may not only offer protection against IHD, but also increase longevity.", "title": "Nut consumption, vegetarian diets, ischemic heart disease risk, and all-cause mortality: evidence from epidemiologic studies." }, { "docid": "MED-2492", "text": "Background: Inorganic arsenic (iAs) causes cancer and possibly other adverse health outcomes. Arsenic-based drugs are permitted in poultry production; however, the contribution of chicken consumption to iAs intake is unknown. Objectives: We sought to characterize the arsenic species profile in chicken meat and estimate bladder and lung cancer risk associated with consuming chicken produced with arsenic-based drugs. Methods: Conventional, antibiotic-free, and organic chicken samples were collected from grocery stores in 10 U.S. metropolitan areas from December 2010 through June 2011. We tested 116 raw and 142 cooked chicken samples for total arsenic, and we determined arsenic species in 65 raw and 78 cooked samples that contained total arsenic at ≥ 10 µg/kg dry weight. Results: The geometric mean (GM) of total arsenic in cooked chicken meat samples was 3.0 µg/kg (95% CI: 2.5, 3.6). Among the 78 cooked samples that were speciated, iAs concentrations were higher in conventional samples (GM = 1.8 µg/kg; 95% CI: 1.4, 2.3) than in antibiotic-free (GM = 0.7 µg/kg; 95% CI: 0.5, 1.0) or organic (GM = 0.6 µg/kg; 95% CI: 0.5, 0.8) samples. Roxarsone was detected in 20 of 40 conventional samples, 1 of 13 antibiotic-free samples, and none of the 25 organic samples. iAs concentrations in roxarsone-positive samples (GM = 2.3 µg/kg; 95% CI: 1.7, 3.1) were significantly higher than those in roxarsone-negative samples (GM = 0.8 µg/kg; 95% CI: 0.7, 1.0). Cooking increased iAs and decreased roxarsone concentrations. We estimated that consumers of conventional chicken would ingest an additional 0.11 µg/day iAs (in an 82-g serving) compared with consumers of organic chicken. Assuming lifetime exposure and a proposed cancer slope factor of 25.7 per milligram per kilogram of body weight per day, this increase in arsenic exposure could result in 3.7 additional lifetime bladder and lung cancer cases per 100,000 exposed persons. Conclusions: Conventional chicken meat had higher iAs concentrations than did conventional antibiotic-free and organic chicken meat samples. Cessation of arsenical drug use could reduce exposure and the burden of arsenic-related disease in chicken consumers.", "title": "Roxarsone, Inorganic Arsenic, and Other Arsenic Species in Chicken: A U.S.-Based Market Basket Sample" }, { "docid": "MED-4508", "text": "Nitrate, an inorganic anion abundant in vegetables, is converted in vivo to bioactive nitrogen oxides including NO. We recently demonstrated that dietary nitrate reduces oxygen cost during physical exercise, but the mechanism remains unknown. In a double-blind crossover trial we studied the effects of a dietary intervention with inorganic nitrate on basal mitochondrial function and whole-body oxygen consumption in healthy volunteers. Skeletal muscle mitochondria harvested after nitrate supplementation displayed an improvement in oxidative phosphorylation efficiency (P/O ratio) and a decrease in state 4 respiration with and without atractyloside and respiration without adenylates. The improved mitochondrial P/O ratio correlated to the reduction in oxygen cost during exercise. Mechanistically, nitrate reduced the expression of ATP/ADP translocase, a protein involved in proton conductance. We conclude that dietary nitrate has profound effects on basal mitochondrial function. These findings may have implications for exercise physiology- and lifestyle-related disorders that involve dysfunctional mitochondria. Copyright © 2011 Elsevier Inc. All rights reserved.", "title": "Dietary inorganic nitrate improves mitochondrial efficiency in humans." }, { "docid": "MED-2110", "text": "Almost all types of newborn respiratory failure are reversible. However, supportive treatment (oxygen and positive airway pressure) can damage the lung, and newborn respiratory failure remains a major cause of morbidity and death in infants. Prolonged extracorporeal membrane oxygenation (ECMO) provides life support while allowing the lung to \"rest.\" We have used ECMO in 45 moribund newborn infants; 25 survived. Neonatologists referred patients who were unresponsive to maximal therapy. The right atrium and aortic arch were cannulated via the jugular vein and carotid artery. Heparin was infused continuously to main activated clotting time at 200 to 300 seconds. Airway oxygenation and pressure were reduced to low levels. Primary diagnoses were hyaline membrane disease, 14 (6 survived, 8 died); meconium aspiration, 22 (15 survived, 7 died); persistent fetal circulation including diaphragmatic hernia, 5 (3 survived, 2 died); and sepsis, 4 (1 survived, 3 died). Growth, development, and brain and lung function are normal in 20 of 25 survivors. ECMO decreased newborn respiratory failure mortality and morbidity rates in this phase I trial. A controlled randomized study is underway. The results suggest that ECMO may be effective in older patients if used before irreversible lung damage occurs.", "title": "Extracorporeal membrane oxygenation for newborn respiratory failure: forty-five cases." }, { "docid": "MED-5246", "text": "BACKGROUND: Caffeine is widely consumed, and its effect on intraocular pressure (IOP) has been reported in conflicting data. The aim of this meta-analysis was to quantitatively summarize the effect of caffeine on IOP in normal individuals and in patients with glaucoma or ocular hypertension (OHT). METHODS: A comprehensive literature search was performed using the Cochrane Collaboration methodology to identify pertinent randomized controlled trials (RCTs) from the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed and EMBASE. A systematic review and meta-analysis was performed. IOP at 0.5 hour (h), 1 h and 1.5 h after caffeine ingestion was the main outcome measurement. RESULTS: Six RCTs (two parallel-designed and four crossover-designed) evaluating 144 participants fulfilled inclusion criteria. The risk of bias for these studies was uncertain. Among the participants, 103 were normal individuals and 41 were patients with glaucoma or OHT. In normal individuals, the IOPs measured at 0.5 h, 1 h and 1.5 h post-intervention were not affected by ingestion of caffeine. The weighted mean difference (WMD) with 95% confidence intervals (95%CI) for each measurement point were -0.740 (-2.454, 0.974), 0.522 (-0.568, 1.613) and 0.580 (-1.524, 2.684). However, in patients with glaucoma or OHT, IOP increased at each measurement point, with the WMD and 95%CI being 0.347 (0.078, 0.616), 2.395 (1.741,3.049) and 1.998 (1.522,2.474) respectively. No publication bias was detected by either Begg's or Egger's test. CONCLUSION: Available evidences showed that caffeine had different effects on IOP in different groups of individuals. For normal individuals, IOP was not changed by ingestion of caffeine, while for patients with glaucoma or OHT, IOP increased significantly. More high-quality RCTs are warranted to confirm this. The mechanisms underlying this phenomenon and the clinical significance are to be explored.", "title": "The effect of caffeine on intraocular pressure: a systematic review and meta-analysis." }, { "docid": "MED-3970", "text": "Various specific and non-specific environmental factors have been associated with the induction and/or exacerbation of disease activity in patients with Crohn's disease and ulcerative colitis. One such factor is the potential role of ingested ultrafine particles. In fact, based on a Western diet, recent data suggest that more than 10(12)ultrafine particles are ingested per person every day. These microparticles have been considered inert although they adsorb endogenous constituents of the intestinal lumen and are taken up by human intestinal lymphoid aggregates. Based on these observations, we determined whether one such dietary microparticle, titanium dioxide (TiO(2)), alters intestinal cell responsiveness to lipopolysaccharide (LPS) using colonic biopsy specimens from 28 patients with ulcerative colitis, 21 with Crohn's disease, and 36 healthy controls. These samples, as well as peripheral blood mononuclear cells when available, were incubated alone (control), or with either (a) LPS (1-2,000 ng/ml), (b) TiO(2)(5 microg/ml) or (c) LPS (1 ng/ml) adsorbed to TiO(2)(5 microg/ml). In each case, the levels of interleukin 1 (IL-1) produced in these assays were quantitated by bioassay and by ELISA. Interestingly, there was dramatic stimulation of peripheral blood mononuclear cells using the TiO(2)-LPS conjugate, with values 30-60-fold above controls and only minor stimulation with LPS or TiO(2)alone. In intestinal organ cultures there was no increase in IL-1 secretion when challenged with TiO(2)alone or with up to 2,000 ng/ml LPS. However, the TiO(2)-LPS conjugate produced a two-to-three-fold, significant increase in the intestinal secretion of IL-1. Our data demonstrate that ultrafine dietary particles are not immunologically inert and may be important adjuncts in overcoming normal gut cell hyporesponsiveness to endogenous luminal molecules. This may be particularly relevant to patients with inflammatory bowel disease where there is abnormal intestinal permeability. Copyright 2000 Academic Press.", "title": "Immune potentiation of ultrafine dietary particles in normal subjects and patients with inflammatory bowel disease." }, { "docid": "MED-3430", "text": "BACKGROUND: Erectile dysfunction (ED) shares similar modifiable risks factors with coronary artery disease (CAD). Lifestyle modification that targets CAD risk factors may also lead to improvement in ED. We conducted a systematic review and meta-analysis of randomized controlled trials evaluating the effect of lifestyle interventions and pharmacotherapy for cardiovascular (CV) risk factors on the severity of ED. METHODS: A comprehensive search of multiple electronic databases through August 2010 was conducted using predefined criteria. We included randomized controlled clinical trials with follow-up of at least 6 weeks of lifestyle modification intervention or pharmacotherapy for CV risk factor reduction. Studies were selected by 2 independent reviewers. The main outcome measure of the study is the weighted mean differences in the International Index of Erectile Dysfunction (IIEF-5) score with 95% confidence intervals (CIs) using a random effects model. RESULTS: A total of 740 participants from 6 clinical trials in 4 countries were identified. Lifestyle modifications and pharmacotherapy for CV risk factors were associated with statistically significant improvement in sexual function (IIEF-5 score): weighted mean difference, 2.66 (95% CI, 1.86-3.47). If the trials with statin intervention (n = 143) are excluded, the remaining 4 trials of lifestyle modification interventions (n = 597) demonstrate statistically significant improvement in sexual function: weighted mean difference, 2.40 (95% CI, 1.19-3.61). CONCLUSION: The results of our study further strengthen the evidence that lifestyle modification and pharmacotherapy for CV risk factors are effective in improving sexual function in men with ED.", "title": "The effect of lifestyle modification and cardiovascular risk factor reduction on erectile dysfunction: a systematic review and meta-analysis." }, { "docid": "MED-3170", "text": "Background Few studies have focused on the cognitive morbidity of neurocysticercosis (NCC), one of the most common parasitic infections of the central nervous system. We longitudinally assessed the cognitive status and quality of life (QoL) of patients with incident symptomatic NCC cases and matched controls. Methodology/Principal Findings The setting of the study was the Sabogal Hospital and Cysticercosis Unit, Department of Transmissible Diseases, National Institute of Neurological Sciences, Lima, Peru. The design was a longitudinal study of new onset NCC cases and controls. Participants included a total of 14 patients with recently diagnosed NCC along with 14 healthy neighborhood controls and 7 recently diagnosed epilepsy controls. A standardized neuropsychological battery was performed at baseline and at 6 months on NCC cases and controls. A brain MRI was performed in patients with NCC at baseline and 6 months. Neuropsychological results were compared between NCC cases and controls at both time points. At baseline, patients with NCC had lower scores on attention tasks (p<0.04) compared with epilepsy controls but no significant differences compared to healthy controls. Six months after receiving anti-parasitic treatment, the NCC group significantly improved on tasks involving psychomotor speed (p<0.02). QoL at baseline suggested impaired mental function and social function in both the NCC and epilepsy group compared with healthy controls. QoL gains in social function (p = 0.006) were noted at 6 months in patients with NCC. Conclusions/Significance Newly diagnosed patients with NCC in this sample had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment. Author Summary Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system. Cognitive changes have been frequently reported with this disease but have not been well studied. Our study team recruited a group of new onset NCC cases and a matched set of healthy neighborhood controls and new onset epilepsy controls in Lima, Peru for this study. A neuropsychological battery was administered at baseline and at 6 months to all groups. Brain MRI studies were also obtained on NCC cases at baseline and at 6 months. Newly diagnosed patients with NCC had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment. This study is the first to assess cognitive status and quality of life longitudinally in patients with NCC and provides new data on an important clinical morbidity outcome.", "title": "Cognitive Changes and Quality of Life in Neurocysticercosis: A Longitudinal Study" }, { "docid": "MED-4512", "text": "A cross-sectional survey was conducted in order to describe the use of oral cobalamin among geriatricians, hematologists, and general practitioners, and to explore factors related to its use. The study population consisted of all geriatricians (n = 138) and hematologists (n = 317) listed in the Canadian Medical Directory plus a random sample of 307 general practitioners. The overall response rate was 40%. Intramuscular and oral cobalamin was prescribed by 76 and 32% of the respondents, respectively. Twenty seven percent reported using both oral and intramuscular cobalamin and 6% reported using only oral cobalamin. Only 25% of respondents indicated they were aware of a RCT demonstrating the efficacy of oral cobalamin prior to reading a synopsis of the study in the survey. After multivariate adjustment, only the belief that oral cobalamin was effective and certainty about who carried oral preparations remained independently associated with oral cobalamin use. Oral cobalamin has been shown to be an efficacious, cost efficient and safe method of treating cobalamin deficiency. Nonetheless, it is not used by the majority of physicians treating this condition. Strategies to promote the use of oral cobalamin should be directed at educating physicians of its efficacy and providing them with prescribing information on where it can be purchased.", "title": "Oral cobalamin remains medicine's best kept secret." }, { "docid": "MED-4472", "text": "N-Nitroso compounds were known almost 40 years ago to be present in food treated with sodium nitrite, which made fish meal hepatotoxic to animals through formation of nitrosodimethylamine (NDMA). Since that time, N-nitroso compounds have been shown in animal experiments to be the most broadly acting and the most potent group of carcinogens. The key role of nitrite and nitrogen oxides in forming N-nitroso compounds by interaction with secondary and tertiary amino compounds has led to the examination worldwide of foods for the presence of N-nitroso compounds, which have been found almost exclusively in those foods containing nitrite or which have become exposed to nitrogen oxides. Among these are cured meats, especially bacon-and especially when cooked; concentrations of 100 micrograms kg(-1) have been found or, more usually, near 10 micrograms kg(-1). This would correspond to consumption of 1 microgram of NDMA in a 100-g portion. Much higher concentrations of NDMA (but lower ones of other nitrosamines) have been found in Japanese smoked and cured fish (more than 100 micrograms kg(-1)). Beer is one source of NDMA, in which as much as 70 micrograms l(-1) has been reported in some types of German beer, although usual levels are much lower (10 or 5 micrograms l(-1)); this could mean a considerable intake for a heavy beer drinker of several liters per day. Levels of nitrosamines have been declining during the past three decades, concurrent with a lowering of the nitrite used in food and greater control of exposure of malt to nitrogen oxides in beer making. There have been declines of N-nitroso compound concentrations in many foods during the past two decades. The small amounts of nitrosamines in food are nonetheless significant because of the possibility-even likelihood-that humans are more sensitive to these carcinogens than are laboratory rodents. Although it is probable that alkylnitrosamides (which induce brain tumors in rodents) are present in cured meats and other potentially nitrosated products in spite of much searching, there has been only limited indirect evidence of their presence. Copyright 1999 Elsevier Science B.V.", "title": "N-Nitroso compounds in the diet." }, { "docid": "MED-4464", "text": "Over the last decade, the notion that tumors are maintained by their own stem cells, the so-called cancer stem cells, has created great excitement in the research community. This review attempts to summarize the underlying concepts of this notion, to distinguish hard facts from beliefs and to define the future challenges of the field.", "title": "The cancer stem cell: premises, promises and challenges." }, { "docid": "MED-3706", "text": "Autoimmune diseases are complex diseases resulting of the interaction between both genetics and environmental factors over time. Different phases in the development of autoimmune diseases are characterized by the detection of serum autoantibodies several months or years before the onset of clinical manifestations and subsequent diagnosis. In addition to serum antibodies, genetic susceptibility factors may predict the future development of the disease. Currently, prediction in type 1 diabetes is the most accurate, with the analysis of genetic susceptibility factors in first-degree relatives of patients and several autoantibody tests. In the future, multiple antibodies test, in combination with the analysis of genetics, epigenetics and immunological anomalies in fine models may allow the precise prediction in autoimmune diseases. Prevention measures might thus be introduced as an attempt to avoid or delay the disease. Copyright © 2011 Elsevier B.V. All rights reserved.", "title": "Are autoimmune diseases predictable?" }, { "docid": "MED-3654", "text": "Nutrient profiling of foods, described as the science of ranking foods based on their nutrient content, is fast becoming the basis for regulating nutrition labels, health claims, and marketing and advertising to children. A number of nutrient profile models have now been developed by research scientists, regulatory agencies, and by the food industry. Whereas some of these models have focused on nutrients to limit, others have emphasized nutrients known to be beneficial to health, or some combination of both. Although nutrient profile models are often tailored to specific goals, the development process ought to follow the same science-driven rules. These include the selection of index nutrients and reference amounts, the development of an appropriate algorithm for calculating nutrient density, and the validation of the chosen nutrient profile model against healthy diets. It is extremely important that nutrient profiles be validated rather than merely compared to prevailing public opinion. Regulatory agencies should act only when they are satisfied that the scientific process has been followed, that the algorithms are transparent, and that the profile model has been validated with respect to objective measures of a healthy diet.", "title": "Nutrient profiling of foods: creating a nutrient-rich food index." }, { "docid": "MED-2055", "text": "BACKGROUND: Chronic diarrhea is the most common gastrointestinal symptom of intolerance of cow's milk among children. On the basis of a prior open study, we hypothesized that intolerance of cow's milk can also cause severe perianal lesions with pain on defecation and consequent constipation in young children. METHODS: We performed a double-blind, crossover study comparing cow's milk with soy milk in 65 children (age range, 11 to 72 months) with chronic constipation (defined as having one bowel movement every 3 to 15 days). All had been referred to a pediatric gastroenterology clinic and had previously been treated with laxatives without success; 49 had anal fissures and perianal erythema or edema. After 15 days of observation, the patients received cow's milk or soy milk for two weeks. After a one-week washout period, the feedings were reversed. A response was defined as eight or more bowel movements during a treatment period. RESULTS: Forty-four of the 65 children (68 percent) had a response while receiving soy milk. Anal fissures and pain with defecation resolved. None of the children who received cow's milk had a response. In all 44 children with a response, the response was confirmed with a double-blind challenge with cow's milk. Children with a response had a higher frequency of coexistent rhinitis, dermatitis, or bronchospasm than those with no response (11 of 44 children vs. 1 of 21, P=0.05); they were also more likely to have anal fissures and erythema or edema at base line (40 of 44 vs. 9 of 21, P<0.001), evidence of inflammation of the rectal mucosa on biopsy (26 of 44 vs. 5 of 21, P=0.008), and signs of hypersensitivity, such as specific IgE antibodies to cow's-milk antigens (31 of 44 vs. 4 of 21, P<0.001). CONCLUSIONS: In young children, chronic constipation can be a manifestation of intolerance of cow's milk.", "title": "Intolerance of cow's milk and chronic constipation in children." }, { "docid": "MED-2495", "text": "We investigated whether prenatal exposure from the maternal diet to the toxicants polychlorinated biphenyls (PCBs) and dioxins is associated with the development of immune-related diseases in childhood. Children participating in BraMat, a sub-cohort of the Norwegian Mother and Child Cohort Study (MoBa), were followed in the three first years of life using annual questionnaires (0-3years; n=162, 2-3years; n=180), and blood parameters were examined at three years of age (n=114). The maternal intake of the toxicants was calculated using a validated food frequency questionnaire from MoBa. Maternal exposure to PCBs and dioxins was found to be associated with an increased risk of wheeze and more frequent upper respiratory tract infections. Furthermore, maternal exposure to PCBs and dioxins was found to be associated with reduced antibody response to a measles vaccine. No associations were found between prenatal exposure and immunophenotype data, allergic sensitization and vaccine-induced antibody responses other than measles. Our results suggest that prenatal dietary exposure to PCBs and dioxins may increase the risk of wheeze and the susceptibility to infectious diseases in early childhood. Copyright © 2012 Elsevier Ltd. All rights reserved.", "title": "Prenatal exposure to polychlorinated biphenyls and dioxins from the maternal diet may be associated with immunosuppressive effects that persist int..." }, { "docid": "MED-2156", "text": "BACKGROUND: Coffee is associated with a reduced risk of hepatocellular carcinoma in patients with chronic C hepatitis. This prospective trial was aimed at assessing the mechanisms underlying coffee-related protective effects. METHODS: Forty patients with chronic hepatitis C were randomized into two groups: the first consumed 4 cups of coffee/day for 30 days, while the second remained coffee \"abstinent\". At day 30, the groups were switched over for a second month. RESULTS: At baseline, aspartate aminotransferase and alanine aminotransferase were lower in patients drinking 3-5 (Group B) than 0-2 cups/day (Group A) (56 ± 6 vs 74 ± 11/60 ± 3 vs 73 ± 7 U/L p=0.05/p=0.04, respectively). HCV-RNA levels were significantly higher in Group B [(6.2 ± 1.5) × 10(5)vs (3.9 ± 1.0) × 10(5)UI/mL, p=0.05]. During coffee intake, 8-hydroxydeoxyguanosine and collagen levels were significantly lower than during abstinence (15 ± 3 vs 44 ± 16 8-hydroxydeoxyguanosine/10(5)deoxyguanosine, p=0.05 and 56 ± 9 vs 86 ± 21 ng/mL, p=0.04). Telomere length was significantly higher in patients during coffee intake (0.68 ± 0.06 vs 0.48 ± 0.04 Arbitrary Units, p=0.006). Telomere length and 8-hydroxydeoxyguanosine were inversely correlated. CONCLUSION: In chronic hepatitis C coffee consumption induces a reduction in oxidative damage, correlated with increased telomere length and apoptosis, with lower collagen synthesis, factors that probably mediate the protection exerted by coffee with respect to disease progression. Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.", "title": "Effects of coffee consumption in chronic hepatitis C: a randomized controlled trial." }, { "docid": "MED-1721", "text": "Objective To examine the relation between body mass index (kg/m2) and cancer incidence and mortality. Design Prospective cohort study. Participants 1.2 million UK women recruited into the Million Women Study, aged 50-64 during 1996-2001, and followed up, on average, for 5.4 years for cancer incidence and 7.0 years for cancer mortality. Main outcome measures Relative risks of incidence and mortality for all cancers, and for 17 specific types of cancer, according to body mass index, adjusted for age, geographical region, socioeconomic status, age at first birth, parity, smoking status, alcohol intake, physical activity, years since menopause, and use of hormone replacement therapy. Results 45 037 incident cancers and 17 203 deaths from cancer occurred over the follow-up period. Increasing body mass index was associated with an increased incidence of endometrial cancer (trend in relative risk per 10 units=2.89, 95% confidence interval 2.62 to 3.18), adenocarcinoma of the oesophagus (2.38, 1.59 to 3.56), kidney cancer (1.53, 1.27 to 1.84), leukaemia (1.50, 1.23 to 1.83), multiple myeloma (1.31, 1.04 to 1.65), pancreatic cancer (1.24, 1.03 to 1.48), non-Hodgkin's lymphoma (1.17, 1.03 to 1.34), ovarian cancer (1.14, 1.03 to 1.27), all cancers combined (1.12, 1.09 to 1.14), breast cancer in postmenopausal women (1.40, 1.31 to 1.49) and colorectal cancer in premenopausal women (1.61, 1.05 to 2.48). In general, the relation between body mass index and mortality was similar to that for incidence. For colorectal cancer, malignant melanoma, breast cancer, and endometrial cancer, the effect of body mass index on risk differed significantly according to menopausal status. Conclusions Increasing body mass index is associated with a significant increase in the risk of cancer for 10 out of 17 specific types examined. Among postmenopausal women in the UK, 5% of all cancers (about 6000 annually) are attributable to being overweight or obese. For endometrial cancer and adenocarcinoma of the oesophagus, body mass index represents a major modifiable risk factor; about half of all cases in postmenopausal women are attributable to overweight or obesity.", "title": "Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study" }, { "docid": "MED-1584", "text": "Advances in assisted reproductive technology and increases in the proportion of maternities in older women have both contributed to the steep increase in the incidence of twin pregnancies since the 1980s. Maternal and perinatal complications are higher in twins than in singleton pregnancies. A significant proportion of perinatal mortality and morbidity among twins is due to the high incidence of preterm delivery and the added complication of twin-to-twin transfusion syndrome (TTTS) in monochorionic twins. Monochorionic twins also have a much higher rate of perinatal mortality than dichorionic twins, the greatest risk being before fetal viability (<24 weeks gestation). Early diagnosis of twins and their chorionicity, close fetal surveillance, particularly of monochorionic twins, and prompt therapeutic intervention in TTS are necessary to reduce perinatal mortality. Intrapartum management in the hospital setting with anaesthetic and neonatal facilities, as well as critical assessment of mode of delivery, have led to better outcomes. Ultrasonography is a valuable tool in the management of twin pregnancy. This chapter briefly summarises these topics, with a particular focus on recent literature.", "title": "Obstetric complications of twin pregnancies." }, { "docid": "MED-3019", "text": "Background: Methylmercury (MeHg) is a known neuro-toxicant. Emerging evidence indicates it may have adverse effects on the neuro-logic and other body systems at common low levels of exposure. Impacts of MeHg exposure could vary by individual susceptibility or be confounded by bene-ficial nutrients in fish containing MeHg. Despite its global relevance, synthesis of the available literature on low-level MeHg exposure has been limited. Objectives: We undertook a synthesis of the current knowledge on the human health effects of low-level MeHg exposure to provide a basis for future research efforts, risk assessment, and exposure remediation policies worldwide. Data sources and extraction: We reviewed the published literature for original human epidemio-logic research articles that reported a direct biomarker of mercury exposure. To focus on high-quality studies and those specifically on low mercury exposure, we excluded case series, as well as studies of populations with unusually high fish consumption (e.g., the Seychelles), marine mammal consumption (e.g., the Faroe Islands, circumpolar, and other indigenous populations), or consumption of highly contaminated fish (e.g., gold-mining regions in the Amazon). Data synthesis: Recent evidence raises the possibility of effects of low-level MeHg exposure on fetal growth among susceptible subgroups and on infant growth in the first 2 years of life. Low-level effects of MeHg on neuro-logic outcomes may differ by age, sex, and timing of exposure. No clear pattern has been observed for cardio-vascular disease (CVD) risk across populations or for specific CVD end points. For the few studies evaluating immunologic effects associated with MeHg, results have been inconsistent. Conclusions: Studies targeted at identifying potential mechanisms of low-level MeHg effects and characterizing individual susceptibility, sexual dimorphism, and non-linearity in dose response would help guide future prevention, policy, and regulatory efforts surrounding MeHg exposure.", "title": "Evidence on the Human Health Effects of Low-Level Methylmercury Exposure" } ]
853
Nonhuman primates are incapable of producing neutralizing antibodies in reponse to the Eilat virus (EILV) produced in mosquitos.
[ { "docid": "24922825", "text": "Traditionally, vaccine development involves tradeoffs between immunogenicity and safety. Live-attenuated vaccines typically offer rapid and durable immunity but have reduced safety when compared to inactivated vaccines. In contrast, the inability of inactivated vaccines to replicate enhances safety at the expense of immunogenicity, often necessitating multiple doses and boosters. To overcome these tradeoffs, we developed the insect-specific alphavirus, Eilat virus (EILV), as a vaccine platform. To address the chikungunya fever (CHIKF) pandemic, we used an EILV cDNA clone to design a chimeric virus containing the chikungunya virus (CHIKV) structural proteins. The recombinant EILV/CHIKV was structurally identical at 10 Å to wild-type CHIKV, as determined by single-particle cryo-electron microscopy, and it mimicked the early stages of CHIKV replication in vertebrate cells from attachment and entry to viral RNA delivery. Yet the recombinant virus remained completely defective for productive replication, providing a high degree of safety. A single dose of EILV/CHIKV produced in mosquito cells elicited rapid (within 4 d) and long-lasting (>290 d) neutralizing antibodies that provided complete protection in two different mouse models. In nonhuman primates, EILV/CHIKV elicited rapid and robust immunity that protected against viremia and telemetrically monitored fever. Our EILV platform represents the first structurally native application of an insect-specific virus in preclinical vaccine development and highlights the potential application of such viruses in vaccinology.", "title": "A chikungunya fever vaccine utilizing an insect-specific virus platform" } ]
[ { "docid": "152245", "text": "The genomic RNA of an alphavirus encodes four different nonstructural proteins, nsP1, nsP2, nsP3, and nsP4. The polyprotein P123 is produced when translation terminates at an opal termination codon between nsP3 and nsP4. The polyprotein P1234 is produced when translational readthrough occurs or when the opal termination codon has been replaced by a sense codon in the alphavirus genome. Evolutionary pressures appear to have maintained genomic sequences encoding both a stop codon (opal) and an open reading frame (arginine) as a general feature of the O'nyong-nyong virus (ONNV) genome, indicating that both are required at some point. Alternate replication of ONNVs in both vertebrate and invertebrate hosts may determine predominance of a particular codon at this locus in the viral quasispecies. However, no systematic study has previously tested this hypothesis in whole animals. We report here the results of the first study to investigate in a natural mosquito host the functional significance of the opal stop codon in an alphavirus genome. We used a full-length cDNA clone of ONNV to construct a series of mutants in which the arginine between nsP3 and nsP4 was replaced with an opal, ochre, or amber stop codon. The presence of an opal stop codon upstream of nsP4 nearly doubled (75.5%) the infectivity of ONNV over that of virus possessing a codon for the amino acid arginine at the corresponding position (39.8%). Although the frequency with which the opal virus disseminated from the mosquito midgut did not differ significantly from that of the arginine virus on days 8 and 10, dissemination did began earlier in mosquitoes infected with the opal virus. Although a clear fitness advantage is provided to ONNV by the presence of an opal codon between nsP3 and nsP4 in Anopheles gambiae, sequence analysis of ONNV RNA extracted from mosquito bodies and heads indicated codon usage at this position corresponded with that of the virus administered in the blood meal. These results suggest that while selection of ONNV variants is occurring, de novo mutation at the position between nsP3 and nsP4 does not readily occur in the mosquito. Taken together, these results suggest that the primary fitness advantage provided to ONNV by the presence of an opal codon between nsP3 and nsP4 is related to mosquito infectivity.", "title": "Effects of an opal termination codon preceding the nsP4 gene sequence in the O'Nyong-Nyong virus genome on Anopheles gambiae infectivity." }, { "docid": "10494012", "text": "Amodel that explains both the origin and sporadic nature of cancer argues that cancer cells are a chance result of events that cause genomic and epigenetic variability. The prevailing view is that these events are mutations that affect chromosome segregation or stability. However, genomic and epigenetic variability is also triggered by cell fusion, which is often caused by viruses. Yet, cells fused by viruses are considered harmless because they die. We provide evidence that a primate virus uses both viral and exosomal proteins involved in cell fusion to produce transformed proliferating human cells. Although normal cells indeed fail to proliferate after fusion, expression of an oncogene or a mutated tumor suppressor p53 in just one of the fusion partners is sufficient to produce heterogeneous progeny. We also show that this virus can produce viable oncogenically transformed cells by fusing cells that are otherwise destined to die. Therefore, we argue that viruses can contribute to carcinogenesis by fusing cells.", "title": "A primate virus generates transformed human cells by fusion" }, { "docid": "8883846", "text": "The Global HIV Vaccine Enterprise convened a two-day workshop in May of 2007 to discuss humoral immune responses to HIV and approaches to design vaccines that induce viral neutralizing and other potentially protective antibody responses. The goals of this workshop were to identify key scientific issues, gaps, and opportunities that have emerged since the Enterprise Strategic Plan was first published in 2005 [1], and to make recommendations that Enterprise stakeholders can use to plan new activities. Most effective viral vaccines work, at least in part, by generating antibodies that inactivate or neutralize the invading virus, and the existing data strongly suggest that an optimally effective HIV-1 vaccine should elicit potent antiviral neutralizing antibodies. However, unlike acute viral pathogens, HIV-1 chronically replicates in the host and evades the antibody response. This immune evasion, along with the large genetic variation among HIV-1 strains worldwide, has posed major obstacles to vaccine development. Current HIV vaccine candidates do not elicit neutralizing antibodies against most circulating virus strains, and thus the induction of a protective antibody response remains a major priority for HIV-1 vaccine development. For an antibody-based HIV-1 vaccine, progress in vaccine design is generally gauged by in vitro assays that measure the ability of vaccine-induced antibodies to neutralize a broad spectrum of viral isolates representing the major genetic subtypes (clades) of HIV-1 [2]. Although it is not known what magnitude and breadth of neutralization will predict protection in vaccine recipients, it is clear that current vaccine immunogens elicit antibodies that neutralize only a minority of circulating isolates. Thus, much progress needs to be made in this area. Also, though virus neutralization is considered a critical benchmark for a vaccine, this may not be the only benchmark for predicting success with antibody-based HIV-1 vaccine immunogens. The main targets for neutralizing antibodies to HIV-1 are the surface gp120 and trans-membrane gp41 envelope glycoproteins (Env) that mediate receptor and coreceptor binding and the subsequent membrane fusion events that allow the virus to gain entry into cells [3]. Antibodies neutralize the virus by binding these viral spikes and blocking virus entry into susceptible cells, such as CD4+ T cells [4,5]. In order to chronically replicate in the host, the virus exploits several mechanisms to shield itself against antibody recognition, including a dense outer coating of sugar molecules (N-linked glycans) and the strategic positioning of cysteine–cysteine loop structures on the gp120 molecule [6–8]. These shielding mechanisms, although highly effective, have vulnerabilities imposed by fitness constraints. Information on the precise location and molecular structure of these vulnerable regions could be valuable for the rational design of improved vaccine immunogens. Participants in the workshop identified four areas that, if given proper attention, could provide key information that would bring the field closer to an effective antibody-based HIV-1 vaccine: (1) structure-assisted immunogen design, (2) role of Fc receptors and complement, (3) assay standardization and validation, and (4) immunoregulation of B cell responses.", "title": "Antibody-Based HIV-1 Vaccines: Recent Developments and Future Directions" }, { "docid": "23915841", "text": "The study of the evolution and specificities of neutralizing antibodies during the course of human immunodeficiency virus type 1 (HIV-1) infection may be important in the discovery of possible targets for vaccine design. In this study, we assessed the autologous and heterologous neutralization responses of 14 HIV-1 subtype C-infected individuals, using envelope clones obtained within the first 2 months postinfection. Our data show that potent but relatively strain-specific neutralizing antibodies develop within 3 to 12 months of HIV-1 infection. The magnitude of this response was associated with shorter V1-to-V5 envelope lengths and fewer glycosylation sites, particularly in the V1-V2 region. Anti-MPER antibodies were detected in 4 of 14 individuals within a year of infection, while antibodies to CD4-induced (CD4i) epitopes developed to high titers in 12 participants, in most cases before the development of autologous neutralizing antibodies. However, neither anti-MPER nor anti-CD4i antibody specificity conferred neutralization breadth. These data provide insights into the kinetics, potency, breadth, and epitope specificity of neutralizing antibody responses in acute HIV-1 subtype C infection.", "title": "Neutralizing antibody responses in acute human immunodeficiency virus type 1 subtype C infection." }, { "docid": "19327364", "text": "Sera from 526 Old-World monkeys and apes, representing 50 species and 20 genera and living in US zoos and vivaria, were screened for antibodies to HTLV-I, HTLV-III/LAV, and simian-AIDS retrovirus, type I (SRV-I). Sera were screened initially by ELISA, and ELISA-positive sera, as well as ELISA-negative sera from cage contacts, were further tested by Western blotting. A large number of false-positive and a small number of false-negative ELISA sera were identified. Although most true positive reactions were directed to a single retrovirus, a number of individuals from 4 species were positive for more than one retrovirus. Specific seroreactivity to HTLV-I was found in 39/526 (7%) animals of 15 species. True positive reactions to SRV-I were found in 21/516 (4%) animals, including talapoins and 2 species of macaques. Specific serologic reactions to HTLV-III/LAV were detected in 23/526 (4%) monkeys. Many of the HTLV-III/LAV seropositive animals were from one mixed-species zoo exhibit, containing sooty mangabeys, mandrills, Kolb's guenons, and talapoins. A type D virus was isolated from the blood of 3/10 SRV-I antibody-positive Tonkeana macaques, but from none of 11 seropositive talapoins. A lentivirus was isolated from the blood of 4/7 HTLV-III/LAV seropositive sooty mangabeys, but not from seropositive talapoins in the same exhibit or from 2 seropositive colobus from another zoo. The sooty mangabey lentivirus produced generalized lymphadenopathy, leukopenia, and decreased levels of T4 lymphocytes in 2 experimentally infected rhesus macaques.", "title": "Seroepidemiologic survey of captive Old-World primates for antibodies to human and simian retroviruses, and isolation of a lentivirus from sooty mangabeys (Cercocebus atys)." }, { "docid": "4373433", "text": "Broadly neutralizing antibodies against highly variable viral pathogens are much sought after to treat or protect against global circulating viruses. Here we probed the neutralizing antibody repertoires of four human immunodeficiency virus (HIV)-infected donors with remarkably broad and potent neutralizing responses and rescued 17 new monoclonal antibodies that neutralize broadly across clades. Many of the new monoclonal antibodies are almost tenfold more potent than the recently described PG9, PG16 and VRC01 broadly neutralizing monoclonal antibodies and 100-fold more potent than the original prototype HIV broadly neutralizing monoclonal antibodies. The monoclonal antibodies largely recapitulate the neutralization breadth found in the corresponding donor serum and many recognize novel epitopes on envelope (Env) glycoprotein gp120, illuminating new targets for vaccine design. Analysis of neutralization by the full complement of anti-HIV broadly neutralizing monoclonal antibodies now available reveals that certain combinations of antibodies should offer markedly more favourable coverage of the enormous diversity of global circulating viruses than others and these combinations might be sought in active or passive immunization regimes. Overall, the isolation of multiple HIV broadly neutralizing monoclonal antibodies from several donors that, in aggregate, provide broad coverage at low concentrations is a highly positive indicator for the eventual design of an effective antibody-based HIV vaccine.", "title": "Broad neutralization coverage of HIV by multiple highly potent antibodies" }, { "docid": "21150010", "text": "Metastatic ovarian cancer is the leading cause of death among women with gynecologic malignancies in the United States. The lack of effective treatment for patients with advanced ovarian cancer warrants development of innovative therapies. Cancer therapy using oncolytic viruses represents a promising new approach for controlling tumors. Vaccinia virus has been shown to preferentially infect tumor cells but not normal tissue. However, oncolytic therapy using recombinant viruses faces the limitation of viral clearance due to generation of neutralizing antibodies. In the current study, we found that cyclooxygenase-2 (Cox-2) inhibitors circumvented this limitation, enabling repeated administration of vaccinia virus without losing infectivity. We quantified the antivaccinia antibody response using enzyme-linked immunosorbent assay (ELISA) and neutralization assays to show that treatment of Cox-2 inhibitors inhibited the generation of neutralizing antibodies. Furthermore, we showed that combination treatment of Cox-2 inhibitors with vaccinia virus was more effective that either treatment alone in treating MOSEC/luc tumor-bearing mice. Thus, the combination of Cox-2 inhibitors and vaccinia virus represents a potential innovative approach to controlling ovarian tumors.", "title": "Treatment with cyclooxygenase-2 inhibitors enables repeated administration of vaccinia virus for control of ovarian cancer." }, { "docid": "3566945", "text": "Broadly neutralizing antibodies (bnAbs) to HIV-1 can evolve after years of an iterative process of virus escape and antibody adaptation that HIV-1 vaccine design seeks to mimic. To enable this, properties that render HIV-1 envelopes (Env) capable of eliciting bnAb responses need to be defined. Here, we followed the evolution of the V2 apex directed bnAb lineage VRC26 in the HIV-1 subtype C superinfected donor CAP256 to investigate the phenotypic changes of the virus populations circulating before and during the early phases of bnAb induction. Longitudinal viruses that evolved from the VRC26-resistant primary infecting (PI) virus, the VRC26-sensitive superinfecting (SU) virus and ensuing PI-SU recombinants revealed substantial phenotypic changes in Env, with a switch in Env properties coinciding with early resistance to VRC26. Decreased sensitivity of SU-like viruses to VRC26 was linked with reduced infectivity, altered entry kinetics and lower sensitivity to neutralization after CD4 attachment. VRC26 maintained neutralization activity against cell-associated CAP256 virus, indicating that escape through the cell-cell transmission route is not a dominant escape pathway. Reduced fitness of the early escape variants and sustained sensitivity in cell-cell transmission are both features that limit virus replication, thereby impeding rapid escape. This supports a scenario where VRC26 allowed only partial viral escape for a prolonged period, possibly increasing the time window for bnAb maturation. Collectively, our data highlight the phenotypic plasticity of the HIV-1 Env in evading bnAb pressure and the need to consider phenotypic traits when selecting and designing Env immunogens. Combinations of Env variants with differential phenotypic patterns and bnAb sensitivity, as we describe here for CAP256, may maximize the potential for inducing bnAb responses by vaccination.", "title": "Phenotypic deficits in the HIV-1 envelope are associated with the maturation of a V2-directed broadly neutralizing antibody lineage" }, { "docid": "12885341", "text": "West Nile virus (WNV) is the most common arthropod-borne flavivirus in the United States; however, the vector ligand(s) that participate in infection are not known. We now show that an Aedes aegypti C-type lectin, mosGCTL-1, is induced by WNV, interacts with WNV in a calcium-dependent manner, and facilitates infection in vivo and in vitro. A mosquito homolog of human CD45 in A. aegypti, designated mosPTP-1, recruits mosGCTL-1 to enable viral attachment to cells and to enhance viral entry. In vivo experiments show that mosGCTL-1 and mosPTP-1 function as part of the same pathway and are critical for WNV infection of mosquitoes. A similar phenomenon was also observed in Culex quinquefasciatus, a natural vector of WNV, further demonstrating that these genes participate in WNV infection. During the mosquito blood-feeding process, WNV infection was blocked in vivo with mosGCTL-1 antibodies. A molecular understanding of flaviviral-arthropod interactions may lead to strategies to control viral dissemination in nature.", "title": "A C-Type Lectin Collaborates with a CD45 Phosphatase Homolog to Facilitate West Nile Virus Infection of Mosquitoes" }, { "docid": "7177329", "text": "Neutralizing antibodies are likely to play a crucial part in a preventative HIV-1 vaccine. Although efforts to elicit broadly cross-neutralizing (BCN) antibodies by vaccination have been unsuccessful, a minority of individuals naturally develop these antibodies after many years of infection. How such antibodies arise, and the role of viral evolution in shaping these responses, is unknown. Here we show, in two HIV-1–infected individuals who developed BCN antibodies targeting the glycan at Asn332 on the gp120 envelope, that this glycan was absent on the initial infecting virus. However, this BCN epitope evolved within 6 months, through immune escape from earlier strain-specific antibodies that resulted in a shift of a glycan to position 332. Both viruses that lacked the glycan at amino acid 332 were resistant to the Asn332-dependent BCN monoclonal antibody PGT128 (ref. 8), whereas escaped variants that acquired this glycan were sensitive. Analysis of large sequence and neutralization data sets showed the 332 glycan to be significantly under-represented in transmitted subtype C viruses compared to chronic viruses, with the absence of this glycan corresponding with resistance to PGT128. These findings highlight the dynamic interplay between early antibodies and viral escape in driving the evolution of conserved BCN antibody epitopes.", "title": "Evolution of an HIV glycan–dependent broadly neutralizing antibody epitope through immune escape" }, { "docid": "1071991", "text": "Live attenuated simian immunodeficiency virus (SIV) vaccines (LAVs) remain the most efficacious of all vaccines in nonhuman primate models of HIV and AIDS, yet the basis of their robust protection remains poorly understood. Here we show that the degree of LAV-mediated protection against intravenous wild-type SIVmac239 challenge strongly correlates with the magnitude and function of SIV-specific, effector-differentiated T cells in the lymph node but not with the responses of such T cells in the blood or with other cellular, humoral and innate immune parameters. We found that maintenance of protective T cell responses is associated with persistent LAV replication in the lymph node, which occurs almost exclusively in follicular helper T cells. Thus, effective LAVs maintain lymphoid tissue-based, effector-differentiated, SIV-specific T cells that intercept and suppress early wild-type SIV amplification and, if present in sufficient frequencies, can completely control and perhaps clear infection, an observation that provides a rationale for the development of safe, persistent vectors that can elicit and maintain such responses.", "title": "Lymph node T cell responses predict the efficacy of live attenuated SIV vaccines" }, { "docid": "16939583", "text": "Variation in cerebral cortex size and complexity is thought to contribute to differences in cognitive ability between humans and other animals. Here we compare cortical progenitor cell output in humans and three nonhuman primates using directed differentiation of pluripotent stem cells (PSCs) in adherent two-dimensional (2D) and organoid three-dimensional (3D) culture systems. Clonal lineage analysis showed that primate cortical progenitors proliferate for a protracted period of time, during which they generate early-born neurons, in contrast to rodents, where this expansion phase largely ceases before neurogenesis begins. The extent of this additional cortical progenitor expansion differs among primates, leading to differences in the number of neurons generated by each progenitor cell. We found that this mechanism for controlling cortical size is regulated cell autonomously in culture, suggesting that primate cerebral cortex size is regulated at least in part at the level of individual cortical progenitor cell clonal output.", "title": "2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size." }, { "docid": "45244537", "text": "Evaluation of testicular functions (production of sperm and androgens) is an important aspect of preclinical safety assessment and testicular toxicity is comparatively far more common than ovarian toxicity. This chapter focuses (1) on the histological sequelae of disturbed reproductive endocrinology in rat, dog and nonhuman primates and (2) provides a review of our current understanding of the roles of gonadotropins and androgens. The response of the rodent testis to endocrine disturbances is clearly different from that of dog and primates with different germ cell types and spermatogenic stages being affected initially and also that the end-stage spermatogenic involution is more pronounced in dog and primates compared to rodents. Luteinizing hormone (LH)/testosterone and follicle-stimulating hormone (FSH) are the pivotal endocrine factors controlling testicular functions. The relative importance of either hormone is somewhat different between rodents and primates. Generally, however, both LH/testosterone and FSH are necessary for quantitatively normal spermatogenesis, at least in non-seasonal species.", "title": "Endocrine control of spermatogenesis: Role of FSH and LH/ testosterone." }, { "docid": "9831859", "text": "Pancreatic stellate cells (PSC) produce the stromal reaction in pancreatic cancer, but their role in cancer progression is not fully elucidated. We examined the influence of PSCs on pancreatic cancer growth using (a) an orthotopic model of pancreatic cancer and (b) cultured human PSCs (hPSC) and human pancreatic cancer cell lines MiaPaCa-2 and Panc-1. Athymic mice received an intrapancreatic injection of saline, hPSCs, MiaPaCa-2 cells, or hPSCs + MiaPaCa-2. After 7 weeks, tumor size, metastases, and tumor histology were assessed. In vitro studies assessed the effect of cancer cell secretions on PSC migration and the effect of hPSC secretions on cancer cell proliferation, apoptosis, and migration. Possible mediators of the effects of hPSC secretions on cancer cell proliferation were examined using neutralizing antibodies. Compared with mice receiving MiaPaCa-2 cells alone, mice injected with hPSCs + MiaPaCa-2 exhibited (a) increased tumor size and regional and distant metastasis, (b) fibrotic bands (desmoplasia) containing activated PSCs within tumors, and (c) increased tumor cell numbers. In vitro studies showed that, in the presence of pancreatic cancer cells, PSC migration was significantly increased. Furthermore, hPSC secretions induced the proliferation and migration, but inhibited the apoptosis, of MiaPaCa-2 and Panc-1 cells. The proliferative effect of hPSC secretions on pancreatic cancer cells was inhibited in the presence of neutralizing antibody to platelet-derived growth factor. Our studies indicate a significant interaction between pancreatic cancer cells and stromal cells (PSCs) and imply that pancreatic cancer cells recruit stromal cells to establish an environment that promotes cancer progression.", "title": "Pancreatic stellate cells: partners in crime with pancreatic cancer cells." }, { "docid": "8063697", "text": "Pertussis is a highly contagious respiratory illness caused by the bacterial pathogen Bordetella pertussis. Pertussis rates in the United States have been rising and reached a 50-y high of 42,000 cases in 2012. Although pertussis resurgence is not completely understood, we hypothesize that current acellular pertussis (aP) vaccines fail to prevent colonization and transmission. To test our hypothesis, infant baboons were vaccinated at 2, 4, and 6 mo of age with aP or whole-cell pertussis (wP) vaccines and challenged with B. pertussis at 7 mo. Infection was followed by quantifying colonization in nasopharyngeal washes and monitoring leukocytosis and symptoms. Baboons vaccinated with aP were protected from severe pertussis-associated symptoms but not from colonization, did not clear the infection faster than naïve animals, and readily transmitted B. pertussis to unvaccinated contacts. Vaccination with wP induced a more rapid clearance compared with naïve and aP-vaccinated animals. By comparison, previously infected animals were not colonized upon secondary infection. Although all vaccinated and previously infected animals had robust serum antibody responses, we found key differences in T-cell immunity. Previously infected animals and wP-vaccinated animals possess strong B. pertussis-specific T helper 17 (Th17) memory and Th1 memory, whereas aP vaccination induced a Th1/Th2 response instead. The observation that aP, which induces an immune response mismatched to that induced by natural infection, fails to prevent colonization or transmission provides a plausible explanation for the resurgence of pertussis and suggests that optimal control of pertussis will require the development of improved vaccines.", "title": "Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model." }, { "docid": "6144337", "text": "Activation of the insect innate immune system is dependent on a limited number of pattern recognition receptors (PRRs) capable of interacting with pathogen-associated molecular pattern. Here we report a novel role of an alternatively spliced hypervariable immunoglobulin domain-encoding gene, Dscam, in generating a broad range of PRRs implicated in immune defense in the malaria vector Anopheles gambiae. The mosquito Down syndrome cell adhesion molecule gene, AgDscam, has a complex genome organization with 101 exons that can produce over 31,000 potential alternative splice forms with different combinations of adhesive domains and interaction specificities. AgDscam responds to infection by producing pathogen challenge-specific splice form repertoires. Transient silencing of AgDscam compromises the mosquito's resistance to infections with bacteria and the malaria parasite Plasmodium. AgDscam is mediating phagocytosis of bacteria with which it can associate and defend against in a splice form–specific manner. AgDscam is a hypervariable PRR of the A. gambiae innate immune system.", "title": "AgDscam, a Hypervariable Immunoglobulin Domain-Containing Receptor of the Anopheles gambiae Innate Immune System " }, { "docid": "9539248", "text": "Mosquito-borne viruses cause significant levels of morbidity and mortality in humans and domesticated animals. Maintenance of mosquito-borne viruses in nature requires a biological transmission cycle that involves alternating virus replication in a susceptible vertebrate and mosquito host. Although the vertebrate infection is acute and often associated with disease, continual transmission of these viruses in nature depends on the establishment of a persistent, nonpathogenic infection in the mosquito vector. An antiviral RNAi response has been shown to limit the replication of RNA viruses in flies. However, the importance of the RNAi pathway as an antiviral defense in mammals is unclear. Differences in the immune responses of mammals and mosquitoes may explain why these viruses are not generally associated with pathology in the invertebrate host. We identified virus-derived small interfering RNAs (viRNAs), 21 nt in length, in Aedes aegypti infected with the mosquito-borne virus, Sindbis (SINV). viRNAs had an asymmetric distribution that spanned the length of the SINV genome. To determine the role of viRNAs in controlling pathogenic potential, mosquitoes were infected with recombinant alphaviruses expressing suppressors of RNA silencing. Decreased survival was observed in mosquitoes in which the accumulation of viRNAs was suppressed. These results suggest that an exogenous siRNA pathway is essential to the survival of mosquitoes infected with alphaviruses and, thus, the maintenance of these viruses in nature.", "title": "Alphavirus-derived small RNAs modulate pathogenesis in disease vector mosquitoes." }, { "docid": "22705234", "text": "The African green monkey (AGM) is one of many African species endemically infected with simian immunodeficiency virus (SIV). Like the other natural hosts, AGMs do not succumb to AIDS and understanding the basis for this resistance to disease progression would be of enormous theoretical and practical importance. Early efforts by our group that concentrated on identifying immune mechanisms presumed to keep the virus under control failed to find any obvious candidates. The presumption of virus control was invalidated by the finding that SIVagm replicates in AGMs with the same vigor as HIV-1 does in humans. Focus therefore shifted to identifying possible immunopathologic features present in disease susceptible hosts but absent in the AGM natural host. The apparent immunologic tolerance of AGMs to the SIVagm core protein led to the development of a hypothesis implicating anti-Gag antibodies in the formation of immune complexes, virus trapping in the lymph nodes and immune dysfunction. The idea proved difficult to test in vivo and present work focuses on the possibility that Gag tolerance at the T-cell level plays an important role in preventing the catastrophic demise of the immune system characteristic of immunodeficiency virus infection of the heterologous primate host.", "title": "The role of the immune response during SIVagm infection of the African green monkey natural host." }, { "docid": "14195528", "text": "The role of primate frontal cortex in vocal communication and its significance in language evolution have a controversial history. While evidence indicates that vocalization processing occurs in ventrolateral prefrontal cortex neurons, vocal-motor activity has been conjectured to be primarily subcortical and suggestive of a distinctly different neural architecture from humans. Direct evidence of neural activity during natural vocal communication is limited, as previous studies were performed in chair-restrained animals. Here we recorded the activity of single neurons across multiple regions of prefrontal and premotor cortex while freely moving marmosets engaged in a natural vocal behavior known as antiphonal calling. Our aim was to test whether neurons in marmoset frontal cortex exhibited responses during vocal-signal processing and/or vocal-motor production in the context of active, natural communication. We observed motor-related changes in single neuron activity during vocal production, but relatively weak sensory responses for vocalization processing during this natural behavior. Vocal-motor responses occurred both prior to and during call production and were typically coupled to the timing of each vocalization pulse. Despite the relatively weak sensory responses a population classifier was able to distinguish between neural activity that occurred during presentations of vocalization stimuli that elicited an antiphonal response and those that did not. These findings are suggestive of the role that nonhuman primate frontal cortex neurons play in natural communication and provide an important foundation for more explicit tests of the functional contributions of these neocortical areas during vocal behaviors.", "title": "Responses of primate frontal cortex neurons during natural vocal communication." }, { "docid": "32170702", "text": "Maintenance of hematopoietic stem cells (HSCs) depends on interaction with their niche. Here we show that the long-term (LT)-HSCs expressing the thrombopoietin (THPO) receptor, MPL, are a quiescent population in adult bone marrow (BM) and are closely associated with THPO-producing osteoblastic cells. THPO/MPL signaling upregulated beta1-integrin and cyclin-dependent kinase inhibitors in HSCs. Furthermore, inhibition and stimulation of THPO/MPL pathway by treatments with anti-MPL neutralizing antibody, AMM2, and with THPO showed reciprocal regulation of quiescence of LT-HSC. AMM2 treatment reduced the number of quiescent LT-HSCs and allowed exogenous HSC engraftment without irradiation. By contrast, exogenous THPO transiently increased quiescent HSC population and subsequently induced HSC proliferation in vivo. Altogether, these observations suggest that THPO/MPL signaling plays a critical role of LT-HSC regulation in the osteoblastic niche.", "title": "Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche." }, { "docid": "4404433", "text": "The common marmoset (Callithrix jacchus) is increasingly attractive for use as a non-human primate animal model in biomedical research. It has a relatively high reproduction rate for a primate, making it potentially suitable for transgenic modification. Although several attempts have been made to produce non-human transgenic primates, transgene expression in the somatic tissues of live infants has not been demonstrated by objective analyses such as polymerase chain reaction with reverse transcription or western blots. Here we show that the injection of a self-inactivating lentiviral vector in sucrose solution into marmoset embryos results in transgenic common marmosets that expressed the transgene in several organs. Notably, we achieved germline transmission of the transgene, and the transgenic offspring developed normally. The successful creation of transgenic marmosets provides a new animal model for human disease that has the great advantage of a close genetic relationship with humans. This model will be valuable to many fields of biomedical research.", "title": "Generation of transgenic non-human primates with germline transmission" }, { "docid": "2947124", "text": "During persistent viral infections, chronic immune activation, negative immune regulator expression, an elevated interferon signature, and lymphoid tissue destruction correlate with disease progression. We demonstrated that blockade of type I interferon (IFN-I) signaling using an IFN-I receptor neutralizing antibody reduced immune system activation, decreased expression of negative immune regulatory molecules, and restored lymphoid architecture in mice persistently infected with lymphocytic choriomeningitis virus. IFN-I blockade before and after establishment of persistent virus infection resulted in enhanced virus clearance and was CD4 T cell-dependent. Hence, we demonstrate a direct causal link between IFN-I signaling, immune activation, negative immune regulator expression, lymphoid tissue disorganization, and virus persistence. Our results suggest that therapies targeting IFN-I may help control persistent virus infections.", "title": "Persistent LCMV infection is controlled by blockade of type I interferon signaling." }, { "docid": "13469921", "text": "Recent cross-sectional analyses of HIV-1+ plasmas have indicated that broadly cross-reactive neutralizing antibody responses are developed by 10%-30% of HIV-1+ subjects. The timing of the initial development of such anti-viral responses is unknown. It is also unknown whether the emergence of these responses coincides with the appearance of antibody specificities to a single or multiple regions of the viral envelope glycoprotein (Env). Here we analyzed the cross-neutralizing antibody responses in longitudinal plasmas collected soon after and up to seven years after HIV-1 infection. We find that anti-HIV-1 cross-neutralizing antibody responses first become evident on average at 2.5 years and, in rare cases, as early as 1 year following infection. If cross-neutralizing antibody responses do not develop during the first 2-3 years of infection, they most likely will not do so subsequently. Our results indicate a potential link between the development of cross-neutralizing antibody responses and specific activation markers on T cells, and with plasma viremia levels. The earliest cross-neutralizing antibody response targets a limited number of Env regions, primarily the CD4-binding site and epitopes that are not present on monomeric Env, but on the virion-associated trimeric Env form. In contrast, the neutralizing activities of plasmas from subjects that did not develop cross-neutralizing antibody responses target epitopes on monomeric gp120 other than the CD4-BS. Our study provides information that is not only relevant to better understanding the interaction of the human immune system with HIV but may guide the development of effective immunization protocols. Since antibodies to complex epitopes that are present on the virion-associated envelope spike appear to be key components of earliest cross-neutralizing activities of HIV-1+ plasmas, then emphasis should be made to elicit similar antibodies by vaccination.", "title": "Characteristics of the Earliest Cross-Neutralizing Antibody Response to HIV-1" }, { "docid": "4421578", "text": "Characterization of human monoclonal antibodies is providing considerable insight into mechanisms of broad HIV-1 neutralization. Here we report an HIV-1 gp41 membrane-proximal external region (MPER)-specific antibody, named 10E8, which neutralizes ∼98% of tested viruses. An analysis of sera from 78 healthy HIV-1-infected donors demonstrated that 27% contained MPER-specific antibodies and 8% contained 10E8-like specificities. In contrast to other neutralizing MPER antibodies, 10E8 did not bind phospholipids, was not autoreactive, and bound cell-surface envelope. The structure of 10E8 in complex with the complete MPER revealed a site of vulnerability comprising a narrow stretch of highly conserved gp41-hydrophobic residues and a critical arginine or lysine just before the transmembrane region. Analysis of resistant HIV-1 variants confirmed the importance of these residues for neutralization. The highly conserved MPER is a target of potent, non-self-reactive neutralizing antibodies, suggesting that HIV-1 vaccines should aim to induce antibodies to this region of HIV-1 envelope glycoprotein.", "title": "Broad and potent neutralization of HIV-1 by a gp41-specific human antibody" }, { "docid": "17454301", "text": "A small, isolated outbreak of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) due to dengue virus type 2 (DEN-2) was documented in Santiago de Cuba on the island of Cuba beginning in January 1997. There were 205 DHF/DSS cases, all in persons older than age 15 years. All but three had evidence of a prior dengue infection, with the only known opportunity being the islandwide dengue virus type 1 (DEN-1) epidemic of 1977-1979. Virtually complete clinical and laboratory surveillance of overt disease was achieved. From December 1997 to January 1998, a random, age-stratified serum sample was obtained from 1,151 persons in 40 residential clusters in Santiago. Sera were tested for DEN-1 and DEN-2 neutralizing antibodies. The prevalence of DEN-2 antibodies in children age 15 years and under, born after the 1981 DEN-2 epidemic, was taken as the 1997 DEN-2 infection rate. This was adjusted slightly to accommodate observed cases, resulting in an estimated infection rate of 4.3%. Dengue fever and DHF/DSS attack rates were calculated from estimated total primary and secondary DEN-2 infections. Only 3% of 13,116 primary infections were overt. The DHF/DSS attack rate for adults of all ages was 420 per 10,000 secondary DEN-2 infections.", "title": "Epidemiologic studies on Dengue in Santiago de Cuba, 1997." }, { "docid": "42465769", "text": "Adipocytes are part of hematopoietic microenvironment, even though up to now in humans, their role in hematopoiesis is still questioned. We have previously shown that accumulation of fat cells in femoral bone marrow (BM) coincides with increased expression of neuropilin-1 (NP-1), while it is weakly expressed in hematopoietic iliac crest BM. Starting from this observation, we postulated that adipocytes might exert a negative effect on hematopoiesis mediated through NP-1. To test this hypothesis, we set up BM adipocytes differentiated into fibroblast-like fat cells (FLFC), which share the major characteristics of primitive unilocular fat cells, as an experimental model. As expected, FLFCs constitutively produced macrophage colony stimulating factor and induced CD34(+) differentiation into macrophages independently of cell-to-cell contact. By contrast, granulopoiesis was hampered by cell-to-cell contact but could be restored in transwell culture conditions, together with granulocyte colony stimulating factor production. Both functions were also recovered when FLFCs cultured in contact with CD34(+) cells were treated with an antibody neutralizing NP-1, which proved its critical implication in contact inhibition. An inflammatory cytokine such as interleukin-1 beta or dexamethasone modulates FLFC properties to restore granulopoiesis. Our data provide the first evidence that primary adipocytes exert regulatory functions during hematopoiesis that might be implicated in some pathological processes. Disclosure of potential conflicts of interest is found at the end of this article.", "title": "Human bone marrow adipocytes block granulopoiesis through neuropilin-1-induced granulocyte colony-stimulating factor inhibition." }, { "docid": "37269418", "text": "The cytokine and antibody response to Trichuris trichiura infection was determined for 96 persons living in an area where the parasite is highly endemic and infection exhibits a convex age intensity profile. In response to stimulation with T. trichiura antigen, a small proportion of the study group produced interleukin (IL)-4 (7%), IL-9 (5%), and IL-13 (17%). A larger proportion produced IL-10 (97%), tumor necrosis factor (TNF)-alpha (93%), and interferon (IFN)-gamma (32%). The levels of TNF-alpha (P =.016) and IFN-gamma (P =.012) significantly increased with age, suggesting a switch to a more chronic infection phenotype. The predominant parasite-specific antibodies produced were IgG1, IgG4, IgA, and IgE. Unlike the IgG subclasses and IgA, parasite-specific IgE correlated negatively with infection intensity, as defined by egg output (P =.008), and positively with host age (P =.010). These findings suggest a mixed cytokine response in trichuriasis and an IgE-associated level of protection.", "title": "Age- and infection intensity-dependent cytokine and antibody production in human trichuriasis: the importance of IgE." }, { "docid": "6820680", "text": "MicroRNAs (miRNAs) are short noncoding RNAs that exert posttranscriptional gene silencing and regulate gene expression. In addition to the hundreds of conserved cellular miRNAs that have been identified, miRNAs of viral origin have been isolated and found to modulate both the viral life cycle and the cellular transcriptome. Thus far, detection of virus-derived miRNAs has been largely limited to DNA viruses, suggesting that RNA viruses may be unable to exploit this aspect of transcriptional regulation. Lack of RNA virus-produced miRNAs has been attributed to the replicative constraints that would incur following RNase III processing of a genomic hairpin. To ascertain whether the generation of viral miRNAs is limited to DNA viruses, we investigated whether influenza virus could be designed to deliver functional miRNAs without affecting replication. Here, we describe a modified influenza A virus that expresses cellular microRNA-124 (miR-124). Insertion of the miR-124 hairpin into an intron of the nuclear export protein transcript resulted in endogenous processing and functional miR-124. We demonstrate that a viral RNA genome incorporating a hairpin does not result in segment instability or miRNA-mediated genomic targeting, thereby permitting the virus to produce a miRNA without having a negative impact on viral replication. This work demonstrates that RNA viruses can produce functional miRNAs and suggests that this level of transcriptional regulation may extend beyond DNA viruses.", "title": "Engineered RNA viral synthesis of microRNAs." }, { "docid": "2601135", "text": "A recent study of plasma neutralization breadth in HIV-1 infected individuals at nine International AIDS Vaccine Initiative (IAVI) sites reported that viral load, HLA-A*03 genotype, and subtype C infection were strongly associated with the development of neutralization breadth. Here, we refine the findings of that study by analyzing the impact of the transmitted/founder (T/F) envelope (Env), early Env diversification, and autologous neutralization on the development of plasma neutralization breadth in 21 participants identified during recent infection at two of those sites: Kigali, Rwanda (n = 9) and Lusaka, Zambia (n = 12). Single-genome analysis of full-length T/F Env sequences revealed that all 21 individuals were infected with a highly homogeneous population of viral variants, which were categorized as subtype C (n = 12), A1 (n = 7), or recombinant AC (n = 2). An extensive amino acid sequence-based analysis of variable loop lengths and glycosylation patterns in the T/F Envs revealed that a lower ratio of NXS to NXT-encoded glycan motifs correlated with neutralization breadth. Further analysis comparing amino acid sequence changes, insertions/deletions, and glycan motif alterations between the T/F Env and autologous early Env variants revealed that extensive diversification focused in the V2, V4, and V5 regions of gp120, accompanied by contemporaneous viral escape, significantly favored the development of breadth. These results suggest that more efficient glycosylation of subtype A and C T/F Envs through fewer NXS-encoded glycan sites is more likely to elicit antibodies that can transition from autologous to heterologous neutralizing activity following exposure to gp120 diversification. This initiates an Env-antibody co-evolution cycle that increases neutralization breadth, and is further augmented over time by additional viral and host factors. These findings suggest that understanding how variation in the efficiency of site-specific glycosylation influences neutralizing antibody elicitation and targeting could advance the design of immunogens aimed at inducing antibodies that can transition from autologous to heterologous neutralizing activity.", "title": "Diversification in the HIV-1 Envelope Hyper-variable Domains V2, V4, and V5 and Higher Probability of Transmitted/Founder Envelope Glycosylation Favor the Development of Heterologous Neutralization Breadth" }, { "docid": "18816720", "text": "BACKGROUND Transmission of dengue viruses (DENV), the leading cause of arboviral disease worldwide, is known to vary through time and space, likely owing to a combination of factors related to the human host, virus, mosquito vector, and environment. An improved understanding of variation in transmission patterns is fundamental to conducting surveillance and implementing disease prevention strategies. To test the hypothesis that DENV transmission is spatially and temporally focal, we compared geographic and temporal characteristics within Thai villages where DENV are and are not being actively transmitted. METHODS AND FINDINGS Cluster investigations were conducted within 100 m of homes where febrile index children with (positive clusters) and without (negative clusters) acute dengue lived during two seasons of peak DENV transmission. Data on human infection and mosquito infection/density were examined to precisely (1) define the spatial and temporal dimensions of DENV transmission, (2) correlate these factors with variation in DENV transmission, and (3) determine the burden of inapparent and symptomatic infections. Among 556 village children enrolled as neighbors of 12 dengue-positive and 22 dengue-negative index cases, all 27 DENV infections (4.9% of enrollees) occurred in positive clusters (p < 0.01; attributable risk [AR] = 10.4 per 100; 95% confidence interval 1-19.8 per 100]. In positive clusters, 12.4% of enrollees became infected in a 15-d period and DENV infections were aggregated centrally near homes of index cases. As only 1 of 217 pairs of serologic specimens tested in positive clusters revealed a recent DENV infection that occurred prior to cluster initiation, we attribute the observed DENV transmission subsequent to cluster investigation to recent DENV transmission activity. Of the 1,022 female adult Ae. aegypti collected, all eight (0.8%) dengue-infected mosquitoes came from houses in positive clusters; none from control clusters or schools. Distinguishing features between positive and negative clusters were greater availability of piped water in negative clusters (p < 0.01) and greater number of Ae. aegypti pupae per person in positive clusters (p = 0.04). During primarily DENV-4 transmission seasons, the ratio of inapparent to symptomatic infections was nearly 1:1 among child enrollees. Study limitations included inability to sample all children and mosquitoes within each cluster and our reliance on serologic rather than virologic evidence of interval infections in enrollees given restrictions on the frequency of blood collections in children. CONCLUSIONS Our data reveal the remarkably focal nature of DENV transmission within a hyperendemic rural area of Thailand. These data suggest that active school-based dengue case detection prompting local spraying could contain recent virus introductions and reduce the longitudinal risk of virus spread within rural areas. Our results should prompt future cluster studies to explore how host immune and behavioral aspects may impact DENV transmission and prevention strategies. Cluster methodology could serve as a useful research tool for investigation of other temporally and spatially clustered infectious diseases.", "title": "Spatial and Temporal Clustering of Dengue Virus Transmission in Thai Villages" } ]
1508
How quickly does short float ratio/percent change?
[ { "docid": "41214", "text": "The short float ratio and percent change are all calculated based on the short interest (the total number of shares shorted). The short interest data for Nasdaq and NYSE stocks is published every two weeks. NasdaqTrader.com shows the exact dates for when short interest is published for Nasdaq stocks, and also says the following: FINRA member firms are required to report their short positions as of settlement on (1) the 15th of each month, or the preceding business day if the 15th is not a business day, and (2) as of settlement on the last business day of the month.* The reports must be filed by the second business day after the reporting settlement date. FINRA compiles the short interest data and provides it for publication on the 8th business day after the reporting settlement date. The NYSE also shows the exact dates for when short interest is published for NYSE stocks, and those dates are exactly the same as for Nasdaq stocks. Since the short interest is only updated once every 2 weeks, there is no way to see real-time updating of the short float and percent change. That information only gets updated once every 2 weeks - after each publication of the short interest.", "title": "" } ]
[ { "docid": "192900", "text": "This is the bird's eye view of how shorting works: When you place an order to sell a stock short, your broker attempts to grab the desired number of shares from any accounts of its other customers and makes them available for you to sell. If no other customers own shares of this stock, then generally you are out of luck (It is more complicated like that in practice, but this is just an overview). Your odds are better if the particular stock has a large float (i.e. a large number of shares that are actually available for trading) and its short ratio is low (which means relatively few shares are currently being sold short). Also, a large brokerage may be more likely to have access to the shares than a small niche-market broker. The example you've given, Angie's List (ANGI) is a $600M small-cap with a comparatively low float, and though I haven't been able to glean the short ratio, it appears that a lot of investors are bearish on this stock and probably already had the same idea to short it. There is really no way to find out if a specific broker has shares in inventory available for shorting, short of (forgive the pun) checking directly with the broker.", "title": "" }, { "docid": "562220", "text": "A value of zero or a negative value makes the percent change meaningless. Saying 100% when going from 0 to some other value is simply wrong. I have seen a similar situation several times when looking at a public company with a loss last quarter. On Google Finance or some other service, the PE ratio will be blank, N/A, or something like that. If the company does not currently have earnings, then the PE ratio is meaningless. Likewise, if the company previously did not have earnings, then the percent change of the earnings is meaningless. Also consider the example where the previous value was negative. If the previous value was negative 1 and the current value is positive 99, then this happens: A negative change? But the value went up! Obviously that value does not make sense and should not be shown.", "title": "" }, { "docid": "589476", "text": "\"In the end, this is really not a finance question. It's about changing one's habits. (One step removed, however, since you are helping a friend and not seeking advice for yourself). I've learned a simple cause & effect question - Does someone who wants (goal here) do (this current bad habit)? For example, someone with weight to lose is about to grab the chips to sit and watch TV. They should quickly ask themselves \"\"Does a healthy, energetic person sit in front of the TV eating chips?\"\" The friend needs to make a connection between the expense he'd like to save up for and his current actions. There's a conscious decision in making the takeout purchase, he'd rather spend the money on that meal than to save .5% (or whatever percent) of the trip's cost. If he is clueless in the kitchen, that opens another discussion, one in which I'd remark that on the short list of things parents should teach their kids, cooking is up there. My wife is clueless in the kitchen, I taught our daughter how to be comfortable enough to make her own meals when she wants or when she's off on her own. If this is truly your friend's issue, you might need to be a cooking spirit guide to be successful.\"", "title": "" }, { "docid": "358997", "text": "What is your time horizon? Over long horizons, you absolutely want to minimise the expense ratio – a seemingly puny 2% fee p.a. can cost you a third of your savings over 35 years. Over short horizons, the cost of trading in and trading out might matter more. A mutual fund might be front-loaded, i.e. charge a fixed initial percentage when you first purchase it. ETFs, traded daily on an exchange just like a stock, don't have that. What you'll pay there is the broker commission, and the bid-ask spread (and possibly any premium/discount the ETF has vis-a-vis the underlying asset value). Another thing to keep in mind is tracking error: how closely does the fond mirror the underlying index it attempts to track? More often than not it works against you. However, not sure there is a systematic difference between ETFs and funds there. Size and age of a fund can matter, indeed - I've had new and smallish ETFs that didn't take off close down, so I had to sell and re-allocate the money. Two more minor aspects: Synthetic ETFs and lending to short sellers. 1) Some ETFs are synthetic, that is, they don't buy all the underlying shares replicating the index, actually owning the shares. Instead, they put the money in the bank and enter a swap with a counter-party, typically an investment bank, that promises to pay them the equivalent return of holding that share portfolio. In this case, you have (implicit) credit exposure to that counter-party - if the index performs well, and they don't pay up, well, tough luck. The ETF was relying on that swap, never really held the shares comprising the index, and won't necessarily cough up the difference. 2) In a similar vein, some (non-synthetic) ETFs hold the shares, but then lend them out to short sellers, earning extra money. This will increase the profit of the ETF provider, and potentially decrease your expense ratio (if they pass some of the profit on, or charge lower fees). So, that's a good thing. In case of an operational screw up, or if the short seller can't fulfil their obligations to return the shares, there is a risk of a loss. These two considerations are not really a factor in normal times (except in improving ETF expense ratios), but during the 2009 meltdown they were floated as things to consider. Mutual funds and ETFs re-invest or pay out dividends. For a given mutual fund, you might be able to choose, while ETFs typically are of one type or the other. Not sure how tax treatment differs there, though, sorry (not something I have to deal with in my jurisdiction). As a rule of thumb though, as alex vieux says, for a popular index, ETFs will be cheaper over the long term. Very low cost mutual funds, such as Vanguard, might be competitive though.", "title": "" }, { "docid": "451898", "text": "\"Discussing individual stocks is discouraged here, so I'll make my answer somewhat generic. Keep in mind, some companies go public in a way that takes the shares that are held by the investment VCs (venture capitalists) and cashes them out of their positions, i.e. most if not all shares are made public. In that case, the day after IPO, the original investors have their money, and, short of the risk of being sued for fraud, could not care less what the stock does. Other companies float a small portion up front, and retain the rest. This is a way of creating a market and valuing the company, but not floating so many shares the market has trouble absorbing it. This stock has a \"\"Shares Outstanding\"\" of 2.74B but has only floated 757.21M. The nearly 2 billion shares held by the original investors certainly impact their wallets with how this IPO went. See the key statistics for the details.\"", "title": "" }, { "docid": "419397", "text": "\"TBF - Proshares short 20+ Year Treasury The TBF fund is designed to track (hopefully) 100 percent of the inverse daily returns of the Barclays Capital 20+ Year U.S. Treasury Index. there's some risk of tracking error, and also a compounding effect if it's down several days in a row. (invest with care) There's also a TBT fund, but the risks are even greater since it is leveraged, potentially you could make the right long term call, but lose a lot in the short term due to tracking error and effect of compounding) (that would tend to make this one more appropriate for short term 'bets' on interest rates, and less so for a long term investor) There are also quite a few floating rate closed-end funds (Click here, then click on \"\"loan participation funds\"\") that should do well in a rising rate environment. Just beware that these funds seem to incorporate a substantial amount of credit risk as well as floating interest rate exposure. Closed end funds trade a lot like securities, since the fund is closed, you have to buy shares from another owner that is selling (just like with stocks), that means the shares can sometimes trade above or below the underlying value of the actual assets held by the fund depending on buying/selling pressure and the relative liquidity of a given fund.\"", "title": "" }, { "docid": "295511", "text": "When you buy a stock, the worst case scenario is that it drops to 0. Therefore, the most you can lose when buying a stock is 100% of your investment. When you short a stock, however, there's no limit on how high the stock can go. If you short a stock at 10, and it goes up to 30, then you've lost 200% on your investment. Therefore shorting stocks is riskier than buying stocks, since you can lose more than 100% of your investment when shorting. because the price might go up, but it will never be as big of a change as a regular price drop i suppose... That is not true. Stocks can sometimes go up significantly (50-100% or more) in a very short amount of time on a positive news release (such as an earnings or a buyout announcement). A famous example occurred in 2008, when Volkswagen stock quintupled (went up 400%) in less than 2 days on some corporate news: Porsche, for some reason, wants to control Volkswagen, and by building up its stake has driven up the price. Hedge funds, figuring the share price would fall as soon as Porsche got control and stopped buying, sold a lot of VW shares short. Then last weekend, Porsche disclosed that it owned 42.6 percent of the stock and had acquired options for another 31.5 percent. It said it wanted to go to 75 percent. The result: instant short-squeeze. The German state of Lower Saxony owns a 20 percent stake in VW, which it said it would not sell. That left precious few shares available for anyone else. The shorts scrambled to cover, and the price leaped from about €200, or about $265, to above €1,000.", "title": "" }, { "docid": "133204", "text": "\"Probably the biggest driver of the increased volumes that day was a change in sentiment towards the healthcare sector as a whole that caused many healthcare companies to experience higher volumes ( https://www.bloomberg.com/press-releases/2017-07-11/asset-acquisitions-accelerate-in-healthcare-sector-boosting-potential-revenue-growth ). Following any spike, not just sentiment related spikes, the market tends to bounce back to about where it had been previously as analysts at the investment banks start to see the stock(s) as being overbought or oversold. This is because the effect of a spike on underlying ratios such as the Sharpe ratio or the PE ratio makes the stock look less attractive to buyers and more attractive to sellers, including short sellers. Note, however, that the price is broadly still a little higher than it was before the spike as a result of this change in sentiment. Looking at the price trends on Bloomberg (https://www.bloomberg.com/quote/CDNA:US) the price had been steadily falling for the year prior to the spike but was levelling out at just over $1 in the few months immediately prior to the spike. The increased interest in the sector and the stock likely added to a general change in the direction of the price trend and caused traders (as opposed to investors) to believe that there was a change in the price trend. This will have lead to them trading the stock more heavily intraday exacerbating the spike. Note that there traders will include HFT bots as well as human traders. You question the legality of this volume increase but the simple answer is that we may never know if it was the target of traders manipulating the price or a case of insider trading. What we can see is that (taking \"\"animal spirits\"\" into account) without any evidence of illegality there are plenty of potential reasons why the spike may have occurred. Spikes are common where traders perceive a change in a trend as they rush to cash in on the change before other traders can and then sell out quickly when they realise that the price is fundamentally out of sync with the firm's underlying position. You yourself say that you have been watching the stock for some time and, by that fact alone, it is likely that others are for the same reasons that you are. Otherwise you wouldn't be looking at it. Where people are looking at a stock expecting it to take off or drop you expect volatility and volatility means spikes!\"", "title": "" }, { "docid": "516214", "text": "\"TL;DR - go with something like Barry Ritholtz's All Century Portfolio: 20 percent total U.S stock market 5 percent U.S. REITs 5 percent U.S. small cap value 15 percent Pacific equities 15 percent European equities 10 percent U.S. TIPs 10 percent U.S. high yield corp bonds 20 percent U.S. total bond UK property market are absurdly high and will be crashing a lot very soon The price to rent ratio is certainly very high in the UK. According to this article, it takes 48 years of rent to pay for the same apartment in London. That sounds like a terrible deal to me. I have no idea about where prices will go in the future, but I wouldn't voluntarily buy in that market. I'm hesitant to invest in stocks for the fear of losing everything A stock index fund is a collection of stocks. For example the S&P 500 index fund is a collection of the largest 500 US public companies (Apple, Google, Shell, Ford, etc.). If you buy the S&P 500 index, the 500 largest US companies would have to go bankrupt for you to \"\"lose everything\"\" - there would have to be a zombie apocalypse. He's trying to get me to invest in Gold and Silver (but mostly silver), but I neither know anything about gold or silver, nor know anyone who takes this approach. This is what Jeremy Siegel said about gold in late 2013: \"\"I’m not enthusiastic about gold because I think gold is priced for either hyperinflation or the end of the world.\"\" Barry Ritholtz also speaks much wisdom about gold. In short, don't buy it and stop listening to your friend. Is buying a property now with the intention of selling it in a couple of years for profit (and repeat until I have substantial amount to invest in something big) a bad idea? If the home price does not appreciate, will this approach save you or lose you money? In other words, would it be profitable to substitute your rent payment for a mortgage payment? If not, you will be speculating, not investing. Here's an articles that discusses the difference between speculating and investing. I don't recommend speculating.\"", "title": "" }, { "docid": "163904", "text": "\"The answers here are all correct. This is 100% scam, beyond any reasonable doubt. Don't fall for it. However, I felt it valuable to explain what would happen were you to fall for this. It's not all that hard to understand, but it involves understanding some of the time delays that exist in modern banking today. The most important thing to understand is that depositing a check does not actually put dollars in your account, even though it appears to. A check is not legal tender for debts public and private. It's a piece of paper known as a \"\"bill of exchange.\"\" It's an authorization for a payee (you), to request that their bank pay you the amount on the check. A transaction made with a check does not actually draw to a close until your bank and their bank communicate and cause the actual transfer of funds to take place. This process is called \"\"clearing\"\" the check. Despite living in the modern times, this process is slow. It can take 7-10 days to clear a check (especially if it is an international bank). This is not good for the banking business. You can imagine how difficult it would be to tell a poor client, who is living paycheck to paycheck, that he can't have his pay until the check clears a week later. Banks have an interest in hiding this annoying feature of the modern banking system, so they do. When you deposit a check, the bank will typically advance you the money (an interest free loan, in effect) while the check \"\"floats\"\" (i.e. until it clears). This creates the illusion that the money is actually in your account for most intents and purposes. (presumably a bank would distinguish between the floating check and a cleared check if you tried to close out your account, but otherwise it looks and feels like the money is in your hands). Of course, if the check is dishonored (because the payer had insufficient funds, or the account simply did not exist), your bank will not get the money. At this moment, they will cancel any advances you received and notify you that the check bounced. Again, this happens 7-10 days later. The general pattern of this scam is that they will pay you by a method which clears slowly, like a check. They will then ask you to withdraw the money using a faster clearing method (like a wire transfer or withdrawing the cash). Typically they will be encouraging you to move quickly (they are on a timetable... when their check bounces, the game is up!) At this time, it will appear as though the account has a positive balance, but in fact it has a negative balance plus an advance on the check. This looks great until 7-10 days later, when the check bounces. At that time, the bank will cancel the advance, and reality will set in. You will now have an open bank account, legally opened by you in your own name, which is deeply in debt. Meanwhile, the scammer walks away with all the money that you sent them (which cleared quickly). There are many variants which can hide the details. Some can play games with check kiting to try to make your first check clear (then try to rope you in for a more painful hit). Some will change the instruments they use (checks are the easy ones, so they're simply most common). Don't try to think \"\"maybe this one is legit.\"\" These scammers literally make a living off of making shady transactions look legit. Things I would recommend looking out for:\"", "title": "" }, { "docid": "180404", "text": "\"Intrinsic value is a myth. There is no such thing. Subjective human demand is the only thing that gives anything value. This subjectivity is different person to person and can change very quickly. Historically there are two main uses for gold: jewelry and money. How can you tell when a particular type of money is undervalued? It disappears from circulation since people prefer to use money that is overvalued. This phenomenon is paraphrased in Gresham's Law: Bad money drives out good money. The Coinage Act of 1792 established the US dollar as 371.25 grains of silver or 24.75 grains of gold. This established a government ratio of 15 ounces of silver to 1 ounce of gold. In the late 18th century there was a large production of silver from Mexico and the market ratio of silver to gold increased to 15.75 to 1 by 1805. The government ratio, however, was still 15 to 1. This was enough incentive for people to exchange their silver coins for gold coins at the government ratio, melt the gold, and sell the gold bullion overseas at the market value. Thus, gold coins disappeared from circulation as people either hoarded the gold or sent it abroad. People used the overvalued silver coins (i.e. the \"\"bad\"\" money) domestically and gold coins disappeared from the market. In an attempt to correct the problem of disappearing gold coins the Coinage Act of 1834 was enacted. It kept the US dollar at 371.25 grains of silver but changed the definition to 23.2 grains of gold which established a government ratio of 16 to 1. This was close to the market ratio of gold to silver at the time so both gold and silver coins appeared in circulation again. The gold rush of 1849 produced a lot of gold and the market ratio of silver to gold became 15.46 to 1. Now gold was overvalued so people began exchanging their gold coins for silver coins at the government ratio, melt the silver, and sell the silver bullion overseas at the market value. People used the overvalued gold coins (i.e. the \"\"bad\"\" money) domestically and silver coins disappeared from the market. When you see gold circulating everywhere you will know it is overvalued compared to other types of money. Paper money always drives gold out of circulation since the market ratio of paper to gold severely under values gold. Source here.\"", "title": "" }, { "docid": "459257", "text": "I am going to break rank slightly with the consensus so far. Here's the deal, it probably DOES help your credit slightly to pay it multiple times per month if it isn't a hassle, but the bump is likely to be minimal and very temporary. Here's why: A key component of your score is your credit usage ratio. That is the ratio of how much of your credit limits you are using. You want to keep this number down as low as possible. Now here is where it gets tricky. Although you have a grace period to pay off your card with no interest, the credit card companies don't generally report the balance as of the due date. They either report the high balance or an average balance over the month. That is, it is based on how much you use, not how much balance you carry over each month. It isn't very intuitive, but that's just how it is. So technically, keeping that balance lower over the course of the month WILL probably help you, but the credit usage ratio is generally a rolling average over the last x months, so the effect will wear off quickly. So it is probably not worth doing unless you know you are going to apply for a loan in the next 6 months and need a temporary, small bump. Another consideration is that paying early provides no real financial benefit in terms of finance charges, but you are giving up liquidity which does have some value. 1) You probably could get at least a little interest for keeping the money in your account a few more weeks. 2) If you have a major financial emergency, e.g. broken down car, you might appreciate the fact that you kept your options open to carry that balance over a month.", "title": "" }, { "docid": "296420", "text": "It depends a lot on your investment period and the quality of the bonds that you want to invest. For example, if you want to invest until the maturity of the bonds, and the bonds are very safe (i.e. they are not expected to default), it does not matter that the interest rate rise. That is because at the maturity of the bond it will converge to its maturity value which will be independent of the change of the interest rates (although on the middle of the life the price of the bond will go down, but the coupon should remain constant -unless is a floating coupon bond-). An option could be to invest in an ETF with short term bonds (e.g. 1 year) with AAA credit rating (high quality, so very low default rate). It won't yield much, but is more than 0% if you hold it until maturity.", "title": "" }, { "docid": "499849", "text": "\"They're taking advantage of float. Like so many things in the financial world today, this practice is a (strictly legal) fraud. When you make the transaction, the money is available immediately, for reasons that should be intuitively obvious to anyone who's ever used PayPal. It doesn't take 3 minutes for the broker to get that money, let alone 3 days. But if they can hold on to that money instead of turning it over to you, they can make money from it for themselves, putting money that rightfully belongs to you to work for them instead, earning interest on short-term loans, money market accounts, etc. The SEC mandates that this money must be turned over to you within 3 days so it should not surprise anyone that that's exactly how long the \"\"we have to wait for it to clear\"\" scam runs for. Even if it doesn't seem like very much money per transaction, for a large brokerage with hundreds of thousands of clients, all the little bits add up very quickly. This is why they feel no need to compete by offering better service: offering poor service is making them a lot of money that they would lose by offering better service.\"", "title": "" }, { "docid": "497530", "text": "When property changes hands the sale prices may or may not be used to determine the appraised value of the property, and they may or may not be used to determine the appraised value of other properties. Because of the nature of the transaction: you already have an existing business relationship, the local government is likely to ignore the data point provided by your transaction when determining values of similar properties. They have no idea if there was some other factor used to determine the price. They will also not include in the calculation transactions that are a result of foreclosure becasue the target price is the loan value not the true value. California and some other jurisdictions do add another wrinkle. You will need to determine if the transaction will trigger a reevaluation of the property value. In some states the existing laws of the state limited the annual growth of the assessment, but that could now be recaptured if the jurisdiction rules that this is a new ownership: California Board of Equalization - Change in Ownership - Frequently Asked Questions How does a change in ownership affect property taxes? Each county assessor's office reviews all recorded deeds for that county to determine which properties require reappraisal under the law. The county assessors may also discover changes in ownership through other means, such as taxpayer self-reporting, field inspections, review of building permits and newspapers. Once the county assessor has determined that a change in ownership has occurred, Proposition 13 requires the county assessor to reassess the property to its current fair market value as of the date ownership changed. Since property taxes are based on the assessed value of a property at the time of acquisition, a current market value that is higher than the previously assessed Proposition 13 adjusted base year value will increase the property taxes. Conversely, if the current market value is lower than the previously assessed Proposition 13 adjusted base year value, then the property taxes on that property will decrease. Only that portion of the property that changes ownership, however, is subject to reappraisal. For example, if 50 percent of the property is transferred, the assessor will reassess only 50 percent of the property at its current fair market value as of the date of the transfer, and deduct 50 percent from any existing Proposition 13 base year value. In most cases, when a person buys a residence, the entire property undergoes a change in ownership and 100 percent of the property is reassessed to its current market value.", "title": "" }, { "docid": "351925", "text": "\"1 - in most cases, the difference between filing joint or married filing single is close to zero. When there is a difference you're better off filing joint. 2 - The way the W4 works is based on how many allowances you claim. Unfortunately, even in the day of computers, it does not allow for a simple \"\"well my deduction are $xxx, don't tax that money.\"\" Each allowance is equal to one exemption, same as you get for being you, same as the wife gets, same as each kid. 3 people X $3800 = $11,400 you are telling the employer to take off the top before calculating your tax. She does this by using Circular E and is able to calculate your tax as you request. If one is in the 15% bracket, one more exemption changes the tax withheld by $570. So if you were going to owe $400 in April, one few exemption will have you overpay $170. i.e. in this 15% bracket, each exemption changes annual withholding by that $570. For most people, running the W4 numbers will get them very close, and only if they are getting back or owing over $500, will they even think of adjusting. 3 - My recently published Last Minute Tax Moves offers a number of interesting ideas to address this. The concept of grouping deductions in odd years is worth noting. 4 - I'm not sure what this means, 2 accounts each worth $5000 should grow at the same rate if invested the same. The time it makes sense to load one person's account first is if they have better matching. You say you are not sure what percent your wife's company matches. You need to change this. For both of your retirement plans you need to know every detail, exact way to maximize matching, expense ratios for the investments you choose, any other fees, etc. Knowledge is power, and all that. In What is an appropriate level of 401k fees or expenses in a typical plan? I go on to preach about how fees can wipe out any tax benefit over time. For any new investor, my first warning is always to understand what you are getting into. If you can't explain it to a friend, you shouldn't be in it. Edit - you first need to understand what choices are within the accounts. The 4% and 6% are in hindsight, right? These are not fixed returns. You should look at the choices and more heavily fund the account with the better selection. Deposit to her account at least to grab the match. As far as the longer term goals, see how the house purchase goes. Life has a way of sending you two kids and forcing you to tighten the budget. You may have other ideas in three years. (I have no P2P lending experience, by the way.) Last - many advise that separate finances are a bad path for a couple. It depends. Jane and I have separate check books, and every paycheck just keep enough to write small checks without worry, most of the money goes to the house account. Whatever works for you is what you should do. We've been happily married for most of the 17 years we've been married.\"", "title": "" }, { "docid": "45523", "text": "Most bond ETFs have switched to monthly dividends paid on the first of each month, in an attempt to standardize across the market. For ETFs (but perhaps not bond mutual funds, as suggested in the above answer) interest does accrue in the NAV, so the price of the fund does drop on ex-date by an amount equal to the dividend paid. A great example of this dynamic can be seen in FLOT, a bond ETF holding floating rate corporate bonds. As you can see in this screenshot, the NAV has followed a sharp up and down pattern, almost like the teeth of a saw. This is explained by interest accruing in the NAV over the course of each month, until it is paid out in a dividend, dropping the NAV sharply in one day. The effect has been particularly pronounced recently because the floating coupon payments have increased significantly (benchmark interest rates are higher) and mark-to-market changes in credit spreads of the constituent bonds have been very muted.", "title": "" }, { "docid": "148632", "text": "Also, almost by definition rebalancing involves making more trades than you would have otherwise; wouldn't the additional trading fees you incurred in doing so reduce the benefits of this strategy? You forgot to mention taxes. Rebalancing does or rather can incur costs. One way to minimize the costs is to use the parts of the portfolio that have essentially zero cost of moving. These generally are the funds in your retirement accounts. In the United States they can be in IRAs or 401Ks; they can be regular or Roth. Selling winners withing the structure of the plan doesn't trigger capital gains taxes, and many have funds within them that have zero loads. Another way to reduce trading fees is to only rebalance once a year or once every two years; or by setting a limit on how far out of balance. For example don't rebalance at 61/39 to get back to 60/40 even if it has been two years. Given that the ratio of investments is often rather arbitrary to begin with, how do I know whether I'm selling high and buying low or just obstinately sticking with a losing asset ratio? The ratio used in an example or in an article may be arbitrary, but your desired ratio isn't arbitrary. You selected the ratio of your investments based on several criteria: your age, your time horizon, your goals for the money, how comfortable you are with risk. As these change during your investing career those ratios would also morph. But they aren't arbitrary. These decisions to rebalance are separate from the ones to sell a particular investment. You could sell Computer Company X because of how it is performing, and buy stock in Technology Company Y because you think it has a better chance of growing. That transaction would not be a re-balancing. Selling part of your stock in Domestic Company A to buy stock in international Company B would be part of a re-balancing.", "title": "" }, { "docid": "591461", "text": "\"I recommend you take a look at this lecture (really, the whole series is enlightening), from Swenson. He identifies 3 sources of returns: diversification, timing and selection. He appears to discard timing and selection as impossible. A student kinda calls him out on this. Diversification reduces risk, not increase returns. It turns out they did time the market, by shorting .com's before the bubble, and real estate just before the downturn. In 1990, Yale started a \"\"Absolute Return\"\" unit and allocated like 15 percent to it, mostly by selling US equities, that specializes in these sorts of hedging moves. As for why you might employ managers for specific areas, consider that the expense ratio Wall Street charges you or me still represent a very nice salary when applied to the billions in Yale's portfolio. So they hire internally to reduce expenses, and I'm sure they're kept busy. They also need people to sell off assets to maintain ratios, and figuring out which ones to sell might take specialized knowledge. Finally, in some areas, you functionally cannot invest without management. For example, Yale has a substantial allocation in private equity, and by definition that doesn't trade on the open market. The other thing you should consider is that for all its diversification, Yale lost 25 percent of their portfolio in 2009. For a technique that's supposed to reduce volatility, they seem to have a large range of returns over the past five years.\"", "title": "" }, { "docid": "434279", "text": "\"Here is the \"\"investing for retirement\"\" theoretical background you should have. You should base your investment decisions not simply on the historical return of the fund, but on its potential for future returns and its risk. Past performance does not indicate future results: the past performance is frequently at its best the moment before the bubble pops. While no one knows the specifics of future returns, there are a few types of assets that it's (relatively) safe to make blanket statements about: The future returns of your portfolio will primarily be determined by your asset allocation . The general rules look like: There are a variety of guides out there to help decide your asset allocation and tell you specifically what to do. The other thing that you should consider is the cost of your funds. While it's easy to get lucky enough to make a mutual fund outperform the market in the short term, it's very hard to keep that up for decades on end. Moreover, chasing performance is risky, and expensive. So look at your fund information and locate the expense ratio. If the fund's expense ratio is 1%, that's super-expensive (the stock market's annualized real rate of return is about 4%, so that could be a quarter of your returns). All else being equal, choose the cheap index fund (with an expense ratio closer to 0.1%). Many 401(k) providers only have expensive mutual funds. This is because you're trapped and can't switch to a cheaper fund, so they're free to take lots of your money. If this is the case, deal with it in the short term for the tax benefits, then open a specific type of account called a \"\"rollover IRA\"\" when you change jobs, and move your assets there. Or, if your savings are small enough, just open an IRA (a \"\"traditional IRA\"\" or \"\"Roth IRA\"\") and use those instead. (Or, yell at your HR department, in the event that you think that'll actually accomplish anything.)\"", "title": "" }, { "docid": "192894", "text": "This isn't new. In the mid 80s rules were established by the IRS to differentiate life insurance from Modified Endowment Contracts, placing upper limits on how much money could be placed in life insurance accounts relative to the coverage provided and how quickly (fastest a policy can become paid-in-full is 7 years). None of this closes the fundamental loophole, but it exists for a reason, taxation of life insurance is probably unwise and would result in less people using life insurance as a risk mitigation technique, despite the fact that it's very appropriate for that in some situations. The problem here is that once you get out of everyday-people numbers and into very large sums the vehicle can be clearly abused to avoid taxes on investment gains while living, and possibly avoid them altogether depending on how the estate is structured, and this is bad for the average person who'd like the megarich to pay their percent towards the public needs the same way the average guy does.", "title": "" }, { "docid": "390598", "text": "Since recent changes to credit scoring (July 2017) it may not be necassary to do this, as more emphasis is placed on having a timely payment history and less emphasis is placed on having a low credit utilization ratio. Using what’s known as trended data is the biggest change. The phrase means credit scores will take into account the trajectory of a borrower’s debts on a month-to-month basis. In fact, having a low credit utilization ratio may even negatively effect you (if your available credit line value is high): ... VantageScore will now mark a borrower negatively for having excessively large credit card limits, on the theory that the person could run up a high credit card debt quickly. Those who have prime credit scores may be hurt the most, since they are most likely to have multiple cards open. But those who like to play the credit card rewards program points game could be affected as well. source", "title": "" }, { "docid": "87150", "text": "To point #1: We are moving but I don't know If I can afford the rent as the family grows I would start by looking at your debt-to-income ratio. In the US, most banks look at this for mortgage purposes, but it also gives you a general idea of what monthly mortgage payments will be comfortable given your particular financial situation. Think of it this way, if a bank is unwilling to lend you money because of a high debt-to-income level, this indicates that you have very little leeway with regard to your budget. So a lower number indicates that you will have more flexibility and comfort with meeting your rent/mortgage obligations when unforeseen bills pop up. The article below indicates having < 43% DTI is ideal (in the US). Here's a link to a debt to income calculator and some extra info (I suggest finding one aimed at the UK market): WellsFargo debt to income calculator Why is the 43% debt to income ratio important? Point #2: How can a person measure how much to spend on food, car, bills or rent from his salary? Is there a formula to keep in check? Other answers have addressed how to make a budget, so I will not repeat that. However, here's another angle with regards to spending/saving. This article recommends 50/30/20: According to the popular 50/30/20 rule, you should reserve 50 percent of your budget for essentials like rent and food, 30 percent for discretionary spending, and at least 20 percent for savings. Read more at: https://www.moneyunder30.com/how-much-should-you-save-every-month-2 In the real world, these goals may not be realistic, and different people have different ideas about how aggressive to be with regards to savings. However, you can get a general idea and adapt for your particular needs. Point 3: I find myself looking at my account every single day and get tensed and sad because almost whenever the money (pay) comes in I freak out that after everything there is nothing for us to enjoy or save.", "title": "" }, { "docid": "53637", "text": "\"&gt;No, virtually ever item in the CPI is adjusted using hedonics, which by definition can only be used to lower inflation, not adjust it up. Wow. Just wow. Let's analyze this: &gt;virtually ever item in the CPI is adjusted using hedonics How does one apply hedonics to energy? There are so many items in the CPI basket for which this does not even make sense I don't know where to begin with such a blanket statement. [Here is how the BLS computes CPI](http://www.bls.gov/cpi/cpifaq.htm#Question_6). Note the categories, and that they currently track hundreds of goods in each of about 200 categories, totaling tens of thousands of goods. With a little digging you can find the weighting. [Here is the list of what they apply hedonic weights to](http://www.bls.gov/cpi/cpihqaitem.htm). It is a vastly smaller subset of all goods tracked, and the weightings makes them not affect overall CPI much *at all*. All the precise methodologies are listed on the BLS site, and you can track it all down. As stated below, someone has done the analysis (and there is a PDF on the site) and they obtained that incuding hedonic items affects inflation only by 0.005 percent per year. &gt;which by definition can only be used to lower inflation By your definition? The actual definition does not force either direction. In reality it adjusts up and down as clearly shown in BLS reports, which I'll link below. &gt;, not adjust it up. As I'll list below, it in fact does go both ways. Finally, analysis of hedonics seems to indicate it has a miniscule effect on inflation rates, again papers are cited in the link shown below. [Critics often incorrectly assume that BLS only adjusts for quality increases, not for decreases, and that hedonic adjustments have a large downward impact on the CPI. On the contrary, BLS has used hedonic models in the CPI shelter and apparel components for roughly two decades, and on average hedonic adjustments usually increase the rate of change of those indexes. Since 1998, hedonic models have been introduced in several other components, mostly consumer durables such as personal computers and televisions, but these newer areas have a combined weight of only about one percent in the CPI. A recent article by BLS economists estimated that the hedonic models currently used in the CPI outside of the shelter and apparel areas have increased the annual rate of change of the All Items CPI, but by only about 0.005 percent per year.](http://www.bls.gov/cpi/cpiqa.htm#Question_4). &gt;inflation represents how the value of the dollar has accrued vs the value of a 20\"\" TV, which is what the definition of inflation is. No, inflation must measure the price *of the same good* over time. When some goods are no longer available, other goods must be investigated to provide continuity in the comparisons. Otherwise you'll have me comparing the price of a horse to the price of a car since they both provide transportation, yet over time one replaces the other, and direct comparisons on $ alone does not accurately measure what one gets for their money. You cannot compare the cost of different goods purely on price alone and call that inflation. &gt;So, no, I don't think you're correct on this. Well, [since other places that track inflation](http://bpp.mit.edu/) arrive at very similar results using different methodologies, and a vastly larger pool of goods I think that you overstate that the changes did not increase accuracy of inflation measurement. &gt;This is also kind of glossing over the fact that the CPI essentially makes the bold argument that energy and transportation prices never affect inflation. CPI makes no such claim. What do you think caused inflation in the early 1970s when oil prices shot up? [Here is the most recent CPI data release from BLS](http://www.bls.gov/news.release/cpi.nr0.htm) which quite clearly shows both energy and transportation changes being reflected in the CPI. I think when you make a claim you should at least look up if it matches the actual data. This is tiring trying to find evidence for/against so many dogmatic beliefs.\"", "title": "" }, { "docid": "377364", "text": "That's easy, keep making the payments and go on with life. The number that matters more than loan/market value is loan/equity. As long as you can sell it for enough to pay the balance on your loan you should be okay. Not saying it doesn't suck, but financially you are fine. If you owe more than the house is worth, I'd suggest paying it down as quickly as possible to fix that ratio to reduce your financial risk in case you lose your source of income. Personally, I think it is pretty slimy for people to walk away from house notes or try to short sell them when they can afford to continue payments just because the market value of the house fell. How would you feel if, when house prices were skyrocketing, the bank canceled your loan and repossessed your house because they could resell it for more money? (not that they could realistically, just speaking hypothetically.)", "title": "" }, { "docid": "524030", "text": "John Bogle never said only buy the S&P 500 or any single index Q:Do you think the average person could safely invest for retirement and other goals without expert advice -- just by indexing? A: Yes, there is a rule of thumb I add to that. You should start out heavily invested in equities. Hold some bond index funds as well as stock index funds. By the time you get closer to retirement or into your retirement, you should have a significant position in bond index funds as well as stock index funds. As we get older, we have less time to recoup. We have more money to protect and our nervousness increases with age. We get a little bit worried about that nest egg when it's large and we have little time to recoup it, so we pay too much attention to the fluctuations in the market, which in the long run mean nothing. How much to pay Q: What's the highest expense ratio that one should pay for a domestic equity fund? A: I'd say three-quarters of 1 percent maybe. Q: For an international fund? A: I'd say three-quarters of 1 percent. Q: For a bond fund? A: One-half of 1 percent. But I'd shave that a little bit. For example, if you can buy a no-load bond fund or a no-load stock fund, you can afford a little more expense ratio, because you're not paying any commission. You've eliminated cost No. 2....", "title": "" }, { "docid": "238130", "text": "because it's not cheaper? it's virtually free to run a private chain (no transaction fees, no competition for mining), it doesn't require even a millionth of a fraction of the maintenance resources, and you maintain total operational control over it (bitcoin could crash, it's encryption could be broken, 100's of things could change which would totally shitbrick your internal infrastructure). lastly, if you want, you can destroy the chain (say if you are sharing private documents with another legal firm, you can destroy the chain when the case is done, the documents wont be floating in a public chain for perpetuity). the mega chain is a very stupid idea because it forces everything to be hosted by everyone, which very quickly loses feasibility, instead you will likely see an increase in very specific use case chains.", "title": "" }, { "docid": "455952", "text": "Applying for a mortgage is a bit of paperwork, but not too bad of an experience. Rates are pretty tight, if one lender were more that 1/4% lower than another, they'd be inundated with applications. Above a certain credit score, you get the 'best' rate, a search will show you the rates offered in your area. If you are a first time buyer, there are mortgages that might benefit you. If you are a vet (for non-native English readers, a veteran who served in the US armed forces, not a veterinarian, who is an animal doctor) there are mortgages that offer low-to-no down payment with attractive rates. Yes, avoid PMI, it's a crazy penalty on your overall expense of home purchase. If banks qualify you for different amounts, it shouldn't be a huge difference, a few percent variation. But, the standard ratios are pretty liberal even today, and getting the most you'd qualify for is probably too much. Using the standard 28/36% ratios, a bank will qualify you for 4X your income as a loan. e.g you make $50K, they'll lend you $200K. This is a bit too much in my opinion. If you come up short, you are really looking to borrow too much, and should probably wait. If you owe a bit on loans, it should squeeze in between those two ratios, 28/36. But I wouldn't borrow on a credit line to add to the purchase, that's asking for trouble.", "title": "" }, { "docid": "30373", "text": "S & P's site has a methodology link that contains the following which may be of use: Market Capitalization. Unadjusted market capitalization of US$ 4.6 billion or more for the S&P 500, US$ 1.2 billion to US$ 5.1 billion for the S&P MidCap 400, and US$ 350 million to US$ 1.6 billion for the S&P SmallCap 600. The market cap of a potential addition to an index is looked at in the context of its short- and medium-term historical trends, as well as those of its industry. These ranges are reviewed from time to time to assure consistency with market conditions. Liquidity. Adequate liquidity and reasonable price – the ratio of annual dollar value traded to float adjusted market capitalization should be 1.00 or greater, and the company should trade a minimum of 250,000 shares in each of the six months leading up to the evaluation date. Domicile. U.S. companies. For index purposes, a U.S. company has the following characteristics: The final determination of domicile eligibility is made by the U.S. Index Committee.", "title": "" }, { "docid": "542915", "text": "\"Patience has never been my strong suit Unfortunately this is what you need to build up credit. The activities that increase your credit score are paying your bills on time and not using too much of the available credit that you do have. The rest (age of accounts, recent pulls, etc.) are short-term indicators that indicate changes in behavior that will make lenders pause and understand what the reasons behind the events are. Also keep in mind that your credit score shouldn't run your life. It should be a passive indicator of your financial habits - not something that you actively manipulate. Is there anything I can do to raise my score without having to take out a loan with interest? Pay your bills on time, and don't take out more credit than you need. You're already in the \"\"excellent\"\" category, so there's no reason to panic or try to manipulate it. Even if you temporarily dip below, if you need to make a big purchase (house), your loan-to-value and debt/income ratio will be much bigger factors in what interest rate you can get. As far as the BofA card goes, if you don't need it, cancel it. It might cause a temporary dip in your credit, but it will go away quickly, and you're better off not having credit cards that you don't need.\"", "title": "" } ]
21
70% of burn patients are admitted for hospitalization and further treatment after appearing at hospital emergency wards or outpatient clinics.
[ { "docid": "41493639", "text": "Burns are one of the most devastating conditions encountered in medicine. The injury represents an assault on all aspects of the patient, from the physical to the psychological. It affects all ages, from babies to elderly people, and is a problem in both the developed and developing world. All of us have experienced the severe pain that even a small burn can bring. However the pain and distress caused by a large burn are not limited to the immediate event. The visible physical and the invisible psychological scars are long lasting and often lead to chronic disability. Burn injuries represent a diverse and varied challenge to medical and paramedical staff. Correct management requires a skilled multidisciplinary approach that addresses all the problems facing a burn patient. This series provides an overview of the most important aspects of burn injuries for hospital and non-hospital healthcare workers.​workers. Figure 1 Top: Child with 70% full thickness burns, which required resuscitation, intensive care support, and extensive debridement and skin grafting. Left: The same child one year later at a burns camp, having made a good recovery. A reasonable outcome is possible ...", "title": "ABC of burns. Introduction." } ]
[ { "docid": "45341480", "text": "AIM/PURPOSE The aim of this study was to compare clinical outcome of children with scald burns treated with a hydrofiber dressing (Aquacel(®), Convatec Inc.) with the former standard of care with silver sulfadiazine (Flammazine(®); Solvay Pharmaceuticals), considering surgical intervention and length of stay (LOS). METHODS A retrospective study of all consecutive children from zero to four years with primary scald burns up to 10% admitted to the Burn Centre of the Maasstad Hospital Rotterdam between January 1987 and January 2010 were reviewed. For data collection a prospective computerized database was used. For comparison the study period was divided into two periods representing the period before and after the introduction of the hydrofiber dressing (HFD), respectively 1987-1999 (period 1) and 1999-2010 (period 2). RESULTS Over the whole study period 27.3% of 502 patients treated with silver sulfadiazine (Ag-SD) underwent surgery, while before the introduction of HFD 30.5% of 338 Ag-SD treated patients were operated upon. After the introduction of the HFD 20.7% of 164 patients treated with Ag-SD eventually underwent skin grafting, a significant difference with the 11.6% of 302 patients whose wounds were dressed with HFD (p<0.01). CONCLUSIONS Compared to silver sulfadiazine treatment a reduced number of surgical interventions was observed in mixed partial thickness scald burns up to 10% TBSA burned in children aged 0-4 years after the introduction of hydrofiber dressings. The mode of treatment with this wound dressing also limited hospital length of stay.", "title": "Reduction in skin grafting after the introduction of hydrofiber dressings in partial thickness burns: a comparison between a hydrofiber and silver sulphadiazine." }, { "docid": "13843341", "text": "OBJECTIVE To evaluate the cost effectiveness of standard treatment with and without the addition of ward based non-invasive ventilation in patients admitted to hospital with an acute exacerbation of chronic obstructive pulmonary disease. DESIGN Incremental cost effectiveness analysis of a randomised controlled trial. SETTING Medical wards in 14 hospitals in the United Kingdom. PARTICIPANTS The trial comprised 236 patients admitted to hospital with an acute exacerbation of chronic obstructive pulmonary disease and mild to moderate acidosis (pH 7.25-7.35) secondary to respiratory failure. The economic analysis compared the costs of treatment that these patients received after randomisation. MAIN OUTCOME MEASURE Incremental cost per in-hospital death. RESULTS 24/118 died in the group receiving standard treatment and 12/118 in the group receiving non-invasive ventilation (P=0.05). Allocation to the group receiving non-invasive ventilation was associated with a reduction in costs of 49362 pounds sterling (78741 dollars; 73109 euros), mainly through reduced use of intensive care units. The incremental cost effectiveness ratio was -645 pounds sterling per death avoided (95% confidence interval -2310 pounds sterling to 386 pounds sterling), indicating a dominant (more effective and less costly) strategy. Modelling of these data indicates that a typical UK hospital providing a non-invasive ventilation service will avoid six deaths and three to nine admissions to intensive care units per year, with an associated cost reduction of 12000-53000 pounds sterling per year. CONCLUSIONS Non-invasive ventilation is a highly cost effective treatment that both reduced total costs and improved mortality in hospital.", "title": "Cost effectiveness of ward based non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease: economic analysis of randomised controlled trial." }, { "docid": "14021596", "text": "BACKGROUND The objective of the study was to test the hypothesis that elevated red cell distribution width (RDW) at admission increases the risk of mortality in older patients admitted to the emergency department (ED). METHODS We performed a retrospective analysis of patients admitted to the ED between May 2013 and October 2013. We included patients who were older than 65 years who visited the ED with any medical problems. Baseline RDW values were measured at the time of admission to the ED. The primary outcome was all-cause in-hospital mortality. Multivariate logistic analysis was performed. RESULTS A total of 1,990 patients were finally included in this study. The mean age was 75 years (SD 7), and 936 (47 %) subjects were male. The in-hospital mortality rate was 3.76 % (74 patients). RDW values higher in non-survivors than in survivors (15.9 ± 2.5 vs. 13.8 ± 1.7, p < 0.001). Multivariate logistic analysis showed that RDW was associated with all-cause in-hospital mortality after adjusting for other confounding factors. DISCUSSION RDW value at admission is an independent predictor of all-cause in-hospital mortality among patients older than 65 years. After adjustment for multiple confounders, the all-cause in-hospital mortality rate increased by 21.8% for each 1% increase in RDW. CONCLUSION These results show that RDW at admission is associated with in-hospital mortality among patients older than 65. Thus, RDW at admission may represent a surrogate marker of disease severity. We caution against using these findings to aid clinical decision-making process until they are externally validated.", "title": "The association of Red cell distribution width and in-hospital mortality in older adults admitted to the emergency department" }, { "docid": "34208005", "text": "OBJECTIVES The original objective was to determine whether the use of bilevel positive airway pressure (BiPAP) ventilation would reduce the need for endotracheal intubation, the length of hospital stay, and hospital charges in patients with status asthmaticus. The development of physician treatment bias made patient enrollment difficult. The article subsequently describes the use of Bayesian statistics to explain study results when this bias occurs. METHODS This study was a prospective, randomized controlled clinical trial conducted over a 34.5-month period at an urban university hospital with an emergency department census of 94,000 annual visits. Patients remaining in status asthmaticus after initial standard treatment with inhaled beta-agonists and steroids were randomized to receive BiPAP ventilation plus standard treatment versus standard treatment alone (non-BiPAP), with intubation for either group as needed. Patients with concurrent cardiac or other pulmonary diseases were excluded. The primary outcome measures were endotracheal intubation rate and length of hospital stay. Secondary outcome measures included vital signs (respiratory rate, pulse rate, blood pressure), changes in expiratory peak flow, changes in pulse oximetry values, and hospital charges. Data were analyzed using Fisher's exact test, Mann-Whitney tests, and Bayesian statistics. For patients enrolled in the study more than once, data analysis was performed on the first enrollment only. RESULTS Nineteen patients were enrolled in the BiPAP group and 16 patients in the non-BiPAP group. Patients were frequently enrolled more than once and the data from the subsequent enrollments were excluded from the analysis. A marked decrease in enrollment, due to physician treatment bias, led to a premature termination of the study. Demographics showed that the groups were similar in age, sex, initial peak flow rate, and arterial blood gas measurements. There was a 7.3% increase (95% CI = -22 to +45) in the intubation rate in the non-BiPAP group (n = 2) compared with that for the BiPAP group (n = 1). No significant difference was seen in length of hospital stay or hospital charges, although there was a favorable trend toward the BiPAP group. Complications encountered in the BiPAP group included one patient with discomfort associated with the nasal BiPAP mask. Bayesian analysis demonstrated that in order for the collected data to be convincing at the 95% confidence level, the prior conviction among treating physicians that BiPAP was a successful treatment modality would have had to be 98.9%. CONCLUSIONS In this study, BiPAP appeared to have no deleterious effects in patients with status asthmaticus, with a trend toward decreased endotracheal intubation rate, decreased length of hospital stay, and decreased hospital charges. Although further study with more patients is needed to determine the clinical and statistical significance of this intervention, ethical concerns regarding withholding BiPAP treatment from the patients in the control group forced a premature termination of the study in the authors' institution.", "title": "Ethical dilemmas in a randomized trial of asthma treatment: can Bayesian statistical analysis explain the results?" }, { "docid": "23862975", "text": "INTRODUCTION The face is the central point of the physical features; it transmits expressions and emotions, communicates feelings and allows for individual identity. Facial burns are very common and are devastating to the affected patient and results into numerous physical, emotional and psychosocial sequels. Partial thickness facial burns are very common especially among children. This study compares the effect of standard moist open technique management and a moist closed technique for partial thickness burns of the face. PATIENTS AND METHODS Patients with partial-thickness facial burns admitted in the burn unit, Ain Shams University, Cairo, Egypt in the period from April 2009 to December 2009 were included in this study. They were divided into two groups to receive either open treatment with MEBO(®) (n=20) or coverage with Aquacel(®) Ag (n=20). Demographics (age, gender, ethnicity, TBSA, burn areas), length of hospital stay (LOS), rate of infections, time to total healing, frequency of dressing changes, pain, cost benefit and patient discomfort were compared between the two groups. The long-term outcome (incidence of hypertrophic scarring) was assessed for up to 6 months follow-up period. RESULTS There were no significant differences in demographics between the two groups. In the group treated with the Aquacel(®) Ag, the mean time for re-epithelialization was 10.5 days, while it was 12.4 days in the MEBO(®) group (p<0.05). Frequency of changes, pain and patient discomfort were less with Aquacel(®) Ag. Cost was of no significant difference between the two groups. Scar quality improved in the Aquacel(®) Ag treatment group. Three and 6 months follow-up was done and long-term outcomes were recorded in both groups. CONCLUSION Moist occlusive dressing (Aquacel(®) Ag) significantly improves the management and healing rate of partial thickness facial burns with better long-term outcome compared to moist open dressing (MEBO(®)).", "title": "Moist occlusive dressing (Aquacel(®) Ag) versus moist open dressing (MEBO(®)) in the management of partial-thickness facial burns: a comparative study in Ain Shams University." }, { "docid": "1259359", "text": "The incidence of the acquired immunodeficiency syndrome (AIDS) in Malawi is one of the highest in Central Africa. Since tuberculosis is an important initial manifestations of the disease, consecutive patients admitted to the tuberculosis (TB) wards of Zomba General Hospital, Malawi, were asked for permission to undergo a human immunodeficiency virus (HIV)-antibodies test. In addition, two other studies were done: from September 1986 all medical in-patients, clinically suspected for immune deficiency and from April 1988 all blood donors were tested for HIV seropositivity. Seventy-five percent of the TB patients volunteered; 32 out of 125 (26%) were seropositive. In the high-risk age groups (20-40 years) this percentage rose to 32. Among the medical in-patients suspected of immune deficiency the seropositivity rose sharply from April 1987 to October 1988. Among the blood donors tested, 20% were seropositive.", "title": "HIV seropositivity and tuberculosis in a large general hospital in Malawi." }, { "docid": "32084655", "text": "Mass-screening for lung cancer is rather a unique system in Japan. This study illustrates time from finding abnormality on mass-screening to final diagnosis of lung cancer. Among the 517 patients with lung cancer who were admitted to our hospital over a 10-year period up to December 2001, 83 (16.1%) were detected by mass-screening. We reviewed medical records of the 83 patients and determined the intervals from the mass-screening to the pathological diagnosis with clinical staging. Time from the mass-screening to the date of hospital visit was <2 months in 62 (74.7%) cases. Five (6.0%) patients visited hospital more than 6 months after the mass-screening. With respect to the interval, there was no statistical difference in gender (p=0.0680) and age (p=0.1532). Among 60 patients who were referred from outside, on average, patients visited our hospital 0.5 month after they first sought medical attention at nearby clinic, and at our hospital 0.5 month was required to make a pathological diagnosis of lung cancer with TNM staging. There was a statistical difference in survival between the patients who were diagnosed <4 months and the patients who were diagnosed >4 months from the screening (p=0.0487). The interval in most cases was acceptable. However, further improvements are still needed to minimize the delay and to maximize the benefits of early cancer detection.", "title": "Time from finding abnormality on mass-screening to final diagnosis of lung cancer." }, { "docid": "16390264", "text": "OBJECTIVES To determine the extent to which type of hospital admission (emergency compared with elective) and surgical procedure varied by socioeconomic circumstances, age, sex, and year of admission for colorectal, breast, and lung cancer. DESIGN Repeated cross sectional study with data from individual patients, 1 April 1999 to 31 March 2006. SETTING Hospital episode statistics (HES) dataset. PARTICIPANTS 564 821 patients aged 50 and over admitted with a diagnosis of colorectal, breast, or lung cancer. MAIN OUTCOME MEASURES Proportion of patients admitted as emergencies, and the proportion receiving the recommended surgical treatment. RESULTS Patients from deprived areas, older people, and women were more likely to be admitted as emergencies. For example, the adjusted odds ratio for patients with breast cancer in the least compared with most deprived fifth of deprivation was 0.63 (95% confidence interval 0.60 to 0.66) and the adjusted odds ratio for patients with lung cancer aged 80-89 compared with those aged 50-59 was 3.13 (2.93 to 3.34). There were some improvements in disparities between age groups but not for patients living in deprived areas over time. Patients from deprived areas were less likely to receive preferred procedures for rectal, breast, and lung cancer. These findings did not improve with time. For example, 67.4% (3529/5237) of patients in the most deprived fifth of deprivation had anterior resection for rectal cancer compared with 75.5% (4497/5959) of patients in the least deprived fifth (1.34, 1.22 to 1.47). Over half (54.0%, 11 256/20 849) of patients in the most deprived fifth of deprivation had breast conserving surgery compared with 63.7% (18 445/28 960) of patients in the least deprived fifth (1.21, 1.16 to 1.26). Men were less likely than women to undergo anterior resection and lung cancer resection and older people were less likely to receive breast conserving surgery and lung cancer resection. For example, the adjusted odds ratio for lung cancer patients aged 80-89 compared with those aged 50-59 was 0.52 (0.46 to 0.59). Conclusions Despite the implementation of the NHS Cancer Plan, social factors still strongly influence access to and the provision of care.", "title": "Social variations in access to hospital care for patients with colorectal, breast, and lung cancer between 1999 and 2006: retrospective analysis of hospital episode statistics" }, { "docid": "19464037", "text": "OBJECTIVE To describe outcomes and identify variables associated with hospital and 1-year survival for patients admitted to an intensive care unit (ICU) with an acute exacerbation of chronic obstructive pulmonary disease (COPD). DESIGN Prospective, multicenter, inception cohort study. SETTING Forty-two ICUs at 40 US hospitals. PATIENTS A total of 362 admissions for COPD exacerbation selected from the Acute Physiology and Chronic Health Evaluation (APACHE) III database of 17,440 ICU admissions. MEASUREMENTS AND RESULTS Hospital mortality for the 362 admissions was 24%. For the 167 patients aged 65 years or older, mortality was 30% at hospital discharge, 41% at 90 days, 47% at 180 days, and 59% at 1 year. Median survival for all patients was 224 days, and median survival for the patients who died within 1 year was 30.5 days. On multiple regression analysis, variables associated with hospital mortality included age, severity of respiratory and nonrespiratory organ system dysfunction, and hospital length of stay before ICU admission. Development of nonrespiratory organ system dysfunction was the major predictor of hospital mortality (60% of total explanatory power) and 180-day outcomes (54% of explanatory power). Respiratory physiological variables (respiratory rate, serum pH, PaCO2, PaO2, and alveolar-arterial difference in partial pressure of oxygen [PAO2-PaO2]) indicative of advanced dysfunction were more strongly associated with 180-day mortality rates (22% of explanatory power) than hospital death rates (4% of explanatory power). After controlling for severity of illness, mechanical ventilation at ICU admission was not associated with either hospital mortality or subsequent survival. CONCLUSIONS Patients with COPD admitted to an ICU for an acute exacerbation have a substantial hospital mortality (24%). For patients aged 65 years or older, mortality doubles in 1 year from 30% to 59%. Hospital and longer-term mortality is closely associated with development of nonrespiratory organ system dysfunction; severity of the underlying respiratory function substantially influences mortality following hospital discharge. The need for mechanical ventilation at ICU admission did not influence either short- or long-term outcomes. Physicians should be aware of these relationships when making treatment decisions or evaluating new therapies.", "title": "Hospital and 1-year survival of patients admitted to intensive care units with acute exacerbation of chronic obstructive pulmonary disease." }, { "docid": "26611094", "text": "BACKGROUND An increased volume of patients is associated with improved survival in numerous high-risk medical and surgical conditions. The relationship between the number of patients admitted (hospital volume) and outcome among patients with critical illnesses is unknown. METHODS We analyzed data from 20,241 nonsurgical patients receiving mechanical ventilation at 37 acute care hospitals in the Acute Physiology and Chronic Health Evaluation clinical information system from 2002 through 2003. Multivariate analyses were performed to adjust for the severity of illness and other differences in the case mix. RESULTS An increase in hospital volume was associated with improved survival among patients receiving mechanical ventilation in the intensive care unit (ICU) and in the hospital. Admission to a hospital in the highest quartile according to volume (i.e., >400 patients receiving mechanical ventilation per year) was associated with a 37 percent reduction in the adjusted odds of death in the ICU as compared with admission to hospitals in the lowest quartile (< or =150 patients receiving mechanical ventilation per year, P<0.001). In-hospital mortality was similarly reduced (adjusted odds ratio, 0.66; 95 percent confidence interval, 0.52 to 0.83; P<0.001). A typical patient in a hospital in a low-volume quartile would have an adjusted in-hospital mortality of 34.2 percent as compared with 25.5 percent in a hospital in a high-volume quartile. Among survivors, there were no significant trends in the length of stay in the ICU or the hospital. CONCLUSIONS Mechanical ventilation of patients in a hospital with a high case volume is associated with reduced mortality. Further research is needed to determine the mechanism of the relationship between volume and outcome among patients with a critical illness.", "title": "Hospital volume and the outcomes of mechanical ventilation." }, { "docid": "19308127", "text": "BACKGROUND P2Y12 inhibitor switching has appeared in clinical practice as a consequence of prasugrel and ticagrelor availability, apart from clopidogrel, for use in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). METHODS In the context of the GReek AntiPlatelet REgistry (GRAPE) we assessed the prevalence, predictive factors and short-term outcome of in-hospital P2Y12 inhibitor switching in 1794 ACS patients undergoing PCI. RESULTS Switching occurred in 636 (35.5%) patients of which in the form of clopidogrel to a novel agent, novel agent to clopidogrel and between prasugrel and ticagrelor in 574 (90.4%), 34 (5.3%) and 27 (4.3%) patients, respectively. Presentation to non PCI-capable hospital, bivalirudin use, age ≥75 years (inverse predictor), and regional trends emerged as predictive factors of switching to a novel agent. At combined in-hospital and one-month follow-up, propensity matched pairs analysis showed no differences in major adverse cardiovascular (MACE) or bleeding events between switching from clopidogrel to a novel agent vs novel agent constant administration. More Bleeding Academic Research Consortium type 1, type 2 and any type events and fewer MACE were seen when switching from clopidogrel to a novel agent vs only clopidogrel administration (23.7%, 3.8%, 30.6%, 1.2% vs 8.9%, 1.2%, 12.0%, 3.8% with P < .001, P = .03, P < .001 and P = .03 respectively). CONCLUSIONS In a real-life experience with contemporary antiplatelet treatment in ACS patients undergoing PCI, in-hospital switching represents common clinical practice. Clinical factors and regional practice differences seem to affect this strategy's choice, while switching to a novel agent may be associated with higher risk of bleeding.", "title": "In-hospital switching of oral P2Y12 inhibitor treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention: prevalence, predictors and short-term outcome." }, { "docid": "5596332", "text": "IMPORTANCE Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. OBJECTIVE To evaluate and, as needed, update definitions for sepsis and septic shock. PROCESS A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). KEY FINDINGS FROM EVIDENCE SYNTHESIS Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. RECOMMENDATIONS Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less. CONCLUSIONS AND RELEVANCE These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.", "title": "The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)." }, { "docid": "24575065", "text": "CONTEXT The Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA) altered reimbursements for outpatient chemotherapy drugs and drug administration services. Anecdotal reports suggest that these adjustments may have negatively affected access to chemotherapy for Medicare beneficiaries. OBJECTIVE To compare patient wait times and travel distances for chemotherapy before and after the enactment of the MMA. DESIGN, SETTING, AND PATIENTS Analysis of a nationally representative 5% sample of claims from the Centers for Medicare & Medicaid Services for the period 2003 through 2006. Patients were Medicare beneficiaries with incident breast cancer, colorectal cancer, leukemia, lung cancer, or lymphoma who received chemotherapy in inpatient hospital, institutional outpatient, or physician office settings. MAIN OUTCOME MEASURES Days from incident diagnosis to first chemotherapy visit and distance traveled for treatment, controlling for age, sex, race/ethnicity, cancer type, geographic region, comorbid conditions, and year of diagnosis and treatment. RESULTS There were 5082 incident cases of breast cancer, colorectal cancer, leukemia, lung cancer, or lymphoma in 2003; 5379 cases in 2004; 5116 cases in 2005; and 5288 cases in 2006. Approximately 70% of patients received treatment in physician office settings in each year. Although the distribution of treatment settings in 2004 and 2005 was not significantly different from 2003 (P = .24 and P = .72, respectively), there was a small but significant change from 2003 to 2006 (P = .02). The proportion of patients receiving chemotherapy in inpatient settings decreased from 10.2% in 2003 to 8.8% in 2006 (P = .03), and the proportion in institutional outpatient settings increased from 21.1% to 22.5% (P = .004). The proportion in physician offices remained at 68.7% (P = .29). The median time from diagnosis to initial chemotherapy visit was 28 days in 2003, 27 days in 2004, 29 days in 2005, and 28 days in 2006. In multivariate analyses, average wait times for chemotherapy were 1.96 days longer in 2005 than in 2003 (95% confidence interval [CI], 0.11-3.80 days; P = .04) but not significantly different in 2006 (0.88 days; 95% CI, -0.96 to 2.71 days; P = .35). Median travel distance was 7 miles (11.2 km) in 2003 and 8 miles (12.8 km) in 2004 through 2006. After adjustment, average travel distance remained slightly longer in 2004 (1.47 miles [2.35 km]; 95% CI, 0.87-2.07 miles [1.39-3.31 km]; P < .001), 2005 (1.19 miles [1.90 km]; 95% CI, 0.58-1.80 miles [0.93-2.88 km]; P < .001), and 2006 (1.30 miles [2.08 km]; 95% CI, 0.69-1.90 miles [1.10-3.04 km]; P < .001) compared with 2003. CONCLUSION There have not been major changes in travel distance and patient wait times for chemotherapy in the Medicare population since 2003, the year before MMA-related changes in reimbursement.", "title": "Association between the Medicare Modernization Act of 2003 and patient wait times and travel distance for chemotherapy." }, { "docid": "11718220", "text": "BACKGROUND Deep vein thrombosis (DVT) and pulmonary embolism are common after stroke. In small trials of patients undergoing surgery, graduated compression stockings (GCS) reduce the risk of DVT. National stroke guidelines extrapolating from these trials recommend their use in patients with stroke despite insufficient evidence. We assessed the effectiveness of thigh-length GCS to reduce DVT after stroke. METHODS In this outcome-blinded, randomised controlled trial, 2518 patients who were admitted to hospital within 1 week of an acute stroke and who were immobile were enrolled from 64 centres in the UK, Italy, and Australia. Patients were allocated via a central randomisation system to routine care plus thigh-length GCS (n=1256) or to routine care plus avoidance of GCS (n=1262). A technician who was blinded to treatment allocation undertook compression Doppler ultrasound of both legs at about 7-10 days and, when practical, again at 25-30 days after enrolment. The primary outcome was the occurrence of symptomatic or asymptomatic DVT in the popliteal or femoral veins. Analyses were by intention to treat. This study is registered, number ISRCTN28163533. FINDINGS All patients were included in the analyses. The primary outcome occurred in 126 (10.0%) patients allocated to thigh-length GCS and in 133 (10.5%) allocated to avoid GCS, resulting in a non-significant absolute reduction in risk of 0.5% (95% CI -1.9% to 2.9%). Skin breaks, ulcers, blisters, and skin necrosis were significantly more common in patients allocated to GCS than in those allocated to avoid their use (64 [5%] vs 16 [1%]; odds ratio 4.18, 95% CI 2.40-7.27). INTERPRETATION These data do not lend support to the use of thigh-length GCS in patients admitted to hospital with acute stroke. National guidelines for stroke might need to be revised on the basis of these results. FUNDING Medical Research Council (UK), Chief Scientist Office of Scottish Government, Chest Heart and Stroke Scotland, Tyco Healthcare (Covidien) USA, and UK Stroke Research Network.", "title": "Effectiveness of thigh-length graduated compression stockings to reduce the risk of deep vein thrombosis after stroke (CLOTS trial 1): a multicentre, randomised controlled trial" }, { "docid": "4824840", "text": "Importance Estimates from claims-based analyses suggest that the incidence of sepsis is increasing and mortality rates from sepsis are decreasing. However, estimates from claims data may lack clinical fidelity and can be affected by changing diagnosis and coding practices over time. Objective To estimate the US national incidence of sepsis and trends using detailed clinical data from the electronic health record (EHR) systems of diverse hospitals. Design, Setting, and Population Retrospective cohort study of adult patients admitted to 409 academic, community, and federal hospitals from 2009-2014. Exposures Sepsis was identified using clinical indicators of presumed infection and concurrent acute organ dysfunction, adapting Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria for objective and consistent EHR-based surveillance. Main Outcomes and Measures Sepsis incidence, outcomes, and trends from 2009-2014 were calculated using regression models and compared with claims-based estimates using International Classification of Diseases, Ninth Revision, Clinical Modification codes for severe sepsis or septic shock. Case-finding criteria were validated against Sepsis-3 criteria using medical record reviews. Results A total of 173 690 sepsis cases (mean age, 66.5 [SD, 15.5] y; 77 660 [42.4%] women) were identified using clinical criteria among 2 901 019 adults admitted to study hospitals in 2014 (6.0% incidence). Of these, 26 061 (15.0%) died in the hospital and 10 731 (6.2%) were discharged to hospice. From 2009-2014, sepsis incidence using clinical criteria was stable (+0.6% relative change/y [95% CI, −2.3% to 3.5%], P = .67) whereas incidence per claims increased (+10.3%/y [95% CI, 7.2% to 13.3%], P < .001). In-hospital mortality using clinical criteria declined (−3.3%/y [95% CI, −5.6% to −1.0%], P = .004), but there was no significant change in the combined outcome of death or discharge to hospice (−1.3%/y [95% CI, −3.2% to 0.6%], P = .19). In contrast, mortality using claims declined significantly (−7.0%/y [95% CI, −8.8% to −5.2%], P < .001), as did death or discharge to hospice (−4.5%/y [95% CI, −6.1% to −2.8%], P < .001). Clinical criteria were more sensitive in identifying sepsis than claims (69.7% [95% CI, 52.9% to 92.0%] vs 32.3% [95% CI, 24.4% to 43.0%], P < .001), with comparable positive predictive value (70.4% [95% CI, 64.0% to 76.8%] vs 75.2% [95% CI, 69.8% to 80.6%], P = .23). Conclusions and Relevance In clinical data from 409 hospitals, sepsis was present in 6% of adult hospitalizations, and in contrast to claims-based analyses, neither the incidence of sepsis nor the combined outcome of death or discharge to hospice changed significantly between 2009-2014. The findings also suggest that EHR-based clinical data provide more objective estimates than claims-based data for sepsis surveillance.", "title": "Incidence and Trends of Sepsis in US Hospitals Using Clinical vs Claims Data, 2009-2014" }, { "docid": "44048701", "text": "IMPORTANCE The need for surgery for the majority of patients with displaced proximal humeral fractures is unclear, but its use is increasing. OBJECTIVE To evaluate the clinical effectiveness of surgical vs nonsurgical treatment for adults with displaced fractures of the proximal humerus involving the surgical neck. DESIGN, SETTING, AND PARTICIPANTS A pragmatic, multicenter, parallel-group, randomized clinical trial, the Proximal Fracture of the Humerus Evaluation by Randomization (PROFHER) trial, recruited 250 patients aged 16 years or older (mean age, 66 years [range, 24-92 years]; 192 [77%] were female; and 249 [99.6%] were white) who presented at the orthopedic departments of 32 acute UK National Health Service hospitals between September 2008 and April 2011 within 3 weeks after sustaining a displaced fracture of the proximal humerus involving the surgical neck. Patients were followed up for 2 years (up to April 2013) and 215 had complete follow-up data. The data for 231 patients (114 in surgical group and 117 in nonsurgical group) were included in the primary analysis. INTERVENTIONS Fracture fixation or humeral head replacement were performed by surgeons experienced in these techniques. Nonsurgical treatment was sling immobilization. Standardized outpatient and community-based rehabilitation was provided to both groups. MAIN OUTCOMES AND MEASURES Primary outcome was the Oxford Shoulder Score (range, 0-48; higher scores indicate better outcomes) assessed during a 2-year period, with assessment and data collection at 6, 12, and 24 months. Sample size was based on a minimal clinically important difference of 5 points for the Oxford Shoulder Score. Secondary outcomes were the Short-Form 12 (SF-12), complications, subsequent therapy, and mortality. RESULTS There was no significant mean treatment group difference in the Oxford Shoulder Score averaged over 2 years (39.07 points for the surgical group vs 38.32 points for the nonsurgical group; difference of 0.75 points [95% CI, -1.33 to 2.84 points]; P = .48) or at individual time points. There were also no significant between-group differences over 2 years in the mean SF-12 physical component score (surgical group: 1.77 points higher [95% CI, -0.84 to 4.39 points]; P = .18); the mean SF-12 mental component score (surgical group: 1.28 points lower [95% CI, -3.80 to 1.23 points]; P = .32); complications related to surgery or shoulder fracture (30 patients in surgical group vs 23 patients in nonsurgical group; P = .28), requiring secondary surgery to the shoulder (11 patients in both groups), and increased or new shoulder-related therapy (7 patients vs 4 patients, respectively; P = .58); and mortality (9 patients vs 5 patients; P = .27). Ten medical complications (2 cardiovascular events, 2 respiratory events, 2 gastrointestinal events, and 4 others) occurred in the surgical group during the postoperative hospital stay. CONCLUSIONS AND RELEVANCE Among patients with displaced proximal humeral fractures involving the surgical neck, there was no significant difference between surgical treatment compared with nonsurgical treatment in patient-reported clinical outcomes over 2 years following fracture occurrence. These results do not support the trend of increased surgery for patients with displaced fractures of the proximal humerus. TRIAL REGISTRATION isrctn.com Identifier: ISRCTN50850043.", "title": "Surgical vs nonsurgical treatment of adults with displaced fractures of the proximal humerus: the PROFHER randomized clinical trial." }, { "docid": "40905302", "text": "OBJECTIVE Our objective was to assess the cost implications of changing the intensive care unit staffing model from on-demand presence to mandatory 24-hr in-house critical care specialist presence. DESIGN A pre-post comparison was undertaken among the prospectively assessed cohorts of patients admitted to our medical intensive care unit 1 yr before and 1 yr after the change. Our data were stratified by Acute Physiology and Chronic Health Evaluation III quartile and whether a patient was admitted during the day or at night. Costs were modeled using a generalized linear model with log-link and γ-distributed errors. SETTING A large academic center in the Midwest. PATIENTS All patients admitted to the adult medical intensive care unit on or after January 1, 2005 and discharged on or before December 31, 2006. Patients receiving care under both staffing models were excluded. INTERVENTION Changing the intensive care unit staffing model from on-demand presence to mandatory 24-hr in-house critical care specialist presence. MEASUREMENTS AND MAIN RESULTS Total cost estimates of hospitalization were calculated for each patient starting from the day of intensive care unit admission to the day of hospital discharge. Adjusted mean total cost estimates were 61% lower in the post period relative to the pre period for patients admitted during night hours (7 pm to 7 am) who were in the highest Acute Physiology and Chronic Health Evaluation III quartile. No significant differences were seen at other severity levels. The unadjusted intensive care unit length of stay fell in the post period relative to the pre period (3.5 vs. 4.8) with no change in non-intensive care unit length of stay. CONCLUSIONS We find that 24-hr intensive care unit intensivist staffing reduces lengths of stay and cost estimates for the sickest patients admitted at night. The costs of introducing such a staffing model need to be weighed against the potential total savings generated for such patients in smaller intensive care units, especially ones that predominantly care for lower-acuity patients.", "title": "Economic implications of nighttime attending intensivist coverage in a medical intensive care unit." }, { "docid": "21323587", "text": "Objectives: To study the change in outcome for patients admitted to an intensive care unit following the establishment of a team of resident medical staff and a change from an \"open\" to a \"closed\" organisational format. Design: Database review of prospectively collected data. Setting: Intensive care unit of a postgraduate teaching hospital. Subjects: 1134 admissions to the intensive care unit over a 3-year period, of whom 476 (42%) followed elective surgery. Main outcome measure: Hospital mortality corrected for illness severity by using the APACHE II scoring system. Results: Crude hospital mortality fell from 28% before the changes to 20% afterwards (P=0.01). With correction for case-mix factors, the probability of death after the changes was reduced by almost half (OR 0.51; CI 0.32, 0.82, P=0.005). Conclusion: A \"closed\" format of organisation of the delivery of care may result in improved outcomes for patients admitted to intensive care units.", "title": "The impact of organisational change on outcome in an intensive care unit in the United Kingdom" }, { "docid": "39059143", "text": "CONTEXT The association of an adult tele-intensive care unit (ICU) intervention with hospital mortality, length of stay, best practice adherence, and preventable complications for an academic medical center has not been reported. OBJECTIVE To quantify the association of a tele-ICU intervention with hospital mortality, length of stay, and complications that are preventable by adherence to best practices. DESIGN, SETTING, AND PATIENTS Prospective stepped-wedge clinical practice study of 6290 adults admitted to any of 7 ICUs (3 medical, 3 surgical, and 1 mixed cardiovascular) on 2 campuses of an 834-bed academic medical center that was performed from April 26, 2005, through September 30, 2007. Electronically supported and monitored processes for best practice adherence, care plan creation, and clinician response times to alarms were evaluated. MAIN OUTCOME MEASURES Case-mix and severity-adjusted hospital mortality. Other outcomes included hospital and ICU length of stay, best practice adherence, and complication rates. RESULTS The hospital mortality rate was 13.6% (95% confidence interval [CI], 11.9%-15.4%) during the preintervention period compared with 11.8% (95% CI, 10.9%-12.8%) during the tele-ICU intervention period (adjusted odds ratio [OR], 0.40 [95% CI, 0.31-0.52]). The tele-ICU intervention period compared with the preintervention period was associated with higher rates of best clinical practice adherence for the prevention of deep vein thrombosis (99% vs 85%, respectively; OR, 15.4 [95% CI, 11.3-21.1]) and prevention of stress ulcers (96% vs 83%, respectively; OR, 4.57 [95% CI, 3.91-5.77], best practice adherence for cardiovascular protection (99% vs 80%, respectively; OR, 30.7 [95% CI, 19.3-49.2]), prevention of ventilator-associated pneumonia (52% vs 33%, respectively; OR, 2.20 [95% CI, 1.79-2.70]), lower rates of preventable complications (1.6% vs 13%, respectively, for ventilator-associated pneumonia [OR, 0.15; 95% CI, 0.09-0.23] and 0.6% vs 1.0%, respectively, for catheter-related bloodstream infection [OR, 0.50; 95% CI, 0.27-0.93]), and shorter hospital length of stay (9.8 vs 13.3 days, respectively; hazard ratio for discharge, 1.44 [95% CI, 1.33-1.56]). The results for medical, surgical, and cardiovascular ICUs were similar. CONCLUSION In a single academic medical center study, implementation of a tele-ICU intervention was associated with reduced adjusted odds of mortality and reduced hospital length of stay, as well as with changes in best practice adherence and lower rates of preventable complications.", "title": "Hospital mortality, length of stay, and preventable complications among critically ill patients before and after tele-ICU reengineering of critical care processes." }, { "docid": "45920278", "text": "BACKGROUND Studies have shown that women use more health care services than men. We used important independent variables, such as patient sociodemographics and health status, to investigate gender differences in the use and costs of these services. METHODS New adult patients (N = 509) were randomly assigned to primary care physicians at a university medical center. Their use of health care services and associated charges were monitored for 1 year of care. Self-reported health status was measured using the Medical Outcomes Study Short Form-36 (SF-36). We controlled for health status, sociodemographic information, and primary care physician specialty in the statistical analyses. RESULTS Women had significantly lower self-reported health status and lower mean education and income than men. Women had a significantly higher mean number of visits to their primary care clinic and diagnostic services than men. Mean charges for primary care, specialty care, emergency treatment, diagnostic services, and annual total charges were all significantly higher for women than men; however, there were no differences for mean hospitalizations or hospital charges. After controlling for health status, sociodemographics, and clinic assignment, women still had higher medical charges for all categories of charges except hospitalizations. CONCLUSIONS Women have higher medical care service utilization and higher associated charges than men. Although the appropriateness of these differences was not determined, these findings have implications for health care.", "title": "Gender differences in the utilization of health care services." }, { "docid": "44384384", "text": "AIMS While randomized clinical trials have compared clopidogrel with higher potency adenosine diphosphate (ADP) receptor inhibitors among patients with acute myocardial infarction, little is known about the frequency, effectiveness and safety of switching between ADP receptor inhibitors in routine clinical practice. METHODS AND RESULTS We studied 11,999 myocardial infarction patients treated with percutaneous coronary intervention at 230 hospitals from April 2010 to October 2012 in the TRANSLATE-ACS study. Multivariable Cox regression was used to compare six-month post-discharge risks of major adverse cardiovascular events (MACE: death, myocardial infarction, stroke, or unplanned revascularization) and Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-defined bleeding between in-hospital ADP receptor inhibitor switching versus continuation of the initially selected therapy. Among 8715 patients treated initially with clopidogrel, 994 (11.4%) were switched to prasugrel or ticagrelor; switching occurred primarily after percutaneous coronary intervention (60.9%) and at the time of hospital discharge (26.7%). Among 3284 patients treated initially with prasugrel or ticagrelor, 448 (13.6%) were switched to clopidogrel; 48.2% of switches occurred after percutaneous coronary intervention and 48.0% at hospital discharge. Switching to prasugrel or ticagrelor was not associated with increased bleeding when compared with continuation on clopidogrel (2.7% vs. 3.3%, adjusted hazard ratio 0.96, 95% confidence interval 0.64-1.42, p=0.82). Switching from prasugrel or ticagrelor to clopidogrel was not associated with increased MACE (8.9% vs. 7.7%, adjusted hazard ratio 1.06, 95% confidence interval 0.75-1.49, p=0.76) when compared with continuation on the higher potency agent. CONCLUSIONS In-hospital ADP receptor inhibitor switching occurs in more than one in 10 myocardial infarction patients in contemporary practice. In this observational study, ADP receptor inhibitor switching does not appear to be significantly associated with increased hazard of MACE or bleeding.", "title": "In-hospital switching between adenosine diphosphate receptor inhibitors in patients with acute myocardial infarction treated with percutaneous coronary intervention: Insights into contemporary practice from the TRANSLATE-ACS study." }, { "docid": "2488880", "text": "CONTEXT While it is established that management strategies and outcomes differ by gender for many diseases, its effect on infection has not been adequately studied. OBJECTIVE To investigate the role of gender among hospitalized patients treated for infection. DESIGN Observational cohort study conducted during a 26-month period from December 1996 through January 1999. SETTING University-affiliated hospital. PARTICIPANTS A total of 892 patients in the surgical units of the hospital with 1470 consecutive infectious episodes (782 in men and 688 in women). MAIN OUTCOME MEASURES Mortality during hospitalization by gender for infection episodes overall and for specific infectious sites, including lung, peritoneum, bloodstream, catheter, urine, surgical site, and skin/soft tissue. RESULTS Among all infections, there was no significant difference in mortality based on gender (men, 11.1% vs women, 14.2%; P = .07). After logistic regression analysis, factors independently associated with mortality included higher APACHE (Acute Physiology and Chronic Health Evaluation) II score, older age, malignancy, blood transfusion, and diagnosis of infection more than 7 days after admission, but not gender (female odds ratio [OR] for death, 1.32; 95% confidence interval [CI], 0.90-1.94; P = .16). Mortality was higher in women for lung (men, 18% vs women, 34%; P = .002) and soft tissue (men, 2% vs women, 10%; P < or = .05) infection; for other infectious sites, mortality did not differ by gender. Factors associated with mortality due to pneumonia by logistic regression included higher APACHE II score, malignancy, diabetes mellitus, diagnosis of infection more than 7 days after admission, older age, transplantation, and female gender (OR for death, 2.25; 95% CI, 1.17-4.32; P = .02). CONCLUSIONS Although gender may not be predictive of mortality among all infections, women appear to be at increased risk for death from hospital-acquired pneumonia, even after controlling for other comorbidities.", "title": "Gender-dependent differences in outcome after the treatment of infection in hospitalized patients." }, { "docid": "8190282", "text": "CONTEXT Noninvasive ventilation (NIV) has been associated with lower rates of endotracheal intubation in populations of patients with acute respiratory failure. OBJECTIVE To compare NIV with standard treatment using supplemental oxygen administration to avoid endotracheal intubation in recipients of solid organ transplantation with acute hypoxemic respiratory failure. DESIGN AND SETTING Prospective randomized study conducted at a 14-bed, general intensive care unit of a university hospital. PATIENTS Of 238 patients who underwent solid organ transplantation from December 1995 to October 1997, 51 were treated for acute respiratory failure. Of these, 40 were eligible and 20 were randomized to each group. INTERVENTION Noninvasive ventilation vs standard treatment with supplemental oxygen administration. MAIN OUTCOME MEASURES The need for endotracheal intubation and mechanical ventilation at any time during the study, complications not present on admission, duration of ventilatory assistance, length of hospital stay, and intensive care unit mortality. RESULTS The 2 groups were similar at study entry. Within the first hour of treatment, 14 patients (70%) in the NIV group, and 5 patients (25%) in the standard treatment group improved their ratio of the PaO2 to the fraction of inspired oxygen (FIO2). Over time, a sustained improvement in PaO2 to FIO2 was noted in 12 patients (60%) in the NIV group, and in 5 patients (25%) randomized to standard treatment (P = .03). The use of NIV was associated with a significant reduction in the rate of endotracheal intubation (20% vs 70%; P = .002), rate of fatal complications (20% vs 50%; P = .05), length of stay in the intensive care unit by survivors (mean [SD] days, 5.5 [3] vs 9 [4]; P = .03), and intensive care unit mortality (20% vs 50%; P = .05). Hospital mortality did not differ. CONCLUSIONS These results indicate that transplantation programs should consider NIV in the treatment of selected recipients of transplantation with acute respiratory failure.", "title": "Noninvasive ventilation for treatment of acute respiratory failure in patients undergoing solid organ transplantation: a randomized trial." }, { "docid": "3654468", "text": "Importance Glucagon-like peptide-1 (GLP-1) receptor agonists are effective therapies for the treatment of type 2 diabetes and are all currently available as an injection. Objectives To compare the effects of oral semaglutide with placebo (primary) and open-label subcutaneous semaglutide (secondary) on glycemic control in patients with type 2 diabetes. Design, Setting, and Patients Phase 2, randomized, parallel-group, dosage-finding, 26-week trial with 5-week follow-up at 100 sites (hospital clinics, general practices, and clinical research centers) in 14 countries conducted between December 2013 and December 2014. Of 1106 participants assessed, 632 with type 2 diabetes and insufficient glycemic control using diet and exercise alone or a stable dose of metformin were randomized. Randomization was stratified by metformin use. Interventions Once-daily oral semaglutide of 2.5 mg (n = 70), 5 mg (n = 70), 10 mg (n = 70), 20 mg (n = 70), 40-mg 4-week dose escalation (standard escalation; n = 71), 40-mg 8-week dose escalation (slow escalation; n = 70), 40-mg 2-week dose escalation (fast escalation, n = 70), oral placebo (n = 71; double-blind) or once-weekly subcutaneous semaglutide of 1.0 mg (n = 70) for 26 weeks. Main Outcomes and Measures The primary end point was change in hemoglobing A1c (HbA1c) from baseline to week 26. Secondary end points included change from baseline in body weight and adverse events. Results Baseline characteristics were comparable across treatment groups. Of the 632 randomized patients (mean age, 57.1 years [SD, 10.6]; men, 395 (62.7%); diabetes duration, 6.3 years [SD, 5.2]; body weight, 92.3 kg [SD, 16.8]; BMI, 31.7 [SD, 4.3]), 583 (92%) completed the trial. Mean change in HbA1c level from baseline to week 26 decreased with oral semaglutide (dosage-dependent range, −0.7% to −1.9%) and subcutaneous semaglutide (−1.9%) and placebo (−0.3%); oral semaglutide reductions were significant vs placebo (dosage-dependent estimated treatment difference [ETD] range for oral semaglutide vs placebo, –0.4% to –1.6%; P = .01 for 2.5 mg, <.001 for all other dosages). Reductions in body weight were greater with oral semaglutide (dosage-dependent range, −2.1 kg to −6.9 kg) and subcutaneous semaglutide (−6.4 kg) vs placebo (−1.2 kg), and significant for oral semaglutide dosages of 10 mg or more vs placebo (dosage-dependent ETD range, –0.9 to –5.7 kg; P < .001). Adverse events were reported by 63% to 86% (371 of 490 patients) in the oral semaglutide groups, 81% (56 of 69 patients) in the subcutaneous semaglutide group, and 68% (48 of 71 patients) in the placebo group; mild to moderate gastrointestinal events were most common. Conclusions and Relevance Among patients with type 2 diabetes, oral semaglutide resulted in better glycemic control than placebo over 26 weeks. These findings support phase 3 studies to assess longer-term and clinical outcomes, as well as safety. Trial Registration clinicaltrials.gov Identifier: NCT01923181", "title": "Effect of Oral Semaglutide Compared With Placebo and Subcutaneous Semaglutide on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Clinical Trial" }, { "docid": "24408040", "text": "BACKGROUND Heart failure (HF) is a serious complication and often the cause of death in adults with congenital heart disease (CHD). Therefore, our aims were to determine the frequency of HF-admissions, and to assess risk factors of first HF-admission and of mortality after first HF-admission in adults with CHD. METHODS The Dutch CONCOR registry was linked to the Hospital Discharge Registry and National Mortality Registry to obtain data on HF-admissions and mortality. Risk factors for both HF-admission and mortality were assessed using Cox regression models. RESULTS Of 10,808 adult patients (49% male), 274 (2.5%) were admitted for HF during a median follow-up period of 21 years. The incidence of first HF-admission was 1.2 per 1000 patient-years, but the incidence of HF itself will be higher. Main defect, multiple defects, and surgical interventions in childhood were identified as independent risk factors of HF-admission. Patients admitted for HF had a five-fold higher risk of mortality than patients not admitted (hazard ratio (HR)=5.3; 95% confidence interval 4.2-6.9). One- and three-year mortality after first HF-admission were 24% and 35% respectively. Independent risk factors for three-year mortality after first HF-admission were male gender, pacemaker implantation, admission duration, non-cardiac medication use and high serum creatinine. CONCLUSIONS The incidence of HF-admission in adults with CHD is 1.2 per 1000 patient-years. Mortality risk is substantially increased after HF-admission, which emphasises the importance to identify patients at high risk of HF-admission. These patients might benefit from closer follow-up and earlier medical interventions. The presented risk factors may facilitate surveillance.", "title": "Heart failure admissions in adults with congenital heart disease; risk factors and prognosis." }, { "docid": "22414304", "text": "There is little information about treatment outcome in patients with smear-negative pulmonary tuberculosis (PTB) or extrapulmonary tuberculosis (EPTB) treated under routine programme conditions in subsaharan Africa. A prospective study was carried out to determine treatment outcome in an unselected cohort of TB patients admitted to Zomba General Hospital, Malawi. Eight hundred and twenty-seven adult TB patients (451 men and 376 women) were registered between 1 July and 31 December 1995. Standardized treatment outcomes of treatment completion, death, default, and transfer to another district were assessed in relation to type of TB, human immunodeficiency virus (HIV) serostatus, age and gender. Two hundred and fifty-four patients (31%) died by the end of treatment, half of the deaths occurring in the first month. Death rates were 19% among 386 patients with smear-positive PTB, 46% among 211 patients with smear-negative PTB, and 37% among 230 patients with EPTB; 77% of the patients were HIV seropositive. Among new patients, HIV-positive patients had higher death rates than HIV-negative patients (hazard ratio [HR] 2.5; 95% confidence interval [95% CI] 1.6-3.8). Smear-negative patients had the highest death rates (HR 3.9; 95% CI 2.7-5.5 compared to smear-positive patients), followed by EPTB patients (HR 2.6, 95% CI 1.8-3.7 compared to smear-positive patients). Death rates increased with age but were similar in men and women. Adult patients in Malawi with smear-negative PTB and EPTB have low treatment completion and high death rates, related to high levels of HIV infection. National TB control programmes in areas of high HIV prevalence should no longer ignore treatment outcomes in patients with smear-negative PTB or EPTB.", "title": "Treatment outcome of an unselected cohort of tuberculosis patients in relation to human immunodeficiency virus serostatus in Zomba Hospital, Malawi." }, { "docid": "14724693", "text": "CONTEXT Chronic low back pain (LBP) with degenerative lumbar osteoarthritis (OA) is widespread in the adult population. Although glucosamine is increasingly used by patients with chronic LBP, little is known about its effect in this setting. OBJECTIVE To investigate the effect of glucosamine in patients with chronic LBP and degenerative lumbar OA. DESIGN, SETTING, AND PARTICIPANTS A double-blind, randomized, placebo-controlled trial conducted at Oslo University Hospital Outpatient Clinic, Oslo, Norway, with 250 patients older than 25 years of age with chronic LBP (>6 months) and degenerative lumbar OA. INTERVENTIONS Daily intake of 1500 mg of oral glucosamine (n = 125) or placebo (n = 125) for 6 months, with assessment of effect after the 6-month intervention period and at 1 year (6 months postintervention). MAIN OUTCOME MEASURES The primary outcome was pain-related disability measured with the Roland Morris Disability Questionnaire (RMDQ). Secondary outcomes were numerical scores from pain-rating scales of patients at rest and during activity, and the quality-of-life EuroQol-5 Dimensions (EQ-5D) instrument. Data collection occurred during the intervention period at baseline, 6 weeks, 3 and 6 months, and again 6 months following the intervention at 1 year. Group differences were analyzed using linear mixed models analysis. RESULTS At baseline, mean RMDQ scores were 9.2 (95% confidence interval [CI], 8.4-10.0) for glucosamine and 9.7 (95% CI, 8.9-10.5) for the placebo group (P = .37). At 6 months, the mean RMDQ score was the same for the glucosamine and placebo groups (5.0; 95% CI, 4.2-5.8). At 1 year, the mean RMDQ scores were 4.8 (95% CI, 3.9-5.6) for glucosamine and 5.5 (95% CI, 4.7-6.4) for the placebo group. No statistically significant difference in change between groups was found when assessed after the 6-month intervention period and at 1 year: RMDQ (P = .72), LBP at rest (P = .91), LBP during activity (P = .97), and quality-of-life EQ-5D (P = .20). Mild adverse events were reported in 40 patients in the glucosamine group and 46 in the placebo group (P = .48). CONCLUSIONS Among patients with chronic LBP and degenerative lumbar OA, 6-month treatment with oral glucosamine compared with placebo did not result in reduced pain-related disability after the 6-month intervention and after 1-year follow-up. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00404079.", "title": "Effect of glucosamine on pain-related disability in patients with chronic low back pain and degenerative lumbar osteoarthritis: a randomized controlled trial." }, { "docid": "5185871", "text": "Importance The Sepsis-3 Criteria emphasized the value of a change of 2 or more points in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score, introduced quick SOFA (qSOFA), and removed the systemic inflammatory response syndrome (SIRS) criteria from the sepsis definition. Objective Externally validate and assess the discriminatory capacities of an increase in SOFA score by 2 or more points, 2 or more SIRS criteria, or a qSOFA score of 2 or more points for outcomes among patients who are critically ill with suspected infection. Design, Setting, and Participants Retrospective cohort analysis of 184 875 patients with an infection-related primary admission diagnosis in 182 Australian and New Zealand intensive care units (ICUs) from 2000 through 2015. Exposures SOFA, qSOFA, and SIRS criteria applied to data collected within 24 hours of ICU admission. Main Outcomes and Measures The primary outcome was in-hospital mortality. In-hospital mortality or ICU length of stay (LOS) of 3 days or more was a composite secondary outcome. Discrimination was assessed using the area under the receiver operating characteristic curve (AUROC). Adjusted analyses were performed using a model of baseline risk determined using variables independent of the scoring systems. Results Among 184 875 patients (mean age, 62.9 years [SD, 17.4]; women, 82 540 [44.6%]; most common diagnosis bacterial pneumonia, 32 634 [17.7%]), a total of 34 578 patients (18.7%) died in the hospital, and 102 976 patients (55.7%) died or experienced an ICU LOS of 3 days or more. SOFA score increased by 2 or more points in 90.1%; 86.7% manifested 2 or more SIRS criteria, and 54.4% had a qSOFA score of 2 or more points. SOFA demonstrated significantly greater discrimination for in-hospital mortality (crude AUROC, 0.753 [99% CI, 0.750-0.757]) than SIRS criteria (crude AUROC, 0.589 [99% CI, 0.585-0.593]) or qSOFA (crude AUROC, 0.607 [99% CI, 0.603-0.611]). Incremental improvements were 0.164 (99% CI, 0.159-0.169) for SOFA vs SIRS criteria and 0.146 (99% CI, 0.142-0.151) for SOFA vs qSOFA (P <.001). SOFA (AUROC, 0.736 [99% CI, 0.733-0.739]) outperformed the other scores for the secondary end point (SIRS criteria: AUROC, 0.609 [99% CI, 0.606-0.612]; qSOFA: AUROC, 0.606 [99% CI, 0.602-0.609]). Incremental improvements were 0.127 (99% CI, 0.123-0.131) for SOFA vs SIRS criteria and 0.131 (99% CI, 0.127-0.134) for SOFA vs qSOFA (P <.001). Findings were consistent for both outcomes in multiple sensitivity analyses. Conclusions and Relevance Among adults with suspected infection admitted to an ICU, an increase in SOFA score of 2 or more had greater prognostic accuracy for in-hospital mortality than SIRS criteria or the qSOFA score. These findings suggest that SIRS criteria and qSOFA may have limited utility for predicting mortality in an ICU setting.", "title": "Prognostic Accuracy of the SOFA Score, SIRS Criteria, and qSOFA Score for In-Hospital Mortality Among Adults With Suspected Infection Admitted to the Intensive Care Unit" }, { "docid": "32777637", "text": "BACKGROUND Concurrent use of multiple standing antipsychotics (antipsychotic polypharmacy) is increasingly common among both inpatients and outpatients. Although this has often been cited as a potential quality-of-care problem, reviews of research evidence on antipsychotic polypharmacy have not distinguished between appropriate versus inappropriate use. METHODS A MEDLINE search from 1966 to December 2007 was completed to identify studies comparing changes in symptoms, functioning, and/or side effects between patients treated with multiple antipsychotics and patients treated with a single antipsychotic. The studies were reviewed in two groups on the basis of whether prescribing was concordant with guideline recommendations for multiple-antipsychotic use. RESULTS A review of the literature, including three randomized controlled trials, found no support for the use of antipsychotic polypharmacy in patients without an established history of treatment resistance to multiple trials of monotherapy. In patients with a history of treatment resistance to multiple monotherapy trials, limited data support antipsychotic polypharmacy, but positive outcomes were primarily found in studies of clozapine augmented with a second-generation antipsychotic. DISCUSSION Research evidence is consistent with the goal of avoiding antipsychotic polypharmacy in patients who lack guideline-recommended indications for its use. The Joint Commission is implementing a core measure set for Hospital-Based Inpatient Psychiatric Services. Two of the measures address antipsychotic polypharmacy. The first measure assesses the overall rate. The second measure determines whether clinically appropriate justification has been documented supporting the use of more than one antipsychotic medication.", "title": "When is antipsychotic polypharmacy supported by research evidence? Implications for QI." }, { "docid": "10577574", "text": "BACKGROUND In the year 2000, the organizational structure of the ICU in the Zaandam Medical Centre (ZMC) changed from an open to a closed format ICU. The objective of this study was to evaluate the effect of this organizational change on outcome in high risk surgical patients. METHODS The medical records of all consecutive high risk surgical patients admitted to the ICU from 1996 to 1998 (open format) and from 2003 to 2005 (closed format), were reviewed. High-risk patients were defined according to the Identification of Risk in Surgical patients (IRIS) score. Parameters studied were: mortality, morbidity, ICU length of stay (LOS) and hospital LOS. RESULTS Mortality of ICU patients was 25.7% in the open format group and 15.8% in the closed format group (p = 0.01). Morbidity decreased from 48.6% to 46.1% (p = 0.6). The average length of hospital stay was 17 days in the open format group, and 21 days in the closed format group (p = 0.03). CONCLUSIONS High risk surgical patients in the ICU are patients that have undergone complex and often extensive surgery. These patients are in need of specialized treatment and careful monitoring for maximum safety and optimal care. Our results suggest that closed format is a more favourable setting than open format to minimize the effects of high risk surgery, and to warrant safe outcome in this patient group.", "title": "The impact of open versus closed format ICU admission practices on the outcome of high risk surgical patients: a cohort analysis" } ]
227842
Calling All the Monsters was the second single on a collection of recordings.
[ { "docid": "Calling_All_the_Monsters", "text": "`` Calling All the Monsters '' is a song performed by American pop recording artist China Anne McClain . It was produced by Niclas Molinder and Joacim Persson , who also co-wrote the song Johan Alkenas , and Charlie Mason , for the soundtrack , A.N.T. Farm ( 2011 ) , the soundtrack to the Disney Channel television series , A.N.T. Farm . It was released as the album 's second single on September 20 , 2011 through Walt Disney Records . Musically , the song is prominent electropop that runs through an club oriented beat , and the lyrics are Halloween themed , speaking of dancing with monsters . The song was met with generally positive reviews from critics , with the majority of them praising its playful nature and dance oriented sound . The song achieved its highest national peak in Slovakia , where it reached number one . Elsewhere , the song made the top 75 in the United Kingdom , peaking at number one . It has topped the Radio Disney Top 30 Countdown . The accompanying music video portrays McClain in a haunted house dancing with different types of monsters . The dance movements and the overall theme of the video are said to have been inspired by the music video for Michael Jackson 's 1984 single `` Thriller '' . The video features McClain 's sisters , Lauryn and Sierra , in its beginning and end .", "title": "" } ]
[ { "docid": "Good_Monsters", "text": "Good Monsters is the seventh full-length studio album from Jars of Clay , released by Essential Records on September 5 , 2006 . This is their last album of new material from Essential Records and it is said to be lyrically their most aggressive album to date . It features eleven original songs , and a remake of `` All My Tears '' by Julie Miller . It also features guest appearances by singer/songwriter Kate York ( on `` Even Angels Cry '' ) , Leigh Nash , of Sixpence None the Richer ( on `` Mirrors & Smoke '' ) , and the African Children 's Choir ( on `` Light Gives Heat '' ) . `` Dead Man ( Carry Me ) '' , the first single from the album , was released to radio stations on June 23 , 2006 . `` Work '' was released as the second single , along with its music video , in late August . The band also released a music video for the album track `` Good Monsters '' . In the September 2006 edition of CCM Magazine , the band credited fellow artist Ashley Cleveland with inspiring the improvisational sound of the album . In an editor 's fall albums overview in CCM Magazine , Good Monsters was called , `` the album that Jars of Clay will be remembered for . '' It ended up taking the award for the CCM Magazine staff picks as album of the year , winning four out of the five spaces .", "title": "" }, { "docid": "Mainliner:_Wreckage_from_the_Past", "text": "Mainliner : Wreckage From the Past is a collection of early recordings by Social Distortion . It was released on July 18 , 1995 , and contains songs which were recorded in 1981 . It is a collection of singles and B-sides that had never appeared on any of the band 's full-length albums ( except for `` Moral Threat '' and `` All the Answers '' ) . This album was released by Mike Ness ' Time Bomb Recordings ( distributed by Arista Records ) in 1995 along with the re-release of Mommy 's Little Monster and Prison Bound .", "title": "" }, { "docid": "Monsters_(Funeral_for_a_Friend_song)", "text": "`` Monsters '' was the second single released from Funeral for a Friend 's second album Hours . It charted at number 36 in the UK . The song received a large amount of airplay on Radio 1 at the time , but did not chart that well and is one of the few singles not to appear on their Greatest Hits compilation Your History Is Mine : 2002-2009 . CD1 : 1 . Monsters 2 . Sunday Bloody Sunday ( U2 Cover ) CD2 : 1 . Monsters 2 . The Boys Are Back In Town ( Thin Lizzy Cover ) 3 . Monsters ( Jagz Kooner Remix ) 7 '' A : Monsters B : Babylon 's Burning ( The Ruts Cover ) Category : Funeral for a Friend songs Category :2005 singles Category :2005 songs Category : Atlantic Records singles", "title": "" }, { "docid": "The_Definitive_Collection_(ABBA_album)", "text": "The Definitive Collection is a 2001 greatest hits compilation album of all the singles released by Swedish pop group ABBA . It consisted of two discs : the first featuring the singles from 1972 -- 79 ( `` People Need Love '' to `` Does Your Mother Know '' ) , and the second including the singles from 1979 -- 82 ( `` Voulez-Vous '' to `` Under Attack '' ) , with the tracks being listed in chronological order . The main exception is the track `` Thank You for the Music '' , which , despite being written and recorded in 1977 , was in fact released as a single ( primarily in the UK ) in 1983 after the band had split up . It appears on disc two , along with two bonus tracks , `` Ring Ring '' ( 1974 UK single remix ) , and `` Voulez-Vous '' ( 1979 US promo extended remix ) . The Australian version of The Definitive Collection adds a further two bonus tracks : `` Rock Me '' and `` Hasta Mañana '' . The 1974 remix of `` Ring Ring '' is the first appearance on CD of this version mastered from the original master tape , after the UK single master tapes had been returned to Polar Music by the former UK licensees , Epic Records . The track 's previous appearance on CD , in a 1999 singles boxed set , was mastered from a vinyl single . The Definitive Collection is the only ABBA compilation to include all the UK single releases from 1973 to 1983 . The four `` unofficial '' UK ABBA singles are included , these being the 1974 remix of `` Ring Ring '' , `` Angeleyes '' , `` Lay All Your Love on Me '' and `` Thank You for the Music '' . An `` unofficial single '' is one that was not released by ABBA 's record label , Polar Music , in any Scandinavian country . The Definitive Collection replaced an old collection of ABBA 's singles titled The Singles : The First Ten Years , released in 1982 . A DVD also called The Definitive Collection was released in 2002 , and features all of ABBA 's videos , as well as five bonus videos and a picture gallery . In the US the 2-CD set was bundled with the DVD . In 2003 , the album was ranked number 179 on Rolling Stone magazine 's list of the 500 greatest albums of all time . The album was re-released in 2012 as The Essential Collection with different artwork . This version removed both bonus tracks but added four tracks for which there were promotional videos : `` Bang-A-Boomerang '' , `` That 's Me '' , `` One Man , One Woman '' and `` Happy New Year '' . These tracks were included chronologically , and additionally `` Thank You for the Music '' was moved from the end of the album to its chronological place after `` Eagle '' . The collection was released as a two-CD set , a DVD , and a three-disc set including the DVD and both CDs .", "title": "" }, { "docid": "Ed_Harcourt_discography", "text": "This is the discography of the English singer-songwriter Ed Harcourt . To date , Harcourt has released six studio albums , two compilation albums , three EPs , and fourteen singles ( eleven of which have been released commercially ) . Harcourt 's debut album Here Be Monsters was released in June 2001 , and peaked on the UK Albums Chart at # 84 . His second album From Every Sphere , released in February 2003 , became his highest charting album at # 39 , and also features his highest charting single `` All of Your Days Will Be Blessed '' . Released only one year later was his third album Strangers , which features the single `` This One 's for You '' , Harcourt 's second-highest charting single at # 41 . Two further singles followed throughout the end of 2004 and 2005 : `` Born in the '70s '' and `` Loneliness '' . A download-only compilation entitled Elephant 's Graveyard , collecting B-sides and rarities from 2000 to 2005 , was issued in summer 2005 . Harcourt 's fourth studio album The Beautiful Lie was released in June 2006 . A compilation gathering some of Ed Harcourt 's best work appeared in October 2007 as Until Tomorrow Then : The Best of Ed Harcourt , featuring the new single `` You Put a Spell on Me '' . Additionally , a special limited edition version of the best-of included a bonus disc of completely unreleased material . Harcourt 's contract with Heavenly Records/EMI ended following the compilation 's release ; consequently , his Russian Roulette EP was released by American label Dovecote Records in May 2009 . Following a `` self-imposed sabbatical , '' Harcourt recorded his fifth studio album Lustre , released in June 2010 . The album is also the first release on Harcourt 's own record label , Piano Wolf Recordings .", "title": "" }, { "docid": "I_of_the_Storm", "text": "`` I of the Storm '' is a single recorded by the Icelandic indie folk/indie pop rock band Of Monsters and Men . The song was released as the second single from their second studio album , Beneath the Skin ( 2015 ) . It was written by Nanna Bryndís Hilmarsdóttir and Ragnar Þórhallsson ( of Of Monsters and Men ) . The single artwork was created by artistic director Leif Podhajsky .", "title": "" }, { "docid": "Little_Monster_(song)", "text": "`` Little Monster '' is a song written by Mike Kerr and Ben Thatcher of British rock duo Royal Blood . The song was originally recorded by the duo for release as a single , appearing on the band 's second single of the same name , released by Black Mammoth Records and Warner Bros. . Records on 10 February 2014 . The single marked the band 's first release under Warner Bros. . Records after signing with the label in 2013 . The track later appeared as the second track on the band 's debut extended play Out of the Black , and as the sixth track on the band 's eponymous debut studio album , Royal Blood . It is currently the duo 's highest-charting single . The song is included as a playable track in Guitar Hero Live .", "title": "" }, { "docid": "Monster_Mash", "text": "`` Monster Mash '' is a 1962 novelty song and the best-known song by Bobby `` Boris '' Pickett . The song was released as a single on Gary S. Paxton 's Garpax Records label in August 1962 along with a full-length LP called The Original Monster Mash , which contained several other monster-themed tunes . The `` Monster Mash '' single was # 1 on the Billboard Hot 100 chart on October 20 -- 27 of that year , just before Halloween . It has been a perennial holiday favorite ever since .", "title": "" }, { "docid": "The_Immaculate_Collection", "text": "The Immaculate Collection is the first greatest hits album by American singer and songwriter Madonna . It was released on November 9 , 1990 , by Sire and Warner Bros. . Records . It contains new remixes of fifteen of her hit singles from 1983 to 1990 , as well as two new songs , `` Justify My Love '' and `` Rescue Me '' . The title of the album is a loose pun on the Immaculate Conception , the conception of the Virgin Mary without the stain of original sin . An extended play titled The Holiday Collection was issued in Europe to accompany the compilation and the re-release of the single `` Holiday '' . It is the first album ever to use an audio technology called QSound . `` Justify My Love '' , the album 's first single , became Madonna 's ninth number-one hit on the Billboard Hot 100 and was one of her most controversial singles due to its sexually explicit music video . `` Rescue Me '' was released as the second single and became the highest-debuting single on Hot 100 by a female artist at that time , entering the chart at number fifteen and peaking at number nine . It became Madonna 's second album to be certified diamond by the Recording Industry Association of America for shipment of over ten million copies across the United States . It spent the second highest number of consecutive weeks at number one for a female solo artist in the UK , being at number one for a nine-week stint . The album has sold 30 million copies worldwide , making it the best selling compilation album by a solo artist and one of the best selling albums of all time .", "title": "" }, { "docid": "The_Eleventh_Day:_Single_Collection", "text": "The Eleventh Day : Single Collection is Japanese recording artist Gackt 's greatest hits album released on July 21 , 2010 . It includes all of his singles released in the last five years until then , and it his second single collection after The Sixth Day : Single Collection released in 2004 . The album was released by his former label Nippon Crown , and it is his last album with the label after he transferred to Avex Group 's recording conglomerate .", "title": "" }, { "docid": "Let_Me_Be_the_One_(Angela_Bofill_song)", "text": "`` Let Me Be the One '' is the title of a hit single by acclaimed jazz / R&B vocalist Angela Bofill and was the title track and second single release from her 1984 album Let Me Be The One . The song was produced by David Frank and Mic Murphy of The System and was written by Angela Bofill , Rick Suchow and Alan Palanker . The single reached # 84 on the US R&B Billboard chart . The song was later released on several Angela Bofill `` best of '' collections , including `` The Best of Angela Bofill '' , `` The Definitive Collection '' , and `` Angela Bofill : Platinum and Gold Collection '' , all released by Arista Records . A live version was released as well , on her 2006 CD Live From Manila on the Black Angel label . This song was used in a song called `` The One '' by Jon Phonics . Category :1985 singles Category : Angela Bofill songs", "title": "" }, { "docid": "What_Is_This_Thing_Called_Love?_(Alexander_O'Neal_song)", "text": "`` What Is This Thing Called Love ? '' is a song written by Jimmy Jam and Terry Lewis and recorded by American recording artist Alexander O'Neal . It is the second single from the singer 's fourth solo album , All True Man ( 1991 ) . The song 's distinctive backing vocals were performed by Lisa Keith . Following the successful chart performances of the All True Man single `` All True Man '' , `` What Is This Thing Called Love ? '' was released as the album 's second single .", "title": "" }, { "docid": "Monsters_in_the_Closet_(Swollen_Members_album)", "text": "Monsters in the Closet is Swollen Members ' third studio album released on Battleaxe Records . Monsters in the Closet is a collection of B-sides , rarities and unreleased tracks from the groups back catalog . In order to properly promote the record however , three brand new songs were created , two of which became popular singles . `` Steppin Thru '' led the way , continuing their streak of successful singles . `` Breathe '' was the next one , featuring one of their best known videos courtesy of Todd McFarlane , a Canadian artist primarily known for comic books like Spawn , also the music video ended up reaching # 1 MuchMusic 's Top 30 Countdown . Both singles did exceptionally well with videos that topped the MuchMusic Countdown and helped the record reach Gold Status almost immediately . Notable guest appearances include Canadian artists Nelly Furtado and Saukrates . The album was certified gold by the CRIA with sales of over 70,000 copies across Canada .", "title": "" }, { "docid": "Monster_(Lady_Gaga_song)", "text": "`` Monster '' is a song by American recording artist Lady Gaga , from her third EP , The Fame Monster ( 2009 ) . Inspired by her `` Fear of Attachment Monster '' , the record was written by Gaga , RedOne and Space Cowboy , with RedOne producing the track . Gaga had explained that `` Monster '' describes her fear of sex and relationships , and described the lyrics as being in love with the bad boy all the time , but instead of running away , one keeps going back to the same person . She added that the fear in `` Monster '' erupted from her need to have a stable relationship . Incorporating the usage of heavy bass lines , descending keyboard lines and `` massive '' choruses , `` Monster '' contains zombie like metaphors , and a reference to Gaga 's debut single `` Just Dance '' . `` Monster '' received generally positive reviews from critics who appreciated the song 's musical arrangement and frequently rated it as a top track from The Fame Monster , while some disliked its lyrics . `` Monster '' enjoyed brief commercial success in 2010 , charting on four singles charts , as well as the Billboard Hot Dance Club Songs and Latin Pop Airplay . Gaga has mostly performed `` Monster '' on her 2009 -- 11 The Monster Ball Tour . The performance included the portrayal of homicide and was criticized following a real-life incident at Manchester in the United Kingdom . She also performed `` Monster '' on The Oprah Winfrey Show .", "title": "" }, { "docid": "Pandemonium_–_The_Singles_Collection", "text": "Pandemonium -- The Singles Collection is a greatest hits record released by Swedish band BWO . It contains the hits from their three studio albums , and also includes 3 new songs . One of the songs is Lay Your Love on Me , the 2008 entry of the band in the Swedish preselection of Eurovision , Melodifestivalen . The second new song is called Barcelona . The third new song is The Bells of Freedom , which served as the theme song of the 2008 Europride . The video clip of this song features Alexander 's former band , Army of Lovers . A DVD by the same name , containing all 16 video clips and 2 remix videos , was released in Sweden on October 8 , 2008 .", "title": "" }, { "docid": "The_Tables", "text": "The Tables was an underground/DIY pop group formed in Oslo , Norway , in 1987 , by Bartleby ( vocals , real name Tore Sørensen # , Robert Birdeye #bass , drums , real name Steinar Buholm # , and Reg Trademark #guitar , real name Ståle Caspersen # , from the ashes of a band called The Bottle Collectors . This trio recorded their first 7 '' EP called `` Diary EP '' , released on the new-founded Voices of Wonder label in 1988 #now Voices Music and Entertainment # . For their first vinyl album , `` Shady Whims & Obstacles '' , released on their own Schtooopid Records in 1990 , they recruited Sandy Shore on Farfisa organ #real name Kjersti Gravklev # , and Mono on drums #real name Benedikte Sterner # . The Tables broke up soon after the release , but the original trio reformed in 1996/97 to record their second album called `` Holiday at Wobbledef Grunch '' , released on Perfect Pop Records , a small label that was run by the group members and others from the indie-pop scene in Oslo . However , history repeated itself , the band once again broke up , but reformed in 2000 , resulting in their third and final album , `` Nevermynd the Hillocks #Treble Without A Cause # '' , again on Perfect Pop Records # 2002 # . The band had a host of different members during their last stage , most of them contributing to their last album . Between their 1st and 2nd album they also recorded 8 songs for a split album with Astroburger , under the name Monsters of Doom , consisting of Bartleby , Reg Trademark , Robert Birdeye , Sandy Shore and Mike Mushroom #real name Mikkel Bay Vold # . All of the The Tables and Monsters of Doom output has been released on CD by Oslo-based Perfect Pop Records . The music on all The Tables ' three albums was a mixture of English 60 's popsike #inspired by the Rubble compilation series on Bam Caruso Records ) and early indiepop à la TV Personalities , while the Monsters of Doom tracks were more psychedelic and hard-edged . With their whimsy and part surrealistic lyrics and catchy melodies , The Tables achieved a sort of semi-legendary status in the Norwegian underground and other parts of the world .", "title": "" }, { "docid": "Dave_Gahan_discography", "text": "The discography of Dave Gahan , an English alternative music singer , consists of two studio albums , two live albums , one compilation album , six singles , and one video album . Gahan debuted in 1980 as lead singer of the electronic music band Depeche Mode ( see Depeche Mode discography ) . The group achieved worldwide success , producing fourteen top ten singles in the United Kingdom and selling over 100 million records worldwide . Gahan released his solo debut album Paper Monsters in June 2003 . The album , which was composed with Gahan 's close friend Knox Chandler , reached number thirty-six on the UK albums chart . It reached number five on the German and Swedish album charts . The album produced three singles , all of which reached the top forty in the UK singles chart . Live Monsters , a live video album , and its companion album Soundtrack to Live Monsters were released the following year . His second studio album , Hourglass , was released in October 2007 . It reached number fifty in the UK . In Germany , the album reached number two . The album 's lead single , `` Kingdom '' , reached number one on the United States Billboard Hot Dance Club Play chart .", "title": "" }, { "docid": "Calling_All_Monsters", "text": "Calling All Monsters is the second novel by Chris Westwood , a British author of children 's and young adult fiction . It was first published in the UK in 1990 by Viking Kestrel ( part of the Penguin Group ) and in the US in 1993 by HarperCollins Children 's Books . Optioned for film three times by Steven Spielberg and later Dreamworks , the film version of the book remains unproduced .", "title": "" }, { "docid": "Monster_(Arashi_song)", "text": "`` Monster '' is a song recorded by Japanese boy band Arashi . It was released on May 19 , 2010 by their record label J Storm . `` Monster '' is currently being used as the theme song to the drama starring Arashi member Satoshi Ohno . It was released as a CD single in two formats : a regular edition containing two B-sides and the instrumental of all the songs , and a limited edition containing the B-side and a DVD .", "title": "" }, { "docid": "Monster_Truck_(band)", "text": "Monster Truck are a Canadian rock band from Hamilton , Ontario . After the release of two EPs , their debut album Furiosity was released on Dine Alone Records on May 28 , 2013 and distributed on Universal . The band 's second studio album entitled Sittin ' Heavy was released on Mascot Records on February 19 , 2016 . Members include lead singer and bassist Jon Harvey , guitarist Jeremy Widerman , keyboardist Brandon Bliss and drummer Steve Kiely . Monster Truck 's 2011 EP The Brown EP found success for them in Canada . The single `` Seven Seas Blues '' charted in the top ten of the both the active rock airplay chart and the alternative rock airplay chart in the spring of 2012 . The band won the 2013 Juno Award for Breakthrough Group of the Year . They played the Download Festival in 2013 and supported Vista Chino on their European tour in October and November 2013 . The band started recording the Sittin ' Heavy album in January 2015 after touring with Alice in Chains , opening for them on their Canada/United States North American 2014 tour . Their track `` Sweet Mountain River '' was included in Ubisoft 's music game Rocksmith 2014 , `` Seven Seas Blues '' in EA Sports ' NHL 13 , and `` Old Train '' was used in an episode of Orphan Black , `` Variable and Full of Perturbation '' . The first single from their second studio album was released on October 19 , 2015 , a track called `` Do n't Tell Me How to Live '' . A song , `` The Enforcer '' , was also available only when pre-ordering the album . Their song `` Righteous Smoke '' is featured in EA Sports ' NHL 17 . The song `` The Enforcer '' was also used as the goal song for the Toronto Maple Leafs after every goal scored with a `` Go Leafs Go '' chant added to the song .", "title": "" }, { "docid": "Some_Kind_of_Monster_(song)", "text": "`` Some Kind of Monster '' is the fourth single from the American heavy metal band Metallica 's eighth studio album St. Anger . It was released on July 13 , 2004 through Elektra Records . The live B-sides are all taken from the previous single release `` The Unnamed Feeling '' EP . `` Some Kind of Monster '' was Nominated for Grammy Award for Best Hard Rock Performance in 2005 but lost to Velvet Revolver for the song `` Slither '' . A documentary of the same name was released on January 25 , 2005 and the single served as the film 's soundtrack .", "title": "" }, { "docid": "The_Deep_Purple_Singles_A's_and_B's", "text": "The Deep Purple Singles A 's & B 's is a compilation album of singles released by the British hard rock band Deep Purple . It was released on vinyl in October 1978 . An updated version of the album was issued on CD in 1993 and contains the complete collection of Deep Purple 's UK singles , recorded and released from 1968 to 1976 by the Mk I , II , III and IV line-ups of Deep Purple . In 2010 EMI released another double CD compilation album called Singles & E.P. Anthology '68 - ' 80 . It contains all songs as herein plus 15 tracks . The song `` Kentucky Woman '' is present in the album version , which is 38 seconds longer than the single edit .", "title": "" }, { "docid": "Parallel_(video)", "text": "Parallel is a video feature compiling all of R.E.M. 's Automatic for the People and Monster-era promotional videos , as well as several recorded for this release alone . It was released on video on May 30 , 1995 , and on DVD format on August 22 , 2000 , both on the Warner Brothers label . The release , which runs at 70 minutes , features promotional videos to all of the band 's singles from Automatic for the People and all but one from Monster ( `` Tongue '' had not been released as a single until after this compilation ) . Also included are several avant-garde clips excerpted from 1995 tour films , ranging from ten seconds to two minutes , playing in between each song , as well as an A -- Z of R.E.M. at the end of the feature . There are no bonus features on the DVD ; however , there is an optional lyrics subtitle track . Audio on the DVD-5 is PCM Stereo . The DVD was certified `` 15 '' in the UK due to nudity in ` Nightswimming ' . There were two versions released in the US . The `` A Version '' cut out the nudity from `` Nightswimming , '' while the `` D Version '' contained the uncut video . A Parental Advisory warning was placed on the cover of the `` D Version . ''", "title": "" }, { "docid": "Platinum_&_Gold_Collection_(Cowboy_Junkies_album)", "text": "Platinum & Gold Collection is a 2003 compilation of Cowboy Junkies songs recorded for RCA Records . The album is the second compilation of the band 's singles released by RCA in just three years , following 2001 's Best of the Cowboy Junkies , and is part of the label 's Platinum & Gold Collection series of discount-priced singles anthologies . All songs are drawn from the band 's RCA Records albums : The Trinity Session , The Caution Horses , Black Eyed Man and Pale Sun , Crescent Moon .", "title": "" }, { "docid": "Teeth_(song)", "text": "`` Teeth '' is a song recorded by American singer Lady Gaga . The track appears on The Fame Monster ( 2009 ) , her second major release and her third extended play . The song was written by Gaga , Taja Riley , Pete Wyoming Bender , and Teddy Riley , and produced by Gaga and Teddy Riley . It has an oral theme and has been called a `` perverse '' march and an ode to sadomasochism . `` Teeth '' peaked at number 107 on the UK Singles Chart and received a mixed reception from critics . Gaga performed the song during The Monster Ball Tour . In 2013 , Riley sued Gaga for and punitive damages over the songwriting credits , saying he was not given 25 percent of royalties as he had been promised .", "title": "" }, { "docid": "Monster_(Exo_song)", "text": "`` Monster '' is a song recorded by South Korean boy band Exo for their third studio album Ex ` Act . It was released in Korean and Chinese versions by S.M. Entertainment on June 9 , 2016 as the second single for the album .", "title": "" }, { "docid": "Pete_Fowler", "text": "Pete Fowler ( born 1969 in Cardiff ) is a Welsh artist best known for his artwork for the Welsh band Super Furry Animals and his Monsterism toys and goods . He is a freelance illustrator and `` monster creator '' inspired by animals , music , folklore , myths , psychedelia and super nature . He has also worked on a number of other projects in the UK and Japan , such as television advertisements ( Kia Picanto ) , as well as having art exhibitions in the UK and abroad . Fowler works in a variety of media , including drawing , painting , animation , printmaking and sculpture . The majority of Fowler 's art is made in a postmodern cartoon style and often revolves around a central narrative and features a recurring set of characters . The `` monsters '' Fowler creates all reside on `` Monsterism Island '' . Fowler invents extensive back-stories for his characters ; each has its own specific traits and levels of `` monsterism '' . Fowler is most known for his designer toys of his characters , which he himself manufactures with his own company . A CD called The Sounds of Monsterism Island was released in 2005 by Heavenly Records . According to the press release , `` The record is a compilation album that works as a soundtrack to the world of Monsterism ... The album features psychedelic music from the '60s through to today , much of it unearthed and put on CD for the first time . '' In 2006 , Fowler created a set of comics about Monsterism Island which have been featured in Vice Magazine . The second soundtrack to Monsterism Island , A psychedelic Guide to Monsterism Island , was released in 2009 and features mostly new compositions by a host of contemporary musicians . Fowler is one half of the cosmic deckshoegaze Seahawks who have released extensively on vinyl , CD and download since 2010 and have remixed a variety of bands as well as regularly DJing . Fowler 's solo exhibition ` The Needle and The Damage Done ' took place at Beach London in Shoreditch in August 2013 .", "title": "" }, { "docid": "Steppenwolf_Live", "text": "Steppenwolf Live is primarily a collection of recordings from a single concert early in 1970 at the Santa Monica Civic Center by Steppenwolf staged in support of their 1969 album Monster . Released in April , 1970 by Dunhill Records , it contains Steppenwolf 's well-known hits : `` Born to Be Wild '' , `` Magic Carpet Ride '' and `` The Pusher '' , as well as most of the songs from Monster , including the top 40 hit live version of `` Monster '' . The song `` Hey Lawdy Mama '' was recorded in the studio , but edited in a manner to segue directly into `` Magic Carpet Ride '' , thus retaining the album 's `` live '' feel . ( On original LP copies of Steppenwolf Live , `` Hey Lawdy Mama '' and `` Magic Carpet Ride '' are banded together as a single track , with a total running time of 7:13 ) . A differently edited version of `` Hey Lawdy Mama '' , incorporating a fade-out instead of the segue , was released as a single . The songs `` Twisted '' and `` Corrina , Corrina '' are also studio versions which were eq 'd and given some delay effects to match the actual live recordings and overdubbed with audience sounds at the beginning and ending of the songs . The Bag by Kustom is one of the earliest talk boxes . These devices route the guitar signal from the driver of a speaker through a plastic tube held in the player 's mouth . The sound of that is picked up from a stage microphone . John Kay was one of the first professional musicians to use a talk box having done so in 1969 studio recordings . The studio cuts were added by the record company ( Dunhill ) against the band 's wishes to give the album enough tracks to qualify as a double album .", "title": "" }, { "docid": "Another_State_of_Mind_(song)", "text": "This article refers to the song by Social Distortion . For the documentary film , which also features Social Distortion , see Another State of Mind ( film ) . `` Another State of Mind '' is a song by the American punk rock band Social Distortion . It is the second track on their 1983 debut album Mommy 's Little Monster , and was released as a 7 '' single that year on their then-record label 13th Floor Records . The single was released again in 1989 on Triple X Records to coincide with the reissue of Mommy 's Little Monster . The song also appeared on their 1998 live album Live at the Roxy and 2004 live DVD Live in Orange County , as it had become one of the band 's live staples . It also appeared as the opening track on their 2007 Greatest Hits compilation . Was the first single of the band who archivied sucess along side in the underground scene .", "title": "" }, { "docid": "You're_All_I_Wanna_Do", "text": "`` You 're All I Wan na Do '' is a single by American rock band Cheap Trick , released as the second single from their 1994 album Woke up with a Monster . The song was written by Jim Peterik , Rick Nielsen , Robin Zander , Terry Reid and Tom Petersson . The single was released as a 3inch CD in a snap-pack design for Japan only . A promotional DJ copy 5inch CD single was also released in Japan , with unique photos of each band member . The b-side `` Cry Baby '' was featured on the same album , written by Rick Nielsen , Robin Zander and Tom Petersson . Both tracks were produced by Ted Templeman who had produced the entire `` Woke up with a Monster '' album .", "title": "" } ]
PLAIN-192
Avoiding Dairy to Prevent Parkinson's
[ { "docid": "MED-5327", "text": "OBJECTIVE: To investigate the associations between dietary patterns and mental health in early adolescence. METHOD: The Western Australian Pregnancy Cohort (Raine) Study is a prospective study of 2900 pregnancies recruited from 1989-1992. At 14 years of age (2003-2006; n=1324), the Child Behaviour Checklist (CBCL) was used to assess behaviour (characterising mental health status), with higher scores representing poorer behaviour. Two dietary patterns (Western and Healthy) were identified using factor analysis and food group intakes estimated by a 212-item food frequency questionnaire. Relationships between dietary patterns, food group intakes and behaviour were examined using general linear modelling following adjustment for potential confounding factors at age 14: total energy intake, body mass index, physical activity, screen use, family structure, income and functioning, gender and maternal education at pregnancy. RESULTS: Higher total (b=2.20, 95% CI=1.06, 3.35), internalizing (withdrawn/depressed) (b=1.25, 95% CI=0.15, 2.35) and externalizing (delinquent/aggressive) (b=2.60, 95% CI=1.51, 3.68) CBCL scores were significantly associated with the Western dietary pattern, with increased intakes of takeaway foods, confectionary and red meat. Improved behavioural scores were significantly associated with higher intakes of leafy green vegetables and fresh fruit (components of the Healthy pattern). CONCLUSION: These findings implicate a Western dietary pattern in poorer behavioural outcomes for adolescents. Better behavioural outcomes were associated with a higher intake of fresh fruit and leafy green vegetables.", "title": "The association between dietary patterns and mental health in early adolescence." }, { "docid": "MED-3935", "text": "Background Parkinson’s disease (PD) is the second most common neurodegenerative disorder. People with PD, their families, scientists, health care providers, and the general public are increasingly interested in identifying environmental contributors to PD risk. Methods In June 2007, a multidisciplinary group of experts gathered in Sunnyvale, California, USA, to assess what is known about the contribution of environmental factors to PD. Results We describe the conclusions around which they came to consensus with respect to environmental contributors to PD risk. We conclude with a brief summary of research needs. Conclusions PD is a complex disorder, and multiple different pathogenic pathways and mechanisms can ultimately lead to PD. Within the individual there are many determinants of PD risk, and within populations, the causes of PD are heterogeneous. Although rare recognized genetic mutations are sufficient to cause PD, these account for < 10% of PD in the U.S. population, and incomplete penetrance suggests that environmental factors may be involved. Indeed, interplay among environmental factors and genetic makeup likely influences the risk of developing PD. There is a need for further understanding of how risk factors interact, and studying PD is likely to increase understanding of other neurodegenerative disorders.", "title": "Meeting Report: Consensus Statement—Parkinson’s Disease and the Environment: Collaborative on Health and the Environment and Parkinson’s Action Network (CHE PAN) Conference 26–28 June 2007" }, { "docid": "MED-5341", "text": "The present study investigated the effects of a diet and exercise intervention on known breast cancer (BCa) risk factors, including estrogen, obesity, insulin, and insulin-like growth factor-I (IGF-I), in overweight/obese, postmenopausal women. In addition, using the subjects' pre- and postintervention serum in vitro, serum-stimulated growth and apoptosis of three estrogen receptor-positive BCa cell lines were studied. The women where placed on a low-fat (10-15% kcal), high-fiber (30-40 g per 1,000 kcal/day) diet and attended daily exercise classes for 2 wk. Serum estradiol was reduced in the women on hormone treatment (HT; n = 28) as well as those not on HT (n = 10). Serum insulin and IGF-I were significantly reduced in all women, whereas IGF binding protein-1 was increased significantly. In vitro growth of the BCa cell lines was reduced by 6.6% for the MCF-7 cells, 9.9% for the ZR-75-1 cells, and 18.5% for the T-47D cells. Apoptosis was increased by 20% in the ZR-75-1 cells, 23% in the MCF-7 cells, and 30% in the T-47D cells (n = 12). These results show that a very-low-fat, high-fiber diet combined with daily exercise results in major reductions in risk factors for BCa while subjects remained overweight/obese. These in vivo serum changes slowed the growth and induced apoptosis in serum-stimulated BCa cell lines in vitro.", "title": "Effects of a low-fat, high-fiber diet and exercise program on breast cancer risk factors in vivo and tumor cell growth and apoptosis in vitro." }, { "docid": "MED-5339", "text": "Recently, it has been suggested that the Escherichia coli causing urinary tract infection (UTI) may come from meat and animals. The purpose was to investigate if a clonal link existed between E. coli from animals, meat and UTI patients. Twenty-two geographically and temporally matched B2 E. coli from UTI patients, community-dwelling humans, broiler chicken meat, pork, and broiler chicken, previously identified to exhibit eight virulence genotypes by microarray-detection of approximately 300 genes, were investigated for clonal relatedness by PFGE. Nine isolates were selected and tested for in vivo virulence in the mouse model of ascending UTI. UTI and community-dwelling human strains were closely clonally related to meat strains. Several human derived strains were also clonally interrelated. All nine isolates regardless of origin were virulent in the UTI model with positive urine, bladder and kidney cultures. Further, isolates with the same gene profile also yielded similar bacterial counts in urine, bladder and kidneys. This study showed a clonal link between E. coli from meat and humans, providing solid evidence that UTI is zoonosis. The close relationship between community-dwelling human and UTI isolates may indicate a point source spread, e.g. through contaminated meat.", "title": "Is Escherichia coli urinary tract infection a zoonosis? Proof of direct link with production animals and meat." }, { "docid": "MED-3940", "text": "Objective: To determine whether evidence of neuronal dysfunction or demise preceded deposition of Lewy pathology in vulnerable neurons in Parkinson disease (PD). Methods: We examined the extent of nigral dysfunction and degeneration among 63 normal, incidental Lewy body disease (ILBD), and PD cases based on tyrosine hydroxylase (TH) immunoreactivity and neuron densities, respectively. The relationship between these markers and Lewy pathology (LP) burden in the substantia nigra (SN) and Braak PD stage was assessed. Results: Compared with normal subjects, ILBD cases displayed a significantly higher percentage of TH-negative cells and lower neuronal densities in the SN as early as Braak PD stages 1 and 2, before LP deposition in the nigrostriatal system. ILBD nigral neuron densities were intermediate between normal subjects and PD cases, and TH-negative percentages were higher in ILBD than either normal or PD cases. Furthermore, neuron density and neuronal dysfunction levels remained relatively constant across Braak PD stages in ILBD. Conclusions: These results suggest that significant neurodegeneration and cellular dysfunction precede LP in the SN, challenging the pathogenic role of LP in PD and the assumption that ILBD always represents preclinical PD.", "title": "Lewy pathology is not the first sign of degeneration in vulnerable neurons in Parkinson disease" }, { "docid": "MED-5335", "text": "Three recent case-control studies conclude that diets high in animal fat or cholesterol are associated with a substantial increase in risk for Parkinson's disease (PD); in contrast, fat of plant origin does not appear to increase risk. Whereas reported age-adjusted prevalence rates of PD tend to be relatively uniform throughout Europe and the Americas, sub-Saharan black Africans, rural Chinese, and Japanese, groups whose diets tend to be vegan or quasi-vegan, appear to enjoy substantially lower rates. Since current PD prevalence in African-Americans is little different from that in whites, environmental factors are likely to be responsible for the low PD risk in black Africans. In aggregate, these findings suggest that vegan diets may be notably protective with respect to PD. However, they offer no insight into whether saturated fat, compounds associated with animal fat, animal protein, or the integrated impact of the components of animal products mediates the risk associated with animal fat consumption. Caloric restriction has recently been shown to protect the central dopaminergic neurons of mice from neurotoxins, at least in part by induction of heat-shock proteins; conceivably, the protection afforded by vegan diets reflects a similar mechanism. The possibility that vegan diets could be therapeutically beneficial in PD, by slowing the loss of surviving dopaminergic neurons, thus retarding progression of the syndrome, may merit examination. Vegan diets could also be helpful to PD patients by promoting vascular health and aiding blood-brain barrier transport of L-dopa. Copyright 2001 Harcourt Publishers Ltd.", "title": "Does a vegan diet reduce risk for Parkinson's disease?" }, { "docid": "MED-3937", "text": "BACKGROUND: The goal of the present study was to analyze the epidemiology and specific risk factors of traumatic brain injury (TBI) in the Asterix illustrated comic books. Among the illustrated literature, TBI is a predominating injury pattern. METHODS: A retrospective analysis of TBI in all 34 Asterix comic books was performed by examining the initial neurological status and signs of TBI. Clinical data were correlated to information regarding the trauma mechanism, the sociocultural background of victims and offenders, and the circumstances of the traumata, to identify specific risk factors. RESULTS: Seven hundred and four TBIs were identified. The majority of persons involved were adult and male. The major cause of trauma was assault (98.8%). Traumata were classified to be severe in over 50% (GCS 3-8). Different neurological deficits and signs of basal skull fractures were identified. Although over half of head-injury victims had a severe initial impairment of consciousness, no case of death or permanent neurological deficit was found. The largest group of head-injured characters was constituted by Romans (63.9%), while Gauls caused nearly 90% of the TBIs. A helmet had been worn by 70.5% of victims but had been lost in the vast majority of cases (87.7%). In 83% of cases, TBIs were caused under the influence of a doping agent called \"the magic potion\". CONCLUSIONS: Although over half of patients had an initially severe impairment of consciousness after TBI, no permanent deficit could be found. Roman nationality, hypoglossal paresis, lost helmet, and ingestion of the magic potion were significantly correlated with severe initial impairment of consciousness (p ≤ 0.05).", "title": "Traumatic brain injuries in illustrated literature: experience from a series of over 700 head injuries in the Asterix comic books." }, { "docid": "MED-5322", "text": "BACKGROUND/AIMS: This study aimed to investigate the quantitative and qualitative changes of bacteria, Bacteroides, Bifidobacterium and Clostridium cluster IV in faecal microbiota associated with a vegetarian diet. METHODS: Bacterial abundances were measured in faecal samples of 15 vegetarians and 14 omnivores using quantitative PCR. Diversity was assessed with PCR-DGGE fingerprinting, principal component analysis (PCA) and Shannon diversity index. RESULTS: Vegetarians had a 12% higher abundance of bacterial DNA than omnivores, a tendency for less Clostridium cluster IV (31.86 +/- 17.00%; 36.64 +/- 14.22%) and higher abundance of Bacteroides (23.93 +/- 10.35%; 21.26 +/- 8.05%), which were not significant due to high interindividual variations. PCA suggested a grouping of bacteria and members of Clostridium cluster IV. Two bands appeared significantly more frequently in omnivores than in vegetarians (p < 0.005 and p < 0.022). One was identified as Faecalibacterium sp. and the other was 97.9% similar to the uncultured gut bacteriumDQ793301. CONCLUSIONS: A vegetarian diet affects the intestinal microbiota, especially by decreasing the amount and changing the diversity of Clostridium cluster IV. It remains to be determined how these shifts might affect the host metabolism and disease risks. Copyright 2009 S. Karger AG, Basel.", "title": "Characterization of bacteria, clostridia and Bacteroides in faeces of vegetarians using qPCR and PCR-DGGE fingerprinting." }, { "docid": "MED-5324", "text": "Obesity has important health consequences, including elevating risk for heart disease, diabetes, and cancer. A high-fat diet is known to contribute to obesity. Little is known regarding the effect of a high-fat diet on pulmonary function, despite the dramatic increase in the prevalence of respiratory ailments (e.g., asthma). The purpose of our study was to determine whether a high-fat meal (HFM) would increase airway inflammation and decrease pulmonary function in healthy subjects. Pulmonary function tests (PFT) (forced expiratory volume in 1-s, forced vital capacity, forced expiratory flow at 25-75% of vital capacity) and exhaled nitric oxide (eNO; airway inflammation) were performed in 20 healthy (10 men, 10 women), inactive subjects (age 21.9 +/- 0.4 years) pre and 2 h post HFM (1 g fat/1 kg body weight; 74.2 +/- 4.1 g fat). Total cholesterol, triglycerides, and C-reactive protein (CRP; systemic inflammation) were determined via a venous blood sample pre and post HFM. Body composition was measured via dual energy X-ray absorptiometry. The HFM significantly increased total cholesterol by 4 +/- 1%, and triglycerides by 93 +/- 3%. ENO also increased (p < 0.05) due to the HFM by 19 +/- 1% (pre 17.2 +/- 1.6; post 20.6 +/- 1.7 ppb). ENO and triglycerides were significantly related at baseline and post-HFM (r = 0.82, 0.72 respectively). Despite the increased eNO, PFT or CRP did not change (p > 0.05) with the HFM. These results demonstrate that a HFM, which leads to significant increases in total cholesterol, and especially triglycerides, increases exhaled NO. This suggests that a high-fat diet may contribute to chronic inflammatory diseases of the airway and lung.", "title": "Effects of a high-fat meal on pulmonary function in healthy subjects." }, { "docid": "MED-5342", "text": "Background The physical health status of vegetarians has been extensively reported, but there is limited research regarding the mental health status of vegetarians, particularly with regard to mood. Vegetarian diets exclude fish, the major dietary source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), critical regulators of brain cell structure and function. Omnivorous diets low in EPA and DHA are linked to impaired mood states in observational and experimental studies. Methods We examined associations between mood state and polyunsaturated fatty acid intake as a result of adherence to a vegetarian or omnivorous diet in a cross-sectional study of 138 healthy Seventh Day Adventist men and women residing in the Southwest. Participants completed a quantitative food frequency questionnaire, Depression Anxiety Stress Scale (DASS), and Profile of Mood States (POMS) questionnaires. Results Vegetarians (VEG:n = 60) reported significantly less negative emotion than omnivores (OMN:n = 78) as measured by both mean total DASS and POMS scores (8.32 ± 0.88 vs 17.51 ± 1.88, p = .000 and 0.10 ± 1.99 vs 15.33 ± 3.10, p = .007, respectively). VEG reported significantly lower mean intakes of EPA (p < .001), DHA (p < .001), as well as the omega-6 fatty acid, arachidonic acid (AA; p < .001), and reported higher mean intakes of shorter-chain α-linolenic acid (p < .001) and linoleic acid (p < .001) than OMN. Mean total DASS and POMS scores were positively related to mean intakes of EPA (p < 0.05), DHA (p < 0.05), and AA (p < 0.05), and inversely related to intakes of ALA (p < 0.05), and LA (p < 0.05), indicating that participants with low intakes of EPA, DHA, and AA and high intakes of ALA and LA had better mood. Conclusions The vegetarian diet profile does not appear to adversely affect mood despite low intake of long-chain omega-3 fatty acids.", "title": "Vegetarian diets are associated with healthy mood states: a cross-sectional study in Seventh Day Adventist adults" }, { "docid": "MED-5337", "text": "PURPOSE: Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS AND METHODS: Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group. RESULTS: None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. CONCLUSIONS: Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.", "title": "Intensive lifestyle changes may affect the progression of prostate cancer." }, { "docid": "MED-5330", "text": "Although there is a well-established relation between serum cholesterol and coronary artery disease risk, individual and national variations in this association suggest that other factors are involved in atherogenesis. High-fat diet associated triglyceride-rich lipoproteins have also been suggested to be atherogenic. To assess the direct effect of postprandial triglyceride-rich lipoproteins on endothelial function, an early factor in atherogenesis--10 healthy, normocholesterolemic volunteers--were studied before and for 6 hours after single isocaloric high- and low-fat meals (900 calorie; 50 and 0 g fat, respectively). Endothelial function, in the form of flow-mediated vasoactivity, was assessed in the brachial artery using 7.5-MHz ultrasound as percent arterial diameter change 1 minute after 5 minutes of upper-arm arterial occlusion. Serum lipoproteins and glucose were determined before eating and 2 and 4 hours postprandially. Serum triglycerides increased from 94 +/- 55 mg/dl preprandially to 147 +/- 80 mg/dl 2 hours after the high-fat meal (p = 0.05). Flow-dependent vasoactivity decreased from 21 +/- 5% preprandially to 11 +/- 4%, 11 +/- 6%, and 10 +/- 3% at 2, 3, and 4 hours after the high-fat meal, respectively (all p <0.05 compared with low-fat meal data). No changes in lipoproteins or flow-mediated vasoactivity were observed after the low-fat meal. Fasting low-density lipoprotein cholesterol correlated inversely (r = -0.47, p = 0.04) with preprandial flow-mediated vasoactivity, but triglyceride level did not. Mean change in postprandial flow-mediated vasoactivity at 2, 3, and 4 hours correlated with change in 2-hour serum triglycerides (r = -0.51, p = 0.02). These results demonstrate that a single high-fat meal transiently impairs endothelial function. These findings identify a potential process by which a high-fat diet may be atherogenic independent of induced changes in cholesterol.", "title": "Effect of a single high-fat meal on endothelial function in healthy subjects." }, { "docid": "MED-4726", "text": "The aim of these studies was to evaluate the potential of some nutritional approaches to prevent or reduce the body load of organochlorines (OC) in humans. Study 1 compared plasma OC concentrations between vegans and omnivores while study 2 verified if the dietary fat substitute olestra could prevent the increase in OC concentrations that is generally observed in response to a weight-reducing programme. In study 1, nine vegans and fifteen omnivores were recruited and the concentrations of twenty-six OC (beta-hexachlorocyclohexane (beta-HCH), p, p'-dichlorodiphenyldichloroethane (p, p'-DDE), p, p'-dichlorodiphenyltrichloroethane (p, p'-DDT), hexachlorobenzene, mirex, aldrin, alpha-chlordane, gamma-chlordane, oxychlordane, cis-nonachlor, trans-nonachlor, polychlorinated biphenyl (PCB) nos. 28, 52, 99, 101, 105, 118, 128, 138, 153, 156, 170, 180, 183 and 187, and aroclor 1260) were determined. In study 2, the concentrations of these twenty-six OC were measured before and after weight loss over 3 months in thirty-seven obese men assigned to one of the following treatments: standard group (33 % fat diet; n 13), fat-reduced group (25 % fat diet; n 14) or fat-substituted group (1/3 of dietary lipids substituted by olestra; n 10). In study 1, plasma concentrations of five OC compounds (aroclor 1260 and PCB 99, PCB 138, PCB 153 and PCB 180) were significantly lower in vegans compared with omnivores. In study 2, beta-HCH was the only OC which decreased in the fat-substituted group while increasing in the other two groups (P = 0.045). In conclusion, there was a trend toward lesser contamination in vegans than in omnivores, and olestra had a favourable influence on beta-HCH but did not prevent plasma hyperconcentration of the other OC during ongoing weight loss.", "title": "Impact of adopting a vegan diet or an olestra supplementation on plasma organochlorine concentrations: results from two pilot studies." }, { "docid": "MED-5363", "text": "OBJECTIVE: Although several studies have reported associations of depressive state with specific nutrients and foods, few studies examined the association with dietary patterns in adults. We investigated the association between major dietary patterns and depressive symptoms in Japanese. METHODS: Subjects were 521 municipal employees (309 men and 212 women), aged 21-67 years, who participated in a health survey at the time of periodic checkup. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale. Dietary patterns were derived by using principal component analysis of the consumption of 52 food and beverage items, which was assessed by a validated brief diet history questionnaire. Logistic regression analysis was used to estimate odds ratios of depressive symptoms (CES-D >or=16) with adjustment for potential confounding variables. RESULTS: We identified three dietary patterns. A healthy Japanese dietary pattern characterized by high intakes of vegetables, fruit, mushrooms and soy products was associated with fewer depressive symptoms. The multivariate-adjusted odds ratios (95% confidence intervals) of having depressive symptoms for the lowest through highest tertiles of the healthy Japanese dietary pattern score were 1.00 (reference), 0.99 (0.62-1.59) and 0.44 (0.25-0.78), respectively (P for trend=0.006). Other dietary patterns were not appreciably associated with depressive symptoms. CONCLUSIONS: Our findings suggest that a healthy Japanese dietary pattern may be related to decreased prevalence of depressive status.", "title": "Dietary patterns and depressive symptoms among Japanese men and women." }, { "docid": "MED-5325", "text": "Objective Previous work studying vegetarians has often found that they have lower blood pressure (BP). Reasons may include their lower BMI and higher intake levels of fruit and vegetables. Here we seek to extend this evidence in a geographically diverse population containing vegans, lacto-ovo vegetarians and omnivores. Design Data are analysed from a calibration sub-study of the Adventist Health Study-2 (AHS-2) cohort who attended clinics and provided validated FFQ. Criteria were established for vegan, lacto-ovo vegetarian, partial vegetarian and omnivorous dietary patterns. Setting Clinics were conducted at churches across the USA and Canada. Dietary data were gathered by mailed questionnaire. Subjects Five hundred white subjects representing the AHS-2 cohort. Results Covariate-adjusted regression analyses demonstrated that the vegan vegetarians had lower systolic and diastolic BP (mmHg) than omnivorous Adventists (β =−6·8, P<0·05 and β = −6·9, P<0·001). Findings for lacto-ovo vegetarians (β = −9·1, P<0·001 and β = −5·8, P<0·001) were similar. The vegetarians (mainly the vegans) were also less likely to be using antihypertensive medications. Defining hypertension as systolic BP > 139 mmHg or diastolic BP > 89 mmHg or use of antihypertensive medications, the odds ratio of hypertension compared with omnivores was 0·37 (95 % CI 0·19, 0·74), 0·57 (95 % CI 0·36, 0·92) and 0·92 (95 % CI 0·50, 1·70), respectively, for vegans, lacto-ovo vegetarians and partial vegetarians. Effects were reduced after adjustment for BMI. Conclusions We conclude from this relatively large study that vegetarians, especially vegans, with otherwise diverse characteristics but stable diets, do have lower systolic and diastolic BP and less hypertension than omnivores. This is only partly due to their lower body mass.", "title": "Vegetarian diets and blood pressure among white subjects: results from the Adventist Health Study-2 (AHS-2)" }, { "docid": "MED-5328", "text": "Aim To evaluate the relationship of diet to incident diabetes among non-Black and Black participants in the Adventist Health Study-2. Methods and Results Participants were 15,200 men and 26,187 women (17.3% Blacks) across the U.S. and Canada who were free of diabetes and who provided demographic, anthropometric, lifestyle and dietary data. Participants were grouped as vegan, lacto ovo vegetarian, pesco vegetarian, semi-vegetarian or non-vegetarian (reference group). A follow-up questionnaire after two years elicited information on the development of diabetes. Cases of diabetes developed in 0.54% of vegans, 1.08% of lacto ovo vegetarians, 1.29% of pesco vegetarians, 0.92% of semi-vegetarians and 2.12% of non-vegetarians. Blacks had an increased risk compared to non-Blacks (odds ratio [OR] 1.364; 95% confidence interval [CI], 1.093–1.702). In multiple logistic regression analysis controlling for age, gender, education, income, television watching, physical activity, sleep, alcohol use, smoking and BMI, vegans (OR 0.381; 95% CI 0.236–0.617), lacto ovo vegetarians (OR 0.618; 95% CI 0.503–0.760) and semi-vegetarians (OR 0.486, 95% CI 0.312–0.755) had a lower risk of diabetes than non-vegetarians. In non-Blacks vegan, lacto ovo and semi-vegetarian diets were protective against diabetes (OR 0.429, 95% CI 0.249–0.740; OR 0.684, 95% CI 0.542–0.862; OR 0.501, 95% CI 0.303–0.827); among Blacks vegan and lacto ovo vegetarian diets were protective (OR 0.304, 95% CI 0.110–0.842; OR 0.472, 95% CI 0.270–0.825). These associations were strengthened when BMI was removed from the analyses. Conclusion Vegetarian diets (vegan, lacto ovo, semi-) were associated with a substantial and independent reduction in diabetes incidence. In Blacks the dimension of the protection associated with vegetarian diets was as great as the excess risk associated with Black ethnicity.", "title": "Vegetarian diets and incidence of diabetes in the Adventist Health Study-2" }, { "docid": "MED-5323", "text": "This study reviewed the literature on the relations between exposure to chemicals with endocrine-disrupting abilities and obesity in humans. The studies generally indicated that exposure to some of the endocrine-disrupting chemicals was associated with an increase in body size in humans. The results depended on the type of chemical, exposure level, timing of exposure and gender. Nearly all the studies investigating dichlorodiphenyldichloroethylene (DDE) found that exposure was associated with an increase in body size, whereas the results of the studies investigating polychlorinated biphenyl (PCB) exposure were depending on dose, timing and gender. Hexachlorobenzene, polybrominated biphenyls, beta-hexachlorocyclohexane, oxychlordane and phthalates were likewise generally associated with an increase in body size. Studies investigating polychlorinated dibenzodioxins and polychlorinated dibenzofurans found either associations with weight gain or an increase in waist circumference, or no association. The one study investigating relations with bisphenol A found no association. Studies investigating prenatal exposure indicated that exposure in utero may cause permanent physiological changes predisposing to later weight gain. The study findings suggest that some endocrine disruptors may play a role for the development of the obesity epidemic, in addition to the more commonly perceived putative contributors. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.", "title": "Endocrine-disrupting chemicals and obesity development in humans: a review." }, { "docid": "MED-5331", "text": "A global health transition is currently underway. The burden of non-communicable diseases (NCDs) is increasing rapidly in the developing world, very much as a result of changes in lifestyles. In addition to changes in tobacco use and physical activity, major changes are taking place in diets, contributing greatly to the growing epidemic of NCD. Thus, a huge global public health challenge is how to influence the trends in diet and nutrition for effective global NCD prevention. The health transition took place rapidly in Finland after World War II and mortality from cardiovascular disease (CVD) was exceptionally high. The North Karelia Project was launched in 1972 as a community-based, and later as a national, programme to influence diet and other lifestyles that are crucial in the prevention of CVD. The intervention had a strong theory base and it employed comprehensive strategies. Broad community organisation and the strong participation of people were the key elements. Evaluation has shown how the diet (particularly fat consumption) has changed and how these changes have led to a major reduction in population serum cholesterol and blood pressure levels. It has also shown how ischaemic heart disease mortality in a working-age population has declined by 73% in North Karelia and by 65% in the whole country from 1971 to 1995. Although Finland is an industrialised country, North Karelia was rural, of rather low socio-economic level and with many social problems in the 1970s and 1980s. The project was based on low-cost intervention activities, where people's participation and community organisations played a key role. Comprehensive interventions in the community were eventually supported by national activities--from expert guidelines and media activities to industry collaboration and policy. Similar principles for nutrition intervention programmes could be used in developing countries, obviously tailored to the local conditions. This paper discusses the experiences of the North Karelia Project in the light of needs from the less-industrialised countries and makes some general recommendations.", "title": "Influencing public nutrition for non-communicable disease prevention: from community intervention to national programme--experiences from Finland." }, { "docid": "MED-5340", "text": "In Asia, vegetarianism is a well-established eating behavior. It appears that the adoption of a vegan diet leads to a lessening of several health risk factors. Although vegetarianism has some notable effects on the hematological system, the effect on the nephrological system has not been well clarified. The pattern of renal function parameters was studied in 25 Thai vegans compared with 25 non-vegetarians. Of the studied parameters, it was found that urine protein was significantly different (p < 0.05) in vegans and controls. Vegans had significantly lower urine protein level.", "title": "Renal function parameters of Thai vegans compared with non-vegans." }, { "docid": "MED-3938", "text": "Polychlorinated biphenyls (PCBs) are synthetic chemicals primarily used as coolants and insulators in electrical equipment. Although banned for several decades, PCBs continue to exist in the environment because of their long half-life, continued presence in items produced before the ban, and poor disposal practices. Epidemiological and experimental studies have identified exposure to PCBs as a potential risk factor for Parkinson’s disease, perhaps more so in females. The objective of this work was to examine the association between PCB levels in post-mortem human brain tissue and the diagnosis of Parkinson’s disease, as well as the degree of nigral depigmentation. We also sought to determine if this association was more significant when patients were stratified by sex. Post-mortem brain samples from control patients and those diagnosed with Parkinson’s disease were obtained from the Emory University Brain Bank and from the Nun Study. Concentrations of eight prevalent PCB congeners were extracted from post-mortem brain tissue and analyzed using gas chromatography-mass spectrometry. PCB congeners 153 and 180 were significantly elevated in the brains of Parkinson’s disease patients. When stratified by sex, the female Parkinson’s disease group demonstrated significantly elevated concentrations of total PCBs and specifically congeners 138, 153, and 180 compared to controls, whereas PCB concentrations in males were not significantly different between control and Parkinson’s disease groups. In a separate population of women (Nun Study) who had no clinical signs or symptoms of PD, elevated concentrations total PCB and congeners 138, 153 and 180 were also observed in post-mortem brain tissue exhibiting moderate nigral depigmentation compared to subjects with mild or no depigmentation. These quantitative data demonstrate an association between brain PCB levels and Parkinson’s disease-related pathology. Furthermore, these data support epidemiological and laboratory studies reporting a link between PCB exposure and an increased risk for Parkinson’s disease, including greater susceptibility of females.", "title": "Association between polychlorinated biphenyls and Parkinson’s disease neuropathology" }, { "docid": "MED-3939", "text": "Excerpt This Statistical Brief presents data from the Healthcare Cost and Utilization Project (HCUP) on the treatment of TBI in U.S. hospitals in 2004. Hospital utilization and costs for TBI admissions are compared with hospital stays for all other injuries. Additionally, trends in hospital stays for TBI and differences in the distribution of TBI admissions by various patient characteristics are examined. Finally, common causes of TBIs resulting in hospital admission, as well as the coexisting conditions often associated with these injuries, are described. All differences between estimates noted in the text are statistically significant at the 0.05 level or better.", "title": "Hospital Admissions for Traumatic Brain Injuries, 2004: Statistical Brief #27" }, { "docid": "MED-5333", "text": "BACKGROUND/AIM: A vegetarian diet is known to prevent a series of diseases but may influence the balance of carbohydrate and fat metabolism as well as collagen synthesis. This study compares expression patterns of relevant genes in oral mucosa of omnivores and vegetarians. METHODS: Quantitative reverse transcriptase polymerase chain reaction was applied for analysis of mRNA levels from carnitine transporter OCTN2, hepatic CPT1A and nonhepatic CPT1B isoforms of carnitine palmitoyltransferase and collagen (CCOL2A1) in oral mucosa. RESULTS: Compared with volunteers with traditional eating habits, carbohydrate consumption was significantly higher (+22%) in vegetarians. This was associated with a significant stimulation of CPT1A (+50%) and OCTN2 (+10%) and a lowered collagen synthesis (-10%). CONCLUSION: These novel findings provide further insight into the association of a changed fat metabolism and reduced collagen synthesis in vegetarians, which could also play a role in the aging process. Copyright 2008 S. Karger AG, Basel.", "title": "Vegetarian diet affects genes of oxidative metabolism and collagen synthesis." }, { "docid": "MED-5332", "text": "The gastrointestinal microbiota produces short-chain fatty acids, especially butyrate, which affect colonic health, immune function and epigenetic regulation. To assess the effects of nutrition and aging on the production of butyrate, the butyryl-CoA:acetate CoA-transferase gene and population shifts of Clostridium clusters lV and XlVa, the main butyrate producers, were analysed. Faecal samples of young healthy omnivores (24 ± 2.5 years), vegetarians (26 ± 5 years) and elderly (86 ± 8 years) omnivores were evaluated. Diet and lifestyle were assessed in questionnaire-based interviews. The elderly had significantly fewer copies of the butyryl-CoA:acetate CoA-transferase gene than young omnivores (P=0.014), while vegetarians showed the highest number of copies (P=0.048). The thermal denaturation of the butyryl-CoA:acetate CoA-transferase gene variant melting curve related to Roseburia/Eubacterium rectale spp. was significantly more variable in the vegetarians than in the elderly. The Clostridium cluster XIVa was more abundant in vegetarians (P=0.049) and in omnivores (P<0.01) than in the elderly group. Gastrointestinal microbiota of the elderly is characterized by decreased butyrate production capacity, reflecting increased risk of degenerative diseases. These results suggest that the butyryl-CoA:acetate CoA-transferase gene is a valuable marker for gastrointestinal microbiota function. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.", "title": "Quantification of butyryl CoA:acetate CoA-transferase genes reveals different butyrate production capacity in individuals according to diet and age." }, { "docid": "MED-5334", "text": "Until recently, intact protein that is rich in tryptophan was not seen as an alternative to pharmaceutical-grade tryptophan because protein also contains large neutral amino acids (LNAAs) that compete for transport sites across the blood-brain barrier. Recent evidence indicates that when deoiled gourd seed (a rich source of tryptophan with approximately 22 mg/g protein) is combined with glucose (a carbohydrate that reduces serum levels of competing LNAAs) a clinical effect similar to that of pharmaceutical-grade tryptophan is achieved. Objective and subjective measures of anxiety in those suffering from social phobia (also known as social anxiety disorder) were employed to measure changes in anxiety in response to a stimulus as part of a double-blind, placebo-controlled, crossover study with a wash-out period of 1 week between study sessions. Subjects were randomly assigned to start with either (i) protein-source tryptophan (deoiled gourd seed) in combination with carbohydrate or (ii) carbohydrate alone. One week after the initial session, subjects returned for a follow-up session and received the opposite treatment of that received at the first session. All 7 subjects who began the study completed the 2-week protocol. Protein-source tryptophan with carbohydrate, but not carbohydrate alone, resulted in significant improvement on an objective measure of anxiety. Protein-source tryptophan combined with a high glycemic carbohydrate is a potential anxiolytic to those suffering from social phobia.", "title": "Protein-source tryptophan as an efficacious treatment for social anxiety disorder: a pilot study." }, { "docid": "MED-5326", "text": "The effect of meat consumption on cancer risk is a controversial issue. However, recent meta-analyses show that high consumers of cured meats and red meat are at increased risk of colorectal cancer. This increase is significant but modest (20-30%). Current WCRF-AICR recommendations are to eat no more than 500 g per week of red meat, and to avoid processed meat. Moreover, our studies show that beef meat and cured pork meat promote colon carcinogenesis in rats. The major promoter in meat is heme iron, via N-nitrosation or fat peroxidation. Dietary additives can suppress the toxic effects of heme iron. For instance, promotion of colon carcinogenesis in rats by cooked, nitrite-treated and oxidized high-heme cured meat was suppressed by dietary calcium and by α-tocopherol, and a study in volunteers supported these protective effects in humans. These additives, and others still under study, could provide an acceptable way to prevent colorectal cancer. Copyright © 2011 Elsevier B.V. All rights reserved.", "title": "Red meat and colon cancer: should we become vegetarians, or can we make meat safer?" }, { "docid": "MED-5338", "text": "Summary Background and objectives Patients with advanced chronic kidney disease (CKD) are in positive phosphorus balance, but phosphorus levels are maintained in the normal range through phosphaturia induced by increases in fibroblast growth factor-23 (FGF23) and parathyroid hormone (PTH). This provides the rationale for recommendations to restrict dietary phosphate intake to 800 mg/d. However, the protein source of the phosphate may also be important. Design, setting, participants, & measurements We conducted a crossover trial in nine patients with a mean estimated GFR of 32 ml/min to directly compare vegetarian and meat diets with equivalent nutrients prepared by clinical research staff. During the last 24 hours of each 7-day diet period, subjects were hospitalized in a research center and urine and blood were frequently monitored. Results The results indicated that 1 week of a vegetarian diet led to lower serum phosphorus levels and decreased FGF23 levels. The inpatient stay demonstrated similar diurnal variation for blood phosphorus, calcium, PTH, and urine fractional excretion of phosphorus but significant differences between the vegetarian and meat diets. Finally, the 24-hour fractional excretion of phosphorus was highly correlated to a 2-hour fasting urine collection for the vegetarian diet but not the meat diet. Conclusions In summary, this study demonstrates that the source of protein has a significant effect on phosphorus homeostasis in patients with CKD. Therefore, dietary counseling of patients with CKD must include information on not only the amount of phosphate but also the source of protein from which the phosphate derives.", "title": "Original Articles: Vegetarian Compared with Meat Dietary Protein Source and Phosphorus Homeostasis in Chronic Kidney Disease" }, { "docid": "MED-3936", "text": "Background Exposure to pesticides has been reported to increase the risk of Parkinson disease (PD), but identification of the specific pesticides is lacking. Three studies have found elevated levels of organochlorine pesticides in postmortem PD brains. Objective To determine whether elevated levels of organochlorine pesticides are present in the serum of patients with PD. Design Case-control study. Setting An academic medical center. Participants Fifty patients with PD, 43 controls, and 20 patients with Alzheimer disease. Main Outcome Measures Levels of 16 organochlorine pesticides in serum samples. Results β-Hexachlorocyclohexane (β-HCH) was more often detectable in patients with PD (76%) compared with controls (40%) and patients with Alzheimer disease (30%). The median level of β-HCH was higher in patients with PD compared with controls and patients with Alzheimer disease. There were no marked differences in detection between controls and patients with PD concerning any of the other 15 organochlorine pesticides. Finally, we observed a significant odds ratio for the presence of β-HCH in serum to predict a diagnosis of PD vs control (odds ratio, 4.39; 95% confidence interval, 1.67–11.6) and PD vs Alzheimer disease (odds ratio, 5.20), which provides further evidence for the apparent association between serum β-HCH and PD. Conclusions These data suggest that β-HCH is associated with a diagnosis of PD. Further research is warranted regarding the potential role of β-HCH as a etiologic agent for some cases of PD.", "title": "Elevated Serum Pesticide Levels and Risk of Parkinson Disease" }, { "docid": "MED-5329", "text": "OBJECTIVE: This study was conducted to demonstrate the effectiveness of a strictly vegetarian, very low-fat diet on cardiac risk factor modification. METHODS: Five hundred men and women, participants in an intensive 12-day live-in program, were studied. The program focused on dietary modification, moderate exercise, and stress management at a hospital-based health-center. RESULTS: During this short time period, cardiac risk factors improved: there was an average reduction of total serum cholesterol of 11% (p < 0.001), of blood pressure of 6% (p < 0.001) and a weight loss of 2.5 kg for men and 1 kg for women. Serum triglycerides did not increase except for two subgroups: females age > or = 65 years with serum cholesterol < 6.5 mmol/L and for females 50 to 64 years with baseline serum cholesterol between 5.2-6.5 mmol/L. High-density lipoprotein cholesterol measured on 66 subjects decreased by 19%. CONCLUSION: A strict, very low-fat vegetarian diet free from all animal products combined with lifestyle changes that include exercise and weight loss is an effective way to lower serum cholesterol and blood pressure.", "title": "Rapid reduction of serum cholesterol and blood pressure by a twelve-day, very low fat, strictly vegetarian diet." } ]
[ { "docid": "MED-5196", "text": "The authors prospectively investigated the association between dairy intake and risk of Parkinson’s disease among 57,689 men and 73,175 women from the Cancer Prevention Study II Nutrition Cohort from the American Cancer Society. A total of 250 men and 138 women with Parkinson’s disease were identified during the follow-up (1992–2001). Dairy consumption was positively associated with the risk of Parkinson’s disease: compared with the lowest intake quintile, the corresponding relative risks (RRs) for quintiles 2–5 were 1.4, 1.4, 1.4, and 1.6 (95 percent confidence interval (CI): 1.1–2.2; p for trend=0.05). A higher risk among dairy consumers was found in both men and women, although the association in women appeared non-linear. The meta-analysis of all prospective studies confirmed a moderately elevated risk of Parkinson’s disease among individuals with high dairy consumption: the RRs between extreme intake categories were 1.6 (95 percent CI: 1.3–2.0) for men and women combined, 1.8 for men (95 percent CI: 1.4–2.4), and 1.3 for women (95 percent CI: 0.8–2.1). These data suggest that dairy consumption may increase the risk of Parkinson’s disease, particularly in men. More studies are needed to further examine these findings and to explore the underlying mechanisms.", "title": "Dairy products and risk of Parkinson’s disease" }, { "docid": "MED-4939", "text": "Parkinson's disease (PD) is increasingly recognized as a neurodegenerative disorder strongly associated with environmental chemical exposures. Recent epidemiological data demonstrate that environmental risk factors may play a dominant role as compared to genetic factors in the etiopathogenesis of idiopathic Parkinson's disease. Identification of key genetic defects such as alpha-synuclein and parkin mutations in PD also underscores the important role of genetic factors in the disease. Thus, understanding the interplay between genes and environment in PD may be critical to unlocking the mysteries of this 200-year-old neurodegenerative disease. Pesticides and metals are the most common classes of environmental chemicals that promote dopaminergic degeneration. The organochlorine pesticide dieldrin has been found in human PD postmortem brain tissues, suggesting that this pesticide has potential to promote nigral cell death. Though dieldrin has been banned, humans continue to be exposed to the pesticide through contaminated dairy products and meats due to the persistent accumulation of the pesticide in the environment. This review summarizes various neurotoxic studies conducted in both cell culture and animals models following dieldrin exposure and discusses their relevance to key pathological mechanisms associated with nigral dopaminergic degeneration including oxidative stress, mitochondrial dysfunction, protein aggregation, and apoptosis.", "title": "Dieldrin-induced neurotoxicity: relevance to Parkinson's disease pathogenesis." }, { "docid": "MED-5134", "text": "This position paper on complementary feeding summarizes evidence for health effects of complementary foods. It focuses on healthy infants in Europe. After reviewing current knowledge and practices, we have formulated these conclusions: Exclusive or full breast-feeding for about 6 months is a desirable goal. Complementary feeding (ie, solid foods and liquids other than breast milk or infant formula and follow-on formula) should not be introduced before 17 weeks and not later than 26 weeks. There is no convincing scientific evidence that avoidance or delayed introduction of potentially allergenic foods, such as fish and eggs, reduces allergies, either in infants considered at increased risk for the development of allergy or in those not considered to be at increased risk. During the complementary feeding period, >90% of the iron requirements of a breast-fed infant must be met by complementary foods, which should provide sufficient bioavailable iron. Cow's milk is a poor source of iron and should not be used as the main drink before 12 months, although small volumes may be added to complementary foods. It is prudent to avoid both early (<4 months) and late (>or=7 months) introduction of gluten, and to introduce gluten gradually while the infant is still breast-fed, inasmuch as this may reduce the risk of celiac disease, type 1 diabetes mellitus, and wheat allergy. Infants and young children receiving a vegetarian diet should receive a sufficient amount ( approximately 500 mL) of breast milk or formula and dairy products. Infants and young children should not be fed a vegan diet.", "title": "Complementary feeding: a commentary by the ESPGHAN Committee on Nutrition." }, { "docid": "MED-3932", "text": "Background Caffeine consumption has been associated with a reduced risk of Parkinson disease. The association is strong and consistent in men, but uncertain in women, possibly because of an interaction with hormone replacement therapy. We sought to confirm these findings using data on Parkinson disease incidence in the CPS II Nutrition Cohort, a large prospective study of men and women. Methods We conducted a prospective study of caffeine intake and risk of PD within the Cancer Prevention Study II Nutrition Cohort. Intakes of coffee and other sources of caffeine were assessed at baseline. Incident cases of PD (n = 317; 197 men and 120 women) were confirmed by treating physicians and medical record review. Relative risks (RR) were estimated using proportional hazards models, adjusting for age, smoking and alcohol consumption. Results After adjustment for age, smoking and alcohol intake, high caffeine consumption was associated with a reduced risk of PD. The relative risk comparing the 5th to the 1st quintile of caffeine intake was 0.43 (CI: 0.26, 0.71, p-trend = <0.002) in men, and 0.61 (95% CI: 0.34, 1.09; p for trend =0.05) in women. Among women, this association was stronger among never users of hormone replacement therapy (RR=0.32) than among ever users (RR=0.81, p-interaction = 0.15). Consumption of decaffeinated coffee was not associated with PD risk. Conclusion Findings from this large prospective study of men and women are consistent with a protective effect of caffeine intake on PD incidence, with an attenuating influence of hormone replacement therapy in women.", "title": "Caffeine and risk of Parkinson disease in a large cohort of men and women" }, { "docid": "MED-1408", "text": "OBJECTIVE: This meta-analysis aims to quantitatively synthesize all studies that examine the association between adherence to a Mediterranean diet and risk of stroke, depression, cognitive impairment, and Parkinson disease. METHODS: Potentially eligible publications were those providing effect estimates of relative risk (RR) for the association between Mediterranean diet and the aforementioned outcomes. Studies were sought in PubMed up to October 31, 2012. Maximally adjusted effect estimates were extracted; separate analyses were performed for high and moderate adherence. RESULTS: Twenty-two eligible studies were included (11 covered stroke, 9 covered depression, and 8 covered cognitive impairment; only 1 pertained to Parkinson's disease). High adherence to Mediterranean diet was consistently associated with reduced risk for stroke (RR = 0.71, 95% confidence interval [CI] = 0.57-0.89), depression (RR = 0.68, 95% CI = 0.54-0.86), and cognitive impairment (RR = 0.60, 95% CI = 0.43-0.83). Moderate adherence was similarly associated with reduced risk for depression and cognitive impairment, whereas the protective trend concerning stroke was only marginal. Subgroup analyses highlighted the protective actions of high adherence in terms of reduced risk for ischemic stroke, mild cognitive impairment, dementia, and particularly Alzheimer disease. Meta-regression analysis indicated that the protective effects of Mediterranean diet in stroke prevention seemed more sizeable among males. Concerning depression, the protective effects of high adherence seemed independent of age, whereas the favorable actions of moderate adherence seemed to fade away with more advanced age. INTERPRETATION: Adherence to a Mediterranean diet may contribute to the prevention of a series of brain diseases; this may be of special value given the aging of Western societies. © 2013 American Neurological Association.", "title": "Mediterranean diet, stroke, cognitive impairment, and depression: A meta-analysis." }, { "docid": "MED-5249", "text": "Coffee is the leading worldwide beverage after water and its trade exceeds US $10 billion worldwide. Controversies regarding its benefits and risks still exist as reliable evidence is becoming available supporting its health promoting potential; however, some researchers have argued about the association of coffee consumption with cardiovascular complications and cancer insurgence. The health-promoting properties of coffee are often attributed to its rich phytochemistry, including caffeine, chlorogenic acid, caffeic acid, hydroxyhydroquinone (HHQ), etc. Many research investigations, epidemiological studies, and meta-analyses regarding coffee consumption revealed its inverse correlation with that of diabetes mellitus, various cancer lines, Parkinsonism, and Alzheimer's disease. Moreover, it ameliorates oxidative stress because of its ability to induce mRNA and protein expression, and mediates Nrf2-ARE pathway stimulation. Furthermore, caffeine and its metabolites help in proper cognitive functionality. Coffee lipid fraction containing cafestol and kahweol act as a safeguard against some malignant cells by modulating the detoxifying enzymes. On the other hand, their higher levels raise serum cholesterol, posing a possible threat to coronary health, for example, myocardial and cerebral infarction, insomnia, and cardiovascular complications. Caffeine also affects adenosine receptors and its withdrawal is accompanied with muscle fatigue and allied problems in those addicted to coffee. An array of evidence showed that pregnant women or those with postmenopausal problems should avoid excessive consumption of coffee because of its interference with oral contraceptives or postmenopausal hormones. This review article is an attempt to disseminate general information, health claims, and obviously the risk factors associated with coffee consumption to scientists, allied stakeholders, and certainly readers. © Taylor and Francis Group, LLC", "title": "Coffee and its consumption: benefits and risks." }, { "docid": "MED-3925", "text": "This study describes how foods rich in fisetin and hexacosanol added to a strict diet reversed most symptoms of Parkinson's disease (PD) in one patient. This is a case report involving outpatient care. The subject was a dietitian diagnosed with idiopathic PD in 2000 at the age of 53 years old, with a history of exposure to neurotoxins and no family history of PD. A basic diet started in 2000 consisted of predominantly fruits, vegetables, 100% whole grains, extra virgin olive oil, nuts, seeds, nonfat milk products, tea, coffee, spices, small amounts of dark chocolate, and less than 25 g of animal fat daily. The basic diet alone failed to prevent decline due to PD. In 2009, the basic diet was enhanced with a good dietary source of both fisetin and hexacosanol. Six months after the patient started the enhanced diet rich in fisetin and hexacosanol, a clinically significant improvement in symptoms was noted; the patient's attending neurologist reported that the clinical presentation of cogwheel rigidity, micrographia, bradykinesia, dystonia, constricted arm swing with gait, hypomimia, and retropulsion appeared to be resolved. The only worsening of symptoms occurred when the diet was not followed precisely. Little improvement in tremor or seborrhea was observed. The clinical improvement has persisted to date. To the best of our knowledge, this is the first case where adjunctive diet therapy resulted in a significant reduction of symptoms of PD without changing the type or increasing the amount of medications.", "title": "A diet low in animal fat and rich in N-hexacosanol and fisetin is effective in reducing symptoms of Parkinson's disease." }, { "docid": "MED-5192", "text": "High dietary intakes of calcium and dairy products have been hypothesized to enhance prostate cancer risk, but available prospective data regarding these associations are inconsistent. We examined dietary intakes of calcium and dairy products in relation to risk of prostate cancer in the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study, a cohort of 29,133 male smokers aged 50-69 years at study entry. Dietary intake was assessed at baseline using a validated 276-item food use questionnaire. Cox proportional hazards regression was used to adjust for known or suspected risk factors for prostate cancer. During 17 years of follow-up, we ascertained 1,267 incident cases of prostate cancer. High versus low intake of dietary calcium was associated with a marked increase in prostate cancer risk. The multivariate relative risk (RR) of prostate cancer for > or =2,000 mg/day compared to <1,000 mg/day of calcium intake was 1.63 (95% confidence interval (CI), 1.27-2.10; p trend < 0.0001). Total dairy intake was also positively associated with risk of prostate cancer. The multivariate RR of prostate cancer comparing extreme quintiles of intake was 1.26 (95% CI, 1.04-1.51; p trend = 0.03). However, no association with total dairy intake remained after we adjusted for calcium (p trend = 0.17). Findings were similar by stage and grade of prostate cancer. The results from this large prospective study suggest that intake of calcium or some related component contained in dairy foods is associated with increased prostate cancer risk.", "title": "A prospective study of dietary calcium, dairy products and prostate cancer risk (Finland)." }, { "docid": "MED-1595", "text": "Hormones work in harmony in the body, and this status must be maintained to avoid metabolic disequilibrium and the subsequent illness. Besides, it has been reported that exogenous steroids (presence in the environment and food products) influence the development of several important illnesses in humans. Endogenous steroid hormones in food of animal origin are unavoidable as they occur naturally in these products. The presence of hormones in food has been connected with several human health problems. Bovine milk contains considerable quantities of hormones and it is of particular concern. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, based on hydroxylamine derivatisation, has been developed and validated for the quantification of six sex hormones in milk [pregnenolone (P₅), progesterone (P₄), estrone (E₁), testosterone (T), androstenedione (A) and dehydroepiandrosterone (DHEA)]. This method has been applied to real raw milk samples and the existence of differences between milk from pregnant and non-pregnant cows has been statistically confirmed. Basing on a revision of existing published data, it could be concluded that maximum daily intakes for hormones are not reached through milk ingestion. Although dairy products are an important source of hormones, other products of animal origin must be considered as well for intake calculations.", "title": "Development of an LC-MS/MS method to quantify sex hormones in bovine milk and influence of pregnancy in their levels." }, { "docid": "MED-1230", "text": "This study examined the relationship between funding sources and the outcomes of published obesity-related research. A list of funded projects for human nutrition research linking food intake to obesity in 2001-2005 was drawn from two distinct sources: (a) the federal government's semi-public generic commodity promotion or \"checkoff\" programs for Fluid Milk and Dairy and (b) the National Institutes of Health (NIH). The Principal Investigator for each funded project was determined. Published literature by that individual was located using an Ovid MEDLINE and PubMed author search. All articles related to both dairy and obesity were included. Financial sponsorship for each article and article conclusions were classified by independent groups of co-investigators. Seventy-nine relevant articles were included in the study. Of these, 62 were sponsored by the checkoff programs and 17 by the NIH. The study did not find consistent evidence that checkoff-funded projects were more likely to support an obesity prevention benefit from dairy consumption. The study did identify a new research methodology for the investigation of bias by source of sponsorship. Copyright © 2012 Elsevier Inc. All rights reserved.", "title": "Relationship between funding sources and outcomes of obesity-related research." }, { "docid": "MED-2917", "text": "The effect of alternative dietary habits and prolonged lactation on the nutrient and contaminant concentrations in human milk was studied. The study sample consisted of mothers on macrobiotic diets, containing little or no diary products and meat, at 2-3 months postpartum (n = 9) and 9-13 months postpartum (n = 12), and mothers on omnivorous diets at 2-3 months postpartum (n = 10). Protein and zinc concentrations in breast-milk from macrobiotic mothers decreased with stage of lactation. After adjustment for stage of lactation, milk from macrobiotic mothers contained less calcium, magnesium and saturated fatty acids C15:0-C20:0, and more polyunsaturated fatty acids. Observed tendencies for lower protein and fat and higher lactose concentrations in the macrobiotic group were not statistically significant. Concentrations of vitamin B12, HCB and polychlorinated biphenyls (PCB 118, PCB 138, PCB 153 and PCB 180) were lower in the macrobiotic group. After adjustment for confounding variables, meat and fish consumption, but not dairy products, contributed to vitamin B12 concentrations. Meat and diary products strongly contributed to breast-milk concentrations of dieldrin and PCBs, fish to PCB 118, and smoking to DDT and dieldrin. Our findings suggest that breast-milk contamination could be reduced by abstinence from smoking and a moderate intake of animal products. However, risk of nutritional deficiencies rules out complete avoidance of meat, fish or diary products. Quantitative research on the effects of a reduced consumption of animal products, as well as smoking, on breast-milk contamination is warranted.", "title": "Nutrients and contaminants in human milk from mothers on macrobiotic and omnivorous diets." }, { "docid": "MED-1499", "text": "Nature has gifted mankind with a plethora of flora-bearing fruits, vegetables and nuts. The diverse array of bioactive nutrients present in these natural products plays a pivotal role in prevention and cure of various neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease and other neuronal dysfunctions. Accumulated evidence suggests that naturally occurring phyto-compounds, such as polyphenolic antioxidants found in fruits, vegetables, herbs and nuts, may potentially hinder neurodegeneration, and improve memory and cognitive function. Nuts such as walnut have also demonstrated neuroprotective effect against AD. The molecular mechanisms behind the curative effects rely mainly on the action of phytonutrients on distinct signalling pathways associated with protein folding and neuroinflammation. The neuroprotective effects of various naturally occurring compounds in AD is evaluating in this review.", "title": "Neuroprotective effect of natural products against Alzheimer's disease." }, { "docid": "MED-3931", "text": "Although a plant-based diet can provide some benefits in Parkinson's disease (PD), no study to date has evaluated the effectiveness of a plant-food diet in the management of the disease. In this pilot study, we compared the effect of a plant-food menu (PFD) and of a omnivorous menu on motor performance of 25 PD patients, 12 in the intervention group (PDi) and 13 in the control group (PDc). After 4 weeks, the PDi group showed a significant reduction (Mann-Whitney test) in the Unified Parkinson's Disease Rating Scale, total score (47.67 vs. 74.46, P = 0.008) and sub-score III motor performances (25.42 vs. 46.46, P = 0.001), and the modified Hoehn and Yahr Staging Scale (1.96 vs. 3.15, P = 0.005). These data suggest that PFD may be useful in the management of PD patients by improving their motor performances. Additional studies are needed in order to confirm these preliminary results.", "title": "Pilot dietary study with normoproteic protein-redistributed plant-food diet and motor performance in patients with Parkinson's disease." }, { "docid": "MED-5033", "text": "This year, more than 1 million Americans and more than 10 million people worldwide are expected to be diagnosed with cancer, a disease commonly believed to be preventable. Only 5–10% of all cancer cases can be attributed to genetic defects, whereas the remaining 90–95% have their roots in the environment and lifestyle. The lifestyle factors include cigarette smoking, diet (fried foods, red meat), alcohol, sun exposure, environmental pollutants, infections, stress, obesity, and physical inactivity. The evidence indicates that of all cancer-related deaths, almost 25–30% are due to tobacco, as many as 30–35% are linked to diet, about 15–20% are due to infections, and the remaining percentage are due to other factors like radiation, stress, physical activity, environmental pollutants etc. Therefore, cancer prevention requires smoking cessation, increased ingestion of fruits and vegetables, moderate use of alcohol, caloric restriction, exercise, avoidance of direct exposure to sunlight, minimal meat consumption, use of whole grains, use of vaccinations, and regular check-ups. In this review, we present evidence that inflammation is the link between the agents/factors that cause cancer and the agents that prevent it. In addition, we provide evidence that cancer is a preventable disease that requires major lifestyle changes.", "title": "Cancer is a Preventable Disease that Requires Major Lifestyle Changes" }, { "docid": "MED-5239", "text": "Epidemiological evidence points to increased dairy and meat consumption, staples of the Western diet, as major risk factors for the development of type 2 diabetes (T2D). This paper presents a new concept and comprehensive review of leucine-mediated cell signaling explaining the pathogenesis of T2D and obesity by leucine-induced over-stimulation of mammalian target of rapamycin complex 1 (mTORC1). mTORC1, a pivotal nutrient-sensitive kinase, promotes growth and cell proliferation in response to glucose, energy, growth factors and amino acids. Dairy proteins and meat stimulate insulin/insulin-like growth factor 1 signaling and provide high amounts of leucine, a primary and independent stimulator for mTORC1 activation. The downstream target of mTORC1, the kinase S6K1, induces insulin resistance by phosphorylation of insulin receptor substrate-1, thereby increasing the metabolic burden of β-cells. Moreover, leucine-mediated mTORC1-S6K1-signaling plays an important role in adipogenesis, thus increasing the risk of obesity-mediated insulin resistance. High consumption of leucine-rich proteins explains exaggerated mTORC1-dependent insulin secretion, increased β-cell growth and β-cell proliferation promoting an early onset of replicative β-cell senescence with subsequent β-cell apoptosis. Disturbances of β-cell mass regulation with increased β-cell proliferation and apoptosis as well as insulin resistance are hallmarks of T2D, which are all associated with hyperactivation of mTORC1. In contrast, the anti-diabetic drug metformin antagonizes leucine-mediated mTORC1 signaling. Plant-derived polyphenols and flavonoids are identified as natural inhibitors of mTORC1 and exert anti-diabetic and anti-obesity effects. Furthermore, bariatric surgery in obesity reduces increased plasma levels of leucine and other branched-chain amino acids. Attenuation of leucine-mediated mTORC1 signaling by defining appropriate upper limits of the daily intake of leucine-rich animal and dairy proteins may offer a great chance for the prevention of T2D and obesity, as well as other epidemic diseases of civilization with increased mTORC1 signaling, especially cancer and neurodegenerative diseases, which are frequently associated with T2D.", "title": "Leucine signaling in the pathogenesis of type 2 diabetes and obesity" }, { "docid": "MED-1487", "text": "PURPOSE An informed decision to accept a health care intervention requires an understanding of its likely benefit. This study assessed participants' estimates of the benefit, as well as minimum acceptable benefit, of screening for breast and bowel cancer and medication to prevent hip fracture and cardiovascular disease. METHODS Three general practitioners sent questionnaires to all registered patients aged 50 to 70 years. Patients agreeing to participate in the study were asked to estimate the number of events (fractures or deaths) prevented in a group of 5,000 patients undergoing each intervention over a period of 10 years, and to indicate the minimum number of events avoided by the intervention that they considered justified its use. The proportions of participants that overestimated each intervention's benefit were calculated, and univariate and multivariable analyses of predictors of response were performed. RESULTS The participation rate was 36%: 977 patients were invited to participate in the study, and 354 returned a completed questionnaire. Participants overestimated the degree of benefit conferred by all interventions: 90% of participants overestimated the effect of breast cancer screening, 94% overestimated the effect of bowel cancer screening, 82% overestimated the effect of hip fracture preventive medication, and 69% overestimated the effect of preventive medication for cardiovascular disease. Estimates of minimum acceptable benefit were more conservative, but other than for cardiovascular disease mortality prevention, most respondents indicated a minimum benefit greater than these interventions achieve. A lower level of education was associated with higher estimates of minimum acceptable benefit for all interventions. CONCLUSION Patients overestimated the risk reduction achieved with 4 examples of screening and preventive medications. A lower level of education was associated with higher minimum benefit to justify intervention use. This tendency to overestimate benefits may affect patients' decisions to use such interventions, and practitioners should be aware of this tendency when discussing these interventions with patients.", "title": "Patients' Expectations of Screening and Preventive Treatments" }, { "docid": "MED-2121", "text": "The purpose of this paper is to highlight the endocrine signaling of Western diet, a fundamental environmental factor involved in the pathogenesis of epidemic acne. Western nutrition is characterized by high calorie uptake, high glycemic load, high fat and meat intake, as well as increased consumption of insulin- and IGF-1-level elevating dairy proteins. Metabolic signals of Western diet are sensed by the nutrient-sensitive kinase, mammalian target of rapamycin complex 1 (mTORC1), which integrates signals of cellular energy, growth factors (insulin, IGF-1) and protein-derived signals, predominantly leucine, provided in high amounts by milk proteins and meat. mTORC1 activates SREBP, the master transcription factor of lipogenesis. Leucine stimulates mTORC1-SREBP signaling and leucine is directly converted by sebocytes into fatty acids and sterols for sebaceous lipid synthesis. Over-activated mTORC1 increases androgen hormone secretion and most likely amplifies androgen-driven mTORC1 signaling of sebaceous follicles. Testosterone directly activates mTORC1. Future research should investigate the effects of isotretinoin on sebocyte mTORC1 activity. It is conceivable that isotretinoin may downregulate mTORC1 in sebocytes by upregulation of nuclear levels of FoxO1. The role of Western diet in acne can only be fully appreciated when all stimulatory inputs for maximal mTORC1 activation, i.e., glucose, insulin, IGF-1 and leucine, are adequately considered. Epidemic acne has to be recognized as an mTORC1-driven disease of civilization like obesity, type 2 diabetes, cancer and neurodegenerative diseases. These new insights into Western diet-mediated mTORC1-hyperactivity provide a rational basis for dietary intervention in acne by attenuating mTORC1 signaling by reducing (1) total energy intake, (2) hyperglycemic carbohydrates, (3) insulinotropic dairy proteins and (4) leucine-rich meat and dairy proteins. The necessary dietary changes are opposed to the evolution of industrialized food and fast food distribution of Westernized countries. An attenuation of mTORC1 signaling is only possible by increasing the consumption of vegetables and fruit, the major components of vegan or Paleolithic diets. The dermatologist bears a tremendous responsibility for his young acne patients who should be advised to modify their dietary habits in order to reduce activating stimuli of mTORC1, not only to improve acne but to prevent the harmful and expensive march to other mTORC1-related chronic diseases later in life.", "title": "Dietary intervention in acne" }, { "docid": "MED-3385", "text": "Diacetyl-containing butter flavor was identified as the cause of an outbreak of bronchiolitis obliterans (BO) and other lung diseases in popcorn-plant workers. Litigation documents show that the outbreak was both predictable and preventable. The industry trade organization was aware of BO cases in workers at butter-flavoring and popcorn-manufacturing plants but often failed to implement industrial hygiene improvements and actively hid pertinent warning information. Due to weaknesses in the organization and mandates of regulatory bodies, organizations such as NIOSH, OSHA, the FDA, particularly the \"generally recognized as safe\" (GRAS) system, and the EPA failed to detect and prevent the outbreak, which highlights the need for systemic changes in food-product regulation, including the need for corporations to act responsibly, for stronger regulations with active enforcement, for a restructuring of the GRAS system, and for criminal penalties against corporations and professionals who knowingly hide information relevant to worker protection.", "title": "Popcorn-worker lung caused by corporate and regulatory negligence: an avoidable tragedy." }, { "docid": "MED-4391", "text": "Cancer is a leading cause of death worldwide. There are a lot of cancer causing agents which are divided as physical carcinogens, chemical carcinogens and biological carcinogens. But most of the carcinogens or causes of cancer are related to our lifestyle like diet, habit, occupation, radiation and some infection, etc. Chemoprevention is highly necessary to prevent cancer related preterm death. For this besides avoiding the causes of cancer we should concentrate ourselves on our diet. Because, numerous phytochemicals derived from edible plants have been reported to interfere with a specific stage of the carcinogenic process. Many mechanisms have been shown to account for the anticarcinogenic actions of dietary constituents and recently attention has been focused on intracellular-signalling cascades as common molecular targets for various chemopreventive phytochemicals. In this study, we tried to describe lifestyle related causes of cancer and the molecular basis of cancer prevention through the phytochemicals.", "title": "Lifestyle related causes of cancer and chemoprevention through phytonutrients." }, { "docid": "MED-5185", "text": "There is some evidence that dietary factors may modify the risk of squamous cell carcinoma (SCC) of the skin, but the association between food intake and SCC has not been evaluated prospectively. We examined the association between food intake and SCC incidence among 1,056 randomly selected adults living in an Australian sub-tropical community. Measurement-error corrected estimates of intake in 15 food groups were defined from a validated food frequency questionnaire in 1992. Associations with SCC risk were assessed using Poisson and negative binomial regression to the persons affected and tumour counts, respectively, based on incident, histologically confirmed tumours occurring between 1992 and 2002. After multivariable adjustment, none of the food groups was significantly associated with SCC risk. Stratified analysis in participants with a past history of skin cancer showed a decreased risk of SCC tumours for high intakes of green leafy vegetables (RR = 0.45, 95% CI = 0.22-0.91; p for trend = 0.02) and an increased risk for high intake of unmodified dairy products (RR = 2.53, 95% CI: 1.15-5.54; p for trend = 0.03). Food intake was not associated with SCC risk in persons who had no past history of skin cancer. These findings suggest that consumption of green leafy vegetables may help prevent development of subsequent SCCs of the skin among people with previous skin cancer and that consumption of unmodified dairy products, such as whole milk, cheese and yoghurt, may increase SCC risk in susceptible persons. Copyright 2006 Wiley-Liss, Inc.", "title": "Food intake and risk of squamous cell carcinoma of the skin in a community: the Nambour skin cancer cohort study." }, { "docid": "MED-2177", "text": "Four persons developed marked parkinsonism after using an illicit drug intravenously. Analysis of the substance injected by two of these patients revealed primarily 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) with trace amounts of 1-methyl-4-phenyl-4-propionoxy-piperidine (MPPP). On the basis of the striking parkinsonian features observed in our patients, and additional pathological data from one previously reported case, it is proposed that this chemical selectively damages cells in the substantia nigra.", "title": "Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis." }, { "docid": "MED-3927", "text": "Objective: Epidemiologic studies consistently link caffeine, a nonselective adenosine antagonist, to lower risk of Parkinson disease (PD). However, the symptomatic effects of caffeine in PD have not been adequately evaluated. Methods: We conducted a 6-week randomized controlled trial of caffeine in PD to assess effects upon daytime somnolence, motor severity, and other nonmotor features. Patients with PD with daytime somnolence (Epworth >10) were given caffeine 100 mg twice daily ×3 weeks, then 200 mg twice daily ×3 weeks, or matching placebo. The primary outcome was the Epworth Sleepiness Scale score. Secondary outcomes included motor severity, sleep markers, fatigue, depression, and quality of life. Effects of caffeine were analyzed with Bayesian hierarchical models, adjusting for study site, baseline scores, age, and sex. Results: Of 61 patients, 31 were randomized to placebo and 30 to caffeine. On the primary intention-to-treat analysis, caffeine resulted in a nonsignificant reduction in Epworth Sleepiness Scale score (−1.71 points; 95% confidence interval [CI] −3.57, 0.13). However, somnolence improved on the Clinical Global Impression of Change (+0.64; 0.16, 1.13, intention-to-treat), with significant reduction in Epworth Sleepiness Scale score on per-protocol analysis (−1.97; −3.87, −0.05). Caffeine reduced the total Unified Parkinson's Disease Rating Scale score (−4.69 points; −7.7, −1.6) and the objective motor component (−3.15 points; −5.50, −0.83). Other than modest improvement in global health measures, there were no changes in quality of life, depression, or sleep quality. Adverse events were comparable in caffeine and placebo groups. Conclusions: Caffeine provided only equivocal borderline improvement in excessive somnolence in PD, but improved objective motor measures. These potential motor benefits suggest that a larger long-term trial of caffeine is warranted. Classification of evidence: This study provides Class I evidence that caffeine, up to 200 mg BID for 6 weeks, had no significant benefit on excessive daytime sleepiness in patients with PD.", "title": "Caffeine for treatment of Parkinson disease" }, { "docid": "MED-1705", "text": "Despite an archive of over 73,000 research papers published in the last two decades on the subject of Alzheimer's disease (AD), little clinical progress has been made relative to how people get sporadic AD and what can be done to help them avoid it. This review spotlights strategic steps that could be a turning point in the dramatic lowering of Alzheimer prevalence. The main strategy includes application of four pillars of prevention: 1) early identification of AD vascular risk factors; 2) early detection of AD vascular risk factors; 3) early intervention of AD vascular risk factors based on evidence-based medical decisions; 4) patient follow-up to assess and modify interventions as needed. Tandem to these four pillars of prevention, a proactive lifestyle consisting of a healthy diet coupled to physical and mental activity should be applied as part of any therapeutic intervention. We are persuaded by mounting and compelling evidence that AD is a multifactorial disorder kindled by vascular risk factors that generate chronic brain hypoperfusion (CBH) during advanced aging. A pathobiological cascade of biochemical events in the presence of CBH that leads to oxidative stress and neurodegeneration appears to involve multiple biofactors including micronutrients, trace metals, lipids, and pro-oxidants, as reviewed in this special issue of BioFactors. Modulation of these biofactors may help prevent or control incipient AD. © 2012 International Union of Biochemistry and Molecular Biology, Inc. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.", "title": "A turning point for Alzheimer's disease?" }, { "docid": "MED-3933", "text": "In this study, the effects of a diet rich in insoluble fiber (DRIF) on motor disability and the peripheral pharmacokinetics of orally administered L-dopa in Parkinsonian patients with marked constipation are analyzed. We found a useful effect of a DRIF on plasma L-dopa concentration and motor function. The greatest effect on the plasma L-dopa levels was found early (at 30 and 60 min) after oral administration. There was a relationship between the improvement of constipation and the higher bioavailability of L-dopa. DRIF can be a coadjuvant treatment in patients with Parkinson's disease.", "title": "Clinical and pharmacokinetic effects of a diet rich in insoluble fiber on Parkinson disease." }, { "docid": "MED-1988", "text": "PURPOSE OF REVIEW: To review recent literature on important topics in pediatric office practice: bullying, screening for the prediabetic state, and pediatric oral health. RECENT FINDINGS: Recent literature shows that bullying behaviors are common in children as young as kindergarten age, that there is a strong association between being a bully or victim and a range of psychosomatic and depressive symptoms in children, and that interventions including family therapy and school-based programs are effective for bullies and victims. Recent studies have further delineated glucose and insulin metabolism. Recent work has provided new models to help practitioners screen for the prediabetic state in hope of providing earlier opportunities to intervene and avoid the morbidities associated with type 2 diabetes mellitus. Recent literature emphasizes continued gaps in dental healthcare for patients who are most at risk. Recent studies emphasize the important role that diet and sealants have in preventing dental caries. SUMMARY: Recent literature emphasizes the important role that office-based pediatricians have in identifying patients who are involved in bullying, at risk of developing type 2 diabetes mellitus, or have poor dental health. Future research will help delineate these problems and provide us with refined primary prevention and treatment guidelines.", "title": "Pediatrician's role in screening and treatment: bullying, prediabetes, oral health." }, { "docid": "MED-3534", "text": "Background Numerous antioxidant and anti‐inflammatory agents have been identified in tart cherries. Objective To test the efficacy of a tart cherry juice blend in preventing the symptoms of exercise induced muscle damage. Methods This was a randomised, placebo controlled, crossover design. Fourteen male college students drank 12 fl oz of a cherry juice blend or a placebo twice a day for eight consecutive days. A bout of eccentric elbow flexion contractions (2 × 20 maximum contractions) was performed on the fourth day of supplementation. Isometric elbow flexion strength, pain, muscle tenderness, and relaxed elbow angle were recorded before and for four days after the eccentric exercise. The protocol was repeated two weeks later with subjects who took the placebo initially, now taking the cherry juice (and vice versa). The opposite arm performed the eccentric exercise for the second bout to avoid the repeated bout protective effect. Results Strength loss and pain were significantly less in the cherry juice trial versus placebo (time by treatment: strength p<0.0001, pain p  =  0.017). Relaxed elbow angle (time by treatment p  =  0.85) and muscle tenderness (time by treatment p  =  0.81) were not different between trials. Conclusions These data show efficacy for this cherry juice in decreasing some of the symptoms of exercise induced muscle damage. Most notably, strength loss averaged over the four days after eccentric exercise was 22% with the placebo but only 4% with the cherry juice.", "title": "Efficacy of a tart cherry juice blend in preventing the symptoms of muscle damage" }, { "docid": "MED-1773", "text": "STUDY QUESTION Is increased consumption of dairy foods associated with lower semen quality? SUMMARY ANSWER We found that intake of full-fat dairy was inversely related to sperm motility and morphology. These associations were driven primarily by intake of cheese and were independent of overall dietary patterns. WHAT IS KNOWN ALREADY It has been suggested that environmental estrogens could be responsible for the putative secular decline in sperm counts. Dairy foods contain large amounts of estrogens. While some studies have suggested dairy as a possible contributing factor for decreased semen quality, this finding has not been consistent across studies. STUDY DESIGN, SIZE, DURATION The Rochester Young Men's Study (n = 189) was a cross-sectional study conducted between 2009 and 2010 at the University of Rochester. PARTICIPANTS/MATERIALS, SETTING, METHODS Men aged 18–22 years were included in this analysis. Diet was assessed via food frequency questionnaire. Linear regression was used to analyze the relation between dairy intake and conventional semen quality parameters (total sperm count, sperm concentration, progressive motility, morphology and ejaculate volume) adjusting for age, abstinence time, race, smoking status, body mass index, recruitment period, moderate-to-intense exercise, TV watching and total calorie intake. MAIN RESULTS AND THE ROLE OF CHANCE Total dairy food intake was inversely related to sperm morphology (P-trend = 0.004). This association was mostly driven by intake of full-fat dairy foods. The adjusted difference (95% confidence interval) in normal sperm morphology percent was −3.2% (−4.5 to −1.8) between men in the upper half and those in the lower half of full-fat dairy intake (P < 0.0001), while the equivalent contrast for low-fat dairy intake was less pronounced [−1.3% (−2.7 to −0.07; P= 0.06)]. Full-fat dairy intake was also associated with significantly lower percent progressively motile sperm (P= 0.05). LIMITATIONS, REASONS FOR CAUTION As it was a cross-sectional study, causal inference is limited. WIDER IMPLICATIONS OF THE FINDINGS Further research is needed to prove a causal link between a high consumption of full-fat dairy foods and detrimental effects on semen quality. If verified our findings would mean that intake of full-fat dairy foods should be considered in attempts to explain secular trends in semen quality and that men trying to have children should restrict their intake. STUDY FUNDING/COMPETING INTEREST(S) European Union Seventh Framework Program (Environment), ‘Developmental Effects of Environment on Reproductive Health’ (DEER) grant 212844. Grant P30 {\"type\":\"entrez-nucleotide\",\"attrs\":{\"text\":\"DK046200\",\"term_id\":\"187635970\",\"term_text\":\"DK046200\"}}DK046200 and Ruth L. Kirschstein National Research Service Award T32 DK007703-16 from the National Institutes of Health. None of the authors has any conflicts of interest to declare.", "title": "Dairy food intake in relation to semen quality and reproductive hormone levels among physically active young men" }, { "docid": "MED-1679", "text": "BACKGROUND: Healthy lifestyle choices such as eating a prudent diet, exercising regularly, managing weight, and not smoking may substantially reduce coronary heart disease (CHD) risk by improving lipids, blood pressure, and other risk factors. The burden of CHD that could be avoided through adherence to these modifiable lifestyle factors has not been assessed among middle-aged and older US men, specifically men taking medications for hypertension or hypercholesterolemia. METHODS AND RESULTS: We prospectively monitored 42 847 men in the Health Professionals Follow-up Study, 40 to 75 years of age and free of disease in 1986. Lifestyle factors were updated through self-reported questionnaires. Low risk was defined as (1) absence of smoking, (2) body mass index <25 kg/m2, (3) moderate-to-vigorous activity > or = 30 min/d, (4) moderate alcohol consumption (5 to 30 g/d), and (5) the top 40% of the distribution for a healthy diet score. Over 16 years, we documented 2183 incident cases of CHD (nonfatal myocardial infarction and fatal CHD). In multivariate-adjusted Cox proportional hazards models, men who were at low risk for 5 lifestyle factors had a lower risk of CHD (relative risk: 0.13; 95% confidence interval [CI]: 0.09, 0.19) compared with men who were at low risk for no lifestyle factors. Sixty-two percent (95% CI: 49%, 74%) of coronary events in this cohort may have been prevented with better adherence to these 5 healthy lifestyle practices. Among men taking medication for hypertension or hypercholesterolemia, 57% (95% CI: 32%, 79%) of all coronary events may have been prevented with a low-risk lifestyle. Compared with men who did not make lifestyle changes during follow-up, those who adopted > or = 2 additional low-risk lifestyle factors had a 27% (95% CI: 7%, 43%) lower risk of CHD. CONCLUSIONS: A majority of CHD events among US men may be preventable through adherence to healthy lifestyle practices, even among those taking medications for hypertension or hypercholesterolemia.", "title": "Healthy lifestyle factors in the primary prevention of coronary heart disease among men: benefits among users and nonusers of lipid-lowering and an..." }, { "docid": "MED-3928", "text": "Seven patients with Parkinson's disease who experienced severe motor fluctuations in response to levodopa were studied in detail with relation to the effect of dietary protein on their motor function. The levodopa dose for each patient was not changed during the period of study, and no other antiparkinsonian drugs were used. Regular and high-protein diets resulted in a marked elevation in the plasma concentrations of large neutral amino acids (LNAAs) that are known to compete with levodopa for transport across the blood-brain barrier. Despite elevated plasma levodopa levels, all patients with elevated LNAA levels experienced parkinsonian symptoms. When the amino acid level dropped while plasma levodopa levels were elevated, patients experienced relief of these symptoms. On a low-protein diet, LNAA levels remained low and all patients were consistently dyskinetic throughout the day, even though the mean plasma levodopa levels were somewhat lower than when the patients consumed a high-protein diet. A redistribution diet that is virtually protein free until supper and then unrestricted until bedtime is tolerated by patients because this simple manipulation permits near-normal daytime motor function.", "title": "Plasma levels of amino acids correlate with motor fluctuations in parkinsonism." }, { "docid": "MED-5194", "text": "BACKGROUND: Dairy consumption affects biological pathways associated with carcinogenesis. Evidence for a link between cancer risk and dairy consumption in adulthood is increasing, but associations with childhood dairy consumption have not been studied adequately. OBJECTIVE: We investigated whether dairy consumption in childhood is associated with cancer incidence and mortality in adulthood. DESIGN: From 1937 through 1939, some 4,999 children living in England and Scotland participated in a study of family food consumption, assessed from 7-d household food inventories. The National Health Service central register was used to ascertain cancer registrations and deaths between 1948 and 2005 in the 4,383 traced cohort members. Per capita household intake estimates for dairy products and calcium were used as proxy for individual intake. RESULTS: During the follow-up period, 770 cancer registrations or cancer deaths occurred. High childhood total dairy intake was associated with a near-tripling in the odds of colorectal cancer [multivariate odds ratio: 2.90 (95% CI: 1.26, 6.65); 2-sided P for trend = 0.005] compared with low intake, independent of meat, fruit, and vegetable intakes and socioeconomic indicators. Milk intake showed a similar association with colorectal cancer risk. High milk intake was weakly inversely associated with prostate cancer risk (P for trend = 0.11). Childhood dairy intake was not associated with breast and stomach cancer risk; a positive association with lung cancer risk was confounded by smoking behavior during adulthood. CONCLUSIONS: A family diet rich in dairy products during childhood is associated with a greater risk of colorectal cancer in adulthood. Confirmation of possible underlying biological mechanisms is needed.", "title": "Childhood dairy intake and adult cancer risk: 65-y follow-up of the Boyd Orr cohort." } ]
45
A mutation in HNF4A leads to an increased risk of diabetes by the age of 14 years.
[ { "docid": "56893404", "text": "Background Macrosomia is associated with considerable neonatal and maternal morbidity. Factors that predict macrosomia are poorly understood. The increased rate of macrosomia in the offspring of pregnant women with diabetes and in congenital hyperinsulinaemia is mediated by increased foetal insulin secretion. We assessed the in utero and neonatal role of two key regulators of pancreatic insulin secretion by studying birthweight and the incidence of neonatal hypoglycaemia in patients with heterozygous mutations in the maturity-onset diabetes of the young (MODY) genes HNF4A (encoding HNF-4α) and HNF1A/TCF1 (encoding HNF-1α), and the effect of pancreatic deletion of Hnf4a on foetal and neonatal insulin secretion in mice.", "title": "Macrosomia and Hyperinsulinaemic Hypoglycaemia in Patients with Heterozygous Mutations in the HNF4A Gene" } ]
[ { "docid": "7552215", "text": "OBJECTIVE To summarise the long term efficacy of anti-obesity drugs in reducing weight and improving health status. DESIGN Updated meta-analysis of randomised trials. DATA SOURCES Medline, Embase, the Cochrane controlled trials register, the Current Science meta-register of controlled trials, and reference lists of identified articles. All data sources were searched from December 2002 (end date of last search) to December 2006. STUDIES REVIEWED Double blind randomised placebo controlled trials of approved anti-obesity drugs used in adults (age over 18) for one year or longer. RESULTS 30 trials of one to four years' duration met the inclusion criteria: 16 orlistat (n=10 631 participants), 10 sibutramine (n=2623), and four rimonabant (n=6365). Of these, 14 trials were new and 16 had previously been identified. Attrition rates averaged 30-40%. Compared with placebo, orlistat reduced weight by 2.9 kg (95% confidence interval 2.5 kg to 3.2 kg), sibutramine by 4.2 kg (3.6 kg to 4.7 kg), and rimonabant by 4.7 kg (4.1 kg to 5.3 kg). Patients receiving active drug treatment were significantly more likely to achieve 5% and 10% weight loss thresholds. Orlistat reduced the incidence of diabetes and improved concentrations of total cholesterol and low density lipoprotein cholesterol, blood pressure, and glycaemic control in patients with diabetes but increased rates of gastrointestinal side effects and slightly lowered concentrations of high density lipoprotein. Sibutramine improved [corrected] concentrations of high density lipoprotein cholesterol and triglycerides [corrected] Rimonabant improved concentrations of high density lipoprotein cholesterol and triglycerides, blood pressure, and glycaemic control in patients with diabetes but increased the risk of mood disorders. CONCLUSIONS Orlistat, sibutramine, and rimonabant modestly reduce weight, have differing effects on cardiovascular risk profiles, and have specific adverse effects.", "title": "Long term pharmacotherapy for obesity and overweight: updated meta-analysis." }, { "docid": "1387104", "text": "CONTEXT Venous thrombosis is a common complication in patients with cancer, leading to additional morbidity and compromising quality of life. OBJECTIVE To identify individuals with cancer with an increased thrombotic risk, evaluating different tumor sites, the presence of distant metastases, and carrier status of prothrombotic mutations. DESIGN, SETTING, AND PATIENTS A large population-based, case-control (Multiple Environmental and Genetic Assessment [MEGA] of risk factors for venous thrombosis) study of 3220 consecutive patients aged 18 to 70 years, with a first deep venous thrombosis of the leg or pulmonary embolism, between March 1, 1999, and May 31, 2002, at 6 anticoagulation clinics in the Netherlands, and separate 2131 control participants (partners of the patients) reported via a questionnaire on acquired risk factors for venous thrombosis. Three months after discontinuation of the anticoagulant therapy, all patients and controls were interviewed, a blood sample was taken, and DNA was isolated to ascertain the factor V Leiden and prothrombin 20210A mutations. MAIN OUTCOME MEASURE Risk of venous thrombosis. RESULTS The overall risk of venous thrombosis was increased 7-fold in patients with a malignancy (odds ratio [OR], 6.7; 95% confidence interval [CI], 5.2-8.6) vs persons without malignancy. Patients with hematological malignancies had the highest risk of venous thrombosis, adjusted for age and sex (adjusted OR, 28.0; 95% CI, 4.0-199.7), followed by lung cancer and gastrointestinal cancer. The risk of venous thrombosis was highest in the first few months after the diagnosis of malignancy (adjusted OR, 53.5; 95% CI, 8.6-334.3). Patients with cancer with distant metastases had a higher risk vs patients without distant metastases (adjusted OR, 19.8; 95% CI, 2.6-149.1). Carriers of the factor V Leiden mutation who also had cancer had a 12-fold increased risk vs individuals without cancer and factor V Leiden (adjusted OR, 12.1; 95% CI, 1.6-88.1). Similar results were indirectly calculated for the prothrombin 20210A mutation in patients with cancer. CONCLUSIONS Patients with cancer have a highly increased risk of venous thrombosis especially in the first few months after diagnosis and in the presence of distant metastases. Carriers of the factor V Leiden and prothrombin 20210A mutations appear to have an even higher risk.", "title": "Malignancies, prothrombotic mutations, and the risk of venous thrombosis." }, { "docid": "13282296", "text": "CONTEXT Although acute hypoglycemia may be associated with cognitive impairment in children with type 1 diabetes, no studies to date have evaluated whether hypoglycemia is a risk factor for dementia in older patients with type 2 diabetes. OBJECTIVE To determine if hypoglycemic episodes severe enough to require hospitalization are associated with an increased risk of dementia in a population of older patients with type 2 diabetes followed up for 27 years. DESIGN, SETTING, AND PATIENTS A longitudinal cohort study from 1980-2007 of 16,667 patients with a mean age of 65 years and type 2 diabetes who are members of an integrated health care delivery system in northern California. MAIN OUTCOME MEASURE Hypoglycemic events from 1980-2002 were collected and reviewed using hospital discharge and emergency department diagnoses. Cohort members with no prior diagnoses of dementia, mild cognitive impairment, or general memory complaints as of January 1, 2003, were followed up for a dementia diagnosis through January 15, 2007. Dementia risk was examined using Cox proportional hazard regression models, adjusted for age, sex, race/ethnicity, education, body mass index, duration of diabetes, 7-year mean glycated hemoglobin, diabetes treatment, duration of insulin use, hyperlipidemia, hypertension, cardiovascular disease, stroke, transient cerebral ischemia, and end-stage renal disease. RESULTS At least 1 episode of hypoglycemia was diagnosed in 1465 patients (8.8%) and dementia was diagnosed in 1822 patients (11%) during follow-up; 250 patients had both dementia and at least 1 episode of hypoglycemia (16.95%). Compared with patients with no hypoglycemia, patients with single or multiple episodes had a graded increase in risk with fully adjusted hazard ratios (HRs): for 1 episode (HR, 1.26; 95% confidence interval [CI], 1.10-1.49); 2 episodes (HR, 1.80; 95% CI, 1.37-2.36); and 3 or more episodes (HR, 1.94; 95% CI, 1.42-2.64). The attributable risk of dementia between individuals with and without a history of hypoglycemia was 2.39% per year (95% CI, 1.72%-3.01%). Results were not attenuated when medical utilization rates, length of health plan membership, or time since initial diabetes diagnosis were added to the model. When examining emergency department admissions for hypoglycemia for association with risk of dementia (535 episodes), results were similar (compared with patients with 0 episodes) with fully adjusted HRs: for 1 episode (HR, 1.42; 95% CI, 1.12-1.78) and for 2 or more episodes (HR, 2.36; 95% CI, 1.57-3.55). CONCLUSIONS Among older patients with type 2 diabetes, a history of severe hypoglycemic episodes was associated with a greater risk of dementia. Whether minor hypoglycemic episodes increase risk of dementia is unknown.", "title": "Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus." }, { "docid": "3355397", "text": "IMPORTANCE Studies suggest pioglitazone use may increase risk of cancers. OBJECTIVE To examine whether pioglitazone use for diabetes is associated with risk of bladder and 10 additional cancers. DESIGN, SETTING, AND PARTICIPANTS Cohort and nested case-control analyses among persons with diabetes. A bladder cancer cohort followed 193,099 persons aged 40 years or older in 1997-2002 until December 2012; 464 case patients and 464 matched controls were surveyed about additional confounders. A cohort analysis of 10 additional cancers included 236,507 persons aged 40 years or older in 1997-2005 and followed until June 2012. Cohorts were from Kaiser Permanente Northern California. EXPOSURES Ever use, duration, cumulative dose, and time since initiation of pioglitazone as time dependent. MAIN OUTCOMES AND MEASURES Incident cancer, including bladder, prostate, female breast, lung/bronchus, endometrial, colon, non-Hodgkin lymphoma, pancreas, kidney/renal pelvis, rectum, and melanoma. RESULTS Among 193,099 persons in the bladder cancer cohort, 34,181 (18%) received pioglitazone (median duration, 2.8 years; range, 0.2-13.2 years) and 1261 had incident bladder cancer. Crude incidences of bladder cancer in pioglitazone users and nonusers were 89.8 and 75.9 per 100,000 person-years, respectively. Ever use of pioglitazone was not associated with bladder cancer risk (adjusted hazard ratio [HR], 1.06; 95% CI, 0.89-1.26). Results were similar in case-control analyses (pioglitazone use: 19.6% among case patients and 17.5% among controls; adjusted odds ratio, 1.18; 95% CI, 0.78-1.80). In adjusted analyses, there was no association with 8 of the 10 additional cancers; ever use of pioglitazone was associated with increased risk of prostate cancer (HR, 1.13; 95% CI, 1.02-1.26) and pancreatic cancer (HR, 1.41; 95% CI, 1.16-1.71). Crude incidences of prostate and pancreatic cancer in pioglitazone users vs nonusers were 453.3 vs 449.3 and 81.1 vs 48.4 per 100,000 person-years, respectively. No clear patterns of risk for any cancer were observed for time since initiation, duration, or dose. CONCLUSIONS AND RELEVANCE Pioglitazone use was not associated with a statistically significant increased risk of bladder cancer, although an increased risk, as previously observed, could not be excluded. The increased prostate and pancreatic cancer risks associated with ever use of pioglitazone merit further investigation to assess whether they are causal or are due to chance, residual confounding, or reverse causality.", "title": "Pioglitazone Use and Risk of Bladder Cancer and Other Common Cancers in Persons With Diabetes." }, { "docid": "24704139", "text": "OBJECTIVE The Diabetes Prevention Program (DPP) is a 27-center randomized clinical trial designed to evaluate the safety and efficacy of interventions that may delay or prevent development of diabetes in people at increased risk for type 2 diabetes. RESEARCH DESIGN AND METHODS Eligibility requirements were age > or = 25 years, BMI > or = 24 kg/m2 (> or = 22 kg/m2 for Asian-Americans), and impaired glucose tolerance plus a fasting plasma glucose of 5.3-6.9 mmol/l (or < or = 6.9 mmol for American Indians). Randomization of participants into the DPP over 2.7 years ended in June 1999. Baseline data for the three treatment groups--intensive lifestyle modification, standard care plus metformin, and standard care plus placebo--are presented for the 3,234 participants who have been randomized. RESULTS Of all participants , 55% were Caucasian, 20% were African-American, 16% were Hispanic, 5% were American Indian, and 4% were Asian-American. Their average age at entry was 51 +/- 10.7 years (mean +/- SD), and 67.7% were women. Moreover, 16% were < 40 years of age, and 20% were > or = 60 years of age. Of the women, 48% were postmenopausal. Men and women had similar frequencies of history of hypercholesterolemia (37 and 33%, respectively) or hypertension (29 and 26%, respectively). On the basis of fasting lipid determinations, 54% of men and 40% of women fit National Cholesterol Education Program criteria for abnormal lipid profiles. More men than women were current or former cigarette smokers or had a history of coronary heart disease. Furthermore, 66% of men and 71% of women had a first-degree relative with diabetes. Overall, BMI averaged 34.0 +/- 6.7 kg/m2 at baseline with 57% of the men and 73% of women having a BMI > or = 30 kg/m2. Average fasting plasma glucose (6.0 +/- 0.5 mmol/l) and HbA1c (5.9 +/- 0.5%) in men were comparable with values in women (5.9 +/- 0.4 mmol/l and 5.9 +/- 0.5%, respectively). CONCLUSIONS The DPP has successfully randomized a large cohort of participants with a wide distribution of age, obesity, and ethnic and racial backgrounds who are at high risk for developing type 2 diabetes. The study will examine the effects of interventions on the development of diabetes.", "title": "The Diabetes Prevention Program: baseline characteristics of the randomized cohort. The Diabetes Prevention Program Research Group." }, { "docid": "71341302", "text": "Abstract Objective Our previous 6-month, randomized study demonstrated the beneficial effect of a vegetarian (V) compared to a conventional diet (C) with similar caloric restriction on cardiovascular risk factors for patients with type 2 diabetes (T2D), namely increased insulin sensitivity, reduced body weight, reduced volume of visceral and subcutaneous fat, decreased LDL-cholesterol and improved oxidative stress markers and chosen adipokines. We conducted post-trial monitoring to determine whether the improved outcomes persisted 1 year after the end of the study. Methods 62 subjects with T2D who completed the study were asked to come for a 1-year follow-up to measure weight, waist circumference, HbA1c and blood lipids. No attempts were made to maintain their previously assigned diets. Results 44 patients (71%) attended the post-trial monitoring. Hypoglycemic agents were increased by 14% in V and by 26% in C; insulin therapy was introduced in 5% in V and in 13% in C one year after the end of the intervention. Neither weight nor waist circumference changed significantly in either group. HbA1c increased ( p ≤ 0.05) similarly in both groups (+0.49 ± 1.04% in V vs. +0.42 ± 0.8% in C). Blood lipids did not change in either group. Conclusion One year after the end of the intervention, the positive effects of a vegetarian diet on cardiovascular risk factors compared to a conventional diet were partially maintained.", "title": "Vegetarian vs. conventional diabetic diet – A 1-year follow-up" }, { "docid": "3230557", "text": "Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This Review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects.", "title": "The Hallmarks of Aging" }, { "docid": "41264017", "text": "BACKGROUND The prevalence of Alzheimer disease (AD) is increasing in the elderly, and vascular risk factors may increase its risk. OBJECTIVE To explore the association of the aggregation of vascular risk factors with AD. METHODS The authors followed 1,138 individuals without dementia at baseline (mean age 76.2) for a mean of 5.5 years. The presence of vascular risk factors was related to incident possible and probable AD. RESULTS Four risk factors (diabetes, hypertension, heart disease, and current smoking) were associated with a higher risk of AD (p < 0.10) when analyzed individually. The risk of AD increased with the number of risk factors (diabetes + hypertension + heart disease + current smoking). The adjusted hazards ratio of probable AD for the presence of three or more risk factors was 3.4 (95% CI: 1.8, 6.3; p for trend < 0.0001) compared with no risk factors. Diabetes and current smoking were the strongest risk factors in isolation or in clusters, but hypertension and heart disease were also related to a higher risk of AD when clustered with diabetes, smoking, or each other. CONCLUSIONS The risk of Alzheimer disease (AD) increased with the number of vascular risk factors. Diabetes and current smoking were the strongest risk factors, but clusters including hypertension and heart disease also increased the risk of AD. These associations are unlikely to be explained by misclassification of the outcome, given strong associations when only probable AD is considered.", "title": "Aggregation of vascular risk factors and risk of incident Alzheimer disease." }, { "docid": "9822397", "text": "CONTEXT Sugar-sweetened beverages like soft drinks and fruit punches contain large amounts of readily absorbable sugars and may contribute to weight gain and an increased risk of type 2 diabetes, but these relationships have been minimally addressed in adults. OBJECTIVE To examine the association between consumption of sugar-sweetened beverages and weight change and risk of type 2 diabetes in women. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort analyses conducted from 1991 to 1999 among women in the Nurses' Health Study II. The diabetes analysis included 91,249 women free of diabetes and other major chronic diseases at baseline in 1991. The weight change analysis included 51,603 women for whom complete dietary information and body weight were ascertained in 1991, 1995, and 1999. We identified 741 incident cases of confirmed type 2 diabetes during 716,300 person-years of follow-up. MAIN OUTCOME MEASURES Weight gain and incidence of type 2 diabetes. RESULTS Those with stable consumption patterns had no difference in weight gain, but weight gain over a 4-year period was highest among women who increased their sugar-sweetened soft drink consumption from 1 or fewer drinks per week to 1 or more drinks per day (multivariate-adjusted means, 4.69 kg for 1991 to 1995 and 4.20 kg for 1995 to 1999) and was smallest among women who decreased their intake (1.34 and 0.15 kg for the 2 periods, respectively) after adjusting for lifestyle and dietary confounders. Increased consumption of fruit punch was also associated with greater weight gain compared with decreased consumption. After adjustment for potential confounders, women consuming 1 or more sugar-sweetened soft drinks per day had a relative risk [RR] of type 2 diabetes of 1.83 (95% confidence interval [CI], 1.42-2.36; P<.001 for trend) compared with those who consumed less than 1 of these beverages per month. Similarly, consumption of fruit punch was associated with increased diabetes risk (RR for > or =1 drink per day compared with <1 drink per month, 2.00; 95% CI, 1.33-3.03; P =.001). CONCLUSION Higher consumption of sugar-sweetened beverages is associated with a greater magnitude of weight gain and an increased risk for development of type 2 diabetes in women, possibly by providing excessive calories and large amounts of rapidly absorbable sugars.", "title": "Sugar-sweetened beverages, weight gain, and incidence of type 2 diabetes in young and middle-aged women." }, { "docid": "12770738", "text": "BACKGROUND Questions remain as to whether higher levels of cardiorespiratory fitness, a measure of regular physical activity, are associated with lower risk of cardiovascular disease (CVD) mortality in overweight and obese individuals with diabetes. Our objective was to quantify the independent and joint relations of cardiorespiratory fitness (hereafter, fitness) and body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters) with CVD mortality in men with diabetes. METHODS This study was conducted using prospective observational data from the Aerobics Center Longitudinal Study. Study participants comprised 2316 men with no history of stroke or myocardial infarction and who were diagnosed as having diabetes (mean [SD] age, 50 [10] years); had a medical examination, including a maximal exercise test during 1970 to 1997 with mortality surveillance to December 31, 1998; and had a BMI of 18.5 or greater and less than 35.0. The main outcome measure was CVD mortality across levels of fitness with stratification by BMI. RESULTS We identified 179 CVD deaths during a mean (SD) follow-up of 15.9 (7.9) years and 36,710 man-years of exposure. In a model containing age, examination year, fasting glucose level, systolic blood pressure, parental history of premature CVD, total cholesterol level, cigarette smoking, abnormal resting, and exercise electrocardiograms, a significantly higher adjusted risk of mortality was observed in men with a low fitness level who were normal weight (hazard ratio, 2.7 [95% confidence interval, 1.3-5.7]), overweight (hazard ratio, 2.7 [95% confidence interval, 1.4-5.1]), and class 1 obese (hazard ratio, 2.8 [95% confidence interval, 1.4-5.1]) compared with normal weight men with a high fitness level. CONCLUSION In this cohort of men with diabetes, low fitness level was associated with increased risk of CVD mortality within normal weight, overweight, and class 1 obese weight categories.", "title": "Cardiorespiratory fitness and body mass index as predictors of cardiovascular disease mortality among men with diabetes." }, { "docid": "8582337", "text": "IMPORTANCE Understanding the major health problems in the United States and how they are changing over time is critical for informing national health policy. OBJECTIVES To measure the burden of diseases, injuries, and leading risk factors in the United States from 1990 to 2010 and to compare these measurements with those of the 34 countries in the Organisation for Economic Co-operation and Development (OECD) countries. DESIGN We used the systematic analysis of descriptive epidemiology of 291 diseases and injuries, 1160 sequelae of these diseases and injuries, and 67 risk factors or clusters of risk factors from 1990 to 2010 for 187 countries developed for the Global Burden of Disease 2010 Study to describe the health status of the United States and to compare US health outcomes with those of 34 OECD countries. Years of life lost due to premature mortality (YLLs) were computed by multiplying the number of deaths at each age by a reference life expectancy at that age. Years lived with disability (YLDs) were calculated by multiplying prevalence (based on systematic reviews) by the disability weight (based on population-based surveys) for each sequela; disability in this study refers to any short- or long-term loss of health. Disability-adjusted life-years (DALYs) were estimated as the sum of YLDs and YLLs. Deaths and DALYs related to risk factors were based on systematic reviews and meta-analyses of exposure data and relative risks for risk-outcome pairs. Healthy life expectancy (HALE) was used to summarize overall population health, accounting for both length of life and levels of ill health experienced at different ages. RESULTS US life expectancy for both sexes combined increased from 75.2 years in 1990 to 78.2 years in 2010; during the same period, HALE increased from 65.8 years to 68.1 years. The diseases and injuries with the largest number of YLLs in 2010 were ischemic heart disease, lung cancer, stroke, chronic obstructive pulmonary disease, and road injury. Age-standardized YLL rates increased for Alzheimer disease, drug use disorders, chronic kidney disease, kidney cancer, and falls. The diseases with the largest number of YLDs in 2010 were low back pain, major depressive disorder, other musculoskeletal disorders, neck pain, and anxiety disorders. As the US population has aged, YLDs have comprised a larger share of DALYs than have YLLs. The leading risk factors related to DALYs were dietary risks, tobacco smoking, high body mass index, high blood pressure, high fasting plasma glucose, physical inactivity, and alcohol use. Among 34 OECD countries between 1990 and 2010, the US rank for the age-standardized death rate changed from 18th to 27th, for the age-standardized YLL rate from 23rd to 28th, for the age-standardized YLD rate from 5th to 6th, for life expectancy at birth from 20th to 27th, and for HALE from 14th to 26th. CONCLUSIONS AND RELEVANCE From 1990 to 2010, the United States made substantial progress in improving health. Life expectancy at birth and HALE increased, all-cause death rates at all ages decreased, and age-specific rates of years lived with disability remained stable. However, morbidity and chronic disability now account for nearly half of the US health burden, and improvements in population health in the United States have not kept pace with advances in population health in other wealthy nations.", "title": "The state of US health, 1990-2010: burden of diseases, injuries, and risk factors." }, { "docid": "32534305", "text": "OBJECTIVE Hyperinsulinemia may promote mammary carcinogenesis. Insulin resistance has been linked to an increased risk of breast cancer and is also characteristic of type 2 diabetes. We prospectively evaluated the association between type 2 diabetes and invasive breast cancer incidence in the Nurses' Health Study. RESEARCH DESIGN AND METHODS A total of 116,488 female nurses who were 30-55 years old and free of cancer in 1976 were followed through 1996 for the occurrence of type 2 diabetes and through 1998 for incident invasive breast cancer, verified by medical records and pathology reports. RESULTS During 2.3 million person-years of follow-up, we identified 6,220 women with type 2 diabetes and 5,189 incident cases of invasive breast cancer. Women with type 2 diabetes had a modestly elevated incidence of breast cancer (hazard ratio [HR] = 1.17; 95% CI 1.01-1.35) compared with women without diabetes, independent of age, obesity, family history of breast cancer, history of benign breast disease, reproductive factors, physical activity, and alcohol consumption. This association was apparent among postmenopausal women (1.16; 0.98-1.62) but not premenopausal women (0.83; 0.48-1.42). The association was predominant among women with estrogen receptor-positive breast cancer (1.22; 1.01-1.47). CONCLUSIONS Women with type 2 diabetes may have a slightly increased risk of breast cancer.", "title": "Type 2 diabetes and subsequent incidence of breast cancer in the Nurses' Health Study." }, { "docid": "17656445", "text": "OBJECTIVE Fructosamine, glycated albumin, and 1,5-anhydroglucitol (1,5-AG) are of interest for monitoring short-term glycemic control in patients with diabetes; however, their associations with diabetes risk are uncharacterized. RESEARCH DESIGN AND METHODS We used Cox proportional hazards models to examine the associations of fructosamine, glycated albumin, and 1,5-AG with incident diabetes in 1,299 participants, from the Atherosclerosis Risk in Communities (ARIC) Study (2005-2006), who had no history of diagnosed diabetes at baseline. Incident diabetes was self-reported during annual telephone calls. RESULTS There were 119 new cases of diabetes during a median follow-up of 3.3 years. When compared with the lowest quartile, the fourth quartiles of fructosamine and glycated albumin were significantly associated with diabetes risk (hazard ratio [HR] 3.99 [95% CI 1.93-8.28] and 5.22 [2.49-10.94], respectively). The fourth quartile of 1,5-AG was associated with a significantly lower diabetes risk (0.27 [0.14-0.55]). Associations were attenuated but still significant after adjustment for hemoglobin A(1c) (A1C) or fasting glucose. CONCLUSIONS Fructosamine, glycated albumin, and 1,5-AG were associated with the subsequent development of diabetes independently of baseline A1C and fasting glucose. Our results suggest these alternative biomarkers may be useful in identifying persons at risk for diabetes.", "title": "Alternative Markers of Hyperglycemia and Risk of Diabetes" }, { "docid": "2138843", "text": "Diabetes is a group of chronic diseases characterized by hyperglycemia. Modern medical care uses a vast array of lifestyle and pharmaceutical interventions aimed at preventing and controlling hyperglycemia. In addition to ensuring the adequate delivery of glucose to the tissues of the body, treatment of diabetes attempts to decrease the likelihood that the tissues of the body are harmed by hyperglycemia. The importance of protecting the body from hyperglycemia cannot be overstated; the direct and indirect effects on the human vascular tree are the major source of morbidity and mortality in both type 1 and type 2 diabetes. Generally, the injurious effects of hyperglycemia are separated into macrovascular complications (coronary artery disease, peripheral arterial disease, and stroke) and microvascular complications (diabetic nephropathy, neuropathy, and retinopathy). It is important for physicians to understand the relationship between diabetes and vascular disease because the prevalence of diabetes continues to increase in the United States, and the clinical armamentarium for primary and secondary prevention of these complications is also expanding. ### Diabetic retinopathy Diabetic retinopathy may be the most common microvascular complication of diabetes. It is responsible for ∼ 10,000 new cases of blindness every year in the United States alone.1 The risk of developing diabetic retinopathy or other microvascular complications of diabetes depends on both the duration and the severity of hyperglycemia. Development of diabetic retinopathy in patients with type 2 diabetes was found to be related to both severity of hyperglycemia and presence of hypertension in the U.K. Prospective Diabetes Study (UKPDS), and most patients with type 1 diabetes develop evidence of retinopathy within 20 years of diagnosis.2,3 Retinopathy may begin to develop as early as 7 years before the diagnosis of diabetes in patients with type 2 diabetes.1 There are several proposed pathological mechanisms by which diabetes may lead …", "title": "Microvascular and Macrovascular Complications of Diabetes" }, { "docid": "52072815", "text": "Summary Background Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older. Methods Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health. Findings Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2·2% (95% uncertainty interval [UI] 1·5–3·0) of age-standardised female deaths and 6·8% (5·8–8·0) of age-standardised male deaths. Among the population aged 15–49 years, alcohol use was the leading risk factor globally in 2016, with 3·8% (95% UI 3·2–4·3) of female deaths and 12·2% (10·8–13·6) of male deaths attributable to alcohol use. For the population aged 15–49 years, female attributable DALYs were 2·3% (95% UI 2·0–2·6) and male attributable DALYs were 8·9% (7·8–9·9). The three leading causes of attributable deaths in this age group were tuberculosis (1·4% [95% UI 1·0–1·7] of total deaths), road injuries (1·2% [0·7–1·9]), and self-harm (1·1% [0·6–1·5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27·1% (95% UI 21·2–33·3) of total alcohol-attributable female deaths and 18·9% (15·3–22·6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0·0–0·8) standard drinks per week. Interpretation Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption. Funding Bill & Melinda Gates Foundation.", "title": "Alcohol use and burden for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016" }, { "docid": "27428509", "text": "Type 2 diabetes mellitus is becoming a major health problem associated with excess morbidity and mortality. As the prevalence of type 2 diabetes is rapidly increasing, prevention of the disease should be considered as a key objective in the near future. Besides lifestyle changes, various pharmacological treatments have proven their efficacy in placebo-controlled clinical trials, including antidiabetic drugs such as metformin, acarbose and troglitazone, or antiobesity agents such as orlistat. Arterial hypertension, a clinical entity in which insulin resistance is common, is strongly associated with type 2 diabetes and may precede the disease by several years. While antihypertensive agents such as diuretics or β-adrenoceptor antagonists may worsen insulin resistance and impair glucose tolerance, newer antihypertensive agents exert neutral or even slightly positive metabolic effects. Numerous clinical trials have investigated the effects of ACE inhibitors or angiotensin II receptor antagonists (ARAs) on insulin sensitivity in hypertensive patients, with or without diabetes, with no consistent results. Almost half of the studies with ACE inhibitors in hypertensive nondiabetic individuals demonstrated a slight but significant increase in insulin sensitivity as assessed by insulin-stimulated glucose disposal during a euglycaemic hyperinsulinaemic clamp, while the other half failed to reveal any significant change. The effects of ARAs on insulin sensitivity are neutral in most studies. Mechanisms of improvement of glucose tolerance and insulin sensitivity through the inhibition of the renin-angiotensin system (RAS) are complex. They may include improvement of blood flow and microcirculation in skeletal muscles and, thereby, enhancement of insulin and glucose delivery to the insulin-sensitive tissues, facilitating insulin signalling at the cellular level and improvement of insulin secretion by the β cells. Six recent large-scale clinical studies reported a remarkably consistent reduction in the incidence of type 2 diabetes in hypertensive patients treated with either ACE inhibitors or ARAs for 3–6 years, compared with a thiazide diuretic, β-adrenoceptor antagonist, the calcium channel antagonist amlodipine or even placebo. The relative risk reduction averaged 14% (p = 0.034) in the CAPPP (Captopril Prevention Project) with captopril compared with a thiazide or β1-adrenoceptor antagonist, 34% (p < 0.001) in the HOPE (Heart Outcomes Prevention Evaluation) study with ramipril compared with placebo, 30% (p < 0.001) in the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) with lisinopril compared with chlortalidone, 25% (p < 0.001) in the LIFE (Losartan Intervention For Endpoint reduction in hypertension study) with losartan compared with atenolol, and 25% (p = 0.09) in the SCOPE (Study on Cognition and Prognosis in the Elderly) with candesartan cilexetil compared with placebo, and 23% (p < 0.0001) in the VALUE (Valsartan Antihypertensive Long-term Use Evaluation) trial with valsartan compared with amlodipine. All these studies considered the development of diabetes as a secondary endpoint, except the HOPE trial where it was a post hoc analysis. These encouraging observations led to the initiation of two large, prospective, placebo-controlled randomised clinical trials whose primary outcome is the prevention of type 2 diabetes: the DREAM (Diabetes REduction Approaches with ramipril and rosiglitazone Medications) trial with the ACE inhibitor ramipril and the NAVIGATOR (Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research) trial with the ARA valsartan. Finally, ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) will also investigate as a secondary endpoint whether it is possible to prevent the development of type 2 diabetes by blocking the RAS with either an ACE inhibitor or an ARA or a combination of both. Thus, the recent consistent observations of a 14–34% reduction of the development of diabetes in hypertensive patients receiving ACE inhibitors or ARAs are exciting. From a theoretical point of view, they emphasise that there are many aspects of the pathogenesis, prevention and treatment of type 2 diabetes that still need to be uncovered. From a practical point of view, they may offer a new strategy to reduce the ongoing epidemic and burden of type 2 diabetes.", "title": "Prevention of Type 2 Diabetes Mellitus Through Inhibition of the Renin-Angiotensin System" }, { "docid": "13619127", "text": "OBJECTIVE To assess the risks of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia in patients with type 2 diabetes associated with prescribed diabetes drugs, particularly newer agents including gliptins or glitazones (thiazolidinediones). DESIGN Open cohort study in primary care. SETTING 1243 practices contributing data to the QResearch database in England. PARTICIPANTS 469,688 patients with type 2 diabetes aged 25-84 years between 1 April 2007 and 31 January 2015. EXPOSURES Hypoglycaemic agents (glitazones, gliptins, metformin, sulphonylureas, insulin, and other) alone and in combination. MAIN OUTCOME MEASURES First recorded diagnoses of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia recorded on patients' primary care, mortality, or hospital records. Cox models estimated hazard ratios for diabetes treatments adjusting for potential confounders. RESULTS 21,308 (4.5%) and 32,533 (6.9%) patients received prescriptions for glitazones and gliptins during follow-up, respectively. Compared with non-use, glitazones were associated with a decreased risk of blindness (adjusted hazard ratio 0.71, 95% confidence interval 0.57 to 0.89; rate 14.4 per 10,000 person years of exposure) and an increased risk of hypoglycaemia (1.22, 1.10 to 1.37; 65.1); gliptins were associated with a decreased risk of hypoglycaemia (0.86, 0.77 to 0.96; 45.8). Although the numbers of patients prescribed gliptin monotherapy or glitazones monotherapy were relatively low, there were significantly increased risks of severe kidney failure compared with metformin monotherapy (adjusted hazard ratio 2.55, 95% confidence interval 1.13 to 5.74). We found significantly lower risks of hyperglycaemia among patients prescribed dual therapy involving metformin with either gliptins (0.78, 0.62 to 0.97) or glitazones (0.60, 0.45 to 0.80) compared with metformin monotherapy. Patients prescribed triple therapy with metformin, sulphonylureas, and either gliptins (adjusted hazard ratio 5.07, 95% confidence interval 4.28 to 6.00) or glitazones (6.32, 5.35 to 7.45) had significantly higher risks of hypoglycaemia than those prescribed metformin monotherapy, but these risks were similar to those involving dual therapy with metformin and sulphonylureas (6.03, 5.47 to 6.63). Patients prescribed triple therapy with metformin, sulphonylureas, and glitazones had a significantly reduced risk of blindness compared with metformin monotherapy (0.67, 0.48 to 0.94). CONCLUSIONS We have found lower risks of hyperglycaemia among patients prescribed dual therapy involving metformin with either gliptins or glitazones compared with metformin alone. Compared with metformin monotherapy, triple therapy with metformin, sulphonylureas, and either gliptins or glitazones was associated with an increased risk of hypoglycaemia, which was similar to the risk for dual therapy with metformin and sulphonylureas. Compared with metformin monotherapy, triple therapy with metformin, sulphonylureas, and glitazones was associated with a reduced risk of blindness. These results, while subject to residual confounding, could have implications for the prescribing of hypoglycaemic drugs.", "title": "Diabetes treatments and risk of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia: open cohort study in primary care" }, { "docid": "581832", "text": "BACKGROUND Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. METHODS We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. FINDINGS Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2·9 years (95% uncertainty interval 2·9-3·0) for men and 3·5 years (3·4-3·7) for women, while HALE at age 65 years improved by 0·85 years (0·78-0·92) and 1·2 years (1·1-1·3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. INTERPRETATION Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum. FUNDING Bill & Melinda Gates Foundation.", "title": "Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015" }, { "docid": "11953232", "text": "OBJECTIVE To determine the prevalence and clinical associations of impaired awareness of hypoglycemia in a population-based sample of children and adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS A validated questionnaire was administered to 656 patients with type 1 diabetes over a 6-month period to determine hypoglycemia awareness status. Case ascertainment was 79% of the clinic population. The rate of severe hypoglycemia was determined by data collected prospectively in the preceding year. RESULTS Impaired awareness of hypoglycemia was present in 29% of patients. Patients with impaired awareness of hypoglycemia had an earlier onset of diabetes (P < 0.001), were younger (P < 0.001), and had lower mean levels of A1C since diabetes onset (P = 0.006) and at their last visit (P = 0.001). The overall rate of severe hypoglycemia was 24.5 episodes per 100 patient-years in the preceding year. The severe hypoglycemia rate was higher in those with impaired awareness of hypoglycemia (37.1 vs. 19.3 episodes per 100 patient-years, P < 0.001). Among patients aged <6 years (n = 46), 59% of care providers reported impaired awareness of hypoglycemia, and the rate of severe hypoglycemia was significantly higher in those reporting impaired awareness (33.3 vs. 52 episodes per 100 patient-years, P = 0.02). More patients with recurrent hypoglycemia reported impaired awareness of hypoglycemia (47 vs. 28%, P = 0.03). CONCLUSIONS A significant proportion of children and adolescents with type 1 diabetes have impaired awareness of hypoglycemia. Screening for impaired awareness is an important component of routine diabetes care and can identify patients at increased risk of a severe hypoglycemic event.", "title": "Impaired Awareness of Hypoglycemia in a Population-Based Sample of Children and Adolescents With Type 1 Diabetes" }, { "docid": "2138767", "text": "AIMS Cardiovascular disease (CVD) is now the most prevalent and debilitating disease affecting the Chinese population. The goal of the present manuscript was to analyse cardiovascular risk factors and the prevalence of non-fatal CVDs from data gathered from the 2007-2008 China National Diabetes and Metabolic Disorders Study. METHODS AND RESULTS A nationally representative sample of 46 239 adults, 20 years of age or older, was randomly recruited using a multistage stratified design method. Lifestyle factors, diagnosis of CVD, stroke, diabetes, and family history of each subject were collected, and an oral glucose tolerance test or a standard meal test was performed. Various non-fatal CVDs were reported by the subjects. SUDAAN software was used to perform all weighted statistical analyses, with P < 0.05 considered statistically significant. The prevalence of coronary heart disease, stroke, and CVDs was 0.74, 1.07, and 1.78% in males; and 0.51, 0.60, and 1.10% in females, respectively. The presence of CVDs increased with age in both males and females. The prevalence of being overweight or obese, hypertension, dyslipidaemia, or hyperglycaemia was 36.67, 30.09, 67.43, and 26.69% in males; and 29.77, 24.79, 63.98, and 23.62% in females, respectively. In the total sample of 46 239 patients, the prevalence of one subject having 1, 2, 3, or ≥4 of the 5 defined risk factors (i.e. smoking, overweight or obese, hypertension, dyslipidaemia, or hyperglycaemia) was 31.17, 27.38, 17.76, and 10.19%, respectively. Following adjustment for gender and age, the odds ratio of CVDs for those who had 1, 2, 3, or ≥4 risk factors was 2.36, 4.24, 4.88, and 7.22, respectively, when compared with patients with no risk factors. CONCLUSION Morbidity attributed to the five defined cardiovascular risk factors was high in the Chinese population, with multiple risk factors present in the same individual. Therefore, reasonable prevention strategies should be designed to attenuate the rapid rise in cardiovascular morbidity.", "title": "Prevalence of cardiovascular disease risk factor in the Chinese population: the 2007-2008 China National Diabetes and Metabolic Disorders Study." }, { "docid": "24918110", "text": "OBJECTIVE To demonstrate the relation of exercise capacity and BMI to mortality in a population of male veterans with type 2 diabetes. RESEARCH DESIGN AND METHODS After excluding two underweight patients (BMI <18.5 kg/m2), the study population comprised 831 consecutive patients with type 2 diabetes (mean age 61 +/- 9 years) referred for exercise testing for clinical reasons between 1995 and 2006. Exercise capacity was determined from a maximal exercise test and measured in metabolic equivalents (METs). Patients were classified both according to BMI category (18.5-24.9, 25.0-29.9, and > or =30 kg/m2) and by exercise capacity (<5.0 or > or =5.0 maximal METs). The association among exercise capacity, BMI, other clinical variables, and all-cause mortality was assessed by Cox proportional hazards. Study participants were followed for mortality up to 30 June 2006. RESULTS During a mean follow-up of 4.8 +/- 3.0 years, 112 patients died, for an average annual mortality rate of 2.2%. Each 1-MET increase in exercise capacity conferred a 10% survival benefit (hazard ratio 0.90 [95% CI 0.82-0.98]; P = 0.01), but BMI was not significantly associated with mortality. After adjustment for age, ethnicity, examination year, BMI, presence of cardiovascular disease (CVD), and CVD risk factors, diabetic patients achieving <5 maximal METs were 70% more likely to die (1.70 [1.13-2.54]) than those achieving > or =5 maximal METs. CONCLUSIONS There was a strong inverse association between exercise capacity and mortality in this cohort of men with documented diabetes, and this relationship was independent of BMI.", "title": "Exercise capacity and body mass as predictors of mortality among male veterans with type 2 diabetes." }, { "docid": "15521377", "text": "Cellular senescence is a stable form of cell-cycle arrest which is thought to limit the proliferative potential of premalignant cells [1]. The senescence phenotype was initially described by Hayflick and Moorhead in 1961 on human fibroblasts undergoing replicative exhaustion in culture [2]. It has been shown that senescence can be triggered in different cell types in response to diverse forms of cellular damage or stress (for review see [1]). Importantly, while senescence was denounced as a tissue culture phenomenon for many years, recent in vivo studies demonstrated that cellular senescence represents a potent failsafe mechanism against tumorigenesis and contributes to the cytotoxicity of certain anticancer agents (see for example [3-7]). Interestingly, senescent cells have also been observed in certain aged or damaged tissues and there is growing evidence that senescence checkpoints can affect the regenerative reserve of tissues and organismal aging [8-11]. However, senescence may also have positive effects on organ maintenance by limiting pathological responses to acute forms of injury such as fibrotic scarring in response to chemical induced liver injury [12]. Over the past years it was also shown that senescent cells can communicate with their environment by secreting a myriad of cytokines and growth factors. Interestingly, this \"senescence associated secretory phenotype (SASP)\" seems to be a double edged sword regarding tumor initiation and maintenance: i) On the one hand, it has been shown that the SASP can have pro-tumorigenic effects. In an experimental system it was shown that senescent mesenchymal cells can enhance the tumorigenicity of surrounding breast cancer cells [13]. ii) Similarly, it is possible that the SASP enhances selection of transformed cell clones in aged organ systems. It has been shown that loss of proliferative competition of non-transformed cells can accelerate leukemogenesis [14]. It remains to be seen whether aberrant secretion of cytokines and growth factors by the SASP can accelerated this process in aged and chronically damage organ systems. iii) In contrast to its pro-tumorigenic aspect, the SASP could also have anti-tumor effects. A recent study showed that in a mosaic liver cancer mouse model the activation of p53 induced senescence, an upregulation of inflammatory cytokines, and activation of innate immune responses leading to tumour cell clearance [15]. iv) In further support that the SASP could have anti-tumor activities, a series of recent papers showed that components of the SASP can stabilize the senescence cell cycle arrest via an autoregulatory feedback loop [16,17] or induces apoptosis of tumor cells [18]. In addition to its effects on tumorigenesis, the SASP could also influence tissue aging. Studies on aging telomere dysfunctional mice have provided direct experimental evidence for an in vivo activation of the SASP in response to telomere dysfunction [19]. Interestingly, this in vivo SASP provoked alterations in stem cell differentiation (skewing of hematopoiesis towards reduction in lymphopoiesis and enhancement of myelopoiesis) that are also characteristic signs of human aging. Figure 1. Different cellular stresses can induce senescence including telomere shortening, DNA damage, and oncogene activation. Senescence of tumor cells ... In light of the many possible roles o the SASP in aging and carcinogenesis, it appears to be of utmost importance to decipher regulatory pathways controlling the SASP. In a current publication, Bhaumik et al. have identified 2 microRNAs (miR-146a/b) that negatively regulate the secretion of IL-6 and IL-8 - two of the SASP [20]. The authors show that these microRNAs are up-regulated at late stages of senescence, many days after a permanent cell cycle arrest has been established. Interestingly, the inhibitory miRs are most strongly up-regulated in senescence of cell lines that show a strong SASP but not in cell lines characterized by a weak SASP. The authors propose a new concept indicating that miRs 146a and b function in a negative feedback loop preventing an over-activation of the SASP in senescent cells. The authors present some initial data suggesting that activation of this negative feedback loop involves IL-1 receptor, IRAK-1, and NFκB signalling leading to an up-regulation of miRs-146a and b. A direct proof that this proposed feedback loop suppresses over-activation of the SASP remains to be demonstrated in future studies. The authors show that blockage of IL-1-receptor signalling prevents both the up-regulation of miRs-146a and b as well as Il-6 secretion. To confirm their new concept, it would be important to show that a selective blockage of miRs-146a and b results in over-activation of the SASP. The work by Bhaumik et al. places mir-146a/b as central players to control IL-6 and IL-8 expression within the SASP. MicroRNAs are emerging therapeutic targets because their expression levels can be effectively modulated via the use of antagomirs (see for example [21]). Also, for increasing microRNA expression, microRNAs can be delivered into cellsin vivo (see for example [22]). Therefore, it will be interesting to functionally test the impact of mir-146 inhibition on tumorigenesis and aging in relevant mouse models. Such studies will be of particular interest, as recent work showed that IL-6 secretion by senescent cells is relevant for initiating and maintaining the senescene response via an autocrine loop [17]. A reduction of miR-146 could increase IL-6 levels in senescent cells, which should stabilize the senescence program and reduce the risk of malignant transformation. Furthermore, it can be speculated that reduction of mir-146 a/b will increase NfκB activation via IRAK1. As NfκB is modulating the expression of various inflammation associated genes, this may also lead to increased clearance of senescent tumor cells by the innate immune system. However, it should be mentioned that Il-6 secreted by senescent cells can also act as a mitogen for surrounding cells, thus potentially increasing the risk of malignant transformation [13,17]. Besides its function in SASP modulation, miR-146 was also reported to target the mRNAs of the BRCA1 and BRCA2 tumor suppressors. In a recent study a G to C polymorphism in miR-146, which leads to an increased processing and release of the mature microRNA, can predict an early onset of breast cancer [23]. Taken together, the study of Bhaumik et al. opens an interesting new research area dealing with the gene regulatory mechanisms that control activation of the SASP. Given the diverse roles of the SASP in modulating tumor progression, immune surveillance of damaged cells, and the stabilization of the senescence arrest itself, it will be of great interest to analyse the influence of SASP regulatory pathways during aging and cancer.", "title": "Keeping your senescent cells under control" }, { "docid": "2359152", "text": "High-throughput DNA sequencing significantly contributed to diagnosis and prognostication in patients with myelodysplastic syndromes (MDS). We determined the biological and prognostic significance of genetic aberrations in MDS. In total, 944 patients with various MDS subtypes were screened for known/putative mutations/deletions in 104 genes using targeted deep sequencing and array-based genomic hybridization. In total, 845/944 patients (89.5%) harbored at least one mutation (median, 3 per patient; range, 0-12). Forty-seven genes were significantly mutated with TET2, SF3B1, ASXL1, SRSF2, DNMT3A, and RUNX1 mutated in >10% of cases. Many mutations were associated with higher risk groups and/or blast elevation. Survival was investigated in 875 patients. By univariate analysis, 25/48 genes (resulting from 47 genes tested significantly plus PRPF8) affected survival (P<0.05). The status of 14 genes combined with conventional factors revealed a novel prognostic model ('Model-1') separating patients into four risk groups ('low', 'intermediate', 'high', 'very high risk') with 3-year survival of 95.2, 69.3, 32.8, and 5.3% (P<0.001). Subsequently, a 'gene-only model' ('Model-2') was constructed based on 14 genes also yielding four significant risk groups (P<0.001). Both models were reproducible in the validation cohort (n=175 patients; P<0.001 each). Thus, large-scale genetic and molecular profiling of multiple target genes is invaluable for subclassification and prognostication in MDS patients.", "title": "Landscape of genetic lesions in 944 patients with myelodysplastic syndromes" }, { "docid": "26067999", "text": "The U.S. Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific preventive care services for patients without related signs or symptoms. It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment. The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms. Summary of Recommendation and Evidence The USPSTF recommends annual screening for lung cancer with low-dose computed tomography (LDCT) in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery. (B recommendation) See the Clinical Considerations section for suggestions for implementation in practice. See the Figure for a summary of the recommendation and suggestions for clinical practice. Figure. Screening for lung cancer: clinical summary of U.S. Preventive Services Task Force recommendation. Appendix Table 1 describes the USPSTF grades, and Appendix Table 2 describes the USPSTF classification of levels of certainty about net benefit. Appendix Table 1. What the USPSTF Grades Mean and Suggestions for Practice Appendix Table 2. USPSTF Levels of Certainty Regarding Net Benefit Supplement. Consumer Fact Sheet. Rationale Importance Lung cancer is the third most common cancer and the leading cause of cancer-related death in the United States (1). The most important risk factor for lung cancer is smoking, which results in approximately 85% of all U.S. lung cancer cases (2). Although the prevalence of smoking has decreased, approximately 37% of U.S. adults are current or former smokers (2). The incidence of lung cancer increases with age and occurs most commonly in persons aged 55 years or older. Increasing age and cumulative exposure to tobacco smoke are the 2 most common risk factors for lung cancer. Lung cancer has a poor prognosis, and nearly 90% of persons with lung cancer die of the disease. However, early-stage nonsmall cell lung cancer (NSCLC) has a better prognosis and can be treated with surgical resection. Detection Most lung cancer cases are NSCLC, and most screening programs focus on the detection and treatment of early-stage NSCLC. Although chest radiography and sputum cytologic evaluation have been used to screen for lung cancer, LDCT has greater sensitivity for detecting early-stage cancer (3). Benefits of Detection and Early Treatment Although lung cancer screening is not an alternative to smoking cessation, the USPSTF found adequate evidence that annual screening for lung cancer with LDCT in a defined population of high-risk persons can prevent a substantial number of lung cancerrelated deaths. Direct evidence from a large, well-conducted, randomized, controlled trial (RCT) provides moderate certainty of the benefit of lung cancer screening with LDCT in this population (4). The magnitude of benefit to the person depends on that person's risk for lung cancer because those who are at highest risk are most likely to benefit. Screening cannot prevent most lung cancerrelated deaths, and smoking cessation remains essential. Harms of Detection and Early Intervention and Treatment The harms associated with LDCT screening include false-negative and false-positive results, incidental findings, overdiagnosis, and radiation exposure. False-positive LDCT results occur in a substantial proportion of screened persons; 95% of all positive results do not lead to a diagnosis of cancer. In a high-quality screening program, further imaging can resolve most false-positive results; however, some patients may require invasive procedures. The USPSTF found insufficient evidence on the harms associated with incidental findings. Overdiagnosis of lung cancer occurs, but its precise magnitude is uncertain. A modeling study performed for the USPSTF estimated that 10% to 12% of screen-detected cancer cases are overdiagnosedthat is, they would not have been detected in the patient's lifetime without screening. Radiation harms, including cancer resulting from cumulative exposure to radiation, vary depending on the age at the start of screening; the number of scans received; and the person's exposure to other sources of radiation, particularly other medical imaging. USPSTF Assessment The USPSTF concludes with moderate certainty that annual screening for lung cancer with LDCT is of moderate net benefit in asymptomatic persons who are at high risk for lung cancer based on age, total cumulative exposure to tobacco smoke, and years since quitting smoking. The moderate net benefit of screening depends on limiting screening to persons who are at high risk, the accuracy of image interpretation being similar to that found in the NLST (National Lung Screening Trial), and the resolution of most false-positive results without invasive procedures (4). Clinical Considerations Patient Population Under Consideration The risk for lung cancer increases with age and cumulative exposure to tobacco smoke and decreases with time since quitting smoking. The best evidence for the benefit of screening comes from the NLST, which enrolled adults aged 55 to 74 years who had at least a 30 pack-year smoking history and were current smokers or had quit within the past 15 years. As with all screening trials, the NLST tested a specific intervention over a finite period. Because initial eligibility extended through age 74 years and participants received 3 annual screening computed tomographic scans, the oldest participants in the trial were aged 77 years. The USPSTF used modeling studies to predict the benefits and harms of screening programs that use different screening intervals, age ranges, smoking histories, and times since quitting. A program that annually screens adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years is projected to have a reasonable balance of benefits and harms. The model assumes that persons who achieve 15 years of smoking cessation during the screening program discontinue screening. This model predicts the outcomes of continuing the screening program used in the NLST through age 80 years. Screening may not be appropriate for patients with substantial comorbid conditions, particularly those at the upper end of the screening age range. The NLST excluded persons who were unlikely to complete curative lung cancer surgery and those with medical conditions that posed a substantial risk for death during the 8-year trial. The baseline characteristics of the NLST showed a relatively healthy sample, and fewer than 10% of enrolled participants were older than 70 years (5). Persons with serious comorbid conditions may experience net harm, no net benefit, or at least substantially less net benefit. Similarly, persons who are unwilling to have curative lung surgery are unlikely to benefit from a screening program. Assessment of Risk Age, total exposure to tobacco smoke, and years since quitting smoking are important risk factors for lung cancer and were used to determine eligibility in the NLST. Other risk factors include specific occupational exposures, radon exposure, family history, and history of pulmonary fibrosis or chronic obstructive lung disease. The incidence of lung cancer is relatively low in persons younger than 50 years but increases with age, especially after age 60 years. In current and former smokers, age-specific incidence rates increase with age and cumulative exposure to tobacco smoke. Smoking cessation substantially reduces a person's risk for developing and dying of lung cancer. Among persons enrolled in the NLST, those who were at highest risk because of additional risk factors or a greater cumulative exposure to tobacco smoke experienced most of the benefit (6). A validated multivariate model showed that persons in the highest 60% of risk accounted for 88% of all deaths preventable by screening. Screening Tests Low-dose computed tomography has shown high sensitivity and acceptable specificity for the detection of lung cancer in high-risk persons. Chest radiography and sputum cytologic evaluation have not shown adequate sensitivity or specificity as screening tests. Therefore, LDCT is currently the only recommended screening test for lung cancer. Treatment Surgical resection is the current standard of care for localized NSCLC. This type of cancer is treated with surgical resection when possible and also with radiation and chemotherapy. Annual LDCT screening may not be useful for patients with life-limiting comorbid conditions or poor functional status who may not be candidates for surgery. Other Approaches to Prevention Smoking cessation is the most important intervention to prevent NSCLC. Advising smokers to stop smoking and preventing nonsmokers from being exposed to tobacco smoke are the most effective ways to decrease the morbidity and mortality associated with lung cancer. Current smokers should be informed of their continuing risk for lung cancer and offered cessation treatments. Screening with LDCT should be viewed as an adjunct to tobacco cessation interventions. Useful Resources Clinicians have many resources to help patients stop smoking. The Centers for Disease Control and Prevention has developed a Web site with many such resources, including information on tobacco quit lines, available in several languages (www.cdc.gov/tobacco/campaign/tips). Quit l", "title": "Screening for Lung Cancer: U.S. Preventive Services Task Force Recommendation Statement" }, { "docid": "5850219", "text": "BACKGROUND Population-based estimates of prevalence, risk distribution, and intervention uptake inform delivery of control programmes for sexually transmitted infections (STIs). We undertook the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3) after implementation of national sexual health strategies, and describe the epidemiology of four STIs in Britain (England, Scotland, and Wales) and the uptake of interventions. METHODS Between Sept 6, 2010 and Aug 31, 2012 , we did a probability sample survey of 15,162 women and men aged 16-74 years in Britain. Participants were interviewed with computer-assisted face-to-face and self-completion questionnaires. Urine from a sample of participants aged 16-44 years who reported at least one sexual partner over the lifetime was tested for the presence of Chlamydia trachomatis, type-specific human papillomavirus (HPV), Neisseria gonorrhoeae, and HIV antibody. We describe age-specific and sex-specific prevalences of infection and intervention uptake, in relation to demographic and behavioural factors, and explore changes since Natsal-1 (1990-91) and Natsal-2 (1999-2001). FINDINGS Of 8047 eligible participants invited to provide a urine sample, 4828 (60%) agreed. We excluded 278 samples, leaving 4550 (94%) participants with STI test results. Chlamydia prevalence was 1·5% (95% CI 1·1-2·0) in women and 1·1% (0·7-1·6) in men. Prevalences in individuals aged 16-24 years were 3·1% (2·2-4·3) in women and 2·3% (1·5-3·4) in men. Area-level deprivation and higher numbers of partners, especially without use of condoms, were risk factors. However, 60·4% (45·5-73·7) of chlamydia in women and 43·3% (25·9-62·5) in men was in individuals who had had one partner in the past year. Among sexually active 16-24-year-olds, 54·2% (51·4-56·9) of women and 34·6% (31·8-37·4) of men reported testing for chlamydia in the past year, with testing higher in those with more partners. High-risk HPV was detected in 15·9% (14·4-17·5) of women, similar to in Natsal-2. Coverage of HPV catch-up vaccination was 61·5% (58·2-64·7). Prevalence of HPV types 16 and 18 in women aged 18-20 years was lower in Natsal-3 than Natsal-2 (5·8% [3·9-8·6] vs 11·3% [6·8-18·2]; age-adjusted odds ratio 0·44 [0·21-0·94]). Gonorrhoea (<0·1% prevalence in women and men) and HIV (0·1% prevalence in women and 0·2% in men) were uncommon and restricted to participants with recognised high-risk factors. Since Natsal-2, substantial increases were noted in attendance at sexual health clinics (from 6·7% to 21·4% in women and from 7·7% to 19·6% in men) and HIV testing (from 8·7% to 27·6% in women and from 9·2% to 16·9% in men) in the past 5 years. INTERPRETATION STIs were distributed heterogeneously, requiring general and infection-specific interventions. Increases in testing and attendance at sexual health clinics, especially in people at highest risk, are encouraging. However, STIs persist both in individuals accessing and those not accessing services. Our findings provide empirical evidence to inform future sexual health interventions and services. FUNDING Grants from the UK Medical Research Council and the Wellcome Trust, with support from the Economic and Social Research Council and the Department of Health.", "title": "Prevalence, risk factors, and uptake of interventions for sexually transmitted infections in Britain: findings from the National Surveys of Sexual Attitudes and Lifestyles (Natsal)" }, { "docid": "31889025", "text": "OBJECTIVES - To study the relative and population-attributable risks of hypertension for the development of congestive heart failure (CHF), to assess the time course of progression from hypertension to CHF, and to identify risk factors that contribute to the development of overt heart failure in hypertensive subjects. DESIGN - Inception cohort study. SETTING - General community. PARTICIPANTS - Original Framingham Heart Study and Framingham Offspring Study participants aged 40 to 89 years and free of CHF. To reflect more contemporary experience, the starting point of this study was January 1, 1970. EXPOSURE MEASURES - Hypertension (blood pressure of at least 140 mm Hg systolic or 90 mm Hg diastolic or current use of medications for treatment of high blood pressure) and other potential CHF risk factors were assessed at periodic clinic examinations. OUTCOME MEASURE - The development of CHF. RESULTS - A total of 5143 eligible subjects contributed 72422 person-years of observation. During up to 20.1 years of follow-up (mean, 14.1 years), there were 392 new cases of heart failure; in 91% (357/392), hypertension antedated the development of heart failure. Adjusting for age and heart failure risk factors in proportional hazards regression models, the hazard for developing heart failure in hypertensive compared with normotensive subjects was about 2-fold in men and 3-fold in women. Multivariable analyses revealed that hypertension had a high population-attributable risk for CHF, accounting for 39% of cases in men and 59% in women. Among hypertensive subjects, myocardial infarction, diabetes, left ventricular hypertrophy, and valvular heart disease were predictive of increased risk for CHF in both sexes. Survival following the onset of hypertensive CHF was bleak; only 24% of men and 31% of women survived 5 years. CONCLUSIONS - Hypertension was the most common risk factor for CHF, and it contributed a large proportion of heart failure cases in this population-based sample. Preventive strategies directed toward earlier and more aggressive blood pressure control are likely to offer the greatest promise for reducing the incidence of CHF and its associated mortality.", "title": "The progression from hypertension to congestive heart failure." }, { "docid": "9047718", "text": "QT intervals were measured over RR intervals ranging from 500 ms to 1000 ms in 13 normal male subjects, 13 male diabetic subjects without and 13 with autonomic neuropathy. There was a close linear relationship between QT and RR in all subjects. The slope of the regression line was significantly greater in the autonomic neuropathy group than the normal group. Thirty-two male diabetic subjects with varying degrees of autonomic dysfunction had repeat QT measurements 3 (range 2–6) years later. QT and QTC lengthened significantly at the second visit, unrelated to age or time between recordings, but which corresponded with changes in autonomic function. Of 71 male diabetic subjects under 60 years followed for 3 years, 13 had died, 8 unexpectedly. Of those with autonomic neuropathy, QT and QTC were significantly longer in those who subsequently died, despite similar ages and duration of diabetes. We conclude that QT/RR interval relationships are altered in diabetic autonomic neuropathy, and that changes in QT length with time parallel changese in autonomic function. There may be an association between QT interval prolongation and the risk of dying unexpectedly in diabetic autonomic neuropathy.", "title": "Autonomic neuropathy, QT interval lengthening, and unexpected deaths in male diabetic patients" }, { "docid": "8524891", "text": "OBJECTIVE White matter hyperintensities (WMHs) are areas of increased signal on T2-weighted magnetic resonance imaging (MRI) scans that most commonly reflect small vessel cerebrovascular disease. Increased WMH volume is associated with risk and progression of Alzheimer's disease (AD). These observations are typically interpreted as evidence that vascular abnormalities play an additive, independent role contributing to symptom presentation, but not core features of AD. We examined the severity and distribution of WMH in presymptomatic PSEN1, PSEN2, and APP mutation carriers to determine the extent to which WMH manifest in individuals genetically determined to develop AD. METHODS The study comprised participants (n = 299; age = 39.03 ± 10.13) from the Dominantly Inherited Alzheimer Network, including 184 (61.5%) with a mutation that results in AD and 115 (38.5%) first-degree relatives who were noncarrier controls. We calculated the estimated years from expected symptom onset (EYO) by subtracting the affected parent's symptom onset age from the participant's age. Baseline MRI data were analyzed for total and regional WMH. Mixed-effects piece-wise linear regression was used to examine WMH differences between carriers and noncarriers with respect to EYO. RESULTS Mutation carriers had greater total WMH volumes, which appeared to increase approximately 6 years before expected symptom onset. Effects were most prominent for the parietal and occipital lobe, which showed divergent effects as early as 22 years before estimated onset. INTERPRETATION Autosomal-dominant AD is associated with increased WMH well before expected symptom onset. The findings suggest the possibility that WMHs are a core feature of AD, a potential therapeutic target, and a factor that should be integrated into pathogenic models of the disease. Ann Neurol 2016;79:929-939.", "title": "White matter hyperintensities are a core feature of Alzheimer's disease: Evidence from the dominantly inherited Alzheimer network." }, { "docid": "18734652", "text": "Classifying endometrial hyperplasia (EH) according to the severity of glandular crowding (simple hyperplasia (SH) vs complex hyperplasia (CH)) and nuclear atypia (simple atypical hyperplasia (SAH) vs complex atypical hyperplasia (CAH)) should predict subsequent endometrial carcinoma risk, but data on progression are lacking. Our nested case–control study of EH progression included 138 cases, who were diagnosed with EH and then with carcinoma (1970–2003) at least 1 year (median, 6.5 years) later, and 241 controls, who were individually matched on age, date, and follow-up duration and counter-matched on EH classification. After centralised pathology panel and medical record review, we generated rate ratios (RRs) and 95% confidence intervals (CIs), adjusted for treatment and repeat biopsies. With disordered proliferative endometrium (DPEM) as the referent, AH significantly increased carcinoma risk (RR=14, 95% CI, 5–38). Risk was highest 1–5 years after AH (RR=48, 95% CI, 8–294), but remained elevated 5 or more years after AH (RR=3.5, 95% CI, 1.0–9.6). Progression risks for SH (RR=2.0, 95% CI, 0.9–4.5) and CH (RR=2.8, 95% CI, 1.0–7.9) were substantially lower and only slightly higher than the progression risk for DPEM. The higher progression risks for AH could foster management guidelines based on markedly different progression risks for atypical vs non-atypical EH.", "title": "Endometrial carcinoma risk among women diagnosed with endometrial hyperplasia: the 34-year experience in a large health plan" }, { "docid": "27466734", "text": "Objectives To develop and validate updated QRISK3 prediction algorithms to estimate the 10 year risk of cardiovascular disease in women and men accounting for potential new risk factors. Design Prospective open cohort study. Setting General practices in England providing data for the QResearch database. Participants 1309 QResearch general practices in England: 981 practices were used to develop the scores and a separate set of 328 practices were used to validate the scores. 7.89 million patients aged 25-84 years were in the derivation cohort and 2.67 million patients in the validation cohort. Patients were free of cardiovascular disease and not prescribed statins at baseline. Methods Cox proportional hazards models in the derivation cohort to derive separate risk equations in men and women for evaluation at 10 years. Risk factors considered included those already in QRISK2 (age, ethnicity, deprivation, systolic blood pressure, body mass index, total cholesterol: high density lipoprotein cholesterol ratio, smoking, family history of coronary heart disease in a first degree relative aged less than 60 years, type 1 diabetes, type 2 diabetes, treated hypertension, rheumatoid arthritis, atrial fibrillation, chronic kidney disease (stage 4 or 5)) and new risk factors (chronic kidney disease (stage 3, 4, or 5), a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, systemic lupus erythematosus (SLE), atypical antipsychotics, severe mental illness, and HIV/AIDs). We also considered erectile dysfunction diagnosis or treatment in men. Measures of calibration and discrimination were determined in the validation cohort for men and women separately and for individual subgroups by age group, ethnicity, and baseline disease status. Main outcome measures Incident cardiovascular disease recorded on any of the following three linked data sources: general practice, mortality, or hospital admission records. Results 363 565 incident cases of cardiovascular disease were identified in the derivation cohort during follow-up arising from 50.8 million person years of observation. All new risk factors considered met the model inclusion criteria except for HIV/AIDS, which was not statistically significant. The models had good calibration and high levels of explained variation and discrimination. In women, the algorithm explained 59.6% of the variation in time to diagnosis of cardiovascular disease (R2, with higher values indicating more variation), and the D statistic was 2.48 and Harrell's C statistic was 0.88 (both measures of discrimination, with higher values indicating better discrimination). The corresponding values for men were 54.8%, 2.26, and 0.86. Overall performance of the updated QRISK3 algorithms was similar to the QRISK2 algorithms. Conclusion Updated QRISK3 risk prediction models were developed and validated. The inclusion of additional clinical variables in QRISK3 (chronic kidney disease, a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, SLE, atypical antipsychotics, severe mental illness, and erectile dysfunction) can help enable doctors to identify those at most risk of heart disease and stroke.", "title": "Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study" } ]
55205
Winona Ryder's film debut was Lucas.
[ { "docid": "Winona_Ryder", "text": "Winona Ryder ( born Winona Laura Horowitz ; October 29 , 1971 ) is an American actress . One of the most profitable and iconic actresses of the 1990s , she made her film debut in the 1986 film Lucas . As Lydia Deetz , a goth teenager in Tim Burton 's Beetlejuice ( 1988 ) , she won critical acclaim and widespread recognition . After appearances in film and on television , Ryder continued her acting career with the cult film Heathers ( 1988 ) , a controversial satire of teenage suicide and high school life that has since become a landmark teen film . She later appeared in the coming of age drama Mermaids ( 1990 ) , earning a Golden Globe nomination , and in the same year appeared alongside Johnny Depp in Burton 's dark fairy-tale Edward Scissorhands ( 1990 ) , and shortly thereafter with Keanu Reeves in Francis Ford Coppola 's gothic romance Bram Stoker 's Dracula ( 1992 ) . Having played diverse roles in many well-received films in the mid to late 1980s and early 1990s , Ryder won a Golden Globe Award for Best Supporting Actress and an Academy Award nomination in the same category for her role in The Age of Innocence in 1993 , as well as another Academy Award nomination for Best Actress for her role in the literary adaptation of Little Women the following year . She later appeared in the Generation X hit Reality Bites ( 1994 ) , Alien : Resurrection ( 1997 ) , the Woody Allen comedy Celebrity ( 1998 ) , and Girl , Interrupted ( 1999 ) , which she also executive-produced . In 2000 , Ryder received a star on the Hollywood Walk of Fame , honoring her legacy in the film industry . Ryder 's personal life has attracted significant media attention . Her relationship with Johnny Depp in the early 1990s and a 2001 arrest for shoplifting were constant subjects of tabloid journalism . She has been open about her personal struggles with anxiety and depression . In 2002 , she appeared in the box office hit Mr. Deeds alongside Adam Sandler . In 2006 , Ryder returned to the screen after a brief hiatus , appearing in high-profile films such as Star Trek . In 2010 , she was nominated for two Screen Actors Guild Awards : as the lead actress in When Love Is Not Enough : The Lois Wilson Story and as part of the cast of Black Swan . She also reunited with Burton for Frankenweenie ( 2012 ) . Since 2016 , she has starred as Joyce Byers in the Netflix supernatural-horror series Stranger Things , for which she has garnered Golden Globe and SAG nominations .", "title": "" } ]
[ { "docid": "Lucas_(film)", "text": "Lucas is a 1986 American teen tragicomedy film directed by David Seltzer and starring Corey Haim , Kerri Green , Charlie Sheen and Courtney Thorne-Smith . The film was Winona Ryder 's screen debut .", "title": "" }, { "docid": "Lost_Souls_(film)", "text": "Lost Souls is a 2000 American horror film directed by Janusz Kamiński , in his directorial debut . The film stars Winona Ryder , Ben Chaplin , Elias Koteas , and John Hurt .", "title": "" }, { "docid": "The_Age_of_Innocence_(1993_film)", "text": "The Age of Innocence is a 1993 American romantic period piece directed by Martin Scorsese . It is a film adaptation of Edith Wharton 's 1920 novel of the same name . The story takes place during the Gilded Age , portraying New York 's high society . The film was released by Columbia Pictures and stars Daniel Day-Lewis , Michelle Pfeiffer , Winona Ryder and Miriam Margolyes The Age of Innocence won the Academy Award for Best Costume Design , and was nominated for Academy Awards for Best Actress in a Supporting Role ( Winona Ryder ) , Best Adapted Screenplay , Best Original Score and Best Art Direction . The film was dedicated to Martin Scorsese 's father , Luciano Charles Scorsese , who died before it was completed .", "title": "" }, { "docid": "David_Seltzer", "text": "David Seltzer ( born 1940 ) is an American screenwriter , producer and director , perhaps best known for writing the screenplays for The Omen ( 1976 ) and Bird on a Wire ( 1990 ) . As writer-director , Seltzer 's credits include the 1986 teen tragi-comedy Lucas starring Corey Haim , Charlie Sheen and Winona Ryder , the 1988 comedy Punchline starring Sally Field and Tom Hanks , and 1992 's Shining Through starring Melanie Griffith and Michael Douglas .", "title": "" }, { "docid": "List_of_frequent_Tim_Burton_collaborators", "text": "Tim Burton ( born August 25 , 1958 ) is an American film director , film producer , writer and artist who often works with certain actors and crew members in multiple feature film directing projects . The actors who collaborated with Burton the most frequently are Johnny Depp , Helena Bonham Carter and Christopher Lee , who all appeared in eight , seven and six films , respectively . Film composer Danny Elfman composed the music for all of Burton 's feature films with the exception of Ed Wood ( 1994 ) , Sweeney Todd : The Demon Barber of Fleet Street ( 2007 ) and Miss Peregrine 's Home for Peculiar Children ( 2016 ) . He also composed the music for The Nightmare Before Christmas ( 1993 ) , a stop-motion animated film Burton co-wrote and produced . Other actors that Burton has worked with include Danny DeVito , Conchata Ferrell , Albert Finney , Carmen Filpi , Michael Gough , Eva Green , Pat Hingle , Jan Hooks , Rance Howard , Jeffrey Jones , O-Lan Jones , Michael Keaton , Martin Landau , Lisa Marie , Catherine O'Hara , Michelle Pfeiffer , Missi Pyle , Paul Reubens , Alan Rickman , Deep Roy , Winona Ryder , Diane Salinger , Glenn Shadix , Martin Short , Timothy Spall , Sylvia Sidney , Christopher Walken , Frank Welker , Terence Stamp and Paul Whitehouse . Catherine O'Hara , Paul Reubens , and Glenn Shadix also starred in The Nightmare Before Christmas . Actor Jason Hervey appeared in the short film Frankenweenie ( 1984 ) , before appearing in Burton 's feature film directing debut Pee-wee 's Big Adventure ( 1985 ) . Actor Vincent Price worked with Burton on three projects , hosting the television film Hansel and Gretel ( 1982 ) , narrating the short film Vincent ( 1982 ) and appearing in the feature film Edward Scissorhands ( 1990 ) . Actresses Ada and Arlene Tai worked with Burton as extras in Ed Wood before going on to be cast in Big Fish ( 2003 ) . In addition to starring in Beetlejuice , Edward Scissorhands and Frankenweenie , Winona Ryder appeared in the Burton-directed music video for The Killers ' `` Here with Me '' .", "title": "" }, { "docid": "The_Last_Word_(2008_film)", "text": "The Last Word is an offbeat romantic comedy-drama film written and directed by Geoffrey Haley . It stars Winona Ryder and Wes Bentley . It had its world premiere at the Sundance Film Festival in January , and had a wider release in 2008 .", "title": "" }, { "docid": "Welcome_Home,_Roxy_Carmichael", "text": "Welcome Home , Roxy Carmichael is a 1990 American comedy-drama film starring Winona Ryder and Jeff Daniels .", "title": "" }, { "docid": "Reality_Bites", "text": "Reality Bites is a 1994 American romantic comedy-drama film written by Helen Childress and directed by Ben Stiller . It stars Winona Ryder , Ethan Hawke and Stiller , with supporting roles by Janeane Garofalo and Steve Zahn . The plot follows Lelaina ( Ryder ) , an aspiring videographer working on a documentary called Reality Bites about the disenfranchised lives of her friends and roommates . Their challenges exemplify some of the career and lifestyle choices faced by Generation X. The film 's critical reception was mixed , but was successful commercially , grossing $ 20 million in the United States on an $ 11 million budget . Critics highlighted the performances of Ryder , Hawke and Garofalo in particular . However , it has since achieved cult status and has been singled out as one of the films that captured the zeitgeist of the early 1990s grunge scene among 20-somethings , while also bringing attention to various issues that plagued young Americans at the time .", "title": "" }, { "docid": "Simone_(2002_film)", "text": "Simone ( stylized as S1MØNE ) is a 2002 American science-fiction satire film written , produced and directed by Andrew Niccol . It stars Al Pacino , Catherine Keener , Evan Rachel Wood , Rachel Roberts , Jay Mohr and Winona Ryder .", "title": "" }, { "docid": "The_Crucible_(1996_film)", "text": "The Crucible is a 1996 American historical drama film written by Arthur Miller adapting his play of the same title , inspired by the Salem witchcraft trials . It was directed by Nicholas Hytner and stars Daniel Day-Lewis as John Proctor , Winona Ryder as Abigail Williams , Paul Scofield as Judge Thomas Danforth , Bruce Davison as Reverend Parris , and Joan Allen as Elizabeth Proctor . Much of the filming took place on Choate Island in Essex , Massachusetts . Despite the film 's lacklustre box office performance , Arthur Miller was nominated for the Academy Award for Best Adapted Screenplay and Joan Allen received a nomination for Best Supporting Actress . The performances of Day-Lewis , Scofield , and Ryder were also the subjects of critical praise .", "title": "" }, { "docid": "Mermaids_(soundtrack)", "text": "Music From the Original Motion Picture Soundtrack - Mermaids is the soundtrack album from the film Mermaids starring Cher , Winona Ryder , Christina Ricci , and Bob Hoskins .", "title": "" }, { "docid": "Stay_Cool", "text": "Stay Cool is a 2011 American comedy film directed by Michael Polish ( credited as Ted Smith ) , and written by Mark Polish . The film stars Winona Ryder , Mark Polish , Hilary Duff , Sean Astin , Josh Holloway , Jon Cryer , and Chevy Chase .", "title": "" }, { "docid": "Sex_and_Death_101", "text": "Sex and Death 101 is a 2007 dark comedy science fiction film written and directed by Daniel Waters released in the United States on April 4 , 2008 . The film marks the reunion of writer-director Daniel Waters and Winona Ryder , who previously worked on the 1998 film Heathers , written by Waters .", "title": "" }, { "docid": "1969_(film)", "text": "1969 is a 1988 drama film starring Robert Downey , Jr. , Kiefer Sutherland , and Winona Ryder . It was written and directed by Ernest Thompson . The original music score is composed by Michael Small . The film deals with the Vietnam War and the resulting social tensions between those who support and oppose the war in small-town America .", "title": "" }, { "docid": "Autumn_in_New_York_(film)", "text": "Autumn in New York is a 2000 American romantic drama film directed by Joan Chen and starring Richard Gere , Winona Ryder , and Anthony LaPaglia . Written by Allison Burnett , the film follows a successful middle-aged restaurateur and womanizer who falls in love with a sweet young woman who is terminally ill .", "title": "" }, { "docid": "Experimenter_(film)", "text": "Experimenter is a 2015 American biographical drama film written and directed by Michael Almereyda , based on the 1961 Milgram experiment . The film stars Peter Sarsgaard , Taryn Manning , Kellan Lutz , Winona Ryder , Anton Yelchin , John Leguizamo , Lori Singer , Dennis Haysbert , Anthony Edwards , and Jim Gaffigan . The film was released on October 16 , 2015 , by Magnolia Pictures .", "title": "" }, { "docid": "Homefront_(film)", "text": "Homefront is a 2013 American action thriller film directed by Gary Fleder and released nationwide in theaters on November 27 . Based on Chuck Logan 's novel of the same name and adapted into a screenplay by Sylvester Stallone , the film stars Jason Statham , James Franco , Winona Ryder , and Kate Bosworth . Filming began on October 1 , 2012 in New Orleans .", "title": "" }, { "docid": "Edgar_Cantero", "text": "Edgar Cantero ( born 27 May 1981 in Barcelona ) is a Spanish writer and cartoonist working in Catalan , Spanish and English . He is known for his books Dormir amb Winona Ryder , which won the 2007 Joan Crexells Award and The Supernatural Enhancements ( 2014 ) , his debut in the English language .", "title": "" }, { "docid": "How_to_Make_an_American_Quilt", "text": "How to Make an American Quilt is a 1995 American drama film based on the 1991 novel of the same name by Whitney Otto . Directed by Jocelyn Moorhouse , the film stars Winona Ryder , Anne Bancroft , Ellen Burstyn , Kate Nelligan and Alfre Woodard . The film received a nomination for the Screen Actors Guild Award for Outstanding Performance by a Cast in a Motion Picture .", "title": "" }, { "docid": "How_to_Make_an_American_Quilt_(novel)", "text": "How to Make an American Quilt is the debut novel of Whitney Otto . The novel tells the intersecting stories of several generations of women who together are part of the same quilting circle in Grasse , California . The novel was made into a movie of the same name in 1995 directed by Jocelyn Moorhouse and starring Winona Ryder as Finn Dodd .", "title": "" }, { "docid": "Boys_(1996_film)", "text": "Boys is a 1996 American film starring Winona Ryder and Lukas Haas . The film was originally titled The Girl You Want . The film earned $ 516,350 in the United States box office . It is based on a short story called `` Twenty Minutes '' by James Salter . The film is set in an East Coast boys ' boarding school in the United States , and was shot in Baltimore , Maryland and on the campus of St. John 's College in Annapolis , Maryland , which represents the school .", "title": "" }, { "docid": "Winona_(name)", "text": "Winona is a feminine given name , an Anglicized form of the Dakota descriptive term , Winúŋna , meaning `` firstborn daughter . '' People with the name or variations thereof include : The daughter of the Dakota Sioux Chief Wapasha III , sometimes identified with the legendary figure , Winona Winona LaDuke ( born 1959 ) , Native American activist Winona Ryder ( born 1971 ) , American actress Wynona Carr ( 1924 -- 76 ) , African-American gospel , R&B and rock and roll singer-songwriter Wynona Lipman ( c. 1932 -- 99 ) , American politician and New Jersey state senator Wynonna Judd ( born 1964 ) , American country singer Fictional characters so named include : Wenonah , the mother of Hiawatha in Longfellow 's epic poem The Song of Hiawatha ( 1855 ) Winona , a character in the Pokémon universe Winona Kirk , the mother of Star Treks James T. Kirk", "title": "" }, { "docid": "The_Letter_(2012_film)", "text": "The Letter , previously called The Stare , is a 2012 American psychological thriller film written and directed by Jay Anania , starring Winona Ryder and James Franco . Franco is a former student of Anania 's , who teaches directing at NYU . The pair previously collaborated on Shadows and Lies . In 2012 , it was announced that Lionsgate purchased the distribution rights to the film , which was retitled The Letter . The film got its first theatrical showing at the Cincinnati Film Festival on September 9 , 2012 .", "title": "" }, { "docid": "Mermaids_(1990_film)", "text": "Mermaids is a 1990 American comedy-drama film directed by Richard Benjamin and starring Cher , Bob Hoskins , Winona Ryder ( who was nominated for a Golden Globe Award for best supporting actress for her role ) , and Christina Ricci in her first film role . It is based on the 1986 novel of the same title written by Patty Dann . It was shot in and around the town of Ipswich , Massachusetts and Pawtucket , Rhode Island .", "title": "" }, { "docid": "Mr._Deeds", "text": "Mr. Deeds is a 2002 American comedy film directed by Steven Brill and starring Adam Sandler and Winona Ryder . The movie is a remake of the 1936 Frank Capra film Mr. Deeds Goes to Town , and also stars Peter Gallagher , John Turturro , Allen Covert and Steve Buscemi . The movie was produced by Happy Madison and New Line Cinema and was distributed by Columbia Pictures .", "title": "" }, { "docid": "The_Iceman_(film)", "text": "The Iceman is an American biography crime thriller film based on the true story of longtime notorious hitman Richard Kuklinski . Released in 2012 at the Venice Film Festival , the film was directed by Ariel Vromen , and stars Michael Shannon as Kuklinski , Winona Ryder , Chris Evans , and Ray Liotta . The Iceman showed at the 2012 Telluride Film Festival and the 2012 Toronto International Film Festival before receiving a limited release in cinemas in the United States on May 3 , 2013 . It expanded into more cinemas in the USA on May 17 . It was released to DVD on September 3 .", "title": "" }, { "docid": "Ryder_(name)", "text": "Ryder is both a surname and masculine given name . Notable people with the name include : Surname : Albert Pinkham Ryder ( 1847 -- 1917 ) , American painter Alfred Ryder ( 1916 -- 1995 ) American actor , born Alfred Jacob Corn . Arthur W. Ryder ( 1877 -- 1938 ) American professor of Sanskrit and translator Charles W. Ryder ( 1892 -- 1960 ) , US Army General Chauncey Foster Ryder ( 1868 -- 1949 ) , American painter Cynthia Ryder ( born 1966 ) , American rower Dial D. Ryder ( 1938-2011 ) , American gunsmith Don Ryder , Baron Ryder of Eaton Hastings ( 1916 -- 2003 ) , chairman of the UK National Enterprise Board , responsible for the 1975 Ryder Report Donald J. Ryder , U.S. military lawyer , responsible for the 2003 Ryder Report on prisoner abuse in Iraq Dudley Ryder , 1st Earl of Harrowby ( 1762 -- 1847 ) , English politician Dudley Ryder , 2nd Earl of Harrowby ( 1798 -- 1882 ) , English politician Dudley Ryder , 3rd Earl of Harrowby ( 1831 -- 1900 ) , English politician Dudley Ryder , 7th Earl of Harrowby ( 1922 -- 2007 ) , deputy chairman of Coutts bank and NatWest Graham Ryder ( 1949 -- 2002 ) , English lunar scientist Henry Ignatius Dudley Ryder ( 1837-1907 ) , English Roman Catholic priest Jesse Ryder , New Zealand cricketer John Ryder ( disambiguation ) , multiple people Jonathan Ryder , pseudonym of American thriller author Robert Ludlum Michael Ryder ( born 1980 ) , NHL hockey player Mitch Ryder ( born 1945 ) , American musician Patrick Ryder ( born 1988 ) , Australian football player Richard Ryder ( 19th century politician ) ( 1766 -- 1832 ) , British 19th century politician Richard Andrew Ryder ( born 1949 ) , British politician Richard D. Ryder ( born 1940 ) , British animal rights activist Robert Edward Dudley Ryder ( 1908 -- 1986 ) , British military hero and politician Samuel Ryder ( 1858 -- 1936 ) , businessman and golf enthusiast Serena Ryder ( born 1983 ) , Canadian singer/songwriter Shaun Ryder ( born 1962 ) , British singer and songwriter Tom Ryder ( born 1985 ) , Anglo-Scot rugby union player William T. Ryder ( 1913 -- 1992 ) , Brigadier general and first American paratrooper Dr Andrew Ryder ( born 1964 ) researcher and campaigner for Roma communities Winona Ryder ( born 1971 ) , American actress James A. Ryder , founder of Ryder System , Inc. . Zack Ryder ( born 1985 ) , ring name of American professional wrestler Matt Cardona Given name : Ryder Hesjedal ( born 1980 ) , Canadian professional racing cyclist Ryder Matos Santos ( born 1993 ) , Brazilian footballer Ryder Windham , American writer Fictional characters : Honey Ryder , the Bond girl in the film Dr. No Charles Ryder , the protagnaist of Evelyn Waugh 's Brideshead Revisited James Ryder , in The Blue Carbuncle , a Sherlock Holmes story by Arthur Conan Doyle Lance `` Ryder '' Wilson , a fictional character in Grand Theft Auto : San Andreas Red Ryder , a fictional cowboy character Ryder ( comics ) , a fictional character in the Marvel Universe Ryder Callahan , a character on the American soap opera The Young and the Restless John Ryder ( The Hitcher ) , a character in the film The Hitcher Ryder , the main human character of the TV series PAW Patrol Ryder , the protagonist of the Kazuo Ishiguro novel The Unconsoled . Category : Masculine given names", "title": "" }, { "docid": "Winona_Riders_(Tsuki_no_Uragawa)", "text": "is an album by Tsukiko Amano , named after the famous American actress Winona Ryder . It is a collection of all the B-side tracks from the single 箱庭 ( Hakoniwa ) to 鮫 ( Same ) . It was released on March 3 , 2004 , labeled under Otokura Records and distributed by Pony Canyon .", "title": "" }, { "docid": "Robert_Oliveri", "text": "Robert Dane Oliveri ( born April 28 , 1978 ) is a former American actor . He is best known for his portrayal of Nick Szalinski in the 1989 Disney film , Honey , I Shrunk the Kids , for which he was nominated for a Young Artist Award and a Saturn Award . He reprised the role in the 1992 sequel , Honey , I Blew Up the Kid and the 3D film , Honey , I Shrunk the Audience . He is also known as Kevin , Winona Ryder 's little brother , in Tim Burton 's Edward Scissorhands .", "title": "" }, { "docid": "Girl,_Interrupted_(film)", "text": "Girl , Interrupted is a 1999 American psychological drama film , and a loosely based adaptation of Susanna Kaysen 's 1993 memoir of the same name . The film chronicles Kaysen 's 18-month stay at a mental institution . Directed by James Mangold , the film stars Winona Ryder ( who also served as an executive producer on the film ) as Kaysen , with a supporting cast that includes Angelina Jolie , Brittany Murphy , Clea DuVall , Whoopi Goldberg , Elisabeth Moss and Vanessa Redgrave . Girl , Interrupted was released on December 21 , 1999 . Although the film received mixed reviews from film critics , Jolie received praise for her performance and won the Academy Award for Best Supporting Actress , a Golden Globe Award and Screen Actors Guild Award .", "title": "" } ]
10976
Why would a passive investor buy anything other than the market portfolio + risk free assets?
[ { "docid": "382384", "text": "\"Investing is always a matter of balancing risk vs reward, with the two being fairly strongly linked. Risk-free assets generally keep up with inflation, if that; these days advice is that even in retirement you're going to want something with better eturns for at least part of your portfolio. A \"\"whole market\"\" strategy is a reasonable idea, but not well defined. You need to decide wheher/how to weight stocks vs bonds, for example, and short/long term. And you may want international or REIT in the mix; again the question is how much. Again, the tradeoff is trying to decide how much volatility and risk you are comfortable with and picking a mix which comes in somewhere around that point -- and noting which assets tend to move out of synch with each other (stock/bond is the classic example) to help tune that. The recommendation for higher risk/return when you have a longer horizon before you need the money comes from being able to tolerate more volatility early on when you have less at risk and more time to let the market recover. That lets you take a more aggressive position and, on average, ger higher returns. Over time, you generally want to dial that back (in the direction of lower-risk if not risk free) so a late blip doesn't cause you to lose too much of what you've already gained... but see above re \"\"risk free\"\". That's the theoretical answer. The practical answer is that running various strategies against both historical data and statistical simulations of what the market might do in the future suggests some specific distributions among the categories I've mentioned do seem to work better than others. (The mix I use -- which is basically a whole-market with weighting factors for the categories mentioned above -- was the result of starting with a general mix appropriate to my risk tolerance based on historical data, then checking it by running about 100 monte-carlo simulations of the market for the next 50 years.)\"", "title": "" } ]
[ { "docid": "113786", "text": "\"There are two umbrellas in investing: active management and passive management. Passive management is based on the idea \"\"you can't beat the market.\"\" Passive investors believe in the efficient markets hypothesis: \"\"the market interprets all information about an asset, so price is equal to underlying value\"\". Another idea in this field is that there's a minimum risk associated with any given return. You can't increase your expected return without assuming more risk. To see it graphically: As expected return goes up, so does risk. If we stat with a portfolio of 100 bonds, then remove 30 bonds and add 30 stocks, we'll have a portfolio that's 70% bonds/30% stocks. Turns out that this makes expected return increase and lower risk because of diversification. Markowitz showed that you could reduce the overall portfolio risk by adding a riskier, but uncorrelated, asset! Basically, if your entire portfolio is US stocks, then you'll lose money whenever US stocks fall. But, if you have half US stocks, quarter US bonds, and quarter European stocks, then even if the US market tanks, half your portfolio will be unaffected (theoretically). Adding different types of uncorrelated assets can reduce risk and increase returns. Let's tie this all together. We should get a variety of stocks to reduce our risk, and we can't beat the market by security selection. Ideally, we ought to buy nearly every stock in the market so that So what's our solution? Why, the exchange traded fund (ETF) of course! An ETF is basically a bunch of stocks that trade as a single ticker symbol. For example, consider the SPDR S&P 500 (SPY). You can purchase a unit of \"\"SPY\"\" and it will move up/down proportional to the S&P 500. This gives us diversification among stocks, to prevent any significant downside while limiting our upside. How do we diversify across asset classes? Luckily, we can purchase ETF's for almost anything: Gold ETF's (commodities), US bond ETF's (domestic bonds), International stock ETFs, Intl. bonds ETFs, etc. So, we can buy ETF's to give us exposure to various asset classes, thus diversifying among asset classes and within each asset class. Determining what % of our portfolio to put in any given asset class is known as asset allocation and some people say up to 90% of portfolio returns can be determined by asset allocation. That pretty much sums up passive management. The idea is to buy ETFs across asset classes and just leave them. You can readjust your portfolio holdings periodically, but otherwise there is no rapid trading. Now the other umbrella is active management. The unifying idea is that you can generate superior returns by stock selection. Active investors reject the idea of efficient markets. A classic and time proven strategy is value investing. After the collapse of 07/08, bank stocks greatly fell, but all the other stocks fell with them. Some stocks worth $100 were selling for $50. Value investors quickly snapped up these stocks because they had a margin of safety. Even if the stock didn't go back to 100, it could go up to $80 or $90 eventually, and investors profit. The main ideas in value investing are: have a big margin of safety, look at a company's fundamentals (earnings, book value, etc), and see if it promises adequate return. Coke has tremendous earnings and it's a great company, but it's so large that you're never going to make 20% profits on it annually, because it just can't grow that fast. Another field of active investing is technical analysis. As opposed to the \"\"fundamental analysis\"\" of value investing, technical analysis involves looking at charts for patterns, and looking at stock history to determine future paths. Things like resistance points and trend lines also play a role. Technical analysts believe that stocks are just ticker symbols and that you can use guidelines to predict where they're headed. Another type of active investing is day trading. This basically involves buying and selling stocks every hour or every minute or just at a rapid pace. Day traders don't hold onto investments for very long, and are always trying to predict the market in the short term and take advantage of it. Many individual investors are also day traders. The other question is, how do you choose a strategy? The short answer is: pick whatever works for you. The long answer is: Day trading and technical analysis is a lot of luck. If there are consistent systems for trading , then people are keeping them secret, because there is no book that you can read and become a consistent trader. High frequency trading (HFT) is an area where people basically mint money, but it s more technology and less actual investing, and would not be categorized as day trading. Benjamin Graham once said: In the short run, the market is a voting machine but in the long run it is a weighing machine. Value investing will work because there's evidence for it throughout history, but you need a certain temperament for it and most people don't have that. Furthermore, it takes a lot of time to adequately study stocks, and people with day jobs can't devote that kind of time. So there you have it. This is my opinion and by no means definitive, but I hope you have a starting point to continue your study. I included the theory in the beginning because there are too many monkeys on CNBC and the news who just don't understand fundamental economics and finance, and there's no sense in applying a theory until you can understand why it works and when it doesn't.\"", "title": "" }, { "docid": "283202", "text": "\"The fact that some asset (in this case corporate bonds) has positive correlation with some other asset (equity) doesn't mean buying both isn't a good idea. Unless they are perfectly correlated, the best risk/reward portfolio will include both assets as they will sometimes move in opposite directions and cancel out each other's risk. So yes, you should buy corporate bonds. Short-term government bonds are essentially the risk-free asset. You will want to include that as well if you are very risk averse, otherwise you may not. Long-term government bonds may be default free but they are not risk free. They will make money if interest rates fall and lose if interest rates rise. Because of that risk, they also pay you a premium, albeit a small one, and should be in your portfolio. So yes, a passive portfolio (actually, any reasonable portfolio) should strive to reduce risk by diversifying into all assets that it reasonably can. If you believe the capital asset pricing model, the weights on portfolio assets should correspond to market weights (more money in bonds than stocks). Otherwise you will need to choose your weights. Unfortunately we are not able to estimate the true expected returns of risky assets, so no one can really agree on what the true optimal weights should be. That's why there are so many rules of thumb and so much disagreement on the subject. But there is little or no disagreement on the fact that the optimal portfolio does include risky bonds including long-term treasuries. To answer your follow-up question about an \"\"anchor,\"\" if by that you mean a risk-free asset then the answer is not really. Any risk-free asset is paying approximately zero right now. Some assets with very little risk will earn a very little bit more than short term treasuries, but overall there's nowhere to hide--the time value of money is extremely low at short horizons. You want expected returns, you must take risk.\"", "title": "" }, { "docid": "496050", "text": "\"In financial markets, the gains you can expect to make (whether in the form of dividends or capital gains) correspond to the risks you are bearing. There are a variety of REITs but you can expect to make only as much money in them as you bear risk (meaning you can also lose a lot of money in the ones that earn a lot). In that sense they are just like other financial assets like stocks. If you are generically trying to increase your wealth by bearing risk, you can get a better risk/reward ratio in a fully diversified portfolio including stocks and bonds as well and REITs. \"\"Passive income\"\" means making money by bearing risk. REITs alone, without diversifying into other financial assets, do a poor job of generating income for the amount of risk you bear. So why are REITs not very comparable to buying a house and renting it out? Because in the latter case you are being paid not only for bearing the risk of the house depreciating but also you are being compensated for the work you do as a landlord. Moreover, because the house doesn't trade in a liquid market like REITs do, it is possible to actually get a good deal, as opposed to the fair deal you will get on a REIT. TL;DR: The \"\"passive income\"\" generated by REIT investment is more similar to generic equity/bond investment than it is to an investment in a physical home that you rent out. If what you want is to make money without doing anything besides bear risk, you should invest in a fully diversified portfolio of financial assets (equity and bonds being the primary constituents but REITs potentially being a part as well).\"", "title": "" }, { "docid": "577832", "text": "Your question seems to be making assumptions around “investing”, that investing is only about stock market and bonds or similar things. I would suggest that you should look much broader than that in terms of your investments. Investment Types Your should consider (and include) some or all of the following for your investments, depending on your age, your attitude towards risk, the number of dependents you have, your lifestyle, etc. I love @Blackjack’s explanation of diversification into other asset classes producing a lower risk portfolio. Excellent! All the above need to be considered in this spread of risk, depending as I said earlier on your age, your attitude towards risk, the number of dependents you have, your lifestyle, etc. Stock Market Investment I’ll focus most of the rest of my post on the stock markets, as that is where my main experience lies. But the comments are applicable to a greater or lesser extent to other types of investing. We then come to how engaged you want to be with your investments. Two general management styles are passive investment management versus active investment management. @Blackjack says That pretty much sums up passive management. The idea is to buy ETFs across asset classes and just leave them. The difficulty with this idea is that profitability is very dependent upon when the stocks are purchased and when they are sold. This is why active investing should be considered as a viable alternative to passive investment. I don’t have access to a very long time frame of stock market data, but I do have 30 or so years of FTSE data, so let’s say that we invest £100,000 for 10 years by buying an ETF in the FTSE100 index. I know this isn't de-risking across a number of asset classes by purchasing a number of different EFTs, but the logic still applies, if you will bear with me. Passive Investing I have chosen my example dates of best 10 years and worst 10 years as specific dates that demonstrate my point that active investing will (usually) out-perform passive investing. From a passive investing point of view, here is a graph of the FTSE with two purchase dates chosen (for maximum effect), to show the best and worst return you could receive. Note this ignores brokerage and other fees. In these time frames of data I have … These are contrived dates to illustrate the point, on how ineffective passive investing can be, depending if there is a bear/bull market and where you buy in the cycle. One obviously wouldn’t buy all their stocks in one tranche, but I’m just trying to illustrate the point. Active Investing Let’s consider now active investing. I use the following rules for selling and buying:- This is obviously a very simple technical trading system and I would not recommend using it to trade with, as it is overly simplistic and there are some flaws and inefficiencies in it. So, in my simulation, These beat the passive stock market profit for their respective dates. Summary Passive stock market investing is dependent upon the entry and exit prices on the dates the transactions are made and will trade regardless of market cycles. Active stock market trading or investing engages with the market using a set of criteria, which can change over time, but allows one’s investments to be in or out of the market at any point in time. My time frames were arbitrary, but with the logic applied (which is a very simple technical trading methodology), I would suggest that any 10 year time frame active investing would beat passive investing.", "title": "" }, { "docid": "409959", "text": "\"RED FLAG. You should not be invested in 1 share. You should buy a diversified ETF which can have fees of 0.06% per year. This has SIGNIFICANTLY less volatility for the same statistical expectation. Left tail risk is MUCH lower (probability of gigantic losses) since losses will tend to cancel out gains in diversified portfolios. Moreover, your view that \"\"you believe these will continue\"\" is fallacious. Stocks of developed countries are efficient to the extent that retail investors cannot predict price evolution in the future. Countless academic studies show that individual investors forecast in the incorrect direction on average. I would be quite right to objectively classify you as a incorrect if you continued to hold the philosophy that owning 1 stock instead of the entire market is a superior stategy. ALL the evidence favours holding the market. In addition, do not invest in active managers. Academic evidence demonstrates that they perform worse than holding a passive market-tracking portfolio after fees, and on average (and plz don't try to select managers that you think can outperform -- you can't do this, even the best in the field can't do this). Direct answer: It depends on your investment horizon. If you do not need the money until you are 60 then you should invest in very aggressive assets with high expected return and high volatility. These assets SHOULD mainly be stocks (through ETFs or mutual funds) but could also include US-REIT or global-REIT ETFs, private equity and a handful of other asset classes (no gold, please.) ... or perhaps wealth management products which pool many retail investors' funds together and create a diversified portfolio (but I'm unconvinced that their fees are worth the added diversification). If you need the money in 2-3 years time then you should invest in safe assets -- fixed income and term deposits. Why is investment horizon so important? If you are holding to 60 years old then it doesn't matter if we have a massive financial crisis in 5 years time, since the stock market will rebound (unless it's a nuclear bomb in New York or something) and by the time you are 60 you will be laughing all the way to the bank. Gains on risky assets overtake losses in the long run such that over a 20-30 year horizon they WILL do much better than a deposit account. As you approach 45-50, you should slowly reduce your allocation to risky assets and put it in safe haven assets such as fixed income and cash. This is because your investment horizon is now SHORTER so you need a less risky portfolio so you don't have to keep working until 65/70 if the market tanks just before retirement. VERY IMPORTANT. If you may need the savings to avoid defaulting on your home loan if you lose your job or something, then the above does not apply. Decisions in these context are more vague and ambiguous.\"", "title": "" }, { "docid": "513016", "text": "\"There's no such thing as true \"\"passive income.\"\" You are being paid the risk free rate to delay consumption (i.e., the super low rate you are getting on savings accounts and CDs) and a higher rate to bear risk. You will not find truly risk-free investments that earn more than the types of investments you have been looking at...most likely you will not keep up with inflation in risk-free investments. For a person who is very risk averse but wants to make a little more money than the risk-free rate, the solution is not to invest completely in slightly risky things. Instead the best thing you can do is invest partially in a fully diversified portfolio. A diversified portfolio (containing stocks, bonds, etc) will earn you the most return for the given amount of risk. If you want very little risk, put very little in that portfolio and keep the rest in your CDs. Put 90% of your money in a CD or something and the other 10% in stocks/bonds. Or choose a different percentage. You can also buy real assets, like real estate, but you will find yourself taking a different type of risk and doing a different type of work with those assets.\"", "title": "" }, { "docid": "549402", "text": "This answer will assume you know more math than most. An ideal case: For the point of argument, first consider the following admittedly incorrect assumptions: 1) The prices of all assets in your investment universe are continuously differentiable functions of time. 2) Investor R (for rebalance) continuously buys and sells in order to maintain a constant proportion of each of several investments in his portfolio. 3) Investor P (for passive) starts with the same portfolio as R, but neither buys nor sells Then under the assumptions of no taxes or trading costs, it is a mathematical theorem that investor P's portfolio return fraction will be the weighted arithmetic mean of the return fractions of all the individual investments, whereas investor R will obtain the weighted geometric mean of the return fractions of the individual investments. It's also a theorem that the weighted arithmetic mean is ALWAYS greater than or equal to the weighted geometric mean, so regardless of what happens in the market (given the above assumptions) the passive investor P does at least as well as the rebalancing investor R. P will do even better if taxes and trading costs are factored in. The real world: Of course prices aren't continuously differentiable or even continuous, nor can you continuously trade. (Indeed, under such assumptions the optimal investing strategy would be to sample the prices sufficiently rapidly to capture the derivatives and then to move all your assets to the stock increasing at the highest relative rate. This crazy momentum trading would explosively destabilize the market and cause the assumptions to break.) The point of this is not to argue for or against rebalancing, but to point out that any argument for rebalancing which continues to hold under the above ideal assumptions is bogus. (Many such arguments do.) If a stockbroker standing to profit from commission pushes rebalancing on you with an argument that still holds under the above assumptions then he is profiting off of BS.", "title": "" }, { "docid": "310218", "text": "\"If the stock market dropped 30%-40% next month, providing you with a rare opportunity to buy stocks at a deep discount, wouldn't you want to have some of your assets in investments other than stocks? If you don't otherwise have piles of new cash to throw into the market when it significantly tanks, then having some of your portfolio invested elsewhere will enable you to back up the proverbial truck and load up on more stocks while they are on sale. I'm not advocating active market timing. Rather, the way that long-term investors capitalize on such opportunities is by choosing a portfolio asset allocation that includes some percentage of safer assets (e.g. cash, short term bonds, etc.), permitting the investor to rebalance the portfolio periodically back to target allocations (e.g. 80% stocks, 20% bonds.) When rebalancing would have you buy stocks, it's usually because they are on sale. Similarly, when rebalancing would have you sell stocks, it's usually because they are overpriced. So, don't consider \"\"safer investments\"\" strictly as a way to reduce your risk. Rather, they can give you the means to take advantage of market drops, rather than just riding it out when you are already 100% invested in stocks. I could say a lot more about diversification and risk reduction, but there are plenty of other great questions on the site that you can look through instead.\"", "title": "" }, { "docid": "436904", "text": "This is Ellie Lan, investment analyst at Betterment. To answer your question, American investors are drawn to use the S&P 500 (SPY) as a benchmark to measure the performance of Betterment portfolios, particularly because it’s familiar and it’s the index always reported in the news. However, going all in to invest in SPY is not a good investment strategy—and even using it to compare your own diversified investments is misleading. We outline some of the pitfalls of this approach in this article: Why the S&P 500 Is a Bad Benchmark. An “algo-advisor” service like Betterment is a preferable approach and provides a number of advantages over simply investing in ETFs (SPY or others like VOO or IVV) that track the S&P 500. So, why invest with Betterment rather than in the S&P 500? Let’s first look at the issue of diversification. SPY only exposes investors to stocks in the U.S. large cap market. This may feel acceptable because of home bias, which is the tendency to invest disproportionately in domestic equities relative to foreign equities, regardless of their home country. However, investing in one geography and one asset class is riskier than global diversification because inflation risk, exchange-rate risk, and interest-rate risk will likely affect all U.S. stocks to a similar degree in the event of a U.S. downturn. In contrast, a well-diversified portfolio invests in a balance between bonds and stocks, and the ratio of bonds to stocks is dependent upon the investment horizon as well as the individual's goals. By constructing a portfolio from stock and bond ETFs across the world, Betterment reduces your portfolio’s sensitivity to swings. And the diversification goes beyond mere asset class and geography. For example, Betterment’s basket of bond ETFs have varying durations (e.g., short-term Treasuries have an effective duration of less than six months vs. U.S. corporate bonds, which have an effective duration of just more than 8 years) and credit quality. The level of diversification further helps you manage risk. Dan Egan, Betterment’s Director of Behavioral Finance and Investing, examined the increase in returns by moving from a U.S.-only portfolio to a globally diversified portfolio. On a risk-adjusted basis, the Betterment portfolio has historically outperformed a simple DIY investor portfolio by as much as 1.8% per year, attributed solely to diversification. Now, let’s assume that the investor at hand (Investor A) is a sophisticated investor who understands the importance of diversification. Additionally, let’s assume that he understands the optimal allocation for his age, risk appetite, and investment horizon. Investor A will still benefit from investing with Betterment. Automating his portfolio management with Betterment helps to insulate Investor A from the ’behavior gap,’ or the tendency for investors to sacrifice returns due to bad timing. Studies show that individual investors lose, on average, anywhere between 1.2% to 4.3% due to the behavior gap, and this gap can be as high as 6.5% for the most active investors. Compared to the average investor, Betterment customers have a behavior gap that is 1.25% lower. How? Betterment has implemented smart design to discourage market timing and short-sighted decision making. For example, Betterment’s Tax Impact Preview feature allows users to view the tax hit of a withdrawal or allocation change before a decision is made. Currently, Betterment is the only automated investment service to offer this capability. This function allows you to see a detailed estimate of the expected gains or losses broken down by short- and long-term, making it possible for investors to make better decisions about whether short-term gains should be deferred to the long-term. Now, for the sake of comparison, let’s assume that we have an even more sophisticated investor (Investor B), who understands the pitfalls of the behavior gap and is somehow able to avoid it. Betterment is still a better tool for Investor B because it offers a suite of tax-efficient features, including tax loss harvesting, smarter cost-basis accounting, municipal bonds, smart dividend reinvesting, and more. Each of these strategies can be automatically deployed inside the portfolio—Investor B need not do a thing. Each of these strategies can boost returns by lowering tax exposure. To return to your initial question—why not simply invest in the S&P 500? Investing is a long-term proposition, particularly when saving for retirement or other goals with a time horizon of several decades. To be a successful long-term investor means employing the core principles of diversification, tax management, and behavior management. While the S&P might look like a ‘hot’ investment one year, there are always reversals of fortune. The goal with long-term passive investing—the kind of investing that Betterment offers—is to help you reach your investing goals as efficiently as possible. Lastly, Betterment offers best-in-industry advice about where to save and how much to save for no fee.", "title": "" }, { "docid": "513474", "text": "\"Most people advocate a passively managed, low fee mutual fund that simply aims to track a given benchmark (say S&P 500). Few funds can beat the S&P consistently, so investors are often better served finding a no load passive fund. First thing I would do is ask your benefits rep why you don't have an option to invest in a Fidelity passive index fund like Spartan 500. Ideally young people would be heavy in equities and slowly divest for less risky stuff as retirement comes closer, and rebalance the portfolio regularly when market swings put you off risk targets. Few people know how to do this and actually do so. So there are mutual funds that do it for you, for a fee. These in are called \"\"lifecycle\"\" funds (The Freedom funds here). I hesitate to recommend them because they're still fairly new. If you take a look at underlying assets, these things generally just reinvest in the broker's other funds, which themselves have expenses & fees. And there's all kinds personal situations that might lead to you place a portion with a different investment.\"", "title": "" }, { "docid": "283074", "text": "In answer to your last formulation, no. In a perfectly efficient market, different investors still have different risk tolerances (or utility functions). They're maximizing expected utility, not expected value. The portfolios that maximize expected utility for different risk preferences are different, and thus generally have different expected values. (Look up mean-variance utility for a simple-ish example.) Suppose you have log utility for money, u(x) = log(x), and your choice is to invest all of your money in either the risk-free bond or in the risky bond. In the risky bond, you have a positive probability of losing everything, achieving utility u(0) = -\\infty. Your expected utility after purchase of the risky bond is: Pr(default)*u(default) + (1-Pr(default))*u(nominalValue). Since u(default)= -\\infty, your expected utility is also negative infinity, and you would never make this investment. Instead you would purchase the risk-free bond. But another person might have linear utility, u(x) = x, and he would be indifferent between the risk-free and risky bonds at the prices you mention above and might therefore purchase some. (In fact you probably would have bid up the price of the risk-free bond, so that the other investor strictly prefers the risky one.) So two different investors' portfolios will have different expected returns, in general, because of their different risk preferences. Risk-averse investors get lower expected value. This should be very intuitive from portfolio theory in general: stocks have higher expected returns, but more variance. Risk-tolerant people can accept more stocks and more variance, risk-averse people purchase less stocks and more bonds. The more general question about risk premia requires an equilibrium price analysis, which requires assumptions about the distribution of risk preferences among other things. Maybe John Cochrane's book would help with that---I don't know anything about financial economics. I would think that in the setup above, if you have positive quantities of these two investor types, the risk-free bond will become more expensive, so that the risky one offers a higher expected return. This is the general thing that happens in portfolio theory. Anyway. I'm not a financial economist or anything. Here's a standard introduction to expected utility theory: http://web.stanford.edu/~jdlevin/Econ%20202/Uncertainty.pdf", "title": "" }, { "docid": "551590", "text": "\"From http://blog.ometer.com/2008/03/27/index-funds/ , Lots of sensible advisers will tell you to buy index funds, but importantly, the advice is not simply \"\"buy index funds.\"\" There are at least two other critical details: 1) asset allocation across multiple well-chosen indexes, maintained through regular rebalancing, and 2) dollar cost averaging (or, much-more-complex-but-probably-slightly-better, value averaging). The advice is not to take your single lump sum and buy and hold a cap-weighted index forever. The advice is an investment discipline which involves action over time, and an initial choice among indexes. An index-fund-based strategy is not completely passive, it involves some active risk control through rebalancing and averaging. If you'd held a balanced portfolio over the last ten years and rebalanced, and even better if you'd dollar cost averaged, you'd have done fine. Your reaction to the last 10 years incidentally is why I don't believe an almost-all-stocks allocation makes sense for most people even if they're pretty young. More detail in this answer: How would bonds fare if interest rates rose? I think some index fund advocacy and books do people a disservice by focusing too much on the extra cost of active management and why index funds are a good deal. That point is true, but for most investors, asset allocation, rebalancing, and \"\"autopilotness\"\" of their setup are more important to outcome than the expense ratio.\"", "title": "" }, { "docid": "93836", "text": "\"Because ETFs, unlike most other pooled investments, can be easily shorted, it is possible for institutional investors to take an arbitrage position that is long the underlying securities and short the ETF. The result is that in a well functioning market (where ETF prices are what they should be) these institutional investors would earn a risk-free profit equal to the fee amount. How much is this amount, though? ETFs exist in a very competitive market. Not only do they compete with each other, but with index and mutual funds and with the possibility of constructing one's own portfolio of the underlying. ETF investors are very cost-conscious. As a result, ETF fees just barely cover their costs. Typically, ETF providers do not even do their own trading. They issue new shares only in exchange for a bundle of the underlying securities, so they have almost no costs. In order for an institutional investor to make money with the arbitrage you describe, they would need to be able to carry it out for less than the fees earned by the ETF. Unlike the ETF provider, these investors face borrowing and other shorting costs and limitations. As a result it is not profitable for them to attempt this. Note that even if they had no costs, their maximum upside would be a few basis points per year. Lots of low-risk investments do better than that. I'd also like to address your question about what would happen if there was an ETF with exorbitant fees. Two things about your suggested outcome are incorrect. If short sellers bid the price down significantly, then the shares would be cheap relative to their stream of future dividends and investors would again buy them. In a well-functioning market, you can't bid the price of something that clearly is backed by valuable underlying assets down to near zero, as you suggest in your question. Notice that there are limitations to short selling. The more shares are short-sold, the more difficult it is to locate share to borrow for this purpose. At first brokers start charging additional fees. As borrowable shares become harder to find, they require that you obtain a \"\"locate,\"\" which takes time and costs money. Finally they will not allow you to short at all. Unlimited short selling is not possible. If there was an ETF that charged exorbitant fees, it would fail, but not because of short sellers. There is an even easier arbitrage strategy: Investors would buy the shares of the ETF (which would be cheaper than the value of the underlying because of the fees) and trade them back to the ETF provider in exchange for shares of the underlying. This would drain down the underlying asset pool until it was empty. In fact, it is this mechanism (the ability to trade ETF shares for shares of the underlying and vice versa) that keeps ETF prices fair (within a small tolerance) relative to the underlying indices.\"", "title": "" }, { "docid": "216757", "text": "\"Great question! While investing in individual stocks can be very useful as a learning experience, my opinion is that concentrating an entire portfolio in a few companies' stock is a mistake for most investors, and especially for a novice for several reasons. After all, only a handful of professional investors have ever beaten the market over the long term by picking stocks, so is it really worth trying? If you could, I'd say go work on Wall Street and good luck to you. Diversification For many investors, diversification is an important reason to use an ETF or index fund. If they were to focus on a few sectors or companies, it is more likely that they would have a lop-sided risk profile and might be subject to a larger downside risk potential than the market as a whole, i.e. \"\"don't put all your eggs in one basket\"\". Diversification is important because of the nature of compound investing - if you take a significant hit, it will take you a long time to recover because all of your future gains are building off of a smaller base. This is one reason that younger investors often take a larger position in equities, as they have longer to recover from significant market declines. While it is very possible to build a balanced, diversified portfolio from individual stocks, this isn't something I'd recommend for a new investor and would require a substantial college-level understanding of investments, and in any case, this portfolio would have a more discrete efficient frontier than the market as a whole. Lower Volatility Picking individual stocks or sectors would could also significantly increase or decrease the overall volatility of the portfolio relative to the market, especially if the stocks are highly cyclical or correlated to the same market factors. So if they are buying tech stocks, they might see bigger upswings and downswings compared to the market as a whole, or see the opposite effect in the case of utilities. In other words, owning a basket of individual stocks may result in an unintended volatility/beta profile. Lower Trading Costs and Taxes Investors who buy individual stocks tend to trade more in an attempt to beat the market. After accounting for commission fees, transaction costs (bid/ask spread), and taxes, most individual investors get only a fraction of the market average return. One famous academic study finds that investors who trade more trail the stock market more. Trading also tends to incur higher taxes since short term gains (<1 year) are taxed at marginal income tax rates that are higher than long term capital gains. Investors tend to trade due to behavioral failures such as trying to time the market, being overconfident, speculating on stocks instead of long-term investing, following what everyone else is doing, and getting in and out of the market as a result of an emotional reaction to volatility (ie buying when stocks are high/rising and selling when they are low/falling). Investing in index funds can involve minimal fees and discourages behavior that causes investors to incur excessive trading costs. This can make a big difference over the long run as extra costs and taxes compound significantly over time. It's Hard to Beat the Market since Markets are Quite Efficient Another reason to use funds is that it is reasonable to assume that at any point in time, the market does a fairly good job of pricing securities based on all known information. In other words, if a given stock is trading at a low P/E relative to the market, the market as a whole has decided that there is good reason for this valuation. This idea is based on the assumption that there are already so many professional analysts and traders looking for arbitrage opportunities that few such opportunities exist, and where they do exist, persist for only a short time. If you accept this theory generally (obviously, the market is not perfect), there is very little in the way of insight on pricing that the average novice investor could provide given limited knowledge of the markets and only a few hours of research. It might be more likely that opportunities identified by the novice would reflect omissions of relevant information. Trying to make money in this way then becomes a bet that other informed, professional investors are wrong and you are right (options traders, for example). Prices are Unpredictable (Behave Like \"\"Random\"\" Walks) If you want to make money as a long-term investor/owner rather than a speculator/trader, than most of the future change in asset prices will be a result of future events and information that is not yet known. Since no one knows how the world will change or who will be tomorrow's winners or losers, much less in 30 years, this is sometimes referred to as a \"\"random walk.\"\" You can point to fundamental analysis and say \"\"X company has great free cash flow, so I will invest in them\"\", but ultimately, the problem with this type of analysis is that everyone else has already done it too. For example, Warren Buffett famously already knows the price at which he'd buy every company he's interested in buying. When everyone else can do the same analysis as you, the price already reflects the market's take on that public information (Efficent Market theory), and what is left is the unknown (I wouldn't use the term \"\"random\"\"). Overall, I think there is simply a very large potential for an individual investor to make a few mistakes with individual stocks over 20+ years that will really cost a lot, and I think most investors want a balance of risk and return versus the largest possible return, and don't have an interest in developing a professional knowledge of stocks. I think a better strategy for most investors is to share in the future profits of companies buy holding a well-diversified portfolio for the long term and to avoid making a large number of decisions about which stocks to own.\"", "title": "" }, { "docid": "549364", "text": "\"As you alluded to in your question, there is not one answer that will be true for all mutual funds. In fact, I would argue the question is not specific to mutual funds but can be applied to almost anyone who must make an investment decision: a mutual fund manager, hedge fund manager, or an individual investor. Even though money going into a company 401(k) retirement savings plan is typically automatically allocated to different funds as we have specified, this is generally not the case for other investment accounts. For example, I also have a Roth IRA in which I have some money from each paycheck direct deposited and it's up to me to decide whether to leave that money in cash or to invest it somewhere else. Every time you invest more money into a mutual fund, the fund manager has the same decision to make. There are two commonly used mutual fund figures that relate to your question: turnover rate, and cash reserves. Turnover rate measures the percent of a fund's portfolio that changes every year. For example, a turnover rate of 100% indicates that a fund replaces every asset it held at the beginning of the year with something else at the end of the year – funds with turnover rates greater than 100% average a holding period for a given asset of less than one year, and funds with turnover rates less than 100% average a holding period for a given asset of more than one year. Cash reserves simply measure the amount of money funds choose to keep as cash instead of investing in other assets. Another important distinction to make is between actively managed funds and passively managed funds. Passively managed funds are often referred to as \"\"index funds\"\" and have as their goal only to match the returns of a given index or some other benchmark. Actively managed funds on the other hand try to beat the market by exploiting so-called market inefficiencies; e.g. buying undervalued assets, selling overvalued assets, \"\"timing\"\" the market, etc. To answer your question for a specific fund, I would encourage you to look at the fund's prospectus. I take as one example of a passively managed fund the Vanguard 500 Index Fund (VFINX), a mutual fund that was created to track the S&P 500. In its prospectus, the fund states that, \"\"to track its target index as closely as possible, the Fund attempts to remain fully invested in stocks\"\". Furthermore, the prospectus states that \"\"the fund's daily cash balance may be invested in one or more Vanguard CMT Funds, which are very low-cost money market funds.\"\" Therefore, we would expect both this fund's turnover rate and cash reserves to be extremely low. When we look at its portfolio composition, we see this is true – it is currently at a 4.8% turnover rate and holds 0.0% in short term reserves. Therefore, we can assume this fund is regularly purchasing shares (similar to a dollar cost averaging strategy) instead of holding on to cash and purchasing shares together at a specific time. For actively managed funds, the picture will tend to look a little different. For example, if we look at the Magellan Fund's portfolio composition, we can see it has a turnover rate of 42%, and holds around .95% in cash/short term reserves. In this case, we can safely guess that trading activity may not be as regular as a passively managed fund, as an active manager attempts to time the market. You may find mutual funds that have much higher cash reserves – perhaps 10% or even more. Granted, it is impossible to know the exact trading strategy of a mutual fund, and for good reason – if we knew for example, that a fund purchases shares every day at 2:30PM in order to realign with the S&P 500, then sellers of S&P components could up the prices at that time to exploit the mutual fund's trade strategy. Large traders are constantly trying to find ways to conceal their actual trading activity in order to avoid these exact problems. Finally, I feel obligated to note that it is important to keep in mind that trade frequency is linked to transactions costs – in general, the more frequently an investment manager (whether it be you or a mutual fund manager) executes trades, the more that manager will lose in transactions costs.\"", "title": "" }, { "docid": "10526", "text": "\"[...] are all bonds priced in such a way so that they all return the same amount (on average), after accounting for risk? In other words, do risk premiums ONLY compensate for the amount investors might lose? No. GE might be able to issue a bond with lower yield than, say, a company from China with no previous records of its presence in the U.S. markets. A bond price not only contains the risk of default, but also encompasses the servicability of the bond by the issuer with a specific stream of income, location of main business, any specific terms and conditions in the prospectus, e.g.callable or not, insurances against default, etc. Else for the same payoff, why would you take a higher risk? The payoff of a higher risk (not only default, but term structure, e.g. 5 years or 10 years, coupon payments) bond is more, to compensate for the extra risk it entails for the bondholder. The yield of a high risk bond will always be higher than a bond with lower risk. If you travel back in time, to 2011-2012, you would see the yields on Greek bonds were in the range of 25-30%, to reflect the high risk of a Greek default. Some hedge funds made a killing by buying Greek bonds during the eurozone crisis. If you go through the Efficient frontier theory, your argument is a counter statement to it. Same with individual bonds, or a portfolio of bonds. You always want to be compensated for the risk you take. The higher the risk, the higher the compensation, and vice versa. When investors buy the bond at this price, they are essentially buying a \"\"risk free\"\" bond [...] Logically yes, but no it isn't, and you shouldn't make that assumption.\"", "title": "" }, { "docid": "280204", "text": "Putting the money in a bank savings account is a reasonably safe investment. Anything other than that will come with additional risk of various kinds. (That's right; not even a bank account is completely free of risk. Neither is withdrawing cash and storing it somewhere yourself.) And I don't know which country you are from, but you will certainly have access to your country's government bonds and the likes. You may also have access to mutual funds which invest in other countries' government bonds (bond or money-market funds). The question you need to ask yourself really is twofold. One, for how long do you intend to keep the money invested? (Shorter term investing should involve lower risk.) Two, what amount of risk (specifically, price volatility) are you willing to accept? The answers to those questions will determine which asset class(es) are appropriate in your particular case. Beyond that, you need to make a personal call: which asset class(es) do you believe are likely to do better or less bad than others? Low risk usually comes at the price of a lower return. Higher return usually involves taking more risk (specifically price volatility in the investment vehicle) but more risk does not necessarily guarantee a higher return - you may also lose a large fraction of or even the entire capital amount. In extreme cases (leveraged investments) you might even lose more than the capital amount. Gold may be a component of a well-diversified portfolio but I certainly would not recommend putting all of one's money in it. (The same goes for any asset class; a portfolio composed exclusively of stocks is no more well-diversified than a portfolio composed exclusively of precious metals, or government bonds.) For some specifics about investing in precious metals, you may want to see Pros & cons of investing in gold vs. platinum?.", "title": "" }, { "docid": "136515", "text": "\"Bonds still definitely have a place in many passive portfolios. While it is true that interest rates have been unusually low, yields on reasonable passive bond exposures are still around 2-4%. This is significantly better than both recent past inflation and expected inflation both of which are near zero. This is reasonable if not great return, but Bonds continue to have other nice properties like relatively low risk and diversification of stock portfolios (the \"\"offset[ing] losses\"\" you mention in the OP). So to say that bonds are \"\"no longer a good idea\"\" is certainly not correct. One could say bonds may no longer be a good idea for some people that have a particularly high risk tolerance and very high return requirements. However, to some extent, that has always been true. It is worth remembering also that there is some compelling evidence that global growth is starting to broadly slow down and many people believe that future stock returns and, in general, returns on all investments will be lower. This is much much harder to estimate than bond returns though. Depending on who you believe, bond returns may actually look relatively better than the have in the past. Edit in response to comment: Corporate bond correlation with stocks is positive but generally not very strong (except for high-yield junk bonds) so while they don't offset stock volatility (negative correlation) they do help diversify a stock portfolio. Government bonds have essentially zero correlation so they don't really offset volatility as much as just not add any. Negative correlation assets are generally called insurance and you tend to have to pay for them. So there is no free lunch here. Assets that reduce risk cost money, assets that add little risk give less return and assets that are more risky tend to give more return in the long run but you can feel the pain. The mix that is right for you depends on a lot of things, but for many people that mix involves some corporate and government bonds.\"", "title": "" }, { "docid": "483123", "text": "\"The question is: how do you quantify investment risk? As Michael S says, one approach is to treat investment returns as a random variable. Bill Goetzmann (Yale finance professor) told me that if you accept that markets are efficient or that the price of an asset reflects it's underlying value, then changes in price represent changes in value, so standard deviation naturally becomes the appropriate measure for riskiness of an asset. Essentially, the more volatile an asset, the riskier it is. There is another school of thought that comes from Ben Graham and Warren Buffett, which says that volatility is not inherently risky. Rather, risk should be defined as the permanent loss of capital, so the riskiness of an asset is the probability of a permanent loss of capital invested. This is easy to do in casino games, based on basic probability such as roulette or slots. But what has been done with the various kinds of investment risks? My point is saying that certain bonds are \"\"low risk\"\" isn't good enough; I'd like some numbers--or at least a range of numbers--and therefore one could calculate expected payoff (in the statistics sense). Or can it not be done--and if not, why not? Investing is more art than science. In theory, a Triple-A bond rating means the asset is riskless or nearly riskless, but we saw that this was obviously wrong since several of the AAA mortgage backed securities (MBS) went under prior to the recent US recession. More recently, the current threat of default suggests that bond ratings are not entirely accurate, since US Treasuries are considered riskless assets. Investors often use bond ratings to evaluate investments - a bond is considered investment grade if it's BBB- or higher. To adequately price bonds and evaluate risk, there are too many factors to simply refer to a chart because things like the issuer, credit quality, liquidity risk, systematic risk, and unsystematic risk all play a factor. Another factor you have to consider is the overall portfolio. Markowitz showed that adding a riskier asset can actually lower the overall risk of a portfolio because of diversification. This is all under the assumption that risk = variance, which I think is bunk. I'm aware that Wall Street is nothing like roulette, but then again there must be some math and heavy economics behind calculating risk for individual investors. This is, after all, what \"\"quants\"\" are paid to do, in part. Is it all voodoo? I suspect some of it is, but not all of it. Quants are often involved in high frequency trading as well, but that's another note. There are complicated risk management products, such as the Aladdin system by BlackRock, which incorporate modern portfolio theory (Markowitz, Fama, Sharpe, Samuelson, etc) and financial formulas to manage risk. Crouhy's Risk Management covers some of the concepts applied. I also tend to think that when people point to the last x number of years of stock market performance, that is of less value than they expect. Even going back to 1900 provides \"\"only\"\" 110 years of data, and in my view, complex systems need more data than those 40,500 data points. 10,000 years' worth of data, ok, but not 110. Any books or articles that address these issues, or your own informed views, would be helfpul. I fully agree with you here. A lot of work is done in the Santa Fe Institute to study \"\"complex adaptive systems,\"\" and we don't have any big, clear theory as of yet. Conventional risk management is based on the ideas of modern portfolio theory, but a lot of that is seen to be wrong. Behavioral finance is introducing new ideas on how investors behave and why the old models are wrong, which is why I cannot suggest you study risk management and risk models because I and many skilled investors consider them to be largely wrong. There are many good books on investing, the best of which is Benjamin Graham's The Intelligent Investor. Although not a book on risk solely, it provides a different viewpoint on how to invest and covers how to protect investments via a \"\"Margin of Safety.\"\" Lastly, I'd recommend Against the Gods by Peter Bernstein, which covers the history of risk and risk analysis. It's not solely a finance book but rather a fascinating historical view of risk, and it helps but many things in context. Hope it helps!\"", "title": "" }, { "docid": "93882", "text": "\"I hope a wall of text with citations qualifies as \"\"relatively easy.\"\" Many of these studies are worth quoting at length. Long story short, a great deal of research has found that actively-managed funds underperform market indexes and passively-managed funds because of their high turnover and higher fees, among other factors. Longer answer: Chris is right in stating that survivorship bias presents a problem for such research; however, there are several academic papers that address the survivorship problem, as well as the wider subject of active vs. passive performance. I'll try to provide a brief summary of some of the relevant literature. The seminal paper that started the debate is Michael Jensen's 1968 paper titled \"\"The Performance of Mutual Funds in the Period 1945-1964\"\". This is the paper where Jensen's alpha, the ubiquitous measure of the performance of mutual fund managers, was first defined. Using a dataset of 115 mutual fund managers, Jensen finds that The evidence on mutual fund performance indicates not only that these 115 mutual funds were on average not able to predict security prices well enough to outperform a buy-the-market-and-hold policy, but also that there is very little evidence that any individual fund was able to do significantly better than that which we expected from mere random chance. Although this paper doesn't address problems of survivorship, it's notable because, among other points, it found that managers who actively picked stocks performed worse even when fund expenses were ignored. Since actively-managed funds tend to have higher expenses than passive funds, the actual picture looks even worse for actively managed funds. A more recent paper on the subject, which draws similar conclusions, is Martin Gruber's 1996 paper \"\"Another puzzle: The growth in actively managed mutual funds\"\". Gruber calls it \"\"a puzzle\"\" that investors still invest in actively-managed funds, given that their performance on average has been inferior to that of index funds. He addresses survivorship bias by tracking funds across the entire sample, including through mergers. Since most mutual funds that disappear are merged into existing funds, he assumes that investors in a fund that disappear choose to continue investing their money in the fund that resulted from the merger. Using this assumption and standard measures of mutual fund performance, Gruber finds that mutual funds underperform an appropriately weighted average of the indices by about 65 basis points per year. Expense ratios for my sample averaged 113 basis points a year. These numbers suggest that active management adds value, but that mutual funds charge the investor more than the value added. Another nice paper is Mark Carhart's 1997 paper \"\"On persistence in mutual fund performance\"\" uses a sample free of survivorship bias because it includes \"\"all known equity funds over this period.\"\" It's worth quoting parts of this paper in full: I demonstrate that expenses have at least a one-for-one negative impact on fund performance, and that turnover also negatively impacts performance. ... Trading reduces performance by approximately 0.95% of the trade's market value. In reference to expense ratios and other fees, Carhart finds that The investment costs of expense ratios, transaction costs, and load fees all have a direct, negative impact on performance. The study also finds that funds with abnormally high returns last year usually have higher-than-expected returns next year, but not in the following years, because of momentum effects. Lest you think the news is all bad, Russ Wermer's 2000 study \"\"Mutual fund performance: An empirical decomposition into stock‐picking talent, style, transactions costs, and expenses\"\" provides an interesting result. He finds that many actively-managed mutual funds hold stocks that outperform the market, even though the net return of the funds themselves underperforms passive funds and the market itself. On a net-return level, the funds underperform broad market indexes by one percent a year. Of the 2.3% difference between the returns on stock holdings and the net returns of the funds, 0.7% per year is due to the lower average returns of the nonstock holdings of the funds during the period (relative to stocks). The remaining 1.6% per year is split almost evenly between the expense ratios and the transaction costs of the funds. The final paper I'll cite is a 2008 paper by Fama and French (of the Fama-French model covered in business schools) titled, appropriately, \"\"Mutual Fund Performance\"\". The paper is pretty technical, and somewhat above my level at this time of night, but the authors state one of their conclusions bluntly quite early on: After costs (that is, in terms of net returns to investors) active investment is a negative sum game. Emphasis mine. In short, expense ratios, transaction costs, and other fees quickly diminish the returns to active investment. They find that The [value-weight] portfolio of mutual funds that invest primarily in U.S. equities is close to the market portfolio, and estimated before fees and expenses, its alpha is close to zero. Since the [value-weight] portfolio of funds produces an α close to zero in gross returns, the alpha estimated on the net returns to investors is negative by about the amount of fees and expenses. This implies that the higher the fees, the farther alpha decreases below zero. Since actively-managed mutual funds tend to have higher expense ratios than passively-managed index funds, it's safe to say that their net return to the investor is worse than a market index itself. I don't know of any free datasets that would allow you to research this, but one highly-regarded commercial dataset is the CRSP Survivor-Bias-Free US Mutual Fund Database from the Center for Research in Security Prices at the University of Chicago. In financial research, CRSP is one of the \"\"gold standards\"\" for historical market data, so if you can access that data (perhaps for a firm or academic institution, if you're affiliated with one that has access), it's one way you could run some numbers yourself.\"", "title": "" }, { "docid": "365295", "text": "\"Tricky question, basically, you just want to first spread risk around, and then seek abnormal returns after you understand what portions of your portfolio are influenced by (and understand your own investment goals) For a relevant timely example: the German stock exchange and it's equity prices are reaching all time highs, while the Greek asset prices are reaching all time lows. If you just invested in \"\"Europe\"\" your portfolio will experience only the mean, while suffering from exchange rate changes. You will likely lose because you arbitrarily invested internationally, for the sake of being international, instead of targeting a key country or sector. Just boils down to more research for you, if you want to be a passive investor you will get passive investor returns. I'm not personally familiar with funds that are good at taking care of this part for you, in the international markets.\"", "title": "" }, { "docid": "370290", "text": "\"Both explanations are partly true. There are many investors who do not want to sell an asset at a loss. This causes \"\"resistance\"\" at prices where large amounts of the asset were previously traded by such investors. It also explains why a \"\"break-through\"\" of such a \"\"resistance\"\" is often associated with a substantial \"\"move\"\" in price. There are also many investors who have \"\"stop-loss\"\" or \"\"trailing stop-loss\"\" \"\"limit orders\"\" in effect. These investors will automatically sell out of a long position (or buy out of a short position) if the price drops (or rises) by a certain percentage (typically 8% - 10%). There are periods of time when money is flowing into an asset or asset class. This could be due to a large investor trying to quietly purchase the asset in a way that avoids raising the price earlier than necessary. Or perhaps a large investor is dollar-cost-averaging. Or perhaps a legal mandate for a category of investors has changed, and they need to rebalance their portfolios. This rebalancing is likely to take place over time. Or perhaps there is a fad where many small investors (at various times) decide to increase (or decrease) their stake in an asset class. Or perhaps (for demographic reasons) the number of investors in a particular situation is increasing, so there are more investors who want to make particular investments. All of these phenomena can be summarized by the word \"\"momentum\"\". Traders who use technical analysis (including most day traders and algorithmic speculators) are aware of these phenomena. They are therefore more likely to purchase (or sell, or short) an asset shortly after one of their \"\"buy signals\"\" or \"\"sell signals\"\" is triggered. This reinforces the phenomena. There are also poorly-understood long-term cycles that affect business fundamentals and/or the politics that constrain business activity. For example: Note that even if the markets really were a random walk, it would still be profitable (and risk-reducing) to perform dollar-cost-averaging when buying into a position, and also perform averaging when selling out of a position. But this means that recent investor behavior can be used to predict the near-future behavior of investors, which justifies technical analysis.\"", "title": "" }, { "docid": "526422", "text": "\"The question is asking for a European equivalent of the so-called \"\"Couch Potato\"\" portfolio. \"\"Couch Potato\"\" portfolio is defined by the two URLs provided in question as, Criteria for fund composition Fixed-income: Regardless of country or supra-national market, the fixed-income fund should have holdings throughout the entire length of the yield curve (most available maturities), as well as being a mix of government, municipal (general obligation), corporate and high-yield bonds. Equity: The common equity position should be in one equity market index fund. It shouldn't be a DAX-30 or CAC-40 or DJIA type fund. Instead, you want a combination of growth and value companies. The fund should have as many holdings as possible, while avoiding too much expense due to transaction costs. You can determine how much is too much by comparing candidate funds with those that are only investing in highly liquid, large company stocks. Why it is easier for U.S. and Canadian couch potatoes It will be easier to find two good funds, at lower cost, if one is investing in a country with sizable markets and its own currency. That's why the Couch Potato strategy lends itself most naturally to the U.S.A, Canada, Japan and probably Australia, Brazil, South Korea and possibly Mexico too. In Europe, pre-EU, any of Germany, France, Spain, Italy or the Scandinavian countries would probably have worked well. The only concern would be (possibly) higher equity transactions costs and certainly larger fixed-income buy-sell spreads, due to smaller and less liquid markets other than Germany. These costs would be experienced by the portfolio manager, and passed on to you, as the investor. For the EU couch potato Remember the criteria, especially part 2, and the intent as described by the Couch Potato name, implying extremely passive investing. You want to choose two funds offered by very stable, reputable fund management companies. You will be re-balancing every six months or a year, only. That is four transactions per year, maximum. You don't need a lot of interaction with anyone, but you DO need to have the means to quickly exit both sides of the trade, should you decide, for any reason, that you need the money or that the strategy isn't right for you. I would not choose an ETF from iShares just because it is easy to do online transactions. For many investors, that is important! Here, you don't need that convenience. Instead, you need stability and an index fund with a good reputation. You should try to choose an EU based fund manager, or one in your home country, as you'll be more likely to know who is good and who isn't. Don't use Vanguard's FTSE ETF or the equivalent, as there will probably be currency and foreign tax concerns, and possibly forex risk. The couch potato strategy requires an emphasis on low fees with high quality funds and brokers (if not buying directly from the fund). As for type of fund, it would be best to choose a fund that is invested in mostly or only EU or EEU (European Economic Union) stocks, and the same for bonds. That will help minimize your transaction costs and tax liability, while allowing for the sort of broad diversity that helps buy and hold index fund investors.\"", "title": "" }, { "docid": "61518", "text": "\"Your assertion that you will not be selling anything is at odds with the idea that you will be doing tax loss harvesting. Tax loss harvesting always involves some selling (you sell stocks that have fallen in price and lock in the capital losses, which gives you a break on your taxes). If you absolutely prohibit your advisor from selling, then you will not be able to do tax loss harvesting (in that case, why are you using an advisor at all?). Tax loss harvesting has nothing to do with your horizon nor the active/passive difference, really. As a practical matter, a good tax loss harvesting plan involves mechanically selling losers and immediately putting the money in another stock with more-or-less similar risk so your portfolio doesn't change much. In this way you get a stable portfolio that performs just like a static portfolio but gives you a tax benefit each year. The IRS officially prohibits this practice via the \"\"wash sale rule\"\" that says you can't buy a substantially identical asset within a short period of time. However, though two stocks have similar risk, they are not generally substantially similar in a legal sense, so the IRS can't really beat you in court and they don't try. Basically you can't just buy the same stock again. The roboadvisor is advertising that they will perform this service, keeping your portfolio pretty much static in terms of risk, in such a way that your tax benefit is maximized and you don't run afoul of the IRS.\"", "title": "" }, { "docid": "291830", "text": "\"You're right, the asset allocation is one fundamental thing you want to get right in your portfolio. I agree 110%. If you really want to understand asset allocation, I suggest any and all of the following three books, all by the same author, William J. Bernstein. They are excellent – and yes I've read each. From a theory perspective, and being about asset allocation specifically, the Intelligent Asset Allocator is a good choice. Whereas, the next two books are more accessible and more complete, covering topics including investor psychology, history, financial products you can use to implement a strategy, etc. Got the time? Read them all. I finished reading his latest book, The Investor's Manifesto, two weeks ago. Here are some choice quotes from Chapter 3, \"\"The Nature of the Portfolio\"\", that address some of the points you've asked about. All emphasis below is mine. Page 74: The good news is [the asset allocation process] is not really that hard: The investor only makes two important decisions: Page 76: Rather, younger investors should own a higher portion of stocks because they have the ability to apply their regular savings to the markets at depressed prices. More precisely, young investors possess more \"\"human capital\"\" than financial capital; that is, their total future earnings dwarf their savings and investments. From a financial perspective, human capital looks like a bond whose coupons escalate with inflation.   Page 78: The most important asset allocation decision is the overall stock/bind mix; start with age = bond allocation rule of thumb. [i.e. because the younger you are, you already have bond-like income from anticipated employment earnings; the older you get, the less bond-like income you have in your future, so buy more bonds in your portfolio.] He also mentions adjusting that with respect to one's risk tolerance. If you can't take the ups-and-downs of the market, adjust the stock portion down (up to 20% less); if you can stomach the risk without a problem, adjust the stock portion up (up to 20% more). Page 86: [in reference to a specific example where two assets that zig and zag are purchased in a 50/50 split and adjusted back to targets]   This process, called \"\"rebalancing,\"\" provides the investor with an automatic buy-low/sell-high bias that over the long run usually – but not always – improves returns. Page 87: The essence of portfolio construction is the combination of asset classes that move in different directions at least some of the time. Finally, this gem on pages 88 and 89: Is there a way of scientifically picking the very best future allocation, which offers the maximum return for the minimum risk? No, but people still try.   [... continues with description of Markowitz's \"\"mean-variance analysis\"\" technique...]   It took investment professionals quite a while to realize that limitation of mean-variance analysis, and other \"\"black box\"\" techniques for allocating assets. I could go on quoting relevant pieces ... he even goes into much detail on constructing an asset allocation suitable for a large portfolio containing a variety of different stock asset classes, but I suggest you read the book :-)\"", "title": "" }, { "docid": "231195", "text": "I am not interested in watching stock exchange rates all day long. I just want to place it somewhere and let it grow Your intuition is spot on! To buy & hold is the sensible thing to do. There is no need to constantly monitor the stock market. To invest successfully you only need some basic pointers. People make it look like it's more complicated than it actually is for individual investors. You might find useful some wisdom pearls I wish I had learned even earlier. Stocks & Bonds are the best passive investment available. Stocks offer the best return, while bonds are reduce risk. The stock/bond allocation depends of your risk tolerance. Since you're as young as it gets, I would forget about bonds until later and go with a full stock portfolio. Banks are glorified money mausoleums; the interest you can get from them is rarely noticeable. Index investing is the best alternative. How so? Because 'you can't beat the market'. Nobody can; but people like to try and fail. So instead of trying, some fund managers simply track a market index (always successfully) while others try to beat it (consistently failing). Actively managed mutual funds have higher costs for the extra work involved. Avoid them like the plague. Look for a diversified index fund with low TER (Total Expense Ratio). These are the most important factors. Diversification will increase safety, while low costs guarantee that you get the most out of your money. Vanguard has truly good index funds, as well as Blackrock (iShares). Since you can't simply buy equity by yourself, you need a broker to buy and sell. Luckily, there are many good online brokers in Europe. What we're looking for in a broker is safety (run background checks, ask other wise individual investors that have taken time out of their schedules to read the small print) and that charges us with low fees. You probably can do this through the bank, but... well, it defeats its own purpose. US citizens have their 401(k) accounts. Very neat stuff. Check your country's law to see if you can make use of something similar to reduce the tax cost of investing. Your government will want a slice of those juicy dividends. An alternative is to buy an index fund on which dividends are not distributed, but are automatically reinvested instead. Some links for further reference: Investment 101, and why index investment rocks: However the author is based in the US, so you might find the next link useful. Investment for Europeans: Very useful to check specific information regarding European investing. Portfolio Ideas: You'll realise you don't actually need many equities, since the diversification is built-in the index funds. I hope this helps! There's not much more, but it's all condensed in a handful of blogs.", "title": "" }, { "docid": "589088", "text": "\"Some of the other answers recommended peer-to-peer lending and property markets. I would not invest in either of these. Firstly, peer-to-peer lending is not a traditional investment and we may not have enough historical data for the risk-to-return ratio. Secondly, property investments have a great risk unless you diversify, which requires a huge portfolio. Crowd-funding for one property is not a traditional investment, and may have drawbacks. For example, what if you disagree with other crowd-funders about the required repairs for the property? If you invest in the property market, I recommend a well-diversified fund that owns many properties. Beware of high debt leverage used to enhance returns (and, at the same time, risk) and high fees when selecting a fund. However, traditionally it has been a better choice to invest in stocks than to invest in property market. Beware of anyone who says that the property market is \"\"too good to not get into\"\" without specifying which part of the world is meant. Note also that many companies invest in properties, so if you invest only in a well-diversified stock index fund, you may already have property investments in your portfolio! However, in your case I would keep the money in risk-free assets, i.e. bank savings or a genuine low-cost money market fund (i.e. one that doesn't invest in corporate debt or in variable-rate loans which have short duration but long maturity). The reason is that you're going to be unemployed soon, and thus, you may need the money soon. If you have an investment horizon of, say, 10 years, then I would throw stocks into the mix, and if you're saving for retirement, then I would go all in to stocks. In the part of the world where I live in, money market funds generally have better return than bank savings, and better diversification too. However, your 2.8% interest sounds rather high (the money market fund I have in the past invested in currently yields at 0.02%, but then again I live in the eurozone), so be sure to get estimates for the yields of different risk-free assets. So, my advice for investing is simple: risk-free assets for short time horizon, a mixture of stocks and risk-free assets for medium time horizon, and only stocks for long time horizon. In any case, you need a small emergency fund, too, which you should consider a thing separate from your investments. My emergency fund is 20 000 EUR. Your 50 000 AUD is bit more than 30 000 EUR, so you don't really have that much money to invest, only a bit more than a reasonably sized emergency fund. But then again, I live in rental property, so my expenses are probably higher than yours. If you can foresee a very long time horizon for part of your investment, you could perhaps invest 50% of your money to stocks (preference being a geographically diversified index fund or a number of index funds), but I wouldn't invest more because of the need for an emergency fund.\"", "title": "" }, { "docid": "357232", "text": "I think you're missing Simon Moore's point. His point is that, due to low inflation, the returns on almost all asset classes should be less than they have been historically, so we shouldn't rebalance our portfolio or withdraw from the market and hold cash based on the assumption that stocks (or any other asset) seem to be underperforming relative to historical trends. His last paragraph is written in case someone might misunderstand him, he is not advocating to hold cash, just that investors should not expect as good returns as has happened historically, since those happened in higher inflation environments. To explain: If the inflation rate historically has been 5% and now it's 2%, and the risk-free-market return should be about 2%, then historically the return on a risk-free asset would be 7% (2%+5%), and now it should be expected to be 4% (2%+2%). So, if you have had a portfolio over some time you might be concerned that the rate of return is worsening, but Simon's point is that before you sell off your stocks / switch investment brokers, you should try to figure out if inflation is the cause of the performance loss. On the subject of cash: cash always loses value over time from inflation, since inflation is a measure of the increase in prices over time-- it's a part of the definition of what inflation is. That said, cash holdings lose value more slowly when inflation is lower, so they are relatively less worse than before. The future value of cash doesn't go up in low inflation (you'd need deflation for that), it just decreases at a lower rate, that is, it becomes less expensive to hold- but there still is a price. As an addendum, unless a completely new economic paradigm is adopted by world leaders, we will always see cash holdings decrease in value over time, since modern economics holds that deflation is one of the worst things that can happen to an economy.", "title": "" }, { "docid": "307409", "text": "\"JoeTaxpayer's advice is solid - reallocating to your target asset allocation is the right move. You should have an Investor Policy Statement (IPS) that maps out your financial objectives, risk tolerance, liquidity constraints, etc. From the IPS, you can determine your target asset allocation and rebalance accordingly. A few more comments: It sounds like 100% of your 401k is in US stocks. You might have other accounts that make your overall portfolio globally diversified, but if not, you want to make sure to set a target asset allocation for a global portfolio. Your statement \"\"If this were in my brokerage account I'd probably cash out some of the profits and hold onto it and buy more shares as the market eventually comes back down. But this being a 401k which has semi-monthly deposits from my paycheck, do I just leave it?\"\" is a bit counterintuitive. If you are going to try to time the market (a very hard task), it is better to use a retirement account, so you don't have to realize capital gains. Timing the market is probably a bad idea, but if you engage in market timing, it is probably better to use a retirement account than a brokerage account. If you would like to tilt your asset allocation based on the market valuation, I recommend researching Shiller's Cyclically Adjusted Price to Earnings ratio.\"", "title": "" }, { "docid": "414205", "text": "\"they said the expected returns from the stock market are around 7-9%(ish). (emphasis added) The key word in your quote is expected. On average \"\"the market\"\" gains in the 7-9% range (more if you reinvest dividends), but there's a great deal of risk too, meaning that in any given year the market could be down 20% or be up 30%. Your student loan, on the other hand, is risk free. You are guaranteed to pay (lose) 4% a year in interest. You can't directly compare the expected return of a risk-free asset with the expected return of a risky asset. You can compare the risks of two assets with equal expected returns, and the expected returns of assets with equal risks, but you can't directly compare returns of assets with different risks. So in two years, you might be better off if you had invested the money versus paying the loan, or you might be much worse off. In ten years, your chances of coming out ahead are better, but still not guaranteed. What's confusing is I've heard that if you're investing, you should be investing in both stocks and bonds (since I'm young I wouldn't want to put much in bonds, though). So how would that factor in? Bonds have lower risk (uncertainty) than stocks, but lower expected returns. If you invest in both, your overall risk is lower, since sometimes (not always) the gain in stocks are offset by losses in bonds). So there is value in diversifying, since you can get better expected returns from a diversified portfolio than from a single asset with a comparable amount of risk. However, there it no risk-free asset that will have a better return than what you're paying in student loan interest.\"", "title": "" } ]
PLAIN-2802
Cancer, Interrupted: Green Tea
[ { "docid": "MED-4071", "text": "An increased risk of breast cancer has been observed in women who consume \"very well-done\" meats. Heterocyclic amines are mutagenic and carcinogenic pyrolysis products formed during high temperature cooking of meats. In the present study, human milk samples were analyzed for PhIP, one of the most abundant dietary heterocyclic amine. A protocol was developed with a mixed-mode cation exchange sorbent for the extraction of heterocyclic amines from milk. Milk samples were acquired from healthy Canadian women. With LC/MS analysis and the method of isotope dilution for quantification, levels of PhIP were determined in human milk samples. PhIP was detected in 9 of the 11 milk samples, at levels as high as 59 pg/mL (ppt). No PhIP was detected in the milk of the vegetarian donor. Detection of PhIP in milk indicates that ductal mammary epithelial cells are directly exposed to this carcinogen, suggesting that heterocyclic amines are possible human mammary carcinogens.", "title": "Detection of PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) in the milk of healthy women." }, { "docid": "MED-5116", "text": "BACKGROUND: Laboratory research and a growing number of epidemiologic studies have provided evidence for a reduced risk of breast cancer associated with dietary intake of certain classes of flavonoids. However, the effects of flavonoids on survival are not known. In a population-based cohort of breast cancer patients, we investigated whether dietary flavonoid intake before diagnosis is associated with subsequent survival. METHODS: Women ages 25 to 98 years who were newly diagnosed with a first primary invasive breast cancer between August 1, 1996, and July 31, 1997, and participated in a population-based, case-control study (n=1,210) were followed for vital status through December 31, 2002. At the case-control interview conducted shortly after diagnosis, respondents completed a FFQ that assessed dietary intake in the previous 12 months. All-cause mortality (n=173 deaths) and breast cancer-specific mortality (n=113 deaths) were determined through the National Death Index. RESULTS: Reduced hazard ratios [age- and energy-adjusted hazard ratio (95% confidence interval)] for all-cause mortality were observed among premenopausal and postmenopausal women for the highest quintile of intake, compared with the lowest, for flavones [0.63 (0.41-0.96)], isoflavones [0.52 (0.33-0.82)], and anthocyanidins [0.64 (0.42-0.98)]. No significant trends in risk were observed. Results were similar for breast cancer-specific mortality only. CONCLUSION: Mortality may be reduced in association with high levels of dietary flavones and isoflavones among postmenopausal U.S. breast cancer patients. Larger studies are needed to confirm our findings.", "title": "Dietary flavonoid intake and breast cancer survival among women on Long Island." }, { "docid": "MED-4051", "text": "The food mutagens IQ (2-amino-3-methylimidazo[4,5-f]quinoline) and PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) are heterocyclic amines (HCA), generated when heating proteinaceous food. This study investigates the protective potential of the flavonoids quercetin (Q) and rutin (R) against oxidative stress induced in vitro by IQ and PhIP in lymphocytes from healthy individuals and untreated, newly diagnosed colon cancer patients using the Comet assay. In the presence of up to 500μM Q and R, the DNA damage resulting from a high dose of PhIP (75μM) or IQ (150μM) was significantly reduced (P<0.001) to levels comparable to six times lower IQ or 7.5 times lower PhIP doses. Lymphocytes from colon cancer patients had greater baseline DNA damage than those from healthy individuals (P<0.01) and this higher level of damage was also observed throughout in vitro treatment. Except for the >50years of age group and male gender, confounding factors such as smoking, drinking and/or dietary habits were not found to be significant. In conclusion, flavonoids reduced oxidative stress caused by food mutagens in vitro in lymphocytes of healthy individuals and colon cancer patients. Thus, dietary supplementation with flavonoid-rich vegetables and fruits may prove very effective in protecting against oxidative stress. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "The protective effect of the flavonoids on food-mutagen-induced DNA damage in peripheral blood lymphocytes from colon cancer patients." }, { "docid": "MED-4058", "text": "A facile method was established to measure heterocyclic aromatic amines (HAAs) accumulated in human hair and rodent fur. The samples were digested by base hydrolysis, and the liberated HAAs were isolated by tandem solvent/solid-phase extraction. Quantification was done by liquid chromatography/tandem mass spectrometry, using a triple stage quadrupole mass spectrometer in the selected reaction monitoring mode. In a pilot study of 12 human volunteers, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was detected in hair of six meat-eaters at levels ranging from 290 to 890 pg/g hair. 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-9H-pyrido[2,3-b]indole (AαC) were below the limit of quantification (LOQ) (50 pg/g hair) in hair from meat-eaters and six vegetarians. PhIP was detected in the hair from one vegetarian, and at level just above the LOQ (65 pg/g hair), indicating PhIP exposure occurs primarily through meat consumption. The levels of PhIP in hair samples from two meat-eaters varied by less than 24% over a 6-month interval, signifying that the exposure to PhIP and its accumulation in hair are relatively constant over time. In a controlled feeding study, female C57BL/6 mice were given these HAAs in their drinking water for 1 month, at six daily dose concentrations ranging from 0, 0.080 to 800 µg/kg body weight. PhIP was detected in fur of mice at all doses, whereas AαC and MeIQx were detected in fur at dosages ≥0.8 µg AαC/kg body weight and ≥8 µg MeIQx/kg body weight. There was a strong positive relationship between dosage and each of the HAAs accumulated in fur and their DNA adducts formed in liver and colon (p-values <0.0001); however, the levels of HAA in fur did not correlate to the levels of DNA adducts after adjustment of dose. Thus, hair appears to be a promising long-lived biomarker with by which we can assess the exposure to PhIP, a potential human carcinogen.", "title": "Biomonitoring of Carcinogenic Heterocyclic Aromatic Amines in Hair: A Validation Study" }, { "docid": "MED-4047", "text": "The total phenolic contents and antioxidant activities of garlics from California, Oregon, Washington, and New York were determined by Fourier transform infrared (FT-IR) spectroscopy (400-4000 cm(-1)). The total phenolic content was quantified [Folin-Ciocalteu assay (FC)] and three antioxidant activity assays, 2,2-diphenyl-picrylhydrazyl (DPPH) assay, Trolox equivalent antioxidant capacity (TEAC) assay, and ferric reducing antioxidant power (FRAP), were employed for reference measurements. Four independent partial least-squares regression (PLSR) models were constructed with spectra from 25 extracts and their corresponding FC, DPPH, TEAC, and FRAP with values for 20 additional extracts predicted (R > 0.95). The standard errors of calibration and standard error of cross-validation were <1.45 (TEAC), 0.36 (FRAP), and 0.33 μmol Trolox/g FW (DPPH) and 0.55 mg gallic acid/g FW (FC). Cluster and dendrogram analyses could segregate garlic grown at different locations. Hydroxyl and phenolic functional groups most closely correlated with garlic antioxidant activity.", "title": "Determination of total phenolic content and antioxidant activity of garlic (Allium sativum) and elephant garlic (Allium ampeloprasum) by attenuated..." }, { "docid": "MED-4068", "text": "The cooked meat derived genotoxic carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induces cancer of the colon, prostate and mammary gland when fed to rats. Epidemiology studies link these tumours to a Western diet and exposure to heterocyclic amines such as PhIP. We have shown that PhIP is also potently estrogenic and have proposed that this hormonal activity contributes to its target site carcinogenicity. We now postulate that the estrogenic properties of PhIP influence metastatic potential. We have used an in vitro assay for cell invasion based upon digestion and migration through a reconstituted basement membrane model. Zymography and immunoblotting were used to confirm PhIP-mediated changes associated with induction of the invasive phenotype. Treatment of the mammary cancer cell lines MCF-7 and T47D with PhIP induces cells to digest and migrate through a reconstituted basement membrane. The response was dose dependent, observed at sub-nanomolar concentrations of PhIP and was inhibited by the antiestrogen ICI 182,780. The PhIP-induced invasive phenotype was associated with expression of cathepsin D, cyclooxygenase-2 and matrix metalloproteinase activity. These findings emphasise the range and potency of the biological activities associated with this cooked meat product and mechanistically support the tissue-specific carcinogenicity of the chemical. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.", "title": "The cooked meat-derived mammary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine promotes invasive behaviour of breast cancer cells." }, { "docid": "MED-4057", "text": "BACKGROUND: Heterocyclic amines, mutagens formed in meats cooked at high temperatures, have been demonstrated as mammary carcinogens in animals. We conducted a nested, case-control study among 41836 cohort members of the Iowa Women's Health Study to evaluate the potential role of heterocyclic amines and intake of well-done meat in the risk for human breast cancer. METHODS: A questionnaire was mailed to individuals in the cohort who had breast cancer diagnosed during the period from 1992 through 1994 and a random sample of cancer-free cohort members to obtain information on usual intake of meats and on meat preparation practices. Color photographs showing various doneness levels of hamburger, beefsteak, and bacon were included. Multivariate analysis was performed on data from 273 case subjects and 657 control subjects who completed the survey. RESULTS: A dose-response relationship was found between doneness levels of meat consumed and breast cancer risk. The adjusted odds ratios (ORs) for very well-done meat versus rare or medium-done meat were 1.54 (95% confidence interval [CI]=0.96-2.47) for hamburger, 2.21 (95% CI=1.30-3.77) for beef steak, and 1.64 (95% CI=0.92-2.93) for bacon. Women who consumed these three meats consistently very well done had a 4.62 times higher risk (95% CI=1.36-15.70) than that of women who consumed the meats rare or medium done. Risk of breast cancer was also elevated with increasing intake of well-done to very well-done meat. CONCLUSIONS: Consumption of well-done meats and, thus, exposures to heterocyclic amines (or other compounds) formed during high-temperature cooking may play an important role in the risk of breast cancer.", "title": "Well-done meat intake and the risk of breast cancer." }, { "docid": "MED-4332", "text": "There is growing interest in the potential health benefits of tea, including the antimutagenic properties. Four varieties of white tea, which represent the least processed form of tea, were shown to have marked antimutagenic activity in the Salmonella assay, particularly in the presence of S9. The most active of these teas, Exotica China white tea, was significantly more effective than Premium green tea (Dragonwell special grade) against 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and four other heterocyclic amine mutagens, namely 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline (4,8-DiMeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). Mechanism studies were performed using rat liver S9 in assays for methoxyresorufin O-demethylase (MROD), a marker for the enzyme cytochrome P4501A2 that activates heterocyclic amines, as well as Salmonella assays with the direct-acting mutagen 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline (N-hydroxy-IQ). White tea at low concentrations in the assay inhibited MROD activity, and attenuated the mutagenic activity of N-hydroxy-IQ in the absence of S9. Nine of the major constituents found in green tea also were detected in white tea, including high levels of epigallocatechin-3-gallate (EGCG) and several other polyphenols. When these major constituents were mixed to produce \"artificial\" teas, according to their relative levels in white and green teas, the complete tea exhibited higher antimutagenic potency compared with the corresponding artificial tea. The results suggest that the greater inhibitory potency of white versus green tea in the Salmonella assay might be related to the relative levels of the nine major constituents, perhaps acting synergistically with other (minor) constituents, to inhibit mutagen activation as well as \"scavenging\" the reactive intermediate(s).", "title": "Potent antimutagenic activity of white tea in comparison with green tea in the Salmonella assay." }, { "docid": "MED-4073", "text": "The cooked meat carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induces tumours of the breast, colon and prostate in rats. Here we show that in addition to its well-established genotoxicity, which can be detected at concentrations >10(-6) M, PhIP is also oestrogenic. In COS-1 cells transiently transfected with an oestrogen-responsive reporter gene, PhIP (10(-10)-10(-6) M) mediated transcription through oestrogen receptor (ER) alpha, but not ER-beta, and inhibition by the pure ER antagonist ICI 182 780 demonstrated a requirement for a functional ER. In contrast, the structurally related food-derived carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) failed to induce reporter gene transcription. Additionally, we show that in a hormonally responsive breast cancer cell line (MCF-7 cells), PhIP induced transcriptional activation using endogenously expressed ER. Examination of the genotoxic potential of PhIP using a model mammalian cell mutation assay (hprt(-) locus) demonstrated that the genetic toxicology of PhIP was readily detectable, but separate, in terms of effective concentration, from its oestrogenic activity. To determine whether the oestrogenicity of PhIP could mediate oestrogen-dependent responses such as cell growth, we examined the growth of hormonally responsive cells (MCF-7 cells). We show that PhIP can stimulate cell proliferation and, again, this was dependent upon a functional ER. Using ligand blotting, we further show that PhIP can stimulate the expression of progesterone receptor (PR-A and PR-B) and c-MYC and activate the MAPK signal transduction pathway. These responses were similar to that produced by oestradiol, in terms of temporal aspects, potency and a requirement for a functional ER. Each of these dose-dependent mitogenic responses occurred at concentrations of PhIP ( approximately 10(-9)-10(-11)M) that are likely to be equivalent to systemic human exposure via consumption of cooked meat. Thus PhIP can induce cellular responses that encompass altered gene expression and mitogenesis. We suggest that the combination of genetic toxicology and oestrogen-like promotion of genomic and cellular events provide a mechanism for the tissue-specific tumorigenicity of this compound.", "title": "The cooked food derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine is a potent oestrogen: a mechanistic basis for its tissue-speci..." }, { "docid": "MED-4060", "text": "Heteroyclic aromatic amines (HAAs) are a class of hazardous chemicals that are receiving heightened attention as a risk factor for human cancer. HAAs arise during the cooking of meats, fish, and poultry, and several HAAs also occur in tobacco smoke condensate and diesel exhaust. Many HAAs are carcinogenic and induce tumors at multiple sites in rodents. A number of epidemiologic studies have reported that frequent consumption of well-done cooked meats containing HAAs can result in elevated risks for colon, prostate, and mammary cancers. Moreover, DNA adducts of HAAs have been detected in human tissues, demonstrating that HAAs induce genetic damage even though the concentrations of these compounds in cooked meats are generally in the low parts-per-billion (ppb) range. With recent improvements in sensitivity of mass spectrometry instrumentation, HAAs, their metabolites, and DNA adducts can be detected at trace amounts in biological fluids and tissues of humans. The incorporation of HAA biomarkers in epidemologic studies will help to clarify the role of these dietary genotoxicants in the etiology of human cancer.", "title": "Formation and biochemistry of carcinogenic heterocyclic aromatic amines in cooked meats." }, { "docid": "MED-4069", "text": "To examine whether meat intake modifies breast-cancer risk, a case-control study was conducted in Uruguay. Dietary patterns were assessed in detail (for cases, before diagnosis or symptoms occurred) using a food frequency questionnaire involving 64 food items, which allowed total energy intake to be calculated. Nutrient residuals were calculated through regression analysis. After adjustment for potential confounders (which included family history of breast cancer, menopausal status, body-mass index, total energy and total alcohol intake), an increased risk associated with consumption of total meat intake, red meat intake, total fat and saturated fat intake was observed. The strongest effect was observed for red meat intake (OR 4.2, 95% CL 2.3-7.7) for consumption in the upper quartile, after controlling for protein and fat intake. This suggests an independent effect for meat. Since experimental studies have shown a strong effect of heterocyclic amines in rat mammary carcinogenesis, further studies should be performed in human epidemiology, perhaps using biomarkers of heterocyclic amine exposure.", "title": "Meat, fat and risk of breast cancer: a case-control study from Uruguay." }, { "docid": "MED-4050", "text": "Green tea is a commonly consumed beverage in Asia and has been suggested to have anti-inflammatory and possible anti-carcinogenic properties in laboratory studies. We sought to examine the association between green tea consumption and risk of breast cancer incidence or recurrence, using all available epidemiologic evidence to date. We conducted a systematic search of five databases and performed a meta-analysis of studies of breast cancer risk and recurrence published between 1998 and 2009, encompassing 5,617 cases of breast cancer. Summary relative risks (RR) were calculated using a fixed effects model, and tests of heterogeneity across combined studies were conducted. We identified two studies of breast cancer recurrence and seven studies of breast cancer incidence. Increased green tea consumption (more than three cups a day) was inversely associated with breast cancer recurrence (Pooled RR = 0.73, 95% CI: 0.56-0.96). An analysis of case-control studies of breast cancer incidence suggested an inverse association with a pooled RR of 0.81 (95% CI: 0.75, 0.88) while no association was found among cohort studies of breast cancer incidence. Combining all studies of breast cancer incidence resulted in significant heterogeneity. Available epidemiologic evidence supports the hypothesis that increased green tea consumption may be inversely associated with risk of breast cancer recurrence. The association between green tea consumption and breast cancer incidence remains unclear based on the current evidence.", "title": "Green tea consumption and breast cancer risk or recurrence: a meta-analysis." }, { "docid": "MED-4329", "text": "We investigated clinical efficacy of green tea extracts (polyphenon E; poly E and (-)-epigallocatechin-3-gallate [EGCG]) delivered in a form of ointment or capsule in patients with human papilloma virus (HPV) infected cervical lesions. Fifty-one patients with cervical lesions (chronic cervicitis, mild dysplasia, moderate dysplasia and severe dysplasia) were divided into four groups, as compared with 39 untreated patients as a control. Poly E ointment was applied locally to 27 patients twice a week. For oral delivery, a 200 mg of poly E or EGCG capsule was taken orally every day for eight to 12 weeks. In the study, 20 out of 27 patients (74%) under poly E ointment therapy showed a response. Six out of eight patients under poly E ointment plus poly E capsule therapy (75%) showed a response, and three out of six patients (50%) under poly E capsule therapy showed a response. Six out of 10 patients (60%) under EGCG capsule therapy showed a response. Overall, a 69% response rate (35/51) was noted for treatment with green tea extracts, as compared with a 10% response rate (4/39) in untreated controls (P<0.05). Thus, the data collected here demonstrated that green tea extracts in a form of ointment and capsule are effective for treating cervical lesions, suggesting that green tea extracts can be a potential therapy regimen for patients with HPV infected cervical lesions.", "title": "Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions." }, { "docid": "MED-4070", "text": "It has been suggested that mutagens in fried meat may be involved in the cancer process. Therefore the relationships between intake of fried meat and subsequent risk of cancers at different sites were studied among 9,990 Finnish men and women, 15-99 years of age and initially free of cancer. The baseline study was carried out in 1966-1972, and cases of cancer were identified through data linkage with the Finnish Cancer Registry. During a 24-year follow-up, 853 cancer cases were diagnosed. The intake of fried meat was estimated from a dietary history interview covering the total diet of the participants during the previous year. There was a positive association between fried meat intake and the risk of female-hormone-related cancers, i.e., cancer of the breast, endometrium and ovary combined. The relative risk of these cancers combined between persons in the highest and lowest tertiles of daily intake of fried meat adjusted for age, personal characteristics and intake of other main food groups was 1.77 (95% confidence interval = 1.11-2.84). Pancreatic and nervous system cancers also presented non-significant suggestive associations. No associations were observed with respect to other single cancer sites studied or to all sites of cancer combined. Further epidemiological efforts are needed to ascertain the potential link between fried-food mutagens and cancer risk.", "title": "Intake of fried meat and risk of cancer: a follow-up study in Finland." }, { "docid": "MED-4075", "text": "Liquid chromatography electrospray ionization mass spectrometry (MS) with a triple quadrupole MS was used to identify known and novel heterocyclic aromatic amines (HAAs) in human urine. The identities of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were confirmed by their product ion spectra. The constant neutral loss scan mode was employed to probe for other analytes in urine that display the transition [M+H]+-->[M+H-CH3*]+*, which is common to HAAs containing an N-methylimidazo moiety, and led to the detection of a previously unreported isomer of 8-MeIQx [Holland, R., et al. (2004) Chem. Res. Toxicol. 17, 1121-1136]. We now report the identification of another novel HAA, 2-amino-1-methylimidazo[4,5-b]quinoline (IQ[4,5-b]), an isomer of the powerful animal carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). The amounts of IQ[4,5-b] measured in the urine of human volunteers who consumed grilled beef ranged from 15 to 135% of the ingested dose, while the amounts of 8-MeIQx and PhIP excreted in urine were on average <2% of the ingested dose. Base treatment of urine at 70 degrees C increased the concentrations of 8-MeIQx and PhIP by as much as 6-fold, indicating the presence of phase II conjugates; however, the amount of IQ[4,5-b] increased by more than 100-fold. IQ[4,5-b] was also detected in the urine of vegetarians following base hydrolysis. The formation of IQ[4,5-b], but not IQ, 8-MeIQx, or PhIP, also occurred in urine incubated at 37 degrees C. Creatinine and 2-aminobenzaldehyde are likely precursors of IQ[4,5-b]. The detection of IQ[4,5-b] in the urine of both meat eaters and vegetarians suggests that this HAA may be present in nonmeat staples or that IQ[4,5-b] formation may occur endogenously within the urinary bladder or other biological fluids.", "title": "Formation of a mutagenic heterocyclic aromatic amine from creatinine in urine of meat eaters and vegetarians." }, { "docid": "MED-4465", "text": "Adult stem cells of the mammary gland (MaSCs) are a highly dynamic population of cells that are responsible for the generation of the gland during puberty and its expansion during pregnancy. In recent years significant advances have been made in understanding how these cells are regulated during these developmentally important processes both in humans and in mice. Understanding how MaSCs are regulated is becoming a particularly important area of research, given that they may be particularly susceptible targets for transformation in breast cancer. Here, we summarize the identification of MaSCs, how they are regulated and the evidence for their serving as the origins of breast cancer. In particular, we focus on how changes in MaSC populations may explain both the increased risk of developing aggressive ER/PR(−) breast cancer shortly after pregnancy and the long-term decreased risk of developing ER/PR(+) tumors.", "title": "From milk to malignancy: the role of mammary stem cells in development, pregnancy and breast cancer" }, { "docid": "MED-4464", "text": "Over the last decade, the notion that tumors are maintained by their own stem cells, the so-called cancer stem cells, has created great excitement in the research community. This review attempts to summarize the underlying concepts of this notion, to distinguish hard facts from beliefs and to define the future challenges of the field.", "title": "The cancer stem cell: premises, promises and challenges." }, { "docid": "MED-4053", "text": "Heterocyclic amines (HCAs), potent mutagens and a risk factor for human cancers, are produced in meats cooked at high temperature. The aim of this study was to determine the HCA content in cooked meat products (beef, chicken, pork, fish) prepared by various cooking methods (pan frying, oven broiling, and oven baking at 170 to 230°C) that are preferred by U.S. meat consumers. The primary HCAs in these samples were PhIP (2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine) (1.49-10.89ng/g), MeIQx (2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline) (not detected-4.0ng/g), and DiMeIQx (2-amino-3,4,8-trimethyl-imidazo [4,5-f]quinoxaline) (not detected-3.57ng/g). Type and content of HCAs in cooked meat samples were highly dependent on cooking conditions. The total HCA content in well-done meat was 3.5 times higher than that of medium-rare meat. Fried pork (13.91ng/g) had higher levels of total HCAs than fried beef (8.92ng/g) and fried chicken (7.00ng/g). Among the samples, fried bacon contained the highest total HCA content (17.59ng/g). Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Occurrence of heterocyclic amines in cooked meat products." }, { "docid": "MED-4328", "text": "BACKGROUND: In April 2009, experts on sexually transmitted diseases (STDs) were convened to review updates on STD prevention and treatment in preparation for the revision of the Centers for Disease Control and Prevention (CDC) STD Treatment Guidelines. At this meeting, there was a discussion of important updates on human papillomavirus (HPV), genital warts, and cervical cancer screening. METHODS: Key questions were identified with assistance from an expert panel, and systematic reviews of the literature were conducted searching the English-language literature of the PubMed computerized database (US National Library of Medicine). The available evidence was reviewed, and new information was incorporated in the 2010 CDC STD Treatment Guidelines. RESULTS: Two HPV vaccines are now available, the quadrivalent HPV vaccine and the bivalent HPV vaccine; either vaccine is recommended routinely for girls aged 11 or 12 years. The quadrivalent HPV vaccine may be given to boys and men aged 9-26 years. A new patient-applied treatment option for genital warts, sinecatechins 15% ointment, is available and recommended for treatment of external genital warts. This product is a mixture of active ingredients (catechins) from green tea. Finally, updated counseling guidelines and messages about HPV, genital warts, and cervical cancer are included. CONCLUSIONS: This manuscript highlights updates to the 2010 CDC STD Treatment Guidelines for HPV and genital warts. Important additions to the 2010 STD Treatment Guidelines include information on prophylactic HPV vaccine recommendations, new patient-applied treatment options for genital warts, and counseling messages for patients on HPV, genital warts, cervical cancer screening, and HPV tests.", "title": "Updates on human papillomavirus and genital warts and counseling messages from the 2010 Sexually Transmitted Diseases Treatment Guidelines." }, { "docid": "MED-4059", "text": "2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic amine formed in meat and fish during cooking and can be used as a model compound for this class of chemicals possibly involved in human carcinogenesis. Knowing the exposure to heterocyclic amines is important for establishing their role in human diseases. Serum albumin (SA) and globin (Gb) adducts were first tested as biomarkers of exposure to PhIP in male Fischer 344 rats given oral doses of 0.1, 0.5, 1 and 10 mg/kg. Blood samples were collected 24 hr after treatment and PhIP released from SA and Gb after acidic hydrolysis was analyzed by gas chromatography-mass spectrometry or liquid chromatography-tandem mass spectrometry. PhIP-SA and Gb adducts increased linearly with the dose. Studies on 35 volunteers with different dietary habits exhibited that diet was a major determinant in the formation of both adducts. PhIP-SA adducts were significantly higher in meat consumers than in vegetarians (6.7 +/- 1.6 and 0.7 +/- 0.3 fmol/mg SA; respectively, mean +/- SE; p = 0.04, Mann-Whitney U test). The Gb adduct pattern was quantitatively lower but paralleled SA (3 +/- 0.8 in meat consumers and 0.3 +/- 0.1 in vegetarians). PhIP-SA adducts were no different in smokers and in non-smokers. The results show for the first time that PhIP-blood protein adducts are present in humans not given the synthetic compound. Both biomarkers appear to be suitable for assessing dietary exposure and internal PhIP dose and may be promising tools for studying the role of heterocyclic amines in the etiology of colon cancer and other diseases. Copyright 2000 Wiley-Liss, Inc.", "title": "Effect of diet on serum albumin and hemoglobin adducts of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in humans." }, { "docid": "MED-4072", "text": "It was the aim of this study to examine the association of the consumption of meat in general, meat prepared by different cooking methods and the dietary intake of heterocyclic aromatic amines (HCA) with the level of DNA adducts in the breast tissue of women undergoing reduction mammoplasty. Dietary intake of meat and HCA were assessed via questionnaire in 44 women undergoing reduction mammoplasty. DNA adduct analysis in breast tissue was performed by (32)P-postlabelling analysis. Spearman rank correlation coefficients (r) were calculated to examine the association of meat consumption and dietary HCA intake with tissue DNA adduct levels. A median DNA adduct level of 18.45 (interquartile range 12.81-25.65) per 10(9) nucleotides in breast tissue was observed; median HCA intake was 40.43 ng/day (interquartile range 19.55-102.33 ng/day). Total HCA intake (r = 0.33, P = 0.03), consumption of fried meat (r = 0.39, P = 0.01), beef (r = 0.32, P = 0.03) and processed meat (r = 0.51, P = 0.0004) were statistically significantly correlated with the level of DNA adducts in breast tissue. The detected DNA adducts could not be confirmed to be specific HCA-derived DNA adducts by comparison with external standards, using the (32)P-postlabelling assay. We observed strong correlations of dietary HCA intake and consumption of fried and processed meat with DNA adduct levels in breast tissue of 44 women. Since the detected DNA adducts were not necessarily specific only for HCA, it is possible that HCA intake is a surrogate of other genotoxic substances, such as polycyclic aromatic hydrocarbons, in meat prepared at high temperatures.", "title": "Dietary intake of meat and meat-derived heterocyclic aromatic amines and their correlation with DNA adducts in female breast tissue." }, { "docid": "MED-4055", "text": "Heterocyclic amines (HCAs) are formed when meat products such as beef, chicken, pork and fish are cooked at high temperatures. The most abundant HCA found in the human diet is 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP). PhIP causes mammary carcinomas in female rats and mice, and is associated with an increased risk of developing colon, breast, and prostate cancer in humans. PhIP is metabolized by cytochrome P-450s producing N-OH-PhIP. The N-OH-PhIP can be esterified by phase II enzymes forming an arylnitrenium ion that binds to DNA causing adducts. Furthermore, N-OH-PhIP may be reduced by cytochrome b5 reductase producing superoxide anions and hydroxyl radicals causing DNA strand breaks. Diallyl sulfide (DAS) has been shown to prevent cancer in several animal models, presumably by metabolic modulation. We hypothesize that PhIP produces reactive oxygen species causing DNA strand breaks and that DAS will inhibit the formation of PhIP induced DNA strand breaks. To test this hypothesis we treated normal breast epithelial (MCF-10A) cells with PhIP, DAS and a combination of PhIP and DAS. The detection of lipid peroxides was used as a surrogate for ROS. Lipid peroxides were detected using a PeroxiDetect kit (Sigma). PhIP increased the production of lipid peroxides and DAS decreased the PhIP-induced peroxidation by 47%. To determine if PhIP causes DNA strand breaks in MCF-10A cells, cells were treated for 3, 6, 9, and 24 h with PhIP (100 microM), DAS (100 microM) and a combination of PhIP (100 microM) and DAS (100 microM). DNA strand breaks were evaluated using the Comet assay. PhIP produced DNA strand breaks in a dose- and time-dependent fashion. We have shown that DAS inhibits PhIP-induced DNA strand breaks by inhibiting the production of reactive oxygen species. Therefore, we propose that DAS can prevent PhIP-induced breast cancer.", "title": "Diallyl sulfide inhibits PhIP-induced DNA strand breaks in normal human breast epithelial cells." }, { "docid": "MED-4049", "text": "More than 85% of breast cancers are sporadic and attributable to long-term exposure to environmental carcinogens, such as those in the diet, through a multistep disease process progressing from non-cancerous to premalignant and malignant stages. The chemical carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is one of the most abundant heterocyclic amines found in high-temperature cooked meats and is recognized as a mammary carcinogen. However, the PhIP’s mechanism of action in breast cell carcinogenesis is not clear. Here, we demonstrated, for the first time, that cumulative exposures to PhIP at physiologically achievable, pico to nanomolar concentrations effectively induced progressive carcinogenesis of human breast epithelial MCF10A cells from a non-cancerous stage to premalignant and malignant stages in a dose- and exposure-dependent manner. Progressive carcinogenesis was measured by increasingly- acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth, acinar-conformational disruption, proliferation, migration, invasion, tumorigenicity with metastasis and increased stem-like cell populations. These biological changes were accompanied by biochemical and molecular changes, including upregulated H-Ras gene expression, extracellular signal-regulated kinase (ERK) pathway activation, Nox-1 expression, reactive oxygen species (ROS) elevation, increased HIF-1α, Sp1, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2, MMP-9, aldehyde dehydrogenase activity and reduced E-cadherin. The Ras-ERK-Nox-ROS pathway played an important role in not only initiation but also maintenance of cellular carcinogenesis induced by PhIP. Using biological, biochemical and molecular changes as targeted endpoints, we identified that the green tea catechin components epicatechin-3-gallate and epigallocatechin-3-gallate, at non-cytotoxic doses, were capable of suppressing PhIP-induced cellular carcinogenesis and tumorigenicity.", "title": "Intervention of human breast cell carcinogenesis chronically induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine" }, { "docid": "MED-4330", "text": "Scope Observational studies have evaluated the relationship between green tea intake and cancers of the ovary and endometrium, but we are not aware of the published studies on green tea intake and risk of human papillomavirus (HPV)-related cancers of the cervix, vagina, or vulva. Methods and results A critical review of the published literature on tea intake and risk of ovarian and endometrial cancers was conducted. In meta-analyses, we report inverse associations for green tea intake and risk of ovarian cancer (odds ratio [OR] = 0.66; 95% confidence interval [CI]: 0.54, 0.80), and for green tea and risk of endometrial cancer (OR = 0.78, 95% CI: 0.62, 0.98). There was no association for black tea and ovarian cancer risk (OR = 0.94, 95% CI: 0.87, 1.02) and a positive association with endometrial cancer risk (OR = 1.20, 95% CI: 1.05, 1.38). We summarized the experimental evidence supporting the antiviral and immunomodulatory activities of green tea catechins, and results from randomized clinical trials that demonstrated green tea catechin efficacy on treatment of cervical lesions and external genital warts. Conclusion Observational data support a protective role of green tea on risk of ovarian and endometrial cancers. Observational data are needed to evaluate whether green tea reduces risk of human papillomavirus-related cancers.", "title": "Green and black tea in relation to gynecologic cancers" } ]
[ { "docid": "MED-4777", "text": "The current practice of introducing phytochemicals to support the immune system or fight against diseases is based on centuries old traditions. Nutritional support is a recent advancement in the domain of diet-based therapies; green tea and its constituents are one of the important components of these strategies to prevent and cure various malignancies. The anti-carcinogenic and anti-mutagenic activities of green tea were highlighted some years ago suggesting that it could reduce the prevalence of cancer and even provide protection. The pharmacological actions of green tea are mainly attributed to polyphenols that includes epigallocatechin-3-gallate (EGCG), epicatechin, epicatechin-3-gallate, epigallocatechin. Green tea and its components effectively mitigate cellular damage arising due to oxidative stress. Green tea is supposed to enhance humoral and cell-mediated immunity, decreasing the risk of certain cancers, and may have certain advantage in treating inflammatory disorders. Much of the cancer chemopreventive properties of green tea are mediated by EGCG that induces apoptosis and promotes cell growth arrest, by altering the expression of cell cycle regulatory proteins, activating killer caspases, and suppressing nuclear factor kappa-B activation. Besides, it regulates and promotes IL-23 dependent DNA repair and stimulates cytotoxic T cells activities in a tumor microenvironment. It also blocks carcinogenesis by modulating the signal transduction pathways involved in cell proliferation, transformation, inflammation and metastasis. The review is intended to highlight the chemistry of green tea, its antioxidant potential, its immunopotentiating properties and mode of action against various cancer cell lines that showed its potential as a chemopreventive agent against colon, skin, lung, prostate, and breast cancer.", "title": "Green tea: nature's defense against malignancies." }, { "docid": "MED-4775", "text": "PURPOSE: To investigate the association between green tea consumption and mortality from all causes, cancer, and cardiovascular disease (CVD) among elderly people. METHODS: In a population-based, prospective cohort study, a total of 14,001 elderly residents (aged 65-84 years), randomly chosen from all 74 municipalities in Shizuoka, Japan, completed questionnaires that included items about frequency of green tea consumption. They were followed for up to 6 years, from December 1999 to March 2006. Consequently, 12,251 subjects were analyzed to estimate the hazard ratios (HRs) for all-cause mortality, cancer, and CVD. RESULTS: Among 64,002 person-years, 1,224 deaths were identified (follow-up rate, 71.6%). The multivariate HRs and 95% confidence intervals (CIs) for CVD mortality compared those who consumed seven or more cups per day with those who consumed less than one cup per day, were 0.24 (0.14-0.40), 0.30 (0.15-0.61), and 0.18 (0.08-0.40) for total participants, men, and women, respectively. Although green tea consumption was not inversely associated with cancer mortality, green tea consumption and colorectal cancer mortality were inversely associated with a moderate dose-response relationship. CONCLUSIONS: Green tea consumption is associated with reduced mortality from all causes and CVD. This study also suggests that green tea could have protective effects against colorectal cancer.", "title": "Green tea consumption and mortality among Japanese elderly people: the prospective Shizuoka elderly cohort." }, { "docid": "MED-5052", "text": "OBJECTIVE: Habitual green tea consumption has long been associated with health benefits including chemoprevention and cardiovascular protection. This non-systematic literature review presents the clinical evidence to date. METHOD: A literature review of peer-reviewed articles on observational and interventional studies was conducted to include green tea, its extract or its purified polyphenol (-)-epigallocatechin-3-gallate (EGCG). Electronic databases searched included PubMed (1966-2009) and the Cochrane Library (Issue 4, 2008). RESULTS: Observational studies are inconclusive on the benefits of habitual consumption of green tea in the prevention of most cancers. However, there are trends towards prevention in breast and prostate cancers. Interventional studies have demonstrated reduction in relapses following surgical resection in colorectal adenomas and increased survival rates in epithelial ovarian cancer. Observational studies indicate that green tea may provide protection against hypertension and reduce the risk for stroke, and interventional studies are providing biochemical and physiological evidence. CONCLUSION: Although the overall clinical evidence is inconclusive, habitual green tea consumption may be providing some level of chemoprevention in prostate and breast cancer. Green tea may also attenuate the risk factors association with the development of atherosclerosis thus reducing the incidence of cardiovascular events and stoke.", "title": "Can green tea do that? A literature review of the clinical evidence." }, { "docid": "MED-4097", "text": "The identification of modifiable lifestyle factors that could reduce the risk of breast cancer is a research priority. Despite the enormous chemo preventive potential of green tea and compelling evidence from animal studies, its role in breast cancer development in humans is still unclear. Part of the uncertainty is related to the relatively small number of epidemiological studies on green tea and breast cancer and that the overall results from case-control studies and prospective cohort studies are discordant. In addition, the mechanisms by which green tea intake may influence risk of breast cancer in humans remains not well studied. We review the human studies that have evaluated the relationship between green tea intake and four biomarkers (sex steroid hormones, mammographic density, insulin-like growth factor, adiponectin) that are believed to be important in breast cancer development. Results from these biomarker studies are also inconclusive. Limitations of human studies and areas of further investigations are discussed.", "title": "Green Tea and Breast Cancer" }, { "docid": "MED-4098", "text": "To investigate effects of dietary mushrooms and joint effects of mushrooms and green tea on breast cancer, a case-control study was conducted in southeast China in 2004-2005. The incident cases were 1,009 female patients aged 20-87 years with histologically confirmed breast cancer. The 1,009 age-matched controls were healthy women randomly recruited from outpatient breast clinics. Information on frequency and quantity of dietary intake of mushrooms and tea consumption, usual diet, and lifestyle were collected by face-to-face interview using a validated and reliable questionnaire. Compared with nonconsumers, the Odds ratios (Ors) were 0.36 (95% CI = 0.25-0.51) and 0.53 (0.38-0.73) for daily intake of >or=10 g fresh mushrooms and >or=4 g dried mushrooms, based on multivariate logistic regression analysis adjusting for established and potential confounders. There were dose-response relationships with significant tests for trend (p < 0.001). The inverse association was found in both pre- and postmenopausal women. Compared with those who consumed neither mushrooms nor green tea, the ORs were 0.11 (0.06-0.20) and 0.18 (0.11-0.29) for daily high intake of fresh and dried mushrooms combined with consuming beverages made from >or=1.05 g dried green tea leaves per day. The corresponding linear trends were statistically significant for joint effect (p < 0.001). We conclude that higher dietary intake of mushrooms decreased breast cancer risk in pre- and postmenopausal Chinese women and an additional decreased risk of breast cancer from joint effect of mushrooms and green tea was observed. More research is warranted to examine the effects of dietary mushrooms and mechanism of joint effects of phytochemicals on breast cancer.", "title": "Dietary intakes of mushrooms and green tea combine to reduce the risk of breast cancer in Chinese women." }, { "docid": "MED-1109", "text": "BACKGROUND: The distinctive racial/ethnic and geographic distribution of multiple myeloma (MM) suggests that both family history and environmental factors may contribute to its development. METHODS: A hospital-based case-control study consisting of 220 confirmed MM cases and 220 individually matched patient controls, by sex, age and hospital was carried out at 5 major hospitals in Northwest China. A questionnaire was used to obtain information on demographics, family history, and the frequency of food items consumed. RESULTS: Based on multivariate analysis, a significant association between the risk of MM and family history of cancers in first degree relatives was observed (OR=4.03, 95% CI: 2.50-6.52). Fried food, cured/smoked food, black tea, and fish were not significantly associated with the risk of MM. Intake of shallot and garlic (OR=0.60, 95% CI: 0.43-0.85), soy food (OR=0.52, 95% CI: 0.36-0.75) and green tea (OR=0.38, 95% CI: 0.27-0.53) was significantly associated with a reduced risk of MM. In contrast, intake of brined vegetables and pickle was significantly associated with an increased risk (OR=2.03, 95% CI: 1.41-2.93). A more than multiplicative interaction on the decreased risk of MM was found between shallot/garlic and soy food. CONCLUSION: Our study in Northwest China found an increased risk of MM with a family history of cancer, a diet characterized by low consumption of garlic, green tea and soy foods, and high consumption of pickled vegetables. The effect of green tea in reducing the risk of MM is an interesting new finding which should be further confirmed. Copyright © 2012 Elsevier Ltd. All rights reserved.", "title": "Risk factors for multiple myeloma: a hospital-based case-control study in Northwest China." }, { "docid": "MED-4365", "text": "A myriad of health claims are being made in favor of the consumption of green tea. However, mostly due to the easy availability and greater than ever popularity of highly concentrated green tea extracts, sometimes combined with an attitude of more-is-better, certain health risks of green tea consumption have begun to emerge. Among such risks are the possibility of liver damage, the potential to interact with prescription drugs to alter their therapeutic efficacy, and the chance to cause harm when combined with other highly popular herbal remedies. This review will summarize documented examples of adverse effects of green tea in humans, and will discuss risks of copious consumption of highly concentrated green tea extracts as indicated by studies in animals. While there is no intention to minimize any of the scientifically established benefits of the use of green tea, the purpose of this review is to focus primarily on the potential for adverse effects and raise awareness of the rare, yet under-appreciated risks. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.", "title": "Adverse effects of concentrated green tea extracts." }, { "docid": "MED-5047", "text": "Our objective was to examine whether habitual green tea consumption is associated with blood glucose levels and other biomarkers of glucose metabolism. We conducted a cross-sectional study of 35 male volunteers, 23–63 years old and residing in Shizuoka Prefecture in Japan. Biochemical data were measured and we conducted a questionnaire survey on health, lifestyle, and nutrition, as well as frequency of consumption and concentrations (1%, 2%, and 3%) of green tea. Men who consumed a 3% concentration of green tea showed lower mean values of fasting blood glucose and fructosamine than those who consumed a 1% concentration. Fasting blood glucose levels were found to be significantly associated with green tea concentration (β = −0.14, p = 0.03). However, green tea consumption frequency showed no significant differences in mean levels of blood glucose, fructosamine and hemoglobin A1c. In conclusion, our findings suggest that the consumption of green tea at a high concentration has the potential to reduce blood glucose levels.", "title": "The Association between Concentrations of Green Tea and Blood Glucose Levels" }, { "docid": "MED-5049", "text": "OBJECTIVE: To evaluate the hypolipemic and antioxidant effects of soy and green tea alone and/or in association in dyslipidemic subjects. METHODS: One hundred dyslipidemic individuals were allocated into four groups. The soy group ingested 50 g of soy (kinako) daily, and the green tea group ingested 3 g of green tea in 500 mL of water per day. A third group ingested 50 g of soy and 3 g of green tea daily, and the control group had a hypocholesterolemic diet. Evaluations were performed at baseline and after 45 and 90 d. Plasma levels of total cholesterol, high-density lipoprotein, and triacylglycerols were evaluated by automated methods. Low-density lipoprotein (LDL) cholesterol was calculated using the Friedewald equation. LDL was isolated by ultracentrifugation. Total plasma antioxidant capacity and plasma levels of total lipid hydroperoxides and those linked to LDL were evaluated by chemiluminescence. The results were expressed as median values and their 25th to 75th percentiles, with a 5% level of significance. RESULTS: No significant difference occurred in LDL, high-density lipoprotein cholesterol, and triacylglycerol levels across groups. However, a statistically significant difference in total cholesterol occurred within the soy/green tea group 45 and 90 d after intervention. No statistically significant difference occurred in plasma levels of lipid hydroperoxides or those linked to LDL in any of the groups studied. All the groups that used soy and/or green tea presented increased total plasma antioxidant potential. CONCLUSION: Soy and green tea, alone or in combination, increased the total antioxidant potential of hypercholesterolemic patients, whereas only the combination decreased total cholesterol levels.", "title": "Association between soy and green tea (Camellia sinensis) diminishes hypercholesterolemia and increases total plasma antioxidant potential in dysli..." }, { "docid": "MED-4780", "text": "OBJECTIVE: To examine the association between green tea consumption and tooth loss. METHODS: We analyzed cross-sectional data from the Ohsaki Cohort 2006 Study. Usable self-administered questionnaires about green tea consumption and tooth loss were returned from 25,078 persons (12,019 men and 13,059 women) aged 40 to 64 years in Japan. Multivariate logistic regression analysis was used to calculate odds ratios (ORs) for tooth loss using 3 cut-off points of 10, 20, and 25 teeth relative to each category of green tea consumption. RESULTS: Consumption of > or = 1 cup/day of green tea was significantly associated with decreased odds for tooth loss, and the association appeared to fit a threshold model. In men, the multivariate-adjusted ORs for tooth loss with a cut-off point of <20 teeth associated with different frequencies of green tea consumption were 1.00 (reference) for <1 cup/day, 0.82 (95% CI, 0.74-0.91) for 1-2 cups/day, 0.82 (95% CI, 0.73-0.92) for 3-4 cups/day, and 0.77 (95% CI, 0.66-0.89) for > or = 5 cups/day. The corresponding data for women and the results for cut-off points of 10 and 25 teeth were essentially the same. CONCLUSIONS: The present findings indicate an association of green tea consumption with decreased odds for tooth loss. Copyright 2010 Elsevier Inc. All rights reserved.", "title": "Association between green tea consumption and tooth loss: cross-sectional results from the Ohsaki Cohort 2006 Study." }, { "docid": "MED-2094", "text": "INTRODUCTION: An increasing number of people all around the world are turning to the nature by using the natural herbal products in both prophylaxes and treatment of different diseases. Green tea with active chemical ingredients posses diverse pharmacological properties that include anti-inflammatory, anticariogenic, antioxidant and antibacterial effects. AIMS: To assess the possible protective properties of green tea on oral health. METHODS: The researchers used the following measurements: Streptococcus mutans count in saliva and plaque, Salivary and plaque pH values, Gingival Bleeding Index (GBI). The above-mentioned measurements were applied to a sample consists of 25 subjects before and after rinsing with green tea for 5 min (short-term study). While, S. mutans count for saliva and plaque and GBI measurements, this experimental intervention study was carried out in the El-Azhar University dental clinic. RESULTS: The results of this study showed that there was a statistically significant difference among subjects pre- and post-rinsing with 2% green tea for 5 min concerning S. mutans count in saliva and plaque, salivary and plaque pH values and GBI. CONCLUSION: This study supports the effectiveness of local application of green tea as antibacterial and anticariogenic material as it decreases the acidity of the saliva and plaque, so it is a cost-effective caries prevention measures especially in developing countries. © 2009 John Wiley & Sons A/S.", "title": "A pilot study of the role of green tea use on oral health." }, { "docid": "MED-4468", "text": "Many constituents present in the human diet may inhibit endogenous formation of N-nitroso compounds (NOC). Studies with human volunteers showed inhibiting effects of intake of ascorbic acid and green tea consumption on nitrosation using the N-nitrosoproline test. The aim of the present study was to evaluate the effects of ascorbic acid and green tea on urinary excretion of carcinogenic N-nitrosodimethylamine (NDMA) and N-nitrosopiperidine (NPIP) in humans. Twenty-five healthy female volunteers consumed a fish meal rich in amines as nitrosatable precursors in combination with intake of nitrate-containing drinking water at the Acceptable Daily Intake level during 7 consecutive days. During 1 week before and after nitrate intake a diet low in nitrate was consumed. Using the same protocol, the effect of two different doses of ascorbic acid (250 mg and 1 g/day) and two different doses of green tea (2 g and 4 g/day) on formation of NDMA and NPIP was studied. Mean nitrate excretion in urine significantly increased from control (76+/-24) to 167+/-25 mg/24 h. Intake of nitrate and fish resulted in a significant increase in mean urinary excretion of NDMA compared with the control weeks: 871+/-430 and 640+/-277 ng/24 h during days 1-3 and 4-7, respectively, compared with 385+/-196 ng/24 h (p<0.0002). Excretion of NPIP in urine was not related to nitrate intake and composition of the diet. Intake of 250 mg and 1 g of ascorbic acid per day resulted in a significant decrease in urinary NDMA excretion during days 4-7 (p=0.0001), but not during days 1-3. Also, consumption of four cups of green tea per day (2 g) significantly decreased excretion of NDMA during days 4-7 (p=0.0035), but not during days 1-3. Surprisingly, consumption of eight cups of green tea per day (4 g) significantly increased NDMA excretion during days 4-7 (p=0.0001), again not during days 1-3. This increase is probably a result of catalytic effects of tea polyphenols on nitrosation, or of another, yet unknown, mechanism. These results suggest that intake of ascorbic acid and moderate consumption of green tea can reduce endogenous NDMA formation.", "title": "Effect of ascorbic acid and green tea on endogenous formation of N-nitrosodimethylamine and N-nitrosopiperidine in humans." }, { "docid": "MED-1645", "text": "BACKGROUND: Tea consumption is associated with decreased cardiovascular risk. Flow-mediated dilatation (FMD) of the brachial artery is related to coronary endothelial function and it is an independent predictor of cardiovascular risk. Black tea has a beneficial effect on endothelial function; the effect, however, of green tea on brachial artery reactivity has not been defined yet. DESIGN AND METHODS: We studied 14 healthy individuals (age 30+/-3 years) with no cardiovascular risk factors except from smoking (50%) on three separate occasions on which they took: (a) 6 g of green tea, (b) 125 mg of caffeine (the amount contained in 6 g of tea), or (c) hot water. FMD of the brachial artery was measured before each intervention and 30, 90, and 120 min afterward. High-sensitivity C-reactive protein, interleukins 6 (Il-6) and 1b (Il-1b), total plasma antioxidative capacity, and total plasma oxidative status/stress were measured at baseline and at 120 min after each intervention. RESULTS: Resting and hyperemic brachial artery diameter did not change either with tea or with caffeine. FMD increased significantly with tea (by 3.69%, peak at 30 min, P<0.02), whereas it did not change significantly with caffeine (increase by 1.72%, peak at 30 min, P=NS). Neither tea nor caffeine had any effect on high-sensitivity C-reactive protein, Il-6, Il-1b, total plasma antioxidative capacity, or total plasma oxidative status/stress. CONCLUSION: Green tea consumption has an acute beneficial effect on endothelial function, assessed with FMD of the brachial artery, in healthy individuals. This may be involved in the beneficial effect of tea on cardiovascular risk.", "title": "The acute effect of green tea consumption on endothelial function in healthy individuals." }, { "docid": "MED-5048", "text": "Despite the continuing reports supporting the hepatoprotective effects of green tea against ethanol intoxication, there remain controversies regarding the active compound(s) and molecular mechanism. These issues were addressed in the present study using cultured HepG2 cells exposed to a lethal dose of ethanol. Gamma-glutamyl transferase (GGT) was chosen as a marker of ethanol toxicity because it is widely used in clinics. When the cells were treated with ethanol at various concentrations, there was a dose-dependent increase of GGT activity in the culture media and loss of cell viability. Pretreatment of the cells with green tea extract attenuated the changes significantly. Among the green tea constituents, (-)-epigallocatechin gallate (EGCG) attenuated the ethanol cytotoxicity effectively, whereas L-theanine and caffeine had no effects. The ethanol cytotoxicity was also attenuated by alcohol dehydrogenase inhibitor 4-methyl pyrazol and GGT inhibitor acivicin as well as by thiol modulators such as S-adenosyl-L-methionine, N-acetyl-L-cysteine and glutathione. EGCG failed to prevent the intracellular glutathione loss caused by ethanol, but it appeared to be a strong GGT inhibitor. Therefore the cytoprotective effects of green tea could be attributed to the inhibition of GGT activity by EGCG. This study suggests that GGT inhibitors including EGCG may provide a novel strategy for attenuating ethanol-induced liver damage.", "title": "Effect of green tea and (-)-epigallocatechin gallate on ethanol-induced toxicity in HepG2 cells." }, { "docid": "MED-4776", "text": "Tea (Camellia sinensis, Theaceae) and tea polyphenols have been studied for the prevention of chronic diseases, including obesity. Obesity currently affects >20% of adults in the United States and is a risk factor for chronic diseases such as type II diabetes, cardiovascular disease, and cancer. Given this increasing public health concern, the use of dietary agents for the prevention of obesity would be of tremendous benefit. Whereas many laboratory studies have demonstrated the potential efficacy of green or black tea for the prevention of obesity, the underlying mechanisms remain unclear. The results of human intervention studies are mixed and the role of caffeine has not been clearly established. Finally, there is emerging evidence that high doses of tea polyphenols may have adverse side effects. Given that the results of scientific studies on dietary components, including tea polyphenols, are often translated into dietary supplements, understanding the potential toxicities of the tea polyphenols is critical to understanding their potential usefulness in preventing obesity. In this review, we will critically evaluate the evidence for the prevention of obesity by tea, discuss the relevance of proposed mechanisms in light of tea polyphenol bioavailability, and review the reports concerning the toxic effects of high doses of tea polyphenols and the implication that this has for the potential use of tea for the prevention of obesity. We hope that this review will expose areas for further study and encourage research on this important public health issue.", "title": "Laboratory, Epidemiological, and Human Intervention Studies Show That Tea (Camellia sinensis) May Be Useful in the Prevention of Obesity" }, { "docid": "MED-5046", "text": "Epidemiological evidence suggests a role for tea catechins in reduction of chronic disease risk. However, stability of catechins under digestive conditions is poorly understood. The objective of this study was to characterize the effect of common food additives on digestive recovery of tea catechins. Green tea water extracts were formulated in beverages providing 4.5, 18, 23, and 3.5 mg per 100 mL epicatechin (EC), epigallocatechin (EGC), epigallocatechin-gallate (EGCG), and epicatechin-gallate (ECG), respectively. Common commercial beverage additives; citric acid (CA), BHT, EDTA, ascorbic acid (AA), milk (bovine, soy, and rice), and citrus juice (orange, grapefruit, lemon, and lime) were formulated into finished tea beverages at incremental dosages. Samples were then subjected to in vitro digestion simulating gastric and small intestinal conditions with pre- and post-digestion catechin profiles assessed by HPLC. Catechin stability in green tea was poor with <20% total catechins remaining post-digestion. EGC and EGCG were most sensitive with less, not double equals 10% recovery. Teas formulated with 50% bovine, soy, and rice milk increased total catechin recovery significantly to 52, 55, and 69% respectively. Including 30 mg AA in 250 mL of tea beverage significantly (p<0.05) increased catechin recovery of EGC, EGCG, EC, and ECG to 74, 54, 82, and 45% respectively. Juice preparation resulted in the highest recovery of any formulation for EGC (81-98%), EGCG (56-76%), EC (86-95%), and ECG (30-55%). These data provide evidence that tea consumption practices and formulation factors likely impact catechin digestive recovery and may result in diverse physiological profiles.", "title": "Common tea formulations modulate in vitro digestive recovery of green tea catechins." }, { "docid": "MED-1844", "text": "Total aluminum, chromium, copper, iron, manganese, and nickel were determined in black tea, green tea, Hibiscus sabdariffa, and Ilex paraguariensis (mate) by electrothermal atomic absorption spectrometry after nitric/perchloric acid digestion. In each case, one ground sample of commercially available leafy material was prepared and three 0.5-g subsamples were run in parallel. The infusions were also analyzed and the percentage of each element leached into the liquor was evaluated. The obtained results indicated that hibiscus and mate contained lower levels of aluminum (272+/-19 microg/g and 369+/-22 microg/g, respectively) as referred to black tea (759+/-31 microg/g) or green tea (919micro29 microg/g) and suggested that mate drinking could be a good dietary source of essential micronutrient manganese (total content 2223+/-110 microg/g, 48.1% leached to the infusion). It was also found that the infusion of hibiscus could supply greater amounts of iron (111+/-5 microg/g total, 40.5% leached) and copper (5.9+/-0.3 microg/g total, 93.4% leached) as compared to other infusions. Moreover, it was found that the percentage of element leached to the infusion was strongly related to the tannins content in the beverage (correlation coefficients > 0.82 with the exception for nickel); for lower tannins level, better leaching was observed.", "title": "Determination of total aluminum, chromium, copper, iron, manganese, and nickel and their fractions leached to the infusions of black tea, green tea..." }, { "docid": "MED-3554", "text": "A great deal of effort is now being devoted to the development of new drugs that hopefully will control the spread of inoperable cancer by safely inhibiting tumor-evoked angiogenesis. However, there is growing evidence that certain practical nutritional measures have the potential to slow tumor angiogenesis, and it is reasonable to anticipate that, by combining several measures that work in distinct but complementary ways to impede the angiogenic process, a clinically useful 'multifocal angiostatic therapy' (MAT) might be devised. Several measures which might reasonably be included in such a protocol are discussed below, and include: a low-fat, low-glycemic index vegan diet, which may down-regulate the systemic IGF-I activity that supports angiogenesis; supplemental omega-3-rich fish oil, which has been shown to inhibit endothelial expression of Flk-1, a functionally crucial receptor for VEGF, and also can suppress tumor production of pro-angiogenic eicosanoids; high-dose selenium, which has recently been shown to inhibit tumor production of VEGF; green tea polyphenols, which can suppress endothelial responsiveness to both VEGF and fibroblast growth factor; and high-dose glycine, whose recently reported angiostatic activity may reflect inhibition of endothelial cell mitosis, possibly mediated by activation of glycine-gated chloride channels. In light of evidence that tumor-evoked angiogenesis has a high requirement for copper, copper depletion may have exceptional potential as an angiostatic measure, and is most efficiently achieved with the copper-chelating drug tetrathiomolybdate. If logistical difficulties make it difficult to acquire this experimental drug, high-dose zinc supplementation can achieve a slower depletion of the body's copper pool, and in any case can be used as maintenance therapy to maintain an adequate level of copper depletion. A provisional protocol is offered for a nutritionally based MAT entailing a vegan diet and supplemental intakes of fish oil, selenium, green tea polyphenols, glycine, and zinc. Inasmuch as cox-2 is overexpressed in many cancers, and cAMP can boost tumor production of various angiogenic factors as well as autogenous growth factors, adjunctive use of cox-2-specific NSAIDS may be warranted in some cases.", "title": "A wholly nutritional 'multifocal angiostatic therapy' for control of disseminated cancer." }, { "docid": "MED-1853", "text": "PURPOSE: To measure the pH, titratable acidity, fluoride concentration and erosive potential of brewed teas. METHODS: Bag teas were purchased to represent black, green, citrus, fruity, and floral tea flavors from Tulsi, Bigelow, HyVee, Tazo, and Yogi brands and brewed (1 bag/240 ml) in boiling water for 3 minutes. The pH, titratable acidity, and fluoride concentrations were measured. Following these measurements, a representative tea from each flavor was selected for investigation of erosion potential. Six extracted human molars were randomly assigned to each tea. Teeth were painted with fingernail polish to expose a 1 x 4 mm window and then soaked in tea for a total of 25 hours with teas refreshed every 5 hours. Teeth were then sectioned using a microtome and photographed using a polarized light microscope. Lesion depths (i.e., eroded surfaces) were measured using Image Pro Plus software. Differences in physiochemical properties and lesion depths between beverages were investigated using one-way ANOVA with post-hoc Tukey's HSD test. Relationships among lesion depths and physiochemical properties were evaluated using the Pearson correlation test. RESULTS: pH, titratable acidity and fluoride concentrations differed between tea flavors (P < 0.05) and between brands (P < 0.05). Lesion depths produced by the citrus tea (83.1 +/- 10.3 microm) were greater than those produced by the fruity tea (56.5 +/- 6.1 microm); both teas produced greater depths than black (30.1 +/- 7.4 microm), floral (25.0 +/- 3.2 microm) or green (22.3 +/- 6.3 microm) teas (P < 0.05). pH (r = -0.96; P = 0.009) was inversely and titratable acidity (r = 0.97; P = 0.006) was positively associated with lesion depths.", "title": "Erosive potentials of brewed teas." }, { "docid": "MED-4864", "text": "To elucidate the health benefit of herbal teas on the cytotoxicity induced by H(2)O(2) in V79-4 cells, herbal extracts and its flavonoids were tested using lactate dehydrogenase release and determining intracellular reactive oxygen species generation and antioxidant activity with superoxide radical scavenging assay. Significant decrease in cell viability was observed on V79-4 cells treated with H(2)O(2) (1 mM), while herbal extracts and its flavonoids including catechin and epigallocatechin gallate prevented the LDH release from H(2)O(2) cytotoxicity. Total catechin contents of green tea (65.6 mg/g of dry matter) were significantly higher than other herbal teas (35.8 to 1.2 mg/g of DM). The relative concentration of the 4 major tea catechins ranked EGCG > EGC > EC > C. Green tea exhibited the lowest IC(50) values (2 g fresh herb/100 mL) of superoxide radical scavenging activity among the tested herbal tea, which indicates powerful antioxidant activity in O(2)(*-) radicals scavenging, followed by black tea, dandelion, hawthorn, rose hip, chamomile.", "title": "Comparative flavonoids contents of selected herbs and associations of their radical scavenging activity with antiproliferative actions in V79-4 cells." }, { "docid": "MED-945", "text": "We assess the evidence for health benefits of three commonly consumed plant food supplements (PFS), green tea, isoflavone and aloe vera, based on published systematic reviews of randomised controlled trials (RCTs). Whilst the potential benefits of green tea have been reported in a wide range of health areas, it is only in the area of the metabolic syndrome that the number of RCTs is approaching sufficient to judge such efficacy. Isoflavone supplements are widely used, and RCTs indicate that they affect bone resorption at lower doses in postmenopausal women undergoing estrogen-related bone loss, but this is only translated to attenuation of bone loss at higher doses of isoflavones. A systematic review on RCTs concluded that the effects of isoflavones on hot flashes in postmenopausal women were highly variable and no conclusions could be drawn. Despite the popularity of aloe vera as a PFS, the evaluation of its efficacy as a coadjuvant therapy for certain metabolic or digestive pathologies remains scarce; it constitutes a typical example of a naturally occurring ingredient whose efficacy in topical applications presupposes its efficacy in systemic applications. Nevertheless, its possible toxic effects on oral consumption call for caution in its utility as a PFS. Since 2007, efficacy evaluation of PFS in Europe has been covered by European Union Nutrition and Health Claims legislation. The European Food Safety Authority has adopted an approach relying on RCTs, while medicinal effects are accepted based on traditional use. In general, there are insufficient RCTs for claims to be made, and conclusive results on PFS should be obtained in the future by conducting studies with more homogeneous populations, by using supplements with optimised and measured bioavailability, and by conducting larger RCTs.", "title": "Review of the efficacy of green tea, isoflavones and aloe vera supplements based on randomised controlled trials." }, { "docid": "MED-4413", "text": "Estimation of total antioxidant intake is the first step to investigate the protective effects of antioxidants on oxidative stress-mediated disease. The present study was designed to develop an algorithm to estimate total antioxidant capacity (TAC) of the US diet. TAC of individual antioxidants and 50 popular antioxidant-rich food items in the US diet were determined by 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) assay and the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Theoretical TAC of foods was calculated as the sum of individual antioxidant capacities of compounds. The top 10 TAC food items in the US diet according to standard serving size were blueberry > plum > green tea > strawberry > green tea (decaffeinated) > red wine > grape juice > black tea > cherry > grape. Major contributors to TAC were the total phenolic content (r = 0.952, P < 0.001) and flavonoid content (r = 0.827, P < 0.001) of 50 foods. Theoretical TAC was positively correlated to experimental TAC of 50 foods determined by the ABTS assay (r = 0.833, P < 0.001) and the DPPH assay (r = 0.696, P < 0.001), and to TAC from the USDA database for the oxygen radical absorbance capacity (r = 0.484, P = 0.001, n = 44). The TAC database of the US diet has been established and validated. In future studies, TAC of the US diet can be linked to biomarkers of chronic disease.", "title": "Development and validation of an algorithm to establish a total antioxidant capacity database of the US diet." }, { "docid": "MED-5156", "text": "Tea leaves produce organic compounds that may be involved in the defense of the plants against invading pathogens including insects, bacteria, fungi, and viruses. These metabolites include polyphenolic compounds, the six so-called catechins, and the methyl-xanthine alkaloids caffeine, theobromine, and theophylline. Postharvest inactivation of phenol oxidases in green tea leaves prevents oxidation of the catechins, whereas postharvest enzyme-catalyzed oxidation (fermentation) of catechins in tea leaves results in the formation of four theaflavins as well as polymeric thearubigins. These substances impart the black color to black teas. Black and partly fermented oolong teas contain both classes of phenolic compounds. A need exists to develop a better understanding of the roles of polyphenolic tea compounds in food and medical microbiology. This overview surveys and interprets our present knowledge of activities of tea flavonoids and teas against foodborne and other pathogenic bacteria, virulent protein toxins produced by some of the bacteria, virulent bacteriophages, pathogenic viruses and fungi. Also covered are synergistic, mechanistic, and bioavailability aspects of the antimicrobial effects. Further research is suggested for each of these categories. The herein described findings are not only of fundamental interest, but also have practical implications for nutrition, food safety, and animal and human health.", "title": "Overview of antibacterial, antitoxin, antiviral, and antifungal activities of tea flavonoids and teas." }, { "docid": "MED-2677", "text": "Population differences in age-related diseases and cancer could stem from differences in diet. To characterize DNA strand-breaking activities in selected foods/beverages, flavorings, and some of their constituent chemicals, we used p53R cells, a cellular assay sensitive to such breaks. Substances testing positive included reference chemicals: quinacrine (peak response, 51X) and etoposide (33X); flavonoids: EGCG (19X), curcumin (12X), apigenin (9X), and quercetin (7X); beverages: chamomile (11X), green (21X), and black tea (26X) and coffee (3 to 29X); and liquid smoke (4 to 28X). Damage occurred at dietary concentrations: etoposide near 5 μg/ml produced responses similar to a 1:1000 dilution of liquid smoke, a 1:20 dilution of coffee, and a 1:5 dilution of tea. Pyrogallol-related chemicals and tannins are present in dietary sources and individually produced strong activity: pyrogallol (30X), 3-methoxycatechol (25X), gallic acid (21X), and 1,2,4-benzenetriol (21X). From structure-activity relationships, high activities depended on specific orientations of hydroxyls on the benzene ring. Responses accompanied cellular signals characteristic of DNA breaks such as H2AX phosphorylation. Breaks were also directly detected by comet assay. Cellular toxicological effects of foods and flavorings could guide epidemiologic and experimental studies of potential disease risks from DNA strand-breaking chemicals in diets.", "title": "Biological Clues to Potent DNA-Damaging Activities in Food and Flavoring" }, { "docid": "MED-1850", "text": "A microwave-assisted acid digestion procedure coupled with a graphite furnace atomic absorption method has been applied in the determination of aluminum (Al) in urine to verify the correlation of free forms of Al in tea infusions and urinary excretion of Al. Significant urinary Al excretion has been found in 24-h urine of four volunteers after tea drinking. However, the difference in amount of Al excretion in urine between the consumption of Oolong (black tea) and Long-Jin (green tea), each of them with unique Al contents and species, was not significant. These findings indicated that the high levels of free Al species in tea infusions did not result in significant change in urinary excretion of the metal, possibly owing to the transformation by ligands present in food and the gastrointestinal tract (GIT). However, it could not be assumed that there was no big difference in absorption of the metal in the human body if fractions of consumed Al retained in the body or excreted by bile or feces were considered.", "title": "Urine levels of aluminum after drinking tea." }, { "docid": "MED-870", "text": "Ilex paraguariensis dried and minced leaves are made into a brewed tea, prepared in a sui generis manner by large populations in South America, having evolved from a tea drunk by the Guarani ethnic group to a beverage that has a social and almost ritualistic role in some South American modern societies. It is used both as a source of caffeine, in lieu or in parallel with tea and coffee, but also as a therapeutic agent for its alleged pharmacological properties. Although with some exceptions, research on biomedical properties of this herb has had a late start and strongly lags behind the impressive amount of literature on green tea and coffee. However, in the past 15 years, there was a several-fold increase in the literature studying Ilex paraguariensis properties showing effects such as antioxidant properties in chemical models and ex vivo lipoprotein studies, vaso-dilating and lipid reduction properties, antimutagenic effects, controversial association with oropharyngeal cancer, anti-glycation effects and weight reduction properties. Lately, promising results from human intervention studies have surfaced and the literature offers several developments on this area. The aim of this review is to provide a concise summary of the research published in the past three years, with an emphasis on translational studies, inflammation and lipid metabolism. Ilex paraguariensis reduces LDL-cholesterol levels in humans with Ilex paraguariensis dyslipoproteinemia and the effect is synergic with that of statins. Plasma antioxidant capacity as well as expression of antioxidant enzymes is positively modulated by intervention with Ilex paraguariensis in human cohorts. A review on the evidence implicating Ilex paraguariensis heavy consumption with some neoplasias show data that are inconclusive but indicate that contamination with alkylating agents during the drying process of the leaves should be avoided. On the other hand, several new studies confirm the antimutagenic effects of Ilex paraguariensis in different models, from DNA double breaks in cell culture models to mice studies. Novel interesting work has emerged showing significant effect on weight reduction both in mice and in rat models. Some mechanisms involved are inhibition of pancreatic lipase, activation of AMPK and uncoupling of electron transport. Intervention studies in animals have provided strong evidence of anti-inflammatory effects of Ilex paraguariensis, notably protecting cigarette-induced lung inflammation acting on macrophage migration and inactivating matrix-metalloproteinase. Research on the effects of Ilex paraguariensis in health and disease has confirmed its antioxidant, anti-inflammatory, antimutagenic and lipid-lowering activities. Although we are still waiting for the double-blind, randomized prospective clinical trial, the evidence seems to provide support for beneficial effects of mate drinking on chronic diseases with inflammatory component and lipid metabolism disorders. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.", "title": "Recent advances on Ilex paraguariensis research: minireview." }, { "docid": "MED-851", "text": "Barrett's oesophagus normally affects the distal oesophagus when metaplastic columnar lined epithelium replaces stratified squamous epithelium which predisposes to cancer development. This develops as a consequence of chronic gastroesophageal reflux (GORD). Those with Barrett's have a 40 fold increased risk of oesophageal adenocarcinoma [1]. There are is still a lack of understanding of the natural history of the cell of origin. This does hamper research into this area. We accept that there is a limitation in testing of the pathogenesis of Barrett's oesophagus due to a lack of a universally accepted animal model. The major questions surrounding Barrett's oesophagus include validity of surveillance strategies, the optimal treatment and more importantly an agent that can prevent progression to cancer without unacceptable side effects. The main chemopreventative agents that show promise are aspirin and proton pump inhibitors (PPIs). There are other agents such as green tea, berries and antioxidants and diet that have been suggested; we discuss the evidence available for these strategies. We hope for continued improvement in the clinical trial infrastructure to facilitate testing of new pharmacological and endoscopic interventions for Barrett's oesophagus. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Chemoprevention in Barrett's oesophagus." }, { "docid": "MED-4587", "text": "A polyphenol-rich (P-R) juice drink was developed as a potential approach to increase intake of dietary polyphenols. Analysis of the beverage by HPLC with PDA, fluorescence, and MS detection facilitated the identification/partial identification of 40 flavonoids and related phenolic compounds. The main constituents were (-)-epigallocatechin and other green tea flavan-3-ols, phloretin-2'-O-glucoside, gallic acid, hesperetin-7-O-rutinoside, 5-O-caffeoylquinic acid, and procyanidins, with trace levels of several flavonols and purple grape juice anthocyanins also being present. Healthy human subjects (n = 10) consumed 350 mL of the P-R juice drink, after which plasma and urine samples were collected over a 0-24 h period. HPLC-MS analysis identified 13 metabolites in plasma and a further 20 in urine. Qualitatively, the profiles of the glucuronide, sulfated, and methylated metabolites were very similar to those detected in earlier investigations when the main components in the juice drink were consumed separately in feeding studies with coffee, green tea, orange juice, and apple cider.", "title": "Identification of metabolites in human plasma and urine after consumption of a polyphenol-rich juice drink." }, { "docid": "MED-3920", "text": "Green tea is reported to have wide ranging beneficial health outcomes across epidemiological studies, which have been attributed to its flavonoid content. We investigated whether the flavonoid epigallocatechin gallate (EGCG) modulates brain activity and self-reported mood in a double-blind, placebo controlled crossover study. Participants completed baseline assessments of cognitive and cardiovascular functioning, mood and a resting state electroencephalogram (EEG) before and then 120 min following administration of 300 mg EGCG or matched placebo. EGCG administration was associated with a significant overall increase in alpha, beta and theta activity, also reflected in overall EEG activity, more dominant in midline frontal and central regions, specifically in the frontal gyrus and medial frontal gyrus. In comparison to placebo the EGCG treatment also increased self-rated calmness and reduced self rated stress. This pattern of results suggests that participants in the EGCG condition may have been in a more relaxed and attentive state after consuming EGCG. This is in keeping with the widespread consumption of green tea for its purported relaxing/refreshing properties. The modulation of brain function due to EGCG is deserving of further controlled human studies. Copyright © 2011 Elsevier Ltd. All rights reserved.", "title": "Acute neurocognitive effects of epigallocatechin gallate (EGCG)." }, { "docid": "MED-2200", "text": "Cancer of the gallbladder is rare but fatal, and has an unusual geographic and demographic distribution. Gallstones and obesity have been suggested as possible risk factors. As diet is known to influence both these factors, we carried out the present study to evaluate the possible role of diet in gallbladder carcinogenesis. A case-control study involving 64 newly diagnosed cases of gallbladder cancer and 101 cases of gallstones was carried out. The dietary evaluation was carried out by the dietary recall method based on a preset questionnaire developed specifically for the present study, keeping in mind the common dietary habits prevailing in this part of the world. Odds ratios (OR) and 95% confidence interval (CI) were calculated for various dietary items. A significant reduction in odds ratio was seen with the consumption of radish (OR 0.4; 95% CI 0.17-0.94), green chilli (OR 0.45; 95% CI 0.21-0.94) and sweet potato (OR 0.33; 95% CI 0.13-0.83) among vegetables, and mango (OR 0.4; 95% CI 0.16-0.99), orange (OR; 0.45; 95% CI 0.22-0.93), melon (OR 0.3; 95% CI 0.14-0.64) and papaya (OR 0.44; 95% 0.2-0.64) among fruits. A reduction in odds was also seen with the consumption of cruciferous vegetables, beans, onion and turnip, however the difference was not statistically significant. On the other hand, an increase in the odds was observed with consumption of capsicum (OR 2.2), beef (OR 2.58), tea (OR 1.98), red chilli (OR 1.29) and mutton (OR 1.2), however the difference was statistically not significant. In conclusion, the results of the present study show a protective effect of vegetables and fruits on gallbladder carcinogenesis, but red meat (beef and mutton) was found to be associated with increased risk of gallbladder cancer.", "title": "Diet and gallbladder cancer: a case-control study." } ]
4315
How to invest in the Russian oil market?
[ { "docid": "581038", "text": "The Russian ETFs may be broad, but a quick glance at ERUS and RBL's sector breakdown shows they're 45% and 47% energy sector, and their top holding is Gazprom comprising 9% and 14% of each ETF respectively, with plenty more oil and gas companies in their top 10 too. A harder question would be how to invest in Russia and avoid oil I think (and even then, the economy is thoroughly bound up in it). To rework a meme... In Soviet Russia, oil invest YOU!", "title": "" } ]
[ { "docid": "24911", "text": "Gee. Wouldn't it be nice to have that Russian car market back again? And how about oil &amp; gas field technology services (lucrative). If only there was no regime-changing US State Department led by meddlesome neocon Victoria Nuland on too long a leash together with such bit part players as ^the ^former ^US ^Ambassador ^to ^Honduras, everything would have gone along swimmingly. Farcical.", "title": "" }, { "docid": "526094", "text": "Russia main reserve is Euro, Gold and Yuan. They have dumped good sums of dollar since way back. The rest of oil buyers would gladly pay russians in whatever currency they want, specially if it is non dollar. Cheap oil on cheaper currency? Who doesn't want that? The chinese pay their oil in Yuan. Russian gladly takes Yuan, since its the most liquid currency in pacific, not to mention china is their no.1 trading partner.", "title": "" }, { "docid": "374809", "text": "nope. They say, by now they can live with ultra low oil price ...forever... (China currency agreement, export-import realignment, internal cost adjustment.) Russia has industry and warming relationship with China. Saudi does not. China oil demand is nearly infinity as far as russians are concern. This is reflected from Russia trade and budgetary situation. (they are back to huge current account surplus, and quickly shrinking deficit.) And they are not even back into global debt market yet. In time of wall st. bubble explosion.", "title": "" }, { "docid": "262925", "text": "\"It is important to first understand that true causation of share price may not relate to historical correlation. Just like with scientific experiments, correlation does not imply causation. But we use stock price correlation to attempt to infer causation, where it is reasonable to do so. And to do that you need to understand that prices change for many reasons; some company specific, some industry specific, some market specific. Companies in the same industry may correlate when that industry goes up or down; companies with the same market may correlate when that market goes up or down. In general, in most industries, it is reasonable to assume that competitor companies have stocks which strongly correlate (positively) with each-other to the extent that they do the same thing. For a simple example, consider three resource companies: \"\"Oil Ltd.\"\" [100% of its assets relate to Oil]; \"\"Oil and Iron Inc.\"\" [50% of its value relates to Oil, 50% to Iron]; and \"\"Iron and Copper Ltd.\"\" [50% of its value relates to Iron, 50% to Copper]. For each of these companies, there are many things which affect value, but one could naively simplify things by saying \"\"value of a resource company is defined by the expected future volume of goods mined/drilled * the expected resource price, less all fixed and variable costs\"\". So, one major thing that impacts resource companies is simply the current & projected price of those resources. This means that if the price of Oil goes up or down, it will partially affect the value of the two Oil companies above - but how much it affects each company will depend on the volume of Oil it drills, and the timeline that it expects to get that Oil. For example, maybe Oil and Iron Ltd. has no currently producing Oil rigs, but it has just made massive investments which expect to drill Oil in 2 years - and the market expects Oil prices to return to a high value in 2 years. In that case, a drop in Oil would impact Oil Inc. severely, but perhaps it wouldn't impact Oil and Iron Ltd. as much. In this case, for the particular share price movement related to the price of Oil, the two companies would not be correlated. Iron and Copper Ltd. would be unaffected by the price of Oil [this is a simplification; Oil prices impact many areas of the economy], and therefore there would be no correlation at all between this company's shares. It is also likely that competitors face similar markets. If consumer spending goes down, then perhaps the stock of most consumer product companies would go down as well. There would be outliers, because specific companies may still succeed in a falling market, but in generally, there would be a lot of correlation between two companies with the same market. In the case that you list, Sony vs Samsung, there would be some factors that correlate positively, and some that correlate negatively. A clean example would be Blackberry stock vs Apple stock - because Apple's success had specifically negative ramifications for Blackberry. And yet, other tech company competitors also succeeded in the same time period, meaning they did not correlate negatively with Apple.\"", "title": "" }, { "docid": "384757", "text": "I wouldn't doubt it. Apparently the oil pipeline to transfer oil from Iran to China through Pakistan has already been built, just needs to be activated, just needs the go ahead now. As for US track record, yeah, they have very bad one and it's only getting worse. I suspect the GOP will blame a lot of this on Obama on their next run for presidency and then they will blunder even more. Coincidently as well, a lot of people will say Russian or any non-western sources of news are not reliable because it's propaganda yet they are the western medias not spewing their on propaganda?", "title": "" }, { "docid": "315930", "text": "Here is some good advice, read your UCO prospectus. It seems to hold 20% of it's value ($600MM out of $3B) via 13800 of the Apr 21st 2015 contracts. (expiring in 30 days) Those will be rolled very quickly into the May contracts at a significant loss of NAV. (based on current oil futures chains) Meaning if crude oil stays exactly the same price, you'd still lose 1% (5% spread loss * .20% the percentage of NAV based off futures contracts) on the roll each month. Their other $2.4Billion is held in swaptions or cash, unsure how to rate that exposure. All I know is those 13,800 contracts are in contango danger during roll week for the next few months (IMO). I wonder if there is a website that tracks inflows and outflows to see if they match up with before and after the roll periods. http://www.proshares.com/funds/uco_daily_holdings.html How Oil ETFs Work Many oil ETFs invest in oil futures contracts. An oil futures contract is a commitment to buy a given amount of crude oil at a given price on a particular date in the future. Since the purpose of oil ETFs is only to serve as an investment vehicle to track the price of oil, the creators of the fund have no interest in stockpiling actual oil. Therefore, oil ETFs such as USO periodically “roll over” their futures contracts by selling the contracts that are approaching expiration and buying contracts that expire farther into the future. The Contango Problem While this process of continually rolling over futures contracts may seem like a great way to track the price of crude oil, there’s a practical problem with the method: contango. The rollover method would work perfectly if oil funds could sell their expiring contracts for the exact same price that they pay for the futures contracts they buy each month. However, in reality, it’s often true that oil futures contracts get more expensive the farther their expiration date is in the future. That means that every time the oil ETFs roll over their contracts, they lose the difference in value between the contracts they sell and the contracts they buy. That’s why funds like USO, which invests only in WTI light, sweet crude oil futures contracts, don’t directly track the performance of the WTI crude oil spot price. http://www.etftrends.com/2015/01/positioning-for-an-oil-etf-rebound-watch-for-contango/ Due to these reasons, I'd deem UCO for swing trading, not for 'investing' (buy-and-hold). Maybe later I'll remember why one shouldn't buy and hold leveraged vehicles (leverage slippage/decay). Do you have an exit price in mind ? or are you buy and hold ?", "title": "" }, { "docid": "248133", "text": "Russia has become more risky as an investment, thus investors, basically the market, wants to be paid more for investing in or owning those bonds. As yields go up, prices go down. So right now you can buy a low priced Russian bond with a high yield because the market views the risk involved as higher than risks involved in other similar securities.", "title": "" }, { "docid": "552934", "text": "What I'm saying is the NATO thing is also aggressive, and the coup was aggressive. Also I think ukraine is just another battle in a very long war between Russian and American oil interests. That's why I don't want to take a side, except keep the American military out of it.", "title": "" }, { "docid": "445535", "text": "\"I think all transportation uses only 1/3 of oil produced at best. That includes many things that won't be electrifed soon, like planes and ships. Don't forget how much oil agriculture uses in both fertilizer, pesticides and the least in running the equipment itself. So while demand may soften over time, it's not like will suddenly glut. Peak Oil (which we reached with \"\"conventional oil\"\" vs fracked) kinda says that each subsequent barrel will get more and more expensive to pump out (rather the popular perception we will suddenly run out). That basically has been a truism since over a century, because ERoEI on oil has declined. At peak return, iirc in the 1930s or so, we were getting something like 300 barrels of oil out for every barrel of energy invested on some fields in Saudi Arabia, now the overall average is down to around 10 or less? Point is, oil won't go to $10. Oil industry could not survive on it and they know we don't have alternatives for many oil uses (it's the most easily portable liquid with the highest energy concentration), so why price it as such? If people really wanted to reduce their carbon/oil footprint, they'd stop pining for electric cars and switch to a plantbased diet - which will have a far greater impact for much less investment. On top of all the health benefits they accumulate.\"", "title": "" }, { "docid": "154229", "text": "\"In this environment, I don't think that it is advisable to buy a broad emerging market fund. Why? \"\"Emerging market\"\" is too broad... Look at the top 10 holdings of the fund... You're exposed to Russia & Brazil (oil driven), Chinese and Latin American banks and Asian electronics manufacturing. Those are sectors that don't correlate, in economies that are unstable -- a recipie for trouble unless you think that the global economy is heading way up. I would recommend focusing on the sectors that you are interested in (ie oil, electronics, etc) via a low cost vehicle like an index ETF or invest using a actively managed emerging markets fund with a strategy that you understand. Don't invest a dime unless you understand what you are getting into. An index fund is just sorting companies by market cap. But... What does market cap mean when you are buying a Chinese bank?\"", "title": "" }, { "docid": "179201", "text": "The US has been the most trusted since WWII. I'll be happy to take my chances with the US stock market over any other. Yea, there are definitely bubbles in the US economy, where else would you put your money then? Bitcoin, gold, in the euro, Chinese stock market (LOL), land in the US or German bunds? how about oil or Japanese stock market? I'll take US land and US equity any day of the week over any of the other. Maybe some gold sprinkled in. You can invest in the Chinese stock market and the European stock exchanges", "title": "" }, { "docid": "501384", "text": "\"This is only a partial answer to your question #1. If you have a conservative approach to savings (and, actually, even if you don't), you should not invest all of your money in any single industry or product. If you want to invest some money in oil, okay, but don't overdo it. If your larger goal is to invest the money in a manner that is less risky but still more lucrative than a savings account, you should read up on personal finance and investing to get a sense of what options are available. A commonly-recommended option is to invest in low-cost index funds that mirror the performance of the stock market as a whole. The question of \"\"how should I invest\"\" is very broad, but you can find lots of starting points in other questions on this site, by googling, or by visiting your local library.\"", "title": "" }, { "docid": "74615", "text": "\"The VDE fund is an energy fund so this is a function of recent price changes in oil (and gas, coal, &c). For example. Lets say last year when oil was $100 per barrel a bunch of companies saw a good return and put $ 100 million into a bunch of leases, boreholes, pumps, &c to return $10 million per year, and the market says yeah, they're all together worth 100M. Now oil is less, maybe $40 per the link. These exploration companies don't have a lot of labor or variable costs; they are operationally profitable, may have \"\"use it or lose it\"\" leases or minimum pumping requirements for contract or engineering reasons. Lets say the cash flow is 7M so the market values them at 70M. They still have about 100M book value so here we are at .7 and I believe the scenario in the question. Nobody would invest in new capacity at this oil price. The well equipment could be repurposed but not the borehole or lease, so the best use is to continue pumping and value it on cash flow. If an individual well runs negative long enough and goes bust, either a different pumper will pay the minimum price that gives profitable cash flow, or that borehole that cost millions to dig is shut off and rendered valueless. The CNBC article says some explorers are playing games with debt to maintain yield, so there is that too. In the ETF, your bet is that the market is wrong and oil will go up, increasing future cash flows (or you like the current yield, taking on the risk that some of these oil explorers could go bust).\"", "title": "" }, { "docid": "347874", "text": "\"The 8% rate offered by Russian banks on US Dollar accounts reflects the financial problems they have. They would prefer to lend US Dollars on the international financial markets at the same rate as US banks, but loans to Russian banks are considered to be more risky. In fact, the estimated \"\"default\"\" risk is ~6%. Your ruble deposits at Russian banks are most likely backed by state guarantees, which reduces the risk and therefore the effective interest rate.\"", "title": "" }, { "docid": "590917", "text": "Well, it's the same fundamental principals as all investing. Buy low, sell high. Buy things that will be scarce in the future while they're abundant. Buy up everything and create artificial scarcity. It's the same thing that's done with diamonds and was done with oil for quite some time. Small markets like tickets to a show are just much more vulnerable to being cornered. How do you legislate against ticket scalpers without turning yourself into a hypocrite? Obviously you're not going to pull the plug on Wall Street or angel investing or any other investing strategy, and you'd have a hell of a time shutting down DeBeers. Capitalism isn't perfect if your desire is fairness.", "title": "" }, { "docid": "464502", "text": "So far we have a case for yes and no. I believe the correct answer is... maybe. You mention that most of your expenses are in dollars which is definitely correct, but there is an important complication that I will try to simplify greatly here. Many of the goods you buy are priced on the international market (a good example is oil) or are made from combinations of these goods. When the dollar is strong the price of oil is low but when the dollar is weak the price of oil is high. However, when you buy stuff like services (think a back massage) then you pay the person in dollars and the person you are paying just wants dollars so the strength of the dollar doesn't really matter. Most people's expenses are a mix of things that are priced internationally and locally with a bias toward local expenses. If they also have a mix of investments some of which are international and depend on the strength of the dollar and some are domestic and do not, then they don't have to worry much about the strength/weakness of the dollar later when they sell their investments and buy what they want. If the dollar is weak than the international goods will be more expensive, but at the same time international part of their portfolio will be worth more. If you plan on retiring in a different country or have 100% of your investments in emerging market stocks than it is worth thinking about either currency hedging or changing your investment mix. However, for many people a good mix of domestic and international investments covers much of the risk that their currency will weaken while offering the benefits of diversification. The best part is you don't need to guess if the dollar will get stronger or weaker. tl;dr: If you want your portfolio to not depend on currency moves then hedge. If you want your retirement to not depend on currency moves then have a good mix of local and unhedged international investments.", "title": "" }, { "docid": "154611", "text": "\"In layman's terms, oil on the commodities market has a \"\"spot price\"\" and a \"\"future price\"\". The spot price is what the last guy paid to buy a barrel of oil right now (and thus a pretty good indicator of what you'll have to pay). The futures price is what the last guy paid for a \"\"futures contract\"\", where they agreed to buy a barrel of oil for $X at some point in the future. Futures contracts are a form of hedging; a futures contract is usually sold at a price somewhere between the current spot price and the true expected future spot price; the buyer saves money versus paying the spot price, while the seller still makes a profit. But, the buyer of a futures contract is basically betting that the spot price as of delivery will be higher, while the seller is betting it will be lower. Futures contracts are available for a wide variety of acceptable future dates, and form a curve when plotted on a graph that will trend in one direction or the other. Now, as Chad said, oil companies basically get their cut no matter what. Oil stocks are generally a good long-term bet. As far as the best short-term time to buy in to an oil stock, look for very short windows when the spot and near-future price of gasoline is trending downward but oil is still on the uptick. During those times, the oil companies are paying their existing (high) contracts for oil, but when the spot price is low it affects futures prices, which will affect the oil companies' margins. Day traders will see that, squawk \"\"the sky is falling\"\" and sell off, driving the price down temporarily. That's when you buy in. Pretty much the only other time an oil stock is a guaranteed win is when the entire market takes a swan dive and then bottoms out. Oil has such a built-in demand, for the foreseeable future, that regardless of how bad it gets you WILL make money on an oil stock. So, when the entire market's in a panic and everyone's heading for gold, T-debt etc, buy the major oil stocks across the spectrum. Even if one stock tanks, chances are really good that another company will see that and offer a buyout, jacking the bought company's stock (which you then sell and reinvest the cash into the buying company, which will have taken a hit on the news due to the huge drop in working capital). Of course, the one thing to watch for in the headlines is any news that renewables have become much more attractive than oil. You wait; in the next few decades some enterprising individual will invent a super-efficient solar cell that provides all the power a real, practical car will ever need, and that is simultaneously integrated into wind farms making oil/gas plants passe. When that happens oil will be a thing of the past.\"", "title": "" }, { "docid": "100721", "text": "a) Nothing would support this company going back to $.50 per share b) Fundamentally the market for this sectors has been obliterated and the fundamentals don't look like they will improve. Similar companies experience what this one is and will be going through, they borrow the hilt and hope they can pump enough oil and sell the oil at a high price. Oil goes below, WAYYY below the price they can sell it at and even break even, so they are burning cash until they declare bankruptcy. This company is not an exception. So here is what to look at on their balance sheet: assets and liabilities. Liabilities are debt. Their debt is over 50% of their assets, that debt has interest and there is NO WAY they are making a profit. Their website's last financial statement is from September 30th.. LOL, so they haven't even released a quarterly financial statement in two quarters straight, so have they released anything? Given what we know about the dire state of the entire oil drilling industry, lets see if these guys are the exception to the rule (spoiler; they aren't) February 15th, 2015 http://www.marketwatch.com/story/strategic-oil-gas-ltd-provides-operations-update-2015-02-19-16173591 The Company prudently elected to stop the winter Muskeg drilling program in order to preserve capital. So now they aren't even getting new assets to resale, they aren't making any money from that operation, their debt still has interest payments though. Approximately 700 Boe/d of production has been shut-in by suspending operations at Bistcho, Cameron Hills and Larne, which are not economic at current commodity prices. Predictable. Also, you should notice from their actual financial statements (from 6 months ago, lol) (when the price of oil was over 100% higher than it is today, lol), this company already wasn't a good performer. They have been financing themselves by doing private placements, by issuing shares to investors that are not you, and diluting the share value of ALL OTHER SHAREHOLDERS. Dead in the water. I got this from skimming their financial report, without even being familiar with how canadian companies report. Its just bad news. You shouldn't be married to this investment.", "title": "" }, { "docid": "306189", "text": "There are those who would suggest that due to the Efficient Market Hypothesis, stocks are always fairly valued. Consider, if non-professional posters on SE (here) had a method that worked beyond random chance, everyone seeking such a method would soon know it. If everyone used that method, it would lose its advantage. In theory, this is how stocks' values remain rational. That said, Williams %R is one such indicator. It can be seen in action on Yahoo finance - In the end, I find such indicators far less useful than the news itself. BP oil spill - Did anyone believe that such a huge oil company wouldn't recover from that disaster? It recovered by nearly doubling from its bottom after that news. A chart of NFLX (Netflix) offers a similar news disaster, and recovery. Both of these examples are not quantifiable, in my opinion, just gut reactions. A quick look at the company and answer to one question - Do I feel this company will recover? To be candid - in the 08/09 crash, I felt that way about Ford and GM. Ford returned 10X from the bottom, GM went through bankruptcy. That observation suggests another question, i.e. where is the line drawn between 'investing' and 'gambling'? My answer is that buying one stock hoping for its recovery is gambling. Being able to do this for 5-10 stocks, or one every few months, is investing.", "title": "" }, { "docid": "1103", "text": "Investing only in one industry may be problematic as it is highly correlated. There are factor outside your (or anyones) knowledge which may affect all the industry: If you are familiar with the industry it may happen that you work in that (ignore rest of paragraph if this is not the case). In such case you are likely to have problems at work (frozen salary, no bonus, position terminated) and you need to liquidate the investments at that point (see many advice regarding ESPP). Depending on your field you may have some inside knowledge so even if you would took a position without it you may need to somehow prove it. On the other hand diversifying the investment might reduce the volatility of investment. Rise in oil will cause problems for air industry but will be a boom for oil industry etc. In this way you smooth the grow of the investments. Investing part of portfolio into specific industry may make more sense. It still possibly worth to avoid it at the beginning investor may have trouble to beat the market (for example according to behavioural economics you are exposed to various biases, or if markets are efficient then prices most likely already take into account any information you may have). (I'm still new to all this so it's mostly based on what I read rather then any personal experience. Also a standard disclaimer that this is not an investment, or any other, advice and I'm not licensed financial advisor in any jurisdiction)", "title": "" }, { "docid": "563015", "text": "\"Yes, undeniable facts: sleazy Hillary conspires with fake-news CNN to cheat on debate questions, something that my son would be expelled from school if he cheated like that on his test, something that NEVER EVER happened in presidential debates before and there was no need for it (it's just debate questions, that Trump handled very well). These facts and MANY other facts demonstrated to the American people how corrupt, evil, untrustworthy and conspiring is the DNC and Hillary are. So Trump won the presidency, congress, senate and governors. He won also the popular vote if California did not allow millions of illegal aliens to vote. **And now you want to believe that \"\"Russians!\"\" made Hillary, the DNC, Podesta, Loretta Lynch, Donna Brazile, Debbie Schultz, etc do all those things, so Trump will win? And all this \"\"Russians!\"\" happening while under the watch of Obama in charge of the FBI?** Darling, there was no \"\"Russians!\"\" collusion! The \"\"Russians!\"\" collusion is just to divert attention from corrupt Democrats to Trump. I am not worried: so far Hillary is under several investigations and Tump is not under a single investigation!!!!! (Investigating \"\"Russians!\"\" is not investigating Trump). Trump will win 2020 again and Hillary and her friends will be rotting in jail.\"", "title": "" }, { "docid": "519025", "text": "The papers you would need to buy are called 'futures', and they give you the right to buy (or sell) a certain amount of oil at a certain location (some large harbor typically), for a certain price, on a certain day. You can typically sell these futures anytime (if you find someone that buys them), and depending on the direction you bought, you will make or lose money according to oil rice changes - if you have the future to get oil for 50 $, and the market price is 60, this paper is obviously worth 10 $. Note that you will have to sell the future at some day before it runs out, or you get real oil in some harbor somewhere for it, which might not be very useful to you. As most traders don't want really any oil, that might happen automatically or by default, but you need to make sure of that. Note also that worst case you could lose a lot more money than you put in - if you buy a future to deliver oil for 50 $, and the oil price runs, you will have to procure the oil for new price, meaning pay the current price for it. There is no theoretical limit, so depending on what you trade, you could lose ten times or a thousand times what you invested. [I worded that without technical lingo so it is clear for beginners - this is the concept, not the full technical explanation]", "title": "" }, { "docid": "316444", "text": "The Oil futures are exactly that. They are people forecasting the price of oil at a point of time in the future where they are willing to buy oil at that price. That said, Do you have evidence of a correlation of Price of oil to the shares of oil stocks? Oil companies that are good investments are generally good investments regardless of the cost of oil. If you did not know about oil futures then you might be best served by consulting an investment professional for some guidance.", "title": "" }, { "docid": "209349", "text": "\"I'll take a stab at this question and offer a disclosure: I recently got in RING (5.1), NEM (16.4), ASX:RIO (46.3), and FCX (8.2). While I won't add to my positions at current prices, I may add other positions, or more to them if they fall further. This is called catching a falling dagger and it's a high risk move. Cons (let's scare everyone away) Pros The ECB didn't engage in as much QE as the market hoped and look at how it reacted, especially commodities. Consider that the ECB's actions were \"\"tighter\"\" than expected and the Fed plans to raise rates, or claims so. Commodities should be falling off a cliff on that news. While most American/Western attention is on the latest news or entertainment, China has been seizing commodities around the globe like crazy, and the media have failed to mention that even with its market failing, China is still seizing commodities. If China was truly panicked about its market, it would stop investing in other countries and commodities and just bail out its own country. Yet, it's not doing that. The whole \"\"China crisis\"\" is completely oversold in the West; China is saying one thing (\"\"oh no\"\"), but doing another (using its money to snap up cheap commodities). Capitalism works because hard times strengthen good companies. You know how many bailouts ExxonMobil has received compared to Goldman Sachs? You know who owns more real wealth? Oil doesn't get bailed out, banks do, and banks can't innovate to save their lives, while oil innovates. Hard times strengthen good companies. This means that this harsh bust in commodities will separate the winners from the losers and history shows the winners do very well in the long run. Related to the above point: how many bailouts from tax payers do you think mining companies will get? Zero. At least you're investing in companies that don't steal your money through government confiscation. If you're like me, you can probably find at least 9 people out of 10 who think \"\"investing in miners is a VERY BAD idea.\"\" What do they think is a good idea? \"\"Duh, Snapchat and Twitter, bruh!\"\" Then there's the old saying, \"\"Be greedy when everyone's fearful and fearful when everyone's greedy.\"\" Finally, miners own hard assets. Benjamin Graham used to point this out with the \"\"dead company\"\" strategy like finding a used cigarette with one more smoke. You're getting assets cheap, while other investors are overpaying for stocks, hoping that the Fed unleashes moar QE! Think strategy here: seize cheap assets, begin limiting the supply of these assets (if you're the saver and not borrowing), then watch as the price begins to rise for them because of low supply. Remember, investors are part owners in companies - take more control to limit the supply. Using Graham's analogy, stock pile those one-puff cigarettes for a day when there's a low supply of cigarettes. Many miners are in trouble now because they've borrowed too much and must sell at a low profit, or in some cases, must lose. When you own assets debt free, you can cut the supply. This will also help the Federal Reserve, who's been desperately trying to figure out how to raise inflation. The new patriotic thing to do is stimulate the economy by sending inflation up, and limiting the supply here is key.\"", "title": "" }, { "docid": "102698", "text": "\"Anthony Russell - I agree with JohnFx. Petroleum is used in making many things such as asphalt, road oil, plastic, jet fuel, etc. It's also used in some forms of electricity generation, and some electric cars use gasoline as a backup form of energy, petrol is also used in electricity generation outside of cars. Source can be found here. But to answer your question of why shares of electric car companies are not always negatively related to one another deals with supply and demand. If investors feel positively about petroleum and petroleum related prospects, then they are going to buy or attempt to buy shares of \"\"X\"\" petrol company. This will cause the price of \"\"X\"\", petrol company to rise, ceteris paribus. Just because the price of petroleum is high doesn't mean investors are going to buy shares of an electric car company. Petrol prices could be high, but numerous electric car companies could be doing poorly, now, with that being said you could argue that sales of electric cars may go up when petrol prices are high, but there are numerous factors that come into play here. I think it would be a good idea to do some more research if you are planning on investing. Also, remember, after a company goes public they no longer set the price of the shares of their stock. The price of company \"\"X\"\" shares are determined by supply and demand, which is inherently determined by investors attitudes and expectations, ultimately defined by past company performance, expectations of future performance, earnings, etc.. It could be that when the market is doing well - it's a good sign of other macroeconomic variables (employment, GDP, incomes, etc) and all these factors power how often individuals travel, vacation, etc. It also has to deal with the economy of the country producing the oil, when you have OPEC countries selling petrol to the U.S. it is likely much cheaper per barrel than domestic produced and refined petrol because of the labor laws, etc. So a strong economy may be somewhat correlated with oil prices and a strong market, but it's not necessarily the case that strong oil prices drive the economy..I think this is a great research topic that cannot be answered in one post.. Check this article here. From here you can track down what research the Fed of Cleveland has done concerning this. My advice to you is to not believe everything your peers tell you, but to research everything your peers tell you. With just a few clicks you can figure out the legitimacy of many things to at least some degree.\"", "title": "" }, { "docid": "78586", "text": "\"Question 2 Some financial institutions can provide a way to invest small amounts with low or no cost fees over a period of time (like monthly, weekly, etc). For instance, a few brokerages have a way to buy specific ETFs for no cost (outside of the total expense ratio). Question 3 When someone says that investing is like buying a lottery ticket, they are comparing an event that almost always has at least a 99.9% of no return (large winnings) to an event that has much better odds. Even if I randomly pick a stock in the S&P 500 and solely invest in it, over the course of a given year, I do not face a 99.9% chance of losing everything. So comparing the stock market to a lottery, unless a specific lottery has much better odds (keep in mind that some of these jackpots have a 99.9999999% of no return) is not the same. Unfortunately, nothing truly safe exists - risk may mutate, but it's always present; instead, the probability of something being safe and (or) generating a return may be true for a given period of time, while in another given period of time, may become untrue. One may argue that holding cash is safer than buying an index fund (or stock, ETF, mutual fund, etc), and financially that may be true over a given period of time (for instance, the USD beat the SPY for the year of 2008). Benjamin Franklin, per a biography I'm reading, argued that the stock market was superior to gold (from the context, it sounds like the cash of his day) because of what the stock market represents: essentially you're betting on the economic output of workers. It's like saying, in an example using oil, that I believe that even though oil becomes a rare resource in the long run, human workers will find an alternative to oil and will lead to better living standards for all of us. Do civilizations like the Mongolian, Roman, and Ottoman empires collapse? Yes, and would holding the market in those days fail? Yes. But cash and gold might be useless too because we would still need someone to exchange goods with and we would need to have the correct resources to do so (if everyone in a city owns gold, gold has little value). The only \"\"safe bet\"\" in those days would be farming skill, land, crops and (or) livestock because even without trading, one could still provide some basic necessities.\"", "title": "" }, { "docid": "116921", "text": "Because we need energy in the form of oil. If more of our money is spent on oil, there is less money to spend on other items especially luxuries like dining out and new cars (ironically) Since there is less money available, the price of other things shift with it and the whole economy moves. Since less money is available, the value of a single dollar goes up. Basically, it is because we as a species (let alone nations) are unbelievably dependent on having oil at this point in our existence. How do currency markets work? What factors are behind why currencies go up or down?", "title": "" }, { "docid": "485976", "text": "America's economy is a War based economy, you need to understand that and chew on it and admit it to yourself. We are not some happy happy charlie and the chocolate fucking factory economy, we profit from war, human misery and of course really really bad banking practices and exporting inflation as the retarded Indians are going to find out soon, not the Red ones we gave cholera &amp; Small pox to, the ones that think they are our friends and we are going to build F-16s in their land of open defecation and cow piss consumption. Now everything was really great and we were about to get our hands on some really cheap Iraqi oil, but the fucking Taliban we trained and armed to fight the Russians decided they wanted to fight us when we attacked them. Problem was we didn't need M1 Abrahams and F-35s and nuclear subs to fight them. And then the Bloody Iraqis wouldn't quit and it turned out we didn't need M1s, and F-35s and Nuclear subs to fight them. In fact we didn't have anything that made it cost effective to fight a guy with a rocket launcher and a pick up truck and our economy started to fail and we landed up in a depression which we called a recession, but it was a depression and thats why our central bank is still trying to get rid of that shit they sold to raise US $ 2.4 Trillion dollars for the Iraq war. Really bad investment that. Well a reemergent Russia, was like a god send, we could restart the cold war and start making M1s and F-35s and Subs again and have a worthy foe, we would have to scare the shit out of the American people to divert the money to the military, but that would get factories cracking again and corporate lending going again, and NATO would just have to buy our shit up . .right? Turns out it wasn't a God send, the priests were busy diddling the choir boys and the rabbi's selling Palestinian spare parts, and the rest of the godless lot getting confused about the gender and the Russians were actually dead serious, scared the shit out of Ukraine and annex Crimea . . .and we couldn't do shit. North Korea . . .the Fuckers got nuclear missiles and a freaking hydrogen bomb, I mean shit . . .we were just play acting to get the economy booming again and this guy had to start blowing shit up. And Iran they are sure to go next, and then the whole middle east. We gave the Israelis F-35s, even though they can barely fly . .that junk has just taken so long to develop, they ain't never going to figure the code out and make it work. The God damned Missile shield is only good enough for fire crackers and scuds. These guys are lobbing ICBMS and now everybody knows our missile shield is really good to look at but doesn't do much, did you see the Japanese ducking for cover. And the Chinese . .god damn . . You just can't guess what is happening behind those eyes . .they can crash our economy like swatting a fly, yet the sit there and we talk shit day after day after day and the just smile and say some diplomatic shit, they are playing the long game for sure and we have no clue what the fuck it is. I guess we are going to have to pick a fight with Canada soon, everybody else is so edgy and starts wanting to shoot back at us, how the fuck is one supposed to run an economy when the keep threatening to bomb us. At least there is a Wall between the Chinese and US . .not sure who built it. .could have been the Mexicans . . .didn't get the bill, definitely not paying for it.", "title": "" }, { "docid": "449827", "text": "Foreign business doesn't land in Russia because of its despotic nature. Russian state assets have been looted since the year 1991. The first generation gang was Moscow based Boris Yeltsin providing it breastfeeding. Since the year 2000 the Baskov Lane dwarf has seated the throne breastfeeding his buddies from Petrograd. Not Germans nor anyone else is willing to invest to a country driven by a bunch of ill behaving buccaneers. Not even Russian money stays in the country but is emigrating. I wonder why is that.", "title": "" }, { "docid": "583695", "text": "\"The above answers are great. I would only add to the \"\"rainy day\"\" part, that even though the cash provides a good cushion, \"\"a stormy day\"\" could mean even losing those emergency savings to the unignorable randomness that governs the world economy. Though unlikely, what happened to the russian ruble and the latest decision of the swiss cental bank are just two recent reminders that uncertainty must be treated as a constant. I would therefore advise you to invest some of the money in land capable of agriculture. How expensive is land over there in the UK?\"", "title": "" } ]
PLAIN-2298
Uruguay
[ { "docid": "MED-4071", "text": "An increased risk of breast cancer has been observed in women who consume \"very well-done\" meats. Heterocyclic amines are mutagenic and carcinogenic pyrolysis products formed during high temperature cooking of meats. In the present study, human milk samples were analyzed for PhIP, one of the most abundant dietary heterocyclic amine. A protocol was developed with a mixed-mode cation exchange sorbent for the extraction of heterocyclic amines from milk. Milk samples were acquired from healthy Canadian women. With LC/MS analysis and the method of isotope dilution for quantification, levels of PhIP were determined in human milk samples. PhIP was detected in 9 of the 11 milk samples, at levels as high as 59 pg/mL (ppt). No PhIP was detected in the milk of the vegetarian donor. Detection of PhIP in milk indicates that ductal mammary epithelial cells are directly exposed to this carcinogen, suggesting that heterocyclic amines are possible human mammary carcinogens.", "title": "Detection of PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) in the milk of healthy women." }, { "docid": "MED-4073", "text": "The cooked meat carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induces tumours of the breast, colon and prostate in rats. Here we show that in addition to its well-established genotoxicity, which can be detected at concentrations >10(-6) M, PhIP is also oestrogenic. In COS-1 cells transiently transfected with an oestrogen-responsive reporter gene, PhIP (10(-10)-10(-6) M) mediated transcription through oestrogen receptor (ER) alpha, but not ER-beta, and inhibition by the pure ER antagonist ICI 182 780 demonstrated a requirement for a functional ER. In contrast, the structurally related food-derived carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) failed to induce reporter gene transcription. Additionally, we show that in a hormonally responsive breast cancer cell line (MCF-7 cells), PhIP induced transcriptional activation using endogenously expressed ER. Examination of the genotoxic potential of PhIP using a model mammalian cell mutation assay (hprt(-) locus) demonstrated that the genetic toxicology of PhIP was readily detectable, but separate, in terms of effective concentration, from its oestrogenic activity. To determine whether the oestrogenicity of PhIP could mediate oestrogen-dependent responses such as cell growth, we examined the growth of hormonally responsive cells (MCF-7 cells). We show that PhIP can stimulate cell proliferation and, again, this was dependent upon a functional ER. Using ligand blotting, we further show that PhIP can stimulate the expression of progesterone receptor (PR-A and PR-B) and c-MYC and activate the MAPK signal transduction pathway. These responses were similar to that produced by oestradiol, in terms of temporal aspects, potency and a requirement for a functional ER. Each of these dose-dependent mitogenic responses occurred at concentrations of PhIP ( approximately 10(-9)-10(-11)M) that are likely to be equivalent to systemic human exposure via consumption of cooked meat. Thus PhIP can induce cellular responses that encompass altered gene expression and mitogenesis. We suggest that the combination of genetic toxicology and oestrogen-like promotion of genomic and cellular events provide a mechanism for the tissue-specific tumorigenicity of this compound.", "title": "The cooked food derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine is a potent oestrogen: a mechanistic basis for its tissue-speci..." } ]
[ { "docid": "MED-4069", "text": "To examine whether meat intake modifies breast-cancer risk, a case-control study was conducted in Uruguay. Dietary patterns were assessed in detail (for cases, before diagnosis or symptoms occurred) using a food frequency questionnaire involving 64 food items, which allowed total energy intake to be calculated. Nutrient residuals were calculated through regression analysis. After adjustment for potential confounders (which included family history of breast cancer, menopausal status, body-mass index, total energy and total alcohol intake), an increased risk associated with consumption of total meat intake, red meat intake, total fat and saturated fat intake was observed. The strongest effect was observed for red meat intake (OR 4.2, 95% CL 2.3-7.7) for consumption in the upper quartile, after controlling for protein and fat intake. This suggests an independent effect for meat. Since experimental studies have shown a strong effect of heterocyclic amines in rat mammary carcinogenesis, further studies should be performed in human epidemiology, perhaps using biomarkers of heterocyclic amine exposure.", "title": "Meat, fat and risk of breast cancer: a case-control study from Uruguay." }, { "docid": "MED-4741", "text": "BACKGROUND: Previous studies have suggested that egg consumption may increase the risk of colorectal cancer and some other cancers. However, the evidence is still limited. To further explore the association between egg intake and cancer risk we conducted a case-control study of 11 cancer sites in Uruguay between 1996 and 2004, including 3,539 cancer cases and 2,032 hospital controls. RESULTS: In the multivariable model with adjustment for age, sex (when applicable), residence, education, income, interviewer, smoking, alcohol intake, intake of fruits and vegetables, grains, dairy products, fatty foods, meat, energy intake and BMI, there was a significant increase in the odds of cancers of the oral cavity and pharynx (OR= 2.02, 95% CI: 1.19-3.44), upper aerodigestive tract (OR= 1.67, 95% CI: 1.17-2.37), colorectum (OR= 1.64, 95% CI: 1.02-2.63), lung (OR= 1.59, 95% CI: 1.10-2.29), breast (OR= 2.86, 95% CI: 1.66-4.92), prostate (OR= 1.89, 95% CI: 1.15-3.10), bladder (OR= 2.23, 95% CI: 1.30-3.83) and all cancer sites combined (OR= 1.71, 95% CI: 1.35-2.17) with a high vs low egg intake. CONCLUSIONS: We found an association between higher intake of eggs and increased risk of several cancers. Further prospective studies of these associations are warranted.", "title": "Egg consumption and the risk of cancer: a multisite case-control study in Uruguay." }, { "docid": "MED-3424", "text": "The purpose of this study is to investigate the possible underlying pathogenesis of erectile dysfunction(ED) in young men with low risk of coronary heart disease and no well-known aetiology. To conduct this study, 122 patients with ED under the age of 40 were enrolled, along with 33 age-matched normal control subjects. The patients with ED had significantly higher levels of systolic blood pressure (SBP), total cholesterol and triglyceride, high sensitivity C-reactive protein (hs-CRP), greater carotid intima-media thickness (CIMT) and Framingham risk score (FRS) than the control group, though all of these values were within the respective normal range. Further, the brachial artery flow- mediated vasodilation (FMD) values were significantly lower in ED patients and correlated positively with the severity of ED (r = 0.714, p < 0.001). When these significant factors were studied in the multivariate logistic regression model, FMD, SBP, hs-CRP and FRS remained the statistical significance. The receiver-operating characteristic (ROC) analysis demonstrated that FMD had a high ability to predict ED in young male with low FRS [area under the curve (AUC) 0.921, p < 0.001]. The cutoff value of FMD <10.25% had sensitivity of 82.8% and specificity of 100% for diagnosis of ED. FRS and hs- CRP were also proven to be predictors of ED (AUC 0.812, p < 0.001; AUC 0.645, p = 0.011, respectively). The results of this study validated that subclinical endothelial dysfunction and low-grade inflammation may be the underlying pathogenesis of ED with no well-known aetiology. Young patients complaining of ED should be screened for cardiovascular risk factors and possible subclinical atherosclerosis. Measurement of FMD, hs-CRP and FRS can improve our ability to predict and treat ED, as well as subclinical cardiovascular disease early for young male. © 2012 The Authors. International Journal of Andrology © 2012 European Academy of Andrology.", "title": "Subclinical endothelial dysfunction and low-grade inflammation play roles in the development of erectile dysfunction in young men with low risk of ..." }, { "docid": "MED-3990", "text": "BACKGROUND: The available evidence on vitamin D and mortality is inconclusive. OBJECTIVES: To assess the beneficial and harmful effects of vitamin D for prevention of mortality in adults. SEARCH STRATEGY: We searched The Cochrane Library, MEDLINE, EMBASE, LILACS, the Science Citation Index Expanded, and Conference Proceedings Citation Index-Science (to January 2011). We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials. SELECTION CRITERIA: We included randomised trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention. Vitamin D could have been administered as supplemental vitamin D (vitamin D(3) (cholecalciferol) or vitamin D(2) (ergocalciferol)) or an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol) or 1,25-dihydroxyvitamin D (calcitriol)). DATA COLLECTION AND ANALYSIS: Six authors extracted data independently. Random-effects and fixed-effect model meta-analyses were conducted. For dichotomous outcomes, we calculated the risk ratios (RR). To account for trials with zero events, meta-analyses of dichotomous data were repeated using risk differences (RD) and empirical continuity corrections. Risk of bias was considered in order to minimise risk of systematic errors. Trial sequential analyses were conducted to minimise the risk of random errors. MAIN RESULTS: Fifty randomised trials with 94,148 participants provided data for the mortality analyses. Most trials included elderly women (older than 70 years). Vitamin D was administered for a median of two years. More than one half of the trials had a low risk of bias. Overall, vitamin D decreased mortality (RR 0.97, 95% confidence interval (CI) 0.94 to 1.00, I(2) = 0%). When the different forms of vitamin D were assessed separately, only vitamin D(3) decreased mortality significantly (RR 0.94, 95% CI 0.91 to 0.98, I(2) = 0%; 74,789 participants, 32 trials) whereas vitamin D(2), alfacalcidol, or calcitriol did not. Trial sequential analysis supported our finding regarding vitamin D(3), corresponding to 161 individuals treated to prevent one additional death. Vitamin D(3) combined with calcium increased the risk of nephrolithiasis (RR 1.17, 95% CI 1.02 to 1.34, I(2) = 0%). Alfacalcidol and calcitriol increased the risk of hypercalcaemia (RR 3.18, 95% CI 1.17 to 8.68, I(2) = 17%). Data on health-related quality of life and health economics were inconclusive. AUTHORS' CONCLUSIONS: Vitamin D in the form of vitamin D(3) seems to decrease mortality in predominantly elderly women who are mainly in institutions and dependent care. Vitamin D(2), alfacalcidol, and calcitriol had no statistically significant effect on mortality. Vitamin D(3) combined with calcium significantly increased nephrolithiasis. Both alfacalcidol and calcitriol significantly increased hypercalcaemia.", "title": "Vitamin D supplementation for prevention of mortality in adults." }, { "docid": "MED-1203", "text": "BACKGROUND: Clinical mood disorders often become clinically manifest in the later teenage years and early twenties and can be associated with a poor long-term prognosis. The primary prevention of these disorders would therefore have great public health value. Nutritional supplements are a feasible intervention for primary prevention and several epidemiological studies have indicated links between low folate status and depressive symptomatology in the general population. METHOD: A randomised, double blind, parallel group, placebo-controlled trial in which participants, aged 14-24 years, at increased familial risk of mood disorder, were randomised to folic acid (2.5 mg daily) or identical placebo liquid for a maximum of 36 months. Primary outcome data (the onset of a DSM-IV mood disorder) were collected from 112 participants; 56 per group. RESULTS: The incidence of mood disorder in the folic acid and placebo groups were 14.3% and 17.9% respectively, a non-significant difference. However, there was post-hoc evidence that folic acid delayed the time to onset of mood disorder in those participants who became unwell. LIMITATIONS: Small sample size and rate of onset of mood disorders lower than expected. CONCLUSIONS: Although long term folic acid supplementation was well tolerated, with high levels of adherence, there was no evidence that it reduced the incidence of mood disorder compared to those taking placebo. Copyright © 2014 Elsevier B.V. All rights reserved.", "title": "Folic acid supplementation for prevention of mood disorders in young people at familial risk: a randomised, double blind, placebo controlled trial." }, { "docid": "MED-4839", "text": "We encountered a 62-year-old woman with a progressively worsening sore throat and a sharp lump located in her left upper neck, which appeared several hours before admission. After questioning, she underwent rigid esophagoscopy at a local hospital for suspected fish bone impaction but this gave a negative result. Unusual signs caused us to arrange a computed tomography scan, which showed that a foreign body had penetrated the left sternocleidomastoid muscle to the subcutaneous layer, with extensive emphysema in the neck. We extracted the foreign body with a 1-cm horizontal incision of the neck under general anesthesia. The patient returned to a normal diet and was discharged on day 5 of hospitalization without further morbidity. This is another rare case of a migrating foreign body presenting as a neck lump. On reviewing the literature, most cases involving subcutaneously migrating fish bones show development of a neck lump several weeks to months after ingestion, with relatively stable conditions. However, our case showed a neck lump 1 day after ingestion with acute toxic symptoms.", "title": "Migrating fish bone presenting as acute onset of neck lump." }, { "docid": "MED-3925", "text": "This study describes how foods rich in fisetin and hexacosanol added to a strict diet reversed most symptoms of Parkinson's disease (PD) in one patient. This is a case report involving outpatient care. The subject was a dietitian diagnosed with idiopathic PD in 2000 at the age of 53 years old, with a history of exposure to neurotoxins and no family history of PD. A basic diet started in 2000 consisted of predominantly fruits, vegetables, 100% whole grains, extra virgin olive oil, nuts, seeds, nonfat milk products, tea, coffee, spices, small amounts of dark chocolate, and less than 25 g of animal fat daily. The basic diet alone failed to prevent decline due to PD. In 2009, the basic diet was enhanced with a good dietary source of both fisetin and hexacosanol. Six months after the patient started the enhanced diet rich in fisetin and hexacosanol, a clinically significant improvement in symptoms was noted; the patient's attending neurologist reported that the clinical presentation of cogwheel rigidity, micrographia, bradykinesia, dystonia, constricted arm swing with gait, hypomimia, and retropulsion appeared to be resolved. The only worsening of symptoms occurred when the diet was not followed precisely. Little improvement in tremor or seborrhea was observed. The clinical improvement has persisted to date. To the best of our knowledge, this is the first case where adjunctive diet therapy resulted in a significant reduction of symptoms of PD without changing the type or increasing the amount of medications.", "title": "A diet low in animal fat and rich in N-hexacosanol and fisetin is effective in reducing symptoms of Parkinson's disease." }, { "docid": "MED-2091", "text": "BACKGROUND: The aim of this study was to evaluate and compare the effectiveness of 0.5% tea, 2% neem, and 0.2% chlorhexidine mouthwashes on oral health. MATERIALS AND METHODS: A randomized blinded controlled trial with 30 healthy human volunteers of age group 18-25 years was carried out. The subjects were randomly assigned to 3 groups i.e., group A - 0.2% chlorhexidine gluconate (bench mark control), Group B - 2% neem, and group C - 0.5% tea of 10 subjects per group. Plaque accumulation and gingival condition were recorded using plaque index and gingival index. Oral hygiene was assessed by simplified oral hygiene index (OHIS). Salivary pH was assessed by indikrom pH strips. Plaque, gingival, and simplified OHI scores as well as salivary pH were recorded at baseline, immediately after 1 st rinse, after 1 week, 2 nd week, and 3 rd week. The 3 rd week was skipped for group A. RESULTS: Mean plaque and gingival scores were reduced over the 3 week trial period for experimental and control groups. Anti-plaque effectiveness was observed in all groups and the highest being in group C (P < 0.05). Neem and tea showed comparative effectiveness on gingiva better than chlorhexidine (P < 0.05). The salivary pH rise was sustained and significant in Group B and C compared to Group A. Oral hygiene improvement was better appreciated in Group B and Group C. CONCLUSION: The effectiveness of 0.5% tea was more compared to 2% neem and 0.2% chlorhexidine mouth rinse.", "title": "Comparison of the effectiveness of 0.5% tea, 2% neem and 0.2% chlorhexidine mouthwashes on oral health: a randomized control trial." }, { "docid": "MED-4129", "text": "Pigs are considered as a major reservoir of human pathogenic Yersinia enterocolitica and a source of human yersiniosis. However, the transmission route of Y. enterocolitica from farm to pork is still unclear. The transmission of pathogenic Y. enterocolitica from pigs to carcasses and pluck sets was investigated by collecting samples from 364 individual ear-tagged pigs on the farm and at the slaughterhouse. In addition, isolated strains were analyzed, using pulsed-field gel electrophoresis. Isolation of similar genotypes of pathogenic Y. enterocolitica 4/O:3 in animals on the farm and at the slaughterhouse and in carcasses shows that carcass contamination originates from the strains a pig carries during the fattening period. Direct contamination from the carrier pig to its subsequent pluck set is also the primary contamination route for pluck sets, but cross-contamination appears to have a larger impact on pluck set contamination than on carcasses. In this study, the within-farm prevalence of pathogenic Y. enterocolitica varied from 0% to 100%, indicating specific farm factors affect the prevalence of Y. enterocolitica in pigs. The association of farm factors with the high prevalence of pathogenic Y. enterocolitica on farms was studied for the first time, using correlation and two-level logistic regression analyses. Specific farm factors, i.e. drinking from a nipple, absence of coarse feed or bedding for slaughter pigs, and no access of pest animals to pig house, were associated with a high prevalence of pathogenic Y. enterocolitica 4/O:3.", "title": "Contamination of carcasses with human pathogenic Yersinia enterocolitica 4/O:3 originates from pigs infected on farms." }, { "docid": "MED-3641", "text": "Cranberry juice is known to inhibit bacterial adhesion. We examined the inhibitory effect of cranberry juice on the adhesion of oral streptococci strains labeled with [3H]-thymidine to saliva-coated hydroxyapatite beads (s-HA). When the bacterial cells were momentarily exposed to cranberry juice, their adherence to s-HA decreased significantly compared with the control (P < 0.01). Their hydrophobicity also decreased dependently with the concentration of cranberry juice. We also evaluated the inhibitory effect of cranberry juice on biofilm formation. By using a microplate system, we found that the high molecular mass constituents of cranberry juice inhibited the biofilm formation of the tested streptococci. The inhibitory activity was related to the reduction of the hydrophobicity. The present findings suggest that cranberry juice component(s) can inhibit colonization by oral streptococci to the tooth surface and can thus slow development of dental plaque. Copyright Blackwell Munksgaard, 2004.", "title": "Inhibitory effects of cranberry juice on attachment of oral streptococci and biofilm formation." }, { "docid": "MED-1802", "text": "Hypotheses regarding the role of meat consumption in body weight modulation are contradictory. Prospective studies on an association between meat consumption and BMI change are limited. We assessed the association between meat consumption and change in BMI over time in 3902 men and women aged 55-69 y from the Netherlands Cohort Study. Dietary intake was estimated at baseline using a FFQ. BMI was ascertained through baseline self-reported height (1986) and weight (1986, 1992, and 2000). Analyses were based on sex-specific categories of daily total fresh meat, red meat, beef, pork, minced meat, chicken, processed meat, and fish consumption at baseline. Linear mixed effect modeling adjusted for confounders was used to assess longitudinal associations. Significant cross-sectional differences in BMI between quintiles of total meat intake were observed (P-trend < 0.01; both sexes). No association between total fresh meat consumption and prospective BMI change was observed in men (BMI change highest vs. lowest quintile after 14 y: -0.06 kg/m²; P = 0.75) and women (BMI change: 0.26 kg/m²; P = 0.20). Men with the highest intake of beef experienced a significantly lower increase in BMI after 6 and 14 y than those with the lowest intake (BMI change after 14 y 0.60 kg/m²). After 14 y, a significantly higher increase in BMI was associated with higher intakes of pork in women (BMI change highest vs. lowest quintile: 0.47 kg/m²) and chicken in both sexes (BMI change highest vs. lowest category in both men and women: 0.36 kg/m²). The results remained similar when stratifying on median baseline BMI, and age-stratified analyses yielded mixed results. Differential BMI change effects were observed for several subtypes of meat. However, total meat consumption, or factors directly related to total meat intake, was not strongly associated with weight change during the 14-y prospective follow-up in this elderly population.", "title": "Longitudinal changes in BMI in older adults are associated with meat consumption differentially, by type of meat consumed." }, { "docid": "MED-5193", "text": "BACKGROUND: The relation between dairy product intake and the risk of ischemic heart disease (IHD) remains controversial. OBJECTIVE: We aimed to explore biomarkers of dairy fat intake in plasma and erythrocytes and to assess the hypothesis that higher concentrations of these biomarkers are associated with a greater risk of IHD in US women. DESIGN: Among 32,826 participants in the Nurses' Health Study who provided blood samples in 1989-1990, 166 incident cases of IHD were ascertained between baseline and 1996. These cases were matched with 327 controls for age, smoking, fasting status, and date of blood drawing. RESULTS: Among controls, correlation coefficients between average dairy fat intake in 1986-1990 and 15:0 and trans 16:1n-7 content were 0.36 and 0.30 for plasma and 0.30 and 0.32 for erythrocytes, respectively. In multivariate analyses, with control for age, smoking, and other risk factors of IHD, women with higher plasma concentrations of 15:0 had a significantly higher risk of IHD. The multivariate-adjusted relative risks (95% CI) from the lowest to highest tertile of 15:0 concentrations in plasma were 1.0 (reference), 2.18 (1.20, 3.98), and 2.36 (1.16, 4.78) (P for trend = 0.03). Associations for other biomarkers were not significant. CONCLUSIONS: Plasma and erythrocyte contents of 15:0 and trans 16:1n-7 can be used as biomarkers of dairy fat intake. These data suggest that a high intake of dairy fat is associated with a greater risk of IHD.", "title": "Plasma and erythrocyte biomarkers of dairy fat intake and risk of ischemic heart disease." }, { "docid": "MED-1992", "text": "Summary Prediabetes (or “intermediate hyperglycaemia”), based on glycaemic parameters above normal but below diabetes thresholds is a high risk state for diabetes with an annualized conversion rate of 5%–10%; with similar proportion converting back to normoglycaemia. The prevalence of prediabetes is increasing worldwide and it is projected that >470 million people will have prediabetes in 2030. Prediabetes is associated with the simultaneous presence of insulin resistance and β-cell dysfunction, abnormalities that start before glucose changes are detectable. Observational evidence shows associations of prediabetes with early forms of nephropathy, chronic kidney disease, small fibre neuropathy, diabetic retinopathy, and increased risk of macrovascular disease. Multifactorial risk scores could optimize the estimation of diabetes risk using non-invasive parameters and blood-based metabolic traits in addition to glycaemic values. For prediabetic individuals, lifestyle modification is the cornerstone of diabetes prevention with evidence of a 40%–70% relative risk reduction. Accumulating data also suggests potential benefits from pharmacotherapy.", "title": "Prediabetes: A high-risk state for developing diabetes" }, { "docid": "MED-3534", "text": "Background Numerous antioxidant and anti‐inflammatory agents have been identified in tart cherries. Objective To test the efficacy of a tart cherry juice blend in preventing the symptoms of exercise induced muscle damage. Methods This was a randomised, placebo controlled, crossover design. Fourteen male college students drank 12 fl oz of a cherry juice blend or a placebo twice a day for eight consecutive days. A bout of eccentric elbow flexion contractions (2 × 20 maximum contractions) was performed on the fourth day of supplementation. Isometric elbow flexion strength, pain, muscle tenderness, and relaxed elbow angle were recorded before and for four days after the eccentric exercise. The protocol was repeated two weeks later with subjects who took the placebo initially, now taking the cherry juice (and vice versa). The opposite arm performed the eccentric exercise for the second bout to avoid the repeated bout protective effect. Results Strength loss and pain were significantly less in the cherry juice trial versus placebo (time by treatment: strength p<0.0001, pain p  =  0.017). Relaxed elbow angle (time by treatment p  =  0.85) and muscle tenderness (time by treatment p  =  0.81) were not different between trials. Conclusions These data show efficacy for this cherry juice in decreasing some of the symptoms of exercise induced muscle damage. Most notably, strength loss averaged over the four days after eccentric exercise was 22% with the placebo but only 4% with the cherry juice.", "title": "Efficacy of a tart cherry juice blend in preventing the symptoms of muscle damage" }, { "docid": "MED-2211", "text": "BACKGROUND: China is increasingly facing the challenge of control of the growing burden of non-communicable diseases. We assessed the epidemiology of Alzheimer's disease and other forms of dementia in China between 1990, and 2010, to improve estimates of the burden of disease, analyse time trends, and inform health policy decisions relevant to China's rapidly ageing population. METHODS: In our systematic review we searched for reports of Alzheimer's disease or dementia in China, published in Chinese and English between 1990 and 2010. We searched China National Knowledge Infrastructure, Wanfang, and PubMed databases. Two investigators independently assessed case definitions of Alzheimer's disease and dementia: we excluded studies that did not use internationally accepted case definitions. We also excluded reviews and viewpoints, studies with no numerical estimates, and studies not done in mainland China. We used Poisson regression and UN demographic data to estimate the prevalence (in nine age groups), incidence, and standardised mortality ratio of dementia and its subtypes in China in 1990, 2000, and 2010. FINDINGS: Our search returned 12,642 reports, of which 89 met the inclusion criteria (75 assessed prevalence, 13 incidence, and nine mortality). In total, the included studies had 340,247 participants, in which 6357 cases of Alzheimer's disease were recorded. 254,367 people were assessed for other forms of dementia, of whom 3543 had vascular dementia, frontotemporal dementia, or Lewy body dementia. In 1990 the prevalence of all forms of dementia was 1·8% (95% CI 0·0-44·4) at 65-69 years, and 42·1% (0·0-88·9) at age 95-99 years. In 2010 prevalence was 2·6% (0·0-28·2) at age 65-69 years and 60·5% (39·7-81·3) at age 95-99 years. The number of people with dementia in China was 3·68 million (95% CI 2·22-5·14) in 1990, 5·62 million (4·42-6·82) in 2000, and 9·19 million (5·92-12·48) in 2010. In the same period, the number of people with Alzheimer's disease was 1·93 million (1·15-2·71) in 1990, 3·71 million (2·84-4·58) people in 2000, and 5·69 million (3·85-7·53) in 2010. The incidence of dementia was 9·87 cases per 1000 person-years, that of Alzheimer's disease was 6·25 cases per 1000 person-years, that of vascular dementia was 2·42 cases per 1000 person-years, and that of other rare forms of dementia was 0·46 cases per 1000 person-years. We retrieved mortality data for 1032 people with dementia and 20,157 healthy controls, who were followed up for 3-7 years. The median standardised mortality ratio was 1·94:1 (IQR 1·74-2·45). INTERPRETATION: Our analysis suggests that previous estimates of dementia burden, based on smaller datasets, might have underestimated the burden of dementia in China. The burden of dementia seems to be increasing faster than is generally assumed by the international health community. Rapid and effective government responses are needed to tackle dementia in low-income and middle-income countries. FUNDING: Nossal Institute of Global Health (University of Melbourne, Australia), the National 12th Five-Year Major Projects of China, National Health and Medical Research Council Australia-China Exchange Fellowship, Importation and Development of High-Calibre Talents Project of Beijing Municipal Institutions, and the Bill & Melinda Gates Foundation. Copyright © 2013 Elsevier Ltd. All rights reserved.", "title": "Epidemiology of Alzheimer's disease and other forms of dementia in China, 1990-2010: a systematic review and analysis." }, { "docid": "MED-1162", "text": "Consumers are frequently urged to avoid imported foods as well as specific fruits and vegetables due to health concerns from pesticide residues and are often encouraged to choose organic fruits and vegetables rather than conventional forms. Studies have demonstrated that while organic fruits and vegetables have lower levels of pesticide residues than do conventional fruits and vegetables, pesticide residues are still frequently detected on organic fruits and vegetables; typical dietary consumer exposure to pesticide residues from conventional fruits and vegetables does not appear to be of health significance. Similarly, research does not demonstrate that imported fruits and vegetables pose greater risks from pesticide residues than do domestic fruits and vegetables or that specific fruits and vegetables singled out as being the most highly contaminated by pesticides should be avoided in their conventional forms.", "title": "Pesticide residues in imported, organic, and \"suspect\" fruits and vegetables." }, { "docid": "MED-2182", "text": "Over the past century, a major shift in North American food practices has been taking place. However, the literature on this topic is lacking in several areas. Some available research on food and cooking practices in the current context is presented, with a focus on how these are affecting health and how they might be contributing to health inequalities within the population. First, cooking and cooking skills are examined, along with the ambiguities related to terms associated with cooking in the research literature. Food choice, cooking, and health are described, particularly in relation to economic factors that may lead to health inequalities within the population. The importance of developing an understanding of factors within the wider food system as part of food choice and cooking skills is presented, and gaps in the research literature are examined and areas for future research are presented. Cooking practices are not well studied but are important to an understanding of human nutritional health as it relates to cultural, environmental, and economic factors.", "title": "Food, cooking skills, and health: a literature review." }, { "docid": "MED-3302", "text": "In November 2007 a novel neuropathy, immune-mediated polyradiculoneuropathy (IP), was identified among workers at a Minnesota swine abattoir where a unique compressed air technique was used to remove porcine brains. An epidemiologic investigation at another abattoir in Indiana that also uses this process was launched to evaluate workers self-reporting neurologic illness compatible with IP. A nested case-control study was performed to identify cases and risk factors. Six confirmed, one probable, and three possible IP cases were detected. IP cases were 28-52 years old, of Latino origin, and 62.5% female. Onset dates ranged from April 2005-December 2007; 60% were hospitalized. IP cases at this plant were similar in clinical presentation and exposure risks to those detected in Minnesota. Swine abattoirs using similar brain extraction methods should discontinue this process.", "title": "A clustering of immune-mediated polyradiculoneuropathy among swine abattoir workers exposed to aerosolized porcine brains, Indiana, United States." }, { "docid": "MED-4281", "text": "Over the past 20 years, growing interest in the biochemistry, nutrition, and pharmacology of L-arginine has led to extensive studies to explore its nutritional and therapeutic roles in treating and preventing human metabolic disorders. Emerging evidence shows that dietary L-arginine supplementation reduces adiposity in genetically obese rats, diet-induced obese rats, finishing pigs, and obese human subjects with Type-2 diabetes mellitus. The mechanisms responsible for the beneficial effects of L-arginine are likely complex, but ultimately involve altering the balance of energy intake and expenditure in favor of fat loss or reduced growth of white adipose tissue. Recent studies indicate that L-arginine supplementation stimulates mitochondrial biogenesis and brown adipose tissue development possibly through the enhanced synthesis of cell-signaling molecules (e.g., nitric oxide, carbon monoxide, polyamines, cGMP, and cAMP) as well as the increased expression of genes that promote whole-body oxidation of energy substrates (e.g., glucose and fatty acids) Thus, L-arginine holds great promise as a safe and cost-effective nutrient to reduce adiposity, increase muscle mass, and improve the metabolic profile in animals and humans.", "title": "Beneficial effects of L-arginine on reducing obesity: potential mechanisms and important implications for human health." }, { "docid": "MED-1164", "text": "We assessed organophosphorus (OP) pesticide exposure from diet by biological monitoring among Seattle, Washington, preschool children. Parents kept food diaries for 3 days before urine collection, and they distinguished organic and conventional foods based on label information. Children were then classified as having consumed either organic or conventional diets based on analysis of the diary data. Residential pesticide use was also recorded for each home. We collected 24-hr urine samples from 18 children with organic diets and 21 children with conventional diets and analyzed them for five OP pesticide metabolites. We found significantly higher median concentrations of total dimethyl alkylphosphate metabolites than total diethyl alkylphosphate metabolites (0.06 and 0.02 micro mol/L, respectively; p = 0.0001). The median total dimethyl metabolite concentration was approximately six times higher for children with conventional diets than for children with organic diets (0.17 and 0.03 micro mol/L; p = 0.0003); mean concentrations differed by a factor of nine (0.34 and 0.04 micro mol/L). We calculated dose estimates from urinary dimethyl metabolites and from agricultural pesticide use data, assuming that all exposure came from a single pesticide. The dose estimates suggest that consumption of organic fruits, vegetables, and juice can reduce children's exposure levels from above to below the U.S. Environmental Protection Agency's current guidelines, thereby shifting exposures from a range of uncertain risk to a range of negligible risk. Consumption of organic produce appears to provide a relatively simple way for parents to reduce their children's exposure to OP pesticides.", "title": "Organophosphorus pesticide exposure of urban and suburban preschool children with organic and conventional diets." }, { "docid": "MED-1028", "text": "The present studies explored whether faecal retention in the colon is a causative factor in functional bowel disease, appendicitis, and haemorrhoids. Faecal retention was characterized by colon transit time (CTT) after radio-opaque marker ingestion and estimation of faecal loading on abdominal radiographs at 48 h and 96 h. Specific hypotheses were tested in patients (n = 251 plus 281) and in healthy random controls (n = 44). A questionnaire was completed for each patient, covering abdominal and anorectal symptoms and without a priori grouping. Patients with functional bowel disorders, predominantly women, had a significantly increased CTT and faecal load compared to controls. The CTT was significantly and positively correlated with segmental and total faecal loading. The faecal load was equal at 48 h and 96 h, mirroring the presence of permanent faecal reservoirs. In these first clinical studies to correlate bowel symptoms with CTT and colon faecal loading, abdominal bloating was significantly correlated with faecal loading in the right colon, total faecal load, and CTT. Abdominal pain was significantly and positively correlated to distal faecal loading and significantly associated with bloating. A new phenomenon with a high faecal load and a normal CTT was observed in a subset of patients (n = 90), proving faecal retention as hidden constipation. The CTT and faecal load were significantly higher in the right-side compared to the left and distal segments. Within the control group of healthy persons, the right-sided faecal load was significantly greater than the left and distal load. The CTT and faecal load significantly positively correlated with a palpable mass in the left iliac fossa and meteorism. Cluster analysis revealed that CTT and faecal load positively correlated with a symptom factor consisting of bloating, proctalgia and infrequent defecation of solid faeces. On the other hand, CTT and faecal load negatively correlated with a symptom factor comprising frequent easy defecations, repetitiveness, and incompleteness with solid or liquid faeces. The majority of patients with a heavy faecal load but normal CTT had repetitive daily defecation, mostly with ease and with altering faecal consistence. Flue-like episodes co-existed in symptom factors with abdominal pain and meteorism, and these symptoms together with a palpable right iliac fossa mass and tenderness, and in other factors with seldom and difficult defecation, and with epigastric discomfort and halitosis. Patients with seldom and difficult defecation of solid faeces experienced abdominal pain significantly more often and presented a palpable mass in the right iliac fossa with tenderness and meteorism. The CTT was significantly prolonged and faecal load significantly increased. In patients with a normal CTT and increased faecal load, only patients with abdominal pain had a significant correlation between faecal loading and bloating. CTT and faecal load were shown for the first time to increase significantly with the number of colonic redundancies (colon length), which also resulted in significantly increased bloating and pain. Intervention with a bowel stimulation regimen combining a fibre-rich diet, fluid, physical activity, and a prokinetic drug was essential to proving that abdominal symptoms and defecation disorders are caused by faecal retention, with or without a prolonged CTT. The CTT was significantly reduced, as was faecal load. Bloating and pain were reduced significantly. The defecation became easy with solid faeces, towards one per day and with significant reductions in incompleteness and repetitiveness. Proctalgia and flue-like episodes were significantly reduced. The intervention significantly reduced the presence of a tender palpable mass in the right fossa and rectal constipation. In patients with a normal CTT but increased faecal load, the intervention did not significantly change the CTT or load, but bloating and pain were significantly reduced, just as defecation improved overall. The novel knowledge of faecal retention in the patients does not explain why faecal retention occurs. However, it may be inferred from the present results that a constipated or irritable bowel may belong to the same underlying disease dimension, where faecal retention is a common factor. Thus, measuring CTT and faecal load is suggested as a guide to a positive functional diagnosis of bowel disorders compared to the constellation of symptoms alone. Thirty-five patients underwent surgery after being refractory to the conservative treatment for constipation. They had a significantly prolonged CTT and heavy faecal loading, which was responsible for the aggravated abdominal and defaecatory symptoms. The operated patients presented with a redundant colon (dolichocolon) significantly more often. These patients also had an extremely high rate of previous appendectomy. Twenty-one patients underwent hemicolectomy, and 11 patients had a subtotal colectomy with an ileosigmoidal anastomosis; three patients received a stoma. However, some patients had to have the initial segmental colectomy converted to a final subtotal colectomy because of persisting symptoms. Six more subtotal colectomies have been performed and the leakage rate of all colectomies is then 4.9 % (one patient died). After a mean follow-up of 5 years, the vast majority of patients were without abdominal pain and bloating, having two to four defecations daily with control and their quality of life had increased considerably. A faecalith is often located in the appendix, the occlusion of which is responsible for many cases of acute appendicitis, which is infrequent in all except white populations. An effort to trace the origin of the faecalith to faecal retention in the colon was made in a case control study (56 patients and 44 random controls). The CTT was longer and faecal load greater in patients with appendicitis compared to controls, though the difference was not significant. Power calculations showed that more patients were needed to reach statistical significance for these parameters. The presence of a faecalith was most often associated with a gangrenous or perforated appendix. No significant differences were found between the CTT and faecal load of patients who had or did not have a faecalith. However, the right-sided faecal load was significantly higher than the left and distal load. Haemorrhoids are often a consequence of constipation and defaecatory disorders and were found in every second patient with functional bowel disorders. The present studies are the first Danish reports of a novel operation to cure this disease, stapled haemorrhoidopexy (n = 40 and 258 patients). The majority of patients had prolapsed haemorrhoids, and the durability of procedure was confirmed with a follow-up of up to 5 years, meaning a normal anus. The operation time was short, post-operative pain was low, and recovery was rapid. No incontinence was observed, and patient satisfaction was high and significantly correlated with the appearance of a normal anus without prolapse. The cumulative risk of re-operation was greatest in the first 2 years after the stapled haemorrhoidopexy. Patients with persisting haemorrhoidal prolapse had the procedure repeated with results as good as those obtained in the rest of the patients. It was shown in a statistical model that the preoperative severity of haemorrhoidal disease and the immediate postoperative result contributed significantly to predicting the outcome that is the durability of the operation. The most frequent post-operative complication was bleeding requiring surgical haemostasis. One serious complication occurred after an anastomotic leak from a highly placed anastomosis, resulting in retro rectal, retro- and intra-peritoneal, and mediastinal gas. The patient recovered after conservative treatment and without surgical intervention. The stapling technique now used has revolutionized the surgical treatment of prolapsing haemorrhoids. Finally, a common cause may be suspected for diseases constantly associated with one another. Epidemiological evidence has recognized that constipation, diverticulosis and IBS increase the risk of colon cancer (and adenomas), diseases exceedingly rare in communities exempt from appendicitis. Haemorrhoids are a colonic co-morbidity as well. Notably, the patients with a functional bowel disorder had a much higher rate of a previous appendectomy than the background population. In addition, the patients who had previously had an appendectomy had a significantly longer CTT compared to patients, who had not. The data points to the involvement of faecal retention in the origin of faecaliths and, thus, acute appendicitis. Faecal reservoirs were shown in the right and left colon segments in both patients and controls, which are the same areas bearing the highest incidences of adenomateous polyps and malignancies. Familial colorectal cancer occurred significantly more often in patients who had a higher faecal load than the controls. Four malignancies and 25 adenomas were identified. An increased faecal load in the colon with or without delayed transit will increase bacterial counts and create a chronic inflammation of the colonic mucosa, which is a risk factor for cancer onset. A functional bowel disorder is then likely to occur with gradually transition from a primary functional disease into specific organic diseases. A diet rich in fibre and regular physical activity have a therapeutic and preventive effect on colorectal diseases associated with faecal retention.", "title": "Faecal retention: a common cause in functional bowel disorders, appendicitis and haemorrhoids--with medical and surgical therapy." }, { "docid": "MED-1636", "text": "Coffee drinking has been associated with increased serum cholesterol levels in some, but not all, studies. A Medline search of the English-language literature published prior to December 1998, a bibliography review, and consultations with experts were performed to identify 14 published trials of coffee consumption. Information was abstracted independently by two reviewers using a standardized protocol. With a random-effects model, treatment effects were estimated by pooling results from individual trials after weighting the results by the inverse of total variance. A dose-response relation between coffee consumption and both total cholesterol and LDL cholesterol was identified (p < 0.01). Increases in serum lipids were greater in studies of patients with hyperlipidemia and in trials of caffeinated or boiled coffee. Trials using filtered coffee demonstrated very little increase in serum cholesterol. Consumption of unfiltered, but not filtered, coffee increases serum levels of total and LDL cholesterol.", "title": "Coffee consumption and serum lipids: a meta-analysis of randomized controlled clinical trials." }, { "docid": "MED-4040", "text": "The consumption of cooked meat appears to predispose individuals to colonic cancer and heterocyclic aromatic amines (HA), formed during the cooking of meat, have been suggested as aetiological agents. Consumption of cruciferous vegetables is thought to protect against cancer. To study the effect of cruciferous vegetables on heterocyclic aromatic amine metabolism in man, a three-period, dietary intervention study has been carried out with 20 non-smoking Caucasian male subjects consuming cooked meat meals containing known amounts of these carcinogens. A high cruciferous vegetable diet (250 g each of Brussels sprouts and broccoli per day) was maintained during period 2 but such vegetables were excluded from periods 1 and 3. At the end of each period, subjects consumed a cooked meat meal and urinary excretion of the HA 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) was measured. Following a 12 day period of cruciferous vegetable consumption (period 2), induction of hepatic CYP1A2 activity was apparent from changes in the kinetics of caffeine metabolism. Excretion of MeIQx and PhIP in urine at the end of this period of the study was reduced by 23 and 21%, respectively, compared with period 1. This reduction in excretion is probably due to an increase in amine metabolism that might be expected given the observed increase in CYP1A2 activity, since this enzyme has been shown to be primarily responsible for the oxidative activation of MeIQx and PhIP in man. In period 2, urinary mutagenicity was increased relative to period 1 by 52 and 64% in the absence and presence, respectively, of a human liver microsomal activation system, yet no evidence was found of PhIP adduction to lymphocyte DNA, a potential biomarker of the activation process. After another 12 days without cruciferous vegetables (period 3 of the study), the kinetics of caffeine metabolism had returned to original values but excretion of MeIQx and PhIP was still reduced by 17 and 30%, respectively, and urinary mutagenicity (with metabolic activation) was still elevated compared with period 1. This prolonged response of amine metabolism to the cruciferous vegetable diet, shown especially with PhIP, suggests that enzyme systems other than CYP1A2 are involved and affected by a cruciferous vegetable diet.", "title": "Effect of cruciferous vegetable consumption on heterocyclic aromatic amine metabolism in man." }, { "docid": "MED-2180", "text": "Objectives To compare the energy and macronutrient content of main meals created by television chefs with ready meals sold by supermarkets, and to compare both with nutritional guidelines published by the World Health Organization and UK Food Standards Agency. Design Cross sectional study. Setting Three supermarkets with the largest share of the grocery market in the United Kingdom, 2010. Samples 100 main meal recipes from five bestselling cookery books by UK television chefs and 100 own brand ready meals from the three leading UK supermarkets. Main outcome measures Number of meals for which the nutritional content complied with WHO recommendations, and the proportion of nutrients classified as red, amber, or green using the UK FSA’s “traffic light” system for labelling food. Results No recipe or ready meal fully complied with the WHO recommendations. The ready meals were more likely to comply with the recommended proportions of energy derived from carbohydrate (18% v 6%, P=0.01) and sugars (83% v 81%, P=0.05) and fibre density (56% v 14% P<0.01). The recipes were more likely to comply with the recommended sodium density (36% v 4%, P<0.01), although salt used for seasoning was not assessed. The distributions of traffic light colours under the FSA’s food labelling recommendations differed: the modal traffic light was red for the recipes (47%) and green for ready meals (42%). Overall, the recipes contained significantly more energy (2530 kJ v 2067 kJ), protein (37.5 g v 27.9 g), fat (27.1 g v 17.2 g), and saturated fat (9.2 g v 6.8 g; P<0.01 for all) and significantly less fibre (3.3 g v 6.5 g, P<0.01) per portion than the ready meals. Conclusions Neither recipes created by television chefs nor ready meals sold by three of the leading UK supermarkets complied with WHO recommendations. Recipes were less healthy than ready meals, containing significantly more energy, protein, fat, and saturated fat, and less fibre per portion than the ready meals.", "title": "Christmas 2012: Research: Nutritional content of supermarket ready meals and recipes by television chefs in the United Kingdom: cross sectional study" }, { "docid": "MED-3145", "text": "Urine morphine levels after the consumption of poppy seeds were measured in two separate trials. Maximum levels of approximately 18 micrograms/ml were found using RIA, EMIT-ST and GC methodologies. Positive immunoassay results were seen up to 60 h post-ingestion. Several different lots of seeds from various sources were assayed for morphine and found to range from 4-200 mg/kg. Differentiation of poppy seed eaters from opiate users was not possible via the identification of minor alkaloid constituents of poppy seeds. It is, however, possible to analyse opiate urines with respect to 6-O-acetylmorphine. Below the level of approximately 5 micrograms/ml total opiates, GC/MS is the method of choice for this analysis.", "title": "Morphine levels in urine subsequent to poppy seed consumption." }, { "docid": "MED-1948", "text": "Over the last ten years curcumin has been reported to be effective against a wide variety of diseases and is characterized as having anti-carcinogenic, hepatoprotective, thrombosuppressive, cardioprotective, anti-arthritic, and anti-infectious properties. Recent studies performed in both vertebrate and invertebrate models have been conducted to determine whether curcumin was also neuroprotective. The efficacy of curcumin in several pre-clinical trials for neurodegenerative diseases has created considerable excitement mainly due to its lack of toxicity and low cost. This suggests that curcumin could be a worthy candidate for nutraceutical intervention. Since aging is a common risk factor for neurodegenerative diseases, it is possible that some compounds that target aging mechanisms could also prevent these kinds of diseases. One potential mechanism to explain several of the general health benefits associated with curcumin is that it may prevent aging-associated changes in cellular proteins that lead to protein insolubility and aggregation. This loss in protein homeostasis is associated with several age-related diseases. Recently, curcumin has been found to help maintain protein homeostasis and extend lifespan in the model invertebrate Caenorhabditis elegans. Here, we review the evidence from several animal models that curcumin improves healthspan by preventing or delaying the onset of various neurodegenerative diseases.", "title": "Curcumin and neurodegenerative diseases" }, { "docid": "MED-5327", "text": "OBJECTIVE: To investigate the associations between dietary patterns and mental health in early adolescence. METHOD: The Western Australian Pregnancy Cohort (Raine) Study is a prospective study of 2900 pregnancies recruited from 1989-1992. At 14 years of age (2003-2006; n=1324), the Child Behaviour Checklist (CBCL) was used to assess behaviour (characterising mental health status), with higher scores representing poorer behaviour. Two dietary patterns (Western and Healthy) were identified using factor analysis and food group intakes estimated by a 212-item food frequency questionnaire. Relationships between dietary patterns, food group intakes and behaviour were examined using general linear modelling following adjustment for potential confounding factors at age 14: total energy intake, body mass index, physical activity, screen use, family structure, income and functioning, gender and maternal education at pregnancy. RESULTS: Higher total (b=2.20, 95% CI=1.06, 3.35), internalizing (withdrawn/depressed) (b=1.25, 95% CI=0.15, 2.35) and externalizing (delinquent/aggressive) (b=2.60, 95% CI=1.51, 3.68) CBCL scores were significantly associated with the Western dietary pattern, with increased intakes of takeaway foods, confectionary and red meat. Improved behavioural scores were significantly associated with higher intakes of leafy green vegetables and fresh fruit (components of the Healthy pattern). CONCLUSION: These findings implicate a Western dietary pattern in poorer behavioural outcomes for adolescents. Better behavioural outcomes were associated with a higher intake of fresh fruit and leafy green vegetables.", "title": "The association between dietary patterns and mental health in early adolescence." }, { "docid": "MED-1779", "text": "The imbalance between reactive oxygen species (ROS) production and total antioxidant capacity (TAC) in seminal fluid indicates oxidative stress and is correlated with male infertility. A composite ROS-TAC score may be more strongly correlated with infertility than ROS or TAC alone. We measured ROS, TAC, and ROS-TAC scores in semen from 127 patients and 24 healthy controls. Of the patients, 56 had varicocele, eight had varicocele with prostatitis, 35 had vasectomy reversals, and 28 had idiopathic infertility. ROS levels were higher among infertile men, especially those with varicocele with prostatitis (mean +/- SE, 3.25 +/- 0.89) and vasectomy reversals (2.65 +/- 1.01). All infertile groups had significantly lower ROS-TAC scores than control. ROS-TAC score identified 80% of patients and was significantly better than ROS at identifying varicocele and idiopathic infertility. The 13 patients whose partners later achieved pregnancies had a mean ROS-TAC score of 47.7 +/- 13.2, similar to controls but significantly higher than the 39 patients who remained infertile (35.8 +/- 15.0; P < 0.01). ROS-TAC score is a novel measure of oxidative stress and is superior to ROS or TAC alone in discriminating between fertile and infertile men. Infertile men with male factor or idiopathic diagnoses had significantly lower ROS-TAC scores than controls, and men with male factor diagnoses that eventually were able to initiate a successful pregnancy had significantly higher ROS-TAC scores than those who failed.", "title": "The reactive oxygen species-total antioxidant capacity score is a new measure of oxidative stress to predict male infertility." }, { "docid": "MED-897", "text": "The effects of different polyphenol-containing beverages on Fe absorption from a bread meal were estimated in adult human subjects from the erythrocyte incorporation of radio-Fe. The test beverages contained different polyphenol structures and were rich in either phenolic acids (chlorogenic acid in coffee), monomeric flavonoids (herb teas, camomile (Matricaria recutita L.), vervain (Verbena officinalis L.), lime flower (Tilia cordata Mill.), pennyroyal (Mentha pulegium L.) and peppermint (Mentha piperita L.), or complex polyphenol polymerization products (black tea and cocoa). All beverages were potent inhibitors of Fe absorption and reduced absorption in a dose-dependent fashion depending on the content of total polyphenols. Compared with a water control meal, beverages containing 20-50 mg total polyphenols/serving reduced Fe absorption from the bread meal by 50-70%, whereas beverages containing 100-400 mg total polyphenols/serving reduced Fe absorption by 60-90%. Inhibition by black tea was 79-94%, peppermint tea 84%, pennyroyal 73%, cocoa 71%, vervain 59%, lime flower 52% and camomile 47%. At an identical concentration of total polyphenols, black tea was more inhibitory than cocoa, and more inhibitory than herb teas camomile, vervain, lime flower and pennyroyal, but was of equal inhibition to peppermint tea. Adding milk to coffee and tea had little or no influence on their inhibitory nature. Our findings demonstrate that herb teas, as well as black tea, coffee and coca can be potent inhibitors of Fe absorption. This property should be considered when giving dietary advice in relation to Fe nutrition.", "title": "Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages." }, { "docid": "MED-2417", "text": "BACKGROUND: Inconsistent associations have been reported between diet and breast cancer. OBJECTIVE: We prospectively examined the association between dietary patterns and postmenopausal breast cancer risk in a US-wide cohort study. DESIGN: Data were analyzed from 40 559 women who completed a self-administered 61-item Block food-frequency questionnaire in the Breast Cancer Detection Demonstration Project, 1987-1998; 1868 of those women developed breast cancer. Dietary patterns were defined by using principal components factor analysis. Cox proportional hazard regression was used to assess breast cancer risk. RESULTS: Three major dietary patterns emerged: vegetable-fish/poultry-fruit, beef/pork-starch, and traditional southern. The vegetable-fish/poultry-fruit pattern was associated with higher education than were the other patterns, but was similar in nutrient intake to the traditional southern pattern. After adjustment for confounders, there was no significant association between the vegetable-fish/poultry-fruit and beef/pork-starch patterns and breast cancer. The traditional southern pattern, however, was associated with a nonsignificantly reduced breast cancer risk among all cases (in situ and invasive) that was significant for invasive breast cancer (relative hazard = 0.78; 95% CI = 0.65, 0.95; P for trend = 0.003). This diet was also associated with a reduced risk in women without a family history of breast cancer (P = 0.05), who were underweight or normal weight [body mass index (in kg/m(2)) < 25; P = 0.02], or who had tumors positive for estrogen receptor (P = 0.01) or progesterone receptor (P = 0.003). Foods in the traditional southern pattern associated with reduced breast cancer risk were legumes, low mayonnaise-salad dressing intake, and possibly cabbage. CONCLUSIONS: The traditional southern diet or its components are associated with a reduced risk of invasive breast cancer in postmenopausal women.", "title": "Empirically derived dietary patterns and risk of postmenopausal breast cancer in a large prospective cohort study." } ]